Arecoline induces dual modulation of blood pressure in rat, including an initial downregulation and a subsequent upregulation

Purpose: To determine the role of arecoline in cardiovascular modulation in rats.Methods: After rats were anaesthetized with intraperitoneal urethane (1.4 g/kg body weight), saline or arecoline (at doses of 1.0, 3.0 and 10.0 mg/kg) was intraperitoneally administered, and blood pressure (BP) was continuously recorded using a physiological apparatus. Mean arterial pressure (MAP), maximum changes in MAP and reaction time due to arecoline stimulations were calculated and analyzed.Results: Arecoline induced biphasic modulation in BP, including an initial downregulation followed by a subsequent upregulation. The MAP and maximum change in MAP exhibited a concentration-dependent effect in the downregulation phase (p < 0.001 within each group), but not in the upregulation phase (p > 0.05 within each group), while BP reaction time showed a dose-dependent prolongation in both downregulation and upregulation phases (ps < 0.01 within each group). Remarkably, arecoline-induced BP downregulation more rapidly and drastically than upregulation in each arecoline group.Conclusion: These results indicate that arecoline exerts a complex effect in cardiovascular modulation that should be considered as side effects in the clinical use of arecoline and/or with the habitual chewing of areca nuts. Keywords: Arecoline, Blood pressure, Downregulation, Upregulatio

Accurately identifying hemagglutinin using sequence information and machine learning methods

IntroductionHemagglutinin (HA) is responsible for facilitating viral entry and infection by promoting the fusion between the host membrane and the virus. Given its significance in the process of influenza virus infestation, HA has garnered attention as a target for influenza drug and vaccine development. Thus, accurately identifying HA is crucial for the development of targeted vaccine drugs. However, the identification of HA using in-silico methods is still lacking. This study aims to design a computational model to identify HA.MethodsIn this study, a benchmark dataset comprising 106 HA and 106 non-HA sequences were obtained from UniProt. Various sequence-based features were used to formulate samples. By perform feature optimization and inputting them four kinds of machine learning methods, we constructed an integrated classifier model using the stacking algorithm.Results and discussionThe model achieved an accuracy of 95.85% and with an area under the receiver operating characteristic (ROC) curve of 0.9863 in the 5-fold cross-validation. In the independent test, the model exhibited an accuracy of 93.18% and with an area under the ROC curve of 0.9793. The code can be found from https://github.com/Zouxidan/HA_predict.git. The proposed model has excellent prediction performance. The model will provide convenience for biochemical scholars for the study of HA

Benefits and risks of drug combination therapy for diabetes mellitus and its complications: a comprehensive review

Diabetes is a chronic metabolic disease, and its therapeutic goals focus on the effective management of blood glucose and various complications. Drug combination therapy has emerged as a comprehensive treatment approach for diabetes. An increasing number of studies have shown that, compared with monotherapy, combination therapy can bring significant clinical benefits while controlling blood glucose, weight, and blood pressure, as well as mitigating damage from certain complications and delaying their progression in diabetes, including both type 1 diabetes (T1D), type 2 diabetes (T2D) and related complications. This evidence provides strong support for the recommendation of combination therapy for diabetes and highlights the importance of combined treatment. In this review, we first provided a brief overview of the phenotype and pathogenesis of diabetes and discussed several conventional anti-diabetic medications currently used for the treatment of diabetes. We then reviewed several clinical trials and pre-clinical animal experiments on T1D, T2D, and their common complications to evaluate the efficacy and safety of different classes of drug combinations. In general, combination therapy plays a pivotal role in the management of diabetes. Integrating the effectiveness of multiple drugs enables more comprehensive and effective control of blood glucose without increasing the risk of hypoglycemia or other serious adverse events. However, specific treatment regimens should be tailored to individual patients and implemented under the guidance of healthcare professionals

A New Method for Finding the Shape of the Main Cable in the Special Cable Plane

The main cable and suspender of the spatial special-shaped suspension bridge are in the state of spatial stress; the structural stress is more complex than that of the parallel cable plane and finding the shape of the main cable of the spatial special-shaped cable plane is more difficult. In order to solve the problem of finding the shape of the main cable of the special-shaped suspension bridge, a new calculation model and algorithm of the main cable are proposed in this paper. The new calculation model adds constraints on the transverse bridge direction coordinates of the midspan on the basis of the original calculation model. The new calculation model can timely correct the calculation errors in all directions of the control node during the main cable shape finding process and improve the calculation accuracy. The new algorithm is a hybrid algorithm. The algorithm first uses the modified quantum genetic algorithm to solve and calculate the cable end force close to the real value, and then uses the cable end force obtained by the modified quantum genetic algorithm as the initial value to iterate through the modified least squares method. In this paper, a single cable plane curved suspension bridge is taken as the research background, and the differences of different calculation models in the shape-finding calculation of the main cable of the spatial special-shaped cable plane are compared. The results show that the proposed model is more stable in the calculation process, and the proposed algorithm has high accuracy and strong adaptability

A New Method for Finding the Shape of the Main Cable in the Special Cable Plane

The main cable and suspender of the spatial special-shaped suspension bridge are in the state of spatial stress; the structural stress is more complex than that of the parallel cable plane and finding the shape of the main cable of the spatial special-shaped cable plane is more difficult. In order to solve the problem of finding the shape of the main cable of the special-shaped suspension bridge, a new calculation model and algorithm of the main cable are proposed in this paper. The new calculation model adds constraints on the transverse bridge direction coordinates of the midspan on the basis of the original calculation model. The new calculation model can timely correct the calculation errors in all directions of the control node during the main cable shape finding process and improve the calculation accuracy. The new algorithm is a hybrid algorithm. The algorithm first uses the modified quantum genetic algorithm to solve and calculate the cable end force close to the real value, and then uses the cable end force obtained by the modified quantum genetic algorithm as the initial value to iterate through the modified least squares method. In this paper, a single cable plane curved suspension bridge is taken as the research background, and the differences of different calculation models in the shape-finding calculation of the main cable of the spatial special-shaped cable plane are compared. The results show that the proposed model is more stable in the calculation process, and the proposed algorithm has high accuracy and strong adaptability

MoTe2 : semiconductor or semimetal?

Transition metal tellurides (TMTs) have attracted intense interest due to their intriguing physical properties arising from their diverse phase topologies. To date, a wide range of physical properties have been discovered for TMTs, including that they can act as topological insulators, semiconductors, Weyl semimetals, and superconductors. Among the TMT families, MoTe2 is a representative material because of its Janus nature and rich phases. In this Perspective, we first introduce phase structures in monolayer and bulk MoTe2 and then summarize MoTe2 synthesis strategies. We highlight recent advances of Janus MoTe2 in terms of material structures and emerging quantum states. We also provide insight into the opportunities and challenges faced by MoTe2-associated device design and applications.Ministry of Education (MOE)Nanyang Technological UniversityNational Research Foundation (NRF)Submitted/Accepted versionZ.L. acknowledges support from National Research Foundation Singapore programme NRF-CRP22-2019-0007 and NRFCRP21-2018-0007.This work is also supported by the Ministry of Education, Singapore, under its AcRF Tier 3 Programme “Geometrical Quantum Materials” (MOE2018-T3-1-002). X.Z. acknowledges support from Singapore NTU Presidential Postdoctoral Fellowship (03INS000973C150). G.L. acknowledges support from National Basic Research Program of China from the MOST (2016YFA0300601, 2014CB920904, and 2015CB921402), National Natural Science Foundation of China (92065203, 11527806, and 11874406), Beijing Municipal Science & Technology Commission of China (Z191100007219008), Beijing Academy of Quantum Information Sciences (Y18G08), Strategic Priority Research Program of the Chinese Academy of Sciences (XDB33010300), and by the Synergic Extreme Condition User Facility

Whole genome HBV deletion profiles and the accumulation of preS deletion mutant during antiviral treatment

Abstract Background Hepatitis B virus (HBV), because of its error-prone viral polymerase, has a high mutation rate leading to widespread substitutions, deletions, and insertions in the HBV genome. Deletions may significantly change viral biological features complicating the progression of liver diseases. However, the clinical conditions correlating to the accumulation of deleted mutants remain unclear. In this study, we explored HBV deletion patterns and their association with disease status and antiviral treatment by performing whole genome sequencing on samples from 51 hepatitis B patients and by monitoring changes in deletion variants during treatment. Clone sequencing was used to analyze preS regions in another cohort of 52 patients. Results Among the core, preS, and basic core promoter (BCP) deletion hotspots, we identified preS to have the highest frequency and the most complex deletion pattern using whole genome sequencing. Further clone sequencing analysis on preS identified 70 deletions which were classified into 4 types, the most common being preS2. Also, in contrast to the core and BCP regions, most preS deletions were in-frame. Most deletions interrupted viral surface epitopes, and are possibly involved in evading immuno-surveillance. Among various clinical factors examined, logistic regression showed that antiviral medication affected the accumulation of deletion mutants (OR = 6.81, 95% CI = 1.296 ~ 35.817, P = 0.023). In chronic carriers of the virus, and individuals with chronic hepatitis, the deletion rate was significantly higher in the antiviral treatment group (Fisher exact test, P = 0.007). Particularly, preS2 deletions were associated with the usage of nucleos(t)ide analog therapy (Fisher exact test, P = 0.023). Dynamic increases in preS1 or preS2 deletions were also observed in quasispecies from samples taken from patients before and after three months of ADV therapy. In vitro experiments demonstrated that preS2 deletions alone were not responsible for antiviral resistance, implying the coordination between wild type and mutant strains during viral survival and disease development. Conclusions We present the HBV deletion distribution patterns and preS deletion substructures in viral genomes that are prevalent in northern China. The accumulation of preS deletion mutants during nucleos(t)ide analog therapy may be due to viral escape from host immuno-surveillance.</p

Hierarchical and ultrathin copper nanosheets synthesized via galvanic replacement for selective electrocatalytic carbon dioxide conversion to carbon monoxide

Electrochemical conversion of carbon dioxide (CO2) to desirable products with high selectivity and efficiency remains critical challenges in balancing carbon cycle for sustainable society. Herein, we demonstrate the hierarchical porous architectures assembled by ultrathin copper (Cu) nanosheets (NS) via a simple galvanic replacement method for the improved selectivity of CO2 conversion with a large current density. Specifically, the optimized hierarchical Cu electrodes achieve high selectivity and activity to convert CO2 into CO, showing a Faradaic efficiency (FE) of 74.1%, record-high partial current density of 23.0 mA cm−2, and turnover frequency of 0.092 s-1 for CO product as well as FE of 24.8% for H2 at potential of -1.0 V vs RHE. The onset potential for the CO2 conversion is -0.29 V vs RHE. Theoretical calculations indicate that the abundant vacancy defects exposed on ultrathin Cu nanosheets can accelerate the initial kinetics of CO formation during the CO2 conversion process. As demonstrated by experimental and computational analyses, the unique hierarchical architecture of integrated Cu electrode contributes the outstanding electrocatalytic performance due to the rapid mass and electrons transport as well as the abundant active sites and associated intrinsic activity.This work is financially supported by National 1000 Young Talents Program of China. The Fundamental Research Funds for the Central Universities (2018KFYXKJC044, 2018KFYYXJJ121, 2017KFXKJC002, 2017KFYXJJ164) and the Innovation Foundation of Shenzhen Government (JCYJ20160408173202143) are also acknowledged. H. S. Park acknowledges financial support from the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning of the Korean Government (NRF-2015R1A1A1A05027727). The authors also acknowledge the support of the Analytical and Testing Center of Huazhong University of Science and Technology for XRD, SEM, TEM and AFM measurements

Connexin32 gap junction channels deliver miR155-3p to mediate pyroptosis in renal ischemia-reperfusion injury

Abstract Objectives To explore whether the gap junction (GJ) composed by connexin32(Cx32) mediated pyroptosis in renal ischemia-reperfusion(I/R) injury via transmitting miR155-3p, with aim to provide new strategies for the prevention and treatment of acute kidney injury (AKI) after renal I/R. Methods 8–10 weeks of male C57BL/ 6 wild-type mice and Cx32 knockdown mice were divided into two groups respectively: control group and renal I/R group. MCC950 (50 mg/kg. ip.) was used to inhibit NLRP3 in vivo. Human kidney tubular epithelial cells (HK - 2) and rat kidney tubular epithelial cells (NRK-52E) were divided into high-density group and low-density group, and treated with hypoxia reoxygenation (H/R) to mimic I/R. The siRNA and plasmid of Cx32, mimic and inhibitor of miR155-3p were transfected into HK - 2 cells respectively. Kidney pathological and functional injuries were measured. Western Blot and immunofluorescent staining were used to observe the expression of NLRP3, GSDMD, GSDMD-N, IL - 18, and mature IL-18. The secretion of IL-18 and IL-1β in serum, kidney tissue and cells supernatant were detected by enzyme-linked immuno sorbent assay (ELISA) kit, and the expression of NLPR3 and miR155-3p were detected by RT-qPCR and fluorescence in situ hybridization (FISH). Results Tubular pyroptosis were found to promote AKI after I/R in vivo and Cx32-GJ regulated pyroptosis by affecting the expression of miR155-3p after renal I/R injury. In vitro, H/R could lead to pyroptosis in HK-2 and NRK-52E cells. When the GJ channels were not formed, and Cx32 was inhibited or knockdown, the expression of miR155-3p was significantly reduced and the pyroptosis was obviously inhibited, leading to the reduction of injury and the increase of survival rate. Moreover, regulating the level of miR155-3p could affect survival rate and pyroptosis in vitro after H/R. Conclusions The GJ channels composed of Cx32 regulated tubular pyroptosis in renal I/R injury by transmitting miR155-3p. Inhibition of Cx32 could reduce the level of miR155-3p further to inhibit pyroptosis, leading to alleviation of renal I/R injury which provided a new strategy for preventing the occurrence of AKI. Video Abstrac

Hepatitis B virus genotype is an independent prognostic factor of telbivudine and tenofovir treatment in hepatitis B surface antigen-positive pregnant women

To investigate whether HBV genotype influences the effect of tenofovir and telbivudine on HBV DNA and RNA levels in HBsAg-positive pregnant women. This was a retrospective study of 74 HBsAg-positive pregnant women in Guizhou of China. All patients were treated with telbivudine or tenofovir from 12 weeks of pregnancy and HBV infection to the date of delivery. Blood samples were collected at 12–24, 28–32, and 36–40 weeks of pregnancy for the measurement of genotype, HBsAg, hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA, and liver function, including alanine transaminase, aspartate transaminase, total bilirubin, total bile acids, cholinesterase, alkaline phosphatase (ALP), and gamma-glutamyl transferase. All women with HBsAg were followed up. The HBV genotype was B in 64.9% and C in 35.1%. There were 37 patients of telbivudine and tenofovir group respectively. The telbivudine and tenofovir groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log10(HBV DNA), and log10(HBV RNA). Compared with baseline (12–24 weeks), telbivudine group showed a significant increase in ALP and significant reductions in HBsAg, HBeAg, log10(HBV DNA), and log10(HBV RNA) at 36–40 weeks (p &lt; .05). Tenofovir group exhibited a significant increase in ALP and significant reductions in HBeAg, log10(HBV DNA), and log10(HBV RNA) at 36–40 weeks, compared with baseline (p &lt; .05). HBV genotype (B vs. C) was independently associated with HBV DNA change after therapy (p = .005). In telbivudine group, log10 (HBV DNA) increased from 3.38 (2.00–7.30) to 7.43 (4.68–8.70). In tenofovir group, log10 (HBV DNA) decreased from 7.52 (3.32–8.70) to 2.98 (2.00–5.01). HBV genotype was independently associated with HBV DNA change response to telbivudine or tenofovir in pregnant women with hepatitis B. These findings might be helpful for risk assessment regarding vertical transmission of HBV in HBeAg-positive mothers treated with nucleos(t)ide analogues