Role of Ubiquitin-Conjugating Enzyme UBE2C in Gastrointestinal Cancers

Ubiquitin-conjugating enzyme UBE2C is one of the important members of ubiquitin-proteasome pathway(UPP).Amplification and/or overexpression of UBE2C have been reported in many malignancies,and a high expression of UBE2C is associated with poor clinical outcomes.In this review,the pathological role of dysregulated UBE2C in gastrointestinal cancers and its potential role as a diagnostic and/or a prognostic marker as well as a therapeutic target in these cancers are discussed.

Effect of visceral obesity on outcomes of fluorescence-guided lymphadenectomy during laparoscopic gastrectomy for gastric cancer:Post hoc analysis of a randomized phase 3 trial

Objective:To explore the impact of visceral fat area(VFA)on the short-and long-term efficacy of indocyanine green(ICG)-guided D2 lymphadenectomy for gastric cancer(GC).Methods:A post hoc analysis was performed in patients who participated in a phase 3 randomized clinical trial of ICG-guided laparoscopic radical gastrectomy vs.conventional laparoscopic radical gastrectomy from November 2018 to July 2019.The VFA was calculated based on preoperative computed tomography images.Short-term efficacy included the quality of lymph node(LN)dissection and surgical outcomes,while long-term efficacy included overall survival(OS)and recurrence-free survival(RFS).Results:This study included 126 patients each in the ICG(high-VFA,n=43)and non-ICG groups(high-VFA,n=38).Compared with the non-ICG group,the ICG group had significantly more retrieved LNs(low-VFA:50.1 vs.43.9,P=0.001;high-VFA:49.6 vs.37.5,P<0.001)and a significantly lower LN noncompliance rate(low-VFA:32.5%vs.50.0%,P=0.020;high-VFA:32.6%vs.73.7%,P<0.001),regardless of the VFA.The ICG group had a shorter postoperative hospital stay and fewer intra-abdominal infections than the ICG group in the high-VFA patients(P=0.025 and P=0.020,respectively)but not in the low-VFA patients.Regardless of the VFA,the 3-year OS(RFS)was better in the ICG group than in the non-ICG group[low-VFA:83.1%(76.9%)vs.73.9%(67.0%);high-VFA:90.7%(90.7%)vs.73.7%(73.5%);P for interaction=0.474(0.547)].Conclusions:The short-and long-term efficacies of ICG tracing were not influenced by visceral obesity.

Fluorine-doped carbon quantum dots with deep-red emission for hypochlorite determination and cancer cell imaging

As a type of new carbon-based nanomaterials,carbon dots(CDs)possess exceptional optical properties,making them highly desirable for use in fluorescent sensors.However,the CDs with deep-red(DR)or near-infrared(NIR)emission have rarely been reported.In this work,we prepared deep-red emissive fluorine-doped carbon quantum dots(F-CDs)by introducing a precursor simultaneously containing fluorine and amidogen.The synergistic effect of nitrogen doping and D-π-A pattern production contributed to the maximum emission of F-CDs at 636 nm with an absolute quantum yield of 36.00%±0.68%.Moreover,we designed an F-CDs-based fluorescence assay to determine the content of hypochlorite(ClO^(-)),with a limit of detection(LOD)as low as 15.4 nmol/L,indicating the high sensitivity of F-CDs to ClO^(-).In real samples,the F-CDs-based fluorescent sensor exhibited excellent sensitivity and selectivity in the detection of ClO^(-),with an error below 2%,suggesting their great potential in daily life.In cancer cell imaging,the F-CDs not only demonstrated high sensitivity to ClO^(-)but also exhibited excellent mitochondria targeting,as evidenced by the high Pearson's correlation coefficient(PCC)of 0.93 in colocalization analysis.The work presented here suggests the great potential of replacing commercial dyes with F-CDs for highly specific mitochondria labeling and cell imaging.

Utilization of 3D printing technology in hepatopancreatobiliary surgery

The technology of three-dimensional(3D)printing emerged in the late 1970s and has since undergone considerable development to find numerous applications in mechanical engineering,industrial design,and biomedicine.In biomedical science,several studies have initially found that 3D printing technology can play an important role in the treatment of diseases in hepatopancreatobiliary surgery.For example,3D printing technology has been applied to create detailed anatomical models of disease organs for preoperative personalized surgical strategies,surgical simulation,intraoperative navigation,medical training,and patient education.Moreover,cancer models have been created using 3D printing technology for the research and selection of chemotherapy drugs.With the aim to clarify the development and application of 3D printing technology in hepatopancreatobiliary surgery,we introduce seven common types of 3D printing technology and review the status of research and application of 3D printing technology in the field of hepatopancreatobiliary surgery.

Does cranial-medial mixed dominant approach have a unique advantage for laparoscopic right hemicolectomy with complete mesocolic excision?

BACKGROUND Complete mesocolic excision(CME)with central vascular ligation(CVL)was proposed by Hohenberger in 2009.The CME principle has gradually become the technical standard for colon cancer surgery.How to achieve CME with CVL in laparoscopic right hemicolectomy(LRH)is controversial,and a unified standard approach is not yet available.In recent years,the authors’team has integrated the theory of membrane anatomy,tried to combine the cephalic approach with the classic medial approach(MA)for technical optimization,and proposed a cranialmedial mixed dominant approach(CMA).AIM To explore the feasibility of operational approaches for LRH with CME.METHODS In this retrospective cohort study,the clinical data of 57 patients with right-sided colon cancer(TNM stage I,II,or III)who underwent LRH with CME from January 2016 to June 2020 were collected and summarized.There were 31 patients in the traditional MA group and 26 in the CMA group.RESULTS There were no significant differences in baseline data between the two groups.The operation was shorter and the number of lymph nodes dissected was higher in the CMA group than in the MA group,but there was no significant difference in the number of positive lymph nodes,intraoperative blood loss,postoperative exhaust time,feeding time,postoperative hospital stay or postoperative complication incidence.CONCLUSION Our study shows that the CMA is a safe and feasible procedure for LRH with CME and has a unique advantage.

Roles and Molecular Mechanisms of Biomarkers in Hepatocellular Carcinoma with Microvascular Invasion: A Review

Hepatocellular carcinoma(HCC)being a leading cause of cancer-related death,has high associated mortality and recurrence rates.It has been of great necessity and urgency to find effective HCC diagnosis and treatment measures.Studies have shown that microvascular invasion(MVI)is an independent risk factor for poor prognosis after hepatectomy.The abnormal expression of biomacromolecules such as circ-RNAs,lncRNAs,STIP1,and PD-L1 in HCC patients is strongly correlated with MVI.Deregulation of several markers mentioned in this review affects the proliferation,invasion,metastasis,EMT,and anti-apoptotic processes of HCC cells through multiple complex mechanisms.Therefore,these biomarkers may have an important clinical role and serve as promising interventional targets for HCC.In this review,we provide a comprehensive overview on the functions and regulatory mechanisms of MVI-related biomarkers in HCC.

Specific pupylation as IDEntity reporter(SPIDER)for the identification of protein-biomolecule interactions

Protein-biomolecule interactions play pivotal roles in almost all biological processes.For a biomolecule of interest,the identification of the interacting protein(s)is essential.For this need,although many assays are available,highly robust and reliable methods are always desired.By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin(SA)-biotin system,we developed the Specific Pupylation as IDEntity Reporter(SPIDER)method for identifying protein-biomolecule interactions.Using SPIDER,we validated the interactions between the known binding proteins of protein,DNA,RNA,and small molecule.We successfully applied SPIDER to construct the global protein interactome for m^(6)A and m RNA,identified a variety of uncharacterized m^(6)A binding proteins,and validated SRSF7 as a potential m^(6)A reader.We globally identified the binding proteins for lenalidomide and Cob B.Moreover,we identified SARS-CoV-2-specific receptors on the cell membrane.Overall,SPIDER is powerful and highly accessible for the study of proteinbiomolecule interactions.

Association of food intake with a risk of metabolic dysfunction-associated fatty liver disease:a cross-sectional study

Background:Metabolic dysfunction-associated fatty liver disease(MAFLD)is a common liver disease,the risk of which can be increased by poor diet.The objective of this study was to evaluate the associations between food items and MAFLD,and to propose reasonable dietary recommendations for the prevention of MAFLD.Methods:Physical examination data were collected from April 2015 through August 2017 at Nanping First Hospital(n=3,563).Dietary intakes were assessed using a semi-quantitative food frequency questionnaire.The association between food intake and the risk of MAFLD was assessed by using the inverse probability weighted propensity score.Results:Beverages(soft drinks and sugar-sweetened beverages)and instant noodles were positively associated with MAFLD risk,adjusting for smoking,drinking,tea intake,and weekly hours of physical activity[adjusted odds ratio(ORadjusted):1.568;P=0.044;ORadjusted:4.363;P=0.001].Milk,tubers,and vegetables were negatively associated with MAFLD risk(ORadjusted:0.912;P=0.002;ORadjusted:0.633;P=0.007;ORadjusted:0.962;P=0.028).In subgroup analysis,the results showed that women[odds ratio(OR):0.341,95%confidence interval(CI):0.172–0.676]had a significantly lower risk of MAFLD through consuming more tubers than men(OR:0.732,95%CI:0.564–0.951).Conclusions:These findings suggest that reducing consumption of beverages(soft drinks and sugar-sweetened beverages)and instant noodles,and consuming more milk,vegetables,and tubers may reduce the risk of MAFLD.

Systematic evaluation of IgG responses to SARS-CoV-2 spike protein-derived peptides for monitoring COVID-19 patients

Serological tests play an essential role in monitoring and combating the COVID-19 pandemic.Recombinant spike protein(S protein),especially the S1 protein,is one of the major reagents used for serological tests.However,the high cost of S protein production and possible cross-reactivity with other human coronaviruses pose unavoidable challenges.By taking advantage of a peptide microarray with full spike protein coverage,we analyzed 2,434 sera from 858 COVID-19 patients,63 asymptomatic patients and 610 controls collected from multiple clinical centers.Based on the results,we identified several S protein-derived 12-mer peptides that have high diagnostic performance.In particular,for monitoring the IgG response,one peptide(aa 1148-1159 or S2-78)exhibited a sensitivity(95.5%,95%CI 93.7-96.9%)and specificity(96.7%,95%CI 94.8-98.0%)comparable to those of the S1 protein for the detection of both symptomatic and asymptomatic COVID-19 cases.Furthermore,the diagnostic performance of the S2-78(aa 1148-1159)IgG was successfully validated by ELISA in an independent sample cohort.A panel of four peptides,S1-93(aa 553-564),S1-97(aa 577-588),S1-101(aa 601-612)and S1-105(aa 625-636),that likely will avoid potential cross-reactivity with sera from patients infected by other coronaviruses was constructed.The peptides identified in this study may be applied independently or in combination with the S1 protein for accurate,affordable,and accessible COVID-19 diagnosis.

Hepatoprotective drugs for prevention of liver injury resulting from anti-tuberculosis treatment:A meta-analysis of cohort studies

Background:The incidence of liver injury caused by anti-tuberculous(TB)drugs is very high.However,owing to a lack of sufficient evidence,preventive use of hepatoprotective drugs is not yet recommended.Therefore,we aimed to assess the protective effect of hepatoprotective drugs for anti-TB drug-induced liver injury.Methods:We conducted a literature search in China Biology Medicine disc,China National Knowledge Infras-tructure,WanFang,Chinese Scientific and Technological Journal,PubMed,Cochrane Library,Web of Science,and Embase.We performed meta-analysis using R 4.0 and Review Manager 5.3 software.Results:A total of 18 studies involving 3589 patients from 2 groups were included.Use of hepatoprotective drugs contributed to a lower incidence of liver injury as compared with conventional anti-TB treatment alone(relative risk[RR]=0.39,95%confidence interval[CI]:0.28-0.53,p<0.001).In subgroup analysis,significant protective effects were noted for mild liver injury(RR=0.30,95%CI 0.15-0.58),moderate(or severe)liver injury(RR=0.35,95%CI 0.19-0.65),and liver injury within 2-4 weeks(RR=0.37,95%CI 0.19-0.71).We also found a statistically significant difference in the incidence of drug withdrawal(RR=0.58,95%CI 0.34-0.97,p=0.040).Conclusions:Our results demonstrate that hepatoprotective drugs are effective in preventing liver injury in pa-tients receiving anti-TB treatment,to some extent.

m6A-TSHub:Unveiling the Context-specific m^(6)A Methylation and m^(6)A-affecting Mutations in 23 Human Tissues

As the most pervasive epigenetic marker present on mRNAs and long non-coding RNAs(lncRNAs),N6-methyladenosine(m^(6)A)RNA methylation has been shown to participate in essential biological processes.Recent studies have revealed the distinct patterns of m^(6)A methylome across human tissues,and a major challenge remains in elucidating the tissue-specific presence and circuitry of m^(6)A methylation.We present here a comprehensive online platform,m^(6)A-TSHub,for unveiling the context-specific m^(6)A methylation and genetic mutations that potentially regulate m^(6)A epigenetic mark.m^(6)A-TSHub consists of four core components,including(1)m^(6)A-TSDB,a comprehensive database of 184,554 functionally annotated m^(6)A sites derived from 23 human tissues and 499,369 m^(6)A sites from 25 tumor conditions,respectively;(2)m^(6)A-TSFinder,a web server for high-accuracy prediction of m^(6)A methylation sites within a specific tissue from RNA sequences,which was constructed using multi-instance deep neural networks with gated attention;(3)m^(6)ATSVar,a web server for assessing the impact of genetic variants on tissue-specific m^(6)A RNA modifications;and(4)m^(6)A-CAVar,a database of 587,983 The Cancer Genome Atlas(TCGA)cancer mutations(derived from 27 cancer types)that were predicted to affect m^(6)A modifications in the primary tissue of cancers.The database should make a useful resource for studying the m^(6)A methylome and the genetic factors of epitranscriptome disturbance in a specific tissue(or cancer type).m^(6)A-TSHub is accessible at www.xjtlu.edu.cn/biologicalsciences/m^(6)ats.

COVID-ONE-hi:The One-stop Database for COVID-19-specific Humoral Immunity and Clinical Parameters

Coronavirus disease 2019(COVID-19),which is caused by SARS-CoV-2,varies with regard to symptoms and mortality rates among populations.Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19.However,differences in immune responses and clinical features among COVID-19 patients remain largely unknown.Here,we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters(named COVID-ONE-hi).COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients.In addition,96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database.Furthermore,COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups.A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters.After the“START”button is clicked,one can readily obtain a comprehensive analysis report for further interpretation.COVID-ONE-hi is freely available at www.COVID-ONE.cn.