Journal articles on the topic 'Cheng ren jiao yu'

Abstract Background: Fibroblast growth factors (FGFs) and their receptors (FGFRs) regulate numerous cellular processes. Dysregulation of FGFR signaling due to receptor fusion, mutation or amplification is observed across multiple cancer types, making activated FGFRs an important therapeutic target. Herein, we present the preclinical characterization of HMPL-453, a highly potent and selective inhibitor of FGFR1, 2, and 3, discovered and being currently developed in phase II clinical trial (NCT04353375) by HUTCHMED. Methods: Kinase activity was measured by Transcreener™ Fluorescence Polarization assay or Z’-LYTE kinase assay. In vitro anti-proliferation activity was measured by CellTiter-Glo luminescent or CCK-8 assay. The effect of HMPL-453 on FGFR signaling pathway was detected by western blot. Multiple tumor models with FGFR alteration were applied in Nu/Nu nude mice to determine anti-tumor efficacy of 453 as a single agent. A model in immune-competent BALB/c mice inoculated with the constructed NIH/3T3 cells carrying FGFR2-AHCYL1 fusion was chosen to investigate the combination effect of HMPL-453 with anti-PD-1 antibody. Results: HMPL-453 potently inhibited the tyrosine kinase activities of recombinant FGFR 1, 2, and 3 in vitro (IC50 values of 6, 4, and 6 nM, respectively) with weaker activity against FGFR4 (IC50 = 425 nM). HMPL-453 selectively inhibited proliferation of tumor cell lines with dysregulated FGFR signaling (GI50s: 3~105 nM) compared with cell lines lacking FGFR aberrations (GI50s > 1.5 µM). HMPL-453 demonstrated strong inhibition of phosphorylation of FGFR and downstream protein in tumor cell lines harboring FGFR2 fusion. Oral administration of HMPL-453 could induce time- and dose-dependent inhibition of phosphorylation of FGFR and resulted in remarkable and dose-dependent anti-tumor activity in multiple FGFR-altered tumor models. HMPL-453 at the dose of 50 mg/kg/day could induce tumor regression in most tumor models tested. Moreover, HMPL-453 significantly improved anti-tumor activity of anti-PD-1 antibody in a FGFR2 fusion model by priming the immune environment. Conclusion: HMPL-453 is a highly potent and selective inhibitor of FGFR 1, 2, and 3 with strong activity against FGFR-deregulated tumors in preclinical models, supporting continued investigation in patients with FGFR alterations (such as fusion and mutation) either as a single agent or in combination with PD-1 blockade. Citation Format: Jia Hu, Jun Ni, Longxian Jiao, Jinghong Zhou, Shiming Fan, Renxiang Tang, Wei Zhang, Xuelei Ge, Qihang Zhang, Juntao Yu, Ying Yu, Dongxia Shi, Min Cheng, Weifang Xue, Sumei Xia, Zeyu Zhong, Jian Wang, Yang Sai, Weiguo Qing, Guangxiu Dai, Yongxin Ren, Michael Shi, Weiguo Su. HMPL-453, a highly selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays potent activity in FGFR-altered tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6321.

Oracle-bone scholars have long uniformly read the charges (i.e., the portion that mentions the event being divined) of Shang oracle-bone inscriptions as questions. Since the 1970's, many foreign oracle-bone scholars have proposed a new view that the charges are never questions, or at least are generally not questions. Whether or not the charges are actually questions is a very important question bearing not only on oracle bone studies, but also on research on ancient divination and on ancient Chinese grammar. Based on an examination of a great number of Shang oracle-bone inscriptions, the author of this essay believes that charges that can now be determined to be questions are mainly those choice-type charges in early inscriptions that contain the final particles yi and zhi, and true-or-false type charges that contain yi. Charges of the type “V bu V” (such as “rain not rain” [yu bu yu]) and “V bu,” regarded by many as choice-type questions, are actually comprised of the charge and a verification or use notation, the “bu V” being a verification and the “bu” being either a verification or a use notation (similar to the notation bu yong, “do not use”). Charges that can now be determined not to be questions are mainly in those inscriptions with complex charges, such as “this *spring the king ought not ally with Wang Cheng to attack Xia Wei, (for if he does) he will not receive divine assistance” (jin ?chun wang wu bi Wang Cheng fa Xia? Wei, fu qi shou you you, and “On ren we ought not hunt, (for if we do) it will rain” (ren wu tian, qi yu), the syntax of which shows that they cannot be questions.

Abstract Background: Mutations in isocitrate dehydrogenase (IDH) 1/2 are frequently identified in various cancers, such as AML, cholangiocarcinoma, chondrosarcoma and glioma. Mutant IDHs (mIDHs) cause accumulated 2-HG, leading to blockage of cell differentiation, thereby inducing malignant transformation. Rare cases were identified carrying co-existing mutations in IDH1 and IDH2. mIDH isoform switching, from mutant IDH1 to mutant IDH2 and vice versa, have been reported as a mechanism of acquired resistance to IDH inhibition in AML and cholangiocarcinoma. Thus, simultaneous inhibition on both mIDH1 and mIDH2 may be a promising strategy to overcome resistance and improve clinical efficacy. HMPL-306, a dual inhibitor of mIDH1/mIDH2, developed by HUTCHMED, is being evaluated in clinical trials. Methods: The inhibition of HMPL-306 on IDH enzymes, including mutant and wild type, was determined by fluorescence-based assay. The selectivity of HMPL-306 was evaluated in 322 kinases (SelectScreenTM) and 88 proteins (Cerep). For cellular activities of HMPL-306, 2-HG production and differentiation were detected in cells harboring mIDH. Human tumor xenograft models carrying IDH1 or 2 mutations were established for evaluating mIDH inhibition by detecting 2-HG in plasma and tumor, and anti-tumor efficacies. Results: HMPL-306 inhibited mutant IDH enzyme activities including IDH1R132H, IDH2R140Q and IDH2R172K, while showed weaker inhibition on IDH1/2 wild type enzymes. HMPL-306 had a superior selectivity profile in a kinase panel and a safety panel, while enasidenib, an approved mIDH2 inhibitor, inhibited Adenosine-A3 with IC50 of 12 nM. In cellular assays, HMPL-306 displayed comparable activities to enasidenib and ivosidenib (approved mIDH1 inhibitor) and suppressed 2-HG through inhibition of mIDH1 or mIDH2 at similar level, indicating an equal potency against mIDH1 and 2. Moreover, in both mIDH1/2 cells, HMPL-306 reduced the levels of histone methylation, and promoted hemoglobin γ and Kruppel1 gene expression, which led to differentiation from immature malignant cells to mature normal cells. Oral administration of HMPL-306 remarkably decreased 2-HG level in plasma and tumor tissues in xenograft models carrying mIDH1 or mIDH2 and the inhibition is more potent and durable than either ivosidenib or enasidenib at the same dose. Pharmacokinetics (PK) study in rodents showed high exposures of HMPL-306 in brain and cerebrospinal fluid, a desirable feature for glioma therapy. Combination treatment of HMPL-306 and azacitidine synergized in releasing the differentiation block in mIDH AML cells. HMPL-306 also significantly improved in vivo anti-tumor efficacy of chemotherapy drugs in solid tumor models with mIDH1/2. Conclusion: HMPL-306 is a potent, dual inhibitor of IDH1/2 mutation. The strong activity and favorable PK profiles support further clinical evaluation. Citation Format: Na Yang, Jia Hu, Tingwen Li, Juntao Yu, Dongxia Shi, Min Cheng, Zeyu Zhong, Jian Wang, Yang Sai, Weiguo Qing, Guangxiu Dai, Yongxin Ren, Michael Shi, Weiguo Su. Preclinical characteristic of HMPL-306, a CNS-penetrable dual inhibitor of mutant IDH1 and IDH2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 543.

Abstract Background: Immune checkpoint inhibitors (CPIs) targeting PD-(L)1 have become a standard of care for untreated, advanced melanoma, but demonstrated limited efficacy in mucosal melanoma. Tebotelimab, also known as MGD013, is a PD-1/LAG-3 bispecific tetravalent DART® molecule with synergistic antitumor activity shown in preclinical studies. We conducted an open-label, single-arm, multi-cohort phase 1 study (NCT04653038) to assess the efficacy and safety of tebotelimab in melanoma patients (pts) including those with CPI-naïve mucosal melanoma. Methods: The CPI-naïve cohort of this study enrolled pts with unresectable, recurrent or metastatic, mucosal or acral melanoma who had received no systemic therapy. Tebotelimab 600 mg was administered intravenously once every two weeks. The primary endpoint was overall response rate (ORR) assessed by independent radiologic review committee (IRC) per RECIST v1.1 in the efficacy analysis set consisting of pts who received ≥1 dose of tebotelimab. A post-hoc sensitivity analysis was conducted in the IRC-response evaluable set consisting of pts with IRC-assessed target lesions in the efficacy analysis set who received ≥1 post-baseline tumor assessment by IRC or died within 13 weeks after first dose. Results are reported for mucosal melanoma. Results: At data cut-off (January 19, 2022), 25 pts with mucosal melanoma were enrolled (median age, 61 years; male, 40%; ECOG 1, 40%; TNM Stage IV, 92%; metastatic, 80%). LAG-3 expression level was ≥1% in seven (28%), <1% in 15 (60%), and unknown in three (12%). PD-L1 expression was positive (CPS≥1) in three (12%), negative (CPS<1) in 19 (76%), and unknown in three (12%). All pts received ≥1 dose of tebotelimab. In the efficacy analysis set (n=25), three, three, and four pts achieved complete response (CR), partial response (PR), and stable disease (SD), respectively, leading to a confirmed ORR of 24% (95% confidence interval [CI], 9-45), with median duration of response (DOR) not reached, and a disease control rate (DCR) of 40% (95% CI, 21-61). In the IRC-response evaluable set (n=20), three, three, and four pts achieved CR, PR, and SD, respectively, leading to a confirmed ORR of 30% (95% CI, 12-54), with median DOR not reached, and a DCR of 50% (95% CI, 27-73). Immune-related treatment-emergent adverse events occurred in 11 (44%) pts, most commonly, hypothyroidism (20%), hyperthyroidism (16%), and white blood cell count decreased (12%). Grade ≥3 and serious treatment-related adverse events (TRAEs) were reported in three (12%) and four (16%) pts, respectively. TRAEs led to treatment discontinuation and death each in one (4%). Conclusions: Tebotelimab demonstrated preliminary but promising antitumor activity and a tolerable safety profile in pts with untreated, unresectable, recurrent or metastatic, mucosal melanoma. Citation Format: Si Lu, Yu Chen, Meiyu Fang, Zhengyun Zou, Di Wu, Zhiguo Luo, Jian Zhang, Jing Chen, Gang Huang, Hongming Pan, Xiubao Ren, Ying Cheng, Haichuan Su, Yuan Xin, Qiong Hua, Jianmei Hou, Jun Guo. Tebotelimab, a PD-1/LAG-3 bispecific antibody, in patients with untreated, unresectable, recurrent or metastatic, mucosal melanoma: An open-label, single-arm, Phase 1 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT208.

Derivatives of graphene have become important materials due to their excellent properties. Graphene oxide and reduced graphene oxide are especially interesting because they are produced relatively easily, cheaply and quickly. Among many possible applications, reduced graphene oxide is a good candidate for sensor applications. Its properties can be controlled at the production stage. The precursor used and the method of oxidation have a significant influence on its properties. Therefore, it is worth take a closer look at them. In this paper we analyse the influence of the oxidation method on the size of the reduced graphene stock which determine the sensitivity of the rGO layer. We used AFM microscopy for this purpose. Full Text: PDF ReferencesS.M. Majhi, A. Mirzaei, H.W. Kim, S.S. Kim, "Reduced Graphene Oxide (rGO)-Loaded Metal-Oxide Nanofiber Gas Sensors: An Overview", Sensors 21, 4 (2021). CrossRef M. Pumera, "Graphene-based nanomaterials for energy storage", Energy Environ. Sci. 4 3 (2011). CrossRef X. Yu, H. Cheng, M. Zhang, Y. Zhao, L. Qu, G. Shi, "Graphene-based smart materials", Nat. Rev. Mater. 2, 9 (2017). CrossRef M.Y. Xia, Y. Xie, C.H. Yu, G.Y. Chen, Y.H. Li, T., Zhang, Q. Peng, "Graphene-based nanomaterials: the promising active agents for antibiotics-independent antibacterial applications", J. Control. Release 10 (2019). CrossRef X. Zhu, Y. Zhou, Y. Guo, H. Ren, C. Gao, "Nitrogen dioxide sensing based on multiple-morphology cuprous oxide mixed structures anchored on reduced graphene oxide nanosheets at room temperature", Nanotechnology 30 45 (2019). CrossRef Z. Wu, Y. Wang, S. Ying, M. Huang, C. Peng, "Fabrication of rGO/Cuprous Oxide Nanocomposites for Gas Sensing", IOP Conf. Ser.: Earth Environ. Sci. 706, 1 (2021). CrossRef S. Pei, H.M. Cheng, "The reduction of graphene oxide", Carbon 50, 9 (2012). CrossRef K. Spilarewicz-Stanek, A. Kisielewska, J. Ginter, K. Bałuszyńska, I. Piwoński, "Elucidation of the function of oxygen moieties on graphene oxide and reduced graphene oxide in the nucleation and growth of silver nanoparticles", RSC Adv. 6, 65 (2016). CrossRef R. Muzyka, S. Drewniak, T. Pustelny, M. Sajdak, Ł. Drewniak, "Characterization of Graphite Oxide and Reduced Graphene Oxide Obtained from Different Graphite Precursors and Oxidized by Different Methods Using Raman Spectroscopy Statistical Analysis", Materials 14, 4 (2021) CrossRef B. Lesiak, G. Trykowski, J. Tóth, et al. "Chemical and structural properties of reduced graphene oxide—dependence on the reducing agent", J Mater. Sci. 56 (2021). CrossRef .

In recent years, many attempts have been made to improve the sensory properties of SnO2, including design of sensors based on one-dimensional nanostructures of this material, such as nanofibers, nanotubes or nanowires. One of the simpler methods of producing one-dimensional tin oxide nanomaterials is to combine the electrospinning method with a sol-gel process. The purpose of this work was to produce SnO2 nanowires using a hybrid electrospinning method combined with a heat treatment process at the temperature of 600 °C and to analyze the morphology and structure of the one-dimensional nanomaterial produced in this way. Analysis of the morphology of composite one-dimensional tin oxide nanostructures showed that smooth, homogeneous and crystalline nanowires were obtained. Full Text: PDF ReferencesN. Dharmaraj, C.H. Kim, K.W. Kim, H.Y. Kim, E.K. Suh, "Spectral studies of SnO2 nanofibres prepared by electrospinning method", Spectrochim. Acta - Part A Mol. Biomol. Spectrosc. 64, (2006) CrossRef N. Gao, H.Y. Li, W. Zhang, Y. Zhang, Y. Zeng, H. Zhixiang, ... & H. Liu, "QCM-based humidity sensor and sensing properties employing colloidal SnO2 nanowires", Sens. Actuators B Chem. 293, (2019), 129-135. CrossRef W. Ge, Y. Chang, V. Natarajan, Z. Feng, J. Zhan, X. Ma, "In2O3-SnO2 hybrid porous nanostructures delivering enhanced formaldehyde sensing performance", J.Alloys and Comp. 746, (2018) CrossRef M. Zhang, Y. Zhen, F. Sun, C. Xu, "Hydrothermally synthesized SnO2-graphene composites for H2 sensing at low operating temperature", Mater. Sci. Eng. B. 209, (2016), 37-44. CrossRef Y. Zhang, X. He, J. Li, Z. Miao, F. Huang, "Fabrication and ethanol-sensing properties of micro gas sensor based on electrospun SnO2 nanofibers", Sens. Actuators B Chem. 132, (2008), 67-73. CrossRef W.Q. Li, S.Y. Ma, J. Luo, Y.Z. Mao, L. Cheng, D.J. Gengzang, X.L. Xu, S H. Yan, "Synthesis of hollow SnO2 nanobelts and their application in acetone sensor", Mater. Lett. 132, (2014), 338-341. CrossRef E. Mudra, I. Shepa, O. Milkovic, Z. Dankova, A. Kovalcikova, A. Annusova, E. Majkova, J. Dusza, "Effect of iron doping on the properties of SnO2 nano/microfibers", Appl. Surf. Sci. 480, (2019), 876-881. CrossRef P. Mohanapriya, H. Segawa, K. Watanabe, K. Watanabe, S. Samitsu, T.S. Natarajan, N.V. Jaya, N. Ohashi, "Enhanced ethanol-gas sensing performance of Ce-doped SnO2 hollow nanofibers prepared by electrospinning", Sens. Actuators B Chem. 188, (2013), 872-878. CrossRef W.Q. Li, S.Y. Ma, Y.F. Li, X.B. Li, C.Y. Wang, X.H. Yang, L. Cheng, Y.Z. Mao, J. Luo, D.J. Gengzang, G.X. Wan, X.L. Xu, "Preparation of Pr-doped SnO2 hollow nanofibers by electrospinning method and their gas sensing properties", J.Alloys and Comp. 605, (2014), 80-88. CrossRef X.H. Xu, S.Y. Ma, X.L. Xu, T. Han, S.T. Pei, Y. Tie, P.F. Cao, W.W. Liu, B.J. Wang, R. Zhang, J.L. Zhang, "Ultra-sensitive glycol sensing performance with rapid-recovery based on heterostructured ZnO-SnO2 hollow nanotube", Mater. Lett, 273, (2020), 127967. CrossRef F. Li, X. Gao, R. Wang, T. Zhang, G. Lu, Sens. "Study on TiO2-SnO2 core-shell heterostructure nanofibers with different work function and its application in gas sensor", Actuators B Chem, 248, (2017), 812-819. CrossRef S. Bai, W. Guo, J. Sun, J. Li, Y. Tian, A. Chen, R. Luo, D. Li, "Synthesis of SnO2–CuO heterojunction using electrospinning and application in detecting of CO", Sens Actuators B Chem, 226, (2016), 96-103. CrossRef H. Du, P.J. Yao, Y. Sun, J. Wang, H. Wang, N. Yu, "Electrospinning Hetero-Nanofibers In2O3/SnO2 of Homotype Heterojunction with High Gas Sensing Activity", Sensors, 17, (2017), 1822. CrossRef X. Wang, H. Fan, P. Ren, "Electrospinning derived hollow SnO2 microtubes with highly photocatalytic property", Catal. Commun. 31, (2013), 37-41. CrossRef L. Cheng, S.Y. Ma, T.T. Wang, X.B. Li, J. Luo, W.Q. Li, Y.Z. Mao, D.J Gengzang, "Synthesis and characterization of SnO2 hollow nanofibers by electrospinning for ethanol sensing properties", Mater. Lett. 131, (2014), 23-26. CrossRef P.H. Phuoc, C.M. Hung, N.V. Toan, N.V. Duy, N.D. Hoa, N.V. Hieu, "One-step fabrication of SnO2 porous nanofiber gas sensors for sub-ppm H2S detection", Sens. Actuators A Phys. 303, (2020), 111722. CrossRef A.E. Deniz, H.A. Vural, B. Ortac, T. Uyar, "Gold nanoparticle/polymer nanofibrous composites by laser ablation and electrospinning", Matter. Lett. 65, (2011), 2941-2943. CrossRef S. Sagadevan, J. Podder, "Investigation on Structural, Surface Morphological and Dielectric Properties of Zn-doped SnO2 Nanoparticles", Mater. Res. 19, (2016), 420-425. CrossRef

Abstract Background/Purpose: Chimeric antigen receptor (CAR) T cell therapy has shown remarkable responses in hematologic malignancies. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptive transferred CAR-T cells, antigen-negative relapses, and impairment by an immunosuppressive tumor microenvironment. We previously developed CD19CAR-T cells secreting PD-1Ab21 fusion protein composed of anti-PD-1 single chain antibody and IL-21(PD-1Ab21-CD19CAR-T). This investigator-initiated clinical trial is designed to assess the safety and efficacy of the novel CAR-T cells in advanced relapsed/refractory acute Lymphoblastic leukemia (ALL). Methods: This study recruited 10 patients with advanced relapsed/refractory B-ALL and half of them relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). All patients received fludarabine and cyclophosphamide before a single infusion of PD-1Ab21-CD19CAR-T cells at dose of 0.3, 1 or 3 x 106 cells/kg of body weight. The patients were monitored for adverse events, clinical response, as well as expansion of CAR-T and lymphocytes. Results: All five non-post-transplant patients achieved complete remission (CR), including two active CNS diseases, and three of them pursued consolidative allo-HSCT. Among the five post-transplant patients, one patient, who had undergone autologous, allogeneic CAR-T cell therapies and allo-HSCT, achieved CR and remained leukemia-free for 5 months, which was longer than the duration of remission (< 4 monthes) after allo-HSCT. The last treated patient achieved CR. Three other post-transplant patients, including two active CNS diseases, eventually died of the infection. One of the patients achieved minimal residual disease negative CR. The other two patients did not undergo laboratory evaluation, but their CNS symptoms disappeared. Once the expansion of CAR-T cells was detected, the proportion of CD8+T cell in CD3+T cells increased dramatically, rapidly reaching 77.8~91.2% and maintaining above 50% for a long time in all treated patients. Except for the three patients who died from infection, other patients experienced no or mild cytokine release syndrome (CRS) (grade ≤2). None of the patients had neurotoxic side effects. Conclusion: This study demonstrates that PD-1Ab21-secreting CAR-T cells are safe and effective therapeutic platform, even in cancer patients with CNS invasion. Our data also suggest that PD-1Ab21-secreting CAR-T therapy can activate endogenous anti-tumor CD8+ T cell responses. Citation Format: Yu Jing, Ying Li, Liping Dou, Shengjuan Zhang, Ran Tian, Guojing Wang, Xiangrui Cheng, Jitao Zhao, Hang Li, Yueyi An, Naibo Yang, Shengdian Wang. Phase I clinical trial of CD19CAR -T cells secreting PD-1-targeting IL-21 in advanced relapsed/refractory acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT180.

Abstract Many TEAD small-molecule inhibitors (SMIs) have recently reported initial clinical evaluations on Hippo-mutated cancer types. Several studies have demonstrated that activation of the YAP1/TEAD transcriptional complex via a Hippo-independent manner can drive resistance to MAPK/ERK pathway inhibitors. Here, we elucidated the potential mechanism of TEAD inhibition overcoming MAPK/ERK pathway resistance with a TEAD SMI (hereafter abbreviated as TEADi). Firstly, the MoA of TEADi was validated in Hippo-mutated cells. TEADi inhibited cell growth of Hippo-mutated cancer cell lines NCI-H226 and NCI-H2052 but not that of MKN45, a YAP1-deletion cell line. Co-IP and qRT-PCR results demonstrated that TEADi disrupted the interaction between YAP1 and TEAD, and thus markedly repressed the expression of CTGF and CYR61, two downstream targets of YAP1/TEAD, in NCI-H226 cells. Secondly, we hypothesized that hyper-activation of TEAD confers resistance to KRAS mutant cancer types. To test this hypothesis, we generated two resistant cell lines. One is KARS G12C inhibitor Sotorasib-resistant NCI-H358 (NCI-H358-R). The other is MEK inhibitor Trametinib-resistant HCT116 (HCT116-R). Immunofluoresence assay showed that YAP1 nucleus translocation was enhanced in both resistant cells (NCI-H358-R and HCT116-R), but not in their parental counterparts (NCI-H358-P and HCT116-P). The enhanced YAP1 nucleus translocation resulted in increased transcription activities of TEAD in both resistant cells, as illustrated by luciferase reporter assay. Accordingly, CTGF and CYR61 were observed upregulated in both resistant cells. The above data indicate that YAP1/TEAD mediated-transactivation plays a role in MAPK pathway resistance. Indeed, TEADi treatment alone displayed substantial difference in cell growth inhibition between parental and resistant cell lines in both NCI-H358 and HCT116, further confirming that the resistant cells are more dependent on YAP1/TEAD signaling. Finally, we evaluated the combinational efficacies of TEADi and MAPK/ERK pathway inhibitors in the resistant cells. It was observed that addition of TEADi could significantly restore the response of NCI-H358-R and HCT116-R to Sotorasib and Trametinib, respectively. Mechanistically, TEADi efficiently suppressed TEAD transcriptional activities and subsequently the expression of CTGF and CYR61 in both resistant cells. Moreover, TEADi had almost no impact on ERK phosphorylation in either of the resistant cells, suggesting that re-sensitization of MAPK/ERK pathway inhibitors by TEADi is independent of primary onco-genetic signaling pathway. Taken together, our study demonstrates that inhibition of YAP1/TEAD signaling would be an efficient approach to overcome resistance to MAPK/ERK pathway inhibitors in the patients carrying KRAS mutations, and provides the scientific basis for development of combination therapy strategies. Citation Format: Xianwen Yang, Guiping Li, Peiling Ren, Xiaoyun Shi, Ying Yu, Baoyu Hao, Pan Wang, Min Cheng, Guangxiu Dai. Targeting YAP1/TEAD signaling re-sensitizes MAPK/ERK pathway inhibitors in KRAS- driven cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1931.

Over the past century, nitrogen fertilization has fed approximately 27% of the world’s population.1 Urea and ammonia are two of the most important nitrogen fertilizers used world-widely. The current industrial production of urea is mainly realized by an energy-intensive reaction of carbon dioxide and ammonia under harsh conditions (150-200 °C, 150-250 bar) with large energy consumption, for which nearly 80% of synthesized ammonia is used.2 Furthermore, ammonia is also produced under extreme condition (350-550 °C, 150-350 bar) by an energy-consuming Haber-Bosch method.3 Therefore, it is of great significance to synthesize urea and ammonia under mild conditions to meet the demands of ever-increasing population in the world. The electrocatalytic co-reduction of CO2 and NO3 - emerges as a promising approach to realize the direct synthesis of urea via C-N coupling, with ammonia produced as a side product. However, the state-of-the-art yield rates of urea and ammonia through this electrosynthesis are typically below 1 mg h-1 mgcat -1 and 3 mg h-1 mgcat -1.4, 5 In this study, we realize high-rate production of urea on an economic Cu-based organic molecule catalyst through electrochemically coupling CO2 with NO3 -, with ammonia as another useful byproduct. The rationally design of the catalysts guarantees the accurate adsorption and activation of NO3 - and CO2, which further promotes the desired electrochemical C-N coupling in urea synthesis. Efficient urea synthesis was achieved with yield rates ranging from 2.7 to 3.6 mg h-1 mgcat -1 in a potential window of -0.49~-0.67V vs. RHE, together with ammonia with high yield rates ranging from 0.15 to 9.7 mg h-1 mgcat -1. This work proposes an appealing route of sustainable production of artificial nitrogen fertilizers with high efficiencies. Widespread adoption of this approach is promising to re-use the greenhouse gas CO2 and NO3 - from waste toward a full circulate of economy and sustainable energy consumption. The demonstrated production of nitrogen fertilizer in conjunction with renewable electricity is of great potential to meet the rising demand for global food security. Acknowledgements Research Grants Council (26206115, 16304821 and 16309418) and Innovation and Technology Commission (grant no. ITC-CNERC14EG03) of the Hong Kong Special Administrative Region. The work described in this paper was substantially supported by a fellowship award from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKUST PDFS2021-4S12). References J. W. Erisman, M. A. Sutton, J. Galloway, Z. Klimont and W. Winiwarter, Nat. Geosci., 2008, 1, 636-639. M. Yuan, J. Chen, Y. Xu, R. Liu, T. Zhao, J. Zhang, Z. Ren, Z. Liu, C. Streb, H. He, C. Yang, S. Zhang and G. Zhang, Energy Environ. Sci., 2021, 14, 6605-6615. A. J. Martín, T. Shinagawa and J. Pérez-Ramírez, Chem, 2019, 5, 263-283. C. Lv, L. Zhong, H. Liu, Z. Fang, C. Yan, M. Chen, Y. Kong, C. Lee, D. Liu, S. Li, J. Liu, L. Song, G. Chen, Q. Yan and G. Yu, Nat. Sustain., 2021, 4, 868-876. X. Wei, X. Wen, Y. Liu, C. Chen, C. Xie, D. Wang, M. Qiu, N. He, P. Zhou, W. Chen, J. Cheng, H. Lin, J. Jia, X.-Z. Fu and S. Wang, J. Am. Chem. Soc., 2022, 144, 11530-11535.

Abstract Background: Pertuzumab is a recombinant humanized monoclonal antibody targeting the extracellular dimerization domain II of HER2. On September 30, 2013, the FDA have granted accelerated approval of a pertuzumab regimen for neoadjuvant treatment of patients (pts) with high-risk, HER2-positive early stage breast cancer. TQB2440 is a pertuzumab (Perjeta®, Roche) biosimilar. This study aimed to compare the efficacy and safety of TQB2440 and the reference pertuzumab combined with trastuzumab and docetaxel in pts with HER2-positive early or locally advanced breast cancer. Methods: In this multicenter, randomized, double-blind phase 3 study, eligible pts were aged 18-75 with operable HER2-positive (IHC 3+ or ISH+) clinical stage II-IIIC breast cancer negative for ER/PR and had an ECOG PS of 0-1. The pts were randomly assigned to receive either TQB2440 or the reference pertuzumab (Perjeta®) (840 mg on day 1, cycle 1, followed by 420 mg on cycle 2-4, q3w) added to trastuzumab (8 mg/kg on day 1, cycle 1, followed by 6 mg/kg for cycles 2-4, q3w) + docetaxel (75 mg/m2, cycle 1-4, q3w). The pts then underwent surgery followed by adjuvant treatment with FEC regimens (fluorouracil 600 mg/m², epirubicin 90 mg/m², cyclophosphamide 600 mg/m², cycle 5-7, q3w), then TQB2440 (840 mg on day 1, cycle 8, followed by 420 mg on cycle 9-20, q3w) + trastuzumab (8 mg/kg on day 1, cycle 8, followed by 6 mg/kg for cycles 9-20, q3w) or until disease progression or intolerable toxicity. The primary endpoint was total pathologic complete response (tpCR) by independent review committee (IRC). Equivalence was established if the 90% confdence intervals (CIs) of the relative ratio [RR] within the interval of 0.76 to 1.32. Secondary endpoints included breast pathologic complete response (bpCR) by IRC, tpCR & bpCR by investigator, breast conserving surgery (BCS) rates, objective response rate (ORR), event-free survival (EFS), disease-free survival (DFS), OS and safety. Results: Between October 21, 2020, and November 21, 2022, 412 pts were enrolled (TQB2440 group, n=207; the reference pertuzumab group, n=205). Data cutoff was November 30, 2022. In the intention-to-treat (ITT) population, the tpCR by IRC of the TQB2440 group and the reference drug group were 58.94% and 58.05%, respectively. The RR was 1.02 (90% CI, 0.89, 1.16), which was within the predefined equivalence interval of 0.76 to 1.32. There was no statistically significant difference in the bpCR by IRC between the TQB2440 group and the reference pertuzumab group (67.63% [95% CI, 60.80%, 73.95%] vs. 63.90% [95% CI, 56.92%, 70.48%], P=0.4249). The BCS rate also comparable between the two groups with 13.04% (95% CI, 8.77%, 18.41%) vs. 13.17% (95% CI, 8.86%, 18.58%) (P=0.9695). Additionally, the results of the PP (per-protocol) population were similar to those of the ITT population. The incidence of treatment-related adverse events (TRAEs) and grade ≥3 TRAEs were similar between the TQB2440 group and the reference pertuzumab group with 79.71% vs. 75.98% and 49.28% vs. 41.67%, respectively. Conclusion: In patients with HER2-positive early or locally advanced breast cancer, TQB2440 demonstrated equivalent efficacy and similar safety to the reference pertuzumab. Clinical trial information: NCT05985187. Research Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd Citation Format: Qingyuan Zhang, Shusen Wang, Nanlin Li, Qiao Cheng, Yu ren, Xuchen Cao, Jianjun Huang, Caigang Liu, Hongwei Yang, Limin Wei, Zhangjun Song, Huadong Zhao, Fangling Ning, Xiaojia Wang, Dehong Zou, Xiaohua Zeng, Jie Hao, Yunjiang Liu, Huijuan Wang, Nie Jianyun, Liang Li, Lina Liu, Tao Sun, Xiaobo Hu, Zhenhua Zhai, Huihua Xiong, Yuanqi Zhang, Enxiang Zhou, Jing Sun, Zhenhai Cai, Antai Zhang, Shui Wang, Junyang Mo, Qun Su, Xiuheng Qi, Guoren Zhou, Shuqun Zhang, Guozhong Cui, Wei Wang, Mingjiang Fan, Xinyu Qian, Xinhong Wu, Zhihong Wang, Jiuda Zhao, Yonghui Luo, Yanming Zhang, Fuguo Tian, Jiye Zhang, Dongning Chai, Qingshan Li. Comparing the Efficacy and Safety of TQB2440 versus the Reference Pertuzumab for the Treatment of HER2-Positive Early or Locally Advanced Breast Cancer: A Multicenter, Randomized, Double-Blind, Parallel-Controlled Phase 3 Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-27-01.

Rapid urbanization rates impact significantly on the nature of Land Cover patterns of the environment, which has been evident in the depletion of vegetal reserves and in general modifying the human climatic systems (Henderson, et al., 2017; Kumar, Masago, Mishra, & Fukushi, 2018; Luo and Lau, 2017). This study explores remote sensing classification technique and other auxiliary data to determine LULCC for a period of 50 years (1967-2016). The LULCC types identified were quantitatively evaluated using the change detection approach from results of maximum likelihood classification algorithm in GIS. Accuracy assessment results were evaluated and found to be between 56 to 98 percent of the LULC classification. The change detection analysis revealed change in the LULC types in Minna from 1976 to 2016. Built-up area increases from 74.82ha in 1976 to 116.58ha in 2016. Farmlands increased from 2.23 ha to 46.45ha and bared surface increases from 120.00ha to 161.31ha between 1976 to 2016 resulting to decline in vegetation, water body, and wetlands. The Decade of rapid urbanization was found to coincide with the period of increased Public Private Partnership Agreement (PPPA). Increase in farmlands was due to the adoption of urban agriculture which has influence on food security and the environmental sustainability. The observed increase in built up areas, farmlands and bare surfaces has substantially led to reduction in vegetation and water bodies. The oscillatory nature of water bodies LULCC which was not particularly consistent with the rates of urbanization also suggests that beyond the urbanization process, other factors may influence the LULCC of water bodies in urban settlements. Keywords: Minna, Niger State, Remote Sensing, Land Surface Characteristics References Akinrinmade, A., Ibrahim, K., & Abdurrahman, A. (2012). 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Graphene-based composites have received a great deal of attention in recent year because the presence of graphene can enhance the conductivity, strength of bulk materials and help create composites with superior qualities. Moreover, the incorporation of metal oxide nanoparticles such as Fe3O4 can improve the catalytic efficiency of composite material. In this work, we have synthesized a composite material with the combination of reduced graphene oxide (rGO), and Fe3O4 modified tissue-paper (mGO-PP) via a simple hydrothermal method, which improved the removal efficiency of the of methylene blue (MB) in water. MB blue is used as the model of contaminant to evaluate the catalytic efficiency of synthesized material by using a Fenton-like reaction. The obtained materials were characterized by SEM, XRD. The removal of materials with methylene blue is investigated by UV-VIS spectroscopy, and the result shows that mGO-PP composite is the potential composite for the color removed which has the removal efficiency reaching 65% in acetate buffer pH = 3 with the optimal time is 7 h. Keywords Graphene-based composite, methylene blue, Fenton-like reaction. References [1] Ma Joshi, Rue Bansal, Reng Purwar, Colour removal from textile effluents, Indian Journal of Fibre & Textile Research, 29 (2004) 239-259 http://nopr.niscair.res.in/handle/123456789/24631.[2] Kannan Nagar, Sundaram Mariappan, Kinetics and mechanism of removal of methylene blue by adsorption on various carbons-a comparative study, Dyes and pigments, 51 (2001) 25-40 https://doi.org/10.1016/S0143-7208(01)00056-0.[3] K Rastogi, J. N Sahu, B. C Meikap, M. N Biswas, Removal of methylene blue from wastewater using fly ash as an adsorbent by hydrocyclone, Journal of hazardous materials, 158 (2008) 531-540.https://doi.org/10.1016/j.jhazmat.2008.01. 105.[4] Qin Qingdong, Ma Jun, Liu Ke, Adsorption of anionic dyes on ammonium-functionalized MCM-41, Journal of Hazardous Materials, 162 (2009) 133-139 https://doi.org/10.1016/j.jhazmat. 2008.05.016.[5] Mui Muruganandham, Rps Suri, Sh Jafari, Mao Sillanpää, Lee Gang-Juan, Jaj Wu, Muo Swaminathan, Recent developments in homogeneous advanced oxidation processes for water and wastewater treatment, International Journal of Photoenergy, 2014 (2014). http://dx. doi.org/10.1155/2014/821674.[6] Herney Ramirez, Vicente Miguel , Madeira Luis Heterogeneous photo-Fenton oxidation with pillared clay-based catalysts for wastewater treatment: a review, Applied Catalysis B: Environmental, 98 (2010) 10-26 https://doi.org/ 10.1016/j.apcatb.2010.05.004.[7] Guo Rong, Jiao Tifeng, Li Ruifei, Chen Yan, Guo Wanchun, Zhang Lexin, Zhou Jingxin, Zhang Qingrui, Peng Qiuming, Sandwiched Fe3O4/carboxylate graphene oxide nanostructures constructed by layer-by-layer assembly for highly efficient and magnetically recyclable dye removal, ACS Sustainable Chemistry & Engineering, 6 (2017) 1279-1288 https://doi.org/10.1021/acssuschemeng.7b03635.[8] Sun Chao, Yang Sheng-Tao, Gao Zhenjie, Yang Shengnan, Yilihamu Ailimire, Ma Qiang, Zhao Ru-Song, Xue Fumin, Fe3O4/TiO2/reduced graphene oxide composites as highly efficient Fenton-like catalyst for the decoloration of methylene blue, Materials Chemistry and Physics, 223 (2019) 751-757 https://doi.org/ 10.1016/j.matchemphys.2018.11.056.[9] Guo Hui, Ma Xinfeng, Wang Chubei, Zhou Jianwei, Huang Jianxin, Wang Zijin, Sulfhydryl-Functionalized Reduced Graphene Oxide and Adsorption of Methylene Blue, Environmental Engineering Science, 36 (2019) 81-89 https://doi. org/10.1089/ees.2018.0157.[10] Zhao Lianqin, Yang Sheng-Tao, Feng Shicheng, Ma Qiang, Peng Xiaoling, Wu Deyi, Preparation and application of carboxylated graphene oxide sponge in dye removal, International journal of environmental research and public health, 14 (2017) 1301 https://doi.org/10.3390/ijerph14111301.[11] Yu Dandan, Wang Hua, Yang Jie, Niu Zhiqiang, Lu Huiting, Yang Yun, Cheng Liwei, Guo Lin, Dye wastewater cleanup by graphene composite paper for tailorable supercapacitors, ACS applied materials & interfaces, 9 (2017) 21298-21306 https://doi.org/10.1021/acsami.7b05318.[12] Wang Hou, Yuan Xingzhong, Wu Yan, Huang Huajun, Peng Xin, Zeng Guangming, Zhong Hua, Liang Jie, Ren MiaoMiao, Graphene-based materials: fabrication, characterization and application for the decontamination of wastewater and wastegas and hydrogen storage/generation, Advances in Colloid and Interface Science, 195 (2013) 19-40 https://doi. org/10.1016/j.cis.2013.03.009.[13] Marcano Daniela C, Kosynkin Dmitry V, Berlin Jacob M, Sinitskii Alexander, Sun Zhengzong, Slesarev Alexander, Alemany Lawrence B, Lu Wei, Tour James M, Improved synthesis of graphene oxide, ACS nano, 4 (2010) 4806-4814 https://doi.org/10.1021/nn1006368.[14] Zhang Jiali, Yang Haijun, Shen Guangxia, Cheng Ping, Zhang Jingyan, Guo Shouwu, Reduction of graphene oxide via L-ascorbic acid, Chemical Communications, 46 (2010) 1112-1114 http://doi. org/10.1039/B917705A [15] Gong Ming, Zhou Wu, Tsai Mon-Che, Zhou Jigang, Guan Mingyun, Lin Meng-Chang, Zhang Bo, Hu Yongfeng, Wang Di-Yan, Yang Jiang, Nanoscale nickel oxide/nickel heterostructures for active hydrogen evolution electrocatalysis, Nature communications, 5 (2014) 4695 https:// doi.org/10.1038/ncomms5695.[16] Wu Zhong-Shuai, Yang Shubin, Sun Yi, Parvez Khaled, Feng Xinliang, Müllen Klaus, 3D nitrogen-doped graphene aerogel-supported Fe3O4 nanoparticles as efficient electrocatalysts for the oxygen reduction reaction, Journal of the American Chemical Society, 134 (2012) 9082-9085 https://doi.org/10.1021/ja3030565.[17] Nguyen Son Truong, Nguyen Hoa Tien, Rinaldi Ali, Nguyen Nam Van, Fan Zeng, Duong Hai Minh, Morphology control and thermal stability of binderless-graphene aerogels from graphite for energy storage applications, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 414 (2012) 352-358 https://doi.org/ 10.1016/j.colsurfa.2012.08.048.[18] Deng Yang, Englehardt James D, Treatment of landfill leachate by the Fenton process, Water research, 40 (2006) 3683-3694 https://doi.org/ 10.1016/j.watres.2006.08.009.

Introduction & Objective: Women with polycystic ovary syndrome (PCOS) are more prone to glucose metabolic abnormalities, which is thought to be related to increased visceral adiposity. This study aimed to evaluate the relationship between fat deposition in the pancreas and liver and glucose metabolism in PCOS. Methods: This study included 160 women with PCOS diagnosed according to the Rotterdam 2003 criteria between April 2019 and September 2022. All participants underwent the anthropometric and biochemical assessments including an oral glucose tolerance test. Magnetic resonance imaging-proton density fat fraction was used to measure fat deposition in the pancreas and liver. Results: Pancreatic interlobular fat volume, pancreatic body fat content and liver fat content were significantly higher in PCOS with diabetes than normal glucose tolerance (P < 0.05). Increased pancreatic body fat [OR 2.21 (95% CI 1.01 - 4.85), P = 0.047] and hepatic average fat [OR 2.92 (95% CI 1.13 - 7.51), P = 0.026] were independently associated with higher risks for impaired glucose regulation (IGR). Patients with high pancreatic body fat and high hepatic average fat had increased risk for IGR after multiple confounding adjustments [OR 5.49 (95% CI 1.63 - 18.47), P = 0.006]. Combining pancreatic body fat and hepatic average fat with age, BMI, WHR, TG and FAI, the AUC for predicting IGR in PCOS was 0.789 with a sensitivity of 0.713 and a specificity of 0.800. Conclusion: Fat contents in the pancreatic body and liver are synergistic risk factors for IGR in PCOS. Disclosure C. Shan: None. J. Yu: None. Y. Zhu: None. J. Zhao: None. L. Wang: None. Y. Li: None. S. Lin: None. W. Liu: None. Q. Lu: None. T. Tao: None. Funding National Natural Science Foundation of China (82170807, 82370797); the Natural Science Foundation of Shanghai (12ZR1417800); the Shanghai Sailing Program (21YF1425300); the National Nature Promotion Project, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine (RJTJ23-ZD-005); the Bethune Charitable Foundation (J202103E006); the Shanghai Medical and Health Development Foundation (SHMHDF DMRFP_II_10) and the Medical Guidance Science and Technology Support Projects of Shanghai Municipal Science and Technology Commission (18411968700).

Object segmentation is an important task which is widely employed in many computer vision applications such as object detection, tracking, recognition, and retrieval. It can be seen as a two-phase process: object detection and segmentation. Object segmentation becomes more challenging in case there is no prior knowledge about the object in the scene. In such conditions, visual attention analysis via saliency mapping may offer a mean to predict the object location by using visual contrast, local or global, to identify regions that draw strong attention in the image. However, in such situations as clutter background, highly varied object surface, or shadow, regular and salient object segmentation approaches based on a single image feature such as color or brightness have shown to be insufficient for the task. This work proposes a new salient object segmentation method which uses a depth map obtained from the input image for enhancing the accuracy of saliency mapping. A deep learning-based method is employed for depth map estimation. Our experiments showed that the proposed method outperforms other state-of-the-art object segmentation algorithms in terms of recall and precision. KeywordsSaliency map, Depth map, deep learning, object segmentation References[1] Itti, C. Koch, E. Niebur, A model of saliency-based visual attention for rapid scene analysis, IEEE Transactions on pattern analysis and machine intelligence 20(11) (1998) 1254-1259.[2] Goferman, L. Zelnik-Manor, A. Tal, Context-aware saliency detection, IEEE transactions on pattern analysis and machine intelligence 34(10) (2012) 1915-1926.[3] Kanan, M.H. Tong, L. Zhang, G.W. Cottrell, Sun: Top-down saliency using natural statistics, Visual cognition 17(6-7) (2009) 979-1003.[4] Liu, Z. Yuan, J. Sun, J. Wang, N. Zheng, X. Tang, H.-Y. Shum, Learning to detect a salient object, IEEE Transactions on Pattern analysis and machine intelligence 33(2) (2011) 353-367.[5] Perazzi, P. Krähenbühl, Y. 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Wang, M. Narwaria, P. Le Callet, W. Lin, Saliency detection for stereoscopic images., IEEE Trans. Image Processing 23(6) (2014) 2625-2636.Hou, L. Zhang, Saliency detection: A spectral residual approach, in: Computer Vision and Pattern Recognition, 2007. CVPR’07. IEEE Conference on, IEEE, 2007, pp. 1-8.Guo, Q. Ma, L. Zhang, Spatio-temporal saliency detection using phase spectrum of quaternion fourier transform, in: Computer vision and pattern recognition, 2008. cvpr 2008. ieee conference on, IEEE, 2008, pp. 1-8.Fang, W. Lin, B.S. Lee, C.T. Lau, Z. Chen, C.W. Lin, Bottom-up saliency detection model based on human visual sensitivity and amplitude spectrum, IEEE Transactions on Multimedia 14(1) (2012) 187-198.Lang, T.V. Nguyen, H. Katti, K. Yadati, M. Kankanhalli, S. Yan, Depth matters: Influence of depth cues on visual saliency, in: Computer vision-ECCV 2012, Springer, 2012, pp. 101-115.Zhang, G. Jiang, M. Yu, K. 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Introdução: O novo coronavírus é responsável pela síndrome respiratória aguda grave, causando óbito, em 5 meses de pandemia, de 646 mil indivíduos mundialmente. As principais formas de transmissão identificadas são gotículas de saliva expelidas ao falar e tossir ou pelo contato em uma superfície com secreções salivares, com característica agressiva de contágio e potencial letalidade. Objetivo: Relatar as práticas do serviço radiológico em tempos de pandemia e evidenciar práticas seguras de biossegurança para o Cirurgião-Dentista. Métodos: Para elaboração deste trabalho foram selecionados 13 artigos utilizando a base de dados do Pubmed. Foram utilizados como descritores “Coronavirus Infections”, “Betacoronavirus”, “Dentistry”, “Radiology” e “Containment of Biohazards. Os critérios de inclusão foram artigos publicados em inglês, espanhol e português com os resumos disponíveis, do ano de 2020. Resultados: Os Cirurgiões-Dentistas estão entre os profissionais que mais sofrem risco de contaminação, uma vez que estão expostos a riscos biológicos e contato direto com a saliva, sendo necessário, neste cenário crítico de pandemia do coronavírus, adotar medidas mais eficazes de prevenção e controle de infecção a fim de evitar ou reduzir ao máximo a transmissão deste vírus. Na Radiologia Odontológica, a baixa incidência de aerossóis não exclui a possibilidade de contaminação pelo contato com fluido salivar nas tomadas radiográficas intrabucais, preconizando radiografias extrabucais. Conclusão: A presente revisão de literatura é baseada em relevantes diretrizes e pesquisas, introduzindo conhecimentos essenciais sobre o coronavírus, condutas a serem adotadas em ambiente odontológico e fornece protocolos de orientações recomendadas para dentistas e estudantes.Descritores: Infecções por Coronavirus; Betacoronavirus; Odontologia; Radiologia; Contenção de Riscos Biológicos.ReferênciasOrganização Mundial da Saúde (OMS). Coronavirus disease (COVID-19) pandemic. 2020. Disponível: https://www.who.int/emergencies/diseases/novel-coronavirus-2019Zhu HD, Zeng CH, Lu J, Teng GJ. COVID-19: What should interventional radiologists know and what can they do? J Vasc Interv Radiol. 2020; 31(6):876-81.Odeh ND, Babkair H, Abu-Hammad S, Borzangy S, Abu-Hammad A, Abu-Hammad O. COVID-19: present and future challenges for dental practice. Int J Environ Res Public Health. 2020; 17(9):3151.Conselho Federal de Odontologia (CFO). Manual de Boas Práticas em Biossegurança para Ambientes Odontológicos. 2020. Disponível em: http://website.cfo.org.br/wp-content/uploads/2020/04/cfo-lanc%CC%A7a-Manual-de-Boas-Pra%CC%81ticas-em-Biosseguranc%CC%A7a-para-Ambientes-Odontologicos.pdfSalzedas LMP, Oliva AH, Coclete GEG, Coclete GA. Protocolo de biossegurança e gerenciamento de resíduos no ensino de radiologia odontológica da Faculdade de Odontologia de Araçatuba-UNESP. Arch Healt Invest. 2014;3(6):20-27.Peng X, Xu X, Li Y, Cheng L, Zhou X, Ren B. Transmission routes of 2019-nCoV and controls in dental practice. Int J Oral Sci. 2020;12(1):9.Fini MB. What dentists need to know about COVID-19. Oral Oncol. 2020;105:104741.Société Française de Stomatologie, Chirurgie Maxillo-Faciale et Chirurgie Orale (SFSCMFCO). Praticiens de la cavité orale. Recommandations professionnelles. Risques infectieux par le COVID-19. Faire front pour faire face. J Stomatol Oral Maxillofac Surg. 2020;121(2):e3-6.Han P, Ivanovski S. Saliva – friend and foe in the COVID-19 outbreak. Diagnostics (Basel). 2020;10:290.Dziedzic A, Wojtyczka R. The impact of coronavírus infectious disease 19 (COVID-19) on oral health. Oral Dis. 2020;101111Wu R, Wang L, Kuo HCD, Shannar A, Peter P, Chuo PJ, Li S, Hudlikar, Liu X, Liu Z, Poiani, Amorosa L, Brunetti L, Kong AN. An update on current therapeutic drugs treating COVID-19. Curr Pharmacol Rep. 2020;11:1-15.Van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, Tamin A, Harcourt JL, Thornburg NJ, Gerber SI, Lloyd-Smith JO, Wit E, Munster VJ. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020;382(16):1564-67.American Dental Association (ADA). What Constitutes a Dental Emergency? 2020. Disponível: https://success.ada.org/~/media/CPS/Files/Open%20Files/ADA_COVID19_Dental_Emergency_DDS.pdf?_ga=2.253879752.110187285.1584496315-1622146531.1565271894Center for Disease Control and Prevention (CDC). Interim Infection Prevention and Control for Patients with Suspected or Confirmed Coronavirus disease 2019 (COVID-19) in Healthcare Settings. 2020. Disponível em: https://www.cdc.gov/coronavirus/2019-ncov/hcp/dental-settings.htmlPeditto M, Scapellato S, Marcianò A, Costa P, Oteri G. Dentistry during the COVID-19 epidemic: an italian workflow for the management of dental practice. Int J Environ Res Public Health. 2020;17(9):3325.Tuñas ITC, Silva ET, Santiago SBS, Maia KD, Silva-Júnior GO. Doença pelo Coronavírus 2019 (COVID-19): Uma abordagem preventiva para Odontologia. Rev Bras Odontol. 2020;77(1):1-6.Salzedas LMP, Oliva AH, Oliveira LQC, Simas MCO, Coclete GA. Biossegurança na clínica de radiologia odontológica. Arch Health Invest. 2014;3(6):6-13.Escola de Educação Permanente do Hospital das Clínicas da USP (HC). COVID-19: dicas e cuidados para enfrentar a pandemia. 2020. Disponível em: https://jornal.usp.br/wp-content/uploads/2020/05/e-book-covid-19.pdfSaki M, Haseli S, Iranpour P. Oral radiology center as a potential source of COVID-19 transmission; Points to consider. Acad Radiol. 2020;27(7):1047-48.Yu J, Ding N, Liu XJ, He WJ, Dai WC, Zhou ZG et al. Infection control against COVID-19 in departments of radiology. Acad Radiol. 2020;27(5):614-17.

Vitamin E (VitE) is a potent antioxidant and contributes as an apoptosis inhibitor by preventing apoptotic death by suppressing cell membrane scrambling with phosphatidylserine translocation and caspase activites. Fas ligand (FasL) is well known to induce cell apoptosis. Activation of phosphoinositide 3 kinase (PI3K) signalling is stimulated by VitE. The present study addressed the effects of VitE on survival of mouse dendritic cells (DCs) and signalling molecules underlying. To this end, mouse bone marrow cells were isolated and cultured to attain bone marrow-derived DCs (BMDCs). The cells were treated with FasL in the presence or absence of VitE. Western blotting and FACS analysis were performed to determine expression of signalling molecules and their involvement in DC apoptosis. As a result, FasL treatment resulted in activation of caspase 8 and an increased number of Annexin V+ cells, the effects were significantly suppressed when VitE was present in the cell culture. Importantly, the anti-apoptotic effects of VitE were abolished by using pharmacological inhibition of PI3K signaling with LY294002. Our results showed that VitE inhibited FasL-mediated DC apoptosis through PI3K signalling, the effect is expected to facilitate the survival of DCs and promote the immune response against pathogens. Keywords Caspase, Dendritic cell; Fas ligand; PI3K and vitamin E. References [1] J. Banchereau, R.M. Steinman, Dendritic cells and the control of immunity, Nature 392 (1998) 245-52.[2] E. Ingulli, A. Mondino, A. Khoruts, M.K. Jenkins, In vivo detection of dendritic cell antigen presentation to CD4(+) T cells, J Exp Med 185 (1997) 2133-41.[3] C. Yang, H.Z. Liu, Z.X. Fu, PEG-liposomal oxaliplatin induces apoptosis in human colorectal cancer cells via Fas/FasL and caspase-8, Cell Biol Int 36 (2012) 289-96.[4] Q.G. Yan, J.G. Shi, F. Zhang, Q.T. Zhao, X.W. Pang, R. Chen, P.Z. Hu, Q.L. Li, Z. Wang, G.S. Huang, Overexpression of CYP2E1 enhances sensitivity of hepG2 cells to fas-mediated cytotoxicity, Cancer Biol Ther 7 (2008) 1280-7.[5] A. Hamai, C. Richon, F. Meslin, F. Faure, A. Kauffmann, Y. Lecluse, A. Jalil, L. Larue, M.F. Avril, S. Chouaib, M. Mehrpour, Imatinib enhances human melanoma cell susceptibility to TRAIL-induced cell death: Relationship to Bcl-2 family and caspase activation, Oncogene 25 (2006) 7618-34.[6] S. Lucken-Ardjomande, J.C. Martinou, Regulation of Bcl-2 proteins and of the permeability of the outer mitochondrial membrane, C R Biol 328 (2005) 616-31.[7] M. Rescigno, V. Piguet, B. Valzasina, S. Lens, R. Zubler, L. French, V. Kindler, J. Tschopp, P. Ricciardi-Castagnoli, Fas engagement induces the maturation of dendritic cells (DCs), the release of interleukin (IL)-1beta, and the production of interferon gamma in the absence of IL-12 during DC-T cell cognate interaction: a new role for Fas ligand in inflammatory responses, J Exp Med 192 (2000) 1661-8.[8] C. Qian, L. Qian, Y. Yu, H. An, Z. Guo, Y. Han, Y. Chen, Y. Bai, Q. Wang, X. Cao, Fas signal promotes the immunosuppressive function of regulatory dendritic cells via the ERK/beta-catenin pathway, J Biol Chem 288 (2013) 27825-35.[9] L. Bo, S. Jiang, Y. Xie, H. Kan, W. Song, J. Zhao, Effect of Vitamin E and Omega-3 Fatty Acids on Protecting Ambient PM2.5-Induced Inflammatory Response and Oxidative Stress in Vascular Endothelial Cells, PLoS One 11 (2016) e0152216.[10] K.S. Ahn, G. Sethi, K. Krishnan, B.B. Aggarwal, Gamma-tocotrienol inhibits nuclear factor-kappaB signaling pathway through inhibition of receptor-interacting protein and TAK1 leading to suppression of antiapoptotic gene products and potentiation of apoptosis, J Biol Chem 282 (2007) 809-20.[11] E. Pierpaoli, V. Viola, F. Pilolli, M. Piroddi, F. Galli, M. Provinciali, Gamma- and delta-tocotrienols exert a more potent anticancer effect than alpha-tocopheryl succinate on breast cancer cell lines irrespective of HER-2/neu expression, Life Sci 86 (2010) 668-75.[12] A.A. Albahrani, R.F. Greaves, Fat-Soluble Vitamins: Clinical Indications and Current Challenges for Chromatographic Measurement, Clin Biochem Rev 37 (2016) 27-47.[13] E. Shumilina, N. Zahir, N.T. Xuan, F. Lang, Phosphoinositide 3-kinase dependent regulation of Kv channels in dendritic cells, Cell Physiol Biochem 20 (2007) 801-8.[14] X. Jin, L. Song, X. Liu, M. Chen, Z. Li, L. Cheng, H. Ren, Protective efficacy of vitamins C and E on p,p'-DDT-induced cytotoxicity via the ROS-mediated mitochondrial pathway and NF-kappaB/FasL pathway, PLoS One 9 (2014) e113257.[15] B.C. Richardson, N.D. Lalwani, K.J. Johnson, R.M. Marks, Fas ligation triggers apoptosis in macrophages but not endothelial cells, Eur J Immunol 24 (1994) 2640-5.[16] J. Tschopp, M. Irmler, M. Thome, Inhibition of fas death signals by FLIPs, Curr Opin Immunol 10 (1998) 552-8.[17] J. Chung, Y.O. Yoon, J.S. Lee, T.K. Ha, S.M. Ryu, K.H. Kim, M.H. Jeong, T.R. Yoon, H.K. Kim, Inulin induces dendritic cells apoptosis through the caspase-dependent pathway and mitochondrial dysfunction, Biol Pharm Bull 34 (2011) 495-500.[18] S. Kreuz, D. Siegmund, J.J. Rumpf, D. Samel, M. Leverkus, O. Janssen, G. Hacker, O. Dittrich-Breiholz, M. Kracht, P. Scheurich, H. Wajant, NFkappaB activation by Fas is mediated through FADD, caspase-8, and RIP and is inhibited by FLIP, J Cell Biol 166 (2004) 369-80.[19] S. Buonocore, S. Van Meirvenne, F.X. Demoor, F. Paulart, K. Thielemans, M. Goldman, V. Flamand, Dendritic cells transduced with viral interleukin 10 or Fas ligand: no evidence for induction of allotolerance in vivo, Transplantation 73 (2002) S27-30.[20] D. Ashany, A. Savir, N. Bhardwaj, K.B. Elkon, Dendritic cells are resistant to apoptosis through the Fas (CD95/APO-1) pathway, J Immunol 163 (1999) 5303-11.[21] D. Ashany, X. Song, E. Lacy, J. Nikolic-Zugic, S.M. Friedman, K.B. Elkon, Th1 CD4+ lymphocytes delete activated macrophages through the Fas/APO-1 antigen pathway, Proc Natl Acad Sci U S A 92 (1995) 11225-9.[22] S. Qi, W. Fu, C. Wang, C. Liu, C. Quan, A. Kourouma, M. Yan, T. Yu, P. Duan, K. Yang, BPA-induced apoptosis of rat Sertoli cells through Fas/FasL and JNKs/p38 MAPK pathways, Reprod Toxicol 50 (2014) 108-16.[23] L.P. Eberl, G. Egidy, F. Pinet, L. Juillerat-Jeanneret, Endothelin receptor blockade potentiates FasL-induced apoptosis in colon carcinoma cells via the protein kinase C-pathway, J Cardiovasc Pharmacol 36 (2000) S354-6.[24] N.T. Xuan, P.T. Trang, N. Van Phong, N.L. Toan, D.M. Trung, N.D. Bac, V.L. Nguyen, N.H. Hoang, N. Van Hai, Klotho sensitive regulation of dendritic cell functions by vitamin E, Biol Res 49 (2016) 45-54.[25] M. Baskiewicz-Masiuk, B. Machalinski, The role of the STAT5 proteins in the proliferation and apoptosis of the CML and AML cells, Eur J Haematol 72 (2004) 420-9.

Introdução: O padrão ouro atual para detectar o RNA de SARS-CoV-2 é por reação em cadeia da polimerase em tempo real de transcrição reversa (RT-rtPCR) em swabs nasofaríngeos (NPS). Por esse motivo, a demanda pelos NPS aumentou e sua escassez se tornou uma realidade em muitos países. Com isso o uso da saliva se mostra uma alternativa promissora na triagem epidemiológica além de ser de fácil coleta e não invasiva. Objetivo: realizar uma revisão sistemática da literatura para avaliar o uso da saliva como um espécime alternativo para a detecção de SARS-CoV-2. Metodologia: A pesquisa sistemática foi realizada em sete bancos de dados (PubMed, Cochrane Library, Lilacs, Scielo, Web of Science, Scopus e Google Scholar) usando a variação dos termos de pesquisa (COVID-19 OR SARS-CoV-2 OR 2019-nCoV) AND "Saliva" no ano de 2020, recuperando 5480 publicações. Resultados: Após a leitura dos títulos e resumos, 411 textos foram conduzidos para leitura integral e 30 publicações foram consideradas para avaliação qualitativa do artigo. Conclusão: A saliva se apresenta um método alternativo eficaz para a detecção de SARS-CoV-2 e diagnóstico de COVID-19.Descritores: Infecções por Coronavírus; Betacoronavirus; Saliva; Diagnóstico.ReferênciasHuang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497-506.Wang L, Wang Y, Ye D, Liu Q. A review of the 2019 Novel Coronavirus (COVID-19) based on current evidence. J Antimicrob Agents 2020;105948.Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 2020;382:727-733.Coronaviridae Study Group of the International Committee on Taxonomy of V. 2020. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020;5:536-544.Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, et al. The incubation period of Coronavirus Disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med. 2020;172:577-82.To KK, Tsang OT, Chik-Yan Yip C, Chan KH, Wu TC, Chan JMC, et al. Consistent detection of 2019 novel coronavirus in saliva. Clin Infect Dis. 2020;149:5734265.Xu R, Cui B, Duan X, Zhang P, Zhou X, Yuan Q. Saliva: potential diagnostic value and transmission of 2019-nCoV. Int J Oral Sci. 2020;12:11.Khurshid Z, Asiri FYI, Al Wadaani H. Human Saliva: Non-Invasive Fluid for Detecting Novel Coronavirus (2019-nCoV). Int J Environ Res Public Health. 2020;17.Khurshid Z, Zohaib S, Najeeb S, Zafar MS, Slowey PD, Almas K. Human Saliva Collection Devices for Proteomics: An Update. Int J Mol Sci. 2016;17.Principais itens para relatar Revisões sistemáticas e Meta-análises: A recomendação PRISMA. Epidemiol. E Serviços Saúde 2015;24:335–42.Abdul MSM, Fatima U, Khanna SS, Bhanot R, Sharma A, Srivastava AP. Oral Manifestations of Covid-19-Are they the introductory symptoms?. J Adv Dent Sci Res. 2020;8:5.Azzi L, Carcano G, Dalla Gasperina D, Sessa F, Maurino V, Baj A. Two cases of COVID-19 with positive salivary and negative pharyngeal or respiratory swabs at hospital discharge: A rising concern. Oral Dis. 2020;00:1-3.Azzi L, Carcano G, Gianfagna F, Grossi P, Dalla Gasperina D, Genoni A, et al. Saliva is a reliable tool to detect SARS-CoV-2. J Infect. 2020;81:45-50.Becker D, Sandoval E, Amin A, De Hoff P, Leonetti N, Lim YW, et al. Saliva is less sensitive than nasopharyngeal swabs for COVID-19 detection in the community setting. medRxiv. 2020;20092338.Braz-Silva PH, Pallos D, Giannecchini S, To KKW. SARS-CoV-2: What can saliva tell us?. Oral Dis. 2020;13365.Chan JFW, Yip CCY, To KKW, Tang THC, Wong SCY, Leung KH, et al. Improved molecular diagnosis of COVID-19 by the novel, highly sensitive and specific COVID-19-RdRp/Hel real-time reverse transcription-PCR assay validated in vitro and with clinical specimens. J Clin Microbiol. 2020;58:5.Chen L, Zhao J, Peng J, Li X, Deng X, Geng Z, et al. Detection of 2019-nCoV in saliva and characterization of oral symptoms in COVID-19 patients. Lancet. 2020;3556665.Cheng VC, Wong SC, Chen JH, Yip CC, Chuang VW, Tsang OT, et al. Escalating infection control response to the rapidly evolving epidemiology of the Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 in Hong Kong. Infect Control Hosp Epidemiol. 2020;41:493-498.Han P, Ivanovski S. Saliva—Friend and Foe in the COVID-19 Outbreak. Diagn. 2020;10:290.Iwasaki S, Fujisawa S, Nakakubo S, Kamada K, Yamashita Y, Fukumoto T, et al. Comparison of SARS-CoV-2 detection in nasopharyngeal swab and saliva. J Infect. 2020;20:30349.Krajewska J, Krajewski W, Zub K, Zatoński T. COVID-19 in otolaryngologist practice: a review of current knowledge. Eur Arch Otorhinolaryngol. 2020;1-13.Lalli MA, Chen X, Langmade SJ, Fronick CC, Sawyer CS, Burcea LC, et al. Rapid and extraction-free detection of SARS-CoV-2 from saliva with colorimetric LAMP. medRxiv. 2020;7273276.Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020;10:101-108.Li H, Liu SM, Yu XH, Tang SL, Tang CK. Coronavirus disease 2019 (COVID-19): current status and future perspective. Int J Antimicrob Agents. 2020;105951.McCormick-Baw C, Morgan K, Gaffney D, Cazares Y, Jaworski K, Byrd A, et al. Saliva as an Alternate Specimen Source for Detection of SARS-CoV-2 in Symptomatic Patients Using Cepheid Xpert Xpress SARS-CoV-2. J Clin Microbiol. 2020;01109-20.Pasomsub E, Watcharananan SP, Boonyawat K, Janchompoo P, Wongtabtim G, Suksuwan W, et al. Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease-2019 (COVID-19): a cross-sectional study. Clin Microbiol Infect. 2020;20302780.Sabino-Silva R, Jardim ACG, Siqueira WL. Coronavirus COVID-19 impacts to dentistry and potential salivary diagnosis. Clinical oral investigations. 2020;1-3.Sapkota D, Thapa SB, Hasséus B, Jensen JL. Saliva testing for COVID-19?. BDJ. 2020;228:658-659.Sharma S, Kumar V, Chawla A, Logani A. Rapid detection of SARS-CoV-2 in saliva: Can an endodontist take the lead in point-of-care COVID-19 testing?. Int Endod J. 2020;13317.Tang YW, Schmitz JE, Persing DH, Stratton CW. Laboratory Diagnosis of COVID-19: Current Issues and Challenges. J Clin Microbiol. 2020;58(6).Tatikonda SS, Reshu P, Hanish A, Konkati S, Madham S. A Review of Salivary Diagnostics and Its Potential Implication in Detection of Covid-19. Cureus. 2020;12(4).To KKW, Tsang OTY, Leung WS, Tam AR, Wu TC, Lung DC, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. 2020;20:565-574.Vinayachandran D, Saravanakarthikeyan B. Salivary diagnostics in COVID-19: Future research implications. J Dent Sci. 2020;7177105.Williams E, Bond K, Zhang B, Putland M, Williamson DA. Saliva as a non-invasive specimen for detection of SARS-CoV-2. J Clin Microbiol. 2020;00776-20.Wyllie AL, Fournier J, Casanovas-Massana A, Campbell M, Tokuyama M, Vijayakumar P, et al. Saliva is more sensitive for SARS-CoV-2 detection in COVID-19 patients than nasopharyngeal swabs. Medrxiv. 2020;20067835.Yoon JG, Yoon J, Song JY, Yoon SY, Lim CS, Seong H, et al. Clinical Significance of a High SARS-CoV-2 Viral Load in the Saliva. J Korean Med Sci. 2020;35(20).Zheng S, Yu F, Fan J, Zou Q, Xie G, Yang X, et al. Saliva as a Diagnostic Specimen for SARS-CoV-2 by a PCR-Based Assay: A Diagnostic Validity Study. Lancet. 2020;3543605.Zhong F, Liang Y, Xu J, Chu M, Tang G, Hu F, et al. Continuously High Detection Sensitivity of Saliva, Viral Shedding in Salivary Glands and High Viral Load in Patients with COVID-19. Lancet. 2020;3576869.

Introdução: A transmissão SARS-CoV-2 de humano para humano pode ocorrer e o risco de propagação no ar durante os procedimentos odontológicos geradores de aerossóis permanece uma preocupação. Acredita-se que um enxaguatório bucal antimicrobiano pré-operacional reduza o número de micróbios orais. No entanto, a eficácia do enxaguatório bucal pré-procedimento na redução do número de microrganismos disseminados por meio do aerossol gerado por procedimentos odontológicos ainda não está clara. Objetivo: avaliar através de uma revisão de literatura o uso de enxaguantes bucais na redução da carga viral do SARS-CoV-2. Materiais e Método: O levantamento literário para esta pesquisa foi realizado no período de dezembro de 2019 a 10 de agosto de 2020 nas bases de dados Scielo e Medline/PubMed. Na estratégia de busca, foram utilizadas as palavras “SARS-CoV-2”, “2019-nCoV”, “COVID-19”, “Dentistry”, “Odontologia”, “Odontología”, “Mouthwashes”, “Antissépticos Bucais” e “Antisépticos Bucales”. Resultados: Uma busca sistematizada foi realizada, foram encontrados 661 artigos, após a realização da leitura criteriosa dos artigos completos foram selecionados 42 artigos. 88% dos estudos indicavam o uso de Peróxido de hidrogênio a 1%, 76% indicavam Povidine 0,2% e apenas 19% o uso da Clorexidina a 0,12%. Conclusão: Os estudos presentes na literatura apresentam divergências nas indicações e porcentagens dos enxaguantes indicados. Os protocolos clínicos devem ser avaliados para reduzir o risco de transmissão e proteger pacientes e profissionais.Descritores: Infecções por Coronavírus; Betacoronavirus; Odontologia; Antissépticos Bucais.ReferênciasGe ZY, Yang LM, Xia JJ, Fu XH, Zhang YZ. Possible aerosol transmission of COVID-19 and special precautions in dentistry. J Zhejiang Univ Sci B. 2020;21(5):361-68. Peng X, Xu X, Li Y, Cheng L, Zhou X, Ren B. Transmission routes of 2019-nCoV and controls in dental practice. Int J Oral Sci. 2020;12(1):9.Fallahi HR, Keyhan SO, Zandian D, Kim SG, Cheshmi B. Being a front-line dentist during the Covid-19 pandemic: a literature review. Maxillofac Plast Reconstr Surg. 2020;42(1):12.Yoon JG, Yoon J, Song JY, Yoon SY, Lim CS, Seong H, et al. Clinical Significance of a High SARS-CoV-2 Viral Load in the Saliva. J Korean Med Sci. 2020;35(20):e195.Alharbi A, Alharbi S, Alqaidi S. Guidelines for dental care provision during the COVID-19 pandemic. Saudi Dent J. 2020;32(4):181-86.Amato A, Caggiano M, Amato M, Moccia G, Capunzo M, De Caro F. Infection Control in Dental Practice During the COVID-19 Pandemic. Int J Environ Res Public Health. 2020;17(13):4769.Amorim, LM, Maske TT, Ferreira SH, Santos RB, Feldens CA, Kramer PF. New Post-COVID-19 Biosafety Protocols in Pediatric Dentistry. Pesqui Bras Odontopediatria Clín. Integr. 2020; 20(Suppl 1): e0117.Araya-Salas,C. Consideraciones para la Atención de Urgencia Odontológica y Medidas Preventivas para COVID-19 (SARS-CoV 2). Int. J. Odontostomat. 2020;14(3):268-70.Ather A, Patel B, Ruparel NB, Diogenes A, Hargreaves KM. Coronavirus Disease 19 (COVID-19): Implications for Clinical Dental Care. J Endod. 2020;46(5):584-95.Bahramian H, Gharib B, Baghalian A. COVID-19 Considerations in Pediatric Dentistry. JDR Clin Trans Res. 2020:2380084420941503.Bajaj N, Granwehr BP, Hanna EY, Chambers MS. Salivary detection of SARS-CoV-2 (COVID-19) and implications for oral health-care providers. Head Neck. 2020;42(7):1543-47.Barabari P, Moharamzadeh K. Novel Coronavirus (COVID-19) and Dentistry-A Comprehensive Review of Literature. Dent J (Basel). 2020;8(2):53.Barca I, Cordaro R, Kallaverja E, Ferragina F, Cristofaro MG. Management in oral and maxillofacial surgery during the COVID-19 pandemic: Our experience. 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Diabetes Mellitus has been becoming a disease of the century, and disease incidence is still rising worldwide. It causes many serious complications, especially in the eye, heart, kidneys, brain, and vascular system, such as diabetic nephropathy, diabetic retinopathy, liver fa­ilure, etc. Moreover, the process of controlling this disease is complicated. Meanwhile, the antidiabetic drugs on the market are facing some problems with a wide range of adverse reactions. Therefore, finding new drugs to treat diabetes has always been a topic that many researchers are interested in, especially drugs derived from nature like microorganisms and medicinal plants. This review is to provide knowledge concerning the effects of α-glucosidase inhibitors, which are oral antidiabetic drugs commonly used for diabetes mellitus type 2. Besides, we show readers the variety of active ingredients originating from nature, particularly the secondary metabolites of Aspergillus spp., which have many applications in the chemical and medicinal industry. Keywords: Diabetes, α-glucosidase inhibitors, Aspergillus. References [1] W. H. Organization, Classification of Diabetes Mellitus, https://www.who.int/westernpacific/health-topics/diabetes (accessed on: May 11th, 2021).[2] J. Thrasher, Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies, Am J Cardiol, Vol. 120, No. 1, 2017, pp. S4-S16, https://doi.org/10.1016/j.amjcard.2017.05.009.[3] W. Hakamata, M. Kurihara, H. Okuda, T. Nishio, T. 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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus , is causing a serious worldwide COVID-19 pandemic. The emergence of strains with rapid spread and unpredictable changes is the cause of the increase in morbidity and mortality rates. A number of drugs as well as vaccines are currently being used to relieve symptoms, prevent and treat the disease caused by this virus. However, the number of approved drugs is still very limited due to their effectiveness and side effects. In such a situation, medicinal plants and bioactive compounds are considered a highly valuable source in the development of new antiviral drugs against SARS-CoV-2. This review summarizes medicinal plants and bioactive compounds that have been shown to act on molecular targets involved in the infection and replication of SARS-CoV-2. Keywords: Medicinal plants, bioactive compounds, antivirus, SARS-CoV-2, COVID-19 References [1] R. Lu, X. Zhao, J. Li, P. Niu, B. Yang, H. 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