Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis

BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.

Polarimeter–interferometer diagnostic using terahertz solid-state sources for fluctuation measurements on Keda Torus e Xperiment(KTX)

A multi-channel polarimeter-interferometer has been developed on the Keda Torus eXperiment(KTX)for the study of equilibrium dynamics and internal magnetic fluctuations.A three-wave technique based on terahertz solid-state sources(-650 GHz)is applied for simultaneous measurements of electron density and Faraday rotation angle.The output power of the microwave source is 2 mW.Faraday rotation effect using a rotating wave plate is tested with phase noise less than 0.8°,and the density phase noise is less than 0.9°.Measurement of Faraday rotation angle and density for discharges on KTX have demonstrated high sensitivity to internal MHD activities.

Literature classification and its applications in condensed matter physics and materials science by natural language processing

The exponential growth of literature is constraining researchers’access to comprehensive information in related fields.While natural language processing(NLP)may offer an effective solution to literature classification,it remains hindered by the lack of labelled dataset.In this article,we introduce a novel method for generating literature classification models through semi-supervised learning,which can generate labelled dataset iteratively with limited human input.We apply this method to train NLP models for classifying literatures related to several research directions,i.e.,battery,superconductor,topological material,and artificial intelligence(AI)in materials science.The trained NLP‘battery’model applied on a larger dataset different from the training and testing dataset can achieve F1 score of 0.738,which indicates the accuracy and reliability of this scheme.Furthermore,our approach demonstrates that even with insufficient data,the not-well-trained model in the first few cycles can identify the relationships among different research fields and facilitate the discovery and understanding of interdisciplinary directions.

Autoimmune hepatitis-primary biliary cholangitis overlap syndrome complicated by various autoimmune diseases:A case report

BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune thyroid disease(AITD)is the most frequently overlapping extrahepatic autoimmune disease.Immunoglobulin(IgG)4-related disease is an autoimmune disease recognized in recent years,characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues.CASE SUMMARY A 68-year-old female patient was admitted with a history of right upper quadrant pain,anorexia,and jaundice on physical examination.Laboratory examination revealed elevated liver enzymes,multiple positive autoantibodies associated with liver and thyroid disease,and imaging and biopsy suggestive of pancreatitis,hepatitis,and PBC.A diagnosis was made of a rare and complex overlap syndrome of AIH,PBC,AITD,and IgG4-related disease.Laboratory features improved on treatment with ursodeoxycholic acid,methylprednisolone,and azathioprine.CONCLUSION This case highlights the importance of screening patients with autoimmune diseases for related conditions.

Pulmonary embolism secondary to acute anterior ST-elevation myocardial infarction:a case report

Thrombophilia denotes a condition,whether acquired or hereditary,characterized by increased susceptibility to hypercoagulation.[1]This condition was first described in 1965,coinciding with the discovery of an inherited predisposition to venous thromboembolism(VTE)in patients deficient in antithrombin III.[2]While arterial and venous thromboses are common in hospitalized patients,acute myocardial infarction(AMI)and pulmonary embolism(PE)stand out as lifethreateningconditions.However,theoccurrenceof AMI complicated by PE is exceedingly rare,especially when considering cases where paradoxical embolism originating from a patent foramen ovale is absent.This report presents a case of AMI complicated with PE.A comprehensive understanding of the pathophysiology of this rare yet critical condition is important for ensuring prompt diagnosis and treatment.

Global status and trends of metabolomics in diabetes: A literature visualization knowledge graph study

BACKGROUND Diabetes is a metabolic disease characterized by hyperglycemia,which has increased the global medical burden and is also the main cause of death in most countries.AIM To understand the knowledge structure of global development status,research focus,and future trend of the relationship between diabetes and metabolomics in the past 20 years.METHODS The articles about the relationship between diabetes and metabolomics in the Web of Science Core Collection were retrieved from 2002 to October 23,2023,and the relevant information was analyzed using CiteSpace6.2.2R(CiteSpace),VOSviewer6.1.18(VOSviewer),and Bibliometrix software under R language.RESULTS A total of 3123 publications were included from 2002 to 2022.In the past two decades,the number of publications and citations in this field has continued to increase.The United States,China,Germany,the United Kingdom,and other relevant funds,institutions,and authors have significantly contributed to this field.Scientific Reports and PLoS One are the journals with the most publications and the most citations.Through keyword co-occurrence and cluster analysis,the closely related keywords are"insulin resistance","risk","obesity","oxidative stress","metabolomics","metabolites"and"biomarkers".Keyword clustering included cardiovascular disease,gut microbiota,metabonomics,diabetic nephropathy,molecular docking,gestational diabetes mellitus,oxidative stress,and insulin resistance.Burst detection analysis of keyword depicted that"Gene","microbiota","validation","kidney disease","antioxidant activity","untargeted metabolomics","management",and"accumulation"are knowledge frontiers in recent years.CONCLUSION The relationship between metabolomics and diabetes is receiving extensive attention.Diabetic nephropathy,diabetic cardiovascular disease,and kidney disease are key diseases for future research in this field.Gut microbiota,molecular docking,and untargeted metabolomics are key research directions in the future.Antioxidant activity,gene,validation,mass spectrometry,management,and accumulation are at the forefront of knowledge frontiers in this field.

Clinical effect of laparoscopic radical resection of colorectal cancer based on propensity score matching

BACKGROUND The incidence of colorectal cancer(CRC)is increasing annually.Laparoscopic radical resection of CRC is a minimally invasive procedure preferred in clinical practice.AIM To investigate the clinical effect of laparoscopic radical resection of CRC on the basis of propensity score matching(PSM).METHODS The clinical data of 100 patients who received inpatient treatment for CRC at Changde Hospital,Xiangya School of Medicine,Central South University(The First People’s Hospital of Changde City)were analyzed retrospectively.The control group included patients who underwent open surgery(n=43),and those who underwent laparoscopic surgery formed the observation group(n=57).The baseline information of both groups was equipoised using 1×1 PSM.Differences in the perioperative parameters,inflammatory response,immune function,degree of pain,and physical status between the groups were analyzed.RESULTS Thirty patients from both groups were successfully matched.After PSM,baseline data showed no statistically significant differences between the groups:(1)Periop-erative parameters:The observation group had a longer surgery time,less intra-operative blood loss,earlier first ambulation and first anal exhaust times,and shorter gastric tube indwelling time than the control group;(2)Inflammatory response:24 h after surgery,the levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α)between groups were higher than preoperatively.IL-6,CRP,and TNF-αlevels in the observation group were lower than in the control group;(3)Immune function:At 24 h after surgery,counts of CD4-positive T-lymphocytes(CD4+)and CD4+/CD8-positive T-lymphocytes(CD8+)in both groups were lower than those before surgery,whereas CD8+was higher than that before surgery.At 24 h after surgery,both CD4+counts and CD4+/CD8+in the observation group were higher than those in the control group,whereas CD8+counts were lower;(4)Degree of pain:The visual analog scale scores in the observation group were lower than those in the control group at 24 and 72 h after surgery;and(5)Physical status:One month after surgery,the Karnofsky performance score in the observation group was higher than that in the control group.CONCLUSION Laparoscopic radical resection of CRC has significant benefits,such as reducing postoperative pain and postoperative inflammatory response,avoiding excessive immune inhibition,and contributing to postoperative recovery.

From Generalized Hamilton Principle to Generalized Schrodinger Equation

The Hamilton principle is a variation principle describing the isolated and conservative systems, its Lagrange function is the difference between kinetic energy and potential energy. By Feynman path integration, we can obtain the standard Schrodinger equation. In this paper, we have given the generalized Hamilton principle, which can describe the heat exchange system, and the nonconservative force system. On this basis, we have further given their generalized Lagrange functions and Hamilton functions. With the Feynman path integration, we have given the generalized Schrodinger equation of nonconservative force system and the heat exchange system.

Exendin-4 and linagliptin attenuate neuroinflammation in a mouse model of Parkinson's disease

Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence of Parkinson's disease in patients with diabetes mellitus.Therefore,using these two treatments may help treat Parkinson's disease.To further investigate the mechanisms of action of these two compounds,we established a model of Parkinson's disease by treating mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and then subcutaneously injected them with the glucagon-like peptide-1 receptor agonist exendin-4 or the dipeptidyl peptidase 4 inhibitor linagliptin.We found that both exendin-4 and linagliptin reversed motor dysfunction,glial activation,and dopaminergic neuronal death in this model.In addition,both exendin-4 and linagliptin induced microglial polarization to the anti-inflammatory M2 phenotype and reduced pro-inflammatory cytokine secretion.Moreover,in vitro experiments showed that treatment with exendin-4 and linagliptin inhibited activation of the nucleotide-binding oligomerization domain-and leucine-rich-repeat-and pyrin-domaincontaining 3/caspase-1/interleukin-1βpathway and subsequent pyroptosis by decreasing the production of reactive oxygen species.These findings suggest that exendin-4 and linagliptin exert neuroprotective effects by attenuating neuroinflammation through regulation of microglial polarization and the nucleotidebinding oligomerization domain-and leucine-rich-repeat-and pyrin-domain-containing 3/caspase-1/interleukin-1βpathway in a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Therefore,these two drugs may serve as novel anti-inflammatory treatments for Parkinson's disease.

Reduced power consumption in stirred vessel with high solid loading by equipping punched baffles

Solid-liquid suspension in stirred tank is a common operation in the chemical industry. The power consumption, flow pattern and flow field instability of three systems named as unbaffled stirred tank, traditional baffled stirred tank and punched baffled stirred tank(Pun-BST) were studied by using the computational fluid dynamic analysis. Results showed that perforating holes in the baffles could reduce power consumption of mixing. Meanwhile, the punched baffle system could maintain the solids in suspension as traditional baffle system. The results also showed that the baffles could increase the “effective flow” of stirred tank even though the whole velocity of the vessel is lower than un-baffled vessel. In addition, both the solid-liquid suspension and “effective flow” were related to instability of the flow field.Perfect solid-liquid suspension results always along with obvious instability of the flow field. But, the strengthening effect of punched baffle on flow field instability mainly happened in the near-wall area.It's because the collision and aggregation among sub-streams induced by holes intensified the unstable fluid flow. On the whole, the Pun-BST system provided much better mixing characteristics and recommended to apply in the industrial process.

Non-invasive model for predicting high-risk esophageal varices based on liver and spleen stiffness

BACKGROUND Acute bleeding due to esophageal varices(EVs)is a life-threatening complication in patients with cirrhosis.The diagnosis of EVs is mainly through upper gastrointestinal endoscopy,but the discomfort,contraindications and complications of gastrointestinal endoscopic screening reduce patient compliance.According to the bleeding risk of EVs,the Baveno VI consensus divides varices into high bleeding risk EVs(HEVs)and low bleeding risk EVs(LEVs).We sought to identify a non-invasive prediction model based on spleen stiffness measurement(SSM)and liver stiffness measurement(LSM)as an alternative to EVs screening.AIM To develop a safe,simple and non-invasive model to predict HEVs in patients with viral cirrhosis and identify patients who can be exempted from upper gastrointestinal endoscopy.METHODS Data from 200 patients with viral cirrhosis were included in this study,with 140 patients as the modelling group and 60 patients as the external validation group,and the EVs types of patients were determined by upper gastrointestinal endoscopy and the Baveno Ⅵ consensus.Those patients were divided into the HEVs group(66 patients)and the LEVs group(74 patients).The effect of each parameter on HEVs was analyzed by univariate and multivariate analyses,and a noninvasive prediction model was established.Finally,the discrimination ability,calibration ability and clinical efficacy of the new model were verified in the modelling group and the external validation group.RESULTS Univariate and multivariate analyses showed that SSM and LSM were associated with the occurrence of HEVs in patients with viral cirrhosis.On this basis,logistic regression analysis was used to construct a prediction model:Ln[P/(1-P)]=-8.184-0.228×SSM+0.642×LSM.The area under the curve of the new model was 0.965.When the cut-off value was 0.27,the sensitivity,specificity,positive predictive value and negative predictive value of the model for predicting HEVs were 100.00%,82.43%,83.52%,and 100%,respectively.Compared with the four prediction models of liver stiffness-spleen diameter to platelet ratio score,variceal risk index,aspartate aminotransferase to alanine aminotransferase ratio,and Baveno VI,the established model can better predict HEVs in patients with viral cirrhosis.CONCLUSION Based on the SSM and LSM measured by transient elastography,we established a non-invasive prediction model for HEVs.The new model is reliable in predicting HEVs and can be used as an alternative to routine upper gastrointestinal endoscopy screening,which is helpful for clinical decision making.

Localized-domains staging structure and evolution in lithiated graphite

Intercalation provides to the host materials a means for controlled variation of many physical/chemical properties and dominates the reactions in metal‐ion batteries.Of particular interest is the graphite intercalation compounds with intriguing staging structures,which however are still unclear,especially in their nanostructure and dynamic transition mechanism.Herein,the nature of the staging structure and evolution of the lithium(Li)‐intercalated graphite was revealed by cryogenic‐transmission electron microscopy and other methods at the nanoscale.The intercalated Li‐ions distribute unevenly,generating local stress and dislocations in the graphitic structure.Each staging compound is found macroscopically ordered but microscopically inhomogeneous,exhibiting a localized‐domains structural model.Our findings uncover the correlation between the long‐range ordered structure and short‐range domains,refresh the insights on the staging structure and transition of Li‐intercalated/deintercalated graphite,and provide effective ways to enhance the reaction kinetic in rechargeable batteries by defect engineering.

Anode Interfacial Issues in Solid-State Li Batteries:Mechanistic Understanding and Mitigating Strategies

All-solid-state Li metal batteries(ASSLBs)using inorganic solid electrolyte(SE)are considered promising alternatives to conventional Li-ion batteries,offering improved safety and boosted energy density.While significant progress has been made on improving the ionic conductivity of SEs,the degradation and instability of Li metal/inorganic SE interfaces have become the critical challenges that limit the coulombic efficiency,power performance,and cycling stability of ASSLBs.Understanding the mechanisms of complex/dynamic interfacial phenomena is of great importance in addressing these issues.Herein,recent studies on identifying,understanding,and solving interfacial issues on anode side in ASSLBs are comprehensively reviewed.Typical issues at Li metal/SE interface include Li dendrite growth/propagation,SE cracking,physical contact loss,and electrochemical reactions,which lead to high interfacial resistance and cell failure.The causes of these issues relating to the chemical,physical,and mechanical properties of Li metal and SEs are systematically discussed.Furthermore,effective mitigating strategies are summarized and their effects on suppressing interfacial reactions,improving interfacial Li-ion transport,maintaining interfacial contact,and stabilizing Li plating/stripping are highlighted.The in-depth mechanistic understanding of interfacial issues and complete investigations on current solutions provide foundations and guidance for future research and development to realize practical application of high-performance ASSLB.

Progressive Collapse Resistance of a New Staggered Story Isolated System

A new staggered isolated system developed from the mid-story isolated system is the new staggered story isolated system. There are not many studies on this structure currently. In this study, an 18-story new staggered story isolated system model is established using SAP2000. The dynamic nonlinear dynamic alternate method is used to analyze the structure against progressive collapse. Results show that the structure has good resistance to progressive collapse, and there is no progressive collapse under each working condition. The progressive collapse does not occur for the case of removing only one vertical structural member of the new staggered of isolated system. The side column has big influence on this isolated structures’ progressive collapse;the removal of vertical structural member of the isolation layer has less impact on the structure than the removal of the bottom vertical structural member. After the removing of the member, the internal force of the structure will be redistributed, and the axial force of the adjacent columns will change obviously, showing a trend of “near large and far small”.

Resistance characteristics of paste pipeline flow in a pulse-pumping environment

Paste flow patterns and microscopic particle structures were studied in a pressurized environment generated by a pulse pump.Complex loop-pipe experiments and fluid-solid coupling-based simulations were conducted.The scanning electron microscopy technique was also applied.Results revealed that flow resistance is closely related to pipeline curvature and angle in a complex pipe network.The vertical downward-straight pipe-inclined downward combination was adopted to effectively reduce the loss in resistance along with reducing the number of bends or increasing the radius of bend curvature.The maximum velocity ratio and velocity offset values could quantitatively characterize the influences of different pipeline layouts on the resistance.The correlation reached 96%.Particle distribution and interparticle forces affected flow resistance.Uniform particle states and weak interparticle forces were conducive to steady transport.Pulse pump pressure led to high flow resistance.It could improve pipe flow stability by increasing flow uniformity and particle motion stability.These results can contribute to safe and efficient paste filling.

Semaphorin 7A promotes human vascular smooth muscle cell proliferation and migration through theβ-catenin signaling pathway

Background:Vascular smooth muscle cells(VSMCs)undergo a conversion from a contractile phenotype to a proliferative synthetic phenotype,contributing to the pathogenesis of cardiovascular diseases.Semaphorin 7A(SEMA7A)is a glycosylphosphatidylinositol-anchored membrane protein that plays an important role in vascular homeostasis by regulating endothelial cell behaviors.However,the expression and role of SEMA7A in VSMCs remain unclear.Methods:In this study,we screened for VSMC-regulating genes in publicly available datasets and analyzed the expression of SEMA7A in human coronary artery smooth muscle cells(hCASMCs)treated with platelet-derived growth factor-BB(PDGF-BB).The effects of SEMA7A overexpression and knockdown on hCASMC proliferation and migration were examined.The signaling pathways involved in the action of SEMA7A in hCASMCs were determined.Results:Bioinformatic analysis showed that SEMA7A was significantly dysregulated in VSMCs treated with oxidized low-density lipoprotein or overexpressing progerin,a pro-atherogenic gene.The PDGF-BB stimulation led to a concentration-and time-dependent induction of SEMA7A.Depletion of SEMA7A attenuated PDGF-BB-induced hCASMC proliferation and migration.Conversely,overexpression of SEMA7A enhanced hCASMC proliferation and migration.Mechanistically,SEMA7A stimulated the activation of theβ-catenin pathway and upregulated c-Myc,CCND1,and MMP7.Knockdown ofβ-catenin impaired SEMA7A-induced hCASMC proliferation and migration.Conclusions:SEMA7A triggers phenotype switching in VSMCs through theβ-catenin signaling pathway and may serve as a potential therapeutic target for cardiovascular diseases.

Clinical features of retinal amyloid angiopathy with transthyretin Gly83Arg variant

AIM:To report on the clinical features of patients with retinal amyloid angiopathy(RAA)who were identified to be caused by the transthyretin(TTR)Gly83Arg variant.METHODS:Case series of five patients diagnosed with RAA was collected at Affiliated Hospital of Zunyi Medical University from January 2010 to December 2021.The clinical features,therapeutic strategies,and prognoses of all patients were reviewed.RESULTS:Five patients with a mean age of 52.00±7.23y were diagnosed as RAA.These patients were previously diagnosed with hereditary transthyretin amyloidosis caused by the TTR Gly83Arg variant.Vitreous opacity was found in all 10 eyes,and 7 eyes developed RAA 2 to 20y after the onset of hereditary transthyretin amyloidosis.The clinical manifestations were recurrent vitreous hemorrhage in 2 eyes(29%),neovascular glaucoma in 2 eyes(29%),and iris neovascularization in 1 eye(14%).Microangioma lesions were found in all affected eyes that underwent fundus fluorescein angiography(FFA)in this group of cases,and the incidence of the retinal non-perfusion area was 67%.Although no cases of retinal neovascularization were found,the prognosis of visual acuity was not ideal.CONCLUSION:This is the first report of RAA in patients with the TTR Gly83Arg variant.Complications such as RAA and glaucoma will seriously affect the visual prognosis of patients.Thereafter,regular ophthalmic follow-up of patients with hereditary transthyretin amyloidosis is essential.And FFA after vitrectomy is very important,which can help ophthalmologists detect RAA earlier and treat it in time.

An Intelligent Identification Approach of Assembly Interface for CAD Models

Kinematic semantics is often an important content of a CAD model(it refers to a single part/solid model in this work)in many applications,but it is usually not the belonging of the model,especially for the one retrieved from a common database.Especially,the effective and automatic method to reconstruct the above information for a CAD model is still rare.To address this issue,this paper proposes a smart approach to identify each assembly interface on every CAD model since the assembly interface is the fundamental but key element of reconstructing kinematic semantics.First,as the geometry of an assembly interface is formed by one or more adjacent faces on each model,a face-attributed adjacency graph integrated with face structure fingerprint is proposed.This can describe each CAD model as well as its assembly interfaces uniformly.After that,aided by the above descriptor,an improved graph attention network is developed based on a new dual-level anti-interference filtering mechanism,which makes it have the great potential to identify all representative kinds of assembly interface faces with high accuracy that have various geometric shapes but consistent kinematic semantics.Moreover,based on the abovementioned graph and face-adjacent relationships,each assembly interface on a model can be identified.Finally,experiments on representative CAD models are implemented to verify the effectiveness and characteristics of the proposed approach.The results show that the average assembly-interface-face-identification accuracy of the proposed approach can reach 91.75%,which is about 2%–5%higher than those of the recent-representative graph neural networks.Besides,compared with the state-of-the-art methods,our approach is more suitable to identify the assembly interfaces(with various shapes)for each individual CAD model that has typical kinematic pairs.

Teaching Reform and Practice of Finance under the Background of New Liberal Arts

Under the background of new liberal arts,the problems existing in the teaching process of Finance were re-examined.For instance,the setting of teaching objectives does not meet the requirements of construction of new liberal arts,and teaching content emphasizes theory;teaching method is single,and teaching assessment is not reasonable.It is proposed that the curriculum reform should be carried out from five dimensions:teaching objective,teaching content,teaching method,practice system and teaching evaluation,so as to meet the requirements of construction of new liberal arts.

Structure-based multi-ligand molecular modeling to predict the synergistic effects of limonin and obacunone from Simiao pill against nitric oxide synthase 3 associated with hyperuricemia

Hyperuricemia(HUA)mainly occurs because of purine metabolism disorders.We recently proposed that limonin from Simiao pill may have therapeutic effects on nitric oxide synthase 3(NOS3)that is related to HUA.Concurrently,our previous work employed a new method,structure-based multi-ligand molecular modeling,to identify potential agents from a herbal formula that may produce synergistic effects and may have the potential to develop combination drugs.Therefore,we employed multi-ligand modeling to seek compounds with potential synergistic effects with limonin against NOS3.We obtained 403 multi-ligand docking results between 403 compounds and the limonin-NOS3 complex(average affinity–8.297 kcal/mol).Then we selected the top 10 highest binding affinity compounds for virtual pharmacokinetic and toxicity screening and we found that only obacunone passed all filters.We further subjected obacunone,bound to limonin and NOS3,to molecular dynamics simulations.We found that the NOS3-limonin-obacunone complex was more stable than the NOS3-limonin complex,based on the root mean square deviation of backbone Cαatoms and root mean square fluctuation,which suggests that synergistic effects may exist between limonin and obacunone.Further cell and animal experimental research is required to verify our results.