Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-through...Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.展开更多
The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evi...The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.展开更多
BACKGROUND Medial dished(MD)liner designs for cruciate-retaining(CR)total knee arthroplasty(TKA)are a relatively novel development.MD tibial inserts have a more constraining medial side,which allows for more similar k...BACKGROUND Medial dished(MD)liner designs for cruciate-retaining(CR)total knee arthroplasty(TKA)are a relatively novel development.MD tibial inserts have a more constraining medial side,which allows for more similar kinematics and function to a native knee.AIM To evaluate the clinical results and patient-reported outcomes after CR TKA procedures utilizing a kinematically designed medial dish system.METHODS A multicenter,retrospective cohort review of 139 primary elective TKAs utilizing a kinematically designed CR Knee System(JOURNEY™II CR MD;Smith and Nephew,Memphis,TN,United States)at three different institutions with a minimum of two years of follow-up.Demographic information,clinical outcomes,and patient-reported outcome measures were collected and analyzed.RESULTS With up to 3.7 years from surgery,overall implant survivorship was 98.6%.There were significant postoperative increases in the average Knee Injury and Osteoarthritis Outcome Score for Joint Replacement scores(17.4 at 6 months,26.1 points at two years or more,P<0.001).CONCLUSION The combination of high implant survivorship and substantial improvements in patient-reported outcome measures suggests that the medial dish tibial insert represents a safe and effective option within TKA.Additional investigation is necessary to evaluate the long-term survivorship of this design.展开更多
Neuroinflammation is a crucial factor in the progression of various diseases,ranging from immune-related conditions such as sepsis to neurodegenerative disorders such as Alzheimer’s disease(AD)(Ravichandran and Henek...Neuroinflammation is a crucial factor in the progression of various diseases,ranging from immune-related conditions such as sepsis to neurodegenerative disorders such as Alzheimer’s disease(AD)(Ravichandran and Heneka,2024).This perspective article,which draws on insights from diverse fields including neuroscience,immunology,and pathology,p rovides a critical analysis of ongoing research efforts in inflammasome biology,with specific emphasis on Nod-like receptor(NLR)and pyrin domain-containing protein 3(NLRP3).展开更多
Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders...Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.展开更多
Background Maternal obesity during pregnancy can lead to increased risk for metabolic disease in offspring during adulthood,helping fuel the worldwide increase in obesity.Fortunately,studies in rodent models have esta...Background Maternal obesity during pregnancy can lead to increased risk for metabolic disease in offspring during adulthood,helping fuel the worldwide increase in obesity.Fortunately,studies in rodent models have established that female dams(F0)that perform voluntary wheel running exercise during pregnancy have first-generation(F1)offspring with improved glucose tolerance,suggesting a potential means to reduce the burden of generational metabolic disease transmission.We have shown that maternal exercise also affects F1 male offspring as sires,as their progeny(F2)have similarly improved metabolic health.Whether maternal exercise can affect F1 females in a manner that improves F2 offspring metabolism is not known.Here,we determined whether voluntary exercise by F0 grandmothers,via their F1 female progeny,produced F2 male and female offspring with an improved metabolic phenotype.Methods Six-week-old C57BL/6 N female mice(F0)were fed a chow diet and either kept sedentary or exercise trained by voluntary wheel running for 2 weeks preconception and during pregnancy.Chow-fed sedentary F1 female offspring at 8 weeks of age were bred with age-matched untreated virgin males to generate F2 offspring.F2 were kept sedentary and chow fed and studied up to 52 weeks of age.Metabolic parameters were assessed,including food intake,body weight,body composition,glucose tolerance,systemic glucose and insulin levels,and liver metabolism.Results Grandmaternal exercise did not significantly alter male and female F2 offspring body weights measured throughout the first year of life,nor was there an effect of grandmaternal exercise on F2 offspring fat mass or lean mass.Remarkably,despite the lack of effect on body weight parameters,grandmaternal exercise resulted in improved glucose tolerance and homeostatic model assessment for insulin resistance(HOMA-IR)in F2 offspring at 52 weeks of age,effects that were more pronounced in male F2 offspring.Conclusion Voluntary wheel running exercise in female mice during pregnancy leads to metabolic improvements in her grand offspring,despite no direct intervention of the intermediate maternal generation.Maternal physical activity during pregnancy may reduce metabolic diseases in later generations.展开更多
NaNbO_(3)-based lead-free dielectric ceramics possess significant application prospects in the field of dielectric capacitors.However,their development is hindered by low recoverable energy storage density(W_(rec))and...NaNbO_(3)-based lead-free dielectric ceramics possess significant application prospects in the field of dielectric capacitors.However,their development is hindered by low recoverable energy storage density(W_(rec))and energy storage efficiency(η).Herein,novel NaNbO_(3)-based ceramics,(1-x)[0.7Na_(0.97)Sm_(0.01)NbO_(3)–0.3(Sr_(0.7)Bi_(0.2))(Ti_(0.8)Zr_(0.2))O_(3)]–xCaTiO_(3),were created by adding CaTiO_(3) linear dielectric,aiming to improve their energy storage performance(ESP).The phase structure,microstructure,dielectric properties,energy storage and charge–discharge performances of the ceramics were methodically analyzed.All components of the ceramics exhibit a perovskite structure consisting of two phases:antiferroelectric P-phase(AFE P)and antiferroelectric R-phase(AFE R),with the AFE R phase increasing as x rises.All ceramic surfaces exhibit clear grain morphology.The resultant ceramics have an appropriate dielectric constant and a small dielectric loss,which are beneficial for improving breakdown field strength(E_(b)).Finally,at an E_(b) of 470 kV/cm,0.85[0.7Na_(0.97)Sm_(0.01)NbO_(3)–0.3(Sr_(0.7)Bi_(0.2))(Ti_(0.8)Zr_(0.2))O_(3)]–0.15CaTiO_(3) ceramic achieves optimal ESP:W_(rec)=3.9 J/cm^(3),η=72.49%.In addition,it has remarkable stability with temperature and frequency in energy storage and displays ultrafast speed in the charge–discharge process(t_(0.9)=27 ns).展开更多
Maraging steels are known for their exceptional strength but suffer from limited work hardening and ductility.Here,we report an intermittent printing strategy to tailor the microstructure and mechanical properties of ...Maraging steels are known for their exceptional strength but suffer from limited work hardening and ductility.Here,we report an intermittent printing strategy to tailor the microstructure and mechanical properties of maraging 250 steel via tuning the thermal history during wire-arc directed energy deposition.By introducing a dwell time between adjacent layers,the maraging 250 steel is cooled below the martensite start temperature,triggering thermally-driven martensitic transformation during the printing process.Thermal cycling during subsequent layer deposition results in the formation of reverted austenite which shows a refined microstructure and induces elemental segregation between martensite and reverted austenite.The Ni enrichment in the austenite promotes stabilization of the reverted austenite upon cooling to room temperature.The reverted austenite is metastable during deformation,leading to strain-induced martensitic transformation under loading.Specifically,a 3 min interlayer dwell time produces a maraging 250 steel with approximately 8% reverted austenite,resulting in improved work hardening via martensitic transformation induced plasticity during deformation.Meanwhile,the higher cooling rate and refined prior austenite grains lead to substantially refined martensitic grains(by approximately fivefold)together with an increased dislocation density.With 3 min interlayer dwell time,the yield strength of the printed maraging 250 steel increases from 836 MPa to 990 MPa,and the uniform elongation is doubled from 3.2% to 6.5%.This intermittent deposition strategy demonstrates the potential to tune the microstructure of maraging steels for achieving strength-ductility synergy by engineering the thermal history during additive manufacturing.展开更多
AIM:To compare spontaneous brain regional activities between diabetic vitreous hemorrhage patients(DVHs)and healthy controls(HCs).METHODS:Thirty-two DVHs and 32 HCs were enrolled in this study.Baseline demographic and...AIM:To compare spontaneous brain regional activities between diabetic vitreous hemorrhage patients(DVHs)and healthy controls(HCs).METHODS:Thirty-two DVHs and 32 HCs were enrolled in this study.Baseline demographic and vision data were compared between groups using an independent sample t-test.Resting-state functional magnetic resonance imaging(rs-fMRI)was used in all participants.fMRI data was obtained and analyzed using MRIcro and SPM8 software.Fractional amplitude of low-frequency fluctuation(fALFF)technology was used to measure regional spontaneous brain activity,and sensitivity was tested using receiver operating characteristic curves(ROCs).The fALFF values were analyzed using REST software and two-sample t-tests were used to compare values between groups.Hospital anxiety and depression scale(HADS)score was assessed in DVHs and Pearson’s correlation was used to test relationships between mean fALFF value and both HADS score and duration of DVH.RESULTS:Except for the best-corrected visual acuity(BCVA)in both eyes,which showed a statistically significant difference(P<0.05),there were no statistically significant differences in the other indicators(P>0.05)between the HCs and DVHs group.Compared with controls,fALFF value was higher in DVH in cerebellum posterior lobe(CPL)and lower in right anterior cingulate cortex(ACC)and right medial orbitofrontal cortex(OFC).In DVH patients,mean fALFF value of CPL was positively correlated with HADS score and duration of diabetes.However,no such correlation was found,for right ACC or right medial OFC.DVH may lead to abnormal activities in certain brain regions related to visual control and mood.CONCLUSION:Visual impairment caused by DVH may lead to adjustment in regional visual brain activities and may be related to depression or reward system processing in some brain regions.展开更多
Overt and harmful diabetes mellitus(DM)has detrimental effects on individuals and,by extension,the community.Among the microvascular DM complications is diabetic retinopathy(DR).DR may cause irreversible vision deteri...Overt and harmful diabetes mellitus(DM)has detrimental effects on individuals and,by extension,the community.Among the microvascular DM complications is diabetic retinopathy(DR).DR may cause irreversible vision deterioration in cases of poor blood glucose regulation.Changes in vascular permeability are key trigger points for diabetic macular edema(DME),a condition characterized by the accumulation of fluid in the macula.The development of vascular endothelial growth factor(VEGF)pathway inhibitors has provided a pathogenesis-based treatment approach for DME.Optical coherence tomography(OCT)provides highresolution imaging of the anatomy,including the aging of DME and its structural damage,in distinct morphologic subtypes of macular edema,thereby supporting the assessment of macular edema treatment.The availability of repeated OCT monitoring provides clinical reassurance through the treatment.OCT angiography(OCTA)provides retinal blood flow maps with high spatial resolution.The ability promotes an understanding of disease pathogenesis and facilitates the implementation of new therapeutic methods.This review compares the potential of OCT and OCTA in the diagnosis and treatment of DME,as well as their respective therapeutic applications.展开更多
Fine particulatematter(PM_(2.5))samples were collected in two neighboring cities,Beijing and Baoding,China.High-concentration events of PM_(2.5) in which the average mass concentration exceeded 75μg/m^(3) were freque...Fine particulatematter(PM_(2.5))samples were collected in two neighboring cities,Beijing and Baoding,China.High-concentration events of PM_(2.5) in which the average mass concentration exceeded 75μg/m^(3) were frequently observed during the heating season.Dispersion Normalized Positive Matrix Factorization was applied for the source apportionment of PM_(2.5) as minimize the dilution effects of meteorology and better reflect the source strengths in these two cities.Secondary nitrate had the highest contribution for Beijing(37.3%),and residential heating/biomass burning was the largest for Baoding(27.1%).Secondary nitrate,mobile,biomass burning,district heating,oil combustion,aged sea salt sources showed significant differences between the heating and non-heating seasons in Beijing for same period(2019.01.10–2019.08.22)(Mann-Whitney Rank Sum Test P<0.05).In case of Baoding,soil,residential heating/biomass burning,incinerator,coal combustion,oil combustion sources showed significant differences.The results of Pearson correlation analysis for the common sources between the two cities showed that long-range transported sources and some sources with seasonal patterns such as oil combustion and soil had high correlation coefficients.Conditional Bivariate Probability Function(CBPF)was used to identify the inflow directions for the sources,and joint-PSCF(Potential Source Contribution Function)was performed to determine the common potential source areas for sources affecting both cities.These models facilitated a more precise verification of city-specific influences on PM_(2.5) sources.The results of this study will aid in prioritizing air pollution mitigation strategies during the heating season and strengthening air quality management to reduce the impact of downwind neighboring cities.展开更多
Background:Renal cell carcinoma(RCC)is a prevalent malignancy characterized by a rising incidence and significant mortality.Interleukins(ILs)are crucial in regulating immune cell trafficking and exhibit anti-tumor pro...Background:Renal cell carcinoma(RCC)is a prevalent malignancy characterized by a rising incidence and significant mortality.Interleukins(ILs)are crucial in regulating immune cell trafficking and exhibit anti-tumor properties.However,limited research has explored the expression levels and prognostic significance of interleukins in RCC.Methods:In this comprehensive study,we performed a detailed analysis of interleukins in RCC patients using multiple bioinformatics tools,including Oncomine,UALCAN,GEPIA,Kaplan-Meier plotter,cBioPortal,GeneMANIA,TRRUST,STRING,and Linked Omics.Results:Our analysis demonstrated a significant upregulation in the transcriptional levels of IL4,IL7,IL15,IL16,IL23A,IL26,and IL32 were significantly upregulated in RCC tissues,indicating their potential involvement in the pathogenesis of this malignancy.In contrast,IL1A,IL11,and IL27 were downregulated,indicating their potential function as tumor suppressors.Significant correlations were identified between the expression levels of IL11,IL23A,IL27,IL32,and the pathological stage of RCC patients.The expression levels of IL1A,IL4,IL11,IL15,IL16,IL23A,IL26,IL27,and IL32 were significantly correlated with improved prognosis.The differentially expressed interleukins primarily function in cytokine-cytokine receptor interactions and immune response-regulating signaling pathways.homeobox A10(HOXA10),v-myb myeloblastosis viral oncogene homolog(avian)(MYB),v-rel reticuloendotheliosis viral oncogene homolog A(avian)(RELA),and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1(NFKB1)are key transcription factors for ILs,while LCK proto-oncogene(LCK),LYN proto-oncogene(LYN),spleen associated tyrosine kinase(SYK),Janus kinase 3(JAK3),and FER tyrosine kinase(FER)are IL targets.IL expression significantly correlated with the infiltration of six distinct immune cell types.IL1A potentially exerts an anti-tumor effect in RCC prognosis by inducing neutrophil extracellular traps(NETs).Additionally,NFKB1 may positively regulate IL1A,providing a rationale for further in vivo and clinical studies.Conclusion:In conclusion,our study demonstrates the potential role of IL 1A in the prognosis of RCC and establishes a theoretical foundation for subsequent in vivo and clinical investigations.展开更多
BACKGROUND There has been an increasing focus in recent years on health-care disparities.Studies investigating return to work(RTW)or sports are often performed in large,urban areas.Relatively few studies have investig...BACKGROUND There has been an increasing focus in recent years on health-care disparities.Studies investigating return to work(RTW)or sports are often performed in large,urban areas.Relatively few studies have investigated rates of return to farming or other heavy labor that is of interest to patients in rural areas.AIM To evaluate the literature regarding RTW in farming or heavy labor after orthopedic hip,knee,or shoulder surgery.METHODS A search was performed in the PubMed and EMBASE databases using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.Studies were included if they reported patients employed in farming or heavy labor,RTW rates after orthopedic surgery of the hip,knee,or shoulder,and had a minimum 6-month follow-up.A meta-analysis of proportions using a random-effects model was performed on three single-arm observational studies to estimate the pooled RTW rate following arthroscopic shoulder surgery.RESULTS Ten studies were included,and 101 farmers were identified among 440 total patients.One study involved hip surgery,two studies involved knee surgery,and seven studies involved shoulder surgery.RTW rates across studies varied by type of surgery and follow-up interval,ranging from 24%to 100%.The RTW rate was only 53.6%at 1 year following total hip arthroplasty.No studies investigated RTW in farmers following total knee arthroplasty.Among non-comparative studies,meta-analysis revealed a pooled RTW rate of 89%following arthroscopic shoulder surgery,with low heterogeneity(I^(2)=30.1%).Among comparative studies,one study reported significantly higher RTW odds for patients undergoing anatomic total shoulder arthroplasty compared to reverse shoulder arthroplasty(odds ratio=5.45).Overall,surgical intervention for shoulder pathology was associated with a high likelihood of RTW across multiple techniques,with particularly favorable outcomes for anatomic total shoulder arthroplasty.CONCLUSION This systematic review highlights the high rates of RTW in farmers and heavy laborers after shoulder surgery.However,our findings also underscore the need for more rural-specific research to guide patient counseling,rehabilitation expectations,and shared decision-making in this underserved population,particularly for orthopedic surgery of the hip and knee.展开更多
In this study,we explored a one-step direct synthesis of NH3 under mild experimental conditions utilizing pulse-modulated microwave plasma technology at atmospheric pressure.At a substantial gas flow rate,a microwave ...In this study,we explored a one-step direct synthesis of NH3 under mild experimental conditions utilizing pulse-modulated microwave plasma technology at atmospheric pressure.At a substantial gas flow rate,a microwave plasma jet was formed and the microwave-assisted ammonia synthesis can be realized.Impacts of various parameters including the gas flow rate,gas component,microwave absorbed power,pulse modulation frequency,and pulse duty cycle on ammonia synthesis were systematically investigated.To indicate the reaction path of ammonia synthesis,the distributions of both the gas temperature and active species were also studied using optical emission spectra technology.It is found that a considerable amount of ammonia was directly synthesized without involvement of any catalysts,the highest ammonia production rate and energy efficiency(EE),up to 2.93μmol·min^(-1) and 6.64×10^(-2)g·(k W·h)^(-1),respectively,were achieved under low microwave power of 84.42 W.The duty cycle has obvious influences on the synthesis efficiency,compared to a duty cycle of 80%,the ammonia synthesis rate,EE and nitrogen conversion decreased by about 22%at a duty cycle of 100%.This finding underscores the significance of incorporating pulse modulation in the microwave discharge process for ammonia synthesis.Furthermore,it was found that vibrational excitation of microwave plasma has a significant driving effect on ammonia synthesis.展开更多
Acute exposure to high altitude can cause acute altitude illnesses and is associated with impaired cognitive and physical performance.The most effective preventive strategies currently recommended include environmenta...Acute exposure to high altitude can cause acute altitude illnesses and is associated with impaired cognitive and physical performance.The most effective preventive strategies currently recommended include environmental acclimatization(slow ascent and/or pre-acclimatization)or pharmacological support of acclimatization using acetazolamide.However,these strategies are not practical for high-altitude exposures that require rapid and unplanned ascent,high physical and mental performance,such as rescue missions or military operations.Dexamethasone and other modulators of the glucocorticoid system take effect quickly and are effective alternatives for preventing acute altitude illnesses when rapidly ascending to high altitudes.As the efficacy of dexamethasone in preventing acute mountain illnesses remains controversial,a review of existing studies on the use of dexamethasone for the prevention of acute mountain sickness was conducted,aiming to determine the best strategy.Possible mechanisms of protection against acute altitude illnesses are discussed based on the results of clinical trials.The data indicate that dexamethasone is most effective at altitudes above 4000 m at doses of 8–16 mg/d.Appropriately designed and powered trials are needed to obtain more evidence-based results on the dosage and timing of dexamethasone administration,and to provide optimized recommendations for the application of this powerful pharmacological tool.展开更多
Cholangiocarcinoma(CCA)is a fatal bile duct malignancy.CCA is intrinsically resistant to standard chemotherapy,responds poorly to it,and has a poor prognosis.Effective treatments for cholangiocarcinoma remain elusive,...Cholangiocarcinoma(CCA)is a fatal bile duct malignancy.CCA is intrinsically resistant to standard chemotherapy,responds poorly to it,and has a poor prognosis.Effective treatments for cholangiocarcinoma remain elusive,and a breakthrough in CCA treatment is still awaited.The human epidermal growth factor receptor 2(HER2)plays an oncogenic role by promoting an aggressive cancer phenotype through multiple pathways.While HER2 has shown increasing potential as an effective target for breast and gastric cancers over the last decade,this has not been the case for CCA.This review explores the possibility of targeting HER2 in CCA immunotherapy.Key findings suggest that HER2 alterations have been reported as one of the signatures associated with a poorer prognosis in liver fluke-associated CCA,the most prevalent subtype in Southeast Asia.Furthermore,we assess recent advances in HER2-targeted therapeutic approaches,presenting the current stage,rationale,and evidence supporting the use of HER2 as a promising therapeutic target for cancer immunotherapy in CCA.We also emphasize the crucial role of animal models in developing anticancer therapies.In summary,focusing on HER2 expression could provide alternative strategies for the HER2-altered CCA cluster.展开更多
Sexual selection is thought to play a major role in the evolution of color due to the correlation between a signaler’s physiological state and the displayed color.As such,researchers often investigate how color corre...Sexual selection is thought to play a major role in the evolution of color due to the correlation between a signaler’s physiological state and the displayed color.As such,researchers often investigate how color correlates to the quality of the signaler.However,research on the relationship between color and individual quality is often taxonomically limited and researchers typically investigate how color phenotypes relate to one index of quality,such as a linear measure of body size.Here,we investigated the relationship among body size,claw size,claw muscle mass,lipid content,and the color of the claw in male fiddler crabs(Leptuca uruguayensis)which wield an exaggerated claw that varies in color from brown to red.We hypothesized that if the color was correlated to one or more indices of male quality,the color displayed on the claws of male L.uruguayensis could be under sexual selection.We found L.uruguayensis claw color varies substantially among the individuals we photographed.However,we did not find a correlation between claw color and indices of quality;neither brightness nor hue correlated to the indices of quality we measured.Our findings suggest that claw color in L.uruguayensis is unlikely to have evolved to signal quality,but may instead function as a species identity or as a non-indicator sexual signal.展开更多
BACKGROUND Familial Mediterranean fever(FMF)is an autosomal recessive autoinflammatory disorder marked by recurrent episodes of fever and serositis.Resistin,a proinflammatory cytokine,may play a role in FMF pathogenes...BACKGROUND Familial Mediterranean fever(FMF)is an autosomal recessive autoinflammatory disorder marked by recurrent episodes of fever and serositis.Resistin,a proinflammatory cytokine,may play a role in FMF pathogenesis by promoting the release of interleukin-1beta,tumour necrosis factor alpha,and interleukin-6.AIM To evaluate serum resistin levels in children with FMF during acute attacks and remission,and to assess its potential as a biomarker for disease activity and progression.METHODS A case-control study was conducted involving 40 pediatric patients with FMF and 40 age-and sex-matched healthy controls.Serum resistin and inflammatory markers—including total leukocyte count(TLC),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),serum amyloid A(SAA),and fibrinogen—were measured using enzyme-linked immunosorbent assay and standard assays.RESULTS No significant differences were found in age or sex between FMF patients and controls.Among FMF patients,fever was the most prevalent symptom(95%),followed by abdominal pain(75%).The most frequently detected genetic mutation was M694I,followed by M694V,E148Q,M680I,and V726A.Compound heterozygous mutations,including M694I/V726A and M694I/M694V,were equally represented.During acute attacks,FMF patients exhibited significantly elevated levels of TLC,ESR,CRP,SAA,and fibrinogen compared to attack-free periods and controls.Serum resistin levels were markedly higher during acute attacks and showed a strong positive correlation with other acute inflammatory markers.Receiver operating characteristic curve analysis demonstrated high sensitivity and specificity of resistin as a potential biomarker for FMF.CONCLUSION Resistin is significantly elevated in children with FMF during acute episodes and correlates with established inflammatory markers.These findings support its potential role as a non-invasive biomarker for disease activity and severity in pediatric FMF.展开更多
Zero-click attacks represent an advanced cybersecurity threat,capable of compromising devices without user interaction.High-profile examples such as Pegasus,Simjacker,Bluebugging,and Bluesnarfing exploit hidden vulner...Zero-click attacks represent an advanced cybersecurity threat,capable of compromising devices without user interaction.High-profile examples such as Pegasus,Simjacker,Bluebugging,and Bluesnarfing exploit hidden vulnerabilities in software and communication protocols to silently gain access,exfiltrate data,and enable long-term surveillance.Their stealth and ability to evade traditional defenses make detection and mitigation highly challenging.This paper addresses these threats by systematically mapping the tactics and techniques of zero-click attacks using the MITRE ATT&CK framework,a widely adopted standard for modeling adversarial behavior.Through this mapping,we categorize real-world attack vectors and better understand how such attacks operate across the cyber-kill chain.To support threat detection efforts,we propose an Active Learning-based method to efficiently label the Pegasus spyware dataset in alignment with the MITRE ATT&CK framework.This approach reduces the effort of manually annotating data while improving the quality of the labeled data,which is essential to train robust cybersecurity models.In addition,our analysis highlights the structured execution paths of zero-click attacks and reveals gaps in current defense strategies.The findings emphasize the importance of forward-looking strategies such as continuous surveillance,dynamic threat profiling,and security education.By bridging zero-click attack analysis with the MITRE ATT&CK framework and leveraging machine learning for dataset annotation,this work provides a foundation for more accurate threat detection and the development of more resilient and structured cybersecurity frameworks.展开更多
Mn_(3)Si_(2)Te_(6) is a ferrimagnetic nodal-line semiconductor with colossal angular magnetoresistance at ambient pressure.In this work,we investigated the effect of hydrostatic pressure on its electrical transport pr...Mn_(3)Si_(2)Te_(6) is a ferrimagnetic nodal-line semiconductor with colossal angular magnetoresistance at ambient pressure.In this work,we investigated the effect of hydrostatic pressure on its electrical transport properties,magnetic transition,and crystal structure by measuring resistivity,DC and AC magnetic susceptibility,and XRD under various pressures up to~20 GPa.Our results confirmed the occurrence of pressure-induced structural transition at P_(c)≈10–12 GPa accompanied by a concurrent drop of room-temperature resistance in Mn_(3)Si_(2)Te_(6).In the low-pressure phase at PP_(c),the sample exhibits a metallic behavior in the whole temperature range and its resistivity exhibits a kink anomaly at T_(M),characteristic of critical scattering around a magnetic transition.Recovery of the Raman spectrum upon decompression indicated that pressure-induced structural transition is reversible without amorphization under hydrostatic pressure conditions.Our present work not only resolves some existing controversial issues but also provides new insights into pressure-driven diverse behaviors of Mn_(3)Si_(2)Te_(6).展开更多
基金the Deanship of Research and Graduate Studies at King Khalid University,KSA,for funding this work through the Large Research Project under grant number RGP2/164/46.
文摘Background:Stomach cancer(SC)is one of the most lethal malignancies worldwide due to late-stage diagnosis and limited treatment.The transcriptomic,epigenomic,and proteomic,etc.,omics datasets generated by high-throughput sequencing technology have become prominent in biomedical research,and they reveal molecular aspects of cancer diagnosis and therapy.Despite the development of advanced sequencing technology,the presence of high-dimensionality in multi-omics data makes it challenging to interpret the data.Methods:In this study,we introduce RankXLAN,an explainable ensemble-based multi-omics framework that integrates feature selection(FS),ensemble learning,bioinformatics,and in-silico validation for robust biomarker detection,potential therapeutic drug-repurposing candidates’identification,and classification of SC.To enhance the interpretability of the model,we incorporated explainable artificial intelligence(SHapley Additive exPlanations analysis),as well as accuracy,precision,F1-score,recall,cross-validation,specificity,likelihood ratio(LR)+,LR−,and Youden index results.Results:The experimental results showed that the top four FS algorithms achieved improved results when applied to the ensemble learning classification model.The proposed ensemble model produced an area under the curve(AUC)score of 0.994 for gene expression,0.97 for methylation,and 0.96 for miRNA expression data.Through the integration of bioinformatics and ML approach of the transcriptomic and epigenomic multi-omics dataset,we identified potential marker genes,namely,UBE2D2,HPCAL4,IGHA1,DPT,and FN3K.In-silico molecular docking revealed a strong binding affinity between ANKRD13C and the FDA-approved drug Everolimus(binding affinity−10.1 kcal/mol),identifying ANKRD13C as a potential therapeutic drug-repurposing target for SC.Conclusion:The proposed framework RankXLAN outperforms other existing frameworks for serum biomarker identification,therapeutic target identification,and SC classification with multi-omics datasets.
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC).
文摘The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.
文摘BACKGROUND Medial dished(MD)liner designs for cruciate-retaining(CR)total knee arthroplasty(TKA)are a relatively novel development.MD tibial inserts have a more constraining medial side,which allows for more similar kinematics and function to a native knee.AIM To evaluate the clinical results and patient-reported outcomes after CR TKA procedures utilizing a kinematically designed medial dish system.METHODS A multicenter,retrospective cohort review of 139 primary elective TKAs utilizing a kinematically designed CR Knee System(JOURNEY™II CR MD;Smith and Nephew,Memphis,TN,United States)at three different institutions with a minimum of two years of follow-up.Demographic information,clinical outcomes,and patient-reported outcome measures were collected and analyzed.RESULTS With up to 3.7 years from surgery,overall implant survivorship was 98.6%.There were significant postoperative increases in the average Knee Injury and Osteoarthritis Outcome Score for Joint Replacement scores(17.4 at 6 months,26.1 points at two years or more,P<0.001).CONCLUSION The combination of high implant survivorship and substantial improvements in patient-reported outcome measures suggests that the medial dish tibial insert represents a safe and effective option within TKA.Additional investigation is necessary to evaluate the long-term survivorship of this design.
基金supported by Texas Alzheimer’s Research and Care Consortium-TARCC 2022-26,The National Football League Players Association-NFLPA,NIH/NIA Grant 1R01 AG072491 to TB and FDP.
文摘Neuroinflammation is a crucial factor in the progression of various diseases,ranging from immune-related conditions such as sepsis to neurodegenerative disorders such as Alzheimer’s disease(AD)(Ravichandran and Heneka,2024).This perspective article,which draws on insights from diverse fields including neuroscience,immunology,and pathology,p rovides a critical analysis of ongoing research efforts in inflammasome biology,with specific emphasis on Nod-like receptor(NLR)and pyrin domain-containing protein 3(NLRP3).
基金supported by the NIA/NIH(1K01AG060040).Studies performed by JN were funded by the NICHD/NIH(5R00HD096117)Microscopy Core Facility supported,in part,with funding from NIH-NCI Cancer Center Support Grant P30 CA016059.
文摘Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.
基金supported by NIH awards R01 DK101043 to LJG and P30 DK036836 to Joslin Diabetes Centersupported by American Diabetes Association Grant No.1-17-PMF-009+1 种基金supported by American Diabetes Association(Grant No.1-25-PDF-67)supported by fellowships from Sunstar Foundation,Japan Society for the Promotion of Science(JSPS),Kanae Foundation,and Meiji Yasuda Life Foundation of Health and Welfare.
文摘Background Maternal obesity during pregnancy can lead to increased risk for metabolic disease in offspring during adulthood,helping fuel the worldwide increase in obesity.Fortunately,studies in rodent models have established that female dams(F0)that perform voluntary wheel running exercise during pregnancy have first-generation(F1)offspring with improved glucose tolerance,suggesting a potential means to reduce the burden of generational metabolic disease transmission.We have shown that maternal exercise also affects F1 male offspring as sires,as their progeny(F2)have similarly improved metabolic health.Whether maternal exercise can affect F1 females in a manner that improves F2 offspring metabolism is not known.Here,we determined whether voluntary exercise by F0 grandmothers,via their F1 female progeny,produced F2 male and female offspring with an improved metabolic phenotype.Methods Six-week-old C57BL/6 N female mice(F0)were fed a chow diet and either kept sedentary or exercise trained by voluntary wheel running for 2 weeks preconception and during pregnancy.Chow-fed sedentary F1 female offspring at 8 weeks of age were bred with age-matched untreated virgin males to generate F2 offspring.F2 were kept sedentary and chow fed and studied up to 52 weeks of age.Metabolic parameters were assessed,including food intake,body weight,body composition,glucose tolerance,systemic glucose and insulin levels,and liver metabolism.Results Grandmaternal exercise did not significantly alter male and female F2 offspring body weights measured throughout the first year of life,nor was there an effect of grandmaternal exercise on F2 offspring fat mass or lean mass.Remarkably,despite the lack of effect on body weight parameters,grandmaternal exercise resulted in improved glucose tolerance and homeostatic model assessment for insulin resistance(HOMA-IR)in F2 offspring at 52 weeks of age,effects that were more pronounced in male F2 offspring.Conclusion Voluntary wheel running exercise in female mice during pregnancy leads to metabolic improvements in her grand offspring,despite no direct intervention of the intermediate maternal generation.Maternal physical activity during pregnancy may reduce metabolic diseases in later generations.
基金Project supported by the Natural Science Foundation of Anhui Provincial Education Department(Grant No.KJ2019A0054)。
文摘NaNbO_(3)-based lead-free dielectric ceramics possess significant application prospects in the field of dielectric capacitors.However,their development is hindered by low recoverable energy storage density(W_(rec))and energy storage efficiency(η).Herein,novel NaNbO_(3)-based ceramics,(1-x)[0.7Na_(0.97)Sm_(0.01)NbO_(3)–0.3(Sr_(0.7)Bi_(0.2))(Ti_(0.8)Zr_(0.2))O_(3)]–xCaTiO_(3),were created by adding CaTiO_(3) linear dielectric,aiming to improve their energy storage performance(ESP).The phase structure,microstructure,dielectric properties,energy storage and charge–discharge performances of the ceramics were methodically analyzed.All components of the ceramics exhibit a perovskite structure consisting of two phases:antiferroelectric P-phase(AFE P)and antiferroelectric R-phase(AFE R),with the AFE R phase increasing as x rises.All ceramic surfaces exhibit clear grain morphology.The resultant ceramics have an appropriate dielectric constant and a small dielectric loss,which are beneficial for improving breakdown field strength(E_(b)).Finally,at an E_(b) of 470 kV/cm,0.85[0.7Na_(0.97)Sm_(0.01)NbO_(3)–0.3(Sr_(0.7)Bi_(0.2))(Ti_(0.8)Zr_(0.2))O_(3)]–0.15CaTiO_(3) ceramic achieves optimal ESP:W_(rec)=3.9 J/cm^(3),η=72.49%.In addition,it has remarkable stability with temperature and frequency in energy storage and displays ultrafast speed in the charge–discharge process(t_(0.9)=27 ns).
基金the U.S.Army Research Laboratory under Cooperative Agreement Award No.HQ0034-15-2-0007the U.S.National Science Foundation(DMR-2207965).
文摘Maraging steels are known for their exceptional strength but suffer from limited work hardening and ductility.Here,we report an intermittent printing strategy to tailor the microstructure and mechanical properties of maraging 250 steel via tuning the thermal history during wire-arc directed energy deposition.By introducing a dwell time between adjacent layers,the maraging 250 steel is cooled below the martensite start temperature,triggering thermally-driven martensitic transformation during the printing process.Thermal cycling during subsequent layer deposition results in the formation of reverted austenite which shows a refined microstructure and induces elemental segregation between martensite and reverted austenite.The Ni enrichment in the austenite promotes stabilization of the reverted austenite upon cooling to room temperature.The reverted austenite is metastable during deformation,leading to strain-induced martensitic transformation under loading.Specifically,a 3 min interlayer dwell time produces a maraging 250 steel with approximately 8% reverted austenite,resulting in improved work hardening via martensitic transformation induced plasticity during deformation.Meanwhile,the higher cooling rate and refined prior austenite grains lead to substantially refined martensitic grains(by approximately fivefold)together with an increased dislocation density.With 3 min interlayer dwell time,the yield strength of the printed maraging 250 steel increases from 836 MPa to 990 MPa,and the uniform elongation is doubled from 3.2% to 6.5%.This intermittent deposition strategy demonstrates the potential to tune the microstructure of maraging steels for achieving strength-ductility synergy by engineering the thermal history during additive manufacturing.
基金Supported by National Natural Science Foundation of China(No.82160195,No.82460203)Zhejiang Traditional Chinese Medicine Science and Technology Plan Project(No.2025ZR172).
文摘AIM:To compare spontaneous brain regional activities between diabetic vitreous hemorrhage patients(DVHs)and healthy controls(HCs).METHODS:Thirty-two DVHs and 32 HCs were enrolled in this study.Baseline demographic and vision data were compared between groups using an independent sample t-test.Resting-state functional magnetic resonance imaging(rs-fMRI)was used in all participants.fMRI data was obtained and analyzed using MRIcro and SPM8 software.Fractional amplitude of low-frequency fluctuation(fALFF)technology was used to measure regional spontaneous brain activity,and sensitivity was tested using receiver operating characteristic curves(ROCs).The fALFF values were analyzed using REST software and two-sample t-tests were used to compare values between groups.Hospital anxiety and depression scale(HADS)score was assessed in DVHs and Pearson’s correlation was used to test relationships between mean fALFF value and both HADS score and duration of DVH.RESULTS:Except for the best-corrected visual acuity(BCVA)in both eyes,which showed a statistically significant difference(P<0.05),there were no statistically significant differences in the other indicators(P>0.05)between the HCs and DVHs group.Compared with controls,fALFF value was higher in DVH in cerebellum posterior lobe(CPL)and lower in right anterior cingulate cortex(ACC)and right medial orbitofrontal cortex(OFC).In DVH patients,mean fALFF value of CPL was positively correlated with HADS score and duration of diabetes.However,no such correlation was found,for right ACC or right medial OFC.DVH may lead to abnormal activities in certain brain regions related to visual control and mood.CONCLUSION:Visual impairment caused by DVH may lead to adjustment in regional visual brain activities and may be related to depression or reward system processing in some brain regions.
文摘Overt and harmful diabetes mellitus(DM)has detrimental effects on individuals and,by extension,the community.Among the microvascular DM complications is diabetic retinopathy(DR).DR may cause irreversible vision deterioration in cases of poor blood glucose regulation.Changes in vascular permeability are key trigger points for diabetic macular edema(DME),a condition characterized by the accumulation of fluid in the macula.The development of vascular endothelial growth factor(VEGF)pathway inhibitors has provided a pathogenesis-based treatment approach for DME.Optical coherence tomography(OCT)provides highresolution imaging of the anatomy,including the aging of DME and its structural damage,in distinct morphologic subtypes of macular edema,thereby supporting the assessment of macular edema treatment.The availability of repeated OCT monitoring provides clinical reassurance through the treatment.OCT angiography(OCTA)provides retinal blood flow maps with high spatial resolution.The ability promotes an understanding of disease pathogenesis and facilitates the implementation of new therapeutic methods.This review compares the potential of OCT and OCTA in the diagnosis and treatment of DME,as well as their respective therapeutic applications.
基金supported by the National Institute of Environmental Research(NIER)funded by the Ministry of Environment(No.NIER-2019-04-02-039)supported by Particulate Matter Management Specialized Graduate Program through the Korea Environmental Industry&Technology Institute(KEITI)funded by the Ministry of Environment(MOE).
文摘Fine particulatematter(PM_(2.5))samples were collected in two neighboring cities,Beijing and Baoding,China.High-concentration events of PM_(2.5) in which the average mass concentration exceeded 75μg/m^(3) were frequently observed during the heating season.Dispersion Normalized Positive Matrix Factorization was applied for the source apportionment of PM_(2.5) as minimize the dilution effects of meteorology and better reflect the source strengths in these two cities.Secondary nitrate had the highest contribution for Beijing(37.3%),and residential heating/biomass burning was the largest for Baoding(27.1%).Secondary nitrate,mobile,biomass burning,district heating,oil combustion,aged sea salt sources showed significant differences between the heating and non-heating seasons in Beijing for same period(2019.01.10–2019.08.22)(Mann-Whitney Rank Sum Test P<0.05).In case of Baoding,soil,residential heating/biomass burning,incinerator,coal combustion,oil combustion sources showed significant differences.The results of Pearson correlation analysis for the common sources between the two cities showed that long-range transported sources and some sources with seasonal patterns such as oil combustion and soil had high correlation coefficients.Conditional Bivariate Probability Function(CBPF)was used to identify the inflow directions for the sources,and joint-PSCF(Potential Source Contribution Function)was performed to determine the common potential source areas for sources affecting both cities.These models facilitated a more precise verification of city-specific influences on PM_(2.5) sources.The results of this study will aid in prioritizing air pollution mitigation strategies during the heating season and strengthening air quality management to reduce the impact of downwind neighboring cities.
基金supported by Natural Science Foundation of Anhui Province(2008085MH273)Anhui Fund for Distinguished Young Scholars(2022AH020050)+3 种基金the Scientific Research Platform Improvement Project of Anhui Medical University(2022xkjT045)the Natural Science Foundation of Anhui Province(No.2108085MH278)Graduate Research and Practice Innovation Project of Anhui Medical University(YJS20230110)the Science and Technology Program of Ma’anshan City(No.YL-2022-8)。
文摘Background:Renal cell carcinoma(RCC)is a prevalent malignancy characterized by a rising incidence and significant mortality.Interleukins(ILs)are crucial in regulating immune cell trafficking and exhibit anti-tumor properties.However,limited research has explored the expression levels and prognostic significance of interleukins in RCC.Methods:In this comprehensive study,we performed a detailed analysis of interleukins in RCC patients using multiple bioinformatics tools,including Oncomine,UALCAN,GEPIA,Kaplan-Meier plotter,cBioPortal,GeneMANIA,TRRUST,STRING,and Linked Omics.Results:Our analysis demonstrated a significant upregulation in the transcriptional levels of IL4,IL7,IL15,IL16,IL23A,IL26,and IL32 were significantly upregulated in RCC tissues,indicating their potential involvement in the pathogenesis of this malignancy.In contrast,IL1A,IL11,and IL27 were downregulated,indicating their potential function as tumor suppressors.Significant correlations were identified between the expression levels of IL11,IL23A,IL27,IL32,and the pathological stage of RCC patients.The expression levels of IL1A,IL4,IL11,IL15,IL16,IL23A,IL26,IL27,and IL32 were significantly correlated with improved prognosis.The differentially expressed interleukins primarily function in cytokine-cytokine receptor interactions and immune response-regulating signaling pathways.homeobox A10(HOXA10),v-myb myeloblastosis viral oncogene homolog(avian)(MYB),v-rel reticuloendotheliosis viral oncogene homolog A(avian)(RELA),and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1(NFKB1)are key transcription factors for ILs,while LCK proto-oncogene(LCK),LYN proto-oncogene(LYN),spleen associated tyrosine kinase(SYK),Janus kinase 3(JAK3),and FER tyrosine kinase(FER)are IL targets.IL expression significantly correlated with the infiltration of six distinct immune cell types.IL1A potentially exerts an anti-tumor effect in RCC prognosis by inducing neutrophil extracellular traps(NETs).Additionally,NFKB1 may positively regulate IL1A,providing a rationale for further in vivo and clinical studies.Conclusion:In conclusion,our study demonstrates the potential role of IL 1A in the prognosis of RCC and establishes a theoretical foundation for subsequent in vivo and clinical investigations.
文摘BACKGROUND There has been an increasing focus in recent years on health-care disparities.Studies investigating return to work(RTW)or sports are often performed in large,urban areas.Relatively few studies have investigated rates of return to farming or other heavy labor that is of interest to patients in rural areas.AIM To evaluate the literature regarding RTW in farming or heavy labor after orthopedic hip,knee,or shoulder surgery.METHODS A search was performed in the PubMed and EMBASE databases using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.Studies were included if they reported patients employed in farming or heavy labor,RTW rates after orthopedic surgery of the hip,knee,or shoulder,and had a minimum 6-month follow-up.A meta-analysis of proportions using a random-effects model was performed on three single-arm observational studies to estimate the pooled RTW rate following arthroscopic shoulder surgery.RESULTS Ten studies were included,and 101 farmers were identified among 440 total patients.One study involved hip surgery,two studies involved knee surgery,and seven studies involved shoulder surgery.RTW rates across studies varied by type of surgery and follow-up interval,ranging from 24%to 100%.The RTW rate was only 53.6%at 1 year following total hip arthroplasty.No studies investigated RTW in farmers following total knee arthroplasty.Among non-comparative studies,meta-analysis revealed a pooled RTW rate of 89%following arthroscopic shoulder surgery,with low heterogeneity(I^(2)=30.1%).Among comparative studies,one study reported significantly higher RTW odds for patients undergoing anatomic total shoulder arthroplasty compared to reverse shoulder arthroplasty(odds ratio=5.45).Overall,surgical intervention for shoulder pathology was associated with a high likelihood of RTW across multiple techniques,with particularly favorable outcomes for anatomic total shoulder arthroplasty.CONCLUSION This systematic review highlights the high rates of RTW in farmers and heavy laborers after shoulder surgery.However,our findings also underscore the need for more rural-specific research to guide patient counseling,rehabilitation expectations,and shared decision-making in this underserved population,particularly for orthopedic surgery of the hip and knee.
基金supported by National Natural Science Foundation of China(Nos.52077026,51977023,52177126 and 12475253)the Fundamental Research Funds for the Central Universities(No.DUT23YG227)the Dalian Life&Health Guiding Project(No.2023ZXYG34)。
文摘In this study,we explored a one-step direct synthesis of NH3 under mild experimental conditions utilizing pulse-modulated microwave plasma technology at atmospheric pressure.At a substantial gas flow rate,a microwave plasma jet was formed and the microwave-assisted ammonia synthesis can be realized.Impacts of various parameters including the gas flow rate,gas component,microwave absorbed power,pulse modulation frequency,and pulse duty cycle on ammonia synthesis were systematically investigated.To indicate the reaction path of ammonia synthesis,the distributions of both the gas temperature and active species were also studied using optical emission spectra technology.It is found that a considerable amount of ammonia was directly synthesized without involvement of any catalysts,the highest ammonia production rate and energy efficiency(EE),up to 2.93μmol·min^(-1) and 6.64×10^(-2)g·(k W·h)^(-1),respectively,were achieved under low microwave power of 84.42 W.The duty cycle has obvious influences on the synthesis efficiency,compared to a duty cycle of 80%,the ammonia synthesis rate,EE and nitrogen conversion decreased by about 22%at a duty cycle of 100%.This finding underscores the significance of incorporating pulse modulation in the microwave discharge process for ammonia synthesis.Furthermore,it was found that vibrational excitation of microwave plasma has a significant driving effect on ammonia synthesis.
文摘Acute exposure to high altitude can cause acute altitude illnesses and is associated with impaired cognitive and physical performance.The most effective preventive strategies currently recommended include environmental acclimatization(slow ascent and/or pre-acclimatization)or pharmacological support of acclimatization using acetazolamide.However,these strategies are not practical for high-altitude exposures that require rapid and unplanned ascent,high physical and mental performance,such as rescue missions or military operations.Dexamethasone and other modulators of the glucocorticoid system take effect quickly and are effective alternatives for preventing acute altitude illnesses when rapidly ascending to high altitudes.As the efficacy of dexamethasone in preventing acute mountain illnesses remains controversial,a review of existing studies on the use of dexamethasone for the prevention of acute mountain sickness was conducted,aiming to determine the best strategy.Possible mechanisms of protection against acute altitude illnesses are discussed based on the results of clinical trials.The data indicate that dexamethasone is most effective at altitudes above 4000 m at doses of 8–16 mg/d.Appropriately designed and powered trials are needed to obtain more evidence-based results on the dosage and timing of dexamethasone administration,and to provide optimized recommendations for the application of this powerful pharmacological tool.
基金supported in part by the e-ASIA Joint Research Program from the Japan Agency for Medical Research and Development(AMED)(grant number:21jm0210062h0004).
文摘Cholangiocarcinoma(CCA)is a fatal bile duct malignancy.CCA is intrinsically resistant to standard chemotherapy,responds poorly to it,and has a poor prognosis.Effective treatments for cholangiocarcinoma remain elusive,and a breakthrough in CCA treatment is still awaited.The human epidermal growth factor receptor 2(HER2)plays an oncogenic role by promoting an aggressive cancer phenotype through multiple pathways.While HER2 has shown increasing potential as an effective target for breast and gastric cancers over the last decade,this has not been the case for CCA.This review explores the possibility of targeting HER2 in CCA immunotherapy.Key findings suggest that HER2 alterations have been reported as one of the signatures associated with a poorer prognosis in liver fluke-associated CCA,the most prevalent subtype in Southeast Asia.Furthermore,we assess recent advances in HER2-targeted therapeutic approaches,presenting the current stage,rationale,and evidence supporting the use of HER2 as a promising therapeutic target for cancer immunotherapy in CCA.We also emphasize the crucial role of animal models in developing anticancer therapies.In summary,focusing on HER2 expression could provide alternative strategies for the HER2-altered CCA cluster.
基金funded by Fundacao de Amparoà Pesquisa do Estado de Sao Paulo(process no:2016/22679-3)funded through an undergraduate student scholarship for scientific research provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq,process no:144202/2018-2).
文摘Sexual selection is thought to play a major role in the evolution of color due to the correlation between a signaler’s physiological state and the displayed color.As such,researchers often investigate how color correlates to the quality of the signaler.However,research on the relationship between color and individual quality is often taxonomically limited and researchers typically investigate how color phenotypes relate to one index of quality,such as a linear measure of body size.Here,we investigated the relationship among body size,claw size,claw muscle mass,lipid content,and the color of the claw in male fiddler crabs(Leptuca uruguayensis)which wield an exaggerated claw that varies in color from brown to red.We hypothesized that if the color was correlated to one or more indices of male quality,the color displayed on the claws of male L.uruguayensis could be under sexual selection.We found L.uruguayensis claw color varies substantially among the individuals we photographed.However,we did not find a correlation between claw color and indices of quality;neither brightness nor hue correlated to the indices of quality we measured.Our findings suggest that claw color in L.uruguayensis is unlikely to have evolved to signal quality,but may instead function as a species identity or as a non-indicator sexual signal.
文摘BACKGROUND Familial Mediterranean fever(FMF)is an autosomal recessive autoinflammatory disorder marked by recurrent episodes of fever and serositis.Resistin,a proinflammatory cytokine,may play a role in FMF pathogenesis by promoting the release of interleukin-1beta,tumour necrosis factor alpha,and interleukin-6.AIM To evaluate serum resistin levels in children with FMF during acute attacks and remission,and to assess its potential as a biomarker for disease activity and progression.METHODS A case-control study was conducted involving 40 pediatric patients with FMF and 40 age-and sex-matched healthy controls.Serum resistin and inflammatory markers—including total leukocyte count(TLC),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),serum amyloid A(SAA),and fibrinogen—were measured using enzyme-linked immunosorbent assay and standard assays.RESULTS No significant differences were found in age or sex between FMF patients and controls.Among FMF patients,fever was the most prevalent symptom(95%),followed by abdominal pain(75%).The most frequently detected genetic mutation was M694I,followed by M694V,E148Q,M680I,and V726A.Compound heterozygous mutations,including M694I/V726A and M694I/M694V,were equally represented.During acute attacks,FMF patients exhibited significantly elevated levels of TLC,ESR,CRP,SAA,and fibrinogen compared to attack-free periods and controls.Serum resistin levels were markedly higher during acute attacks and showed a strong positive correlation with other acute inflammatory markers.Receiver operating characteristic curve analysis demonstrated high sensitivity and specificity of resistin as a potential biomarker for FMF.CONCLUSION Resistin is significantly elevated in children with FMF during acute episodes and correlates with established inflammatory markers.These findings support its potential role as a non-invasive biomarker for disease activity and severity in pediatric FMF.
文摘Zero-click attacks represent an advanced cybersecurity threat,capable of compromising devices without user interaction.High-profile examples such as Pegasus,Simjacker,Bluebugging,and Bluesnarfing exploit hidden vulnerabilities in software and communication protocols to silently gain access,exfiltrate data,and enable long-term surveillance.Their stealth and ability to evade traditional defenses make detection and mitigation highly challenging.This paper addresses these threats by systematically mapping the tactics and techniques of zero-click attacks using the MITRE ATT&CK framework,a widely adopted standard for modeling adversarial behavior.Through this mapping,we categorize real-world attack vectors and better understand how such attacks operate across the cyber-kill chain.To support threat detection efforts,we propose an Active Learning-based method to efficiently label the Pegasus spyware dataset in alignment with the MITRE ATT&CK framework.This approach reduces the effort of manually annotating data while improving the quality of the labeled data,which is essential to train robust cybersecurity models.In addition,our analysis highlights the structured execution paths of zero-click attacks and reveals gaps in current defense strategies.The findings emphasize the importance of forward-looking strategies such as continuous surveillance,dynamic threat profiling,and security education.By bridging zero-click attack analysis with the MITRE ATT&CK framework and leveraging machine learning for dataset annotation,this work provides a foundation for more accurate threat detection and the development of more resilient and structured cybersecurity frameworks.
基金supported by the National Key R&D Program of China (Grant Nos. 2023YFA1406100, 2022YFA1403900, 2024YFA1408400, 2021YFA1400200, 2022YFA1403800, and 2023YFA1406500)the National Natural Science Foundation of China (Grant Nos. 12174424, 12025408, 11921004, U22A6005, and 12274459)+1 种基金the Youth Innovation Promotion Association of Chinese Academy of Sciences (Grant No. 2023007)the Chinese Academy of Sciences President’s International Fellowship Initiative (Grant No. 2024PG0003)。
文摘Mn_(3)Si_(2)Te_(6) is a ferrimagnetic nodal-line semiconductor with colossal angular magnetoresistance at ambient pressure.In this work,we investigated the effect of hydrostatic pressure on its electrical transport properties,magnetic transition,and crystal structure by measuring resistivity,DC and AC magnetic susceptibility,and XRD under various pressures up to~20 GPa.Our results confirmed the occurrence of pressure-induced structural transition at P_(c)≈10–12 GPa accompanied by a concurrent drop of room-temperature resistance in Mn_(3)Si_(2)Te_(6).In the low-pressure phase at PP_(c),the sample exhibits a metallic behavior in the whole temperature range and its resistivity exhibits a kink anomaly at T_(M),characteristic of critical scattering around a magnetic transition.Recovery of the Raman spectrum upon decompression indicated that pressure-induced structural transition is reversible without amorphization under hydrostatic pressure conditions.Our present work not only resolves some existing controversial issues but also provides new insights into pressure-driven diverse behaviors of Mn_(3)Si_(2)Te_(6).
