BACKGROUND Scrub typhus is a naturally occurring acute infectious disease that is primarily transmitted through the bites of chiggers or larval mites infected by Orientia tsutsugamushi(O.tsutsugamushi).Omadacycline,a ...BACKGROUND Scrub typhus is a naturally occurring acute infectious disease that is primarily transmitted through the bites of chiggers or larval mites infected by Orientia tsutsugamushi(O.tsutsugamushi).Omadacycline,a novel tetracycline,exhibits potent antibacterial efficacy against both typical bacteria and atypical pathogens.However,omadacycline application in the treatment of scrub typhus remains limited.CASE SUMMARY In the present work,we report several cases of scrub typhus,with the main clinical symptoms being fever,the formation of eschars or ulcers,local or systemic lymphadenopathy,headache,myalgia and rash.Blood samples were collected before omadacycline was administered,and O.tsutsugamushi infection was confirmed through targeted next-generation sequencing(tNGS).After two days of treatment,the patients’symptoms,including fever,were alleviated,with no adverse drug reactions.CONCLUSION tNGS is an effective method for diagnosing scrub typhus.Omadacycline can be considered an alternative option for antiinfective therapy in patients with O.tsutsugamushi infections.展开更多
BACKGROUND Lung abscess found on chest X-ray and computed tomography examinations is rare in infants and young children.Several pathogens can cause lung abscesses,with the most common pathogens being anaerobes,Strepto...BACKGROUND Lung abscess found on chest X-ray and computed tomography examinations is rare in infants and young children.Several pathogens can cause lung abscesses,with the most common pathogens being anaerobes,Streptococci and Staphylococcus aureus.Streptococcus pseudopneumoniae(S.pseudopneumoniae)is a member of the Streptococcaceae family,and is mainly isolated from respiratory tract specimens.There are currently no cases of lung abscess caused by S.pseudopneumoniae in the literature.CASE SUMMARY A 2-year-old boy was admitted to hospital due to persistent cough and fever.Lung computed tomography examination suggested the formation of a lung abscess.His diagnosis was not confirmed by testing for serum respiratory pathogens(6 items),respiratory pathogen nucleic acid(27 items),and laboratory culture.Finally,metagenomic next-generation sequencing of bronchoalveolar lavage fluid revealed the presence of S.pseudopneumoniae,confirming its role in causing the lung abscess.After receiving antibiotic treatment,reexamination with lung computed tomography showed that the abscess was resorbed and the patient’s outcome was good.CONCLUSION This is the first report of a lung abscess in a child caused by S.pseudopneumoniae infection.Metagenomic next-generation sequencing of bronchoalveolar lavage fluid is helpful in achieving rapid and accurate pathogen identification.展开更多
Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of...Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of care therapies, including targeted therapies like sorafenib. Novel therapeutic options like immune checkpoint inhibitors may pose new challenges to identification and validation of such markers. Currently, PD-L1 expression via immunohistochemistry and tumor mutational burden via next-generation sequencing are explored as predictive biomarkers for these novel treatments. Limited tissue availability due to lack of biopsies still restricts the use of tissue based approaches. Novel methods exploring circulating or cell free nucleic acids(DNA, RNA or miRNAcontaining exosomes) could provide a new opportunity to establish predictive biomarkers. Epigenetic profiling and next-generation sequencing approaches from liquid biopsies are under development. Sample size, etiologic and geographical background need to be carefully addressed in such studies to achieve meaningful results that could be translated into clinical practice. Proteomics, metabolomics and molecular imaging are further emerging technologies.展开更多
BACKGROUND Non-small-cell lung cancer(NSCLC)has the highest morbidity and mortality rates among all malignant tumor types.Although therapies targeting the mutated genes such as KRAS have been used in the clinic for ma...BACKGROUND Non-small-cell lung cancer(NSCLC)has the highest morbidity and mortality rates among all malignant tumor types.Although therapies targeting the mutated genes such as KRAS have been used in the clinic for many years,the prognosis remains poor.Therefore,it is necessary to further study the aberrant expression or mutation of non-target genes affecting the survival and prognosis.AIM To explore the impact of simultaneous abnormalities of multiple genes on the prognosis and survival of patients.METHODS We used R packages to analyze gene expression data and clinical data downloaded from The Cancer Genome Atlas(TCGA)database.We also collected samples from 85 NSCLC patients from the First People’s Hospital of Jingzhou City and retrospectively followed the patients.Multivariate Cox regression analysis and survival analysis were performed.RESULTS Analysis of gene expression data from TCGA revealed that the overexpression of the following single genes affected overall survival:TP53(P=0.79),PTEN(P=0.94),RB1(P=0.49),CTNNB1(P=0.24),STK11(P=0.32),and PIK3CA(P=0.013).However,the probability of multiple genes(TP53,PTEN,RB1,and STK11)affecting survival was 0.025.Retrospective analysis of clinical data revealed that sex(hazard ratio[HR]=1.29;[95%CI:0.64-2.62]),age(HR=1.05;[95%CI:1.02-1.07]),smoking status(HR=2.26;[95%CI:1.16-4.39]),tumor histology(HR=0.58;[95%CI:0.30-1.11]),cancer stage(HR=16.63;[95%CI:4.8-57.63]),epidermal growth factor receptor(EGFR)mutation(HR=1.82;[95%CI:1.05-3.16]),abundance(HR=4.95;[95%CI:0.78-31.36]),and treatment with tyrosine kinase inhibitors(TKIs)(HR=0.58;[95%CI:0.43-0.78])affected patient survival.Co-occurring mutations of TP53,PTEN,RB1,and STK11 did not significantly affect the overall survival of patients receiving chemotherapy(P=0.96)but significantly affected the overall survival of patients receiving TKIs(P=0.045).CONCLUSION Co-occurring mutation or overexpression of different genes has different effects on the overall survival and prognosis of NSCLC patients.Combined with TKI treatment,the co-occurring mutation of some genes may have a synergistic effect on the survival and prognosis of NSCLC patients.展开更多
Auricularia heimuer,an edible jelly fungus,is in considerable demand in Asia due to its high nutritive,economic and medicinal values.RNA-Seq was used to investigate and analyze the mycelium transcriptome of A.heimuer ...Auricularia heimuer,an edible jelly fungus,is in considerable demand in Asia due to its high nutritive,economic and medicinal values.RNA-Seq was used to investigate and analyze the mycelium transcriptome of A.heimuer for gene discovery.A total of 26,857 unigenes with an N50 length of 1333 bp were assembled by de novo sequencing.In addition,unigenes were annotated by publicly available databases,including gene descriptions,gene ontology(GO),clusters of orthologous group(COG),Kyoto Encyclopedia of Genes and Genomes(KEGG)metabolic pathways,and protein family(Pfam)terms.A.heimuer was also studied for its wood degradation ability.Thirty-eight putative FOLymes(fungal oxidative lignin enzymes)and 251 CAZymes(carbohydrate-active enzymes)were located from A.heimuer transcriptome.Our study provides a comprehensive sequence resource for A.heimuer at the transcriptional level,which will lay a strong foundation for functional genomics studies and gene discovery of this promising fungus.展开更多
The identification of several genetic mutations in colorectal cancer(CRC)has allowed a better comprehension of the prognosis and response to different antineoplastic treatments.Recently,through a systematic process,co...The identification of several genetic mutations in colorectal cancer(CRC)has allowed a better comprehension of the prognosis and response to different antineoplastic treatments.Recently,through a systematic process,consensus molecular subtypes(CMS)have been described to characterize genetic and molecular mutations in CRC patients.Through CMS,CRC patients can be categorized into four molecular subtypes of CRC by wide transcriptional genome analysis.CMS1 has microsatellite instability and mutations in CIMP and BRAF pathways.CMS2,distinguished by mutations in specific pathways linked to cellular metabolism,also has a better prognosis.CMS3 has a KRAS mutation as a hallmark.CMS4 presents mutations in fibrogenesis pathways and mesenchymalepithelial transition,associated with a worse prognosis.CMS classification can be a meaningful step in providing possible answers to important issues in CRC,such as the use of adjuvant chemotherapy in stage II,personalized first-line chemotherapy for metastasic CRC,and possible new target treatments that address specific pathways in each molecular subtype.Understanding CMS is a crucial step in personalized medicine,although prospective clinical trials selecting patients by CMS are required to pass proof-of-concept before becoming a routine clinical tool in oncology routine care.展开更多
Bacteria of the genus Myroides （Myroides spp.） are rare opportunistic pathogens. Myroides sp. infections have been reported mainly in China. Myroides sp. is highly resistant to most available antibiotics, but the re...Bacteria of the genus Myroides （Myroides spp.） are rare opportunistic pathogens. Myroides sp. infections have been reported mainly in China. Myroides sp. is highly resistant to most available antibiotics, but the resistance mechanisms are not fully elucidated. Current strain identification methods based on biochemical traits are unable to identify strains accurately at the species level. While 16S ribosomal RNA （rRNA） gene sequencing can accurately achieve this, it fails to give information on the status and mechanisms of antibiotic resistance, because the 16S rRNA sequence contains no information on resistance genes, resistance islands or enzymes. We hypothesized that ob- taining the whole genome sequence of Myroides sp., using next generation sequencing methods, would help to clarify the mechanisms of pathogenesis and antibiotic resistance, and guide antibiotic selection to treat Myroides sp. infec- tions. As Myroides sp. can survive in hospitals and the environment, there is a risk of nosocomial infections and pandemics. For better management of Myroides sp. infections, it is imperative to apply next generation sequencing technologies to clarify the antibiotic resistance mechanisms in these bacteria.展开更多
The soil microbiome that plays important ecological roles in mountains and forests is influenced by anthropogenic and natural causes.Human activity,particularly harvesting or thinning,affects the soil microbiome in fo...The soil microbiome that plays important ecological roles in mountains and forests is influenced by anthropogenic and natural causes.Human activity,particularly harvesting or thinning,affects the soil microbiome in forests by altering environmental conditions,such as vegetation,microclimate,and soil physicochemical properties.The purpose of this study was to investigate the effects on forest thinning on the diversity and composition of the soil bacterial community.From next-generation sequencing results of the 16S rRNA gene,we examined differences in soil bacterial diversity and community composition before and after thinning at Mt.Janggunbong,South Korea.We identified 40 phyla,103 classes,192 orders,412families,947 genera,and 3,145 species from the soil samples.Acidobacteria and Proteobacteria were the most dominant bacterial phyla in the forest soil of Mt.Janggunbong.Soil bacterial diversity measures(richness,Shannon diversity index,and evenness)at the phylum level increased after thinning,whereas species-level taxonomic richness decreased after thinning.Thinning provided new opportunities for bacterial species in Chloroflexi,Verrucomicrobia,Nitrospirae,and other nondominant bacterial taxa,especially for those not found in Mt.Janggunbong before thinning,to settle and adapt to the changing environment.Our results suggested that thinning affected the diversity and composition of soil bacterial communities in forests and mountains.展开更多
BACKGROUND Microsatellite instability(MSI)is a predictive biomarker for cancer immunotherapy.The tumor-agnostic nature of MSI makes it a denominator for immunotherapy in several solid tumors.It can be assessed using n...BACKGROUND Microsatellite instability(MSI)is a predictive biomarker for cancer immunotherapy.The tumor-agnostic nature of MSI makes it a denominator for immunotherapy in several solid tumors.It can be assessed using next-generation sequencing(NGS),fluorescent multiplex PCR,and immunohistochemistry(IHC).CASE SUMMARY Here,we report 3 cases with discordant MSI results detected using different methods.A cholangiocellular carcinoma case revealed proficient mismatch repair(MMR)by IHC but high MSI(MSI-H)by liquid NGS.A cervical cancer case revealed deficient MMR by IHC,microsatellite stable by PCR,and MSI-H by NGS.Lastly,an endometrial cancer case revealed proficient MMR by IHC but MSI-H by NGS.CONCLUSION IHC for MMR status is the first choice due to several advantages.However,in cases of indeterminate IHC results,molecular testing by MSI-PCR is preferred.Recently,NGS-based MSI assays are being widely used to detect MSI-H tumors.All three methods have high accuracy;however,the inconsistencies between them may lead to misdiagnosis.展开更多
Follicular lymphoma(FL)is the most common indolent B-cell lymphoma(BCL)globally.Recently,its incidence has increased in Europe,the United States,and Asia,with the number of gastrointestinal FL cases expected to increa...Follicular lymphoma(FL)is the most common indolent B-cell lymphoma(BCL)globally.Recently,its incidence has increased in Europe,the United States,and Asia,with the number of gastrointestinal FL cases expected to increase.Genetic abnormalities related to t(14;18)translocation,BCL2 overexpression,NF-κB pathway-related factors,histone acetylases,and histone methyltransferases cause FL and enhance its proliferation.Meanwhile,microRNAs are commonly used in diagnosing FL and predicting patient prognosis.Many clinical trials on novel therapeutics targeting these genetic abnormalities and immunomodulatory mechanisms have been conducted,resulting in a marked improvement in therapeutic outcomes for FL.Although developing these innovative therapeutic agents targeting specific genetic mutations and immune pathways has provided hope for curative options,FL treatment has become more complex,requiring combinatorial therapeutic regimens.However,optimal treatment combinations have not yet been achieved,highlighting the importance of a complete understanding regarding the pathogenesis of gastrointestinal FL.Accordingly,this article reviews key research on the molecular pathogenesis of nodal FL and novel therapies targeting the causative genetic mutations.Moreover,the results of clinical trials are summarized,with a particular focus on treating nodal and gastrointestinal FLs.展开更多
Inflammatory myofibroblastic tumor(IMT)of the biliary tract is rare,and often difficult to diagnose or to distinguish from other tumors due to its atypical clinical presentation and nonspecific radiological features.H...Inflammatory myofibroblastic tumor(IMT)of the biliary tract is rare,and often difficult to diagnose or to distinguish from other tumors due to its atypical clinical presentation and nonspecific radiological features.Histologically,IMTs are(myo)fibroblastic neoplasms with a prominent inflammatory infiltrate.They are characterized by receptor tyrosine kinase gene rearrangements,most often involving an anaplastic lymphoma kinase(ALK)translocation.The final diagnosis of IMT depends on histopathology and immunohistochemical examination.In this manuscript,we provide a clinical and morphomolecular overview of IMT and the difficulties that may arise in using immunohistochemical and molecular techniques in diagnosing IMT.展开更多
Oncogenic gene fusions occur across a broad range of cancers and are a defining feature of some cancer types.Cancers driven by gene fusion products tend to respond well to targeted therapies,where available;thus,detec...Oncogenic gene fusions occur across a broad range of cancers and are a defining feature of some cancer types.Cancers driven by gene fusion products tend to respond well to targeted therapies,where available;thus,detection of potentially targetable oncogenic fusions is necessary to select optimal treatment.Detection methods include non-sequencing methods,such as fluorescence in situ hybridization and immunohistochemistry,and sequencing methods,such as DNA-and RNA-based nextgeneration sequencing(NGS).While NGS is an efficient way to analyze multiple genes of interest at once,economic and technical factors may preclude its use in routine care globally,despite several guideline recommendations.The aim of this review is to present a summary of oncogenic gene fusions,with a focus on fusions that affect tyrosine kinase signaling,and to highlight the importance of testing for oncogenic fusions.We present an overview of the identification of oncogenic gene fusions and therapies approved for the treatment of cancers harboring gene fusions,and summarize data regarding treating fusion-positive cancers with no current targeted therapies and clinical studies of fusion-positive cancers.Although treatment options may be limited for patients with rare alterations,healthcare professionals should identify patients most likely to benefit from oncogenic gene fusion testing and initiate the appropriate targeted therapy to achieve optimal treatment outcomes.展开更多
The growing demand for efficient and sustainable energy storage technologies has spurred significant research into alternatives to traditional lithium-ion batteries.Benefiting from the high energy density and abundant...The growing demand for efficient and sustainable energy storage technologies has spurred significant research into alternatives to traditional lithium-ion batteries.Benefiting from the high energy density and abundant,environmentally friendly properties of sulfur,metal−sulfur(M-S)batteries represent some of the most promising candidates for nextgeneration energy storage.1,2 Among them,lithium−sulfur(Li−S)and sodium−sulfur(Na−S)batteries have garnered attention due to their potential to surpass the performance of current energy storage technologies in terms of both energy capacity and cost-effectiveness,making them particularly attractive for applications in electric vehicles(EVs),gridscale energy storage,and portable electronics,where high energy density is a crucial factor.展开更多
Objective:Recent cholera outbreaks in Anhui Province have been linked to Vibrio cholerae O139,but information on these strains is limited.We established the first genomic dataset of local O139 strains to analyze the g...Objective:Recent cholera outbreaks in Anhui Province have been linked to Vibrio cholerae O139,but information on these strains is limited.We established the first genomic dataset of local O139 strains to analyze the genomic characteristics and evolution of antibiotic resistance.Methods:Thirty-four Vibrio cholerae O139 isolates from Anhui(2013–2024)were sequenced using nextgeneration sequencing.Genes for virulence,antimicrobial resistance,pathogenicity islands,and mobile genetic elements were predicted using ABRicate and other online tools.To construct a phylogenetic tree,124 publicly available O139 genomes were included in the single-nucleotide polymorphism analysis alongside the study isolates.Results:Strains formed two clusters that were genetically closer to China isolates than with those from Bangladesh and India.All strains harbored ctxA and ctxB,with partial deletions in virulence genes and pathogenicity islands;over 50%lacked vgrG-2 in the T6SS.Strains from 2022–2024 exhibited higher azithromycin but lower trimethoprimsulfamethoxazole resistance than those collected during 2013–2017.Conclusion:Vibrio cholerae O139 in Anhui are endemic to China,with limited virulence but strong colonization abilities.The increased azithromycin resistance rate may be driven by its clinical antimicrobial usage,suggesting its potential for continued antibiotic resistance evolution.展开更多
Dynamic chemistry based on reversible chemical bonds has emerged as a pivotal strategy for the development of nextgeneration materials.This highlight discusses a breakthrough reported by Zheng,Xie,and colleagues[1]fro...Dynamic chemistry based on reversible chemical bonds has emerged as a pivotal strategy for the development of nextgeneration materials.This highlight discusses a breakthrough reported by Zheng,Xie,and colleagues[1]from Zhejiang University in a recent science article,where they discovered a thermally reversible photo-click thiol-aldehyde reaction and applied it to achieve closed-loop recycling of 3D photo-printed polymers.展开更多
Chickens are one of the most important domesticated animals,serving as an important protein source.Studying genetic variations in chickens to enhance their production performance is of great potential value.The emerge...Chickens are one of the most important domesticated animals,serving as an important protein source.Studying genetic variations in chickens to enhance their production performance is of great potential value.The emergence of next-generation sequencing has enabled precise analysis of single nucleotide polymorphisms and insertions/deletions in chicken,while third-generation sequencing achieves the accurate structural variant identification.However,the high cost of third-generation sequencing technology limits its application in population studies.The graph-based pan-genome strategy can overcome this challenge by enabling the detection of structural variations using cost-effective next-generation sequencing data.This study constructed a graph-based pangenome for chickens using 12 high-quality genomes.This pan-genome used linear genome GRCg6a as the reference genome,containing variant information from two commercial and nine native chicken breeds.Compared to the linear genome,the pan-genome provided significant improvements in the efficiency of structural variation identification.On the basis of the graph-based pan-genome,high-frequency structural variations related to high egg production in Leghorn chicken were predicted.Additionally,it was discovered that potential structural variations was associated with highland adaptation in Tibetan chickens according to next-generation sequencing and transcriptomics data.Using the pan-genome graph,a new strategy to identify structural variations related to traits of interest in chickens is presented.展开更多
基金Supported by National Natural Science Foundation of China,No.81800721the Postdoctoral Foundation of China,2020M671387.
文摘BACKGROUND Scrub typhus is a naturally occurring acute infectious disease that is primarily transmitted through the bites of chiggers or larval mites infected by Orientia tsutsugamushi(O.tsutsugamushi).Omadacycline,a novel tetracycline,exhibits potent antibacterial efficacy against both typical bacteria and atypical pathogens.However,omadacycline application in the treatment of scrub typhus remains limited.CASE SUMMARY In the present work,we report several cases of scrub typhus,with the main clinical symptoms being fever,the formation of eschars or ulcers,local or systemic lymphadenopathy,headache,myalgia and rash.Blood samples were collected before omadacycline was administered,and O.tsutsugamushi infection was confirmed through targeted next-generation sequencing(tNGS).After two days of treatment,the patients’symptoms,including fever,were alleviated,with no adverse drug reactions.CONCLUSION tNGS is an effective method for diagnosing scrub typhus.Omadacycline can be considered an alternative option for antiinfective therapy in patients with O.tsutsugamushi infections.
基金Supported by Corps Guiding Plan Project of Xinjiang Uygur Autonomous Region,China,No.2022ZD031Financial Science and Technology Plan Project of Shihezi,Xinjiang Uygur Autonomous Region of China,No.2022NY01Research Project of Shihezi University of Shihezi,Xinjiang Uygur Autonomous Region of China,No.ZZZC202072A.
文摘BACKGROUND Lung abscess found on chest X-ray and computed tomography examinations is rare in infants and young children.Several pathogens can cause lung abscesses,with the most common pathogens being anaerobes,Streptococci and Staphylococcus aureus.Streptococcus pseudopneumoniae(S.pseudopneumoniae)is a member of the Streptococcaceae family,and is mainly isolated from respiratory tract specimens.There are currently no cases of lung abscess caused by S.pseudopneumoniae in the literature.CASE SUMMARY A 2-year-old boy was admitted to hospital due to persistent cough and fever.Lung computed tomography examination suggested the formation of a lung abscess.His diagnosis was not confirmed by testing for serum respiratory pathogens(6 items),respiratory pathogen nucleic acid(27 items),and laboratory culture.Finally,metagenomic next-generation sequencing of bronchoalveolar lavage fluid revealed the presence of S.pseudopneumoniae,confirming its role in causing the lung abscess.After receiving antibiotic treatment,reexamination with lung computed tomography showed that the abscess was resorbed and the patient’s outcome was good.CONCLUSION This is the first report of a lung abscess in a child caused by S.pseudopneumoniae infection.Metagenomic next-generation sequencing of bronchoalveolar lavage fluid is helpful in achieving rapid and accurate pathogen identification.
文摘Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of care therapies, including targeted therapies like sorafenib. Novel therapeutic options like immune checkpoint inhibitors may pose new challenges to identification and validation of such markers. Currently, PD-L1 expression via immunohistochemistry and tumor mutational burden via next-generation sequencing are explored as predictive biomarkers for these novel treatments. Limited tissue availability due to lack of biopsies still restricts the use of tissue based approaches. Novel methods exploring circulating or cell free nucleic acids(DNA, RNA or miRNAcontaining exosomes) could provide a new opportunity to establish predictive biomarkers. Epigenetic profiling and next-generation sequencing approaches from liquid biopsies are under development. Sample size, etiologic and geographical background need to be carefully addressed in such studies to achieve meaningful results that could be translated into clinical practice. Proteomics, metabolomics and molecular imaging are further emerging technologies.
基金Supported by the Natural Science Foundation of Hubei Province,No. 2017CFB786the Hubei Province Health and Family Planning Scientific Research Project,No. WJ2016Y10+1 种基金the Jingzhou Science and Technology Bureau Project,No. 2017-93the College Students Innovative Entrepreneurial Training Program in Yangtze University,No. 2019376
文摘BACKGROUND Non-small-cell lung cancer(NSCLC)has the highest morbidity and mortality rates among all malignant tumor types.Although therapies targeting the mutated genes such as KRAS have been used in the clinic for many years,the prognosis remains poor.Therefore,it is necessary to further study the aberrant expression or mutation of non-target genes affecting the survival and prognosis.AIM To explore the impact of simultaneous abnormalities of multiple genes on the prognosis and survival of patients.METHODS We used R packages to analyze gene expression data and clinical data downloaded from The Cancer Genome Atlas(TCGA)database.We also collected samples from 85 NSCLC patients from the First People’s Hospital of Jingzhou City and retrospectively followed the patients.Multivariate Cox regression analysis and survival analysis were performed.RESULTS Analysis of gene expression data from TCGA revealed that the overexpression of the following single genes affected overall survival:TP53(P=0.79),PTEN(P=0.94),RB1(P=0.49),CTNNB1(P=0.24),STK11(P=0.32),and PIK3CA(P=0.013).However,the probability of multiple genes(TP53,PTEN,RB1,and STK11)affecting survival was 0.025.Retrospective analysis of clinical data revealed that sex(hazard ratio[HR]=1.29;[95%CI:0.64-2.62]),age(HR=1.05;[95%CI:1.02-1.07]),smoking status(HR=2.26;[95%CI:1.16-4.39]),tumor histology(HR=0.58;[95%CI:0.30-1.11]),cancer stage(HR=16.63;[95%CI:4.8-57.63]),epidermal growth factor receptor(EGFR)mutation(HR=1.82;[95%CI:1.05-3.16]),abundance(HR=4.95;[95%CI:0.78-31.36]),and treatment with tyrosine kinase inhibitors(TKIs)(HR=0.58;[95%CI:0.43-0.78])affected patient survival.Co-occurring mutations of TP53,PTEN,RB1,and STK11 did not significantly affect the overall survival of patients receiving chemotherapy(P=0.96)but significantly affected the overall survival of patients receiving TKIs(P=0.045).CONCLUSION Co-occurring mutation or overexpression of different genes has different effects on the overall survival and prognosis of NSCLC patients.Combined with TKI treatment,the co-occurring mutation of some genes may have a synergistic effect on the survival and prognosis of NSCLC patients.
基金The work was supported by the Fundamental Research Funds for the Central Universities,(Project No.2572017CF01)the Harbin University Scientific Research Foundation project,(Project No.HUDF2018105).
文摘Auricularia heimuer,an edible jelly fungus,is in considerable demand in Asia due to its high nutritive,economic and medicinal values.RNA-Seq was used to investigate and analyze the mycelium transcriptome of A.heimuer for gene discovery.A total of 26,857 unigenes with an N50 length of 1333 bp were assembled by de novo sequencing.In addition,unigenes were annotated by publicly available databases,including gene descriptions,gene ontology(GO),clusters of orthologous group(COG),Kyoto Encyclopedia of Genes and Genomes(KEGG)metabolic pathways,and protein family(Pfam)terms.A.heimuer was also studied for its wood degradation ability.Thirty-eight putative FOLymes(fungal oxidative lignin enzymes)and 251 CAZymes(carbohydrate-active enzymes)were located from A.heimuer transcriptome.Our study provides a comprehensive sequence resource for A.heimuer at the transcriptional level,which will lay a strong foundation for functional genomics studies and gene discovery of this promising fungus.
基金Agencia Nacional de Investigación y Desarrollo de Chile,Fondo Nacional de Investigación y Desarrollo en Salud,FONIS,No.SA20I0059.
文摘The identification of several genetic mutations in colorectal cancer(CRC)has allowed a better comprehension of the prognosis and response to different antineoplastic treatments.Recently,through a systematic process,consensus molecular subtypes(CMS)have been described to characterize genetic and molecular mutations in CRC patients.Through CMS,CRC patients can be categorized into four molecular subtypes of CRC by wide transcriptional genome analysis.CMS1 has microsatellite instability and mutations in CIMP and BRAF pathways.CMS2,distinguished by mutations in specific pathways linked to cellular metabolism,also has a better prognosis.CMS3 has a KRAS mutation as a hallmark.CMS4 presents mutations in fibrogenesis pathways and mesenchymalepithelial transition,associated with a worse prognosis.CMS classification can be a meaningful step in providing possible answers to important issues in CRC,such as the use of adjuvant chemotherapy in stage II,personalized first-line chemotherapy for metastasic CRC,and possible new target treatments that address specific pathways in each molecular subtype.Understanding CMS is a crucial step in personalized medicine,although prospective clinical trials selecting patients by CMS are required to pass proof-of-concept before becoming a routine clinical tool in oncology routine care.
基金Project supported by the Huaqiao University Graduate Student Scientific Research Innovation Ability Cultivation Plan Projectsthe Major Program of Department of Science and Technology of Fujian Province(No.2012Y4009)+4 种基金the Science and Technology Planning Project of Xiamen(No.3502Z20123036)the Xiamen Southern Oceanographic Center(No.14GYY008NF08)the Construction Project for Yun Leung Laboratory for Molecular Diagnostics(No.14X30127)the Technology Planning Projects of Quanzhou Social Development Fields(No.2014Z24)the Major Support Research Project of National Key Colleges Construction of Quanzhou Medical College(No.2013A13),China
文摘Bacteria of the genus Myroides （Myroides spp.） are rare opportunistic pathogens. Myroides sp. infections have been reported mainly in China. Myroides sp. is highly resistant to most available antibiotics, but the resistance mechanisms are not fully elucidated. Current strain identification methods based on biochemical traits are unable to identify strains accurately at the species level. While 16S ribosomal RNA （rRNA） gene sequencing can accurately achieve this, it fails to give information on the status and mechanisms of antibiotic resistance, because the 16S rRNA sequence contains no information on resistance genes, resistance islands or enzymes. We hypothesized that ob- taining the whole genome sequence of Myroides sp., using next generation sequencing methods, would help to clarify the mechanisms of pathogenesis and antibiotic resistance, and guide antibiotic selection to treat Myroides sp. infec- tions. As Myroides sp. can survive in hospitals and the environment, there is a risk of nosocomial infections and pandemics. For better management of Myroides sp. infections, it is imperative to apply next generation sequencing technologies to clarify the antibiotic resistance mechanisms in these bacteria.
基金support of R&D Program for Forest Science Technology (Project No. 2013069D10-1719-AA03) provided by Korea Forest Service (Korea Forestry Promotion Institute)
文摘The soil microbiome that plays important ecological roles in mountains and forests is influenced by anthropogenic and natural causes.Human activity,particularly harvesting or thinning,affects the soil microbiome in forests by altering environmental conditions,such as vegetation,microclimate,and soil physicochemical properties.The purpose of this study was to investigate the effects on forest thinning on the diversity and composition of the soil bacterial community.From next-generation sequencing results of the 16S rRNA gene,we examined differences in soil bacterial diversity and community composition before and after thinning at Mt.Janggunbong,South Korea.We identified 40 phyla,103 classes,192 orders,412families,947 genera,and 3,145 species from the soil samples.Acidobacteria and Proteobacteria were the most dominant bacterial phyla in the forest soil of Mt.Janggunbong.Soil bacterial diversity measures(richness,Shannon diversity index,and evenness)at the phylum level increased after thinning,whereas species-level taxonomic richness decreased after thinning.Thinning provided new opportunities for bacterial species in Chloroflexi,Verrucomicrobia,Nitrospirae,and other nondominant bacterial taxa,especially for those not found in Mt.Janggunbong before thinning,to settle and adapt to the changing environment.Our results suggested that thinning affected the diversity and composition of soil bacterial communities in forests and mountains.
文摘BACKGROUND Microsatellite instability(MSI)is a predictive biomarker for cancer immunotherapy.The tumor-agnostic nature of MSI makes it a denominator for immunotherapy in several solid tumors.It can be assessed using next-generation sequencing(NGS),fluorescent multiplex PCR,and immunohistochemistry(IHC).CASE SUMMARY Here,we report 3 cases with discordant MSI results detected using different methods.A cholangiocellular carcinoma case revealed proficient mismatch repair(MMR)by IHC but high MSI(MSI-H)by liquid NGS.A cervical cancer case revealed deficient MMR by IHC,microsatellite stable by PCR,and MSI-H by NGS.Lastly,an endometrial cancer case revealed proficient MMR by IHC but MSI-H by NGS.CONCLUSION IHC for MMR status is the first choice due to several advantages.However,in cases of indeterminate IHC results,molecular testing by MSI-PCR is preferred.Recently,NGS-based MSI assays are being widely used to detect MSI-H tumors.All three methods have high accuracy;however,the inconsistencies between them may lead to misdiagnosis.
文摘Follicular lymphoma(FL)is the most common indolent B-cell lymphoma(BCL)globally.Recently,its incidence has increased in Europe,the United States,and Asia,with the number of gastrointestinal FL cases expected to increase.Genetic abnormalities related to t(14;18)translocation,BCL2 overexpression,NF-κB pathway-related factors,histone acetylases,and histone methyltransferases cause FL and enhance its proliferation.Meanwhile,microRNAs are commonly used in diagnosing FL and predicting patient prognosis.Many clinical trials on novel therapeutics targeting these genetic abnormalities and immunomodulatory mechanisms have been conducted,resulting in a marked improvement in therapeutic outcomes for FL.Although developing these innovative therapeutic agents targeting specific genetic mutations and immune pathways has provided hope for curative options,FL treatment has become more complex,requiring combinatorial therapeutic regimens.However,optimal treatment combinations have not yet been achieved,highlighting the importance of a complete understanding regarding the pathogenesis of gastrointestinal FL.Accordingly,this article reviews key research on the molecular pathogenesis of nodal FL and novel therapies targeting the causative genetic mutations.Moreover,the results of clinical trials are summarized,with a particular focus on treating nodal and gastrointestinal FLs.
文摘Inflammatory myofibroblastic tumor(IMT)of the biliary tract is rare,and often difficult to diagnose or to distinguish from other tumors due to its atypical clinical presentation and nonspecific radiological features.Histologically,IMTs are(myo)fibroblastic neoplasms with a prominent inflammatory infiltrate.They are characterized by receptor tyrosine kinase gene rearrangements,most often involving an anaplastic lymphoma kinase(ALK)translocation.The final diagnosis of IMT depends on histopathology and immunohistochemical examination.In this manuscript,we provide a clinical and morphomolecular overview of IMT and the difficulties that may arise in using immunohistochemical and molecular techniques in diagnosing IMT.
文摘Oncogenic gene fusions occur across a broad range of cancers and are a defining feature of some cancer types.Cancers driven by gene fusion products tend to respond well to targeted therapies,where available;thus,detection of potentially targetable oncogenic fusions is necessary to select optimal treatment.Detection methods include non-sequencing methods,such as fluorescence in situ hybridization and immunohistochemistry,and sequencing methods,such as DNA-and RNA-based nextgeneration sequencing(NGS).While NGS is an efficient way to analyze multiple genes of interest at once,economic and technical factors may preclude its use in routine care globally,despite several guideline recommendations.The aim of this review is to present a summary of oncogenic gene fusions,with a focus on fusions that affect tyrosine kinase signaling,and to highlight the importance of testing for oncogenic fusions.We present an overview of the identification of oncogenic gene fusions and therapies approved for the treatment of cancers harboring gene fusions,and summarize data regarding treating fusion-positive cancers with no current targeted therapies and clinical studies of fusion-positive cancers.Although treatment options may be limited for patients with rare alterations,healthcare professionals should identify patients most likely to benefit from oncogenic gene fusion testing and initiate the appropriate targeted therapy to achieve optimal treatment outcomes.
基金supported by Singapore Ministry of Education Tier 2 Grant(No.MOE-T2EP10223-0006)Tier 1 Grant(No.RG91/23).
文摘The growing demand for efficient and sustainable energy storage technologies has spurred significant research into alternatives to traditional lithium-ion batteries.Benefiting from the high energy density and abundant,environmentally friendly properties of sulfur,metal−sulfur(M-S)batteries represent some of the most promising candidates for nextgeneration energy storage.1,2 Among them,lithium−sulfur(Li−S)and sodium−sulfur(Na−S)batteries have garnered attention due to their potential to surpass the performance of current energy storage technologies in terms of both energy capacity and cost-effectiveness,making them particularly attractive for applications in electric vehicles(EVs),gridscale energy storage,and portable electronics,where high energy density is a crucial factor.
基金Supported by the National Disease Control and Prevention Administration Public Health Talent Training Program(202303)the Open Fund of the State Key Laboratory of Tea Plant Biology and Utilization(SKLTOF20200131)+1 种基金the Scientific Research Projects of Health Commission of Anhui Province in 2022(AHWJ2022a022)the Scientific Research Projects of Health Commission of Anhui Province in 2023(AHWJ2023A20398).
文摘Objective:Recent cholera outbreaks in Anhui Province have been linked to Vibrio cholerae O139,but information on these strains is limited.We established the first genomic dataset of local O139 strains to analyze the genomic characteristics and evolution of antibiotic resistance.Methods:Thirty-four Vibrio cholerae O139 isolates from Anhui(2013–2024)were sequenced using nextgeneration sequencing.Genes for virulence,antimicrobial resistance,pathogenicity islands,and mobile genetic elements were predicted using ABRicate and other online tools.To construct a phylogenetic tree,124 publicly available O139 genomes were included in the single-nucleotide polymorphism analysis alongside the study isolates.Results:Strains formed two clusters that were genetically closer to China isolates than with those from Bangladesh and India.All strains harbored ctxA and ctxB,with partial deletions in virulence genes and pathogenicity islands;over 50%lacked vgrG-2 in the T6SS.Strains from 2022–2024 exhibited higher azithromycin but lower trimethoprimsulfamethoxazole resistance than those collected during 2013–2017.Conclusion:Vibrio cholerae O139 in Anhui are endemic to China,with limited virulence but strong colonization abilities.The increased azithromycin resistance rate may be driven by its clinical antimicrobial usage,suggesting its potential for continued antibiotic resistance evolution.
文摘Dynamic chemistry based on reversible chemical bonds has emerged as a pivotal strategy for the development of nextgeneration materials.This highlight discusses a breakthrough reported by Zheng,Xie,and colleagues[1]from Zhejiang University in a recent science article,where they discovered a thermally reversible photo-click thiol-aldehyde reaction and applied it to achieve closed-loop recycling of 3D photo-printed polymers.
基金supported by the National Key Research and Development Program of China(2023YFF1001000)。
文摘Chickens are one of the most important domesticated animals,serving as an important protein source.Studying genetic variations in chickens to enhance their production performance is of great potential value.The emergence of next-generation sequencing has enabled precise analysis of single nucleotide polymorphisms and insertions/deletions in chicken,while third-generation sequencing achieves the accurate structural variant identification.However,the high cost of third-generation sequencing technology limits its application in population studies.The graph-based pan-genome strategy can overcome this challenge by enabling the detection of structural variations using cost-effective next-generation sequencing data.This study constructed a graph-based pangenome for chickens using 12 high-quality genomes.This pan-genome used linear genome GRCg6a as the reference genome,containing variant information from two commercial and nine native chicken breeds.Compared to the linear genome,the pan-genome provided significant improvements in the efficiency of structural variation identification.On the basis of the graph-based pan-genome,high-frequency structural variations related to high egg production in Leghorn chicken were predicted.Additionally,it was discovered that potential structural variations was associated with highland adaptation in Tibetan chickens according to next-generation sequencing and transcriptomics data.Using the pan-genome graph,a new strategy to identify structural variations related to traits of interest in chickens is presented.
