BACKGROUND ATP-binding cassette subfamily B member 4(ABCB4)deficiency is associated with cholestatic liver disease primarily because of missense mutations,and many variants remain unidentified.Here,we validate the pat...BACKGROUND ATP-binding cassette subfamily B member 4(ABCB4)deficiency is associated with cholestatic liver disease primarily because of missense mutations,and many variants remain unidentified.Here,we validate the pathogenicity and mechanism of ABCB4 variants in clinical and in vitro trials,hypothesizing that these variants are responsible for impaired biliary function and contribute to the development of cholestatic liver diseases.AIM To clarify the functional features and pathogenicity of ABCB4 variants.METHODS Clinical data were collected from five patients with cholestatic liver disease that was initially not detected by routine examinations.Later,whole-exome sequencing confirmed ABCB4 variants and the patients were treated from January 2017 to December 2023.Pathogenic mechanisms were analyzed using bioinformatics tools,and a cell model in vitro was established to investigate ABCB4 mRNA expression,multidrug resistance protein 3(MDR3)expression,cellular localization,and phosphatidylcholine secretion.Results were compared using Student's t-tests.RESULTS Five missense variants(c.1757T>A,c.1865G>A,c.2362C>T,c.2777C>T and c.3250C>T),one intron variant(c.537-32G>T),and one synonymous(c.C504T)variant were identified.Three of the five patients had various degrees of cholestasis,two presented with liver cirrhosis,and all had elevated gamma-glutamyl transferase.Three of the four patients who underwent a liver biopsy had bile duct dilation,and one had gallstones.Two of the four patients had normal and reduced MDR3 immunohistochemical levels.Bioinformatic analysis indicated that these variants were likely pathogenic except c.C504T variant.None of the missense variants influenced subcellular MDR3 Localization in vitro.However,the c.1865G>A variant significantly decreased ABCB4 mRNA values,and all missense variants down-regulated phosphatidylcholine secretion.CONCLUSION This study uncovered new ABCB4 variants and emphasized the pathogenic potential of specific variants.The findings from five patients provided insight into the pathogenic mechanisms underlying ABCB4-related diseases.展开更多
BACKGROUND Cholangiocarcinoma(CCA)is a lethal malignancy with limited treatment options and poor prognosis.The PEA3 subfamily of E26 transformation specific genes:ETV1,ETV4,and ETV5 are known to play significant roles...BACKGROUND Cholangiocarcinoma(CCA)is a lethal malignancy with limited treatment options and poor prognosis.The PEA3 subfamily of E26 transformation specific genes:ETV1,ETV4,and ETV5 are known to play significant roles in various cancers by influencing cell proliferation,invasion,and metastasis.AIM To analyze PEA3 subfamily gene expression levels in CCA and their correlation with clinical parameters to determine their prognostic value for CCA.METHODS The expression levels of PEA3 subfamily genes in pan-cancer and CCA data in the cancer genome atlas and genotype-tissue expression project databases were analyzed with R language software.Survival curve and receiver operating characteristic analyses were performed using the SurvMiner,Survival,and Procr language packages.The gene expression profiling interactive analysis 2.0 database was used to analyze the expression levels of PEA3 subfamily genes in different subtypes and stages of CCA.Web Gestalt was used to perform the gene ontology/Kyoto encyclopedia of genes and genomes(GO/KEGG)analysis,and STRING database analysis was used to determine the genes and proteins related to PEA3 subfamily genes.RESULTS ETV1,ETV4,and ETV5 expression levels were significantly increased in CCA.There were significant differences in ETV1,ETV4,and ETV5 expression levels among the different subtypes of CCA,and predictive analysis revealed that only high ETV1 and ETV4 expression levels were significantly associated with shorter overall survival in patients with CCA.GO/KEGG analysis revealed that PEA3 subfamily genes were closely related to transcriptional misregulation in cancer.In vitro and in vivo experiments revealed that PEA3 silencing inhibited the invasion and metastasis of CCA cells.CONCLUSION The expression level of ETV4 may be a predictive biomarker of survival in patients with CCA.展开更多
The ATP-binding cassette(ABC)transporter is a gene superfamily in plants.ATP-binding cassette subfamily C(ABCC)protein is a multidrug resistance-associated(MRP)transporter.They play various roles in plant growth,devel...The ATP-binding cassette(ABC)transporter is a gene superfamily in plants.ATP-binding cassette subfamily C(ABCC)protein is a multidrug resistance-associated(MRP)transporter.They play various roles in plant growth,development,and secondary metabolite transport.However,there are few studies on ABCC transporters in tea plants.In this study,genome-wide association study(GWAS)analysis of epigallocatechin gallate(EGCG)content in 108 strains of Kingbird revealed that CsABCCs may be involved in EGCG transport.We identified 25 CsABCC genes at the genomic level of the tea plant,their phylogenetic tree,gene structure,targeted miRNA and other bioinformatics were analyzed.The expression patterns of CsABCCs in eight different tissues and abiotic stress indicate that they have potential roles in regulating the growth,development,and defense of tea plants.The correlation analysis revealed that the expression of the CsABCC11 gene was closely related to the EGCG content in tea buds of 108 strains of the Kingbird,and the subcellular localization experiments in tobacco showed that CsABCC11 protein was localized on the plasma membrane.The virus-induced gene silencing(VIGS)strategy in tea plants further verified that CsABCC11 was involved in EGCG accumulation.Our study laid a foundation for studying the biological function of CsABCC and provided a new candidate molecular marker gene for further EGCG-related variety breeding,which will be of great interest to breeders.展开更多
The B3 transcription factors(TFs)in plants play vital roles in numerous biological processes.Although B3 genes have been broadly identified in many plants,little is known about their potential functions in mediating s...The B3 transcription factors(TFs)in plants play vital roles in numerous biological processes.Although B3 genes have been broadly identified in many plants,little is known about their potential functions in mediating seed development and material accumulation.Castor bean(Ricinus communis)is a non-edible oilseed crop considered an ideal model system for seed biology research.Here,we identified a total of 61 B3 genes in the castor bean genome,which can be classified into five subfamilies,including ABI3/VP1,HSI,ARF,RAV and REM.The expression profiles revealed that RcABI3/VP1 subfamily genes are significantly up-regulated in the middle and later stages of seed development,indicating that these genes may be associated with the accumulation of storage oils.Furthermore,through yeast one-hybrid and tobacco transient expression assays,we detected that ABI3/VP1 subfamily member RcLEC2 directly regulates the transcription of RcOleosin2,which encodes an oil-body structural protein.This finding suggests that RcLEC2,as a seed-specific TF,may be involved in the regulation of storage materials accumulation.This study provides novel insights into the potential roles and molecular basis of B3 family proteins in seed development and material accumulation.展开更多
Aphids are marked by their high polymorphism, but species reported from the Early Cretaceous are known only from alate morphs. The discovery of an apterous adult morph in Lebanese amber and a larva of the same species...Aphids are marked by their high polymorphism, but species reported from the Early Cretaceous are known only from alate morphs. The discovery of an apterous adult morph in Lebanese amber and a larva of the same species are very important for the understanding of both the morphological and biological evolution of this insect group at the very early stage of development. Gondvanoaphis estephani new subfamily, new genus and species of the recent aphids family Thelaxidae is described. The characters of the new genus in respect to other genera placed in Thelaxidae are reviewed. The palaeoeeological and palaeogeographical data concerning Gondvanoaphis new genus are also discussed.展开更多
Ferritins can generally be divided into four subfamilies based on their structural characteristics,namely,the classic ferritins(Ftns),bacterioferritins(Bfrs),DNA-binding proteins from starved cells(Dps’),and encapsul...Ferritins can generally be divided into four subfamilies based on their structural characteristics,namely,the classic ferritins(Ftns),bacterioferritins(Bfrs),DNA-binding proteins from starved cells(Dps’),and encapsulated ferritins(Enc Ftns).However,the ferritin from Mycoplasma penetrans(Mpef)possesses a particular ferroxidase center with an extreme low activity and exhibits unusual characteristics,indicating that it could be a member of a quite different subfamily of ferritins.Hereby,the crystal structure of the ferritin from Ureaplasma urealyticum(Uurf)is presented,Mpef and Uurf have very similar properties,though they display very low sequence similarity.Thus,ferritins from Mycoplasma with these unique properties do not belong to any known subfamily,but they should rather be placed in a novel ferritin subfamily,which we term Mycoplasma Ferritin(Mfr).展开更多
Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)seems to employ two routes of entrance to the host cell;via membrane fusion(with the cells expressing both angiotensin converting enzyme 2(ACE2)and transmembr...Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)seems to employ two routes of entrance to the host cell;via membrane fusion(with the cells expressing both angiotensin converting enzyme 2(ACE2)and transmembrane peptidase/serine subfamily member 2/4(TMPRSS2/4))or via receptor-mediated endocytosis(to the target cells expressing only ACE2).The second mode is associated with cysteine cathepsins(probably cathepsin L)involvement in the virus spike protein(S protein)proteolytic activation.Also furin might activate the virus S protein enabling it to enter cells.Gastrointestinal tract(GIT)involvement in SARS-CoV-2 infection is evident in a subset of coronavirus disease 2019(COVID-19)patients exhibiting GIT symptoms,such as diarrhea,and presenting viral-shedding in feces.Considering the abundance and co-localization of ACE2 and TMPRSS2 in the lower GIT(especially brush-border enterocytes),these two receptors seem to be mainly involved in SARS-CoV-2 invasion of the digestive tract.Additionally,in vitro studies have demonstrated the virions capability of infection and replication in the human epithelial cells lining GIT.However,also furin and cysteine cathepsins(cathepsin L)might participate in the activation of SARS-CoV-2 spike protein contributing to the virus invasiveness within GIT.Moreover,cathepsin L(due to its involvement in extracellular matrix components degradation and remodeling,the processes enhanced during SARS-CoV-2-induced inflammation)might be responsible for the dysregulation of absorption/digestion functions of GIT,thus adding to the observed in some COVID-19 patients symptoms such as diarrhea.展开更多
BACKGROUND 17α-Hydroxylase deficiency(17-OHD)is a rare form of congenital adrenal hyperplasia,characterized by hypertension,hypokalemia,and gonadal dysplasia.However,due to the lack of a comprehensive understanding o...BACKGROUND 17α-Hydroxylase deficiency(17-OHD)is a rare form of congenital adrenal hyperplasia,characterized by hypertension,hypokalemia,and gonadal dysplasia.However,due to the lack of a comprehensive understanding of this disease,it is prone to misdiagnosis and missed diagnosis,and there is no complete cure.CASE SUMMARY We report a female patient with 17-OHD.The patient was admitted to the Department of Neurology of our hospital due to limb weakness.During treatment,it was found that the patient’s condition was difficult to correct except for hypokalemia,and her blood pressure was difficult to control with various antihypertensive drugs.She was then transferred to our department for further treatment.On physical examination,the patient's gonadal development was found to be abnormal,and chromosome analysis demonstrated karyotype 46,XY.Considering the possibility of 17-OHD,the cytochrome P450 family 17 subfamily A member 1(CYP17A1)test was performed to confirm the diagnosis.CONCLUSION The clinical manifestations of 17-OHD are complex.Hormone determination,imaging examination,chromosome determination and CYP17A1 gene test are helpful for early diagnosis.展开更多
For nonlinear feedback shift registers （NFSRs）, their greatest common subfamily may be not unique. Given two NFSRs, the authors only consider the case that their greatest common subfamily exists and is unique. If th...For nonlinear feedback shift registers （NFSRs）, their greatest common subfamily may be not unique. Given two NFSRs, the authors only consider the case that their greatest common subfamily exists and is unique. If the greatest common subfamily is exactly the set of all sequences which can be generated by both of them, the authors can determine it by Grobner basis theory. Otherwise, the authors can determine it under some conditions and partly solve the problem.展开更多
The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whe...The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517（300 mg/kg）, a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.展开更多
Flavonoids,the largest class of polyphenols,exhibit substantial structural and functional diversity,yet their evolutionary diversification and specialized functions remain largely unexplored.The genus Scutellaria is n...Flavonoids,the largest class of polyphenols,exhibit substantial structural and functional diversity,yet their evolutionary diversification and specialized functions remain largely unexplored.The genus Scutellaria is notable for its rich flavonoid diversity,particularly of 6/8-hydroxylated variants biosynthesized by the cytochrome P450 subfamily CYP82D.Our study analyzes metabolic differences between Scutellaria baicalensis and Scutellaria barbata,and the results suggest that CYP82Ds have acquired a broad range of catalytic functions over their evolution.By integrating analyses of metabolic networks and gene evolution across 22 Scutellaria species,we rapidly identified 261 flavonoids and delineated five clades of CYP82Ds associated with various catalytic functions.This approach revealed a unique catalytic mode for 6/8-hydroxylation of flavanone substrates and the first instance of 7-O-demethylation of flavonoid substrates catalyzed by a cytochrome P450.Ancestral sequence reconstruction and functional validation demonstrated that gradual neofunctionalization of CYP82Ds has driven the chemical diversity of flavonoids in the genus Scutellaria throughout its evolutionary history.These findings enhance our understanding of flavonoid diversity,reveal the intricate roles of CYP82Ds in Scutellaria species,and highlight the extensive catalytic versatility of cytochrome P450 members within plant taxa.展开更多
Objective To investigate the expression and regulatory role of adenosine triphosphate binding transporter C4(ABCC4) in patients with type 2 diabetes mellitus(T2DM) and macrovascular disease (MD).Methods A total of 137...Objective To investigate the expression and regulatory role of adenosine triphosphate binding transporter C4(ABCC4) in patients with type 2 diabetes mellitus(T2DM) and macrovascular disease (MD).Methods A total of 137 patients with T2DM were enrolled in this study from Zhongnan Hospital of Wuhan University during March 2015 and March 2017.展开更多
OBJECTIVE:To explore the therapeutic mechanisms of Xiaoyin Anshen Yin( 消银安神饮, XYAS) in treating psoriasis associated with sleep focusing on melatonin and the regulation of the nuclear factor kappa-B(NF-κB) pathw...OBJECTIVE:To explore the therapeutic mechanisms of Xiaoyin Anshen Yin( 消银安神饮, XYAS) in treating psoriasis associated with sleep focusing on melatonin and the regulation of the nuclear factor kappa-B(NF-κB) pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into four groups, and administered distilled water, XYAS and its two different disassembly prescriptions by gavage respectively. Four types of drug-containing serums corresponding to the four groups were then prepared. Tumor necrosis factor(TNF)-α stimulated Ha Ca T was used to establish a psoriasis cell model, and the serums and the retinoid related orphan receptor alpha(RORα) inverse agonist were used respectively to intervene in the model. Enzyme-linked immunosorbent assay was used to detect the levels of interleukin(IL)-6 and melatonin in each group;flow cytometry was used to detect the levels of reactive oxygen species(ROS), mitochondrial membrane potential, and apoptosis;Western blot was used to evaluate the levels of superoxide dismutase 2(SOD2), cytochrome-c(Cyt-c), inhibitor of kappa-B alpha(IκBα), p65 and phosphorylated p65. RESULTS:XYAS and its disassembly prescriptions inhibited the secretion of inflammatory factors such as IL-6, reduced the ROS content and Cyt-c expression, increased the mitochondrial membrane potential and SOD2 content, promoted the apoptosis in Ha Ca T cells and inhibited the activation of the NF-κB pathway. XYAS was also found increase the melatonin content. The above effects are beneficial in the treatment of psoriasis combined with sleep disorders. Meanwhile, XYAS no longer had a significant ameliorative effect after applying the RORα inverse agonist, suggesting that the therapeutic effect of XYAS is related to RORα. CONCLUSIONS:The results of this study confirm that XYAS can be utilized for the treatment of psoriasis combined with sleep disorders via inhibiting the NF-κB pathway, anti-inflammatory, antioxidant and proapoptotic, which is in part related to the regulatory role of melatonin and its receptor RORα.展开更多
BACKGROUND The pathophysiology of diabetic kidney disease(DKD)is complex.Interfering with the processes of pyroptosis and fibrosis is an effective strategy for slowing DKD progression.Previous studies have revealed th...BACKGROUND The pathophysiology of diabetic kidney disease(DKD)is complex.Interfering with the processes of pyroptosis and fibrosis is an effective strategy for slowing DKD progression.Previous studies have revealed that nuclear receptor subfamily 4 group A member 1(NR4A1)may serve as a novel pathogenic element in DKD;however,the specific mechanism by which it contributes to pyroptosis and fibrosis in DKD is unknown.AIM To investigate the role of NR4A1 in renal pyroptosis and fibrosis in DKD and possible molecular mechanisms.METHODS Streptozotocin 60 mg/kg was injected intraperitoneally to establish a rat model of DKD.Typically,45 mmol/L glucose[high glucose(HG)]was used to activate HK-2 cells to mimic the DKD model in vitro.HK-2 cells were transfected with NR4A1 siRNA to silence NR4A1.RESULTS NR4A1 was elevated in renal tissues of DKD rats and HG-stimulated HK-2 cells.Concurrently,NOD-like receptor protein 3(NLRP3)and phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathways were triggered,and pyroptosis and expression of fibrosis-linked elements was increased in vivo and in vitro.These alterations were significantly reversed via NR4A1 silencing.CONCLUSION Inhibition of NR4A1 mitigated pyroptosis and fibrosis via suppressing NLRP3 activation and the PI3K/AKT pathway in HG-activated HK-2 cells.展开更多
Background:As a major histopathological subtype of gastric cancer(GC),stomach adenocarcinoma(STAD)is an important malignant tumor in the digestive system.Increasing evidence also indicates that endoplasmic reticulum(E...Background:As a major histopathological subtype of gastric cancer(GC),stomach adenocarcinoma(STAD)is an important malignant tumor in the digestive system.Increasing evidence also indicates that endoplasmic reticulum(ER)stress plays a pivotal role in the pathogenesis and progression of GC.Therefore,this study aims to screen and identify vital ER stress-related genes that could contribute to the malignant development and poor prognosis for STAD.Methods:A novel ER stress-related risk score signature was developed employingmachine learning techniques.Then,a prognostic prediction nomogram was also built based on the clinicopathological characteristics and the risk score signature.The tumor immune microenvironment characteristics and pathway enrichment analysis in different risk groups were also explored.Furthermore,through the single-cell RNA sequencing(scRNA-seq)analysis,the study highlightedCytochrome P450 Family 19 SubfamilyAMember 1(CYP19A1)as the pivotal research target and detected its effect on cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide(MTT)and the expression of ER stress-related genes by RT-qPCR in STAD.Results:Based on the evaluation of five screened key ER stressrelated genes(AKR1B1,SERPINE1,ADCYAP1,MATN3,CYP19A1),our ER stress-related risk score signature offers a novel approach for assessing STAD prognosis hazards.The novel prognostic prediction nomogram based on the signature also accurately predicted the survival outcomes of patients with STAD.Furthermore,the expression of CYP19A1 is significantly higher in STAD tissues than in normal tissues.High expression of CYP19A1 was related to a poor survival outcome for patients with STAD.Besides,compared to normal gastric epithelial cells,the expression of CYP19A1 was significantly higher in STAD cell lines.Silencing the expression of CYP19A1 significantly inhibited the cell proliferation ability and decreased the expression of ER stress-related genes,including ATF4,DDIT3 and XBP1 in STAD.Conclusions:In conclusion,our study developed a novel prognosis prediction signature and identified the novel diagnostic and therapeutic target CYP19A1 for patients with STAD.展开更多
Background:Oral squamous cell carcinoma(OSCC)is the most common head and neck malig-nancy with a low five-year survival rate.ATP-binding cassette subfamily B member 5(ABCB5)has been linked to tumorigenesis.However,its...Background:Oral squamous cell carcinoma(OSCC)is the most common head and neck malig-nancy with a low five-year survival rate.ATP-binding cassette subfamily B member 5(ABCB5)has been linked to tumorigenesis.However,its role in inducing OSCC remains unclear.Methods:Quantitative reverse transcription polymerase chain reaction(qRT-PCR),western blot,and immunocytochemistry(ICC)were performed to examine the level of ABCB5 in OSCC(CAL27 and HSC-3)and human oral keratinocyte(HOK).ABCB5 was knocked down in CAL27 cells using ABCB5-specific small interfering RNA(ABCB5 siRNA),and its contribution to migration,invasion,and epithelial-mesenchymal transition(EMT),a process by which epithelial cells lose their tight junction and acquire an increased migratory and invasive phenotype resembling that of mesenchymal cells,were evaluated by three-dimension and transwell migration and invasion assays,qRT-PCR and ICC.An in vivo OSCC model was established using 4-nitroquinoline-1-oxide(4NQO),a carcinogenic chemical that is commonly used to develop OSCC by destroying DNA synthesis and oxidative stress.Pathological alterations,ABCB5,and EMT markers were evaluated by H&E staining,immunohistochemistry,and qRT-PCR.Results:ABCB5 was significantly upregulated in CAL27 and HSC-3 cells as compared to HOK.Knockdown of ABCB5 significantly reduced the number of migrated and invaded CAL27 cells,accompanied by the significantly increased E-cadherin and decreased Vimentin and N-cadherin under Transforming growth factorβ(TGF-β)treatment.In vivo,as OSCC advanced,a notable rise in the expressions of ABCB5,N-cadherin,and Vimentin,while a statistical decrease in E-cadherin was demonstrated.Conclusion:ABCB5 promotes the migration,invasion,and EMT of OSCC.ABCB5 might be a new biomarker and potential therapeutic target for OSCC.展开更多
Importance: The ATP-binding cassette subfamily A member 3 (ABCA3) protein plays a vital role in surfactant homeostasis. Mutations in the ABCA3 gene lead to the development of interstitial lung disease. In the most sev...Importance: The ATP-binding cassette subfamily A member 3 (ABCA3) protein plays a vital role in surfactant homeostasis. Mutations in the ABCA3 gene lead to the development of interstitial lung disease. In the most severe manifestation, mutations can lead to a fatal respiratory distress syndrome in neonates. ABCA3 belongs to the same ATP-binding cassette transporter superfamily as the cystic fibrosis transmembrane conductance regulator (CFTR), the gene that causes cystic fibrosis. Objective: To classify ABCA3 mutations in a manner similar to CFTR mutations in order to take advantage of recent advances in therapeutics. Methods: Sequence homology between the CFTR protein and the ABCA3 protein was established. The region of CFTR that is a target for the new potentiator class of drugs was of particular interest. We performed a literature search to obtain all published mutations that were thought to be disease causing. We classified these mutations using the established CFTR classification system. When possible, we drew on previous experimental classification of ABCA3 mutations. Results: Although the proteins share the same overall structure, only a 19％identity was established between CFTR and ABCA3. The CFTR therapeutic target region has a 22％ homology with the corresponding ABCA3 region. Totally 233 unique protein mutations were identified. All protein mutations were classified and mapped to a schematic diagram of the ABCA3 protein. Interpretation: This new classification system for ABCA3, based on CFTR classification, will likely aid further research of clinical outcomes and identification of mutation-tailored therapeutics, with the aim for improving clinical care for patients with ABCA3 mutations.展开更多
This paper reports a new subfamily, a new genus and a new species, that is, Pacrinae subfam, nov., Pacris gen. nov and Pacris xizangensis sp. nov in Gomphoceridae. The new subfamily is allied to Orinhippinae of Gompho...This paper reports a new subfamily, a new genus and a new species, that is, Pacrinae subfam, nov., Pacris gen. nov and Pacris xizangensis sp. nov in Gomphoceridae. The new subfamily is allied to Orinhippinae of Gomphoeeridae and it differs from the latter by wings and tympanum absent. The new genus is similar to Orinhippus Uvarov, 1921 but differs from the latter in： （i） foveolae absent; （ii） tegmina absent; （iii） tympanum absent; （iv） hind margin of pronotum with incised in the middle. Type specimens are deposited in the Museum of Hebei University, Baoding, China.展开更多
The complete genome sequences of 11 Drosophila species provide an opportunity to investigate the gene family evolution in closely related species. Drosophila Piwi subfamily, including three members, piwi, Aub and Ago3...The complete genome sequences of 11 Drosophila species provide an opportunity to investigate the gene family evolution in closely related species. Drosophila Piwi subfamily, including three members, piwi, Aub and Ago3, has attracted increasing attention as it participates in the biogenesis of piRNA. Here, we identified 33 Piwi homologs from the genome of 11 Drosophila species. The full-length cDNA sequences ofpiwi and Aub genes were obtained by using New GENSCAN Web Server. The Ago3 homologs were difficult regarding full-length information because they had long introns. The genomic structure of Piwi subfamily genes are highly conserved among diverse Drosophila species. Insect piwi and Aub genes have long first introns. The average length of the first intron is 1 284 bp for piwi and 840 bp for Aub, which is much larger than those of other introns （93 bp for Piwi and 54 bp for Aub）. However, this phenomenon is not observed in mammalian piwi genes. We also found that there were abundant repeat sequences in both exons and introns of insect Ago3 genes. Due to recent insertions of long terminal repeat elements in four Drosophila species, part of the third introns exhibit higher conservation than adjacent exons and other introns. An evolutional tree created by Minimum Evolution method indicates that mammalian piwi genes are more closely related to the insect Ago3 Piwi subfamily.展开更多
Objective To investigate the expression and clinical significance of T-cell receptor(TCR)Vβsubfamily in hepatitis B virus(HBV)-related acute-on-chronic liverfailure(HBV-ACLF)patients.Methods Twenty-eight patients wit...Objective To investigate the expression and clinical significance of T-cell receptor(TCR)Vβsubfamily in hepatitis B virus(HBV)-related acute-on-chronic liverfailure(HBV-ACLF)patients.Methods Twenty-eight patients with HBV-ACLF(HBV-ACLF group)and 32patients with chronic hepatitis B flare(CHB-F group),who were treated in The Second People’s Hospital展开更多
基金Supported by the National Natural Science Foundation of China,No.81970454.
文摘BACKGROUND ATP-binding cassette subfamily B member 4(ABCB4)deficiency is associated with cholestatic liver disease primarily because of missense mutations,and many variants remain unidentified.Here,we validate the pathogenicity and mechanism of ABCB4 variants in clinical and in vitro trials,hypothesizing that these variants are responsible for impaired biliary function and contribute to the development of cholestatic liver diseases.AIM To clarify the functional features and pathogenicity of ABCB4 variants.METHODS Clinical data were collected from five patients with cholestatic liver disease that was initially not detected by routine examinations.Later,whole-exome sequencing confirmed ABCB4 variants and the patients were treated from January 2017 to December 2023.Pathogenic mechanisms were analyzed using bioinformatics tools,and a cell model in vitro was established to investigate ABCB4 mRNA expression,multidrug resistance protein 3(MDR3)expression,cellular localization,and phosphatidylcholine secretion.Results were compared using Student's t-tests.RESULTS Five missense variants(c.1757T>A,c.1865G>A,c.2362C>T,c.2777C>T and c.3250C>T),one intron variant(c.537-32G>T),and one synonymous(c.C504T)variant were identified.Three of the five patients had various degrees of cholestasis,two presented with liver cirrhosis,and all had elevated gamma-glutamyl transferase.Three of the four patients who underwent a liver biopsy had bile duct dilation,and one had gallstones.Two of the four patients had normal and reduced MDR3 immunohistochemical levels.Bioinformatic analysis indicated that these variants were likely pathogenic except c.C504T variant.None of the missense variants influenced subcellular MDR3 Localization in vitro.However,the c.1865G>A variant significantly decreased ABCB4 mRNA values,and all missense variants down-regulated phosphatidylcholine secretion.CONCLUSION This study uncovered new ABCB4 variants and emphasized the pathogenic potential of specific variants.The findings from five patients provided insight into the pathogenic mechanisms underlying ABCB4-related diseases.
基金Science and Technology Development Plan Project of Hangzhou,No.20201203B56.
文摘BACKGROUND Cholangiocarcinoma(CCA)is a lethal malignancy with limited treatment options and poor prognosis.The PEA3 subfamily of E26 transformation specific genes:ETV1,ETV4,and ETV5 are known to play significant roles in various cancers by influencing cell proliferation,invasion,and metastasis.AIM To analyze PEA3 subfamily gene expression levels in CCA and their correlation with clinical parameters to determine their prognostic value for CCA.METHODS The expression levels of PEA3 subfamily genes in pan-cancer and CCA data in the cancer genome atlas and genotype-tissue expression project databases were analyzed with R language software.Survival curve and receiver operating characteristic analyses were performed using the SurvMiner,Survival,and Procr language packages.The gene expression profiling interactive analysis 2.0 database was used to analyze the expression levels of PEA3 subfamily genes in different subtypes and stages of CCA.Web Gestalt was used to perform the gene ontology/Kyoto encyclopedia of genes and genomes(GO/KEGG)analysis,and STRING database analysis was used to determine the genes and proteins related to PEA3 subfamily genes.RESULTS ETV1,ETV4,and ETV5 expression levels were significantly increased in CCA.There were significant differences in ETV1,ETV4,and ETV5 expression levels among the different subtypes of CCA,and predictive analysis revealed that only high ETV1 and ETV4 expression levels were significantly associated with shorter overall survival in patients with CCA.GO/KEGG analysis revealed that PEA3 subfamily genes were closely related to transcriptional misregulation in cancer.In vitro and in vivo experiments revealed that PEA3 silencing inhibited the invasion and metastasis of CCA cells.CONCLUSION The expression level of ETV4 may be a predictive biomarker of survival in patients with CCA.
基金supported by the Guizhou University Talent Introduction Program([2021]05)Guizhou University Cultivation Program([2020]48)+2 种基金Institute of Technology of YF([2022]017)Guizhou Province High-Level Innovative Talents“Hundred”Level Talent Project(Qiankehe Platform Talent)GCC[2023]014Supported by the earmarked fund for GZMARS-Tea and Research on the Planting Technology of China HUANENG Photovoltaic Tea Garden(Project No.HNKJ2022-H135).
文摘The ATP-binding cassette(ABC)transporter is a gene superfamily in plants.ATP-binding cassette subfamily C(ABCC)protein is a multidrug resistance-associated(MRP)transporter.They play various roles in plant growth,development,and secondary metabolite transport.However,there are few studies on ABCC transporters in tea plants.In this study,genome-wide association study(GWAS)analysis of epigallocatechin gallate(EGCG)content in 108 strains of Kingbird revealed that CsABCCs may be involved in EGCG transport.We identified 25 CsABCC genes at the genomic level of the tea plant,their phylogenetic tree,gene structure,targeted miRNA and other bioinformatics were analyzed.The expression patterns of CsABCCs in eight different tissues and abiotic stress indicate that they have potential roles in regulating the growth,development,and defense of tea plants.The correlation analysis revealed that the expression of the CsABCC11 gene was closely related to the EGCG content in tea buds of 108 strains of the Kingbird,and the subcellular localization experiments in tobacco showed that CsABCC11 protein was localized on the plasma membrane.The virus-induced gene silencing(VIGS)strategy in tea plants further verified that CsABCC11 was involved in EGCG accumulation.Our study laid a foundation for studying the biological function of CsABCC and provided a new candidate molecular marker gene for further EGCG-related variety breeding,which will be of great interest to breeders.
基金National Natural Science Foundation of China(31661143002,81760507,31571709,31771839,31701123 and 31501034)Yunnan Applied Basic Research Projects(2016FA011,2016FB060 and 2016FB040)+1 种基金the National R&D Infrastructure and Facility development Program of China"Fundamental Science Data Sharing Platform(DKA 201712-02-16)the 13th Five-year informatization Plan of Chinese Academy of Sciences(No.XXH13506)。
文摘The B3 transcription factors(TFs)in plants play vital roles in numerous biological processes.Although B3 genes have been broadly identified in many plants,little is known about their potential functions in mediating seed development and material accumulation.Castor bean(Ricinus communis)is a non-edible oilseed crop considered an ideal model system for seed biology research.Here,we identified a total of 61 B3 genes in the castor bean genome,which can be classified into five subfamilies,including ABI3/VP1,HSI,ARF,RAV and REM.The expression profiles revealed that RcABI3/VP1 subfamily genes are significantly up-regulated in the middle and later stages of seed development,indicating that these genes may be associated with the accumulation of storage oils.Furthermore,through yeast one-hybrid and tobacco transient expression assays,we detected that ABI3/VP1 subfamily member RcLEC2 directly regulates the transcription of RcOleosin2,which encodes an oil-body structural protein.This finding suggests that RcLEC2,as a seed-specific TF,may be involved in the regulation of storage materials accumulation.This study provides novel insights into the potential roles and molecular basis of B3 family proteins in seed development and material accumulation.
文摘Aphids are marked by their high polymorphism, but species reported from the Early Cretaceous are known only from alate morphs. The discovery of an apterous adult morph in Lebanese amber and a larva of the same species are very important for the understanding of both the morphological and biological evolution of this insect group at the very early stage of development. Gondvanoaphis estephani new subfamily, new genus and species of the recent aphids family Thelaxidae is described. The characters of the new genus in respect to other genera placed in Thelaxidae are reviewed. The palaeoeeological and palaeogeographical data concerning Gondvanoaphis new genus are also discussed.
基金supported partially by the National Natural Science Foundation of China(Nos.62075118,21601112)the Natural Science Foundation of Shanxi Province(No.20210302123433)+2 种基金Key R&D program of Shanxi Province(International Cooperation,No.201903D421070,2021XM21)Shanxi Key Laboratory of Pharmaceutical Biotechnology(No.KF202003)Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2019L0020)。
文摘Ferritins can generally be divided into four subfamilies based on their structural characteristics,namely,the classic ferritins(Ftns),bacterioferritins(Bfrs),DNA-binding proteins from starved cells(Dps’),and encapsulated ferritins(Enc Ftns).However,the ferritin from Mycoplasma penetrans(Mpef)possesses a particular ferroxidase center with an extreme low activity and exhibits unusual characteristics,indicating that it could be a member of a quite different subfamily of ferritins.Hereby,the crystal structure of the ferritin from Ureaplasma urealyticum(Uurf)is presented,Mpef and Uurf have very similar properties,though they display very low sequence similarity.Thus,ferritins from Mycoplasma with these unique properties do not belong to any known subfamily,but they should rather be placed in a novel ferritin subfamily,which we term Mycoplasma Ferritin(Mfr).
文摘Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)seems to employ two routes of entrance to the host cell;via membrane fusion(with the cells expressing both angiotensin converting enzyme 2(ACE2)and transmembrane peptidase/serine subfamily member 2/4(TMPRSS2/4))or via receptor-mediated endocytosis(to the target cells expressing only ACE2).The second mode is associated with cysteine cathepsins(probably cathepsin L)involvement in the virus spike protein(S protein)proteolytic activation.Also furin might activate the virus S protein enabling it to enter cells.Gastrointestinal tract(GIT)involvement in SARS-CoV-2 infection is evident in a subset of coronavirus disease 2019(COVID-19)patients exhibiting GIT symptoms,such as diarrhea,and presenting viral-shedding in feces.Considering the abundance and co-localization of ACE2 and TMPRSS2 in the lower GIT(especially brush-border enterocytes),these two receptors seem to be mainly involved in SARS-CoV-2 invasion of the digestive tract.Additionally,in vitro studies have demonstrated the virions capability of infection and replication in the human epithelial cells lining GIT.However,also furin and cysteine cathepsins(cathepsin L)might participate in the activation of SARS-CoV-2 spike protein contributing to the virus invasiveness within GIT.Moreover,cathepsin L(due to its involvement in extracellular matrix components degradation and remodeling,the processes enhanced during SARS-CoV-2-induced inflammation)might be responsible for the dysregulation of absorption/digestion functions of GIT,thus adding to the observed in some COVID-19 patients symptoms such as diarrhea.
文摘BACKGROUND 17α-Hydroxylase deficiency(17-OHD)is a rare form of congenital adrenal hyperplasia,characterized by hypertension,hypokalemia,and gonadal dysplasia.However,due to the lack of a comprehensive understanding of this disease,it is prone to misdiagnosis and missed diagnosis,and there is no complete cure.CASE SUMMARY We report a female patient with 17-OHD.The patient was admitted to the Department of Neurology of our hospital due to limb weakness.During treatment,it was found that the patient’s condition was difficult to correct except for hypokalemia,and her blood pressure was difficult to control with various antihypertensive drugs.She was then transferred to our department for further treatment.On physical examination,the patient's gonadal development was found to be abnormal,and chromosome analysis demonstrated karyotype 46,XY.Considering the possibility of 17-OHD,the cytochrome P450 family 17 subfamily A member 1(CYP17A1)test was performed to confirm the diagnosis.CONCLUSION The clinical manifestations of 17-OHD are complex.Hormone determination,imaging examination,chromosome determination and CYP17A1 gene test are helpful for early diagnosis.
基金supported by the Natural Science Foundation of China under Grant Nos.61272042,61100202and 61170235
文摘For nonlinear feedback shift registers （NFSRs）, their greatest common subfamily may be not unique. Given two NFSRs, the authors only consider the case that their greatest common subfamily exists and is unique. If the greatest common subfamily is exactly the set of all sequences which can be generated by both of them, the authors can determine it by Grobner basis theory. Otherwise, the authors can determine it under some conditions and partly solve the problem.
基金supported by the National Natural Science Foundation of China,No.81171178the Natural Science Foundation of Shanxi Province in China,No.2012011036-3Scientific Research Foundation of Shanxi Province of China for the Returned Overseas Chinese Scholars,No.2013011054-2
文摘The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517（300 mg/kg）, a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.
基金National Key Research and Development Program of China,grant 2023YFC3504800(to Y.X.)National Natural Science Foundation of China,grant 82470379(to S.Q.)+7 种基金Young Elite Scientists Sponsorship Program by Cast,grant 2021-QNRC1-02(to S.Q.)Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine,grant 2023YZZ02(to W.S.C.)The Open Fund of Shanghai Key Laboratory of Plant Functional Genomics and Resources,grant PFGR202501(to S.Q.)The National Natural Science Foundation of China,grant 82204577(to R.R.G.)The Research Project of Science and Technology Commission of Shanghai Municipality,grant 21DZ2202300(to S.Q.)Key project at the central government level:“The ability establishment of sustainable use for valuable Chinese medicine resources,”grant 2060302(to S.Q.)The Natural Science Foundation of Shanghai,grant 22ZR1479500(to Q.Z.)The China Postdoctoral Science Foundation,grant 2023M744290(to J.D.H.).
文摘Flavonoids,the largest class of polyphenols,exhibit substantial structural and functional diversity,yet their evolutionary diversification and specialized functions remain largely unexplored.The genus Scutellaria is notable for its rich flavonoid diversity,particularly of 6/8-hydroxylated variants biosynthesized by the cytochrome P450 subfamily CYP82D.Our study analyzes metabolic differences between Scutellaria baicalensis and Scutellaria barbata,and the results suggest that CYP82Ds have acquired a broad range of catalytic functions over their evolution.By integrating analyses of metabolic networks and gene evolution across 22 Scutellaria species,we rapidly identified 261 flavonoids and delineated five clades of CYP82Ds associated with various catalytic functions.This approach revealed a unique catalytic mode for 6/8-hydroxylation of flavanone substrates and the first instance of 7-O-demethylation of flavonoid substrates catalyzed by a cytochrome P450.Ancestral sequence reconstruction and functional validation demonstrated that gradual neofunctionalization of CYP82Ds has driven the chemical diversity of flavonoids in the genus Scutellaria throughout its evolutionary history.These findings enhance our understanding of flavonoid diversity,reveal the intricate roles of CYP82Ds in Scutellaria species,and highlight the extensive catalytic versatility of cytochrome P450 members within plant taxa.
文摘Objective To investigate the expression and regulatory role of adenosine triphosphate binding transporter C4(ABCC4) in patients with type 2 diabetes mellitus(T2DM) and macrovascular disease (MD).Methods A total of 137 patients with T2DM were enrolled in this study from Zhongnan Hospital of Wuhan University during March 2015 and March 2017.
基金National Natural Science Foundation of China:Study on the Mechanism of Cooling Blood and Tranquilizing Mind in the Treatment of Psoriasis with Sleep Disorder based on the Regulation of Oxidative Stress by Melatonin (No. 82074436)。
文摘OBJECTIVE:To explore the therapeutic mechanisms of Xiaoyin Anshen Yin( 消银安神饮, XYAS) in treating psoriasis associated with sleep focusing on melatonin and the regulation of the nuclear factor kappa-B(NF-κB) pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into four groups, and administered distilled water, XYAS and its two different disassembly prescriptions by gavage respectively. Four types of drug-containing serums corresponding to the four groups were then prepared. Tumor necrosis factor(TNF)-α stimulated Ha Ca T was used to establish a psoriasis cell model, and the serums and the retinoid related orphan receptor alpha(RORα) inverse agonist were used respectively to intervene in the model. Enzyme-linked immunosorbent assay was used to detect the levels of interleukin(IL)-6 and melatonin in each group;flow cytometry was used to detect the levels of reactive oxygen species(ROS), mitochondrial membrane potential, and apoptosis;Western blot was used to evaluate the levels of superoxide dismutase 2(SOD2), cytochrome-c(Cyt-c), inhibitor of kappa-B alpha(IκBα), p65 and phosphorylated p65. RESULTS:XYAS and its disassembly prescriptions inhibited the secretion of inflammatory factors such as IL-6, reduced the ROS content and Cyt-c expression, increased the mitochondrial membrane potential and SOD2 content, promoted the apoptosis in Ha Ca T cells and inhibited the activation of the NF-κB pathway. XYAS was also found increase the melatonin content. The above effects are beneficial in the treatment of psoriasis combined with sleep disorders. Meanwhile, XYAS no longer had a significant ameliorative effect after applying the RORα inverse agonist, suggesting that the therapeutic effect of XYAS is related to RORα. CONCLUSIONS:The results of this study confirm that XYAS can be utilized for the treatment of psoriasis combined with sleep disorders via inhibiting the NF-κB pathway, anti-inflammatory, antioxidant and proapoptotic, which is in part related to the regulatory role of melatonin and its receptor RORα.
基金Supported by Research Fund for Academician Lin He New Medicine,No.JYHL2022FMS02.
文摘BACKGROUND The pathophysiology of diabetic kidney disease(DKD)is complex.Interfering with the processes of pyroptosis and fibrosis is an effective strategy for slowing DKD progression.Previous studies have revealed that nuclear receptor subfamily 4 group A member 1(NR4A1)may serve as a novel pathogenic element in DKD;however,the specific mechanism by which it contributes to pyroptosis and fibrosis in DKD is unknown.AIM To investigate the role of NR4A1 in renal pyroptosis and fibrosis in DKD and possible molecular mechanisms.METHODS Streptozotocin 60 mg/kg was injected intraperitoneally to establish a rat model of DKD.Typically,45 mmol/L glucose[high glucose(HG)]was used to activate HK-2 cells to mimic the DKD model in vitro.HK-2 cells were transfected with NR4A1 siRNA to silence NR4A1.RESULTS NR4A1 was elevated in renal tissues of DKD rats and HG-stimulated HK-2 cells.Concurrently,NOD-like receptor protein 3(NLRP3)and phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathways were triggered,and pyroptosis and expression of fibrosis-linked elements was increased in vivo and in vitro.These alterations were significantly reversed via NR4A1 silencing.CONCLUSION Inhibition of NR4A1 mitigated pyroptosis and fibrosis via suppressing NLRP3 activation and the PI3K/AKT pathway in HG-activated HK-2 cells.
基金Natural Science Foundation of Liaoning Province(2022-MS-083)Application Basic Research Plan of Liaoning Province(2023JH2/101300084).
文摘Background:As a major histopathological subtype of gastric cancer(GC),stomach adenocarcinoma(STAD)is an important malignant tumor in the digestive system.Increasing evidence also indicates that endoplasmic reticulum(ER)stress plays a pivotal role in the pathogenesis and progression of GC.Therefore,this study aims to screen and identify vital ER stress-related genes that could contribute to the malignant development and poor prognosis for STAD.Methods:A novel ER stress-related risk score signature was developed employingmachine learning techniques.Then,a prognostic prediction nomogram was also built based on the clinicopathological characteristics and the risk score signature.The tumor immune microenvironment characteristics and pathway enrichment analysis in different risk groups were also explored.Furthermore,through the single-cell RNA sequencing(scRNA-seq)analysis,the study highlightedCytochrome P450 Family 19 SubfamilyAMember 1(CYP19A1)as the pivotal research target and detected its effect on cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide(MTT)and the expression of ER stress-related genes by RT-qPCR in STAD.Results:Based on the evaluation of five screened key ER stressrelated genes(AKR1B1,SERPINE1,ADCYAP1,MATN3,CYP19A1),our ER stress-related risk score signature offers a novel approach for assessing STAD prognosis hazards.The novel prognostic prediction nomogram based on the signature also accurately predicted the survival outcomes of patients with STAD.Furthermore,the expression of CYP19A1 is significantly higher in STAD tissues than in normal tissues.High expression of CYP19A1 was related to a poor survival outcome for patients with STAD.Besides,compared to normal gastric epithelial cells,the expression of CYP19A1 was significantly higher in STAD cell lines.Silencing the expression of CYP19A1 significantly inhibited the cell proliferation ability and decreased the expression of ER stress-related genes,including ATF4,DDIT3 and XBP1 in STAD.Conclusions:In conclusion,our study developed a novel prognosis prediction signature and identified the novel diagnostic and therapeutic target CYP19A1 for patients with STAD.
基金the financial support from the Sichuan Science and Technology Program(No.2024JDRC0040)Luzhou Science and Technology Program(No.2023JYJ002,No.2023SYF139)+4 种基金Southwest Medical University Technology Program(No.2024ZKY018,No.2023ZD001,No.2024KQZX09)National Natural Science Foundation of China(No.82403404)NHCKey Laboratory ofNuclear TechnologyMedical Transformation(Mianyang Central Hospital)(No.2023HYX028)The Science and Technology Strategic Cooperation Programs of Deyang Stomatological Hospital and Southwest Medical University(No.2024DYKQXNYD03)the Affiliated Stomatology Hospital of Southwest Medical University Program(No.2022KQ03)。
文摘Background:Oral squamous cell carcinoma(OSCC)is the most common head and neck malig-nancy with a low five-year survival rate.ATP-binding cassette subfamily B member 5(ABCB5)has been linked to tumorigenesis.However,its role in inducing OSCC remains unclear.Methods:Quantitative reverse transcription polymerase chain reaction(qRT-PCR),western blot,and immunocytochemistry(ICC)were performed to examine the level of ABCB5 in OSCC(CAL27 and HSC-3)and human oral keratinocyte(HOK).ABCB5 was knocked down in CAL27 cells using ABCB5-specific small interfering RNA(ABCB5 siRNA),and its contribution to migration,invasion,and epithelial-mesenchymal transition(EMT),a process by which epithelial cells lose their tight junction and acquire an increased migratory and invasive phenotype resembling that of mesenchymal cells,were evaluated by three-dimension and transwell migration and invasion assays,qRT-PCR and ICC.An in vivo OSCC model was established using 4-nitroquinoline-1-oxide(4NQO),a carcinogenic chemical that is commonly used to develop OSCC by destroying DNA synthesis and oxidative stress.Pathological alterations,ABCB5,and EMT markers were evaluated by H&E staining,immunohistochemistry,and qRT-PCR.Results:ABCB5 was significantly upregulated in CAL27 and HSC-3 cells as compared to HOK.Knockdown of ABCB5 significantly reduced the number of migrated and invaded CAL27 cells,accompanied by the significantly increased E-cadherin and decreased Vimentin and N-cadherin under Transforming growth factorβ(TGF-β)treatment.In vivo,as OSCC advanced,a notable rise in the expressions of ABCB5,N-cadherin,and Vimentin,while a statistical decrease in E-cadherin was demonstrated.Conclusion:ABCB5 promotes the migration,invasion,and EMT of OSCC.ABCB5 might be a new biomarker and potential therapeutic target for OSCC.
文摘Importance: The ATP-binding cassette subfamily A member 3 (ABCA3) protein plays a vital role in surfactant homeostasis. Mutations in the ABCA3 gene lead to the development of interstitial lung disease. In the most severe manifestation, mutations can lead to a fatal respiratory distress syndrome in neonates. ABCA3 belongs to the same ATP-binding cassette transporter superfamily as the cystic fibrosis transmembrane conductance regulator (CFTR), the gene that causes cystic fibrosis. Objective: To classify ABCA3 mutations in a manner similar to CFTR mutations in order to take advantage of recent advances in therapeutics. Methods: Sequence homology between the CFTR protein and the ABCA3 protein was established. The region of CFTR that is a target for the new potentiator class of drugs was of particular interest. We performed a literature search to obtain all published mutations that were thought to be disease causing. We classified these mutations using the established CFTR classification system. When possible, we drew on previous experimental classification of ABCA3 mutations. Results: Although the proteins share the same overall structure, only a 19％identity was established between CFTR and ABCA3. The CFTR therapeutic target region has a 22％ homology with the corresponding ABCA3 region. Totally 233 unique protein mutations were identified. All protein mutations were classified and mapped to a schematic diagram of the ABCA3 protein. Interpretation: This new classification system for ABCA3, based on CFTR classification, will likely aid further research of clinical outcomes and identification of mutation-tailored therapeutics, with the aim for improving clinical care for patients with ABCA3 mutations.
文摘This paper reports a new subfamily, a new genus and a new species, that is, Pacrinae subfam, nov., Pacris gen. nov and Pacris xizangensis sp. nov in Gomphoceridae. The new subfamily is allied to Orinhippinae of Gomphoeeridae and it differs from the latter by wings and tympanum absent. The new genus is similar to Orinhippus Uvarov, 1921 but differs from the latter in： （i） foveolae absent; （ii） tegmina absent; （iii） tympanum absent; （iv） hind margin of pronotum with incised in the middle. Type specimens are deposited in the Museum of Hebei University, Baoding, China.
基金Acknowledgments We thank Jin-jun Qian for assistance in constructing the phylogenetic tree. This work was in part supported by the National Natural Science Foundation of China （30174417）, Natural Science Foundation of Jiangsu Province （BK2007524） and program of New Century Excellent Talents （NCET） to FL.
文摘The complete genome sequences of 11 Drosophila species provide an opportunity to investigate the gene family evolution in closely related species. Drosophila Piwi subfamily, including three members, piwi, Aub and Ago3, has attracted increasing attention as it participates in the biogenesis of piRNA. Here, we identified 33 Piwi homologs from the genome of 11 Drosophila species. The full-length cDNA sequences ofpiwi and Aub genes were obtained by using New GENSCAN Web Server. The Ago3 homologs were difficult regarding full-length information because they had long introns. The genomic structure of Piwi subfamily genes are highly conserved among diverse Drosophila species. Insect piwi and Aub genes have long first introns. The average length of the first intron is 1 284 bp for piwi and 840 bp for Aub, which is much larger than those of other introns （93 bp for Piwi and 54 bp for Aub）. However, this phenomenon is not observed in mammalian piwi genes. We also found that there were abundant repeat sequences in both exons and introns of insect Ago3 genes. Due to recent insertions of long terminal repeat elements in four Drosophila species, part of the third introns exhibit higher conservation than adjacent exons and other introns. An evolutional tree created by Minimum Evolution method indicates that mammalian piwi genes are more closely related to the insect Ago3 Piwi subfamily.
文摘Objective To investigate the expression and clinical significance of T-cell receptor(TCR)Vβsubfamily in hepatitis B virus(HBV)-related acute-on-chronic liverfailure(HBV-ACLF)patients.Methods Twenty-eight patients with HBV-ACLF(HBV-ACLF group)and 32patients with chronic hepatitis B flare(CHB-F group),who were treated in The Second People’s Hospital
