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1
Su, Shuhua, Qingguo Li, and Qi Li. "ZL-Completions for ZL-Semigroups." Symmetry 14, no. 3 (March 15, 2022): 578. http://dx.doi.org/10.3390/sym14030578.
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In this paper, we generalize a common completion pattern of ordered semigroups to the fuzzy setting. Based on a standard L-completion ZL, we introduce the notion of a ZL-semigroup as a generalization of an L-ordered semigroup, where L is a complete residuated lattice. For this asymmetric mathematical structure, we define a ZL-completion of it to be a complete residuated L-ordered semigroup together with a join-dense L-ordered semigroup embedding satisfying the universal property. We prove that: (1) For every compositive ZL, the category CSL of complete residuated L-ordered semigroups is a reflective subcategory of the category SZL of ZL-semigroups; (2) for an arbitrary ZL, there is an adjunction between SZL and the category SZL→E of weakly ZL-continuous L-ordered semigroup embeddings of ZL-semigroups. By appropriate specialization of ZL, the results can be applied to the DML-completion, certain completions associated with fuzzy subset systems, etc.
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Wang, Tiannan, and Guoxun Chen. "Vitamin A Status Regulates the Development of Obesity and Type 2 Diabetes in Zucker Diabetic Fatty Rats." Current Developments in Nutrition 5, Supplement_2 (June 2021): 531. http://dx.doi.org/10.1093/cdn/nzab041_046.
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Abstract Objectives Here, we studied the effects of VA status on the development of obesity and type 2 diabetes in Zucker diabetic fat (ZDF) rats. Methods Zucker Lean (ZL) and ZDF rats at weaning were divided into 6 groups, VA deficient with basal fat (VAD-BF, 0 mg retinyl palmitate (RP)/kg and 22.1% fat energy), VA marginal with BF (VAM-BF, 0.35 mg RP/kg), VA sufficient with BF (VAS-BF, 4.0 mg RP/kg), VAD with high-fat (VAD-HF, 60% fat energy), VAM-HF and VAS-HF diets, and fed for 8 weeks (w). The body mass (BM), and peripheral blood glucose (PBG) were measured weekly. An oral glucose tolerance test (OGTT) were done at 6.5 and 7.5w, respectively. Plasma levels of glucose, insulin, triacylglycerol and cholesterol l were determined using commercially available kits. The expression levels of genes and proteins in the liver of rats were analyzed using PCR and Western blot. Results VAS-BF ZL and ZDF rats from 6w had respectively higher BM than VAD/VAM-BF ZL and ZDF rats. VAS-HF ZL and ZDF rats from 4w had respectively higher BM than VAD/VAM-HF ZL and ZDF rats. VAS-BF/HF ZDF rats from 6w had respectively higher PBG levels than VAD/VAM-BF/HF ZDF rats. The OGTT AUC values of VAS-BF/HF ZL/ZDF rats were respectively higher than that of VAD/VAM-BF/HF ZL/ZDF rats. The levels of glucose, insulin, triacylglycerol and cholesterol in VAD/VAM/VAS-BF ZDF and VAD/VAM/VAS-HF ZDF rats were higher than that in BF ZL rats (except for the glucose level) and HF ZL rats, respectively. The hepatic Gck mRNA and its protein levels in VAD-BF ZL rats were lower than that in VAS-BF ZL rats. The hepatic levels of Fas, and Acl mRNA and FAS, and ACL proteins in VAM/VAS-HF ZF rats were higher than that in VAM/VAS-HF ZL rats. The hepatic retinol content of VAD-BF/HF ZL/ZDF rats were lower than that of VAM groups, which are lower than that of VAS-BF/HF ZL/ZDF rats. Conclusions VA statuses affect BM gain in ZL and ZDF rats fed a BF or a HF diet. The expression levels of mRNAs and proteins in the fatty acid biosynthesis pathways were reduced in VAD-HF ZDF rats. The effects of VA on fatty acid biosynthesis in ZDF rats were masked in a HF diet setting. Reduced VA intake prevents obesity, and type 2 diabetes in ZDF rats. Funding Sources Diabetes Action Research and Education Foundation
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Wang, Tiannan, and Guoxun Chen. "Vitamin A Status Regulates the Development of Obesity and Type 2 Diabetes in Zucker Diabetic Fatty Rats." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 672. http://dx.doi.org/10.1093/cdn/nzaa049_065.
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Abstract Objectives We have shown that vitamin A (VA) status regulates obesity and fuel metabolism in rats. Here, we studied the effects of VA status on the development of obesity and type 2 diabetes in Zucker diabetic fat (ZDF) rats. Methods Zucker Lean (ZL) and ZDF rats at weaning were divided into 6 groups, VA deficient with basal fat (VAD-BF, 0 mg retinyl palmitate (RP)/kg and 22.1% fat energy), VA marginal with BF (VAM-BF, 0.35 mg RP/kg), VA sufficient with BF (VAS-BF, 4.0 mg RP/kg), VAD with high-fat (VAD-HF, 60% fat energy), VAM-HF and VAS-HF diets, and fed for 8 weeks (w). The body mass (BM), and peripheral blood glucose (PBG) were measured weekly. Insulin tolerance test (ITT) and oral glucose tolerance test (OGTT) were done at 6.5 and 7.5 w, respectively. At the end of the feeding, blood, liver and white adipose tissue (WTA) samples were collected. Results VAS-BF ZL and ZDF rats from 6 w had respectively higher BM than VAD/VAM-BF ZL and ZDF rats. VAS-HF ZL and ZDF rats from 4 w had respectively higher BM than VAD/VAM-HF ZL and ZDF rats. The liver/BM and WAT/BM ratios in VAD/VAM-BF/HF ZL and ZDF V rats were respectively lower than that of VAS-BF/HF groups. VAS-BF/HF ZDF rats from 6 w had respectively higher PBG levels than VAD/VAM-BF/HF ZDF rats. In ITT, PBG levels of VAD/VAM/VAS-BF ZL rats dropped until 15 mins. PBG levels of VAD-HF and VAM/VAS-HF ZL rats declined until 30 mins and 15 mins, respectively. PBG levels of VAM-BF and VAS-BF ZDF rats dropped until 15 mins and 5 mins, respectively. PBG levels of VAD-BF ZDF rats start to dropped after 10 mins and stopped after 20 mins. PBG levels of VAD/VAM-HF and VAS-HF ZDF rats dropped until 15 mins and 20 mins, respectively. The OGTT results showed that PBG levels of VAS-BF ZL rats peaked at 10 mins, and VAS-BF/HF ZL rats had respectively higher PBG levels than VAD/VAM-BF/HF ZL rats. PBG levels of all ZDF rats peaked at 60 mins (except for VAS-BF ZDF rats at 30) before dropped. TheOGTT area under the curve values of VAS-BF/HF ZL or ZDF rats were respectively higher than that of VAD/VAM-BF/HF ZL or ZDF rats, and that of VAM-HF ZL rats were higher than that of VAD-HF ZL rats. Conclusions VA statuses affect BM gain in ZL and ZDF rats in BF and HF diets. Reduced VA intake prevents obesity, and type 2 diabetes in ZDF rats. Funding Sources Diabetes Action Research and Education Foundation.
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Lal, Shruti, Bee-Chun Sun, Yuping Chen, Tom Huang, Neil Bhola, Vivian Morton, Kevin Chen, et al. "Abstract 2594: Discovery and characterization of ZL-2201, a potent, highly-selective, and orally bioavailable small-molecule DNA-PK inhibitor." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2594. http://dx.doi.org/10.1158/1538-7445.am2022-2594.
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Abstract DNA-damaging poisons and replicative stress commonly result in increased double-strand breaks (DSBs) in tumor cells. Non-homologous end joining (NHEJ), driven by the enzymatic function of DNA-PK, is one of the critical pathways employed to repair such DSBs. Inhibition of DNA-PK kinase activity impairs NHEJ, potentiates the activity of DNA-damaging agents, and inhibits survival of tumor cells incapable of repairing DSBs via other means, including homologous recombination (HR). We have developed an orally bioavailable, highly potent, and selective pharmacological inhibitor of DNA-PK activity, ZL-2201, for the treatment of cancer. ZL-2201 demonstrates enzymatic inhibition of DNA-PK in the single-digit nM range, with nearly 500-fold or greater selectivity against other phosphatidylinositol 3-kinase-related kinases (PIKKs). In addition, ZL-2201 showed high selectivity for DNA-PK kinase activity in a kinase panel screening study and a clean off-target profile with no appreciable inhibition against a panel of diverse, safety-relevant targets. We demonstrate that ZL-2201 effectively inhibits DNA-PK autophosphorylation and its downstream target phospho-RPA in multiple cell lines in a concentration- and time-dependent manner. DNA-PK has been shown previously to have synthetically lethal interactions with ATM. Therefore, we profiled the impact of ATM expression on the antiproliferative effects of ZL-2201. Cancer cell lines possessing defects in ATM displayed greater sensitivity to ZL-2201 compared to ATM-WT cancer cell lines. These observations were recapitulated in two ATM knockout isogenic cell lines. Moreover, ZL-2201 displayed minimal effects in a DNA-PK deficient model or in normal human and canine colon and kidney cell lines. Independent of ATM status, ZL-2201 showed strong synergy in vitro with topoisomerase II inhibitors. Following oral administration of ZL-2201 in vivo, ZL-2201 demonstrated dose-dependent and exposure-dependent antitumor activity against multiple models, with the greatest activity against ATM deficient human cancer xenografts. Antitumor activity correlated with duration of ZL-2201 exposure and level of target engagement. In addition, ZL-2201 significantly enhanced the activity of DNA-damaging agents in vivo, even in human cancer xenograft models with limited monotherapy antitumor activity for ZL-2201. The projected human PK properties, based on the ADME properties across species and PK properties in preclinical species of ZL-2201, suggest that ZL-2201 is suitable for oral administration. In conclusion, ZL-2201 demonstrates potent and selective inhibition of DNA-PK enzymatic activity, strong synergy with DNA damaging agents in vitro and in vivo, antitumor activity against multiple human xenograft models, and a favorable projected human PK profile. ZL-2201 is expected to enter clinical development in 2022. Citation Format: Shruti Lal, Bee-Chun Sun, Yuping Chen, Tom Huang, Neil Bhola, Vivian Morton, Kevin Chen, Shanghua Xia, Haoyu Zhang, Qiuping Ye, Petter Veiby, David I. Bellovin, Yuhua Ji. Discovery and characterization of ZL-2201, a potent, highly-selective, and orally bioavailable small-molecule DNA-PK inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2594.
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Sultan, Ahmed, Ernest Adeghate, Bright Starling Emerald, Muhammad A. Qureshi, Saeed Tariq Minhas, and Frank Christopher Howarth. "Effects of Obesity and Diabesity on Ventricular Muscle Structure and Function in the Zucker Rat." Life 12, no. 8 (August 11, 2022): 1221. http://dx.doi.org/10.3390/life12081221.
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(1) Background: Cardiovascular complications are a leading cause of morbidity and mortality in diabetic patients. The effects of obesity and diabesity on the function and structure of ventricular myocytes in the Zucker fatty (ZF) rat and the Zucker diabetic fatty (ZDF) rat compared to Zucker lean (ZL) control rats have been investigated. (2) Methods: Shortening and intracellular Ca2+ were simultaneously measured with cell imaging and fluorescence photometry, respectively. Ventricular muscle protein expression and structure were investigated with Western blot and electron microscopy, respectively. (3) Results: The amplitude of shortening was increased in ZF compared to ZL but not compared to ZDF myocytes. Resting Ca2+ was increased in ZDF compared to ZL myocytes. Time to half decay of the Ca2+ transient was prolonged in ZDF compared to ZL and was reduced in ZF compared to ZL myocytes. Changes in expression of proteins associated with cardiac muscle contraction are presented. Structurally, there were reductions in sarcomere length in ZDF and ZF compared to ZL and reductions in mitochondria count in ZF compared to ZDF and ZL myocytes. (4) Conclusions: Alterations in ventricular muscle proteins and structure may partly underlie the defects observed in Ca2+ signaling in ZDF and ZF compared to ZL rat hearts.
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Zhang, Yan, Rui Li, Yang Li, Wei Chen, Shi Zhao, and Guoxun Chen. "Vitamin A status affects obesity development and hepatic expression of key genes for fuel metabolism in Zucker fatty rats." Biochemistry and Cell Biology 90, no. 4 (August 2012): 548–57. http://dx.doi.org/10.1139/o2012-012.
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We hypothesized that vitamin A (VA) status may affect obesity development. Male Zucker lean (ZL) and fatty (ZF) rats after weaning were fed a synthetic VA deficient (VAD) or VA sufficient (VAS) diet for 8 weeks before their plasma parameters and hepatic genes’ expression were analyzed. The body mass (BM) of ZL or ZF rats fed the VAD diet was lower than that of their corresponding controls fed the VAS diet at 5 or 2 weeks, respectively. The VAD ZL and ZF rats had less food intake than the VAS rats after 5 weeks. The VAD ZL and ZF rats had lower plasma glucose, triglyceride, insulin, and leptin levels, as well as lower liver glycogen content, net mass of epididymal fat, and liver/BM and epididymal fat/BM ratios (ZL only) than their respective VAS controls. VAD rats had lower hepatic Cyp26a1, Srebp-1c, Fas, Scd1, Me1, Gck, and Pklr (ZL and ZF); and higher Igfbp1 (ZL and ZF), Pck1(ZF only), and G6pc (ZF only) mRNA levels than their respective VAS controls. We conclude that ZL and ZF rats responded differently to dietary VA deficiency. VA status affected obesity development and altered the expression of hepatic genes for fuel metabolism in ZF rats. The mechanisms will help us to combat metabolic diseases.
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Erdös, Benedek, James A. Snipes, Bela Kis, Allison W. Miller, and David W. Busija. "Vasoconstrictor mechanisms in the cerebral circulation are unaffected by insulin resistance." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 287, no. 6 (December 2004): R1456—R1461. http://dx.doi.org/10.1152/ajpregu.00279.2004.
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Insulin-resistance (IR) impairs agonist-induced relaxation in cerebral arteries, but little is known about its effect on constrictor mechanisms. We examined the vascular responses of the basilar artery (BA) and its side branches in anesthetized Zucker lean (ZL) and IR Zucker obese (ZO) rats using a cranial window technique. Endothelin-1 (ET-1) constricted the BAs in both the ZL and ZO rats, but there was no significant difference between the two groups (ZL: 36 ± 8%; ZO: 33 ± 3% at 10−8 M). Inhibition of the ETA receptors by BQ-123 slightly increased the diameters of the BAs, with no difference shown between the ZL (6 ± 1%) and ZO (5 ± 3%) rats. Expressions of the ETA receptors and ET-1 mRNA examined by immunoblot analysis and RT-PCR, respectively, were also similar in the ZL and ZO groups. Phorbol 12,13-dibutyrate (PDBu), an activator of protein kinase C (PKC), and the thromboxane A2 (TxA2) mimetic U-46619 constricted the BAs, but similarly to ET-1, there was no significant difference between the ZL and ZO groups (10−6 M PDBu: ZL: 33 ± 2%; ZO: 32 ± 4%; and 10−7 M U-46619: ZL: 23 ± 1%; ZO: 19 ± 2%). Inhibition of Rho-kinase with Y-27632 induced dilation of the BAs, and these responses were also comparable in the ZL and ZO rats (ZL: 39 ± 4%; ZO: 38 ± 2% at 10−5 M). In contrast, nitric oxide-dependent relaxation to bradykinin was significantly reduced in the ZO rats (10−6 M: 10 ± 3%) compared with ZLs (29 ± 7%, P < 0.01). These findings indicate that vasoconstrictor responses of the BA mediated by ET-1, TxA2, PKC, and Rho-kinase are not affected by IR.
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Zhang, Xiaojie, Qiaoqiao Zhao, and Ying Huang. "Partitioning of the Nuclear and Mitochondrial tRNA 3′-End Processing Activities between Two different Proteins in Schizosaccharomyces pombe." Journal of Biological Chemistry 288, no. 38 (August 8, 2013): 27415–22. http://dx.doi.org/10.1074/jbc.m113.501569.
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tRNase Z is an essential endonuclease responsible for tRNA 3′-end maturation. tRNase Z exists in a short form (tRNase ZS) and a long form (tRNase ZL). Prokaryotes have only tRNase ZS, whereas eukaryotes can have both forms of tRNase Z. Most eukaryotes characterized thus far, including Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and humans, contain only one tRNase ZL gene encoding both nuclear and mitochondrial forms of tRNase ZL. In contrast, Schizosaccharomyces pombe contains two essential tRNase ZL genes (trz1 and trz2) encoding two tRNase ZL proteins, which are targeted to the nucleus and mitochondria, respectively. Trz1 protein levels are notably higher than Trz2 protein levels. Here, using temperature-sensitive mutants of trz1 and trz2, we provide in vivo evidence that trz1 and trz2 are involved in nuclear and mitochondrial tRNA 3′-end processing, respectively. In addition, trz2 is also involved in generation of the 5′-ends of other mitochondrial RNAs, whose 5′-ends coincide with the 3′-end of tRNA. Thus, our results provide a rare example showing partitioning of the nuclear and mitochondrial tRNase ZL activities between two different proteins in S. pombe. The evolution of two tRNase ZL genes and their differential expression in fission yeast may avoid toxic off-target effects.
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Ghose, Biswajit, and Kailash Chandra Kabra. "What determines firms’ zero-leverage policy in India?" Managerial Finance 42, no. 12 (December 5, 2016): 1138–58. http://dx.doi.org/10.1108/mf-01-2016-0029.
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Purpose This paper studies the relationship between characteristics of firms’ and their propensity to maintain zero-leverage (ZL). Its second objective is to examine the impact of macroeconomic conditions on firms’ ZL policy. Finally, the purpose of this paper is to explore the underlying motives behind eschewing debt for constrained and unconstrained firms. Design/methodology/approach The paper uses data of 2001 non-financial and non-utility listed Indian firms over a period of 2005-2013 from Capitaline database. Size quintiles and dividend payment status have been used to differentiate between constrained and unconstrained firms. It uses t-test and logistic regression to draw inferences. Findings In general, firms pursuing ZL policy are financially constrained. However, there is a sub-section of ZL firms found unconstrained with high profitability. They appear to be “self-sufficient” to meet their financing requirements. Finally, macroeconomic conditions are counter cyclically related to firms’ ZL policy. Research limitations/implications The impact of corporate governance practices on firms’ ZL policy could not be examined due to data inadequacy. However, financial constraints and the presence of ZL firms come out as important factors to be paid special attention for future empirical works on capital structure. Practical implications The findings can be useful for financial managers in designing capital structure on the basis of their financial position. Originality/value Previous studies on ZL phenomenon are based on developed countries. The findings of previous studies conducted for developed countries get revalidated for the first time in the context of an emerging economy like India.
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Katakam, Prasad V. G., James E. Jordan, James A. Snipes, Christina D. Tulbert, Allison W. Miller, and David W. Busija. "Myocardial preconditioning against ischemia-reperfusion injury is abolished in Zucker obese rats with insulin resistance." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 292, no. 2 (February 2007): R920—R926. http://dx.doi.org/10.1152/ajpregu.00520.2006.
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Insulin resistance (IR) precedes the onset of Type 2 diabetes, but its impact on preconditioning against myocardial ischemia-reperfusion injury is unexplored. We examined the effects of diazoxide and ischemic preconditioning (IPC; 5-min ischemia and 5-min reperfusion) on ischemia (30 min)-reperfusion (240 min) injury in young IR Zucker obese (ZO) and lean (ZL) rats. ZO hearts developed larger infarcts than ZL hearts (infarct size: 57.3 ± 3% in ZO vs. 39.2 ± 3.2% in ZL; P < 0.05) and also failed to respond to cardioprotection by IPC or diazoxide (47.2 ± 4.3% and 52.5 ± 5.8%, respectively; P = not significant). In contrast, IPC and diazoxide treatment reduced the infarct size in ZL hearts (12.7 ± 2% and 16.3 ± 6.7%, respectively; P < 0.05). The mitochondrial ATP-activated potassium channel (KATP) antagonist 5-hydroxydecanoic acid inhibited IPC and diazoxide-induced preconditioning in ZL hearts, whereas it had no effect on ZO hearts. Diazoxide elicited reduced depolarization of isolated mitochondria from ZO hearts compared with ZL (73 ± 9% in ZL vs. 39 ± 9% in ZO; P < 0.05). Diazoxide also failed to enhance superoxide generation in isolated mitochondria from ZO compared with ZL hearts. Electron micrographs of ZO hearts revealed a decreased number of mitochondria accompanied by swelling, disorganized cristae, and vacuolation. Immunoblots of mitochondrial protein showed a modest increase in manganese superoxide dismutase in ZO hearts. Thus obesity accompanied by IR is associated with the inability to precondition against ischemic cardiac injury, which is mediated by enhanced mitochondrial oxidative stress and impaired activation of mitochondrial KATP.
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Konno, Hiroyasu, Tracey Lin, Bee-Chun Sun, Renyi Wu, Christopher Szeto, David Bellovin, Karl Hsu, and Omar Kabbarah. "Abstract 621: ZL-1211 exhibits robust anti-tumor activity by enhancing ADCC and activating innate and adaptive immunity in CLDN18.2-high and -low expressing gastric cancer models." Cancer Research 82, no. 12_Supplement (June 15, 2022): 621. http://dx.doi.org/10.1158/1538-7445.am2022-621.
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Abstract CLDN18.2 (Claudin18.2)-targeting therapeutic antibodies have shown promising clinical efficacy in ~30% of gastric cancers expressing high levels of CLDN18.2 and less pronounced activity in the majority of low expressing malignancies. ZL-1211 is a monoclonal antibody targeting CLDN18.2 engineered to promote enhanced ADCC with the goal of achieving more potent activity in a wider spectrum of high- and low-CLDN18.2 expressing tumors than the leading clinical benchmark. To further assess the potency of ZL-1211, we utilized a panel of gastric tumor cell lines that endogenously express CLDN18.2 and more accurately reflect target levels in human gastric tumors than engineered overexpressing models. ZL-1211 demonstrated more robust in vitro ADCC activity than clinical benchmark not only in CLDN18.2-high but also -low expressing gastric cell lines. Greater anti-tumor efficacy was also observed in mouse xenograft models with CLDN18.2-high, -medium, and low-expressing gastric cell lines in response to treatment with ZL-1211 compared to the clinical benchmark. NK cell depletion abrogated ZL-1211-mediated ADCC activity in vitro. ZL-1211 efficacy in vivo was also dependent on the presence of an NK compartment, as CLDN18.2-expressing gastric tumors grown in Balb/c nude with an intact NK function were sensitive to ZL-1211 treatment, while NOD-SCID with partially competent NK activity exhibited minimal response, and NCG without NK cells did not display any evidence of in vivo efficacy. Strikingly, NK cells strongly induced an inflammatory response in response to ZL-1211 treatment, including increased IFNγ, TNFα, and IL-6 production. Interestingly, ZL-1211 treatment led to NK cell and monocyte stimulation and enhanced CD8+ T cell activation, suggesting a mechanism of action that not only involves innate but also adaptive immunity. Taken together, our data suggest that ZL-1211 more effectively targets CLDN18.2-high gastric cancers as well as -low expressing malignancies that are not eligible for treatment with the leading clinical benchmark by inducing a robust ADCC response and activating innate and adaptive immunity to enhance anti-tumor efficacy. Clinical activity of ZL-1211 is currently under evaluation in a Phase I clinical trial (NCT05065710). Citation Format: Hiroyasu Konno, Tracey Lin, Bee-Chun Sun, Renyi Wu, Christopher Szeto, David Bellovin, Karl Hsu, Omar Kabbarah. ZL-1211 exhibits robust anti-tumor activity by enhancing ADCC and activating innate and adaptive immunity in CLDN18.2-high and -low expressing gastric cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 621.
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Song, Guanzheng, Zhongguo Li, Yanbing Han, Jidong Jia, Wenfa Zhou, Xueru Zhang, Yuxiao Wang, and Yinglin Song. "Enhancement of Two-Photon Absorption in Boron-Dipyrromethene (BODIPY) Derivatives." Molecules 27, no. 9 (April 29, 2022): 2849. http://dx.doi.org/10.3390/molecules27092849.
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The linear and nonlinear optical properties of two BODIPY derivatives, 1,7-Diphenyl-3,5-bis(9,9-dimethyl-9H-fluoren-2-yl)-boron-diuoride-azadipyrromethene (ZL-61) and 1,7-Diphenyl-3,5-bis(4-(1,2,2-triphenylvinyl)phenyl)-boron-diuoride-azadipyrromethene (ZL-22), were comprehensively investigated based on experimental and theoretical studies. It was found that both compounds show a strong two-photon absorption response in the near-infrared regime, and the two-photon-absorption cross-section values of ZL-61 and ZL-22 were determined to be 8321 GM and 1864 GM at 800 nm, respectively. The improvement of the two-photon absorption cross section in ZL-61 was attributed to the enhancement of the donor group, which was confirmed by transient absorption measurements and DFT calculation. Our results indicate that these BODIPY derivatives are a promising candidate for optical limiting and two-photon imaging applications.
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Belenchia, Anthony M., Madhavi P. Gavini, Ryan G. Toedebusch, Vincent G. DeMarco, and Lakshmi Pulakat. "Comparison of Cardiac miRNA Transcriptomes Induced by Diabetes and Rapamycin Treatment and Identification of a Rapamycin-Associated Cardiac MicroRNA Signature." Oxidative Medicine and Cellular Longevity 2018 (December 17, 2018): 1–18. http://dx.doi.org/10.1155/2018/8364608.
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Rapamycin (Rap), an inhibitor of mTORC1, reduces obesity and improves lifespan in mice. However, hyperglycemia and lipid disorders are adverse side effects in patients receiving Rap treatment. We previously reported that diabetes induces pansuppression of cardiac cytokines in Zucker obese rats (ZO-C). Rap treatment (750 μg/kg/day for 12 weeks) reduced their obesity and cardiac fibrosis significantly; however, it increased their hyperglycemia and did not improve their cardiac diastolic parameters. Moreover, Rap treatment of healthy Zucker lean rats (ZL-C) induced cardiac fibrosis. Rap-induced changes in ZL-C’s cardiac cytokine profile shared similarities with that of diabetes-induced ZO-C. Therefore, we hypothesized that the cardiac microRNA transcriptome induced by diabetes and Rap treatment could share similarities. Here, we compared the cardiac miRNA transcriptome of ZL-C to ZO-C, Rap-treated ZL (ZL-Rap), and ZO (ZO-Rap). We report that 80% of diabetes-induced miRNA transcriptome (40 differentially expressed miRNAs by minimum 1.5-fold in ZO-C versus ZL-C; p≤0.05) is similar to 47% of Rap-induced miRNA transcriptome in ZL (68 differentially expressed miRNAs by minimum 1.5-fold in ZL-Rap versus ZL-C; p≤0.05). This remarkable similarity between diabetes-induced and Rap-induced cardiac microRNA transcriptome underscores the role of miRNAs in Rap-induced insulin resistance. We also show that Rap treatment altered the expression of the same 17 miRNAs in ZL and ZO hearts indicating that these 17 miRNAs comprise a unique Rap-induced cardiac miRNA signature. Interestingly, only four miRNAs were significantly differentially expressed between ZO-C and ZO-Rap, indicating that, unlike the nondiabetic heart, Rap did not substantially change the miRNA transcriptome in the diabetic heart. In silico analyses showed that (a) mRNA-miRNA interactions exist between differentially expressed cardiac cytokines and miRNAs, (b) human orthologs of rat miRNAs that are strongly correlated with cardiac fibrosis may modulate profibrotic TGF-β signaling, and (c) changes in miRNA transcriptome caused by diabetes or Rap treatment include cardioprotective miRNAs indicating a concurrent activation of an adaptive mechanism to protect the heart in conditions that exacerbate diabetes.
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Wang, Lixia, Wei Ren, Li Wang, Linshen Mao, Maryam Mazhar, Chen Zhou, Houping Xu, and Sijin Yang. "Exploring the Ferroptosis Mechanism of Zhilong Huoxue Tongyu Capsule for the Treatment of Intracerebral Hemorrhage Based on Network Pharmacology and In Vivo Validation." Evidence-Based Complementary and Alternative Medicine 2022 (September 25, 2022): 1–13. http://dx.doi.org/10.1155/2022/5033135.
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Objective. The purpose of this study is to explore the mechanism of the Zhilong Huoxue Tongyu (ZL) capsule in the treatment of intracerebral hemorrhage (ICH) via targeting ferroptosis based on network pharmacology. Methods. The active ingredients and related key targets of the ZL capsule were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were also performed. Finally, identified targets were validated in an in-vivo model of ICH. Results. A total of 30 active ingredients and 33 intersecting targets were identified through a TCMSP database search. Ingredients-Targets-Pathways network was constructed to filter out the key targets according to the degree value. TP53 was selected as the key target. The in-vivo validation studies demonstrated that TP53 was down-regulated and GPX4 was upregulated in rats following ZL capsule treatment. Conclusions. It is concluded that the ZL capsule could alleviate ICH in a muti-target and multi-pathway manner. ZL capsule could alleviate ICH by inhibiting ferroptosis, and TP53 is identified to be the potential target. Further research is needed to clarify the detailed anti-ferroptotic mechanism of the ZL capsule.
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Luck, Christian, Vincent G. DeMarco, Abuzar Mahmood, Madhavi P. Gavini, and Lakshmi Pulakat. "Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats." Oxidative Medicine and Cellular Longevity 2017 (2017): 1–17. http://dx.doi.org/10.1155/2017/5724046.
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Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1). However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750 μg/kg/day) modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL) and diabetic obese Zucker (ZO) rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters (E/E′,E′/A′,E/Vp) initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFNγ, and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes.
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LaBranche, Timothy P., Anna K. Kopec, Srinivasa R. Mantena, Brett D. Hollingshead, Andrew W. Harrington, Zachary S. Stewart, Yutian Zhan, et al. "Zucker Lean Rats With Hepatic Steatosis Recapitulate Asymptomatic Metabolic Syndrome and Exhibit Greater Sensitivity to Drug-Induced Liver Injury Compared With Standard Nonclinical Sprague-Dawley Rat Model." Toxicologic Pathology 48, no. 8 (November 28, 2020): 994–1007. http://dx.doi.org/10.1177/0192623320968716.
Full textAbstract:
Fatty liver disease is a potential risk factor for drug-induced liver injury (DILI). Despite advances in nonclinical in vitro and in vivo models to assess liver injury during drug development, the pharmaceutical industry is still plagued by idiosyncratic DILI. Here, we tested the hypothesis that certain features of asymptomatic metabolic syndrome (namely hepatic steatosis) increase the risk for DILI in certain phenotypes of the human population. Comparison of the Zucker Lean (ZL) and Zucker Fatty rats fed a high fat diet (HFD) revealed that HFD-fed ZL rats developed mild hepatic steatosis with compensatory hyperinsulinemia without increases in liver enzymes. We then challenged steatotic HFD-fed ZL rats and Sprague-Dawley (SD) rats fed normal chow, a nonclinical model widely used in the pharmaceutical industry, with acetaminophen overdose to induce liver injury. Observations in HFD-fed ZL rats included increased liver injury enzymes and greater incidence and severity of hepatic necrosis compared with similarly treated SD rats. The HFD-fed ZL rats also had disproportionately higher hepatic drug accumulation, which was linked with abnormal hepatocellular efflux transporter distribution. Here, we identify ZL rats with HFD-induced hepatic steatosis as a more sensitive nonclinical in vivo test system for modeling DILI compared with SD rats fed normal chow.
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Abduljawad, Suha Hashim. "Digestive Fermentation, Antioxidant Status, and Haemato-Biochemical Indices of Growing Rabbits Fed on Diets Supplemented with Ziziphus spina-christi Leaf." Journal of Nutrition and Metabolism 2020 (March 31, 2020): 1–6. http://dx.doi.org/10.1155/2020/9046862.
Full textAbstract:
The objective of the study was to assess the effect of diets supplemented with Ziziphus spina-christi leaf on digestive fermentation, antioxidant status, and haemato-biochemical indices of growing rabbits. Ziziphus leaves (ZLs) of Ziziphus spina-christi were collected from Sidr trees scattered throughout the city of Medina, Saudi Arabia. Three formulated diets containing 0, 10, and 20 g Ziziphus spina-christi/Kg diet as supplementation were offered ad libitum. The organic matter content of ZL was higher. Chemical compositions were comparable in all of the contents of the tested diet. Quantities of gas released from the control diet were higher, and then the gases released decreased significantly (P<0.05) with the addition of ZL. The values of NH3-N were taken as the same trend. The addition of a high level of ZL to rabbit diets led to a decrease (P<0.05) in the total count of bacteria as well as the number of E. coli and Clostridium spp. However, the number of Enterococcus bacteria was not affected by supplementation. Haemoglobin parameters of the control group and groups 2 and 3 were compared: white blood cell count and red blood cell count. These observations of total protein and albumin within the range of reference values were reported in healthy rabbits, while glucose significantly decreased with the addition of ZL and AST in the blood increased significantly. The values of TP, albumin, and ALT measurements showed no significant differences among groups fed on test diets. Significant differnces in serum immunoglobulins were observed between the groups, while the high levels of ZL supplement led to a significant (P<0.05) increase in the serum IgA, IgG, and IgM levels. Antioxidants expressed as T-AOC, GSH-Px, T-SOD, and CAT in the blood of animals fed on diets containing high levels of ZL were significantly higher. Higher serum T-AOC, T-SOD, and CAT activities were observed in rabbits supplemented with a high level of ZL compared with the control group (P<0.05). The supplementation of ZL tended to increase serum GSH-Px activity. The addition of ZL to rabbit diets led to an increase in dry matter intake. On the other hand, there was no significant change in the apparent digestion coefficient of DM, OM, CP, and fat. Conclusion. Dried ZL supplementation up to 20 g/Kg diet might improve the bacterial community, antioxidants, biochemical parameters and blood constituents of rabbits, and digestibility.
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Hantos, Z., A. Adamicza, E. Govaerts, and B. Daroczy. "Mechanical impedances of lungs and chest wall in the cat." Journal of Applied Physiology 73, no. 2 (August 1, 1992): 427–33. http://dx.doi.org/10.1152/jappl.1992.73.2.427.
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In nine anesthetized and paralyzed cats, the mechanical impedances of the total respiratory system (Zrs) and the lungs (ZL) were measured with small-volume pseudorandom forced oscillations between 0.2 and 20 Hz. ZL was measured after thoracotomy, and chest wall impedance (Zw) was calculated as Zw = Zrs-ZL. All impedances were determined by using input airflow [input impedance (Zi)] and output flow measured with a body box [transfer impedance (Zt)]. The differences between Zi and Zt were small for Zrs and negligible for ZL. At 0.2 Hz, the real and imaginary parts of ZL amounted to 33 +/- 4 and 35 +/- 3% (SD), respectively, of Zrs. Up to 8 Hz, all impedances were consistent with a model containing a frequency-independent resistance and inertance and a constant-phase tissue part (G-jH)/omega alpha, where G and H are coefficients for damping and elastance, respectively, omega is angular frequency, and alpha determines the frequency dependence of the real and imaginary parts. G/H was higher for Zw than for ZL (0.29 +/- 0.05 vs. 0.22 +/- 0.04, P less than 0.01). In four cats, the amplitude dependence of impedances was studied: between oscillation volumes of 0.8 and 3 ml, GL, HL, Gw, and Hw decreased on average by 3, 9, 26, and 29%, respectively, whereas the change in G/H was small for both ZL (7%) and Zw (-4%). The values of H were two to three times higher than the quasistatic elastances estimated with greater volume changes (greater than 20 ml).
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Hazarika, Doli, Naba Kumar Kalita, Amit Kumar, and Vimal Katiyar. "Functionalized poly(lactic acid) based nano-fabric for anti-viral applications." RSC Advances 11, no. 52 (2021): 32884–97. http://dx.doi.org/10.1039/d1ra05352c.
Full textAbstract:
PLA based electrospun nanofabric prepared using ZL and SNC. Incorporation of SNC conferred hydrophobicity. Breathable and reusable nanofabric. PLA/ZL nanofabric demonstrated significant antibacterial & antiviral properties.
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Puspitasari, Tita, Moh Mualliful Ilmi, Nadya Nurdini, Rino R. Mukti, Cynthia L. Radiman, Darmawan Darwis, and Grandprix Thomryes Marth Kadja. "The Physicochemical Characteristics of Natural Zeolites Governing the Adsorption of Pb2+ from Aqueous Environment." Key Engineering Materials 811 (July 2019): 92–98. http://dx.doi.org/10.4028/www.scientific.net/kem.811.92.
Full textAbstract:
The aim of this study is to investigate the effect of natural zeolites characteristics on the adsorption capacity of Pb2+ from an aqueous environment. The used natural zeolites were originated from 3 regions in Indonesia. i.e. Bayah, Banten (coded as ZB) and two samples from South Lampung (coded as ZL-1 and ZL-2) and Nanggung, Bogor (ZN). The characteristics of each natural zeolite were evaluated through a series of detailed analysis including XRD, FTIR, XRF, SEM and N2 physisorption. It was revealed that ZB, ZL-1 and ZL-2 were dominated by clinoptilolite (HEU) frameworks while the major phase of ZN was mordenite (MOR) type. From XRF data, the three natural zeolites (ZB, ZL-1 and ZN) possessed a comparable Si/Al ratio (ca. 5.5 to 6) whereas ZL-2 had slightly lower Si/Al ratio (ca. 4). We found that, at comparable Si/Al ratio, clinoptilolite frameworks has a higher adsorption capacity of Pb2+ compared to that of mordenite due to the compatibility of Pb2+ inside the pores of clinoptilolite. Lower Si/Al ratio of natural zeolite tended to show higher adsorption capacity of Pb2+ since the net charge of zeolite frameworks became more negative. These two factors, the framework type and the Si/Al ratio, are significant for the adsorption capacity. Another factor, i.e. surface area, had no certain effect on the adsorption capacity in this case.
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Haynes, Johnson, B. Surendra Baliga, Boniface Obiako, Solomon Ofori-Acquah, and Betty Pace. "Zileuton induces hemoglobin F synthesis in erythroid progenitors: role of the l-arginine–nitric oxide signaling pathway." Blood 103, no. 10 (May 15, 2004): 3945–50. http://dx.doi.org/10.1182/blood-2003-08-2969.
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Abstract Induction of fetal hemoglobin (Hb F) is an important therapeutic tool in ameliorating complications of sickle cell disease. Nitric oxide has been implicated in the mechanism of Hb F synthesis induced by hydroxyurea (HU). This study examined whether zileuton (ZL), a structural analog of hydroxyurea, possessed Hb F–inducing properties and the potential role nitric oxide plays. ZL caused a dose-dependent increase in γ-globin expression in K562 cells. This effect was confirmed by a dose-dependent increase in Hb F synthesis in erythroid progenitors from individuals with sickle cell anemia and normal hemoglobin genotypes. l-arginine had no effect on Hb F production; however, it dose-dependently inhibited ZL's ability to induce Hb F. The nitric oxide synthase inhibitor NG-monomethyl–l-arginine (l-NMMA) inhibited l-arginine's effect and restored ZL-mediated increase in Hb F synthesis. In addition, 8-PCPT–cGMP (8-(4-chlorophenylthio)guanosine 3′,5′-cyclic monophosphate) inhibited ZL-mediated induction of Hb F synthesis. When comparing l-NMMA effects alone on ZL and HU, a partial reversal of increased Hb F synthesis was seen only with HU. Neither l-arginine alone nor l-arginine in combination with l-NMMA effected hydroxyurea-mediated induction of Hb F synthesis. This study demonstrates that ZL induces Hb F through a mechanism that involves l-arginine/nitric oxide/cGMP in a manner distinctly different from HU.
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Bruce, Clinton R., Jong Sam Lee, and John A. Hawley. "Postexercise muscle glycogen resynthesis in obese insulin-resistant Zucker rats." Journal of Applied Physiology 91, no. 4 (October 1, 2001): 1512–19. http://dx.doi.org/10.1152/jappl.2001.91.4.1512.
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We determined the effect of an acute bout of swimming (8 × 30 min) followed by either carbohydrate administration (0.5 mg/g glucose ip and ad libitum access to chow; CHO) or fasting (Fast) on postexercise glycogen resynthesis in soleus muscle and liver from female lean (ZL) and obese insulin-resistant (ZO) Zucker rats. Resting soleus muscle glycogen concentration ([glycogen]) was similar between genotypes and was reduced by 73 (ZL) and 63% (ZO) after exercise ( P < 0.05). Liver [glycogen] at rest was greater in ZO than ZL (334 ± 31 vs. 247 ± 16 μmol/g wet wt; P < 0.01) and fell by 44 and 94% after exercise ( P < 0.05). The fractional activity of glycogen synthase (active/total) increased immediately after exercise (from 0.22 ± 0.05 and 0.32 ± 0.04 to 0.63 ± 0.08 vs. 0.57 ± 0.05; P < 0.01 for ZL and ZO rats, respectively) and remained elevated above resting values after 30 min of recovery. During this time, muscle [glycogen] in ZO increased 68% with CHO ( P < 0.05) but did not change in Fast. Muscle [glycogen] was unchanged in ZL from postexercise values after both treatments. After 6 h recovery, GLUT-4 protein concentration was increased above resting levels by a similar extent for both genotypes in both fasted (∼45%) and CHO-supplemented (∼115%) rats. Accordingly, during this time CHO refeeding resulted in supercompensation in both genotypes (68% vs. 44% for ZL and ZO). With CHO, liver [glycogen] was restored to resting levels in ZL but remained at postexercise values for ZO after both treatments. We conclude that the increased glucose availability with carbohydrate refeeding after glycogen-depleting exercise resulted in glycogen supercompensation, even in the face of muscle insulin-resistance.
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Nashimoto, Masayuki. "TRUE Gene Silencing." International Journal of Molecular Sciences 23, no. 10 (May 11, 2022): 5387. http://dx.doi.org/10.3390/ijms23105387.
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TRUE gene silencing is an RNA-mediated gene expression control technology and is termed after tRNase ZL-utilizing efficacious gene silencing. In this review, I overview the potentiality of small guide RNA (sgRNA) for TRUE gene silencing as novel therapeutics. First, I describe the physiology of tRNase ZL and cellular small RNA, and then sgRNA and TRUE gene silencing. An endoribonuclease, tRNase ZL, which can efficiently remove a 3′ trailer from pre-tRNA, is thought to play the role in tRNA maturation in the nucleus and mitochondria. There exist various small RNAs including miRNA and fragments from tRNA and rRNA, which can function as sgRNA, in living cells, and human cells appear to be harnessing cytosolic tRNase ZL for gene regulation together with these small RNAs. By utilizing the property of tRNase ZL to recognize and cleave micro-pre-tRNA, a pre-tRNA-like or micro-pre-tRNA-like complex, as well as pre-tRNA, tRNase ZL can be made to cleave any target RNA at any desired site under the direction of an artificial sgRNA that binds a target RNA and forms the pre-tRNA-like or micro-pre-tRNA-like complex. This general RNA cleavage method underlies TRUE gene silencing. Various examples of the application of TRUE gene silencing are reviewed including the application to several human cancer cells in order to induce apoptosis. Lastly, I discuss the potentiality of sgRNA as novel therapeutics for multiple myeloma.
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Cao, Anthony, Jiaqing Yi, Renyi Wu, Christopher Szeto, Quiping Ye, Bing Wan, Karl Hsu, Omar Kabbarah, and Haiying Zhou. "Abstract 3425: The CD47-targeting antibody ZL-1201 enhances anti-tumor activity of standard of care therapeutic antibodies by promoting phagocytosis in hematologic and solid tumor models." Cancer Research 82, no. 12_Supplement (June 15, 2022): 3425. http://dx.doi.org/10.1158/1538-7445.am2022-3425.
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Abstract Therapeutic monoclonal antibodies (mAbs) comprise the standard of care (SoC) for several hematologic and solid cancer indications. These include rituximab for CD20-expressing lymphomas, trastuzumab for HER2-amplified cancers, and cetuximab for EGFR-driven solid tumors. Although the primary mechanism of action for these therapies is tumor-cell targeting, they are rarely curative, partly because tumor cells employ a variety of mechanisms to evade immune surveillance and blunt anti-tumor immune response. CD47 is upregulated in solid tumors and hematological malignancies and provides a critical anti-phagocytic signal to escape destruction by the innate immune system. Thus, CD47 may represent a promising therapeutic target for activating innate and adaptive immunity and enhancing the therapeutic potential of SoC antibodies in the clinic. Here we present preclinical data supporting the combinatorial effects of the CD47-targeting monoclonal antibody ZL-1201 with SoC mAbs in hematologic and solid tumor models. ZL-1201 potently blocked CD47/SIRPα interaction and enhanced phagocytosis as measured by flow cytometry and high-content imaging analysis. Notably, in combination with trastuzumab, cetuximab, and rituximab, ZL-1201 demonstrated enhanced phagocytosis across hematologic and solid tumor models expressing varying levels of CD47 in in vitro co-culture systems. Neutralizing the Fc receptor function of these SoC mAbs by blocking CD16, CD32, and CD64 abrogated the combinatorial effects, indicating that the CD47 blockade sensitized tumors to pro-phagocytic signals provided by ADCP-inducing mAbs in an Fc receptor-dependent manner. Treatment of xenografts with ZL-1201 also drove tumor-specific immune responses and remodeling of the tumor microenvironment, including increased activation of antigen-presenting cells, decreased frequencies of MDSC, and reduced expression of immune checkpoints such as PD-L1. Further, ZL-1201 in combination with trastuzumab, rituximab, or cetuximab significantly delayed tumor growth and increased survival in in vivo xenograft models, highlighting the pivotal role for CD47 as a resistance mechanism to these therapeutic mAbs and the opportunity to overcome resistance with ZL-1201 combination. In conclusion, ZL-1201 enhances the anti-tumor activity of SoC antibodies and augments the immunologic response by overcoming the CD47/SIRPα “don’t-eat-me” myeloid checkpoint. This study indicates that ZL-1201 may combine with a broad range of SoC mAbs to enhance their clinical benefit across a variety of hematologic and solid tumor indications. ZL-1201 is under Ph1 clinical investigation (NCT04257617). Citation Format: Anthony Cao, Jiaqing Yi, Renyi Wu, Christopher Szeto, Quiping Ye, Bing Wan, Karl Hsu, Omar Kabbarah, Haiying Zhou. The CD47-targeting antibody ZL-1201 enhances anti-tumor activity of standard of care therapeutic antibodies by promoting phagocytosis in hematologic and solid tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3425.
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Makni, Mohamed, Raoua Jemai, Walid Kriaa, Yassine Chtourou, and Hamadi Fetoui. "Citrus limon from Tunisia: Phytochemical and Physicochemical Properties and Biological Activities." BioMed Research International 2018 (2018): 1–10. http://dx.doi.org/10.1155/2018/6251546.
Full textAbstract:
Natural plant extracts contain a variety of phenolic compounds which are assigned various biological activities. Our work aims to make a quantitative and qualitative characterization of the Zest (ZL) and the Flesh (FL) of lemon (Citrus limon), to valorize the pharmacological uses of lemon, by evaluating in vitro activities (DPPH, free radical scavenging and reducing power). The antibacterial, antifungal, and antiproliferative activities were sought in the ability of Citrus limon extracts to protect DNA and protein. We found that the ZL contains high amounts of phenolics responsible for the important antioxidant properties of the extract. However, the FL is richer in flavonoids than the ZL. The FL extract was also found to be more effective than the ZL in protecting plasmid DNA against the strand breakage induced by hydroxyl radicals. We also concluded that the FL extract exhibited potent antibacterial activity unlike ZL. Analysis by LC/MS-MS identified 6 compounds (Caffeoyl N-Tryptophan, Hydroxycinnamoyl-Oglucoside acid, Vicenin 2, Eriocitrin, Kaempferol-3-O- rutinoside, and Quercetin-3-rutinoside). These preliminary results showed that Citrus limon has antibacterial and antioxidant activity in vitro. It would be interesting to conduct further studies to evaluate the in vivo potential in an animal model.
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Takimoto, Kohji, Shuji Matsuura, Kei Sano, and Richard M. Feder. "Near-infrared Polarization Charateristics of the Zodiacal Light Observed with DIRBE/COBE." Astrophysical Journal 944, no. 2 (February 1, 2023): 229. http://dx.doi.org/10.3847/1538-4357/acb937.
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Abstract We report near-infrared polarization of the zodiacal light (ZL) measured from space by the Diffuse Infrared Background Experiment (DIRBE) on board the Cosmic Background Explorer in photometric bands centered at 1.25, 2.2, and 3.5 μm. To constrain the physical properties of interplanetary dust, we use DIRBE Weekly Sky Maps to investigate the solar elongation (ϵ), ecliptic latitude (β), and wavelength (λ) dependence of ZL polarization. We find that the polarization of the ZL varies as a function of ϵ and β, consistent with observed polarization at λ = 550 nm. While the polarization dependence on wavelength at (ϵ, β) = (90°, 0°) is modest (increasing from 17.7% ± 0.2% at 1.25% μm to 21.0% ± 0.3% at 3.5 μm), the variation is more pronounced at the north ecliptic pole (23.1% ± 1.6%, 35.1% ± 2.0%, and 39.3% ± 2.1% at 1.25, 2.2, and 3.5 μm, respectively). The variation in ZL polarization with wavelength is not explained by either Rayleigh scattering or absorptive particles larger than 10 μm.
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Eiymo Mwa Mpollo, Marthe-Sandrine, Maa-Ohui Quarmyne, Omar Rayes, Caryn S. Gonsalves, Laurie Vanderah, Christina Canter, Johnson Haynes, et al. "A Phase I Trial Of Zileuton In Sickle Cell Disease." Blood 122, no. 21 (November 15, 2013): 993. http://dx.doi.org/10.1182/blood.v122.21.993.993.
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Abstract Sickle cell disease (SCD) is associated with a high prevalence of airway hyperreactivity (AHR) and chronic inflammation at a steady state in the absence of infection or acute sickle events; SCD patients have also been reported to have increased circulating leukotrienes (LT) (Setty et al, 2002; Jennings et al, 2008): both the pro-inflammatory LT-B4 and cysteinyl leukotrienes (cys-LTs; LT-C4, -D4 and -E4), known to promote AHR. We sought to explore the mechanisms of increased AHR in SCD. Five-lipoxygenase (5LO) is a key enzyme in LT-B4 and cysLT synthesis, we have recently reported that expression of 5LO is significantly increased in blood mononuclear cells (MNCs) in patients with SCD (Patel et al 2009). Zileuton is a specific inhibitor of 5LO that decreases LT production, is licensed for asthma and is now available in BID dosing (Zyflo CR, Cornerstone Therapeutics), but has never been tested in patients with SCD. We performed a phase 1 clinical trial to determine the safety and pharmacodynamics (PK) of twice daily administration of ZL (Zyflo CR, the study drug was provided by Cornerstone Therapeutics) in patients with SCD after obtaining an IND from the FDA. The primary objective of this study was to determine a safe and tolerable dose of ZL using a 3x3 dose escalation design of twice daily ZL for 6 weeks, with monitoring of blood counts, serum and urine chemistries, echo, EKG and clinical events. Patients 7-30 years of age with SCD at steady state that were not on hydroxyurea or chronic transfusions were enrolled. A total of 14 subjects were consented and screened for the ZL trial; 4 failed screening and 11 subjects received the study drug; 2 subjects were withdrawn due to acute sickle events. The 1200 mg BID dose that is approved for asthma was well tolerated by 3 patients; the dose was then escalated to 3000 mg/day. We found that 1800 mg alternating with 1200 mg of ZL was a safe and clinically well tolerated dose in 6 patients. No clinically significant changes of any of the clinical/laboratory safety parameters were observed from baseline values that were attributable to ZL. PK, another primary objective of this study was performed using a D-optimal sampling strategy (day 1 through week 6) and data analyzed by nonlinear mixed effects modeling (NONMEM). ZL plasma concentrations were determined by validated LC-MS/MS assay. The Cmax of ZL were 2445 ± 795 ng/ml and 2510 ± 489 ng/ml at 2400 mg/d and 3000 mg/d and the minimum zileuton exposure as measured by predose troughs were 445.0 ± 137.7 ng/ml and 703.7 ± 172.2 ng/ml at 2400 mg/d and 3000 mg/d respectively. PK details will be presented. The secondary objective was to determine the pharmacodynamics (PD) of ZL in patients with SCD. PD end points were 1. CysLT levels before and after ZL administration for 6 weeks, 2. circulating levels of inflammatory biomarkers: sVCAM, sICAM, IL-6, IL-13 and macrophage chemoattractant protein-1 (MCP-1), 3. Methacholine challenge test (MCT) for AHR and 4. fetal hemoglobin. MCT was negative in 5 of 9 of patients; It is to be noted that exclusion of patients on hydroxyurea and chronic transfusions excluded the majority of patients with moderate to severe SCD that predominantly have AHR; 4 patients had a positive MCT, 2 of them became negative after receiving ZL while there was no change in the other 2 patients. LT and inflammatory markers are under analysis. There was no increase in HbF, F cells/F-retics in any of the patients, unlike results reported in vitro in erythroid cultures (Haynes et al, Blood 2004). Our study shows the safety and PK of ZL in SCD and that a higher dose of ZL (than used for asthma) was safely tolerated by SCD patients with good compliance. This phase I trial may form the basis of a phase II/III trial of zileuton in SCD. Clinicaltrial.gov # NCT01136941. Disclosures: No relevant conflicts of interest to declare.
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Katakam, Prasad V. G., James A. Snipes, Christina D. Tulbert, Keita Mayanagi, Allison W. Miller, and David W. Busija. "Impaired endothelin-induced vasoconstriction in coronary arteries of Zucker obese rats is associated with uncoupling of [Ca2+]i signaling." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 290, no. 1 (January 2006): R145—R153. http://dx.doi.org/10.1152/ajpregu.00405.2005.
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Although insulin resistance (IR) is a major risk factor for coronary artery disease, little is known about the regulation of coronary vascular tone in IR by endothelin-1 (ET-1). We examined ET-1 and PGF2α-induced vasoconstriction in isolated small coronary arteries (SCAs; ∼250 μM) of Zucker obese (ZO) rats and control Zucker lean (ZL) rats. ET-1 response was assessed in the absence and presence of endothelin type A (ETA; BQ-123), type B (ETB; BQ-788), or both receptor inhibitors. ZO arteries displayed reduced contraction to ET-1 compared with ZL arteries. In contrast, PGF2α elicited similar vasoconstriction in both groups. ETA inhibition diminished the ET-1 response in both groups. ETB inhibition alone or in combination with ETA blockade, however, restored the ET-1 response in ZO arteries to the level of ZL arteries. Similarly, inhibition of endothelial nitric oxide (NO) synthase with Nω-nitro-l-arginine methyl ester (l-NAME) enhanced the contraction to ET-1 and abolished the difference between ZO and ZL arteries. In vascular smooth muscle cells from ZO, ET-1-induced elevation of myoplasmic intracellular free calcium concentration ([Ca2+]i) (measured by fluo-4 AM fluorescence), and maximal contractions were diminished compared with ZL, both in the presence and absence of l-NAME. However, increases in [Ca2+]i elicited similar contractions of the vascular smooth muscle cells in both groups. Analysis of protein and total RNA from SCA of ZO and ZL revealed equal expression of ET-1 and the ETA and ETB receptors. Thus coronary arteries from ZO rats exhibit reduced ET-1-induced vasoconstriction resulting from increased ETB-mediated generation of NO and diminished elevation of myoplasmic [Ca2+]i.
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Katakam, Prasad V. G., Christina D. Tulbert, James A. Snipes, Benedek Erdös, Allison W. Miller, and David W. Busija. "Impaired insulin-induced vasodilation in small coronary arteries of Zucker obese rats is mediated by reactive oxygen species." American Journal of Physiology-Heart and Circulatory Physiology 288, no. 2 (February 2005): H854—H860. http://dx.doi.org/10.1152/ajpheart.00715.2004.
Full textAbstract:
Insulin resistance (IR) and associated hyperinsulinemia are major risk factors for coronary artery disease. Mechanisms linking hyperinsulinemia to coronary vascular dysfunction in IR are unclear. We evaluated insulin-induced vasodilation in isolated small coronary arteries (SCA; ∼225 μm) of Zucker obese (ZO) and control Zucker lean (ZL) rats. Vascular responses to insulin (0.1–100 ng/ml), ACh (10−9–10−5 mol/l), and sodium nitroprusside (10−8–10−4 mol/l) were assessed in SCA by measurement of intraluminal diameter using videomicroscopy. Insulin-induced dilation was decreased in ZO compared with ZL rats, whereas ACh and sodium nitroprusside elicited similar vasodilations. Pretreatment of arteries with SOD (200 U/ml), a scavenger of reactive oxygen species (ROS), restored the vasorelaxation response to insulin in ZO arteries, whereas ZL arteries were unaffected. Pretreatment of SCA with N-nitro-l-arginine methyl ester (100 μmol/l), an inhibitor of endothelial nitric oxide (NO) synthase (eNOS), elicited a vasoconstrictor response to insulin that was greater in ZO than in ZL rats. This vasoconstrictor response was reversed to vasodilation in ZO and ZL rats by cotreatment of the SCA with SOD or apocynin (10 μmol/l), a specific inhibitor of vascular NADPH oxidase. Lucigenin-enhanced chemiluminescence showed increased basal ROS levels as well as insulin (330 ng/ml)-stimulated production of ROS in ZO arteries that was sensitive to inhibition by apocynin. Western blot analysis revealed increased eNOS expression in ZO rats, whereas Mn SOD and Cu,Zn SOD expression were similar to ZL rats. Thus IR in ZO rats leads to decreased insulin-induced vasodilation, probably as a result of increased production of ROS by vascular NADPH oxidase, leading to decreased NO bioavailability, despite a compensatory increase in eNOS expression.
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Tabak, Esteban G., and Giulio Trigila. "Conditional expectation estimation through attributable components." Information and Inference: A Journal of the IMA 7, no. 4 (March 15, 2018): 727–54. http://dx.doi.org/10.1093/imaiai/iax023.
Full textAbstract:
Abstract A general methodology is proposed for the explanation of variability in a quantity of interest x in terms of covariates z = (z1, …, zL). It provides the conditional mean $\bar{x}(z)$ as a sum of components, where each component is represented as a product of non-parametric one-dimensional functions of each covariate zl that are computed through an alternating projection procedure. Both x and the zl can be real or categorical variables; in addition, some or all values of each zl can be unknown, providing a general framework for multi-clustering, classification and covariate imputation in the presence of confounding factors. The procedure can be considered as a preconditioning step for the more general determination of the full conditional distribution $\boldsymbol{\rho}(x|z) $ through a data-driven optimal-transport barycenter problem. In particular, just iterating the procedure once yields the second order structure (i.e. the covariance) of $\boldsymbol{\rho}(x|z) $. The methodology is illustrated through examples that include the explanation of variability of ground temperature across the continental United States and the prediction of book preference among potential readers.
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Rotger, M., R. Peslin, D. Navajas, and R. Farre. "Lung and respiratory impedance at low frequency during mechanical ventilation in rabbits." Journal of Applied Physiology 78, no. 6 (June 1, 1995): 2153–60. http://dx.doi.org/10.1152/jappl.1995.78.6.2153.
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We have tested in eight rabbits the feasibility of measuring respiratory (Zrs) and lung (ZL) impedances in the low-frequency domain, including below the breathing frequency (fb), during conventional mechanical ventilation (CMV). The animals were tracheotomized and ventilated with a tidal volume (VT) of 20 ml at a fb of 1 Hz. The excitation signal was provided by a flow generator connected in parallel with the ventilator; it included six components ranging from 0.45 to 14.8 Hz, which met the neither-sum-nor-difference criterion of B. Suki and K. Lutchen (IEEE Trans. Biomed. Eng. 39: 1142-1151, 1992) to minimize the influence of nonlinearities. Zrs and ZL were also measured at the same mean lung volume and with the same excitation signal both during apnea and when the ventilator signal was replaced by a sine wave with the same VT and fb (SMV). The real parts (Re) of both Zrs and ZL, as well as the effective elastances, were significantly larger during apnea than during CMV and SMV over the whole frequency range. Re(Zrs) and Re(ZL) were similar during CMV and SMV above fb but they were lower during CMV at 0.45 Hz. The latter difference seems to be related to the presence of harmonics of fb and of additional frequency components due to pulse amplitude modulation. We conclude that, because of nonlinearities, it is feasible to measure Zrs and ZL during CMV only at and above fb.
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Ledder, Ruth G., Prem K. Sreenivasan, William DeVizio, and Andrew J. McBain. "Evaluation of the specificity and effectiveness of selected oral hygiene actives in salivary biofilm microcosms." Journal of Medical Microbiology 59, no. 12 (December 1, 2010): 1462–68. http://dx.doi.org/10.1099/jmm.0.024372-0.
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The microbiological effects of biocidal products used for the enhancement of oral hygiene relate to the active compound(s) as well as other formulation components. Here, we test the specificities of selected actives in the absence of multiple excipients. Salivary ecosystems were maintained in tissue culture plate-based hydroxyapatite disc models (HDMs) and modified drip-flow biofilm reactors (MDFRs). Test compounds stannous fluoride (SF), SDS, triclosan (TCS), zinc lactate (ZL) and ZL with SF in combination (ZLSF) were delivered to the HDMs once and four times daily for 6 days to MDFRs. Plaques were characterized by differential viable counting and PCR–denaturing gradient gel electrophoresis (DGGE). TCS and SDS were the most effective compounds against HDM plaques, significantly reducing total viable counts (P<0.05), whilst SF, ZL and ZLSF were comparatively ineffective. TCS exhibited specificity for streptococci (P<0.01) and Gram-negative anaerobes (P<0.01) following a single dosing and also on repeated dosing in MDFRs. In contrast to single exposures, multiple dosing with ZLSF also significantly reduced all bacterial groups, whilst SF and ZL caused significant but transient reductions. According to PCR–DGGE analyses, significant (P<0.05) reductions in eubacterial diversity occurred following 6 day dosing with both TCS and ZLSF. Concordance of MDFR eubacterial profiles with salivary inocula ranged between 58 and 97 %. TCS and ZL(SF) exhibited similar specificities to those reported for formulations. TCS was the most potent antibacterial, after single and multiple dosage regimens.
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Agil, Ahmad, Meriem Chayah, Lucia Visiedo, Miguel Navarro-Alarcon, José Manuel Rodríguez Ferrer, Mohamed Tassi, Russel J. Reiter, and Gumersindo Fernández-Vázquez. "Melatonin Improves Mitochondrial Dynamics and Function in the Kidney of Zücker Diabetic Fatty Rats." Journal of Clinical Medicine 9, no. 9 (September 10, 2020): 2916. http://dx.doi.org/10.3390/jcm9092916.
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Obesity and associated diabetes (diabesity) impair kidney mitochondrial dynamics by augmenting fission and diminishing fusion, which results in mitochondrial and renal dysfunction. Based on available evidence, the antioxidant activities of melatonin may improve impaired renal mitochondrial function in obese diabetic animals by restoring the imbalanced dynamics through inhibiting fission and promoting fusion. Male Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally treated either with melatonin (10 mg/kg BW/day) (M-ZDF and M-ZL) or vehicle (C-ZDF and C-ZL) for 17 weeks. Kidney function was evaluated by measurement of total urine volume, proteinuria, creatinine clearance, and assessment of kidney mitochondrial dynamics and function. C-ZDF exhibited impaired dynamics and function of kidney mitochondria in comparison to C-ZL. Melatonin improved nephropathy of ZDF rats and modulated their mitochondrial dynamics by reducing expression of Drp1 fission marker and increasing that of fusion markers, Mfn2 and Opa1. Furthermore, melatonin ameliorated mitochondrial dysfunction by increasing respiratory control index and electron transfer chain complex IV activity. In addition, it lowered mitochondrial oxidative status. Our findings show that melatonin supplementation improves nephropathy likely via modulation of the mitochondrial fission/fusion balance and function in ZDF rats.
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Hidayat, Endar, Hiroyuki Harada, Yoshiharu Mitoma, Seiichiro Yonemura, and Hadi Imran A Halem. "Rapid Removal of Acid Red 88 by Zeolite/Chitosan Hydrogel in Aqueous Solution." Polymers 14, no. 5 (February 24, 2022): 893. http://dx.doi.org/10.3390/polym14050893.
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In the present study, we developed a new adsorbent product with zeolite crosslinked chitosan (ZL–CH hydrogel) to remove acid red 88 (AR88) in an aqueous solution. The effects of several factors, such as the comparison of ZL–CH hydrogel and the absence of chitosan, pH, adsorbent dosage, initial AR88 concentration, contact time, and ion strength, were determined. Obtained results showed that ZL–CH hydrogel improved AR88 removal compared to the absence of chitosan, with an adsorption capacity of 332.48 mg/g in equilibrium time of 1 min, and adding ionic strength had no significant effect. However, with optimal conditions at pH 2.0, dry ZL–CH became hydrogel due to protonation of amino and hydroxyl groups through hydrogen bonds in the AR88 solution. Volume fraction and interaction force decreased with increasing porosity, leading to an increase in adsorption capacity and swelling ratio. Experimental data of the adsorption process showed the Freundlich isotherm model. The equilibrium for adsorption and swelling kinetics studies showed and fitted a pseudo-second-order model. NaOH was successful as a desorbing agent with 93.8%, and it followed the pseudo-second-order kinetics model. The recycling process indicates great potential for AR88 removal.
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Feihl, F., N. Simon, C. Jaeggi, C. Depeursinge, and C. Perret. "Site of airway obstruction: effects on the acoustic impedance of excised pig lungs." Journal of Applied Physiology 64, no. 4 (April 1, 1988): 1387–96. http://dx.doi.org/10.1152/jappl.1988.64.4.1387.
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We investigated the relationship between the site of airway obstruction and the frequency dependence (FD) of lung acoustic impedance (ZL). The real (RL) and imaginary (XL) parts of ZL were measured by forced random noise in excised left pig lungs, before (base line) and after 1) no airway obstruction (controls, n = 10), 2) insufflation of 1-mm (B1, n = 5) or 2-mm (B2, n = 7) beads, and 3) partial reversible obstruction of lower lobar (LL) and then main-stem (MS) bronchus (n = 4). The beads caused both partial and total obstruction of airways with internal diameters of 2 mm (B1) and 2-6 mm (B2). Compared with base line, a negative FD of RL appeared from 4 to 10 Hz in LL, B1, and B2 obstructions. The FD of XL greater than 20 Hz increased in MS and LL obstruction exclusively and was the ZL feature that most clearly differentiated central from peripheral obstruction. In this experimental model, the anatomic limit distal from which obstruction no longer causes the "central" type of ZL change lies in airways with internal diameters notably greater than 2 mm.
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Zhao, Zhen, Wenchen Su, Sheng Yuan, and Ying Huang. "Functional conservation of tRNase ZL among Saccharomyces cerevisiae, Schizosaccharomyces pombe and humans." Biochemical Journal 422, no. 3 (August 27, 2009): 483–92. http://dx.doi.org/10.1042/bj20090743.
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Although tRNase Z from various organisms was shown to process nuclear tRNA 3′ ends in vitro, only a very limited number of studies have reported its in vivo biological functions. tRNase Z is present in a short form, tRNase ZS, and a long form, tRNase ZL. Unlike Saccharomyces cerevisiae, which contains one tRNase ZL gene (scTRZ1) and humans, which contain one tRNase ZL encoded by the prostate-cancer susceptibility gene ELAC2 and one tRNase ZS, Schizosaccharomyces pombe contains two tRNase ZL genes, designated sptrz1+ and sptrz2+. We report that both sptrz1+ and sptrz2+ are essential for growth. Moreover, sptrz1+ is required for cell viability in the absence of Sla1p, which is thought to be required for endonuclease-mediated maturation of pre-tRNA 3′ ends in yeast. Both scTRZ1 and ELAC2 can complement a temperature-sensitive allele of sptrz1+, sptrz1–1, but not the sptrz1 null mutant, indicating that despite exhibiting species specificity, tRNase ZLs are functionally conserved among S. cerevisiae, S. pombe and humans. Overexpression of sptrz1+, scTRZ1 and ELAC2 can increase suppression of the UGA nonsense mutation ade6–704 through facilitating 3′ end processing of the defective suppressor tRNA that mediates suppression. Our findings reveal that 3′ end processing is a limiting step for defective tRNA maturation and demonstrate that overexpression of sptrz1+, scTRZ1 and ELAC2 can promote defective tRNA 3′ processing in vivo. Our results also support the notion that yeast tRNase ZL is absolutely required for 3′ end processing of at least a few pre-tRNAs even in the absence of Sla1p.
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Ran, Jianmin, Tsutomu Hirano, and Mitsuru Adachi. "Angiotensin II type 1 receptor blocker ameliorates overproduction and accumulation of triglyceride in the liver of Zucker fatty rats." American Journal of Physiology-Endocrinology and Metabolism 287, no. 2 (August 2004): E227—E232. http://dx.doi.org/10.1152/ajpendo.00090.2004.
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The effects of angiotensin II type 1 receptor blocker (ARB) on triglyceride (TG) metabolism associated with insulin resistance were explored in Zucker fatty (ZF) rats. Olmesartan medoxomil, a newly developed ARB, was given as a 0.01% drinking solution ad libitum to ZF and Zucker lean (ZL) rats for 4 wk. Olmesartan lowered blood pressure in both strains to the same extent. ZF rats had a markedly low insulin sensitivity index (SI) and glucose effectiveness (SG), together with significantly increased glucose levels. Olmesartan treatment substantially elevated both SI and SG. The ZF rats were hyperlipidemic, with plasma TG levels sixfold higher than those of the ZL rats. Olmesartan remarkably decreased the plasma free fatty acid level in the ZF rats, but it did not exert a significant effect on the plasma TG level. The TG secretion rate assessed by the Triton WR-1339 technique was almost six times higher in the ZF than in the ZL rats, and olmesartan treatment suppressed this TG overproduction by one-half. The TG content in the liver was ten times higher in the ZF than in the ZL rats, and olmesartan halved this high hepatic TG content without affecting the cholesterol content. The fatty liver developed in the ZF rats was ameliorated by olmesartan treatment. Olmesartan treatment had no significant effects on TG metabolism or insulin sensitivity in the ZL rats. Taken in sum, ARB improves the overproduction and accumulation of TG in the liver associated with insulin resistance, and it does so through mechanisms independent of its hypotensive action.
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Roy, S. C. Dutta. "Many Faces of the Maximum Power Transfer Theorem." International Journal of Electrical Engineering & Education 40, no. 2 (April 2003): 103–11. http://dx.doi.org/10.7227/ijeee.40.2.1.
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The celebrated maximum power transfer theorem, which is usually stated for source impedance Zg = Rg + jXg and load impedance ZL = RL + jXL, is revisited, and generalised for other possible situations in which either Zg or ZL or both are parallel combinations of a resistance and a reactance, and for all possible cases of load variability. Many of the results are believed to be new.
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Wang, Xiye, Mingyang Jiang, Dan Li, and Liang Xu. "Analyzing the Therapeutic Mechanism of Mongolian Medicine Zhonglun-5 in Rheumatoid Arthritis Using a Bagging Algorithm with Serum Metabonomics." Evidence-Based Complementary and Alternative Medicine 2022 (December 7, 2022): 1–9. http://dx.doi.org/10.1155/2022/5997562.
Full textAbstract:
Rheumatoid arthritis (RA) is a complex autoimmune disorder. Zhonglun-5 (ZL), a traditional Mongolian medicine, exhibits an excellent clinical effect on RA; however, its molecular mechanism remains unclear. In this study, rat serum metabolomic analysis was performed to identify potential biomarkers for RA and investigate its treatment mechanism. A Dionex Ultimate 3000 ultrahigh-performance liquid chromatography system coupled with a Q-Exactive Focus Orbitrap mass spectrometer was used for metabonomics analysis. Bootstrap aggregation (bagging) classification algorithm was applied to process data from control (CG), model (MG), and treatment administration groups. The classification accuracy was 100.00% (6/6) in the decision tree model and 83.33% (5/6) in the K-nearest neighbor (KNN) model, accompanied by 18 training samples and 6 testing samples. Using volcanic map analysis, 24 biomarkers were identified between CG and MG, including those related to glycosphingolipid biosynthesis, arachidonic acid, fatty acids, amino acids, bile acids, vitamins, and sphingolipids. A set diagram of the heatmap and drug-biomarker network of potential biomarkers was constructed. After ZL administration, the levels of these biomarkers returned to normal, indicating that ZL had a therapeutic effect in rats with RA. This study established a solid theoretical foundation to promote further research on the clinical applicability of ZL.
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Saleh, Asef A., Rakan Khalil Antar, and Harith Ahmed Al-Badrani. "Design of new structure of multilevel inverter based on modified absolute sinusoidal PWM technique." International Journal of Power Electronics and Drive Systems (IJPEDS) 12, no. 4 (December 1, 2021): 2314. http://dx.doi.org/10.11591/ijpeds.v12.i4.pp2314-2321.
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The advantage of multilevel inverters is to produce high output voltage values with distortion as minimum as possible. To reduce total harmonic distortion (THD) and get an output voltage with different step levels using less power electronics switching devices, 15-level inverter is designed in this paper. Single-phase 11-switches with zero-level (ZL) and none-zero-level (NZL) inverter based on modified absolute sinusoidal pulse width modulation (MASPWM) technique is designed, modelled and built by MATLAB/Simulink. Simulation results explained that, multilevel inverter with NZL gives distortion percent less than that with ZL voltage. The THD of the inverter output voltage and current of ZL are 4% and 1%, while with NZL is 3.6% and 0.84%, respectively. These results explain the effectiveness of the suggested power circuit and MASPWM controller to get the required voltage with low THD.
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Schmits, R. J. H., Y. T. M. Vanneste, and A. de Rijk. "Ziekteverzuim en ziekteverzuimbegeleiding volgens M@ZL." JGZ Tijdschrift voor jeugdgezondheidszorg 53, no. 2-3 (March 31, 2021): 73–79. http://dx.doi.org/10.1007/s12452-021-00241-y.
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Su, Shuhua, Shuqun Yang, and Qi Li. "The ZL-completions of fuzzy posets." Journal of Intelligent & Fuzzy Systems 39, no. 1 (July 17, 2020): 1347–59. http://dx.doi.org/10.3233/jifs-200121.
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Tapia Adler, Ana María. "Testimonio de Don Alfred Blueh (zl)." Cuadernos Judaicos, no. 38 (December 23, 2021): 332–38. http://dx.doi.org/10.5354/0718-8749.2021.65805.
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Xu, Jun Chen, and Quan Zhong Liu. "Research on Solidified Mechanism of Compound Consolidated Soil." Advanced Materials Research 671-674 (March 2013): 1231–34. http://dx.doi.org/10.4028/www.scientific.net/amr.671-674.1231.
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By the scanning electron microscopy and experimental study, curing mechanism of the ZL-1 curing agent was studied in this paper, and the curing mechanism of the traditional curing materials in the soil clay was also analyzed. The study found that ZL-1 has a good curing effect on curing agent to the lime and clay mixture ，cement and clay mixture, and has greatly improved water stability, durability. And the best mix proportion was given.
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Zhang, Jing, Wenhua Shi, Min Chen, Xinchuan Dai, Hongshui Liu, Shou Li, Lina Wang, et al. "Abstract 3590: ZL-1218, a novel anti-CCR8 antibody, exerts potent antitumor effect by depleting intratumoral regulatory T cells." Cancer Research 82, no. 12_Supplement (June 15, 2022): 3590. http://dx.doi.org/10.1158/1538-7445.am2022-3590.
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Abstract Despite the promise of immunotherapy for cancer treatment, nearly 80% of patients fail to respond to checkpoint inhibitor (CPI) therapy. Regulatory T cells (Tregs), which inhibit immune responses in the tumor microenvironment via multiple suppressive mechanisms, have been proposed to play a key role in those patients who are not responding to CPI therapy. Therefore, targeted depletion of Tregs should promote more effective antitumor immunity. CCR8 is a chemokine receptor that is selectively expressed on highly activated human tumor-resident Tregs, and these intratumoral CCR8+ Tregs have been shown to drive immunosuppression that leads to poor prognosis for cancer patients. Here, we demonstrate that CCR8 is highly expressed on intratumoral FoxP3+ Treg cells in multiple cancers and is absent on other major immune cell populations in tumor microenvironment including effector T cells, conventional CD4 T cells, B cells, NK cells, some FoxP3+ cells, and myeloid cells. Importantly, no CCR8 protein expression was observed on any peripheral human leukocyte subset examined. These results provide strong rationale for targeting CCR8 as a cancer immunotherapy by selectively depleting the most suppressive intratumoral Treg cells. We have developed a humanized therapeutic antibody, ZL-1218, that binds to human CCR8 with high affinity and specificity and can induce potent ADCC activity enabling strong NK cell-mediated killing of CCR8-expressing Tregs. We show that in human CCR8 knock-in mouse models bearing syngeneic tumors, ZL-1218 reduces intratumoral Treg cells and thus elicits significant tumor growth inhibition in a dose-dependent manner. We have recently explored the potential for ZL-1218 in combination immunotherapy, examining the enhanced antitumor activity when ZL-1218 is combined with anti-PD-1. Using human dissociated tumor samples, we further observed that different tumor types may induce different CCR8 expression levels on intratumoral Tregs leading to multiple, distinct CCR8+ subsets in various indications. We are currently exploring the significance of these distinct populations and the impact of ZL-1218-mediated depletion of both CCR8 high- and CCR8 low-expressing subsets in multiple indications. Together, these data support the advancement of ZL-1218 into clinical evaluation as a novel therapeutic candidate to treat human solid tumors. Citation Format: Jing Zhang, Wenhua Shi, Min Chen, Xinchuan Dai, Hongshui Liu, Shou Li, Lina Wang, Bee-Chun Sun, Monica You, Vivian Morton, Qiuping Ye, Lishan Kang, Bing Wan, Peter Brams, David I. Bellovin. ZL-1218, a novel anti-CCR8 antibody, exerts potent antitumor effect by depleting intratumoral regulatory T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3590.
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Institoris, Adam, James A. Snipes, Prasad V. Katakam, Ferenc Domoki, Krisztina Boda, Ferenc Bari, and David W. Busija. "Impaired vascular responses of insulin-resistant rats after mild subarachnoid hemorrhage." American Journal of Physiology-Heart and Circulatory Physiology 300, no. 6 (June 2011): H2080—H2087. http://dx.doi.org/10.1152/ajpheart.01169.2010.
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Insulin resistance (IR) impairs cerebrovascular responses to several stimuli in Zucker obese (ZO) rats. However, cerebral artery responses after subarachnoid hemorrhage (SAH) have not been described in IR. We hypothesized that IR worsens vascular reactions after a mild SAH. Hemolyzed blood (300 μl) or saline was infused (10 μl/min) into the cisterna magna of 11–13-wk-old ZO ( n = 25) and Zucker lean (ZL) rats ( n = 25). One day later, dilator responses of the basilar artery (BA) and its side branch (BA-Br) to acetylcholine (ACh, 10−6 M), cromakalim (10−7 M, 10−6 M), and sodium nitroprusside (10−7 M) were recorded with intravital videomicroscopy. The baseline diameter of the BA was increased both in the ZO and ZL rats 24 h after the hemolysate injection. Saline-injected ZO animals showed reduced dilation to ACh (BA = 9 ± 3 vs. 22 ± 4%; and BA-Br = 23 ± 5 vs. 37 ± 7%) compared with ZL rats. Hemolysate injection blunted the response to ACh in both the ZO (BA = 4 ± 2%; and BA-Br = 12 ± 3%) and ZL (BA = 7 ± 2%; and BA-Br = 11 ± 3%) rats. Cromakalim (10−6 M)-induced dilation was significantly reduced in the hemolysate-injected ZO animals compared with the saline control (BA = 13 ± 3 vs. 26 ± 5%; and BA-Br = 28 ± 8 vs. 44 ± 9%) and in the hemolysate-injected ZL rats compared with their saline control (BA = 24 ± 4 vs. 32 ± 4%; but not BA-Br = 39 ± 6 vs. 59 ± 9%). No significant difference in sodium nitroprusside reactivity was observed. Western blot analysis of the BA showed a lower baseline level of neuronal nitric oxide synthase expression and an enhanced cyclooxygenase-2 level in the hemolysate-injected ZO animals. In summary, cerebrovascular reactivity to both endothelium-dependent and -independent stimuli is severely compromised by SAH in IR animals.
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Gisvold, B., H. Ödegaard, and M. Föllesdal. "Enhancing the removal of ammonia in nitrifying biofilters by the use of a zeolite containing expanded clay aggregate filtermedia." Water Science and Technology 41, no. 9 (May 1, 2000): 107–14. http://dx.doi.org/10.2166/wst.2000.0182.
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Pilot plant experiments were carried out on a nitrifying biofilter with a zeolite containing expanded clay aggregate filtermedia (Filtralite ZL). The filter removed ammonium from domestic wastewater by a combination of nitrification and ion exchange. An identical filter material, but without sorptive capacity with respect to ammonium, was used as a reference (Filtralite). The experiments demonstrated that Filtralite ZL removed more ammonium at high ammonium loading rates than Filtralite. This was caused by ion exchange of ammonium in addition to nitrification. Under low ammonium loading rates, nitrification of already sorbed ammonium took place. This combined effect of ion exchange and nitrification of ammonium in Filtralite ZL was demonstrated in experiments with constant ammonium loading for periods up to 10 days and as well as in experiments with daily variations in ammonium loading rate. No chemical regeneration was necessary in addition to the biological regeneration during the experimental period of four months.
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Kara, S. Okan, Serkan Akkoyun, and Tuncay Bayram. "Probing for leptophilic gauge boson Zl at ILC with $\sqrt{s} = 1~{\rm TeV}$ by using ANN." International Journal of Modern Physics A 29, no. 30 (December 8, 2014): 1450171. http://dx.doi.org/10.1142/s0217751x14501711.
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We search for leptophilic gauge boson Zl via the process e+e- → μ+μ- at ILC with [Formula: see text]. In the leptonic extension of SM [Formula: see text] we have predicted that ILC with [Formula: see text] will enable searching Zl with masses up to the center-of-mass energy if the related coupling constant gl exceeds 10-3 for 3σ observations and 5σ discovery. Furthermore similar results have been obtained by using artificial neural network (ANN) method.
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Takenaka, Tsuneo, Tsutomu Inoue, Yoichi Ohno, Takashi Miyazaki, Akira Nishiyama, Naohito Ishii, and Hiromichi Suzuki. "Elucidating mechanisms underlying altered renal autoregulation in diabetes." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 303, no. 5 (September 1, 2012): R495—R504. http://dx.doi.org/10.1152/ajpregu.00217.2012.
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Previous studies have reported that high-salt intake paradoxically activates tubuloglomerular feedback (TGF) in type 1 diabetes. Using Zucker lean (ZL) and diabetic fatty (ZDF) rats on normal and high-salt diets, renal hemodynamics and the renin-angiotensin system (RAS) were characterized. On normal salt diet, glomerular filtration rate (GFR) was higher in ZDF than ZL rats. Autoregulation of GFR was less efficient and lithium clearance was lower in ZDF rats than ZL rats. Salt load reduced GFR in ZDF rats with restoration of lithium clearance and partial improvement in autoregulatory index (AI). The administration of 8-cyclopentyl-1,3-dipropylxanthine, a selective adenosine-1 receptor antagonist to ZDF rats on a high-salt diet abolished the improvement of AI in GFR. However, this effect was seen by neither Cx40GAP27 nor Cx37,43GAP27, which inhibits connexin (Cx) 40 or Cx37. Renal ANG II was higher in ZDF than ZL rats on normal salt diet, but the difference was eliminated by a salt load. The present data provide the first demonstration for a salt paradox in type 2 diabetes and implicate that in addition to Cx alterations, an enhanced proximal reabsorption attenuates TGF, underlying glomerular hyperfiltration and RAS activation. These data suggest that a high-salt diet standardizes distal delivery in diabetes, suppressing the RAS, and improving GFR autoregulation and hyperfiltration through adenosine.
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Msaad, Asmaa, Mounir Belbahloul, Samir El Hajjaji, and Abdeljalil Zouhri. "Comparison of novel Ziziphus lotus adsorbent and industrial carbon on methylene blue removal from aqueous solutions." Water Science and Technology 78, no. 10 (November 20, 2018): 2055–63. http://dx.doi.org/10.2166/wst.2018.481.
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Abstract In this work, the use of a novel low-cost adsorbent derived from Ziziphus lotus (ZL) and industrial carbon (IC) has been successfully applied to the removal of methylene blue (MB) from aqueous solutions. The efficiency of this material was studied through Lagergren pseudo-first-order and pseudo-second-order kinetic models. The process for the novel activated carbon and the IC were best represented by the pseudo-second-order rate model. Langmuir and Freundlich isotherms were used to describe the sorption equilibrium data. The Langmuir model turned out to be the most adequate and maximum capacities were measured to be 833.33 and 142.85 mg.g−1 for ZL activated carbon and IC from Sigma Aldrich, respectively. The thermodynamic study revealed that the sorption process is spontaneous and endothermic for the two adsorbents. To explain the effectiveness of MB removal, ZL activated carbon was characterized by scanning electron microscopy, Brunauer–Emmett–Teller surface area, X-ray diffraction and Fourier transform infrared spectroscopy.