The following letter to the editor highlights the article“Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance”in Wor...The following letter to the editor highlights the article“Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance”in World J Diabetes 2023 Oct 15;14(10):1514-1523.It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.展开更多
Congenital melanocytic nevi(CMN) are common skin tumors. Large and specially located nevi cannot be completely removed by surgery, posing the risks of both cosmetic deformities and potential malignancy.Nonsurgical tre...Congenital melanocytic nevi(CMN) are common skin tumors. Large and specially located nevi cannot be completely removed by surgery, posing the risks of both cosmetic deformities and potential malignancy.Nonsurgical treatments, such as laser therapy and physical dermabrasion, can overcome the limitations of surgery;however, the high rate of repigmentation remains an unresolved global challenge. We conducted a self-controlled observational study of a patient with a nevus on the chest. Two areas of the lesion were treated with an Er:YAG laser and 5% imiquimod cream was applied to one of these areas. After nearly 7-months of follow-up, we observed a significant difference in color between the two areas, suggesting that topical imiquimod may inhibit repigmentation and significantly enhance the effectiveness of laser treatment.展开更多
Head and neck squamous cell carcinoma(HNSCC)is characterized by high recurrence or distant metastases rate and the prognosis is challenging.There is mounting evidence that tumor-infiltrating B cells(TIL-Bs)have a cruc...Head and neck squamous cell carcinoma(HNSCC)is characterized by high recurrence or distant metastases rate and the prognosis is challenging.There is mounting evidence that tumor-infiltrating B cells(TIL-Bs)have a crucial,synergistic role in tumor control.However,little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade.Using single-cell RNA sequencing(scRNA-seq)data from the Gene Expression Omnibus(GEO)database,the study identified distinct gene expression patterns in TIL-Bs.HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering.This classification was further validated with TCGA HNSCC data,correlating with patient prognosis,immune cell infiltration,and response to immunotherapy.We found that the B cells activation group exhibited a better prognosis,higher immune cell infiltration,and distinct immune checkpoint levels,including elevated PD-L1.A prognostic model was also developed and validated,highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients.Overall,this study provides a foundational approach for B cells-based tumor classification in HNSCC,offering insights into targeted treatment and immunotherapy strategies.展开更多
gallbladder cancer(gbc), although considered as a relatively rare malignancy, is the most common neoplasm of the biliary tract system. the late diagnosis and abysmal prognosis present challenges to treatment. the over...gallbladder cancer(gbc), although considered as a relatively rare malignancy, is the most common neoplasm of the biliary tract system. the late diagnosis and abysmal prognosis present challenges to treatment. the overall 5-year survival rate for metastatic gbc patients is extremely low. BRC A1 and BRCA2 are the breast cancer susceptibility genes and their mutation carriers are at a high risk for cancer development, both in men and women. Olaparib, an oral poly ADP-ribose polymerase inhibitor, has been approved by the Food and Drug Administration and the European commission for the treatment of ovarian cancer with any BRCA1/2 mutations. the first case of BRCA1-mutated gbc patient who responded to olaparib treatment is reported here.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related deaths worldwide,but there is a shortage of effective biomarkers for its diagnosis.AIM To explore blood exosomal micro ribonucleic...BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related deaths worldwide,but there is a shortage of effective biomarkers for its diagnosis.AIM To explore blood exosomal micro ribonucleic acids(miRNAs)as potential biomarkers for HCC diagnosis.RESULTS The principal component analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of hepatitis B virus positive non-HCC patients through miR-3168 and miR-223-3p.The miRNA profiles also revealed the tumor stages of HCC patients.High expression of miR-455-5p and miR-30c-5p,which significantly correlated with better overall survival in tumor tissues,could also be detected in blood exosomes.Two pairs of miRNAs(miR-584-5p/miR-106-3p and miR-628-3p/miR-941)showed a 94.1%sensitivity and 68.4%specificity to differentiate HCC patients from non-HCC patients.The specificity of the combination was substantially influenced by alcohol consumption habits.CONCLUSION This study suggested that blood exosomal miRNAs can be used as new noninvasive diagnostic tools for HCC.However,their accuracy could be affected by tumor stage and alcohol consumption habits.展开更多
Methyltransferase like 13(METTL13),a kind of methyltransferase,is implicated in protein binding and synthesis.The upregulation of METTL13 has been reported in a variety of tumors.However,little was known about its pot...Methyltransferase like 13(METTL13),a kind of methyltransferase,is implicated in protein binding and synthesis.The upregulation of METTL13 has been reported in a variety of tumors.However,little was known about its potential function in head and neck squamous cell carcinoma(HNSCC)so far.In this study,we found that METTL13 was significantly upregulated in HNSCC at both mRNA and protein level.Increased METTL13 was negatively associated with clinical prognosis.And METTL13 markedly affected HNSCC cellular phenotypes in vivo and vitro.Further mechanism study revealed that METTL13 could regulate EMT signaling pathway by mediating enhancing translation efficiency of Snail,the key transcription factor in EMT,hence regulating the progression of EMT.Furthermore,Snail was verified to mediate METTL13-induced HNSCC cell malignant phenotypes.Altogether,our study had revealed the oncogenic role of METTL13 in HNSCC,and provided a potential therapeutic strategy.展开更多
Intrahepatic cholangiocarcinoma(ICC) is a relatively rare form of liver cancer with a poor prognosis. The therapeutic options for patients with advanced ICC are limited and usually ineffective. There is currently no a...Intrahepatic cholangiocarcinoma(ICC) is a relatively rare form of liver cancer with a poor prognosis. The therapeutic options for patients with advanced ICC are limited and usually ineffective. There is currently no approved targeted therapy for ICC, although accumulating evidence supports inhibition of the PI3K/Akt/m TOR signaling pathway as a promising therapeutic strategy in the treatment of ICC. Here, we report a patient with stage IV ICC harboring a PIK3 CA mutation who responded well to the m TOR inhibitor everolimus. Computed tomography and magnetic resonance imaging demonstrated shrinkage of the tumor and maintenance of a partial response for 6.5 mo after everolimus treatment as the best response. To the best of our knowledge, this is the first clinical case report in the literature of clinical benefit from everolimus treatment in an ICC patient with PIK3 CA mutation.展开更多
Objective To analyze the differential gene expression profile of serum exosomes in patients with acute cerebral infarction(ACI)and clarify the changes in gene expression related to cerebral infarction injury and the p...Objective To analyze the differential gene expression profile of serum exosomes in patients with acute cerebral infarction(ACI)and clarify the changes in gene expression related to cerebral infarction injury and the potential serum markers.Methods Four patients with ACI and five healthy people were enrolled in the PhaseⅠstudy.After serum isolation from peripheral blood,exosomes were extracted with exosomes kits,highthroughput detection of m RNA was performed with gene chips,and differentially expressed m RNAs were screened.Gene Ontology(GO)functional analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed simultaneously.Furthermore,real-time polymerase chain reaction(q RT-PCR)was used to verify the expression levels of the screened differential m RNAs in the serum exosomes collected in PhaseⅡfrom 32 patients each in the ACI case and normal control groups.Results In the PhaseⅠstudy,there were 248 differentially expressed m RNAs(fold change≥2.0,P<0.05)among five patients in the normal control group and four patients in the case group,of which the expression of 242 was upregulated and that of six was downregulated.The results of GO functional enrichment analysis mainly included behavior regulation,cell connection,and antioxidant activity.The results of KEGG pathway enrichment analysis mainly included ribosomes,proteasomes,oxytocin signaling pathways,and oxidative phosphorylation.After researching and screening based on relevant literature,it was found that among the genes with significant differential expression,H3 F3 B m RNA may be associated with and might play an important role in ACI.The q RT-PCR method was used to detect the H3 F3 B mRNA expression in serum exosomes of 32 patients each in the normal control and case groups in PhaseⅡ;the expression was significantly higher in serum exosomes of the case group than in those of the normal control group(P<0.001).H3 F3 B mRNA expression in serum exosomes of the case group positively correlated with age,the National Institutes of Health Stroke Scale(NIHSS)score,and the maximum infarct size(P<0.05).Conclusion ACI can lead to changes in the serum exosomes mRNA expression profile,which may be closely related to the occurrence,development,and prognosis of this condition.These findings will provide direction for research on the molecular mechanism,diagnostic markers,and therapeutic targets of ACI.展开更多
Nypa fruticans(Wurmb),a mangrove palm species with origins dating back to the Late Cretaceous period,is a unique species for investigating long-term adaptation strategies to intertidal environments and the early evolu...Nypa fruticans(Wurmb),a mangrove palm species with origins dating back to the Late Cretaceous period,is a unique species for investigating long-term adaptation strategies to intertidal environments and the early evolution of palms.Here,we present a chromosome-level genome sequence and assembly for N.fruticans.We integrated the genomes of N.fruticans and other palm family members for a comparative genomic analysis,which confirmed that the common ancestor of all palms experienced a whole-genome duplication event around 89 million years ago,shaping the distinctive characteristics observed in this clade.We also inferred a low mutation rate for the N.fruticans genome,which underwent strong purifying selection and evolved slowly,thus contributing to its stability over a long evolutionary period.Moreover,ancient duplicates were preferentially retained,with critical genes having experienced positive selection,enhancing waterlogging tolerance in N.fruticans.Furthermore,we discovered that the pseudogenization of Early Methionine-labelled 1(EM1)and EM6 in N.fruticans underly its crypto-vivipary characteristics,reflecting its intertidal adaptation.Our study provides valuable genomic insights into the evolutionary history,genome stability,and adaptive evolution of the mangrove palm.Our results also shed light on the long-term adaptation of this species and contribute to our understanding of the evolutionary dynamics in the palm family.展开更多
Background:This study aimed to select compounds with unique inhibitory effects on muscle-invasive bladder cancer(MIBC)from coumarone derivatives with similar parent nuclear structures and to reveal their tumor-suppres...Background:This study aimed to select compounds with unique inhibitory effects on muscle-invasive bladder cancer(MIBC)from coumarone derivatives with similar parent nuclear structures and to reveal their tumor-suppressive effects using various approaches.Methods:Bladder cancer cell lines SW780 and T24,as well as human normal bladder epithelial cell line SV-HUC-1 were selected as the study model,and these urinary system cells were co-incubated with various concentrations of(S,E)-4-(4-methylbenzylidene)-3-phenylchroman-3-ol,(S,E)-4-(4-isocyanobenzylidene)-3-phenylchroman-3-ol,(S,E)-4-(4-fluorobenzylidene)-3-phenylchroman-3-ol(FPO),and(S,E)-3-phenyl-4-(4-(trifluoromethoxy)benzylidene)chroman-3-ol.Cell activity was detected using cell counting kit-8.FPO showed the strongest inhibitory effect on MIBC cells;therefore,it was selected for further experiments.We monitored the FPO-induced T24 cell morphological changes with an inverted microscope.The FPO-inhibited migration of T24 cells was examined using a cell scratch assay.We detected the clonogenic ability of T24 cells through a clone formation test and evaluated their proliferative ability using a 5-ethynyl-2’-deoxyuridine fluorescence staining kit.The inhibitory effect of FPO against the cell cycle was monitored using flow cytometry,and its suppressive effect on the DNA replication ability of T24 cells was detected using double fluorescence staining(Ki67 and phalloidin).Results:Among the four candidate coumarone derivatives,FPO showed the most significant inhibitory effect on MIBC cells and was less toxic to normal urothelial cells.FPO inhibited T24 cell growth in time and dose-dependent manners(the half-inhibitory concentration is 8μM).FPO significantly repressed the proliferation,migration,and clonogenic ability of bladder cancer T24 cells.Cell mobility was significantly inhibited by FPO:30μM FPO almost completely repressed migration occurred at after 24 h treatment.Moreover,FPO significantly suppressed the clonogenicity of bladder cancer cells in a dose-dependent manner.Mechanistically,FPO targeted the cell cycle,arresting the S and G2 phases on bladder cancer T24 cells.Conclusion:We discovered a novel anticancer chemical,FPO,and proposed a potential mechanism,through which it suppresses MIBC T24 cells by repressing the cell cycle in the S and G2 phases.This study contributes to the development of novel anticancer drugs for MIBC.展开更多
Copper(0)-mediated reversible-deactivation radical polymerization(Cu(0)-mediated RDRP) of the water-soluble monomer Nisopropylacrylamide(NIPAM) has been challenging with the problems of high dispersity, poor control o...Copper(0)-mediated reversible-deactivation radical polymerization(Cu(0)-mediated RDRP) of the water-soluble monomer Nisopropylacrylamide(NIPAM) has been challenging with the problems of high dispersity, poor control over the molecular weights(MWs) or complex or multi reaction steps, etc. In this work, we report the well-controlled polymerization of NIPAM in water via a facile one-pot and one-step Cu(0)-mediated RDRP. The results of this approach show that the key for kicking off the Cu(0)-mediated NIPAM RDRPs is to ensure sufficient Cu~I at the very beginning, and the key to achieve a well-controlled chain growth is to provide adequate deactivation strength during the polymerization process. For NIPAM, which has a high propagation rate constant, the deactivation control can be effectively enhanced by extra adding deactivator(i.e., Cu~II) to the system. Moreover, a low reaction temperature(4 ℃) is necessary in the controlled synthesis of higher MW poly(Nisopropylacrylamide)(PNIPAM) to avoid the compromise in control caused by the phase transition from its lower critical solution temperature(LCST). Through this new kinetically controlled strategy, PNIPAMs with well-defined structure, narrow molecular weight distributions(MWDs) and varied MWs were successfully achieved.展开更多
The exponential growth of bioinformatics tools in recent years has posed challenges for scientists in selecting the most suitable one for their data analysis assignments.Therefore,to aid scientists in making informed ...The exponential growth of bioinformatics tools in recent years has posed challenges for scientists in selecting the most suitable one for their data analysis assignments.Therefore,to aid scientists in making informed choices,a community-based platform that indexes and rates bioinformatics tools is urgently needed.In this study,we introduce Bio Treasury(http://biotreasury.rjmart.cn),an integrated communitybased repository that provides an interactive platform for users and developers to share their experiences in various bioinformatics tools.Bio Treasury offers a comprehensive collection of well-indexed bioinformatics software,tools,and databases,totaling over 10,000 entries.In the past two years,we have continuously improved and maintained Bio Treasury,adding several exciting features,including creating structured homepages for every tool and user,a hierarchical category of bioinformatics tools and classifying tools using large language model(LLM).Bio Treasury streamlines the tool submission process with intelligent auto-completion.Additionally,Bio Treasury provides a wide range of social features,for example,enabling users to participate in interactive discussions,rate tools,build and share tool collections for the public.We believe Bio Treasury can be a valuable resource and knowledge-sharing platform for the biomedical community.It empowers researchers to effectively discover and evaluate bioinformatics tools,fostering collaboration and advancing bioinformatics research.展开更多
Rheumatoid arthritis(RA)is an inflammatory disease accompanied by abnormal synovial microenvironment(SM).Sesquiterpene lactones(SLs)are the main anti-inflammatory ingredients of many traditional herbs utilized in RA t...Rheumatoid arthritis(RA)is an inflammatory disease accompanied by abnormal synovial microenvironment(SM).Sesquiterpene lactones(SLs)are the main anti-inflammatory ingredients of many traditional herbs utilized in RA treatment.α-Methylene-γ-butyrolactone(α-M-γ-B)is a core moiety that widely exists in natural SLs.This study was designed to investigate the anti-arthritic potential ofα-M-γ-B as an independent small molecule in vitro and in vivo.α-M-γ-B exhibited stronger electrophilicity and anti-inflammatory effects than the other six analogs.α-M-γ-B inhibited the production of pro-inflammatory mediators via repolarizing M1 macrophages into M2 macrophages.The transcriptome sequencing suggested thatα-M-γ-B regulated the immune system pathway.Consistently,α-M-γ-B attenuated collagen type II-induced arthritic(CIA)phenotype,restored the balance of Tregs-macrophages and remodeled SM via repolarizing the synovial-associated macrophages in CIA mice.Mechanistically,althoughα-M-γ-B did not prevent the trans-nucleus of NF-κB it interfered with the DNA binding activity of NF-κB via direct interaction with the sulfhydryl in cysteine residue of NF-κB p65,which blocked the activation of NF-κB.Inhibition of NF-κB reduced the M1 polarization of macrophage and suppressed the synovial hyperplasia and angiogenesis.α-M-γ-B failed to ameliorate CIA in the presence of N-acetylcysteine or when the mice were subjected to the macrophage-specific deficiency of Rela.In conclusion,α-M-γ-B significantly attenuated the CIA phenotype by directly targeting NF-κB p65 and inhibiting its DNA binding ability.These results suggest thatα-M-γ-B has the potential to serve as an alternative candidate for treating RA.The greater electrophilicity ofα-M-γ-B,the basis for triggering strong anti-inflammatory activity,accounts for the reason whyα-M-γ-B is evolutionarily conserved in the SLs by medical plants.展开更多
Immunotherapy has shown robust efficacy in treating a broad spectrum of hematological and solid cancers.Despite the transformative impact of immunotherapy on cancer treatment,several outstanding challenges remain.Thes...Immunotherapy has shown robust efficacy in treating a broad spectrum of hematological and solid cancers.Despite the transformative impact of immunotherapy on cancer treatment,several outstanding challenges remain.These challenges include on-target off-tumor toxicity,systemic toxicity,and the complexity of achieving potent and sustainable therapeutic efficacy.Synthetic biology has emerged as a promising approach to overcome these obstacles,offering innovative tools for engineering living cells with customized functions.This review provides an overview of the current landscape and future prospects of cancer immunotherapy,particularly emphasizing the role of synthetic biology in augmenting its specificity,controllability,and efficacy.We delineate and discuss two principal synthetic biology strategies:those targeting tumor surface antigens with engineered immune cells and those detecting intratumoral disease signatures with engineered gene circuits.This review concludes with a forwardlooking perspective on the enduring challenges in cancer immunotherapy and the potential breakthroughs that synthetic biology may contribute to the field.展开更多
Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype.Molecular stratification and target therapy bring clinical benefit for TNBC patients,but it is difficult to implement comprehensive mole...Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype.Molecular stratification and target therapy bring clinical benefit for TNBC patients,but it is difficult to implement comprehensive molecular testing in clinical practice.Here,using our multi-omics TNBC cohort(N=425),a deep learning-based framework was devised and validated for comprehensive predictions of molecular features,subtypes and prognosis from pathological whole slide images.The framework first incorporated a neural network to decompose the tissue on WSIs,followed by a second one which was trained based on certain tissue types for predicting different targets.Multi-omics molecular features were analyzed including somatic mutations,copy number alterations,germline mutations,biological pathway activities,metabolomics features and immunotherapy biomarkers.It was shown that the molecular features with therapeutic implications can be predicted including the somatic PIK3CA mutation,germline BRCA2 mutation and PD-L1 protein expression(area under the curve[AUC]:0.78,0.79 and 0.74 respectively).The molecular subtypes of TNBC can be identified(AUC:0.84,0.85,0.93 and 0.73 for the basal-like immune-suppressed,immunomodulatory,luminal androgen receptor,and mesenchymal-like subtypes respectively)and their distinctive morphological patterns were revealed,which provided novel insights into the heterogeneity of TNBC.A neural network integrating image features and clinical covariates stratified patients into groups with different survival outcomes(log-rank P<0.001).Our prediction framework and neural network models were externally validated on the TNBC cases from TCGA(N=143)and appeared robust to the changes in patient population.For potential clinical translation,we built a novel online platform,where we modularized and deployed our framework along with the validated models.It can realize real-time one-stop prediction for new cases.In summary,using only pathological WSIs,our proposed framework can enable comprehensive stratifications of TNBC patients and provide valuable information for therapeutic decision-making.It had the potential to be clinically implemented and promote the personalized management of TNBC.展开更多
Enhancer RNAs(eRNAs)are a class of non-coding RNA,which play a critical role in tumor progression.1 Previous studies have indicated abundant CpG methylation,somatic mutation,and copy number variation in eRNA regions i...Enhancer RNAs(eRNAs)are a class of non-coding RNA,which play a critical role in tumor progression.1 Previous studies have indicated abundant CpG methylation,somatic mutation,and copy number variation in eRNA regions in cancers.2,3 We constructed a landscape of genetic alteration-driven eRNAs and provided an integrative pipeline to identify drug candidates that affect eRNA activity.Furthermore,we explored the prognostic value of genetic alteration-driven eRNAs.展开更多
Congenital melanocytic nevi(CMNs)are skin lesions characterized by benign melanocytic proliferations and present at birth or shortly thereafter.Large and giant CMNs,with a projected adult size≥20 cm and 40 cm in diam...Congenital melanocytic nevi(CMNs)are skin lesions characterized by benign melanocytic proliferations and present at birth or shortly thereafter.Large and giant CMNs,with a projected adult size≥20 cm and 40 cm in diameter respectively,are more likely to develop into malignant melanoma.In most cases,melanoma arising from congenital melanocytic nevus(CMN)is particularly aggressive.展开更多
Neuroblastoma(NB)is a common pediatric extracranial solid tumor that exhibits varied characteristics,clinical features,and prognosis.1 Totally 1%-2%of cases show familial history with genetic links like ALK,PHOX2B mut...Neuroblastoma(NB)is a common pediatric extracranial solid tumor that exhibits varied characteristics,clinical features,and prognosis.1 Totally 1%-2%of cases show familial history with genetic links like ALK,PHOX2B mutations,and1p36or11q14-23locusdeletions.Gastrointestinal stromal tumors(GISTs)are rare mesenchymal neoplasms of the gastrointestinal tract.展开更多
To investigate whether genetic variants may provide additional prognostic value to improve the existing clinical staging system for gastric cancer(GC),we performed two genome-wide association studies(GWASs)of GC survi...To investigate whether genetic variants may provide additional prognostic value to improve the existing clinical staging system for gastric cancer(GC),we performed two genome-wide association studies(GWASs)of GC survival in the Jiangsu(N=1049)and Shanghai(N=1405)cohorts.By using a TCGA dataset,we validated genetic markers identified from a meta-analysis of these two Chinese cohorts to determine GC survival-associated loci.Then,we constructed a weighted polygenic hazard score(PHS)and developed a nomogram in combination with clinical variables.We also evaluated prognostic accuracy with the time-dependent receiver operating characteristic(ROC)curve,net reclassification improvement(NRI)and integrated discrimination improvement(IDI).We identified a single nucleotide polymorphism(SNP)of rs1618332 at 15q15.1 that was associated with the survival of GC patients with a P value of 4.12×10^(-8),and we also found additional 25 SNPs having consistent associations among these two Chinese cohort and TCGA cohort.The PHS derived from these 26 SNPs(PHS-26)was an independent prognostic factor for GC survival(all P<0.001).The 5-year AUC of PHS-26 was 0.68,0.66 and 0.67 for Jiangsu,Shanghai and their pooled cohorts,respectively,which increased to 0.80,0.82 and 0.81,correspondingly,after being integrated into a nomogram together with variables of the clinical model.The PHS-26 could improve the NRIs by 16.20%,4.90%and 8.70%,respectively,and the IDIs by 11.90%,8.00%and 9.70%,respectively.The 26-SNP based PHS could substantially improve the accuracy of prognostic assessment and might facilitate precision medicine for GC patients.展开更多
基金Supported by the National Natural Science Foundation of China,No.82170286Basic Research Program of Guizhou Province(Natural Sciences),No.ZK[2023]321+1 种基金Start-up Fund of Guizhou Medical University,No.J2021032Postdoctoral Research Fund of Affiliated Hospital of Guizhou Medical University,No.BSH-Q-2021-10.
文摘The following letter to the editor highlights the article“Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance”in World J Diabetes 2023 Oct 15;14(10):1514-1523.It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.
基金supported by Shanghai Municipal Key Clinical Specialty (grant no. shslczdzk00901)Clinical Research Project of Multi-Disciplinary Team, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
文摘Congenital melanocytic nevi(CMN) are common skin tumors. Large and specially located nevi cannot be completely removed by surgery, posing the risks of both cosmetic deformities and potential malignancy.Nonsurgical treatments, such as laser therapy and physical dermabrasion, can overcome the limitations of surgery;however, the high rate of repigmentation remains an unresolved global challenge. We conducted a self-controlled observational study of a patient with a nevus on the chest. Two areas of the lesion were treated with an Er:YAG laser and 5% imiquimod cream was applied to one of these areas. After nearly 7-months of follow-up, we observed a significant difference in color between the two areas, suggesting that topical imiquimod may inhibit repigmentation and significantly enhance the effectiveness of laser treatment.
基金supported by grants from the National Natural Science Foundation of China(82173362)China Postdoctoral Science Foundation(2022M720175,2023M734003)National Science Foundation of China(82304069).
文摘Head and neck squamous cell carcinoma(HNSCC)is characterized by high recurrence or distant metastases rate and the prognosis is challenging.There is mounting evidence that tumor-infiltrating B cells(TIL-Bs)have a crucial,synergistic role in tumor control.However,little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade.Using single-cell RNA sequencing(scRNA-seq)data from the Gene Expression Omnibus(GEO)database,the study identified distinct gene expression patterns in TIL-Bs.HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering.This classification was further validated with TCGA HNSCC data,correlating with patient prognosis,immune cell infiltration,and response to immunotherapy.We found that the B cells activation group exhibited a better prognosis,higher immune cell infiltration,and distinct immune checkpoint levels,including elevated PD-L1.A prognostic model was also developed and validated,highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients.Overall,this study provides a foundational approach for B cells-based tumor classification in HNSCC,offering insights into targeted treatment and immunotherapy strategies.
基金supported by International Science and Technology Cooperation Projects,No.2015DFA30650 and No.2010DFB33720Capital Special Research Project for Health Development,No.2014-2-4012Capital Research Project for the Characteristics Clinical Application,No.Z151100004015170
文摘gallbladder cancer(gbc), although considered as a relatively rare malignancy, is the most common neoplasm of the biliary tract system. the late diagnosis and abysmal prognosis present challenges to treatment. the overall 5-year survival rate for metastatic gbc patients is extremely low. BRC A1 and BRCA2 are the breast cancer susceptibility genes and their mutation carriers are at a high risk for cancer development, both in men and women. Olaparib, an oral poly ADP-ribose polymerase inhibitor, has been approved by the Food and Drug Administration and the European commission for the treatment of ovarian cancer with any BRCA1/2 mutations. the first case of BRCA1-mutated gbc patient who responded to olaparib treatment is reported here.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related deaths worldwide,but there is a shortage of effective biomarkers for its diagnosis.AIM To explore blood exosomal micro ribonucleic acids(miRNAs)as potential biomarkers for HCC diagnosis.RESULTS The principal component analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of hepatitis B virus positive non-HCC patients through miR-3168 and miR-223-3p.The miRNA profiles also revealed the tumor stages of HCC patients.High expression of miR-455-5p and miR-30c-5p,which significantly correlated with better overall survival in tumor tissues,could also be detected in blood exosomes.Two pairs of miRNAs(miR-584-5p/miR-106-3p and miR-628-3p/miR-941)showed a 94.1%sensitivity and 68.4%specificity to differentiate HCC patients from non-HCC patients.The specificity of the combination was substantially influenced by alcohol consumption habits.CONCLUSION This study suggested that blood exosomal miRNAs can be used as new noninvasive diagnostic tools for HCC.However,their accuracy could be affected by tumor stage and alcohol consumption habits.
基金supported by grants from the National Natural Science Foundation of China(81872409)Natural Science Foundation of Guangdong Province(2018A030313610)+1 种基金the Open Funding of the State Key Laboratory of Oral Diseases(SKLOD2021OF02)Guangdong Basic and Applied Basic Research Foundation(2019A1515110110)。
文摘Methyltransferase like 13(METTL13),a kind of methyltransferase,is implicated in protein binding and synthesis.The upregulation of METTL13 has been reported in a variety of tumors.However,little was known about its potential function in head and neck squamous cell carcinoma(HNSCC)so far.In this study,we found that METTL13 was significantly upregulated in HNSCC at both mRNA and protein level.Increased METTL13 was negatively associated with clinical prognosis.And METTL13 markedly affected HNSCC cellular phenotypes in vivo and vitro.Further mechanism study revealed that METTL13 could regulate EMT signaling pathway by mediating enhancing translation efficiency of Snail,the key transcription factor in EMT,hence regulating the progression of EMT.Furthermore,Snail was verified to mediate METTL13-induced HNSCC cell malignant phenotypes.Altogether,our study had revealed the oncogenic role of METTL13 in HNSCC,and provided a potential therapeutic strategy.
文摘Intrahepatic cholangiocarcinoma(ICC) is a relatively rare form of liver cancer with a poor prognosis. The therapeutic options for patients with advanced ICC are limited and usually ineffective. There is currently no approved targeted therapy for ICC, although accumulating evidence supports inhibition of the PI3K/Akt/m TOR signaling pathway as a promising therapeutic strategy in the treatment of ICC. Here, we report a patient with stage IV ICC harboring a PIK3 CA mutation who responded well to the m TOR inhibitor everolimus. Computed tomography and magnetic resonance imaging demonstrated shrinkage of the tumor and maintenance of a partial response for 6.5 mo after everolimus treatment as the best response. To the best of our knowledge, this is the first clinical case report in the literature of clinical benefit from everolimus treatment in an ICC patient with PIK3 CA mutation.
基金funding support from the National Natural Science Foundation of China(No.82074251)the Hunan Natural Science Foundation of China(No.2018JJ2413)the Hunan Provincial Health and Health Commission Project(No.c2018032)。
文摘Objective To analyze the differential gene expression profile of serum exosomes in patients with acute cerebral infarction(ACI)and clarify the changes in gene expression related to cerebral infarction injury and the potential serum markers.Methods Four patients with ACI and five healthy people were enrolled in the PhaseⅠstudy.After serum isolation from peripheral blood,exosomes were extracted with exosomes kits,highthroughput detection of m RNA was performed with gene chips,and differentially expressed m RNAs were screened.Gene Ontology(GO)functional analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed simultaneously.Furthermore,real-time polymerase chain reaction(q RT-PCR)was used to verify the expression levels of the screened differential m RNAs in the serum exosomes collected in PhaseⅡfrom 32 patients each in the ACI case and normal control groups.Results In the PhaseⅠstudy,there were 248 differentially expressed m RNAs(fold change≥2.0,P<0.05)among five patients in the normal control group and four patients in the case group,of which the expression of 242 was upregulated and that of six was downregulated.The results of GO functional enrichment analysis mainly included behavior regulation,cell connection,and antioxidant activity.The results of KEGG pathway enrichment analysis mainly included ribosomes,proteasomes,oxytocin signaling pathways,and oxidative phosphorylation.After researching and screening based on relevant literature,it was found that among the genes with significant differential expression,H3 F3 B m RNA may be associated with and might play an important role in ACI.The q RT-PCR method was used to detect the H3 F3 B mRNA expression in serum exosomes of 32 patients each in the normal control and case groups in PhaseⅡ;the expression was significantly higher in serum exosomes of the case group than in those of the normal control group(P<0.001).H3 F3 B mRNA expression in serum exosomes of the case group positively correlated with age,the National Institutes of Health Stroke Scale(NIHSS)score,and the maximum infarct size(P<0.05).Conclusion ACI can lead to changes in the serum exosomes mRNA expression profile,which may be closely related to the occurrence,development,and prognosis of this condition.These findings will provide direction for research on the molecular mechanism,diagnostic markers,and therapeutic targets of ACI.
基金supported by the National Natural Science Foundation of China(32170230,31971540,31830005,42276159)the Guangdong Basic and Applied Basic Research Foundation(2023B1515020083)the Innovation Group Project of Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)(311021006)。
文摘Nypa fruticans(Wurmb),a mangrove palm species with origins dating back to the Late Cretaceous period,is a unique species for investigating long-term adaptation strategies to intertidal environments and the early evolution of palms.Here,we present a chromosome-level genome sequence and assembly for N.fruticans.We integrated the genomes of N.fruticans and other palm family members for a comparative genomic analysis,which confirmed that the common ancestor of all palms experienced a whole-genome duplication event around 89 million years ago,shaping the distinctive characteristics observed in this clade.We also inferred a low mutation rate for the N.fruticans genome,which underwent strong purifying selection and evolved slowly,thus contributing to its stability over a long evolutionary period.Moreover,ancient duplicates were preferentially retained,with critical genes having experienced positive selection,enhancing waterlogging tolerance in N.fruticans.Furthermore,we discovered that the pseudogenization of Early Methionine-labelled 1(EM1)and EM6 in N.fruticans underly its crypto-vivipary characteristics,reflecting its intertidal adaptation.Our study provides valuable genomic insights into the evolutionary history,genome stability,and adaptive evolution of the mangrove palm.Our results also shed light on the long-term adaptation of this species and contribute to our understanding of the evolutionary dynamics in the palm family.
基金supported by National Nature Science Foundation of China(82172978)Taishan Scholars Program of Shandong Province(Grant No.tsqn201909147)+1 种基金the Key Project at Central Government Level:the ability establishment of sustainable use for valuable Chinese medicine resources(2060302)the Student Innovation Training Program in Jining Medical University(cx2021116).
文摘Background:This study aimed to select compounds with unique inhibitory effects on muscle-invasive bladder cancer(MIBC)from coumarone derivatives with similar parent nuclear structures and to reveal their tumor-suppressive effects using various approaches.Methods:Bladder cancer cell lines SW780 and T24,as well as human normal bladder epithelial cell line SV-HUC-1 were selected as the study model,and these urinary system cells were co-incubated with various concentrations of(S,E)-4-(4-methylbenzylidene)-3-phenylchroman-3-ol,(S,E)-4-(4-isocyanobenzylidene)-3-phenylchroman-3-ol,(S,E)-4-(4-fluorobenzylidene)-3-phenylchroman-3-ol(FPO),and(S,E)-3-phenyl-4-(4-(trifluoromethoxy)benzylidene)chroman-3-ol.Cell activity was detected using cell counting kit-8.FPO showed the strongest inhibitory effect on MIBC cells;therefore,it was selected for further experiments.We monitored the FPO-induced T24 cell morphological changes with an inverted microscope.The FPO-inhibited migration of T24 cells was examined using a cell scratch assay.We detected the clonogenic ability of T24 cells through a clone formation test and evaluated their proliferative ability using a 5-ethynyl-2’-deoxyuridine fluorescence staining kit.The inhibitory effect of FPO against the cell cycle was monitored using flow cytometry,and its suppressive effect on the DNA replication ability of T24 cells was detected using double fluorescence staining(Ki67 and phalloidin).Results:Among the four candidate coumarone derivatives,FPO showed the most significant inhibitory effect on MIBC cells and was less toxic to normal urothelial cells.FPO inhibited T24 cell growth in time and dose-dependent manners(the half-inhibitory concentration is 8μM).FPO significantly repressed the proliferation,migration,and clonogenic ability of bladder cancer T24 cells.Cell mobility was significantly inhibited by FPO:30μM FPO almost completely repressed migration occurred at after 24 h treatment.Moreover,FPO significantly suppressed the clonogenicity of bladder cancer cells in a dose-dependent manner.Mechanistically,FPO targeted the cell cycle,arresting the S and G2 phases on bladder cancer T24 cells.Conclusion:We discovered a novel anticancer chemical,FPO,and proposed a potential mechanism,through which it suppresses MIBC T24 cells by repressing the cell cycle in the S and G2 phases.This study contributes to the development of novel anticancer drugs for MIBC.
基金financially supported by the Science Foundation Ireland (SFI) Frontiers for the Future 2019 call (No.19/FFP/6522)the National Natural Science Foundation of China (NSFC)(No.51873179)Irish Research Council (IRC) Government of Ireland Postdoctoral Fellowship (No.GOIPD/2022/209)。
文摘Copper(0)-mediated reversible-deactivation radical polymerization(Cu(0)-mediated RDRP) of the water-soluble monomer Nisopropylacrylamide(NIPAM) has been challenging with the problems of high dispersity, poor control over the molecular weights(MWs) or complex or multi reaction steps, etc. In this work, we report the well-controlled polymerization of NIPAM in water via a facile one-pot and one-step Cu(0)-mediated RDRP. The results of this approach show that the key for kicking off the Cu(0)-mediated NIPAM RDRPs is to ensure sufficient Cu~I at the very beginning, and the key to achieve a well-controlled chain growth is to provide adequate deactivation strength during the polymerization process. For NIPAM, which has a high propagation rate constant, the deactivation control can be effectively enhanced by extra adding deactivator(i.e., Cu~II) to the system. Moreover, a low reaction temperature(4 ℃) is necessary in the controlled synthesis of higher MW poly(Nisopropylacrylamide)(PNIPAM) to avoid the compromise in control caused by the phase transition from its lower critical solution temperature(LCST). Through this new kinetically controlled strategy, PNIPAMs with well-defined structure, narrow molecular weight distributions(MWDs) and varied MWs were successfully achieved.
基金supported by the National Key Research and Development Program of China(2021YFA1302100)the National Natural Science Foundation of China(82172861,32200542)+2 种基金the Young Elite Scientists Sponsorship Program by Guangzhou Association for Science and Technology(QT-2023-045)the Youth Talent Support Program of Guangdong Provincial Association for Science and Technology(SKXRC202313)the Young Talents Program of Sun Yat-sen University Cancer Center(YTP-SYSUCC-0033)。
文摘The exponential growth of bioinformatics tools in recent years has posed challenges for scientists in selecting the most suitable one for their data analysis assignments.Therefore,to aid scientists in making informed choices,a community-based platform that indexes and rates bioinformatics tools is urgently needed.In this study,we introduce Bio Treasury(http://biotreasury.rjmart.cn),an integrated communitybased repository that provides an interactive platform for users and developers to share their experiences in various bioinformatics tools.Bio Treasury offers a comprehensive collection of well-indexed bioinformatics software,tools,and databases,totaling over 10,000 entries.In the past two years,we have continuously improved and maintained Bio Treasury,adding several exciting features,including creating structured homepages for every tool and user,a hierarchical category of bioinformatics tools and classifying tools using large language model(LLM).Bio Treasury streamlines the tool submission process with intelligent auto-completion.Additionally,Bio Treasury provides a wide range of social features,for example,enabling users to participate in interactive discussions,rate tools,build and share tool collections for the public.We believe Bio Treasury can be a valuable resource and knowledge-sharing platform for the biomedical community.It empowers researchers to effectively discover and evaluate bioinformatics tools,fostering collaboration and advancing bioinformatics research.
基金support by the National Natural Science Foundation of China(82260801)China Postdoctoral Science Foundation(2023M730815,China)+5 种基金Excellent Young Talents Plan of Guizhou Medical University(2023110,China)the Guizhou Provincial Scientific and Technologic Innovation Base([2023]003,China)the High Level Innovation Talents(GCC[2023]048,China)Science and Technology Development Fund,Macao SAR(0159/2020/A3,China)Guizhou Provincial Science and Technology Project(ZK[2024]152,China)Guizhou Provincial Health Commission Science and Technology Foundation(gzwkj2023-153,China)are gratefully acknowledged.
文摘Rheumatoid arthritis(RA)is an inflammatory disease accompanied by abnormal synovial microenvironment(SM).Sesquiterpene lactones(SLs)are the main anti-inflammatory ingredients of many traditional herbs utilized in RA treatment.α-Methylene-γ-butyrolactone(α-M-γ-B)is a core moiety that widely exists in natural SLs.This study was designed to investigate the anti-arthritic potential ofα-M-γ-B as an independent small molecule in vitro and in vivo.α-M-γ-B exhibited stronger electrophilicity and anti-inflammatory effects than the other six analogs.α-M-γ-B inhibited the production of pro-inflammatory mediators via repolarizing M1 macrophages into M2 macrophages.The transcriptome sequencing suggested thatα-M-γ-B regulated the immune system pathway.Consistently,α-M-γ-B attenuated collagen type II-induced arthritic(CIA)phenotype,restored the balance of Tregs-macrophages and remodeled SM via repolarizing the synovial-associated macrophages in CIA mice.Mechanistically,althoughα-M-γ-B did not prevent the trans-nucleus of NF-κB it interfered with the DNA binding activity of NF-κB via direct interaction with the sulfhydryl in cysteine residue of NF-κB p65,which blocked the activation of NF-κB.Inhibition of NF-κB reduced the M1 polarization of macrophage and suppressed the synovial hyperplasia and angiogenesis.α-M-γ-B failed to ameliorate CIA in the presence of N-acetylcysteine or when the mice were subjected to the macrophage-specific deficiency of Rela.In conclusion,α-M-γ-B significantly attenuated the CIA phenotype by directly targeting NF-κB p65 and inhibiting its DNA binding ability.These results suggest thatα-M-γ-B has the potential to serve as an alternative candidate for treating RA.The greater electrophilicity ofα-M-γ-B,the basis for triggering strong anti-inflammatory activity,accounts for the reason whyα-M-γ-B is evolutionarily conserved in the SLs by medical plants.
文摘Immunotherapy has shown robust efficacy in treating a broad spectrum of hematological and solid cancers.Despite the transformative impact of immunotherapy on cancer treatment,several outstanding challenges remain.These challenges include on-target off-tumor toxicity,systemic toxicity,and the complexity of achieving potent and sustainable therapeutic efficacy.Synthetic biology has emerged as a promising approach to overcome these obstacles,offering innovative tools for engineering living cells with customized functions.This review provides an overview of the current landscape and future prospects of cancer immunotherapy,particularly emphasizing the role of synthetic biology in augmenting its specificity,controllability,and efficacy.We delineate and discuss two principal synthetic biology strategies:those targeting tumor surface antigens with engineered immune cells and those detecting intratumoral disease signatures with engineered gene circuits.This review concludes with a forwardlooking perspective on the enduring challenges in cancer immunotherapy and the potential breakthroughs that synthetic biology may contribute to the field.
基金supported by grants from the National Key Research and Development Program of China(2021YFF1201300 and 2021YFF1201305)the National Natural Science Foundation of China(82103039,81572583,81922048,91959207,U1809205,92159301,61771249 and 62171230)。
文摘Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype.Molecular stratification and target therapy bring clinical benefit for TNBC patients,but it is difficult to implement comprehensive molecular testing in clinical practice.Here,using our multi-omics TNBC cohort(N=425),a deep learning-based framework was devised and validated for comprehensive predictions of molecular features,subtypes and prognosis from pathological whole slide images.The framework first incorporated a neural network to decompose the tissue on WSIs,followed by a second one which was trained based on certain tissue types for predicting different targets.Multi-omics molecular features were analyzed including somatic mutations,copy number alterations,germline mutations,biological pathway activities,metabolomics features and immunotherapy biomarkers.It was shown that the molecular features with therapeutic implications can be predicted including the somatic PIK3CA mutation,germline BRCA2 mutation and PD-L1 protein expression(area under the curve[AUC]:0.78,0.79 and 0.74 respectively).The molecular subtypes of TNBC can be identified(AUC:0.84,0.85,0.93 and 0.73 for the basal-like immune-suppressed,immunomodulatory,luminal androgen receptor,and mesenchymal-like subtypes respectively)and their distinctive morphological patterns were revealed,which provided novel insights into the heterogeneity of TNBC.A neural network integrating image features and clinical covariates stratified patients into groups with different survival outcomes(log-rank P<0.001).Our prediction framework and neural network models were externally validated on the TNBC cases from TCGA(N=143)and appeared robust to the changes in patient population.For potential clinical translation,we built a novel online platform,where we modularized and deployed our framework along with the validated models.It can realize real-time one-stop prediction for new cases.In summary,using only pathological WSIs,our proposed framework can enable comprehensive stratifications of TNBC patients and provide valuable information for therapeutic decision-making.It had the potential to be clinically implemented and promote the personalized management of TNBC.
基金the Natural Science Foundation of Heilongjiang Province(China)(LH2023F012)University Excellent Youth Project of Provincial Scientific Research Institute(Heilongjiang,China)(CZKYF2022-1-C006)+1 种基金Outstanding Youth Foundation of Heilongjiang Province(China)(YQ2023F004)Program for Young Scholars with Creative Talents in Heilongjiang Province(China)(UNPYSCT-2020174).
文摘Enhancer RNAs(eRNAs)are a class of non-coding RNA,which play a critical role in tumor progression.1 Previous studies have indicated abundant CpG methylation,somatic mutation,and copy number variation in eRNA regions in cancers.2,3 We constructed a landscape of genetic alteration-driven eRNAs and provided an integrative pipeline to identify drug candidates that affect eRNA activity.Furthermore,we explored the prognostic value of genetic alteration-driven eRNAs.
基金funded by the National Natural Science Foundation of China(No.82204421 to Hanlin Zeng)the Innovative Research Team of High-Level Local Universities in Shanghai,China(No.SHSMU-ZLCX20211700 to Hanlin Zeng).
文摘Congenital melanocytic nevi(CMNs)are skin lesions characterized by benign melanocytic proliferations and present at birth or shortly thereafter.Large and giant CMNs,with a projected adult size≥20 cm and 40 cm in diameter respectively,are more likely to develop into malignant melanoma.In most cases,melanoma arising from congenital melanocytic nevus(CMN)is particularly aggressive.
基金supported by the National Natural Science Foundation of China (No.82293660,82293665)the Consulting and Research Project of the Chinese Academy of Engineering (No.2019-XY-34).
文摘Neuroblastoma(NB)is a common pediatric extracranial solid tumor that exhibits varied characteristics,clinical features,and prognosis.1 Totally 1%-2%of cases show familial history with genetic links like ALK,PHOX2B mutations,and1p36or11q14-23locusdeletions.Gastrointestinal stromal tumors(GISTs)are rare mesenchymal neoplasms of the gastrointestinal tract.
基金supported by National Natural Science Foundation of China(82125033,81872702,82103932,82003534)Natural Science Foundation of Jiangsu Province(BK20200674).
文摘To investigate whether genetic variants may provide additional prognostic value to improve the existing clinical staging system for gastric cancer(GC),we performed two genome-wide association studies(GWASs)of GC survival in the Jiangsu(N=1049)and Shanghai(N=1405)cohorts.By using a TCGA dataset,we validated genetic markers identified from a meta-analysis of these two Chinese cohorts to determine GC survival-associated loci.Then,we constructed a weighted polygenic hazard score(PHS)and developed a nomogram in combination with clinical variables.We also evaluated prognostic accuracy with the time-dependent receiver operating characteristic(ROC)curve,net reclassification improvement(NRI)and integrated discrimination improvement(IDI).We identified a single nucleotide polymorphism(SNP)of rs1618332 at 15q15.1 that was associated with the survival of GC patients with a P value of 4.12×10^(-8),and we also found additional 25 SNPs having consistent associations among these two Chinese cohort and TCGA cohort.The PHS derived from these 26 SNPs(PHS-26)was an independent prognostic factor for GC survival(all P<0.001).The 5-year AUC of PHS-26 was 0.68,0.66 and 0.67 for Jiangsu,Shanghai and their pooled cohorts,respectively,which increased to 0.80,0.82 and 0.81,correspondingly,after being integrated into a nomogram together with variables of the clinical model.The PHS-26 could improve the NRIs by 16.20%,4.90%and 8.70%,respectively,and the IDIs by 11.90%,8.00%and 9.70%,respectively.The 26-SNP based PHS could substantially improve the accuracy of prognostic assessment and might facilitate precision medicine for GC patients.
