With the efficient and intelligent development of computer-based big data processing,applying machine learning methods to the processing and interpretation of logging data in the field of geophysical well logging has ...With the efficient and intelligent development of computer-based big data processing,applying machine learning methods to the processing and interpretation of logging data in the field of geophysical well logging has broad potential for improving production efficiency.Currently,the Jiyuan Oilfield in the Ordos Basin relies mainly on manual reprocessing and interpretation of old well logging data to identify different fluid types in low-contrast reservoirs,guiding subsequent production work.This study uses well logging data from the Chang 1 reservoir,partitioning the dataset based on individual wells for model training and testing.A deep learning model for intelligent reservoir fluid identification was constructed by incorporating the focal loss function.Comparative validations with five other models,including logistic regression(LR),naive Bayes(NB),gradient boosting decision trees(GBDT),random forest(RF),and support vector machine(SVM),show that this model demonstrates superior identification performance and significantly improves the accuracy of identifying oil-bearing fluids.Mutual information analysis reveals the model's differential dependency on various logging parameters for reservoir fluid identification.This model provides important references and a basis for conducting regional studies and revisiting old wells,demonstrating practical value that can be widely applied.展开更多
Two sharp Chernoff type inequalities are derived for star bodies in R2,one is an extension of the dual Chernoff-Ou-Pan inequality,and the other is the reverse Chernoff type inequality.Furthermore,we establish a genera...Two sharp Chernoff type inequalities are derived for star bodies in R2,one is an extension of the dual Chernoff-Ou-Pan inequality,and the other is the reverse Chernoff type inequality.Furthermore,we establish a generalized dual symmetric mixed Chernoff inequality for two planar star bodies.As a direct consequence,a new proof of the dual symmetric mixed isoperimetric inequality is presented.展开更多
Epithelial-mesenchymal transition(EMT)plays an irreplaceable role in the development of silicosis.However,molecular mechanisms of EMT induced by silica exposure still remain to be addressed.Herein,metabolic profiles o...Epithelial-mesenchymal transition(EMT)plays an irreplaceable role in the development of silicosis.However,molecular mechanisms of EMT induced by silica exposure still remain to be addressed.Herein,metabolic profiles of human alveolar type II epithelial cells(A549 cells)exposed directly to silica were characterized using non-targeted metabolomic approaches.A total of 84 differential metabolites(DMs)were identified in silica-treated A549 cells undergoing EMT,which were mainly enriched in metabolisms of amino acids(e.g.,glutamate,alanine,aspartate),purine metabolism,glycolysis,etc.The number of DMs identified in the A549 cells obviously increased with the elevated exposure concentration of silica.Remarkably,glutamine catabolism was significantly promoted in the silica-treated A549 cells,and the levels of related metabolites(e.g.,succinate)and enzymes(e.g.,α-ketoglutarate(α-KG)dehydrogenase)were substantially up-regulated,with a preference toα-KG pathway.Supplementation of glutamine into the cell culture could substantially enhance the expression levels of both EMT-related markers and Snail(zinc finger transcription factor).Our results suggest that the EMT of human alveolar epithelial cells directly induced by silica can be essential to the development of silicosis.展开更多
Type III acute acquired comitant esotropia(AACE)is a special type of binocular coordination disorder with sudden onset characteristics,but its pathogenesis and treatment strategies remain unclear.This article analyzes...Type III acute acquired comitant esotropia(AACE)is a special type of binocular coordination disorder with sudden onset characteristics,but its pathogenesis and treatment strategies remain unclear.This article analyzes the incidence and classification characteristics of Type III AACE,and explores its pathogenesis from multiple perspectives including clinical medicine,neuroscience,and neuro-ophthalmology.It is found that this disease is associated with factors such as decompensation of phoria,dysfunction of the visual center,abnormalities in the physiological and anatomical structure of extraocular muscles,accommodative factors,and disorders of convergence and divergence.The prognosis of Type III AACE is excellent with treatments such as botulinum toxin injection and surgery,and adjunctive therapies like prism adaptation test and visual function training can enhance the management effect.This article provides an in-depth analysis of the pathogenesis and cutting-edge treatment techniques for patients with Type III AACE,which can offer guidance for the subsequent diagnosis and treatment of such patients.展开更多
Mitral regurgitation (MR) is a highly prevalent valvular heart disease globally,with untreated severe cases demonstrating associations with elevated morbidity,mortality,and adverse cardiovascular outcomes.[1,2]While t...Mitral regurgitation (MR) is a highly prevalent valvular heart disease globally,with untreated severe cases demonstrating associations with elevated morbidity,mortality,and adverse cardiovascular outcomes.[1,2]While transcatheter edge-toedge repair (TEER) has emerged as an alternative option for high surgical risk patients with severe MR,[3,4]severe MR of Carpentier class IIIa (characterized by restricted leaflet motion during both systole and diastole) has been considered a relative contraindication for TEER interventions due to stenosis risk and procedural complexity.[5,6]展开更多
BACKGROUND Radial head fractures constitute approximately one-third of all elbow fractures,significantly impacting the young and active population.While open reduction and internal fixation is the preferred treatment ...BACKGROUND Radial head fractures constitute approximately one-third of all elbow fractures,significantly impacting the young and active population.While open reduction and internal fixation is the preferred treatment for displaced fractures,its high complication rate in comminuted fractures has led to the increasing use of radial head arthroplasty(RHA).RHA provides improved functional outcomes with fewer complications,yet its long-term efficacy remains a topic of debate.AIM To evaluate the functional outcomes of patients undergoing RHA with a modular metallic prosthesis for comminuted Mason type III and IV radial head fractures.METHODS A prospective and retrospective hospital-based study was conducted at Dayanand Medical College and Hospital,Ludhiana over 32 months(January 2021-August 2023).A total of 26 patients with Mason type III and IV fractures were included,with six retrospective and 20 prospective cases.Functional outcomes were assessed using the Mayo Elbow Performance Score(MEPS),elbow range of motion,pain via Visual Analog Scale,and activities of daily living at immediate postoperative,three-month,and six-month follow-ups.RESULTS MEPS at 6 months follow up for 4 cases(15.38%)had good scores,and 22 cases(84.62%)had excellent scores,with a mean±SD of 97.31±6.67.Comparisons showed significant improvement from immediate post-operative to 3 months(P<0.0001),from immediate post-operative to 6 months(P<0.0001),and between 3 months and 6 months(P<0.0001).None of the patients had elbow instability after radial head replacement and 22 cases(84.62%)had no complications,while 3 cases(11.54%)had a stiff elbow,and 1 case(3.85%)had heterotopic ossification.CONCLUSION RHA is an effective treatment for comminuted radial head fractures,providing stable elbow function with minimal complications.展开更多
Type 2 diabetes mellitus(T2DM)significantly elevates the risk of colorectal cancer(CRC)and complicates its treatment by promoting chemoresistance.Poor glycemic control has been linked to exacerbated CRC progression an...Type 2 diabetes mellitus(T2DM)significantly elevates the risk of colorectal cancer(CRC)and complicates its treatment by promoting chemoresistance.Poor glycemic control has been linked to exacerbated CRC progression and diminished chemotherapy efficacy,impacting patient outcomes through various mechanisms such as oxidative stress,activation of metabolic pathways,and altered protein modifications that hinder apoptosis and enhance tumor survival.Clinical evidence shows that T2DM patients experience higher rates of chemoresistance and reduced disease-free survival and overall survival compared to non-diabetic patients.Specifically,those with poor glycemic control exhibit increased chemo-resistance and poorer survival metrics.Antidiabetic treatments,including metformin,acarbose,and gliclazide,show promise in improving chemotherapy response and glycemic management,potentially enhancing patient outcomes.Addressing this challenge requires a comprehensive,multidisciplinary approach involving oncologists,endocrino-logists,and surgeons to optimize patient care.Integrated strategies that prioritize glycemic control are essential for reducing chemoresistance and improving survival in CRC patients with T2DM.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are caused by mutations in the KIT and platelet derived growth factor receptor alpha genes in approximately 90%of cases.A minority of wild-type GISTs are associated wit...BACKGROUND Gastrointestinal stromal tumors(GISTs)are caused by mutations in the KIT and platelet derived growth factor receptor alpha genes in approximately 90%of cases.A minority of wild-type GISTs are associated with neurofibromatosis type 1(NF1),an autosomal dominant genetic disease resulting from pathogenic mutations in the NF1 gene,which encodes the neurofibromin protein.NF1 patients often exhibit multi-system involvement,with café-au-lait macules and neurofibromas being characteristic symptoms.GISTs are a rare complication of NF1,with the tumors most frequently occurring in the small intestine(90%of cases),while occurrences in the stomach are rare.CASE SUMMARY A 51-year-old woman presented to the emergency department with complaints of dizziness,fatigue,chest tightness,and dark stools.Initial examination revealed a red blood cell count of 1.99×1012/L and a hemoglobin level of 43 g/L.She underwent blood transfusions and fluid replacement to stabilize her condition.Further investigations identified typical café-au-lait macules on her trunk,limbs,and face,along with neurofibromas.Endoscopy showed coffee-colored fluid in the gastric cavity,a large submucosal elevation with an exudative covering,and ulcer formation on the gastric fundus.Exploratory laparoscopy confirmed the tumor’s origin in the gastric fundus,and resection of the giant GIST was performed.Pathological analysis revealed a necrotic GIST measuring 18 cm×14 cm,classified as high-risk,with approximately 5 mitotic figures per 10 high-power fields and no tumor at the margins.Immunohistochemistry results were CD117(+),delay of germination 1(+),CD34(+),and succinate dehydrogenase complex iron sulfur subunit B intact expression.Genetic testing using next-generation sequencing confirmed an NF1 gene mutation.The patient underwent successful tumor resection and was discharged home with postoperative regorafenib therapy.A follow-up at one year showed no recurrence.CONCLUSION Given the diversity of clinical symptoms associated with NF1 and the complexity of NF1-related GISTs,surgical resection with complete tumor removal remains the preferred treatment option.However,the absence of a standardized treatment protocol for adjuvant therapy presents numerous challenges for clinicians.展开更多
Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization o...Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization of numerous TA systems in various bacteria,the investigation of these systems within Streptococcus suis is still limited.Here,we systematically analyzed the type Ⅱ TA systems of 95 S.suis genomes available in the GenBank database using TAfinder.A total of 612 putative type Ⅱ TA systems were retrieved and classified into 10 categories by phylogenetic analysis.Notably,an elevated occurrence of these TA systems was observed among the important prevalent serotypes 2,4,5,9,14,Chz,NCL1,and NCL3 strains.The following study identified the activities of TA systems using 2 strategies and confirmed the regulatory effect of HigBA on the type Ⅶ secretion system in S.suis by measuringβ-galactosidase activity and transcriptional changes.Moreover,we unveiled a hitherto uncharacterized,highly prevalent novel TA system,with the composition of antitoxin–toxin–antitoxin(SS-ATA),which regulates the downstream two-component signaling system.Altogether,this study systematically analyzed the type Ⅱ TA systems within S.suis,highlighting the widespread distribution of Hig BA and SS-ATA as important regulatory elements in S.suis.展开更多
In this paper, supose Γ be a boundary of a Jordan domain D and Γ satisfied Альпер condition, the order that rational type interpolating operators at Fejer's points of f(z)∈C(Γ) converge to f(z) in the se...In this paper, supose Γ be a boundary of a Jordan domain D and Γ satisfied Альпер condition, the order that rational type interpolating operators at Fejer's points of f(z)∈C(Γ) converge to f(z) in the sense of uniformly convergence is obtained.展开更多
Intuitionistic fuzzy set is an extended form of Zadeh's fuzzy set. In this paper, the concept of L type intuitionistic fuzzy family based on lattice implication algebras was proposed and some of its properties we...Intuitionistic fuzzy set is an extended form of Zadeh's fuzzy set. In this paper, the concept of L type intuitionistic fuzzy family based on lattice implication algebras was proposed and some of its properties were discussed.展开更多
Recently in [4], the Jessen＇s type inequality for normalized positive C0-semigroups is obtained. In this note, we present few results of this inequality, yielding Holder＇s Type and Minkowski＇s type inequalities for...Recently in [4], the Jessen＇s type inequality for normalized positive C0-semigroups is obtained. In this note, we present few results of this inequality, yielding Holder＇s Type and Minkowski＇s type inequalities for corresponding semigroup. Moreover, a Dresher＇s type inequality for two-parameter family of means, is also proved.展开更多
AIM:To investigate the expressions of type I collagen, α2 integrin and β1 integrin in the posterior sclera of guinea pigs with defocus myopia and whether basic fibroblast growth factor (bFGF) injection inhibits the ...AIM:To investigate the expressions of type I collagen, α2 integrin and β1 integrin in the posterior sclera of guinea pigs with defocus myopia and whether basic fibroblast growth factor (bFGF) injection inhibits the formation and development of myopia by upregulating the expression of type I collagen, α2 integrin and β1 integrin. METHODS:After 14 days of treatment, the refractive state and axial length were measured and the levels of type I collagen, α2 integrin and β1 integrin were assayed in the posterior sclerae of groups of guinea pigs that wore a monocular-7D polymethylmethacrylate (PMMA) lens or had -7D lens wear followed by the peribulbar injection of Phosphate Buffer Solution (PBS) or bFGF. The untreated fellow eye served as a control. Guinea pigs with no treatment served as normal group. ·RESULTS:The results showed that 14 days of monocular defocus increased axial eye length and refraction, while bFGF delivery inhibited them markedly. Further, it was also found that the monocular-7D lens could decrease the levels of type I collagen, α2 integrin and β1 integrin expressions, while, unlike PBS, bFGF increased them significantly in comparison to contralateral control eyes and normal eyes. CONCLUSION:bFGF can prevent the formation anddevelopment of defocus myopia by upregulating the expressions of type I collagen, α2 integrin and β1 integrin. Taken together, our results demonstrate that bFGF promotes sclera remodeling to prevent myopia in guinea pigs.展开更多
Infections by coronaviruses such as severe acute respiratory syndrome （SARS） coronavirus （SCoV） and mouse hepatitis virus A59 （MHV-A59） result in very little type I interferon （IFN） production by host cells, w...Infections by coronaviruses such as severe acute respiratory syndrome （SARS） coronavirus （SCoV） and mouse hepatitis virus A59 （MHV-A59） result in very little type I interferon （IFN） production by host cells, which is potentially responsible for the rapid viral growth and severe immunopathology associated with SARS. However, the molecular mechanisms for the low IFN production in cells infected with coronaviruses remain unclear. Here, we provide evidence that Papain-like protease domain 2 （PLP2）, a catalytic domain of the nonstructural protein 3 （nsp3） of MHV-A59, can bind to IRF3, cause its deubiquitination and prevent its nuclear translocation. As a consequence, co-expression of PLP2 strongly inhibits CARDIF-, TBK1- and IRF3-mediated IFNp reporter activities. In addition, we show that wild-type PLP2 but not the mutant PLP2 lacking the deubiquitinase （DUB） activity can reduce IFN induction and promote viral growth in cells infected with VSV. Thus, our study uncovered a viral DUB which coronaviruses may use to escape from the host innate antiviral responses.展开更多
Transforming growth factor-β （TGF-β） binds with two transmembrane serine/threonine kinase receptors, type Ⅱ （TβRII） and type Ⅰ receptors （TβRⅠ）, and one accessory receptor, type Ⅲ receptor （TβRⅢ）, to...Transforming growth factor-β （TGF-β） binds with two transmembrane serine/threonine kinase receptors, type Ⅱ （TβRII） and type Ⅰ receptors （TβRⅠ）, and one accessory receptor, type Ⅲ receptor （TβRⅢ）, to transduce signals across cell membranes. Previous biochemical studies suggested that TβRI and TβRIII are preexisted homo-dimers. Using single-molecule microscopy to image green fluorescent protein-labeled membrane proteins, for the first time we have demonstrated that TβRI and TβRⅢ could exist as monomers at a low expression level. Upon TGF-β1 stimu- lation, TβRI follows the general ligand-induced receptor dimerization model for activation, but this process is TβRⅡ- dependent. The monomeric status of the non-kinase receptor TβRⅢ is unchanged in the presence of TGF-β1. With the increase of receptor expression, both TβRI and TβRIII can be assembled into dimers on cell surfaces.展开更多
Type I interferons (IFN) are well studied cytokines with anti-viral and immune-modulating functions. Type I IFNsare produced following viral infections, but until recently, the mechanisms of viral recognition leading ...Type I interferons (IFN) are well studied cytokines with anti-viral and immune-modulating functions. Type I IFNsare produced following viral infections, but until recently, the mechanisms of viral recognition leading to IFN productionwere largely unknown. Toll like receptors (TLRs) have emerged as key transducers of type I IFN during viral infectionsby recognizing various viral components. Furthermore, much progress has been made in defining the signaling path-ways downstream of TLRs for type I IFN production. TLR7 and TLR9 have become apparent as universally importantin inducing type I IFN during infection with most viruses, particularly by plasmacytoid dendritic cells. New intracellularviral pattern recognition receptors leading to type I IFN production have been identified. Many bacteria can also inducethe up-regulation of these cytokines. Interestingly, recent studies have found a detrimental effect on host cells if type IIFN is produced during infection with the intracellular gram-positive bacterial pathogen, Listeria monocytogenes. Thisreview will discuss the recent advances made in defining the signaling pathways leading to type I IFN production.展开更多
Viral infection initiates a series of signaling cascades that activate the transcription factors nuclear factor kappa B and interferon regulatory factor 3, which collaborate to induce transcription of genes for type I...Viral infection initiates a series of signaling cascades that activate the transcription factors nuclear factor kappa B and interferon regulatory factor 3, which collaborate to induce transcription of genes for type I interferons （IFNs） and other cytokines. Here we report that the deubiquitinating enzyme ubiquitin-specific protease 17 （USP17） is required for virus-induced RIG-I- and melanoma differentiation-associated protein-5 （MDA5）-mediated type I IFN signaling. Knockdown of endogenous USP17 inhibited virus-, cytoplasmic poly（I：C）- and poly（dA：dT）-induced activation of the IFN-β promoter and cellular antiviral responses. We further found that knockdown of USP17 inhibited RIG-I- and MDA5-induced but not downstream activator-induced activation of the IFN-β promoter, which was correlated with an increase in ubiquitination levels of RIG-I and MDA5. Taken together, our findings suggest that USP17 functions through deubiquitination of RIG-I and MDA5 to regulate virus-induced type I IFN signaling.展开更多
This article proposes a statistical method for working out reliability sampling plans under Type I censored sample for items whose failure times have either normal or lognormal distributions. The quality statistic is ...This article proposes a statistical method for working out reliability sampling plans under Type I censored sample for items whose failure times have either normal or lognormal distributions. The quality statistic is a method of moments estimator of a monotonous function of the unreliability. An approach of choosing a truncation time is recommended. The sample size and acceptability constant are approximately determined by using the Cornish-Fisher expansion for quantiles of distribution. Simulation results show that the method given in this article is feasible.展开更多
Bone morphogenetic proteins （BMPs） have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors （BMPRI and BMPRII）. In recent deca...Bone morphogenetic proteins （BMPs） have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors （BMPRI and BMPRII）. In recent decades, genetic studies in humans and mice have demonstrated that perturbations in BMP signaling via BMPRI resulted in various diseases in bone, cartilage, and muscles. In this review, we focus on all three types of BMPRI, which consist of activin-like kinase 2 （ALK2, also called type IA activin receptor）, activin- llke kinase 3 （ALK3, also called BMPRIA）, and activin-like kinase 6 （ALK6, also called BMPRIB）. The research areas covered include the current progress regarding the roles of these receptors during myogenesis, chondrogenesis, and osteogenesis. Understanding the physiological and pathological functions of these receptors at the cellular and molecular levels will advance drug development and tissue regeneration for treating musculoskeletal diseases and bone defects in the future.展开更多
AIM： Type IV collagenase including MMP-2 and -9 plays an important role in cancer cell invasion and metastasis and is an attractive target for rnAb-directed therapy. The irnrnunoreactivity of rnAb 3G11, a rnAb direct...AIM： Type IV collagenase including MMP-2 and -9 plays an important role in cancer cell invasion and metastasis and is an attractive target for rnAb-directed therapy. The irnrnunoreactivity of rnAb 3G11, a rnAb directed against type Ⅳ collagenase in human colorectal carcinomas, was studied by irnrnuno-histochernical （IHC） staining, rnAb 3G11 was conjugated to an antiturnor antibiotic lidarnycin （LDM）. The antiturnor activity of 3G11-LDM conjugate against colon carcinoma was investigated in mice. METHODS： ELISA, gelatin zyrnography, and Western blot assay were used for the biological characterization of rnAb 3G11. The irnrnunoreactivity of rnAb 3G11 with human colorectal carcinomas was detected by IHC staining. The cytotoxicity of LDM and 3G11-LDM conjugate to human colon carcinoma HT-29 cells was examined by clonogenic assay and MTT assay. The therapeutic effect of conjugate 3G11-LDM was evaluated with colon carcinoma 26 in mice. RESULTS： As shown in ELISA, mAb 3Gll reacted specifically with type IV collagenase, while 3G11-LDM conjugate also recognized specifically its respective antigen. In IHC assay, mAb 3G11 showed positive irnrnunoreactivity in most cases of colorectal carcinoma, and negative irnrnunoreactivity in the adjacent non-malignant tissues. By gelatin zyrnography, the inhibition effect of rnAb 3G11 on the secretion activity of type IV collagenase was proved. In terms of IC50 values in MTT assay, the cytotoxicity of LDM to human colon carcinoma HT-29 cells was 10 000-fold more potent than that of rnitornycin C （MMC） and adriarnycin （ADM）. 3G11- LDM conjugate also displayed extremely potent cytotoxicity to human colon carcinoma HT-29 cells with an IC50 value of 5.6× 10^-19 mol/L. 3G11-LDM conjugate at the doses of 0.05 and 0.1 mg/kg inhibited the growth of colon carcinoma 26 in mice by 70.3 and 81.2%, respectively. CONCLUSION： mAb 3G11 is immunoreactive with human colorectal carcinoma and its conjugate with LDM is highly effective against colon carcinoma in mice.展开更多
基金supported by a project of the Shaanxi Youth Science and Technology Star(2021KJXX-87)public welfare geological survey projects of Shaanxi Institute of Geologic Survey(20180301,201918 and 202103)。
文摘With the efficient and intelligent development of computer-based big data processing,applying machine learning methods to the processing and interpretation of logging data in the field of geophysical well logging has broad potential for improving production efficiency.Currently,the Jiyuan Oilfield in the Ordos Basin relies mainly on manual reprocessing and interpretation of old well logging data to identify different fluid types in low-contrast reservoirs,guiding subsequent production work.This study uses well logging data from the Chang 1 reservoir,partitioning the dataset based on individual wells for model training and testing.A deep learning model for intelligent reservoir fluid identification was constructed by incorporating the focal loss function.Comparative validations with five other models,including logistic regression(LR),naive Bayes(NB),gradient boosting decision trees(GBDT),random forest(RF),and support vector machine(SVM),show that this model demonstrates superior identification performance and significantly improves the accuracy of identifying oil-bearing fluids.Mutual information analysis reveals the model's differential dependency on various logging parameters for reservoir fluid identification.This model provides important references and a basis for conducting regional studies and revisiting old wells,demonstrating practical value that can be widely applied.
基金supported by the Postgraduate Scientic Research Innovation Project of Chongqing Normal University(YKC24010)Chunna Zeng's research was supported by the Major Special Project of the National Natural Science Foundation of China(12141101)+2 种基金the Young Top-Talent program of Chongqing(CQYC2021059145)the Technology Research Foundation of Chongqing Educational committee(KJZD-K202200509)the Natural Science Foundation Project of Chongqing(CSTB2024NSCQ-MSX0937)。
文摘Two sharp Chernoff type inequalities are derived for star bodies in R2,one is an extension of the dual Chernoff-Ou-Pan inequality,and the other is the reverse Chernoff type inequality.Furthermore,we establish a generalized dual symmetric mixed Chernoff inequality for two planar star bodies.As a direct consequence,a new proof of the dual symmetric mixed isoperimetric inequality is presented.
基金supported by the National Natural Science Foundation of China(Nos.22206207,22127810,and 22276224)the Natural Science Foundation of Guangdong Province(Nos.2021A1515011546 and 2023A1515010085)the Science and Technology Planning Project of Guangzhou(No.202102080005)。
文摘Epithelial-mesenchymal transition(EMT)plays an irreplaceable role in the development of silicosis.However,molecular mechanisms of EMT induced by silica exposure still remain to be addressed.Herein,metabolic profiles of human alveolar type II epithelial cells(A549 cells)exposed directly to silica were characterized using non-targeted metabolomic approaches.A total of 84 differential metabolites(DMs)were identified in silica-treated A549 cells undergoing EMT,which were mainly enriched in metabolisms of amino acids(e.g.,glutamate,alanine,aspartate),purine metabolism,glycolysis,etc.The number of DMs identified in the A549 cells obviously increased with the elevated exposure concentration of silica.Remarkably,glutamine catabolism was significantly promoted in the silica-treated A549 cells,and the levels of related metabolites(e.g.,succinate)and enzymes(e.g.,α-ketoglutarate(α-KG)dehydrogenase)were substantially up-regulated,with a preference toα-KG pathway.Supplementation of glutamine into the cell culture could substantially enhance the expression levels of both EMT-related markers and Snail(zinc finger transcription factor).Our results suggest that the EMT of human alveolar epithelial cells directly induced by silica can be essential to the development of silicosis.
文摘Type III acute acquired comitant esotropia(AACE)is a special type of binocular coordination disorder with sudden onset characteristics,but its pathogenesis and treatment strategies remain unclear.This article analyzes the incidence and classification characteristics of Type III AACE,and explores its pathogenesis from multiple perspectives including clinical medicine,neuroscience,and neuro-ophthalmology.It is found that this disease is associated with factors such as decompensation of phoria,dysfunction of the visual center,abnormalities in the physiological and anatomical structure of extraocular muscles,accommodative factors,and disorders of convergence and divergence.The prognosis of Type III AACE is excellent with treatments such as botulinum toxin injection and surgery,and adjunctive therapies like prism adaptation test and visual function training can enhance the management effect.This article provides an in-depth analysis of the pathogenesis and cutting-edge treatment techniques for patients with Type III AACE,which can offer guidance for the subsequent diagnosis and treatment of such patients.
基金supported by the 1·3·5 Project for Disciplines of Excellence from West China Hospital of Sichuan University(ZYGD23021&23HXFH009)Sichuan Science and Technology Program(No.2025ZNSFSC1698)the Sichuan Provincial Cadre Health Research Program(ZH2024-103).
文摘Mitral regurgitation (MR) is a highly prevalent valvular heart disease globally,with untreated severe cases demonstrating associations with elevated morbidity,mortality,and adverse cardiovascular outcomes.[1,2]While transcatheter edge-toedge repair (TEER) has emerged as an alternative option for high surgical risk patients with severe MR,[3,4]severe MR of Carpentier class IIIa (characterized by restricted leaflet motion during both systole and diastole) has been considered a relative contraindication for TEER interventions due to stenosis risk and procedural complexity.[5,6]
文摘BACKGROUND Radial head fractures constitute approximately one-third of all elbow fractures,significantly impacting the young and active population.While open reduction and internal fixation is the preferred treatment for displaced fractures,its high complication rate in comminuted fractures has led to the increasing use of radial head arthroplasty(RHA).RHA provides improved functional outcomes with fewer complications,yet its long-term efficacy remains a topic of debate.AIM To evaluate the functional outcomes of patients undergoing RHA with a modular metallic prosthesis for comminuted Mason type III and IV radial head fractures.METHODS A prospective and retrospective hospital-based study was conducted at Dayanand Medical College and Hospital,Ludhiana over 32 months(January 2021-August 2023).A total of 26 patients with Mason type III and IV fractures were included,with six retrospective and 20 prospective cases.Functional outcomes were assessed using the Mayo Elbow Performance Score(MEPS),elbow range of motion,pain via Visual Analog Scale,and activities of daily living at immediate postoperative,three-month,and six-month follow-ups.RESULTS MEPS at 6 months follow up for 4 cases(15.38%)had good scores,and 22 cases(84.62%)had excellent scores,with a mean±SD of 97.31±6.67.Comparisons showed significant improvement from immediate post-operative to 3 months(P<0.0001),from immediate post-operative to 6 months(P<0.0001),and between 3 months and 6 months(P<0.0001).None of the patients had elbow instability after radial head replacement and 22 cases(84.62%)had no complications,while 3 cases(11.54%)had a stiff elbow,and 1 case(3.85%)had heterotopic ossification.CONCLUSION RHA is an effective treatment for comminuted radial head fractures,providing stable elbow function with minimal complications.
文摘Type 2 diabetes mellitus(T2DM)significantly elevates the risk of colorectal cancer(CRC)and complicates its treatment by promoting chemoresistance.Poor glycemic control has been linked to exacerbated CRC progression and diminished chemotherapy efficacy,impacting patient outcomes through various mechanisms such as oxidative stress,activation of metabolic pathways,and altered protein modifications that hinder apoptosis and enhance tumor survival.Clinical evidence shows that T2DM patients experience higher rates of chemoresistance and reduced disease-free survival and overall survival compared to non-diabetic patients.Specifically,those with poor glycemic control exhibit increased chemo-resistance and poorer survival metrics.Antidiabetic treatments,including metformin,acarbose,and gliclazide,show promise in improving chemotherapy response and glycemic management,potentially enhancing patient outcomes.Addressing this challenge requires a comprehensive,multidisciplinary approach involving oncologists,endocrino-logists,and surgeons to optimize patient care.Integrated strategies that prioritize glycemic control are essential for reducing chemoresistance and improving survival in CRC patients with T2DM.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are caused by mutations in the KIT and platelet derived growth factor receptor alpha genes in approximately 90%of cases.A minority of wild-type GISTs are associated with neurofibromatosis type 1(NF1),an autosomal dominant genetic disease resulting from pathogenic mutations in the NF1 gene,which encodes the neurofibromin protein.NF1 patients often exhibit multi-system involvement,with café-au-lait macules and neurofibromas being characteristic symptoms.GISTs are a rare complication of NF1,with the tumors most frequently occurring in the small intestine(90%of cases),while occurrences in the stomach are rare.CASE SUMMARY A 51-year-old woman presented to the emergency department with complaints of dizziness,fatigue,chest tightness,and dark stools.Initial examination revealed a red blood cell count of 1.99×1012/L and a hemoglobin level of 43 g/L.She underwent blood transfusions and fluid replacement to stabilize her condition.Further investigations identified typical café-au-lait macules on her trunk,limbs,and face,along with neurofibromas.Endoscopy showed coffee-colored fluid in the gastric cavity,a large submucosal elevation with an exudative covering,and ulcer formation on the gastric fundus.Exploratory laparoscopy confirmed the tumor’s origin in the gastric fundus,and resection of the giant GIST was performed.Pathological analysis revealed a necrotic GIST measuring 18 cm×14 cm,classified as high-risk,with approximately 5 mitotic figures per 10 high-power fields and no tumor at the margins.Immunohistochemistry results were CD117(+),delay of germination 1(+),CD34(+),and succinate dehydrogenase complex iron sulfur subunit B intact expression.Genetic testing using next-generation sequencing confirmed an NF1 gene mutation.The patient underwent successful tumor resection and was discharged home with postoperative regorafenib therapy.A follow-up at one year showed no recurrence.CONCLUSION Given the diversity of clinical symptoms associated with NF1 and the complexity of NF1-related GISTs,surgical resection with complete tumor removal remains the preferred treatment option.However,the absence of a standardized treatment protocol for adjuvant therapy presents numerous challenges for clinicians.
基金supported by the National Key Research and Development Program of China(2022YFD1800904)the National Natural Science Foundation of China(31972650 and 32102673)+1 种基金the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(KYCX22_0780)the China Postdoctoral Science Foundation(2020M682297)。
文摘Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization of numerous TA systems in various bacteria,the investigation of these systems within Streptococcus suis is still limited.Here,we systematically analyzed the type Ⅱ TA systems of 95 S.suis genomes available in the GenBank database using TAfinder.A total of 612 putative type Ⅱ TA systems were retrieved and classified into 10 categories by phylogenetic analysis.Notably,an elevated occurrence of these TA systems was observed among the important prevalent serotypes 2,4,5,9,14,Chz,NCL1,and NCL3 strains.The following study identified the activities of TA systems using 2 strategies and confirmed the regulatory effect of HigBA on the type Ⅶ secretion system in S.suis by measuringβ-galactosidase activity and transcriptional changes.Moreover,we unveiled a hitherto uncharacterized,highly prevalent novel TA system,with the composition of antitoxin–toxin–antitoxin(SS-ATA),which regulates the downstream two-component signaling system.Altogether,this study systematically analyzed the type Ⅱ TA systems within S.suis,highlighting the widespread distribution of Hig BA and SS-ATA as important regulatory elements in S.suis.
文摘In this paper, supose Γ be a boundary of a Jordan domain D and Γ satisfied Альпер condition, the order that rational type interpolating operators at Fejer's points of f(z)∈C(Γ) converge to f(z) in the sense of uniformly convergence is obtained.
文摘Intuitionistic fuzzy set is an extended form of Zadeh's fuzzy set. In this paper, the concept of L type intuitionistic fuzzy family based on lattice implication algebras was proposed and some of its properties were discussed.
文摘Recently in [4], the Jessen＇s type inequality for normalized positive C0-semigroups is obtained. In this note, we present few results of this inequality, yielding Holder＇s Type and Minkowski＇s type inequalities for corresponding semigroup. Moreover, a Dresher＇s type inequality for two-parameter family of means, is also proved.
文摘AIM:To investigate the expressions of type I collagen, α2 integrin and β1 integrin in the posterior sclera of guinea pigs with defocus myopia and whether basic fibroblast growth factor (bFGF) injection inhibits the formation and development of myopia by upregulating the expression of type I collagen, α2 integrin and β1 integrin. METHODS:After 14 days of treatment, the refractive state and axial length were measured and the levels of type I collagen, α2 integrin and β1 integrin were assayed in the posterior sclerae of groups of guinea pigs that wore a monocular-7D polymethylmethacrylate (PMMA) lens or had -7D lens wear followed by the peribulbar injection of Phosphate Buffer Solution (PBS) or bFGF. The untreated fellow eye served as a control. Guinea pigs with no treatment served as normal group. ·RESULTS:The results showed that 14 days of monocular defocus increased axial eye length and refraction, while bFGF delivery inhibited them markedly. Further, it was also found that the monocular-7D lens could decrease the levels of type I collagen, α2 integrin and β1 integrin expressions, while, unlike PBS, bFGF increased them significantly in comparison to contralateral control eyes and normal eyes. CONCLUSION:bFGF can prevent the formation anddevelopment of defocus myopia by upregulating the expressions of type I collagen, α2 integrin and β1 integrin. Taken together, our results demonstrate that bFGF promotes sclera remodeling to prevent myopia in guinea pigs.
基金These authors contributed equally to this work. We thank Drs S Vaidya and E Chow （University of California Los Angeles, USA） for their help in setting up critical experimental systems. We greatly thank Dr K Holmes （University of Colorado Health Sciences Center, USA） for sharing with us 17C1-1 cell line and helping to optimize the protocol to produce high titered MHV-A59 virus stock. We also thank Drs R Baric and L Su （University of North Carolina, USA） for the gift of MHV-A59 and guidance of virus infection. We thank Dr K Lim （National Neuroscience Institute, Singapore） for the gift of Ubi plasmids. We thank Dr M Wathelet （University of Cincinnati College of Medicine, USA） for sharing the nsp3 construct. Also we thank Dr G Gao （Institute of Biophysics, CAS） for providing us with VSV. This research was partly supported by grants from the National Natural Science Foundation of China （30728006） to Genhong Cheng and the National Basic Research Program of MOST （2004BA519A61, 2006CB504300, 2007DFC30190） to Hong Tang.
文摘Infections by coronaviruses such as severe acute respiratory syndrome （SARS） coronavirus （SCoV） and mouse hepatitis virus A59 （MHV-A59） result in very little type I interferon （IFN） production by host cells, which is potentially responsible for the rapid viral growth and severe immunopathology associated with SARS. However, the molecular mechanisms for the low IFN production in cells infected with coronaviruses remain unclear. Here, we provide evidence that Papain-like protease domain 2 （PLP2）, a catalytic domain of the nonstructural protein 3 （nsp3） of MHV-A59, can bind to IRF3, cause its deubiquitination and prevent its nuclear translocation. As a consequence, co-expression of PLP2 strongly inhibits CARDIF-, TBK1- and IRF3-mediated IFNp reporter activities. In addition, we show that wild-type PLP2 but not the mutant PLP2 lacking the deubiquitinase （DUB） activity can reduce IFN induction and promote viral growth in cells infected with VSV. Thus, our study uncovered a viral DUB which coronaviruses may use to escape from the host innate antiviral responses.
基金This work was supported by the National Natural Science Foundation of China （90713024, 20821003, 30921004）, the National Basic Research Program of China （2007CB935601, 2010CB833706） and the Chinese Academy of Sciences.
文摘Transforming growth factor-β （TGF-β） binds with two transmembrane serine/threonine kinase receptors, type Ⅱ （TβRII） and type Ⅰ receptors （TβRⅠ）, and one accessory receptor, type Ⅲ receptor （TβRⅢ）, to transduce signals across cell membranes. Previous biochemical studies suggested that TβRI and TβRIII are preexisted homo-dimers. Using single-molecule microscopy to image green fluorescent protein-labeled membrane proteins, for the first time we have demonstrated that TβRI and TβRⅢ could exist as monomers at a low expression level. Upon TGF-β1 stimu- lation, TβRI follows the general ligand-induced receptor dimerization model for activation, but this process is TβRⅡ- dependent. The monomeric status of the non-kinase receptor TβRⅢ is unchanged in the presence of TGF-β1. With the increase of receptor expression, both TβRI and TβRIII can be assembled into dimers on cell surfaces.
基金A. K. Perry is supported by the Howard Hughes Medi-cal Institute predoctoral fellowship (Grant No. 59003787).Part of this work was also supported by National Insti-tutes of Health research grants RO1 CA87924, RO1AI056154, and R37 AI47868 to G. Cheng and from the MajorResearch Plan (30170461, 30430640) +1 种基金Natural ScienceFoundation of China, and the National Basic ResearchProgram of MOST (2002CB513001, 2001CB-510002)H. Tang. H. Tang is also a fellow of Outstanding YoungInvestigators of National Naturual Science Foundation ofChina (30025010).
文摘Type I interferons (IFN) are well studied cytokines with anti-viral and immune-modulating functions. Type I IFNsare produced following viral infections, but until recently, the mechanisms of viral recognition leading to IFN productionwere largely unknown. Toll like receptors (TLRs) have emerged as key transducers of type I IFN during viral infectionsby recognizing various viral components. Furthermore, much progress has been made in defining the signaling path-ways downstream of TLRs for type I IFN production. TLR7 and TLR9 have become apparent as universally importantin inducing type I IFN during infection with most viruses, particularly by plasmacytoid dendritic cells. New intracellularviral pattern recognition receptors leading to type I IFN production have been identified. Many bacteria can also inducethe up-regulation of these cytokines. Interestingly, recent studies have found a detrimental effect on host cells if type IIFN is produced during infection with the intracellular gram-positive bacterial pathogen, Listeria monocytogenes. Thisreview will discuss the recent advances made in defining the signaling pathways leading to type I IFN production.
基金Acknowledgments We thank the members of our laboratory for discussions. This work was supported by grants from the National Basic Re- search Program of China （973 Program） （2006CB504301 and 2010CB911802） and the National Natural Science Foundation of China （30921001 and 30700417）.
文摘Viral infection initiates a series of signaling cascades that activate the transcription factors nuclear factor kappa B and interferon regulatory factor 3, which collaborate to induce transcription of genes for type I interferons （IFNs） and other cytokines. Here we report that the deubiquitinating enzyme ubiquitin-specific protease 17 （USP17） is required for virus-induced RIG-I- and melanoma differentiation-associated protein-5 （MDA5）-mediated type I IFN signaling. Knockdown of endogenous USP17 inhibited virus-, cytoplasmic poly（I：C）- and poly（dA：dT）-induced activation of the IFN-β promoter and cellular antiviral responses. We further found that knockdown of USP17 inhibited RIG-I- and MDA5-induced but not downstream activator-induced activation of the IFN-β promoter, which was correlated with an increase in ubiquitination levels of RIG-I and MDA5. Taken together, our findings suggest that USP17 functions through deubiquitination of RIG-I and MDA5 to regulate virus-induced type I IFN signaling.
基金This work is partially supported by National Natural Science Foundation of China (10071090 and 10271013).
文摘This article proposes a statistical method for working out reliability sampling plans under Type I censored sample for items whose failure times have either normal or lognormal distributions. The quality statistic is a method of moments estimator of a monotonous function of the unreliability. An approach of choosing a truncation time is recommended. The sample size and acceptability constant are approximately determined by using the Cornish-Fisher expansion for quantiles of distribution. Simulation results show that the method given in this article is feasible.
基金supported by the National Natural Science Foundation of China (No. 81500814) (SXL)the National Natural Science Foundation of China (No. 81430012 and No. 81170939) (XJ)+2 种基金the National Basic Research Program of China (973 Program, 2012CB933604)the National Science Fund for Distinguished Young Scholars of China (No. 81225006)the National Institutes of Health Grants DE025014 and R56DE022789 (JQF)
文摘Bone morphogenetic proteins （BMPs） have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors （BMPRI and BMPRII）. In recent decades, genetic studies in humans and mice have demonstrated that perturbations in BMP signaling via BMPRI resulted in various diseases in bone, cartilage, and muscles. In this review, we focus on all three types of BMPRI, which consist of activin-like kinase 2 （ALK2, also called type IA activin receptor）, activin- llke kinase 3 （ALK3, also called BMPRIA）, and activin-like kinase 6 （ALK6, also called BMPRIB）. The research areas covered include the current progress regarding the roles of these receptors during myogenesis, chondrogenesis, and osteogenesis. Understanding the physiological and pathological functions of these receptors at the cellular and molecular levels will advance drug development and tissue regeneration for treating musculoskeletal diseases and bone defects in the future.
基金Supported by the National High Technology Research and Development Program of China, 863 Program, No. 2002AA2Z346D
文摘AIM： Type IV collagenase including MMP-2 and -9 plays an important role in cancer cell invasion and metastasis and is an attractive target for rnAb-directed therapy. The irnrnunoreactivity of rnAb 3G11, a rnAb directed against type Ⅳ collagenase in human colorectal carcinomas, was studied by irnrnuno-histochernical （IHC） staining, rnAb 3G11 was conjugated to an antiturnor antibiotic lidarnycin （LDM）. The antiturnor activity of 3G11-LDM conjugate against colon carcinoma was investigated in mice. METHODS： ELISA, gelatin zyrnography, and Western blot assay were used for the biological characterization of rnAb 3G11. The irnrnunoreactivity of rnAb 3G11 with human colorectal carcinomas was detected by IHC staining. The cytotoxicity of LDM and 3G11-LDM conjugate to human colon carcinoma HT-29 cells was examined by clonogenic assay and MTT assay. The therapeutic effect of conjugate 3G11-LDM was evaluated with colon carcinoma 26 in mice. RESULTS： As shown in ELISA, mAb 3Gll reacted specifically with type IV collagenase, while 3G11-LDM conjugate also recognized specifically its respective antigen. In IHC assay, mAb 3G11 showed positive irnrnunoreactivity in most cases of colorectal carcinoma, and negative irnrnunoreactivity in the adjacent non-malignant tissues. By gelatin zyrnography, the inhibition effect of rnAb 3G11 on the secretion activity of type IV collagenase was proved. In terms of IC50 values in MTT assay, the cytotoxicity of LDM to human colon carcinoma HT-29 cells was 10 000-fold more potent than that of rnitornycin C （MMC） and adriarnycin （ADM）. 3G11- LDM conjugate also displayed extremely potent cytotoxicity to human colon carcinoma HT-29 cells with an IC50 value of 5.6× 10^-19 mol/L. 3G11-LDM conjugate at the doses of 0.05 and 0.1 mg/kg inhibited the growth of colon carcinoma 26 in mice by 70.3 and 81.2%, respectively. CONCLUSION： mAb 3G11 is immunoreactive with human colorectal carcinoma and its conjugate with LDM is highly effective against colon carcinoma in mice.
