Seasonal cycles are essential components of weather and climatic systems. This study utilized observational data from a meteorological station on an island in the South China Sea from 1961 to 2020, along with ERA5 rea...Seasonal cycles are essential components of weather and climatic systems. This study utilized observational data from a meteorological station on an island in the South China Sea from 1961 to 2020, along with ERA5 reanalysis data, to explore the variations in seasonal cycles and thermal comfort characteristics on the island. The observational data revealed that the onset of summer on the island occurred earlier each year, whereas the onset of autumn was gradually delayed,leading to an increase in the duration of summer. Urbanization had played an important role in elevating local temperatures and extending the duration of summer. The thermal comfort index exhibited a clear upward trend annually, reflecting a shift towards warmer and less comfortable conditions due to urbanization. From 1961 to 2020, the annual average thermal comfort index indicated that 36 years(60%) were characterized by hot discomfort, and 24 years(40%) were within the comfortable range. The number of comfortable days per year on the island exhibited a declining trend. Urbanization markedly influenced the thermal comfort levels on the island, contributing to an annual increase in the number of hot discomfort days. However, the reanalysis data did not reflect the actual observed changes in the comfort characteristics on the island.展开更多
Background:Hepatocellular carcinoma(HCC)is a highly lethal malignancy driven by both intrinsic oncogenic pathways and immune microenvironmental regulation.Emerging evidence suggests that DNASE1L3 may influence tumor b...Background:Hepatocellular carcinoma(HCC)is a highly lethal malignancy driven by both intrinsic oncogenic pathways and immune microenvironmental regulation.Emerging evidence suggests that DNASE1L3 may influence tumor biology and immune responses;however,its specific roles in HCC progression and macrophage-mediated regulation remain unclear.This study aimed to elucidate the biological functions of DNASE1L3 in HCC and to determine how it modulates tumor behavior and immune interactions.Methods:Bioinformatics analyses of the GSE41804 and Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC)datasets were used to identify hub genes.Functional assays assessed the impact of DNASE1L3 on HCC cell proliferation,migration,invasion,and cell cycle progression.The effects of DNASE1L3 on macrophage polarization and the Wnt/β-catenin signaling pathway were examined using a co-culture system.An HCC organoid model was established to further validate its regulatory function.Results:Eight prognostic signature genes were identified,with deoxyribonuclease I-like 3(DNase I-like 3)selected as the hub gene.DNASE1L3 overexpression suppressed HCC cell growth,inhibited migration and invasion,induced G1 arrest,and modulated epithelial-mesenchymal transition(EMT)markers.DNASE1L3 knockdown promoted M2-like macrophage polarization.Mechanistically,DNASE1L3 interacted withβ-catenin to enhance its ubiquitination and degradation,thereby inhibiting Wnt/β-catenin signaling and reducing PD-L1 expression.DNASE1L3 overexpression similarly restricted organoid growth and suppressed pathway activity.Conclusion:DNASE1L3 acts as a negative regulator of HCC progression by targeting the Wnt/β-catenin pathway and reducing PD-L1 expression,thereby influencing both tumor cell behavior and macrophage-mediated immune responses.展开更多
(NbZrHfTi)C high-entropy ceramics,as an emerging class of ultra-high-temperature materials,have garnered significant interest due to their unique multi-principal-element crystal structure and exceptional hightemperatu...(NbZrHfTi)C high-entropy ceramics,as an emerging class of ultra-high-temperature materials,have garnered significant interest due to their unique multi-principal-element crystal structure and exceptional hightemperature properties.This study systematically investigates the mechanical properties of(NbZrHfTi)C high-entropy ceramics by employing first-principles density functional theory,combined with the Debye-Grüneisen model,to explore the variations in their thermophysical properties with temperature(0–2000 K)and pressure(0–30 GPa).Thermodynamically,the calculated mixing enthalpy and Gibbs free energy confirm the feasibility of forming a stable single-phase solid solution in(NbZrHfTi)C.The calculated results of the elastic stiffness constant indicate that the material meets the mechanical stability criteria of the cubic crystal system,further confirming the structural stability.Through evaluation of key mechanical parameters—bulk modulus,shear modulus,Young’s modulus,and Poisson’s ratio—we provide comprehensive insight into the macro-mechanical behaviour of the material and its correlation with the underlying microstructure.Notably,compared to traditional binary carbides and their average properties,(NbZrHfTi)C exhibits higher Vickers hardness(Approximately 28.5 GPa)and fracture toughness(Approximately 3.4 MPa⋅m^(1/2)),which can be primarily attributed to the lattice distortion and solid-solution strengthening mechanism.The study also utilizes the quasi-harmonic approximation method to predict the material’s thermophysical properties,including Debye temperature(initial value around 563 K),thermal expansion coefficient(approximately 8.9×10^(−6) K−1 at 2000 K),and other key parameters such as heat capacity at constant volume.The results show that within the studied pressure and temperature ranges,(NbZrHfTi)C consistently maintains a stable phase structure and good thermomechanical properties.The thermal expansion coefficient increasing with temperature,while heat capacity approaches the Dulong-Petit limit at elevated temperatures.These findings underscore the potential of(NbZrHfTi)C applications in ultra-high temperature thermal protection systems,cutting tool coatings,and nuclear structural materials.展开更多
Plasmonic nanolasers are transitioning from empirical optimization to a new paradigm driven by physical mechanisms.Owing to the lack of guidance from internal mechanisms,this transformation process remains highly chal...Plasmonic nanolasers are transitioning from empirical optimization to a new paradigm driven by physical mechanisms.Owing to the lack of guidance from internal mechanisms,this transformation process remains highly challenging.Therefore,elucidating the governing nanoscale light–matter interactions has become essential for unlocking their full performance potential.In this paper,we establish a framework that connects the strength of exciton–plasmon interactions with plasmonic nanolaser performance.The evolution of the laser spectrum under increasing pumping fluence,reflected by variations in intensity,spectral peak position,and full width at half maximum,provides clear evidence of exciton–plasmon interactions.These interactions are further verified by changes in the emission lifetime with incident fluence,and it is found that the lifetime variation correlates with the change in spectral full width at half maximum.Furthermore,we calculate and analyze various loss mechanisms in plasmonic nanolasers,revealing how the strength of exciton–plasmon interactions actively modulates optical loss channels and fundamentally controls the lasing threshold.Understanding exciton–plasmon interaction dynamics is not merely a theoretical pursuit but a critical step toward realizing truly practical and scalable nanophotonic devices.展开更多
In contemporary China,nationalism under Xi Jinping operates through a dual mechanism that integrates domestic identity engineering with outward-facing narratives of moral leadership.This article argues that the Chines...In contemporary China,nationalism under Xi Jinping operates through a dual mechanism that integrates domestic identity engineering with outward-facing narratives of moral leadership.This article argues that the Chinese Communist Party(CCP)’s shift from describing China as a“unified multiethnic state”to promoting a“united community of the Chinese nation”(中华民族共同体)(China Daily,2017)marks a decisive ideological turn that normalizes assimilationist governance and reshapes the cultural and religious life of minority regions.Based on discourse analysis of Xi Jinping’s speeches,official policy documents,and ethnographic fieldwork conducted in Xinjiang in 2024,the study shows how this ideological shift produces a museumized multiculturalism that narrows space for ethnic autonomy and diversity.At the same time,China amplifies a peacebuilding discourse-particularly in its engagement with the Russo-Ukrainian war and conflicts in the Middle East-to present itself as a responsible global actor.The findings reveal three interlocking dynamics:First,cultural homogenization remains central to the Party’s long-term stability strategy;second,China’s civilizational rhetoric resonates most strongly where material partnerships outweigh normative concerns;and third,the contrast between domestic coercion and external reassurance functions not as a contradiction,but as a coherent political pattern.These dynamics show how nationalist ideology,cultural governance,and foreign-policy messaging form an integrated project that expands China’s influence while exposing the limits of its moral legitimacy.展开更多
BACKGROUND The persistent burden of cardiovascular(CV)disease in the United States requires innovative and cost-effective prognostic markers that can be relied upon.AIM To provide insights into how adiponectin can pre...BACKGROUND The persistent burden of cardiovascular(CV)disease in the United States requires innovative and cost-effective prognostic markers that can be relied upon.AIM To provide insights into how adiponectin can predict all-cause mortality and major adverse CV events(MACE)in patients with coronary artery disease(CAD)and to determine the prognostic value of adiponectin in predicting all-cause mortality and MACE in patients with stable CAD.METHODS We conducted a systematic search on PubMed,Scopus,and Google Scholar to find relevant studies published through June 2023 evaluating the long-term prognostic role of adiponectin in patients with stable CAD.Using a random effects model with 95%CI,we estimated the odds ratio(OR)while assessing heterogeneity through I^(2)statistics.To ensure robustness,we performed a sensitivity analysis using the leave-one-out approach.RESULTS After screening,we included five prospective studies involving 3225 patients who were followed up for a median duration of 3.8 years.Within the study population,prevalent risk factors included hypertension,diabetes,hyperlipidemia,and smoking.The commonly prescribed medications were angiotensin-converting enzyme inhibitors,beta blockers,and statins.The combined adjusted OR for all-cause mortality was found to be 2.51(95%CI:1.36–4.62),showing heterogeneity(I^(2)=65.51%,P=0.03).On the other hand,the combined adjusted OR for MACE was determined to be 1.04(95%CI:1.02–1.06)with no significant heterogeneity observed(I^(2)=0%,P=0.68).Through a sensitivity analysis,it was discovered that none of the studies significantly impacted the overall results of the meta-analysis,thus indicating their robustness.CONCLUSION Higher levels of adiponectin were found to be associated with an increased risk of long-term mortality and MACE in patients with CAD,which highlights its potential as a cost-effective marker for risk assessment and guiding treatment strategies.Further research on the role of adiponectin could greatly influence decision-making and resource allocation in CV care.展开更多
Halide solid-state electrolytes have gained significant attention in recent years due to their high ionic conductivity,making them promising candidates for future all-solid-state batteries.Recent studies have identifi...Halide solid-state electrolytes have gained significant attention in recent years due to their high ionic conductivity,making them promising candidates for future all-solid-state batteries.Recent studies have identified numerous crystal structures with the Li_(3)MX_(6)composition,although many remain unexplored across various chemical systems.In this research,we developed a comprehensive method to examine all conceivable space groups and structures within theLi-M-X system,where M includes In,Ga,and La,and X includes F,Cl,Br,and 1.Our findings revealed two metastable structures:Li_(3)InF_(6)with P3c1 symmetry and Li_(3)InI_(6)with C2/c symmetry,exhibiting ionic conductivities of 0.55 and 2.18mS/cm at 300K,respectively.Notably,the trigonal symmetry of Li3InF6 demonstrates that high ionic conductivities are not limited to monoclinic structures but can also be achieved with trigonal symmetries.The electrochemical stability windows,mechanical properties,and reaction energies of these materials with known cathodes suggest their potential for use in all-solid-state batteries.Additionally,we predicted the stability of novel materials,including Li_(5)InCl_(8),Li_(5)InBr_(8),Li_(5)InI_(8),LiIn_(2)Cl_(9),LiIn_(2)Br_(9),and LiIn_(2)I_(9).展开更多
Inflammation plays a key role in driving the secondary brain injury that follows ischemic stroke.Melatonin is an endogenous neuroendocrine hormone that regulates mitochondrial homeostasis.However,the role and mechanis...Inflammation plays a key role in driving the secondary brain injury that follows ischemic stroke.Melatonin is an endogenous neuroendocrine hormone that regulates mitochondrial homeostasis.However,the role and mechanisms by which melatonin regulates microglial pyroptosis and the inflammatory cascade through double-stranded DNA(dsDNA)-sensing cyclic GMP-AMP synthase(cGAS)signaling warrant further study.Using middle cerebral artery occlusion mice,we investigated the effects of melatonin on cGAS-mediated pyroptosis and neuroinflammation.Middle cerebral artery occlusion model mice exhibited significantly increased DNA damage and cytoplasmic dsDNA release,as reflected byγH2AX staining,as well as heightened activation of the cytosolic dsDNA-sensing cGAS-STING pathway,both of which were notably suppressed by melatonin treatment.Melatonin also mitigated NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome activation and nuclear factor(NF)-κB/gasdermin D-mediated pyroptosis in microglia following ischemic stroke,while exhibiting the capacity to attenuate the immune response to ischemia in mice.This led to reduced infiltration of peripheral neutrophils and monocytes/macrophages in the ischemic brain.Specifically,melatonin administration resulted in reductions in the numbers of ionized calcium-binding adapter molecule 1-positive cells and production of interleukin-6 and tumor necrosis factor-αby microglia.Regarding neurological outcomes,melatonin significantly reduced cerebral infarct volume and ameliorated neurological deficits in mice.Notably,the neuroprotective effect of melatonin was correlated with the inhibition of cGAS activity.We also developed and tested melatonin co-loaded macrophage membrane-biomimetic reactive oxygen species-responsive nanoparticles(Mф-MLT@FNGs),which exhibited therapeutic properties in middle cerebral artery occlusion mice.Our findings suggest that melatonin acts on microglial pyroptosis to inhibit neuroinflammation and reshape the immune microenvironment through regulation of the cGAS-STING-NF-κB signaling pathway.By doing so,melatonin rescues damaged brain tissue and protects neurological function,highlighting its potential as a neuroprotective treatment for ischemic stroke.展开更多
Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through...Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through integration of large-scale multi-omics datasets.Methods:We constructed a multi-stage analytical framework encompassing 32 proteomic datasets(covering 2914 unique plasma proteins)and 6 transcriptomic datasets.Multi-omics integration strategies,including two-sample Mendelian randomization,colocalization analysis,and functional enrichment analysis,were employed to identify and validate causal relationships between candidate targets and GCA risk across 4 independent European-ancestry GCA cohorts.Single-cell RNA sequencing analysis of peripheral blood mononuclear cells from untreated GCA patients was performed to characterize hub gene-immune cell relationships.Results:We identified 43 plasma proteins causally associated with GCA[false discovery rate(FDR)<0.05],with 17 representing novel therapeutic targets.Through dual validation using proteome-wide association studies and transcriptome-wide association studies,we identified 13 high-confidence candidate targets with distinct tissue-specific expression patterns.Unc-51 like kinase 3(ULK3)emerged as the strongest protective factor(odds ratio=0.47,95%confidence interval:0.37–0.71)through autophagy regulation,while SLAMF7 represents an immediate drug repositioning opportunity as the target of food and drug administration-approved elotuzumab.Five targets have existing approved drugs(SLAMF7,ICAM1,IL18,IL6ST,CTSS).Single-cell analysis revealed profound disruption of hub gene-immune cell relationships in untreated GCA patients,with cell-type-specific alterations in inflammatory gene expression,and TYMP as the most critical hub gene.Conclusions:This study provides a clinically-actionable atlas of 43 potential therapeutic targets in GCA,identifying novel mechanisms including autophagy modulation and metabolic reprogramming,with immediate drug repositioning opportunities and precision medicine strategies based on tissue-specific and cell-type-specific expression patterns.These findings require experimental validation before clinical translation.展开更多
目的:研究长链非编码RNA(lncRNA)生长阻滞特异性转录物5(GAS5)基因多态性与多囊卵巢综合征(PCOS)发病的关联性。方法:选取2018年5月~2019年5月在广西右江民族医学院附属医院生殖医学中心确诊的236例PCOS患者作为病例组,同时选取同期性...目的:研究长链非编码RNA(lncRNA)生长阻滞特异性转录物5(GAS5)基因多态性与多囊卵巢综合征(PCOS)发病的关联性。方法:选取2018年5月~2019年5月在广西右江民族医学院附属医院生殖医学中心确诊的236例PCOS患者作为病例组,同时选取同期性别、年龄相匹配的277例健康女性作为对照组,采用iMLDR单核苷酸多态性(SNP)分型方法检测GAS5基因rs145204276 I/D、rs55829688 C/T和rs6790 G/A位点基因型。采用logistic回归分析GAS5基因多态性与PCOS的相关性。结果:GAS5基因rs145204276 I/D位点多态性在对照组和PCOS组之间差异有统计学意义,logistic回归分析结果显示,与I/I基因型相比,I/D和D/D基因型以及显性模型I/D+D/D具有较低的PCOS发病风险[I/D vs I/I:OR(95%CI)=0.61(0.42,0.88),P=0.009;D/D vs I/I:OR(95%CI)=0.44(0.23,0.84),P=0.013;I/D+D/D vs I/I:OR(95%CI)=0.57(0.40,0.81),P=0.002];与I等位基因相比,D等位基因显著降低PCOS的发病风险[D vs I:OR(95%CI)=0.62(0.47,0.82),P=0.001]。rs55829688 C/T和rs6790 G/A位点多态性在对照组和PCOS组之间比较差异均无统计学意义(P>0.05)。单倍型联合分析显示D-T-A单倍型在对照组和PCOS组间的分布差异有统计学意义[OR(95%CI)=0.61(0.45,0.84),P=0.002]。结论:GAS5基因rs145204276 I/D位点多态性可能与PCOS遗传易感性相关,即携带D等位基因的个体可能具有较低的PCOS发病风险。展开更多
BACKGROUND Postoperative recurrence is common in Crohn’s disease(CD),with endoscopic lesions in a majority of patients by 12 months after surgery.Ileocolonoscopy is the reference standard but is invasive and poorly s...BACKGROUND Postoperative recurrence is common in Crohn’s disease(CD),with endoscopic lesions in a majority of patients by 12 months after surgery.Ileocolonoscopy is the reference standard but is invasive and poorly suited to frequent surveillance.Intestinal ultrasound(IUS)-including small intestine contrast ultrasound and contrast enhanced ultrasound-is a repeatable,noninvasive alternative.AIM To summarize the evidence on the diagnostic accuracy and prognostic value of IUS for detecting postoperative recurrence in CD.METHODS We systematically searched PubMed and EMBASE through June 2025 for original English-language studies evaluating IUS against clinical or endoscopic outcomes in postoperative CD.This scoping review was conducted and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guideline.After screening 259 unique records,41 full texts were assessed and 20 studies were included.RESULTS Bowel wall thickness thresholds of≥5 mm at the neo-terminal ileum predict endoscopic recurrence with sensitivities 81%-94%and specificities 86%-100%;lower cutoffs at the anastomosis(≥3-3.5 mm)also carry risk(data from singlecenter cohorts).Dualsite assessment(neo-terminal ileum+ileocolonic anastomosis)improves performance.Adding Doppler hyperemia or mesenteric lymphadenopathy increases accuracy;combining bowel wall thickness≥3 mm with fecal calprotectin≥50μg/g yields high specificity(approximately 93%-100%)with a negative predictive value of nearly 95%when both are negative.Contrast enhanced ultrasound-based composite scores reach approximately 98%diagnostic accuracy in prospective cohorts.Small intestine contrast ultrasound shows similarly strong early diagnostic performance-for example,an area under the receiver operating characteristic curve up to 0.95 when using ileocolonic anastomosis wall thickness≥3 mm to 3.5 mm plus lesion length,with 82%-94%sensitivity and>90%specificity reported even within 7 days postresection.Overall,IUS shows moderate agreement with endoscopy(κapproximately 0.5-0.8)and stronger prognostic value when performed within 12 months post-surgery.CONCLUSION IUS can be integrated into postoperative surveillance algorithms-particularly within the first year-and can reduce routine endoscopy in selected patients.Research priorities include standardized thresholds and composite scoring,consensus training/competency,and multicenter validation including artificial intelligenceassisted interpretation.展开更多
BACKGROUND Spinal cord injury(SCI)imposes enduring physical impairments and substantial socio-economic burdens.These injuries are either traumatic incidents or ischemic but exhibit comparable clinical recoveries.This ...BACKGROUND Spinal cord injury(SCI)imposes enduring physical impairments and substantial socio-economic burdens.These injuries are either traumatic incidents or ischemic but exhibit comparable clinical recoveries.This suggests shared underlying neurodegenerative mechanisms,such as neuronal cell death,demyelination,and axonal degeneration,regardless of aetiology.AIM To investigate the relationship between the magnetic resonance imaging(MRI)biomarkers(tissue bridges)and clinical outcome in acute traumatic SCI.METHODS In this prospective study adult patients with acute SCI who were examined clinically and radiologically within first 48 hours and subsequently at intervals were included.Clinical assessment included sensory score,motor score and zone of partial preservation.Radiological scores included measurement kyphotic deformities-sagittal index,regional kyphosis,gardener segmental kyphotic deformity.MRI on 3 Tesla machine was done to evaluate quantitative&qualitative parameters,and tissue bridges at one and 6 months.RESULTS There were 47 patients with a mean age of 40.43±10.73 years and male/female ratio of 34:13.There was a significant(P<0.05)improvement in clinical,radiological,and MRI parameters at 6 months.Maximum spinal cord compression(MSCC),maximal canal compression,lesion length,width,and area;dorsal tissue bridges;ventral tissue bridges,total width of tissue bridges;and midsagittal tissue bridge ratios at one month significantly(P<0.05)correlated with the 6-month total motor score and total sensory score.Further,the regression analysis demonstrated clinical improvement to dimensions of tissue bridges at 6 months.CONCLUSION The MRI imaging biomarkers in SCI patients demonstrated substantial improvement over time.There was a negative correlation between neurological recovery,MSCC,maximum canal compromise,and lesion dimensions(lesion length,lesion width,and lesion area).Higher canal compromise and lesion dimensions were associated with a poorer outcome.The evaluation of the midsagittal tissue bridge(including the ventral tissue bridge,dorsal tissue bridge,total width of the tissue bridge,and tissue bridge ratios)at 1 and 6 months showed a positive correlation with the neurological recovery.展开更多
BACKGROUND Primary percutaneous coronary intervention(PCI)is the preferred treatment for ST-segment elevation myocardial infarction(STEMI).However,in patients with high thrombus burden,immediate stenting during PCI ca...BACKGROUND Primary percutaneous coronary intervention(PCI)is the preferred treatment for ST-segment elevation myocardial infarction(STEMI).However,in patients with high thrombus burden,immediate stenting during PCI can lead to poor outcomes due to the risk of thrombus migration and subsequent microvascular occlusion,resulting in no-reflow phenomena.Deferred stenting offers a potential advantage by allowing for the reduction of thrombus load,which may help to minimize the incidence of slow-flow and no-reflow complications.This study explores the effectiveness of a deferred stenting strategy in improving outcomes for STEMI patients.AIM To evaluate the effectiveness and safety of deferred PCI in a real-world setting in acute STEMI patients.METHODS RESULTS Anterior wall myocardial infarction was the predominant type of STEMI in 62%of the selected 55 patients(mean age:54 years;70%males),and diabetes mellitus was the most common risk factor(18.2%),followed by hypertension(16.2%).On the second angiogram of these patients measures of thrombus grade,thrombolysis in myocardial infarction flow grade,myocardial blush grade,and severity of stenosis of culprit lesion were consid-erably improved compared to the first angiogram,and the average culprit artery diameter had increased by 7.8%.Most patients(60%)had an uneventful hospital stay during the second angiogram and an uneventful intrapro-cedural course(85.19%),with slow-flow/no-reflow occurring only in 7.4%of the patients;these patients recovered after taking vasodilator drugs.In 29.3%of patients,the culprit artery was recanalized,preventing unnecessary stent deployment.CONCLUSION Deferred PCI strategy is safe and reduces the thrombus burden,improves thrombolysis in myocardial infarction(TIMI)flow,improves myocardial blush grade,and prevents unwarranted stent deployment.展开更多
Fish scaleδ^(15)N(δ^(15)N_(sca))records trophic information of the whole life history for marine fishes.Data from gut content and values calculated from white muscle tissue(WMT)are insufficient for assessing trophic...Fish scaleδ^(15)N(δ^(15)N_(sca))records trophic information of the whole life history for marine fishes.Data from gut content and values calculated from white muscle tissue(WMT)are insufficient for assessing trophic level(TL)of marine fishes as they only provide the information of several months or even several days.Stable isotope analysis(SIA)of nitrogen was carried out in fish scales and WMT of 16 species from a total of 28 individuals captured from the Yellow Sea and northern East China Sea in October and November of 2019,aiming at discovering the correlation betweenδ^(15)N_(sca) and fish WMTδ^(15)N(δ^(15)NWMT),so as to useδ^(15)N_(sca) for the characterization of TLs of marine fish.Scales were analyzed without prior carbonate dissolution as a pre-processing step.TL calculated fromδ^(15)N_(sca) was compared to traditional TL formula calculated withδ^(15)N_(WMT) to estimate the accuracy.We found that there was a highly significant and positive correlation(r=0.830,P<0.001)betweenδ^(15)N_(sca) andδ^(15)N_(WMT).TL calculation results using fish scale(TL_(sca))and WMT(TL_(WMT))showed congruence(r=0.773,P<0.001),and the regression coefficient betweenδ^(15)N_(sca) andδ^(15)NWMT was used for calculating TLsca.The conversion was conducted for the purpose of comparison with previousδ^(15)N_(WMT)-based calculation results of TL.TLsca calculation results were 81.25%within the TL range of±10%calculated withδ^(15)NWMT.The findings in the present study showed thatδ^(15)N_(sca) is a viable technique for the characterization of the TL of marine fish and can help to predict food web and support the study of marine ecosystem.展开更多
Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to ...Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to effectively alleviate VH.In this study,neonatal maternal separation(NMS)was used to induce VH in 72 rats and investigated the effects of daily gavage of 3×10^(9) CFU of Lactobacillus and Bifidobacterium on alleviating the symptoms of IBS-D and behavioral interventions,as well as exploring potential mechanisms.The results demonstrated that L.acidophilus and B.breve could alleviate the symptoms of IBS-D such as VH and increased frequency of bowel movements,as well as improving non-spatial memory in NMS rats.These effects were achieved by modulating the composition of gut microbiota and metabolites(including short-chain fatty acids,deoxycholic acid and adenosine),and by regulating the expression of genes and proteins associated with the NGF/TrkA signaling pathway,tryptophan metabolism,and inflammatory factors in the hippocampus.This finding suggests that L.acidophilus and B.breve have promising potential for the alleviation of IBS.展开更多
Deep phenotyping and genetic characterization of individuals are fundamental to assessing the metabolic status and determining nutrition-specific requirements.This study aimed to ascertain the utmost effectiveness of ...Deep phenotyping and genetic characterization of individuals are fundamental to assessing the metabolic status and determining nutrition-specific requirements.This study aimed to ascertain the utmost effectiveness of personalized interventions by aligning dietary adjustments with both the genotype and metabolotype of individuals.Therefore,we assessed here the usefulness of a polygenic score(PGS)characterizing a potential pro-inflammatory profile(PGSi)as a nutrigenetic tool to discern individuals from the Danish PREVENTOMICS cohort that could better respond to precision nutrition(PN)plans,specifically targeted at counteracting the low-grade inflammatory profile typically found in obesity.The cohort followed a PN plan to counteract the pro-inflammatory profile(PNi group)or generic dietary recommendations(Control)for 10 weeks.PGSi was applied for genetic stratification(Low/High).The effects of the intervention on anthropometrics and biomarkers related to inflammatory profile and carbohydrate metabolism were assessed.Around 30%of subjects had a high genetic predisposition to pro-inflammatory status(high-PGSi).These individuals demonstrated the most effective response to the dietary plan,experiencing improved body composition,with significant decreases in body weight(∆:-4.84%;P=0.039)and body fat(∆:-4.86%;P=0.007),and beneficial changes in pro-and anti-inflammatory biomarkers,with significant increases in IL-10(∆:71.3%;P=0.025)and decreases in TNF-α(∆:-3.0%;P=0.048),CRP(∆:-31.1%),ICAM1(∆:-5.8%),and MCP1(∆:-4.2%)circulating levels,compared to low-PGSi individuals.Both phenotypic and genetic stratification contributed to a better understanding of metabolic heterogeneity in response to diet.This approach allows for refinement of the prediction of individual requirements and potentially for better management of obesity.展开更多
Background:While various factors contributing to delinquency have been explored,the role of selfesteem in this specific context has received little attention.Hence,this study aims to investigate the complex issue of a...Background:While various factors contributing to delinquency have been explored,the role of selfesteem in this specific context has received little attention.Hence,this study aims to investigate the complex issue of adolescent delinquency in Iran by focusing on the mediating role of self-esteem in the relationship between parental attachment and delinquent behavior.Methods:Using the multistage cluster random sampling method,the research involved 528 high school students in Tehran.Each student completed validated scales assessing their parental attachment,self-esteem,and delinquency at school.Multiple regression analyses with the Sobel test and bootstrappingmethod were used to examine mediated effects.Results:Thefindings reveal that self-esteem significantly mediates the relationship betweenmaternal attachment and delinquency(standardized coefficient=−0.0292;p=0.04).Adolescents with secure maternal attachments tend to exhibit higher self-esteem,which reduces the likelihood of delinquent behavior.In contrast,paternal attachment did not show a significant mediating effect in this study.These results underscore the importance of cultivating secure maternal relationships and fostering positive self-esteem to address adolescent delinquency.Conclusion:The study suggests that targeted interventions that strengthen maternal attachment and boost self-esteem could effectively mitigate delinquent behaviors among Iranian adolescents.These interventions should prioritize the emotional support and value of secure maternal bonds as key factors in promoting healthy adolescent development.展开更多
BACKGROUND The norursodeoxycholic acid(norUDCA),a side chain-shortened derivative of ursodeoxycholic acid,exhibits unique pharmacological properties that may benefit patients with metabolic dysfunction-associated stea...BACKGROUND The norursodeoxycholic acid(norUDCA),a side chain-shortened derivative of ursodeoxycholic acid,exhibits unique pharmacological properties that may benefit patients with metabolic dysfunction-associated steatotic liver disease(MASLD).AIM To evaluate the efficacy,safety,and tolerability of norUDCA 1500 mg compared to placebo in the patients with MASLD.METHODS This phase III,randomized,double-blind,multi-centric,placebo-controlled trial enrolled patients with MASLD,and were randomized in 2:1 ratio to receive either norUDCA 1500 mg or placebo for 24 weeks.Efficacy and safety were rigorously evaluated through clinical,biochemical,and imaging assessments.Primary endpoints assessed alanine aminotransferase(ALT)normalization and improvement in liver stiffness(FibroScan®)at week 12,while secondary endpoints included changes in nonalcoholic fatty liver disease fibrosis score,liver enzymes,lipid profile,glycosylated hemoglobin,and FibroScan-assessed liver stiffness.Safety was monitored throughout the study.RESULTS Of 165 randomized patients,110 received norUDCA and 55 placebos.At week 12,ALT normalization was achieved in 89%of norUDCA-treated group compared to 76%of placebo-treated group(P=0.022);with a statistically significant adjusted mean difference(P=0.016).Fibrosis improvement was observed in 57%of norUDCA-treated vs 40%in placebo-treated(P=0.035),with highly significant adjusted mean(P=0.002).nonalcoholic fatty liver disease fibrosis score at week 18 and 24(P=0.041 and P=0.032).Similarly,ALT reductions were significant at both week 18 and week 24(P=0.021 and P=0.035).Improvements in lipid profile trended towards norUDCA without statistical significance.Liver stiffness has improved in 90 patients in norUDCA-treated vs 36 patients in placebo group(P=0.009).NorUDCA demonstrated favorable safety profile,with no serious adverse events reported,and only mild to moderate adverse events were observed.CONCLUSION NorUDCA 1500 mg demonstrated clinically meaningful therapeutic efficacy in patients with MASLD,accompanied by consistently favorable safety profile.展开更多
Original sedimentary manganese(Mn)deposits and supergene Mn ores are important Mn resources in China.However,the geochemical information from Chinese supergene Mn ores is scarce,and the relationship between sedimentar...Original sedimentary manganese(Mn)deposits and supergene Mn ores are important Mn resources in China.However,the geochemical information from Chinese supergene Mn ores is scarce,and the relationship between sedimentary Mn deposits and supergene Mn ores is ambiguous.In this study,we collected the original Mn-bearing dolomitic sandstones(ZK20-3 drillcore)and supergene Mn ores(Longmen Section)from eastern Hebei,North China for systematic petrographic,mineralogical and geochemical analyses.Our new data help us to figure out the transformation from original Mn-bearing deposits to supergene ores.The main minerals of original Mn-bearing dolomitic sandstones are quartz and feldspar,with minor muscovite,dolomite,rhodochrosite,ankerite,and kutnohorite.Supergene Mn-oxide ores only emerged in the middle part of the Longmen(LM)Section,and mainly contain quartz,pyrolusite,cryptomelane,todorokite and occasional dolomite.The possible transformation sequence of Mn minerals is:kutnohorite/rhodochrosite→pyrolusite(Ⅰ)→cryptomelane(todorokite)→todorokite(cryptomelane)→pyrolusite(Ⅱ).For Mn-oxide ores,Fe,Na and Si are enriched but Al,Ca,Mg and K are depleted with the enrichment of Mn.For original and supergene ores,the total rare earth element+ytterbium(∑REY)contents range from 105.68×10^(-6)to 250.56×10^(-6)and from 18.08×10^(-6)to 176.60×10^(-6),respectively.Original Mn ores have similar slightly LREE-enriched patterns,but the purer Mn-oxide ore shows a HREE-enriched pattern.In the middle part of the LM Section,positive Ce anomalies in Mn-oxide ores indicate the precipitation of Ce-bearing minerals.It implies the existence of geochemical barriers,which changed p H and Eh values due to the long-time influence of groundwater.展开更多
Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxy...Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxylum bungeanum,which promotes the management of obesity by triggering the browning of white adipose tissue(WAT)targeting the membrane receptor of transient receptor potential vanilloid 1(TRPV1).However,HAS easily undergoes configuration transformation and oxidative degradation.The short peptide CKGGRAKDC or adipose-targeting sequence(ATS)binds specifically to prohibitin on the surface of WAT cells and can be used as recognition assembly to enhance adipocyte targetability.Furthermore,mesoporous silica nanoparticles(MSNs)are widely used in drug delivery systems because of their large specific surface area and pore volume.Therefore,HAS-loaded adipose-targeted MSNs(MSNs-ATS)were developed to enhance the adipocyte targetability,safety,and efficacy of HAS,and tested on mature 3T3-L1 cells and obese mouse models.MSNs-ATS showed higher specificity for adipocyte targetability without obvious toxicity.HAS-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS alone.In conclusion,we successfully developed adipocyte-targeted,HAS-loaded MSNs with good safety and anti-obesity effects.展开更多
基金National Natural Science Foundation of China(U21A6001,42475077)Innovation Platform for Academicians of Hainan Province。
文摘Seasonal cycles are essential components of weather and climatic systems. This study utilized observational data from a meteorological station on an island in the South China Sea from 1961 to 2020, along with ERA5 reanalysis data, to explore the variations in seasonal cycles and thermal comfort characteristics on the island. The observational data revealed that the onset of summer on the island occurred earlier each year, whereas the onset of autumn was gradually delayed,leading to an increase in the duration of summer. Urbanization had played an important role in elevating local temperatures and extending the duration of summer. The thermal comfort index exhibited a clear upward trend annually, reflecting a shift towards warmer and less comfortable conditions due to urbanization. From 1961 to 2020, the annual average thermal comfort index indicated that 36 years(60%) were characterized by hot discomfort, and 24 years(40%) were within the comfortable range. The number of comfortable days per year on the island exhibited a declining trend. Urbanization markedly influenced the thermal comfort levels on the island, contributing to an annual increase in the number of hot discomfort days. However, the reanalysis data did not reflect the actual observed changes in the comfort characteristics on the island.
基金funded by Shanghai Science and Technology Innovation Action Plan Project(22140901100)Shanghai Key Laboratory of Molecular Imaging(18DZ2260400)Shanghai University of Medicine and Health Science Seed Fund(SSF-24-21-01).
文摘Background:Hepatocellular carcinoma(HCC)is a highly lethal malignancy driven by both intrinsic oncogenic pathways and immune microenvironmental regulation.Emerging evidence suggests that DNASE1L3 may influence tumor biology and immune responses;however,its specific roles in HCC progression and macrophage-mediated regulation remain unclear.This study aimed to elucidate the biological functions of DNASE1L3 in HCC and to determine how it modulates tumor behavior and immune interactions.Methods:Bioinformatics analyses of the GSE41804 and Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC)datasets were used to identify hub genes.Functional assays assessed the impact of DNASE1L3 on HCC cell proliferation,migration,invasion,and cell cycle progression.The effects of DNASE1L3 on macrophage polarization and the Wnt/β-catenin signaling pathway were examined using a co-culture system.An HCC organoid model was established to further validate its regulatory function.Results:Eight prognostic signature genes were identified,with deoxyribonuclease I-like 3(DNase I-like 3)selected as the hub gene.DNASE1L3 overexpression suppressed HCC cell growth,inhibited migration and invasion,induced G1 arrest,and modulated epithelial-mesenchymal transition(EMT)markers.DNASE1L3 knockdown promoted M2-like macrophage polarization.Mechanistically,DNASE1L3 interacted withβ-catenin to enhance its ubiquitination and degradation,thereby inhibiting Wnt/β-catenin signaling and reducing PD-L1 expression.DNASE1L3 overexpression similarly restricted organoid growth and suppressed pathway activity.Conclusion:DNASE1L3 acts as a negative regulator of HCC progression by targeting the Wnt/β-catenin pathway and reducing PD-L1 expression,thereby influencing both tumor cell behavior and macrophage-mediated immune responses.
基金supported by the National Natural Science Foundation of China(Nos.92166105 and 52005053)High-Tech Industry Science and Technology Innovation Leading Program of Hunan Province(No.2020GK2085)the Science and Technology Innovation Program of Hunan Province(No.2021RC3096).
文摘(NbZrHfTi)C high-entropy ceramics,as an emerging class of ultra-high-temperature materials,have garnered significant interest due to their unique multi-principal-element crystal structure and exceptional hightemperature properties.This study systematically investigates the mechanical properties of(NbZrHfTi)C high-entropy ceramics by employing first-principles density functional theory,combined with the Debye-Grüneisen model,to explore the variations in their thermophysical properties with temperature(0–2000 K)and pressure(0–30 GPa).Thermodynamically,the calculated mixing enthalpy and Gibbs free energy confirm the feasibility of forming a stable single-phase solid solution in(NbZrHfTi)C.The calculated results of the elastic stiffness constant indicate that the material meets the mechanical stability criteria of the cubic crystal system,further confirming the structural stability.Through evaluation of key mechanical parameters—bulk modulus,shear modulus,Young’s modulus,and Poisson’s ratio—we provide comprehensive insight into the macro-mechanical behaviour of the material and its correlation with the underlying microstructure.Notably,compared to traditional binary carbides and their average properties,(NbZrHfTi)C exhibits higher Vickers hardness(Approximately 28.5 GPa)and fracture toughness(Approximately 3.4 MPa⋅m^(1/2)),which can be primarily attributed to the lattice distortion and solid-solution strengthening mechanism.The study also utilizes the quasi-harmonic approximation method to predict the material’s thermophysical properties,including Debye temperature(initial value around 563 K),thermal expansion coefficient(approximately 8.9×10^(−6) K−1 at 2000 K),and other key parameters such as heat capacity at constant volume.The results show that within the studied pressure and temperature ranges,(NbZrHfTi)C consistently maintains a stable phase structure and good thermomechanical properties.The thermal expansion coefficient increasing with temperature,while heat capacity approaches the Dulong-Petit limit at elevated temperatures.These findings underscore the potential of(NbZrHfTi)C applications in ultra-high temperature thermal protection systems,cutting tool coatings,and nuclear structural materials.
基金supported by the Natural Science Foundation of Anhui Jianzhu University(Grant No.2023QDZ05)the National Natural Science Foundation of China(Grant Nos.62204127 and 12304453)the Shanxi Province Science Foundation for Youths(Grant No.202503021212220)。
文摘Plasmonic nanolasers are transitioning from empirical optimization to a new paradigm driven by physical mechanisms.Owing to the lack of guidance from internal mechanisms,this transformation process remains highly challenging.Therefore,elucidating the governing nanoscale light–matter interactions has become essential for unlocking their full performance potential.In this paper,we establish a framework that connects the strength of exciton–plasmon interactions with plasmonic nanolaser performance.The evolution of the laser spectrum under increasing pumping fluence,reflected by variations in intensity,spectral peak position,and full width at half maximum,provides clear evidence of exciton–plasmon interactions.These interactions are further verified by changes in the emission lifetime with incident fluence,and it is found that the lifetime variation correlates with the change in spectral full width at half maximum.Furthermore,we calculate and analyze various loss mechanisms in plasmonic nanolasers,revealing how the strength of exciton–plasmon interactions actively modulates optical loss channels and fundamentally controls the lasing threshold.Understanding exciton–plasmon interaction dynamics is not merely a theoretical pursuit but a critical step toward realizing truly practical and scalable nanophotonic devices.
文摘In contemporary China,nationalism under Xi Jinping operates through a dual mechanism that integrates domestic identity engineering with outward-facing narratives of moral leadership.This article argues that the Chinese Communist Party(CCP)’s shift from describing China as a“unified multiethnic state”to promoting a“united community of the Chinese nation”(中华民族共同体)(China Daily,2017)marks a decisive ideological turn that normalizes assimilationist governance and reshapes the cultural and religious life of minority regions.Based on discourse analysis of Xi Jinping’s speeches,official policy documents,and ethnographic fieldwork conducted in Xinjiang in 2024,the study shows how this ideological shift produces a museumized multiculturalism that narrows space for ethnic autonomy and diversity.At the same time,China amplifies a peacebuilding discourse-particularly in its engagement with the Russo-Ukrainian war and conflicts in the Middle East-to present itself as a responsible global actor.The findings reveal three interlocking dynamics:First,cultural homogenization remains central to the Party’s long-term stability strategy;second,China’s civilizational rhetoric resonates most strongly where material partnerships outweigh normative concerns;and third,the contrast between domestic coercion and external reassurance functions not as a contradiction,but as a coherent political pattern.These dynamics show how nationalist ideology,cultural governance,and foreign-policy messaging form an integrated project that expands China’s influence while exposing the limits of its moral legitimacy.
文摘BACKGROUND The persistent burden of cardiovascular(CV)disease in the United States requires innovative and cost-effective prognostic markers that can be relied upon.AIM To provide insights into how adiponectin can predict all-cause mortality and major adverse CV events(MACE)in patients with coronary artery disease(CAD)and to determine the prognostic value of adiponectin in predicting all-cause mortality and MACE in patients with stable CAD.METHODS We conducted a systematic search on PubMed,Scopus,and Google Scholar to find relevant studies published through June 2023 evaluating the long-term prognostic role of adiponectin in patients with stable CAD.Using a random effects model with 95%CI,we estimated the odds ratio(OR)while assessing heterogeneity through I^(2)statistics.To ensure robustness,we performed a sensitivity analysis using the leave-one-out approach.RESULTS After screening,we included five prospective studies involving 3225 patients who were followed up for a median duration of 3.8 years.Within the study population,prevalent risk factors included hypertension,diabetes,hyperlipidemia,and smoking.The commonly prescribed medications were angiotensin-converting enzyme inhibitors,beta blockers,and statins.The combined adjusted OR for all-cause mortality was found to be 2.51(95%CI:1.36–4.62),showing heterogeneity(I^(2)=65.51%,P=0.03).On the other hand,the combined adjusted OR for MACE was determined to be 1.04(95%CI:1.02–1.06)with no significant heterogeneity observed(I^(2)=0%,P=0.68).Through a sensitivity analysis,it was discovered that none of the studies significantly impacted the overall results of the meta-analysis,thus indicating their robustness.CONCLUSION Higher levels of adiponectin were found to be associated with an increased risk of long-term mortality and MACE in patients with CAD,which highlights its potential as a cost-effective marker for risk assessment and guiding treatment strategies.Further research on the role of adiponectin could greatly influence decision-making and resource allocation in CV care.
基金supported by the Higher Education and Science Committee of Armenia in the frames of the research projects 20TTSG-2F010, 23AA-2F033 and ANSEF (EN-matsc-2660) grant.
文摘Halide solid-state electrolytes have gained significant attention in recent years due to their high ionic conductivity,making them promising candidates for future all-solid-state batteries.Recent studies have identified numerous crystal structures with the Li_(3)MX_(6)composition,although many remain unexplored across various chemical systems.In this research,we developed a comprehensive method to examine all conceivable space groups and structures within theLi-M-X system,where M includes In,Ga,and La,and X includes F,Cl,Br,and 1.Our findings revealed two metastable structures:Li_(3)InF_(6)with P3c1 symmetry and Li_(3)InI_(6)with C2/c symmetry,exhibiting ionic conductivities of 0.55 and 2.18mS/cm at 300K,respectively.Notably,the trigonal symmetry of Li3InF6 demonstrates that high ionic conductivities are not limited to monoclinic structures but can also be achieved with trigonal symmetries.The electrochemical stability windows,mechanical properties,and reaction energies of these materials with known cathodes suggest their potential for use in all-solid-state batteries.Additionally,we predicted the stability of novel materials,including Li_(5)InCl_(8),Li_(5)InBr_(8),Li_(5)InI_(8),LiIn_(2)Cl_(9),LiIn_(2)Br_(9),and LiIn_(2)I_(9).
基金supported by the Natural Science Foundation of Heilongjiang Province,No.YQ2021H011(to QL)China Postdoctoral Science Foundation,Nos.2020M670925,2022T150172(to QL)+2 种基金Postdoctoral Foundation of Heilongjiang Province,Nos.LBH‐Z19027,LBH‐TZ2019(to QL)Institute Cultivation Fund,No.PYMS2023-1(to QL)Natural Science Foundation of Jiangsu Province,No.BK20241233(to YL).
文摘Inflammation plays a key role in driving the secondary brain injury that follows ischemic stroke.Melatonin is an endogenous neuroendocrine hormone that regulates mitochondrial homeostasis.However,the role and mechanisms by which melatonin regulates microglial pyroptosis and the inflammatory cascade through double-stranded DNA(dsDNA)-sensing cyclic GMP-AMP synthase(cGAS)signaling warrant further study.Using middle cerebral artery occlusion mice,we investigated the effects of melatonin on cGAS-mediated pyroptosis and neuroinflammation.Middle cerebral artery occlusion model mice exhibited significantly increased DNA damage and cytoplasmic dsDNA release,as reflected byγH2AX staining,as well as heightened activation of the cytosolic dsDNA-sensing cGAS-STING pathway,both of which were notably suppressed by melatonin treatment.Melatonin also mitigated NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome activation and nuclear factor(NF)-κB/gasdermin D-mediated pyroptosis in microglia following ischemic stroke,while exhibiting the capacity to attenuate the immune response to ischemia in mice.This led to reduced infiltration of peripheral neutrophils and monocytes/macrophages in the ischemic brain.Specifically,melatonin administration resulted in reductions in the numbers of ionized calcium-binding adapter molecule 1-positive cells and production of interleukin-6 and tumor necrosis factor-αby microglia.Regarding neurological outcomes,melatonin significantly reduced cerebral infarct volume and ameliorated neurological deficits in mice.Notably,the neuroprotective effect of melatonin was correlated with the inhibition of cGAS activity.We also developed and tested melatonin co-loaded macrophage membrane-biomimetic reactive oxygen species-responsive nanoparticles(Mф-MLT@FNGs),which exhibited therapeutic properties in middle cerebral artery occlusion mice.Our findings suggest that melatonin acts on microglial pyroptosis to inhibit neuroinflammation and reshape the immune microenvironment through regulation of the cGAS-STING-NF-κB signaling pathway.By doing so,melatonin rescues damaged brain tissue and protects neurological function,highlighting its potential as a neuroprotective treatment for ischemic stroke.
基金supported by grants from the Fundamental Research Funds for the Central Universities(No.2025ZFJH03)the Central Guidance Fund for Local Science and Technology Development(No.2024ZY01054)the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-045).
文摘Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through integration of large-scale multi-omics datasets.Methods:We constructed a multi-stage analytical framework encompassing 32 proteomic datasets(covering 2914 unique plasma proteins)and 6 transcriptomic datasets.Multi-omics integration strategies,including two-sample Mendelian randomization,colocalization analysis,and functional enrichment analysis,were employed to identify and validate causal relationships between candidate targets and GCA risk across 4 independent European-ancestry GCA cohorts.Single-cell RNA sequencing analysis of peripheral blood mononuclear cells from untreated GCA patients was performed to characterize hub gene-immune cell relationships.Results:We identified 43 plasma proteins causally associated with GCA[false discovery rate(FDR)<0.05],with 17 representing novel therapeutic targets.Through dual validation using proteome-wide association studies and transcriptome-wide association studies,we identified 13 high-confidence candidate targets with distinct tissue-specific expression patterns.Unc-51 like kinase 3(ULK3)emerged as the strongest protective factor(odds ratio=0.47,95%confidence interval:0.37–0.71)through autophagy regulation,while SLAMF7 represents an immediate drug repositioning opportunity as the target of food and drug administration-approved elotuzumab.Five targets have existing approved drugs(SLAMF7,ICAM1,IL18,IL6ST,CTSS).Single-cell analysis revealed profound disruption of hub gene-immune cell relationships in untreated GCA patients,with cell-type-specific alterations in inflammatory gene expression,and TYMP as the most critical hub gene.Conclusions:This study provides a clinically-actionable atlas of 43 potential therapeutic targets in GCA,identifying novel mechanisms including autophagy modulation and metabolic reprogramming,with immediate drug repositioning opportunities and precision medicine strategies based on tissue-specific and cell-type-specific expression patterns.These findings require experimental validation before clinical translation.
文摘目的:研究长链非编码RNA(lncRNA)生长阻滞特异性转录物5(GAS5)基因多态性与多囊卵巢综合征(PCOS)发病的关联性。方法:选取2018年5月~2019年5月在广西右江民族医学院附属医院生殖医学中心确诊的236例PCOS患者作为病例组,同时选取同期性别、年龄相匹配的277例健康女性作为对照组,采用iMLDR单核苷酸多态性(SNP)分型方法检测GAS5基因rs145204276 I/D、rs55829688 C/T和rs6790 G/A位点基因型。采用logistic回归分析GAS5基因多态性与PCOS的相关性。结果:GAS5基因rs145204276 I/D位点多态性在对照组和PCOS组之间差异有统计学意义,logistic回归分析结果显示,与I/I基因型相比,I/D和D/D基因型以及显性模型I/D+D/D具有较低的PCOS发病风险[I/D vs I/I:OR(95%CI)=0.61(0.42,0.88),P=0.009;D/D vs I/I:OR(95%CI)=0.44(0.23,0.84),P=0.013;I/D+D/D vs I/I:OR(95%CI)=0.57(0.40,0.81),P=0.002];与I等位基因相比,D等位基因显著降低PCOS的发病风险[D vs I:OR(95%CI)=0.62(0.47,0.82),P=0.001]。rs55829688 C/T和rs6790 G/A位点多态性在对照组和PCOS组之间比较差异均无统计学意义(P>0.05)。单倍型联合分析显示D-T-A单倍型在对照组和PCOS组间的分布差异有统计学意义[OR(95%CI)=0.61(0.45,0.84),P=0.002]。结论:GAS5基因rs145204276 I/D位点多态性可能与PCOS遗传易感性相关,即携带D等位基因的个体可能具有较低的PCOS发病风险。
文摘BACKGROUND Postoperative recurrence is common in Crohn’s disease(CD),with endoscopic lesions in a majority of patients by 12 months after surgery.Ileocolonoscopy is the reference standard but is invasive and poorly suited to frequent surveillance.Intestinal ultrasound(IUS)-including small intestine contrast ultrasound and contrast enhanced ultrasound-is a repeatable,noninvasive alternative.AIM To summarize the evidence on the diagnostic accuracy and prognostic value of IUS for detecting postoperative recurrence in CD.METHODS We systematically searched PubMed and EMBASE through June 2025 for original English-language studies evaluating IUS against clinical or endoscopic outcomes in postoperative CD.This scoping review was conducted and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guideline.After screening 259 unique records,41 full texts were assessed and 20 studies were included.RESULTS Bowel wall thickness thresholds of≥5 mm at the neo-terminal ileum predict endoscopic recurrence with sensitivities 81%-94%and specificities 86%-100%;lower cutoffs at the anastomosis(≥3-3.5 mm)also carry risk(data from singlecenter cohorts).Dualsite assessment(neo-terminal ileum+ileocolonic anastomosis)improves performance.Adding Doppler hyperemia or mesenteric lymphadenopathy increases accuracy;combining bowel wall thickness≥3 mm with fecal calprotectin≥50μg/g yields high specificity(approximately 93%-100%)with a negative predictive value of nearly 95%when both are negative.Contrast enhanced ultrasound-based composite scores reach approximately 98%diagnostic accuracy in prospective cohorts.Small intestine contrast ultrasound shows similarly strong early diagnostic performance-for example,an area under the receiver operating characteristic curve up to 0.95 when using ileocolonic anastomosis wall thickness≥3 mm to 3.5 mm plus lesion length,with 82%-94%sensitivity and>90%specificity reported even within 7 days postresection.Overall,IUS shows moderate agreement with endoscopy(κapproximately 0.5-0.8)and stronger prognostic value when performed within 12 months post-surgery.CONCLUSION IUS can be integrated into postoperative surveillance algorithms-particularly within the first year-and can reduce routine endoscopy in selected patients.Research priorities include standardized thresholds and composite scoring,consensus training/competency,and multicenter validation including artificial intelligenceassisted interpretation.
文摘BACKGROUND Spinal cord injury(SCI)imposes enduring physical impairments and substantial socio-economic burdens.These injuries are either traumatic incidents or ischemic but exhibit comparable clinical recoveries.This suggests shared underlying neurodegenerative mechanisms,such as neuronal cell death,demyelination,and axonal degeneration,regardless of aetiology.AIM To investigate the relationship between the magnetic resonance imaging(MRI)biomarkers(tissue bridges)and clinical outcome in acute traumatic SCI.METHODS In this prospective study adult patients with acute SCI who were examined clinically and radiologically within first 48 hours and subsequently at intervals were included.Clinical assessment included sensory score,motor score and zone of partial preservation.Radiological scores included measurement kyphotic deformities-sagittal index,regional kyphosis,gardener segmental kyphotic deformity.MRI on 3 Tesla machine was done to evaluate quantitative&qualitative parameters,and tissue bridges at one and 6 months.RESULTS There were 47 patients with a mean age of 40.43±10.73 years and male/female ratio of 34:13.There was a significant(P<0.05)improvement in clinical,radiological,and MRI parameters at 6 months.Maximum spinal cord compression(MSCC),maximal canal compression,lesion length,width,and area;dorsal tissue bridges;ventral tissue bridges,total width of tissue bridges;and midsagittal tissue bridge ratios at one month significantly(P<0.05)correlated with the 6-month total motor score and total sensory score.Further,the regression analysis demonstrated clinical improvement to dimensions of tissue bridges at 6 months.CONCLUSION The MRI imaging biomarkers in SCI patients demonstrated substantial improvement over time.There was a negative correlation between neurological recovery,MSCC,maximum canal compromise,and lesion dimensions(lesion length,lesion width,and lesion area).Higher canal compromise and lesion dimensions were associated with a poorer outcome.The evaluation of the midsagittal tissue bridge(including the ventral tissue bridge,dorsal tissue bridge,total width of the tissue bridge,and tissue bridge ratios)at 1 and 6 months showed a positive correlation with the neurological recovery.
文摘BACKGROUND Primary percutaneous coronary intervention(PCI)is the preferred treatment for ST-segment elevation myocardial infarction(STEMI).However,in patients with high thrombus burden,immediate stenting during PCI can lead to poor outcomes due to the risk of thrombus migration and subsequent microvascular occlusion,resulting in no-reflow phenomena.Deferred stenting offers a potential advantage by allowing for the reduction of thrombus load,which may help to minimize the incidence of slow-flow and no-reflow complications.This study explores the effectiveness of a deferred stenting strategy in improving outcomes for STEMI patients.AIM To evaluate the effectiveness and safety of deferred PCI in a real-world setting in acute STEMI patients.METHODS RESULTS Anterior wall myocardial infarction was the predominant type of STEMI in 62%of the selected 55 patients(mean age:54 years;70%males),and diabetes mellitus was the most common risk factor(18.2%),followed by hypertension(16.2%).On the second angiogram of these patients measures of thrombus grade,thrombolysis in myocardial infarction flow grade,myocardial blush grade,and severity of stenosis of culprit lesion were consid-erably improved compared to the first angiogram,and the average culprit artery diameter had increased by 7.8%.Most patients(60%)had an uneventful hospital stay during the second angiogram and an uneventful intrapro-cedural course(85.19%),with slow-flow/no-reflow occurring only in 7.4%of the patients;these patients recovered after taking vasodilator drugs.In 29.3%of patients,the culprit artery was recanalized,preventing unnecessary stent deployment.CONCLUSION Deferred PCI strategy is safe and reduces the thrombus burden,improves thrombolysis in myocardial infarction(TIMI)flow,improves myocardial blush grade,and prevents unwarranted stent deployment.
基金supported by the Scientific Research Foundation of Hainan Tropical Ocean University(No.RHDRC202312)the Major Science and Technology Project of Yazhou Bay Innovation Institute of Hainan Tropical Ocean University:Research on Hainan Coastal Marine Ecological Environment and Carbon Sink(No.2022CXYZD002).
文摘Fish scaleδ^(15)N(δ^(15)N_(sca))records trophic information of the whole life history for marine fishes.Data from gut content and values calculated from white muscle tissue(WMT)are insufficient for assessing trophic level(TL)of marine fishes as they only provide the information of several months or even several days.Stable isotope analysis(SIA)of nitrogen was carried out in fish scales and WMT of 16 species from a total of 28 individuals captured from the Yellow Sea and northern East China Sea in October and November of 2019,aiming at discovering the correlation betweenδ^(15)N_(sca) and fish WMTδ^(15)N(δ^(15)NWMT),so as to useδ^(15)N_(sca) for the characterization of TLs of marine fish.Scales were analyzed without prior carbonate dissolution as a pre-processing step.TL calculated fromδ^(15)N_(sca) was compared to traditional TL formula calculated withδ^(15)N_(WMT) to estimate the accuracy.We found that there was a highly significant and positive correlation(r=0.830,P<0.001)betweenδ^(15)N_(sca) andδ^(15)N_(WMT).TL calculation results using fish scale(TL_(sca))and WMT(TL_(WMT))showed congruence(r=0.773,P<0.001),and the regression coefficient betweenδ^(15)N_(sca) andδ^(15)NWMT was used for calculating TLsca.The conversion was conducted for the purpose of comparison with previousδ^(15)N_(WMT)-based calculation results of TL.TLsca calculation results were 81.25%within the TL range of±10%calculated withδ^(15)NWMT.The findings in the present study showed thatδ^(15)N_(sca) is a viable technique for the characterization of the TL of marine fish and can help to predict food web and support the study of marine ecosystem.
基金supported by the National Key Research and Development Program of China(2021YFD2100700)the National Natural Science Foundation of China(32021005)+1 种基金the 111 project(BP0719028)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province.
文摘Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to effectively alleviate VH.In this study,neonatal maternal separation(NMS)was used to induce VH in 72 rats and investigated the effects of daily gavage of 3×10^(9) CFU of Lactobacillus and Bifidobacterium on alleviating the symptoms of IBS-D and behavioral interventions,as well as exploring potential mechanisms.The results demonstrated that L.acidophilus and B.breve could alleviate the symptoms of IBS-D such as VH and increased frequency of bowel movements,as well as improving non-spatial memory in NMS rats.These effects were achieved by modulating the composition of gut microbiota and metabolites(including short-chain fatty acids,deoxycholic acid and adenosine),and by regulating the expression of genes and proteins associated with the NGF/TrkA signaling pathway,tryptophan metabolism,and inflammatory factors in the hippocampus.This finding suggests that L.acidophilus and B.breve have promising potential for the alleviation of IBS.
基金supported through the European Union’s Horizon 2020 Research and Innovation Program(818318)。
文摘Deep phenotyping and genetic characterization of individuals are fundamental to assessing the metabolic status and determining nutrition-specific requirements.This study aimed to ascertain the utmost effectiveness of personalized interventions by aligning dietary adjustments with both the genotype and metabolotype of individuals.Therefore,we assessed here the usefulness of a polygenic score(PGS)characterizing a potential pro-inflammatory profile(PGSi)as a nutrigenetic tool to discern individuals from the Danish PREVENTOMICS cohort that could better respond to precision nutrition(PN)plans,specifically targeted at counteracting the low-grade inflammatory profile typically found in obesity.The cohort followed a PN plan to counteract the pro-inflammatory profile(PNi group)or generic dietary recommendations(Control)for 10 weeks.PGSi was applied for genetic stratification(Low/High).The effects of the intervention on anthropometrics and biomarkers related to inflammatory profile and carbohydrate metabolism were assessed.Around 30%of subjects had a high genetic predisposition to pro-inflammatory status(high-PGSi).These individuals demonstrated the most effective response to the dietary plan,experiencing improved body composition,with significant decreases in body weight(∆:-4.84%;P=0.039)and body fat(∆:-4.86%;P=0.007),and beneficial changes in pro-and anti-inflammatory biomarkers,with significant increases in IL-10(∆:71.3%;P=0.025)and decreases in TNF-α(∆:-3.0%;P=0.048),CRP(∆:-31.1%),ICAM1(∆:-5.8%),and MCP1(∆:-4.2%)circulating levels,compared to low-PGSi individuals.Both phenotypic and genetic stratification contributed to a better understanding of metabolic heterogeneity in response to diet.This approach allows for refinement of the prediction of individual requirements and potentially for better management of obesity.
基金supported in part by the Higher Education Sprout Project,Ministry of Education,to the Headquarters of University Advancement at National Cheng Kung University(NCKU).
文摘Background:While various factors contributing to delinquency have been explored,the role of selfesteem in this specific context has received little attention.Hence,this study aims to investigate the complex issue of adolescent delinquency in Iran by focusing on the mediating role of self-esteem in the relationship between parental attachment and delinquent behavior.Methods:Using the multistage cluster random sampling method,the research involved 528 high school students in Tehran.Each student completed validated scales assessing their parental attachment,self-esteem,and delinquency at school.Multiple regression analyses with the Sobel test and bootstrappingmethod were used to examine mediated effects.Results:Thefindings reveal that self-esteem significantly mediates the relationship betweenmaternal attachment and delinquency(standardized coefficient=−0.0292;p=0.04).Adolescents with secure maternal attachments tend to exhibit higher self-esteem,which reduces the likelihood of delinquent behavior.In contrast,paternal attachment did not show a significant mediating effect in this study.These results underscore the importance of cultivating secure maternal relationships and fostering positive self-esteem to address adolescent delinquency.Conclusion:The study suggests that targeted interventions that strengthen maternal attachment and boost self-esteem could effectively mitigate delinquent behaviors among Iranian adolescents.These interventions should prioritize the emotional support and value of secure maternal bonds as key factors in promoting healthy adolescent development.
基金Supported by Shilpa Medicare Limited,Hyderabad,Telangana,India.
文摘BACKGROUND The norursodeoxycholic acid(norUDCA),a side chain-shortened derivative of ursodeoxycholic acid,exhibits unique pharmacological properties that may benefit patients with metabolic dysfunction-associated steatotic liver disease(MASLD).AIM To evaluate the efficacy,safety,and tolerability of norUDCA 1500 mg compared to placebo in the patients with MASLD.METHODS This phase III,randomized,double-blind,multi-centric,placebo-controlled trial enrolled patients with MASLD,and were randomized in 2:1 ratio to receive either norUDCA 1500 mg or placebo for 24 weeks.Efficacy and safety were rigorously evaluated through clinical,biochemical,and imaging assessments.Primary endpoints assessed alanine aminotransferase(ALT)normalization and improvement in liver stiffness(FibroScan®)at week 12,while secondary endpoints included changes in nonalcoholic fatty liver disease fibrosis score,liver enzymes,lipid profile,glycosylated hemoglobin,and FibroScan-assessed liver stiffness.Safety was monitored throughout the study.RESULTS Of 165 randomized patients,110 received norUDCA and 55 placebos.At week 12,ALT normalization was achieved in 89%of norUDCA-treated group compared to 76%of placebo-treated group(P=0.022);with a statistically significant adjusted mean difference(P=0.016).Fibrosis improvement was observed in 57%of norUDCA-treated vs 40%in placebo-treated(P=0.035),with highly significant adjusted mean(P=0.002).nonalcoholic fatty liver disease fibrosis score at week 18 and 24(P=0.041 and P=0.032).Similarly,ALT reductions were significant at both week 18 and week 24(P=0.021 and P=0.035).Improvements in lipid profile trended towards norUDCA without statistical significance.Liver stiffness has improved in 90 patients in norUDCA-treated vs 36 patients in placebo group(P=0.009).NorUDCA demonstrated favorable safety profile,with no serious adverse events reported,and only mild to moderate adverse events were observed.CONCLUSION NorUDCA 1500 mg demonstrated clinically meaningful therapeutic efficacy in patients with MASLD,accompanied by consistently favorable safety profile.
基金supported by the National Key R&D Program of China(No.2022YFF0800200)the NSFC(Nos.U1812402 and 42072131)+6 种基金Most Special Fund(No.MSFGPMR33)from the State Key Laboratory of GPMRthe CUG Scholar Scientific Research Funds(No.2022036)the NSF of Hebei Province(No.D2021334001)Research Project of Talent Engineering Training of Hebei Province(No.B2020005007)Research Project of Postdoctoral Scientific Research Station of HBGMR(No.454-0602-YBN-Z9E4)Natural Science Foundation of Hebei Province(No.D2021334001)the Central Government Guides Local Funds for Scientific and Technological Development(No.236Z7608 G)。
文摘Original sedimentary manganese(Mn)deposits and supergene Mn ores are important Mn resources in China.However,the geochemical information from Chinese supergene Mn ores is scarce,and the relationship between sedimentary Mn deposits and supergene Mn ores is ambiguous.In this study,we collected the original Mn-bearing dolomitic sandstones(ZK20-3 drillcore)and supergene Mn ores(Longmen Section)from eastern Hebei,North China for systematic petrographic,mineralogical and geochemical analyses.Our new data help us to figure out the transformation from original Mn-bearing deposits to supergene ores.The main minerals of original Mn-bearing dolomitic sandstones are quartz and feldspar,with minor muscovite,dolomite,rhodochrosite,ankerite,and kutnohorite.Supergene Mn-oxide ores only emerged in the middle part of the Longmen(LM)Section,and mainly contain quartz,pyrolusite,cryptomelane,todorokite and occasional dolomite.The possible transformation sequence of Mn minerals is:kutnohorite/rhodochrosite→pyrolusite(Ⅰ)→cryptomelane(todorokite)→todorokite(cryptomelane)→pyrolusite(Ⅱ).For Mn-oxide ores,Fe,Na and Si are enriched but Al,Ca,Mg and K are depleted with the enrichment of Mn.For original and supergene ores,the total rare earth element+ytterbium(∑REY)contents range from 105.68×10^(-6)to 250.56×10^(-6)and from 18.08×10^(-6)to 176.60×10^(-6),respectively.Original Mn ores have similar slightly LREE-enriched patterns,but the purer Mn-oxide ore shows a HREE-enriched pattern.In the middle part of the LM Section,positive Ce anomalies in Mn-oxide ores indicate the precipitation of Ce-bearing minerals.It implies the existence of geochemical barriers,which changed p H and Eh values due to the long-time influence of groundwater.
基金supported by the Natural Science Foundation of Sichuan Province(No.2022NSFSC0720)Research Center for the Development of the Comprehensive Health Industry and Rural Revitalization of Sichuan TCM(No.DJKYB202306)State Administration of Traditional Chinese Medicine of Sichuan Province of China(No.2020HJZX001).
文摘Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxylum bungeanum,which promotes the management of obesity by triggering the browning of white adipose tissue(WAT)targeting the membrane receptor of transient receptor potential vanilloid 1(TRPV1).However,HAS easily undergoes configuration transformation and oxidative degradation.The short peptide CKGGRAKDC or adipose-targeting sequence(ATS)binds specifically to prohibitin on the surface of WAT cells and can be used as recognition assembly to enhance adipocyte targetability.Furthermore,mesoporous silica nanoparticles(MSNs)are widely used in drug delivery systems because of their large specific surface area and pore volume.Therefore,HAS-loaded adipose-targeted MSNs(MSNs-ATS)were developed to enhance the adipocyte targetability,safety,and efficacy of HAS,and tested on mature 3T3-L1 cells and obese mouse models.MSNs-ATS showed higher specificity for adipocyte targetability without obvious toxicity.HAS-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS alone.In conclusion,we successfully developed adipocyte-targeted,HAS-loaded MSNs with good safety and anti-obesity effects.
