The rapid advancement of modern science and technology,coupled with the recent surge in new-energy electric vehicles,has significantly boosted the demand for lithium.This has promoted the development and efficient uti...The rapid advancement of modern science and technology,coupled with the recent surge in new-energy electric vehicles,has significantly boosted the demand for lithium.This has promoted the development and efficient utilization of lepidolite as a lithium source.Therefore,the processes for the flotation of lepidolite have been studied in depth,particularly the development and use of lepidolite flotation collectors and the action mechanism of the collectors on the lepidolite surface.Based on the crystal-structure characteristics of lepidolite minerals,this review focuses on the application of anionic collectors,amine cationic collectors(primary amines,quaternary ammonium salts,ether amines,and Gemini amines),and combined collectors to the flotation behavior of lepidolite as well as the adsorption mechanisms.New directions and technologies for the controllable flotation of lepidolite are proposed,including process improvement,reagent synthesis,and mechanistic research.This analysis demonstrates the need for the further study of the complex environment inside lepidolite and pulp.By using modern analytical detection methods and quantum chemical calculations,research on reagents for the flotation of lepidolite has expanded,providing new concepts and references for the efficient flotation recovery and utilization of lepidolite.展开更多
This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to...This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to both screening and diagnosis.For the clinical adaptation of AI,several challenges remain for its effective translation.The establishment of high-quality clinical databases,such as the National Clinical Database and Japan Endoscopy Database in Japan,which covers almost all cases of esophageal cancer,is essential for validating multimodal AI models.This requires rigorous external validation using diverse datasets,including those from different endoscope manufacturers and image qualities.Furthermore,endoscopists’skills significantly affect diagnostic accuracy,suggesting that AI should serve as a supportive tool rather than a replacement.Addressing these challenges,along with country-specific legal and ethical considerations,will facilitate the successful integration of multimodal AI into the management of esophageal cancer,particularly in endoscopic diagnosis,and contribute to improved patient outcomes.Although this review focused on Japan as a case study,the challenges and solutions described are broadly applicable to other high-incidence regions.展开更多
To establish practical,evidence-based strategies for noninvasive assessment and referral of patients with metabolic dysfunction-associated steatotic liver disease(MASLD)in Japan,we must address the urgent clinical nee...To establish practical,evidence-based strategies for noninvasive assessment and referral of patients with metabolic dysfunction-associated steatotic liver disease(MASLD)in Japan,we must address the urgent clinical need for accurate risk stratification and timely specialist intervention.A panel of 11 Japanese hepatology experts conducted a modified Delphi process to evaluate consensus recommendations regarding the use of noninvasive tests(NITs),including the fibrosis-4 index,enhanced liver fibrosis test,Mac-2-binding protein glycosylation isomer,type IV collagen 7S,cytokeratin-18 fragments,and imaging modalities such as ultrasound elastography and magnetic resonance elastography,for MASLD assessment and clinical referral.Practical algorithms were developed based on current Japanese data and panel consensus.The expert panel validated the utility of NITs as reliable tools for identifying patients with MASLD at risk for advanced fibrosis.Sequential use of NITs improved diagnostic accuracy and referral appropriateness while minimizing unnecessary specialist consultations.The proposed algorithms offer stepwise guidance for primary care physicians,supporting efficient,evidence-based decisionmaking.However,prospective longitudinal studies remain necessary for full prognostic validation of NITs in MASLD management.Noninvasive testing algorithms enable effective risk stratification and referral for MASLD in real-world Japanese practice with anticipated benefit for patient outcomes and healthcare systems.Broader adoption and further validation are warranted.展开更多
Developing effective,versatile,and high-precision sensing interfaces remains a crucial challenge in human-machine-environment interaction applications.Despite progress in interaction-oriented sensing skins,limitations...Developing effective,versatile,and high-precision sensing interfaces remains a crucial challenge in human-machine-environment interaction applications.Despite progress in interaction-oriented sensing skins,limitations remain in unit-level reconfiguration,multiaxial force and motion sensing,and robust operation across dynamically changing or irregular surfaces.Herein,we develop a reconfigurable omnidirectional triboelectric whisker sensor array(RO-TWSA)comprising multiple sensing units that integrate a triboelectric whisker structure(TWS)with an untethered hydro-sealing vacuum sucker(UHSVS),enabling reversibly portable deployment and omnidirectional perception across diverse surfaces.Using a simple dual-triangular electrode layout paired with MXene/silicone nanocomposite dielectric layer,the sensor unit achieves precise omnidirectional force and motion sensing with a detection threshold as low as 0.024 N and an angular resolution of 5°,while the UHSVS provides reliable and reversible multi-surface anchoring for the sensor units by involving a newly designed hydrogel combining high mechanical robustness and superior water absorption.Extensive experiments demonstrate the effectiveness of RO-TWSA across various interactive scenarios,including teleoperation,tactile diagnostics,and robotic autonomous exploration.Overall,RO-TWSA presents a versatile and high-resolution tactile interface,offering new avenues for intelligent perception and interaction in complex real-world environments.展开更多
The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory ...The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers.While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord,the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear.As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input,we investigated in this study the plastic potential of glutamatergic(vGlut2)and GABAergic(vGat)fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus,two nuclei important for locomotor function.Using a combination of viral tracing,chemogenetic silencing,and AI-based kinematic analysis,we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury,a period prone to neuronal remodeling.We demonstrate that,in this time frame,while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury,vGat-positive fibers are rather unresponsive to injury.We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery.Using kinematic analysis,we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery.Overall,our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.展开更多
Traffic at urban intersections frequently encounters unexpected obstructions,resulting in congestion due to uncooperative and priority-based driving behavior.This paper presents an optimal right-turn coordination syst...Traffic at urban intersections frequently encounters unexpected obstructions,resulting in congestion due to uncooperative and priority-based driving behavior.This paper presents an optimal right-turn coordination system for Connected and Automated Vehicles(CAVs)at single-lane intersections,particularly in the context of left-hand side driving on roads.The goal is to facilitate smooth right turns for certain vehicles without creating bottlenecks.We consider that all approaching vehicles share relevant information through vehicular communications.The Intersection Coordination Unit(ICU)processes this information and communicates the optimal crossing or turning times to the vehicles.The primary objective of this coordination is to minimize overall traffic delays,which also helps improve the fuel consumption of vehicles.By considering information from upcoming vehicles at the intersection,the coordination system solves an optimization problem to determine the best timing for executing right turns,ultimately minimizing the total delay for all vehicles.The proposed coordination system is evaluated at a typical urban intersection,and its performance is compared to traditional traffic systems.Numerical simulation results indicate that the proposed coordination system significantly enhances the average traffic speed and fuel consumption compared to the traditional traffic system in various scenarios.展开更多
BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models ...BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models are unclear.AIM To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone(CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury.METHODS Sprague-Dawley(SD)and Wistar rats were grouped into sham,model,and modified groups(n=10 each).The treatments for the modified groups were as follows:SD rats received ovalbumin/aluminum hydroxide suspension+acid perfusion±tail clamping(40 minutes/day for 7 days),while Wistar rats received fructose water+tail clamping.Esophageal pathology,visceral sensitivity,and behavior were assessed.Serum CRH,calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and mast cell tryptase(MCT)and central amygdala(CeA)CRH mRNA were measured via ELISA and qRT-PCR.RESULTS Tail clamping induced anxiety,worsening visceral hypersensitivity(lower abdominal withdrawal reflex thresholds,P<0.05)and esophageal injury(dilated intercellular spaces and mitochondrial edema).Both models showed raised serum CRH,CGRP,5-HT,and MCT(P<0.01)and CeA CRH mRNA expression(P<0.01).Behavioral tests confirmed anxiety-like phenotypes.NERD-anxiety rats showed clinical-like symptom severity without erosion.CONCLUSION Tail clamping induces anxiety in NERD models,worsening visceral hypersensitivity via CRH neuroimmune dysregulation,offering a translational model and highlighting CRH as a treatment target.展开更多
Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified n...Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified novel kinesin light chain 2(KLC2)mutations in CML-myeloid blast phase patients.We aimed to examine the functional role of KLC2 mutations in leukemogenesis.Methods:To evaluate the biological role of KLC2 mutants(MT)in CML cells,we expressed KLC2-MT in different human CML cell lines harboring BCR::ABL1 and performed immunoblot,immunofluorescence,cell proliferation,differentiation,and apoptosis;Tyrosine kinase inhibitor(TKI)-drug activities;and clonogenic assays for in vitro functional analyses.We co-expressed KLC2-MT and BCR::ABL1 in mouse bone marrow cells(BMCs)to evaluate their clonogenic and self-renewal abilities ex vivo.Furthermore,we examined tumorigenic activity and drug efficacy in the K562 xenograft model.Results:KLC2-MT overexpression in BCR::ABL1-positive K562 and KU812 CML cells promoted cell proliferation and clonogenic potential,decreased imatinib sensitivity,and reduced apoptosis.Serial colony replating assays revealed that KLC2-MT and BCR::ABL1 co-expression enhanced the self-renewal ability of mouse BMCs with immature morphology.In the K562 xenograft model,KLC2-MT enhanced tumorigenic potential and diminished imatinib efficacy.Further studies reported that KLC2-MT augmented signal transducer and activator of transcription 3(STAT3)activation and nuclear accumulation in imatinib-treated CML cells.KLC2-WT and KLC2-MT interacted with mothers against decapentaplegic homolog 2(SMAD2);however,the latter impaired transforming growth factor-beta(TGF-β)–mediated SMAD2/3 activation while enhancing STAT3 phosphorylation.Conclusions:This study demonstrates the biological and functional importance of KLC2 mutation in CML cells,potentially enabling the development of better treatment strategies for CML patients carrying KLC2 mutations and providing enhanced understanding of the disease progression.展开更多
Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually wit...Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually with>20%mortality.Its progression involves metabolic imbalances,toxin accumulation,and multiorgan failure,often culminating in chronic kidney disease.Current therapies(fluid resuscitation,diuretics,renal replacement therapy)remain limited.Inflammation drives AKI pathogenesis:renal insults(ischemia,toxins)trigger tubular cell release of pro-inflammatory mediators(TNF-α,IL-1β,IL-6),activating neutrophil gelatinase-associated lipocalin(NGAL)and dysregulating P38 MAPK/ERK pathways.This cascade promotes leukocyte infiltration,oxidative stress,and apoptosis,exacerbating renal damage.Ononin,a flavonoid from Astragali Radix,shows multi-target potential by suppressing pro-inflammatory cytokines,modulating signaling,and mitigating oxidative stress.Its dual anti-inflammatory/antioxidant properties position it as a promising candidate for AKI intervention.Exploring the ameliorative effect of ononin on the inflammatory response Ameliorative effect of ononin on the inflammatory response in doxorubicin-induced AKI mice.Methods:We used network pharmacology to explore ononin’s target molecules and AKI-related disease molecules,identified their intersections,and predicted potential mechanisms via enrichment analysis,followed by molecular docking verification.For in-vivo validation,50 mice were randomly divided into five groups(n=10/group):Control,Model,Ononin-L(15 mg/kg),Ononin-H(60 mg/kg),and Dexamethasone(2.6 mg/kg).An AKI model was established by intravenous tail-vein injection of Doxorubicin(15 mg/kg).Samples were collected 12 h post-induction.We calculated the renal coefficient,examined renal histopathology using hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and Masson’s trichrome(MASSON)staining,and observed mitochondrial morphology by electron microscopy(EM).ELISA was used to measure NGAL,serum creatinine(Scr),and blood urea nitrogen(BUN)levels in serum.Immunofluorescence(IF)evaluated the expression of P-P38,P-ERK,NGAL,and KIM-1 in renal tissues.RT-qPCR assessed the gene expression of pro-inflammatory cytokines,MAPK pathway components,and renal injury markers in kidney tissues.Western Blot(WB)quantified P-P38,P38 MAPK,P-ERK,ERK,NGAL,and KIM-1 in renal tissues.Results:Network pharmacology analysis suggested that ononin could attenuate AKI through its anti-inflammatory properties and regulation of the MAPK signaling pathway.The Model group exhibited a significantly elevated renal coefficient(P<0.05),severe histopathological damage,and mitochondrial dysfunction compared to controls.Serum levels of NGAL,Scr,and BUN were markedly increased(P<0.05),indicating impaired renal function.Enhanced fluorescence signals of P-P38 MAPK,P-ERK,NGAL,and KIM-1 suggested activation of MAPK pathways and renal injury.Upregulation of pro-inflammatory cytokines(IL-1β,IL-6,TNF-α)and MAPK-related genes(P38 MAPK,ERK)alongside injury markers(NGAL,KIM-1)(P<0.05).Increased ratios of phosphorylated-to-total proteins(P-P38/P38,P-ERK/ERK)and elevated NGAL/KIM-1 protein levels confirmed pathway dysregulation.Treatment significantly reduced the renal coefficient(P<0.05),attenuated histological damage,and restored mitochondrial integrity.NGAL,Scr,and BUN levels were lowered,reflecting functional recovery.Diminished fluorescence intensities of P-P38,P-ERK,NGAL,and KIM-1 indicated suppression of injury pathways.Downregulation of inflammatory cytokines(IL-1β,IL-6,TNF-α),MAPK components(P38 MAPK,ERK),and injury markers(NGAL,KIM-1)(P<0.05).Reduced phosphorylation ratios(P-P38/P38,P-ERK/ERK)and decreased NGAL/KIM-1 protein expression demonstrated therapeutic efficacy.Conclusion:Ononin ameliorates inflammatory responses in AKI mice via the P38 MAPK/ERK pathway.展开更多
A trace analytical method based on solid-phase extraction gas chromatography-tandem mass spectrometry(SPE–GC–MS/MS)was developed for the rapid detection of 256 semi-volatile organic compounds(SVOCs),including 25 pol...A trace analytical method based on solid-phase extraction gas chromatography-tandem mass spectrometry(SPE–GC–MS/MS)was developed for the rapid detection of 256 semi-volatile organic compounds(SVOCs),including 25 polycyclic aromatic hydrocarbons(PAHs),70 polychlorinated biphenyls(PCBs),123 pesticides,20 phthalate esters(PAEs),4 organophosphate esters(OPEs),9 synthetic musks(SMs),and 5 UV filters(UVs)in water.No-tably,this method provided a decent linearity of calibration standards(R^(2)>0.999),excellent method limits of quantification(MLOQs)(0.12–11.41 ng/L),satisfactory matrix spiking recovery rates(60.4%–126%),and high precision(intra-day relative standard deviations(RSDs):1.0%–10.0%,inter-day RSDs:3.0%–15.0%,and inter-week RSDs:3.4%–15.7%),making it suitable for trace-level studies.Statistical analysis revealed that SVOCs with higher volatility exhibited enhanced recovery rates.Validation of the methodology involved analyzing SVOCs in real spring water and river water samples.Twenty-seven SVOCs were detected in spring water and 58 in river water,with an average concentration of 631.73 and 16,095 ng/L,respectively.Among the detected SVOCs,PAEs constituted the predominant proportion.This study underscored the presence of SVOCs contamination specifi-cally within the spring water,although SVOCs concentrations in river water were significantly greater than those found in spring water.In summary,this sensitive method based on SPE–GC–MS/MS was successfully developed and validated for the rapid analysis of a diverse array of 256 SVOCs at trace levels in water,including not only the traditional highly valued PAHs,PCBs,pesticides,and PAEs,but also the emerging OPEs,UVs,and SMs.展开更多
Post-kidney transplant rejection is a critical factor influencing transplant success rates and the survival of transplanted organs.With the rapid advancement of artificial intelligence technologies,machine learning(ML...Post-kidney transplant rejection is a critical factor influencing transplant success rates and the survival of transplanted organs.With the rapid advancement of artificial intelligence technologies,machine learning(ML)has emerged as a powerful data analysis tool,widely applied in the prediction,diagnosis,and mechanistic study of kidney transplant rejection.This mini-review systematically summarizes the recent applications of ML techniques in post-kidney transplant rejection,covering areas such as the construction of predictive models,identification of biomarkers,analysis of pathological images,assessment of immune cell infiltration,and formulation of personalized treatment strategies.By integrating multi-omics data and clinical information,ML has significantly enhanced the accuracy of early rejection diagnosis and the capability for prognostic evaluation,driving the development of precision medicine in the field of kidney transplantation.Furthermore,this article discusses the challenges faced in existing research and potential future directions,providing a theoretical basis and technical references for related studies.展开更多
TiB_(2)coatings can significantly enhance the high-temperature oxidation resistance of molybdenum,which would broaden the application range of molybdenum and alloys thereof.However,traditional methods for preparing Ti...TiB_(2)coatings can significantly enhance the high-temperature oxidation resistance of molybdenum,which would broaden the application range of molybdenum and alloys thereof.However,traditional methods for preparing TiB_(2)coatings have disadvantages such as high equipment costs,complicated processes,and highly toxic gas emissions.This paper proposes an environmentally friendly method,which requires inexpensive equipment and simple processing,for preparing TiB_(2)coating on molybdenum via electrophoretic deposition within Na3AlF6-based molten salts.The produced TiB_(2)layer had an approximate thickness of 60μm and exhibited high density,outstanding hardness(38.2 GPa)and robust adhesion strength(51 N).Additionally,high-temperature oxidation experiments revealed that,at900℃,the TiB_(2)coating provided effective protection to the molybdenum substrate against oxidation for 3 h.This result indicates that the TiB_(2)coating prepared on molybdenum using molten salt electrophoretic deposition possesses good high-temperature oxidation resistance.展开更多
Hepatocellular carcinoma(HCC)remains one of the most prevalent and lethal malignancies worldwide.Long non-coding RNAs(lncRNAs)have emerged as crucial regulators of gene expression and cancer progression,yet the functi...Hepatocellular carcinoma(HCC)remains one of the most prevalent and lethal malignancies worldwide.Long non-coding RNAs(lncRNAs)have emerged as crucial regulators of gene expression and cancer progression,yet the functional diversity of RP11-derived lncRNAs—originally mapped to bacterial artificial chromosome(BAC)clones from the Roswell Park Cancer Institute—has only recently begun to be appreciated.This mini-review aims to systematically synthesize current findings on RP11-derived lncRNAs in HCC,outlining their genomic origins,molecular mechanisms,and biological significance.We highlight their roles in metabolic reprogramming,microRNA network modulation,and tumor progression,as well as their diagnostic and prognostic value in tissue and serum-based analyses.Finally,we discuss therapeutic opportunities and propose future directions to translate RP11-derived lncRNAs into clinically actionable biomarkers and targets for precision liver cancer therapy.展开更多
The intracontinental subduction of a>200-km-long section of the Tajik-Tarim lithosphere beneath the Pamir Mountains is proposed to explain nearly 30 km of shortening in the Tajik fold-thrust belt and the Pamir upli...The intracontinental subduction of a>200-km-long section of the Tajik-Tarim lithosphere beneath the Pamir Mountains is proposed to explain nearly 30 km of shortening in the Tajik fold-thrust belt and the Pamir uplift.Seismic imaging revealed that the upper slab was scraped and that the lower slab had subducted to a depth of>150 km.These features constitute the tectonic complexity of the Pamirs,as well as the thermal subduction mechanism involved,which remains poorly understood.Hence,in this study,high-resolution three-dimensional(3D)kinematic modeling is applied to investigate the thermal structure and geometry of the subducting slab beneath the Pamirs.The modeled slab configuration reveals distinct along-strike variations,with a steeply dipping slab beneath the southern Pamirs,a more gently inclined slab beneath the northern Pamirs,and apparent upper slab termination at shallow depths beneath the Pamirs.The thermal field reveals a cold slab core after delamination,with temperatures ranging from 400℃to 800℃,enveloped by a hotter mantle reaching~1400℃.The occurrence of intermediate-depth earthquakes aligns primarily with colder slab regions,particularly near the slab tear-off below the southwestern Pamirs,indicating a strong correlation between slab temperature and seismicity.In contrast,the northern Pamirs exhibit reduced seismicity at depth,which is likely associated with thermal weakening and delamination.The central Pamirs show a significant thermal anomaly caused by a concave slab,where the coldest crust does not descend deeply,further suggesting crustal detachment or mechanical failure.The lateral asymmetry in slab temperature possibly explains the mechanism of lateral tearing and differential slab-mantle coupling.展开更多
Aging is a complex biological process characterized by nine hallmarks,including genomic instability,mitochondrial dysfunction,and chronic inflammation,which collectively drive the progression of age-related chronic no...Aging is a complex biological process characterized by nine hallmarks,including genomic instability,mitochondrial dysfunction,and chronic inflammation,which collectively drive the progression of age-related chronic non-communicable diseases.Phytonutrients,a class of bioactive secondary metabolites abundant in plants,have emerged as a promising research focus for intervening in the aging process due to their multifaceted biological activities.This review systematically elaborates on the molecular mechanisms,key signaling pathways,specifically SIRT1,Nrf2/ARE,and AMPK/mTOR,and the synergistic anti-aging effects of four typical phytonutrient categories:polyphenols(e.g.,resveratrol,quercetin),carotenoids(e.g.,lycopene,astaxanthin),sulfur compounds(e.g.,α-lipoic acid,ergothioneine),and phytoestrogens(e.g.,soybean isoflavones).The evidence indicates that these compounds combat aging through a multidimensional network involving direct antioxidant actions,free radical scavenging,metal chelation,promotion of autophagy,and modulation of inflammatory and epigenetic pathways.Crucially,the review highlights that synergistic interactions between different phytonutrients can significantly enhance their efficacy beyond the effect of any single compound.The aim is to consolidate the anti-aging evidence of phytonutrients and address the current translational challenges,such as bioavailability and a lack of robust human trials,thereby providing a comprehensive theoretical framework for developing effective,diet-centered strategies to promote healthy aging and reduce the global burden of non-communicable diseases.展开更多
Heart disease remains a leading cause of mortality worldwide,emphasizing the urgent need for reliable and interpretable predictive models to support early diagnosis and timely intervention.However,existing Deep Learni...Heart disease remains a leading cause of mortality worldwide,emphasizing the urgent need for reliable and interpretable predictive models to support early diagnosis and timely intervention.However,existing Deep Learning(DL)approaches often face several limitations,including inefficient feature extraction,class imbalance,suboptimal classification performance,and limited interpretability,which collectively hinder their deployment in clinical settings.To address these challenges,we propose a novel DL framework for heart disease prediction that integrates a comprehensive preprocessing pipeline with an advanced classification architecture.The preprocessing stage involves label encoding and feature scaling.To address the issue of class imbalance inherent in the personal key indicators of the heart disease dataset,the localized random affine shadowsampling technique is employed,which enhances minority class representation while minimizing overfitting.At the core of the framework lies the Deep Residual Network(DeepResNet),which employs hierarchical residual transformations to facilitate efficient feature extraction and capture complex,non-linear relationships in the data.Experimental results demonstrate that the proposed model significantly outperforms existing techniques,achieving improvements of 3.26%in accuracy,3.16%in area under the receiver operating characteristics,1.09%in recall,and 1.07%in F1-score.Furthermore,robustness is validated using 10-fold crossvalidation,confirming the model’s generalizability across diverse data distributions.Moreover,model interpretability is ensured through the integration of Shapley additive explanations and local interpretable model-agnostic explanations,offering valuable insights into the contribution of individual features to model predictions.Overall,the proposed DL framework presents a robust,interpretable,and clinically applicable solution for heart disease prediction.展开更多
The effect of plasma and charged particle interaction with spacecraft in a low Earth orbit(LEO)environment leads to ion focusing and the formation of an ion void in the downstream region as a result of charging.Simula...The effect of plasma and charged particle interaction with spacecraft in a low Earth orbit(LEO)environment leads to ion focusing and the formation of an ion void in the downstream region as a result of charging.Simulations and investigations using a fixed potential imposed on the spacecraft showed the nonsignificance of geophysical parameter changes to ion focusing.Variation of the temperature ratio(T_(r))contributed only to local ion focusing and manifested as two-ion streamers dispersed at the upper and lower edges of the spacecraft-the outermost layers of the satellite structure at the top and bottom,respectively.A simulation involving changing the ambient plasma density(N_(p))also showed the formation of local ion focusing,in which ions were more concentrated as the density increased.Furthermore,auroral electron density(N_(ae))variation had no clear impact on ion focusing,as indicated by static two-ion structures in the wake field.However,variation of the object potential(ϕ)strongly affected ion focusing formation,leading to distortion of the initial ion void region behind the spacecraft.The formation of ion focusing in this study was subject to the electric field produced by the object potential and the ambipolar electric field resulting from plasma expansion in the downstream region.展开更多
Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival a...Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.展开更多
The purpose of this perspective is to discuss the future development of a potential treatment of glial pathology in Alzheimer's disease(AD) and a new regulatory mechanism, nuclear lipids, which may be involved in ...The purpose of this perspective is to discuss the future development of a potential treatment of glial pathology in Alzheimer's disease(AD) and a new regulatory mechanism, nuclear lipids, which may be involved in the pathogenesis of the disease, based on the work of the authors(Takasugi et al., 2011;Komai et al., 2024).展开更多
BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,...BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,has been shown to significantly improve clinical symptoms in patients with CAG,as demonstrated by a multicenter cohort study(overall effective rate:82.5%,P<0.01).However,the unclear molecular mechanisms and therapeutic targets of AWD limit its international acceptance.AIM To investigate the therapeutic mechanisms of AWD against CAG from an integrated perspective.METHODS In this study,N-methyl-N’-nitro-N-nitrosoguanidine was used to establish a CAG rat model.Serum-derived constituents transferred from AWD were first identified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry.The concentrations of inflammatory cytokines in serum samples were determined by enzyme-linked immunosorbent assay.Moreover,gastric mucosal tissues were analyzed by quantitative realtime polymerase chain reaction to measure messenger RNA(mRNA)levels of the NLRP3 inflammasome.Western blotting was used to detect the protein expression of NLRP3,caspase-1,and interleukin(IL)-1β.To elucidate the regulatory mechanisms underlying AWD treatment,structural alterations of the gut microbiota(GM)and associated metabolites were analyzed using integrated high-throughput sequencing(16S rRNA)and liquid chromatography-mass spectrometry based untargeted metabolomics.This comprehensive approach systematically clarified AWD’s multi-target therapeutic mechanisms against CAG.RESULTS AWD notably reduced serum levels of pro-inflammatory cytokines,such as IL-1β,IL-18,tumor necrosis factor-α,and lipopolysaccharide,demonstrating significant statistical differences(all P<0.01).Additionally,AWD substantially inhibited NLRP3 mRNA expression in gastric mucosal tissue(P<0.01)and concurrently decreased the protein abundance of NLRP3,IL-1β,and caspase-1(all P<0.01),thereby suppressing inflammasome signaling activation.GM analysis indicated that AWD intervention significantly increased the relative abundance of beneficial bacteria.Associated microbial metabolites likely inhibited the NLRP3 inflammasome pathway by modulating immune cell function.Non-targeted metabolomics further indicated that AWD exerted anti-inflammatory effects by regulating critical metabolic pathways,including the Kaposi’s sarcoma-associated herpesvirus infection pathway,autophagy processes,and glycosylphosphatidylinositol-anchor biosynthesis.CONCLUSION AWD alleviates the pathological progression of CAG through multi-target synergistic mechanisms.On one hand,AWD directly suppresses gastric mucosal inflammation by inhibiting NLRP3 inflammasome activation.On the other hand,AWD remodels intestinal microbiota-metabolite homeostasis,enhances intestinal barrier function,and regulates mucosal immune responses.展开更多
基金financially supported by the Excellent Youth Scholars Program of State Key Laboratory of Complex Nonferrous Metal Resource Clean Utilization,Kunming University of Science and Technology,China(No.YXQN-2024003)the Central Government-Guided Local Science and Technology Development Fund Project,China(No.202407AB110022)。
文摘The rapid advancement of modern science and technology,coupled with the recent surge in new-energy electric vehicles,has significantly boosted the demand for lithium.This has promoted the development and efficient utilization of lepidolite as a lithium source.Therefore,the processes for the flotation of lepidolite have been studied in depth,particularly the development and use of lepidolite flotation collectors and the action mechanism of the collectors on the lepidolite surface.Based on the crystal-structure characteristics of lepidolite minerals,this review focuses on the application of anionic collectors,amine cationic collectors(primary amines,quaternary ammonium salts,ether amines,and Gemini amines),and combined collectors to the flotation behavior of lepidolite as well as the adsorption mechanisms.New directions and technologies for the controllable flotation of lepidolite are proposed,including process improvement,reagent synthesis,and mechanistic research.This analysis demonstrates the need for the further study of the complex environment inside lepidolite and pulp.By using modern analytical detection methods and quantum chemical calculations,research on reagents for the flotation of lepidolite has expanded,providing new concepts and references for the efficient flotation recovery and utilization of lepidolite.
基金Supported by Japan Society for the Promotion of Science,No.24K11935.
文摘This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to both screening and diagnosis.For the clinical adaptation of AI,several challenges remain for its effective translation.The establishment of high-quality clinical databases,such as the National Clinical Database and Japan Endoscopy Database in Japan,which covers almost all cases of esophageal cancer,is essential for validating multimodal AI models.This requires rigorous external validation using diverse datasets,including those from different endoscope manufacturers and image qualities.Furthermore,endoscopists’skills significantly affect diagnostic accuracy,suggesting that AI should serve as a supportive tool rather than a replacement.Addressing these challenges,along with country-specific legal and ethical considerations,will facilitate the successful integration of multimodal AI into the management of esophageal cancer,particularly in endoscopic diagnosis,and contribute to improved patient outcomes.Although this review focused on Japan as a case study,the challenges and solutions described are broadly applicable to other high-incidence regions.
基金Supported by Japan Society for the Promotion of Science KAKENHI,No.25K11274.
文摘To establish practical,evidence-based strategies for noninvasive assessment and referral of patients with metabolic dysfunction-associated steatotic liver disease(MASLD)in Japan,we must address the urgent clinical need for accurate risk stratification and timely specialist intervention.A panel of 11 Japanese hepatology experts conducted a modified Delphi process to evaluate consensus recommendations regarding the use of noninvasive tests(NITs),including the fibrosis-4 index,enhanced liver fibrosis test,Mac-2-binding protein glycosylation isomer,type IV collagen 7S,cytokeratin-18 fragments,and imaging modalities such as ultrasound elastography and magnetic resonance elastography,for MASLD assessment and clinical referral.Practical algorithms were developed based on current Japanese data and panel consensus.The expert panel validated the utility of NITs as reliable tools for identifying patients with MASLD at risk for advanced fibrosis.Sequential use of NITs improved diagnostic accuracy and referral appropriateness while minimizing unnecessary specialist consultations.The proposed algorithms offer stepwise guidance for primary care physicians,supporting efficient,evidence-based decisionmaking.However,prospective longitudinal studies remain necessary for full prognostic validation of NITs in MASLD management.Noninvasive testing algorithms enable effective risk stratification and referral for MASLD in real-world Japanese practice with anticipated benefit for patient outcomes and healthcare systems.Broader adoption and further validation are warranted.
基金supported by the National Natural Science Foundation of China(General Program)under Grant 52571385National Key R&D Program of China(Grant No.2024YFC2815000 and No.2024YFB3816000)+12 种基金Open Fund of State Key Laboratory of Deep-sea Manned Vehicles(Grant No.2025SKLDMV07)Shenzhen Science and Technology Program(WDZC20231128114452001,JCYJ20240813112107010 and JCYJ20240813111910014)the Tsinghua SIGS Scientific Research Startup Fund(QD2022021C)the Dreams Foundation of Jianghuai Advance Technology Center(2023-ZM 01 Z006)the Ocean Decade International Cooperation Center(ODCC)(GHZZ3702840002024020000026)Shenzhen Key Laboratory of Advanced Technology for Marine Ecology(ZDSYS20230626091459009)Shenzhen Science and Technology Program(No.KJZD20240903100905008)the National Natural Science Foundation of China(No.22305141)Pearl River Talent Program(No.2023QN10C114)General Program of Guangdong Province(No.2025A1515011700)the Guangdong Innovative and Entrepreneurial Research Team Program(2023ZT10C040)Scientific Research Foundation from Shenzhen Finance Bureau(No.GJHZ20240218113600002)Tsinghua University(JC2023001).
文摘Developing effective,versatile,and high-precision sensing interfaces remains a crucial challenge in human-machine-environment interaction applications.Despite progress in interaction-oriented sensing skins,limitations remain in unit-level reconfiguration,multiaxial force and motion sensing,and robust operation across dynamically changing or irregular surfaces.Herein,we develop a reconfigurable omnidirectional triboelectric whisker sensor array(RO-TWSA)comprising multiple sensing units that integrate a triboelectric whisker structure(TWS)with an untethered hydro-sealing vacuum sucker(UHSVS),enabling reversibly portable deployment and omnidirectional perception across diverse surfaces.Using a simple dual-triangular electrode layout paired with MXene/silicone nanocomposite dielectric layer,the sensor unit achieves precise omnidirectional force and motion sensing with a detection threshold as low as 0.024 N and an angular resolution of 5°,while the UHSVS provides reliable and reversible multi-surface anchoring for the sensor units by involving a newly designed hydrogel combining high mechanical robustness and superior water absorption.Extensive experiments demonstrate the effectiveness of RO-TWSA across various interactive scenarios,including teleoperation,tactile diagnostics,and robotic autonomous exploration.Overall,RO-TWSA presents a versatile and high-resolution tactile interface,offering new avenues for intelligent perception and interaction in complex real-world environments.
基金supported by the Deutsche Forschungsgemeinschaft(DFG),TRR274(Project ID 408885537,Sy Nergy,EXC 2145/ID 390857198,to FMB)。
文摘The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers.While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord,the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear.As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input,we investigated in this study the plastic potential of glutamatergic(vGlut2)and GABAergic(vGat)fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus,two nuclei important for locomotor function.Using a combination of viral tracing,chemogenetic silencing,and AI-based kinematic analysis,we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury,a period prone to neuronal remodeling.We demonstrate that,in this time frame,while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury,vGat-positive fibers are rather unresponsive to injury.We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery.Using kinematic analysis,we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery.Overall,our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.
基金supported by the Japan Society for the Promotion of Science(JSPS)Grants-in-Aid for Scientific Research(C)23K03898.
文摘Traffic at urban intersections frequently encounters unexpected obstructions,resulting in congestion due to uncooperative and priority-based driving behavior.This paper presents an optimal right-turn coordination system for Connected and Automated Vehicles(CAVs)at single-lane intersections,particularly in the context of left-hand side driving on roads.The goal is to facilitate smooth right turns for certain vehicles without creating bottlenecks.We consider that all approaching vehicles share relevant information through vehicular communications.The Intersection Coordination Unit(ICU)processes this information and communicates the optimal crossing or turning times to the vehicles.The primary objective of this coordination is to minimize overall traffic delays,which also helps improve the fuel consumption of vehicles.By considering information from upcoming vehicles at the intersection,the coordination system solves an optimization problem to determine the best timing for executing right turns,ultimately minimizing the total delay for all vehicles.The proposed coordination system is evaluated at a typical urban intersection,and its performance is compared to traditional traffic systems.Numerical simulation results indicate that the proposed coordination system significantly enhances the average traffic speed and fuel consumption compared to the traditional traffic system in various scenarios.
基金Supported by the National Key Specialty of Traditional Chinese Medicine(Spleen and Stomach Diseases),No.0500004National Natural Science Foundation of China,No.82205104 and No.82104850+1 种基金Hospital Capability Enhancement Project of Xiyuan Hospital,CACMS,No.XYZX0303-07the Fundamental Research Funds for the Central Public Welfare Research Institutes,Excellent Young Scientists Training Program of China Academy of Chinese Medical Sciences,No.ZZ16-YQ-002.
文摘BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models are unclear.AIM To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone(CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury.METHODS Sprague-Dawley(SD)and Wistar rats were grouped into sham,model,and modified groups(n=10 each).The treatments for the modified groups were as follows:SD rats received ovalbumin/aluminum hydroxide suspension+acid perfusion±tail clamping(40 minutes/day for 7 days),while Wistar rats received fructose water+tail clamping.Esophageal pathology,visceral sensitivity,and behavior were assessed.Serum CRH,calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and mast cell tryptase(MCT)and central amygdala(CeA)CRH mRNA were measured via ELISA and qRT-PCR.RESULTS Tail clamping induced anxiety,worsening visceral hypersensitivity(lower abdominal withdrawal reflex thresholds,P<0.05)and esophageal injury(dilated intercellular spaces and mitochondrial edema).Both models showed raised serum CRH,CGRP,5-HT,and MCT(P<0.01)and CeA CRH mRNA expression(P<0.01).Behavioral tests confirmed anxiety-like phenotypes.NERD-anxiety rats showed clinical-like symptom severity without erosion.CONCLUSION Tail clamping induces anxiety in NERD models,worsening visceral hypersensitivity via CRH neuroimmune dysregulation,offering a translational model and highlighting CRH as a treatment target.
基金supported by grants from the Ministry of Science and Technology,Taiwan(MOST108-2314-B-182-006,MOST109-2314-B-182-071:Lee-Yung Shih)the Ministry of Health and Welfare,Taiwan(MOHW110-TDU-B-212-134011:Lee-Yung Shih)+3 种基金Chang Gung Memorial Hospital(CMRPG3D1524,OMRPG3E0031:Lee-Yung Shih)the Grant-in-Aid for the Japan Society for the Promotion of Science(JSPS)KAKENHI(JP19H05656:Seishi Ogawa,22K16320:Yotaro Ochi)the Japan Agency for Medical Research and Development(AMED)(JP19cm0106501h0004,JP19ck0106250h0003:Seishi Ogawa)the Ministry of Education,Culture,Sports,Science and Technology of Japan(MEXT)(hp200138,hp210167:Seishi Ogawa)。
文摘Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified novel kinesin light chain 2(KLC2)mutations in CML-myeloid blast phase patients.We aimed to examine the functional role of KLC2 mutations in leukemogenesis.Methods:To evaluate the biological role of KLC2 mutants(MT)in CML cells,we expressed KLC2-MT in different human CML cell lines harboring BCR::ABL1 and performed immunoblot,immunofluorescence,cell proliferation,differentiation,and apoptosis;Tyrosine kinase inhibitor(TKI)-drug activities;and clonogenic assays for in vitro functional analyses.We co-expressed KLC2-MT and BCR::ABL1 in mouse bone marrow cells(BMCs)to evaluate their clonogenic and self-renewal abilities ex vivo.Furthermore,we examined tumorigenic activity and drug efficacy in the K562 xenograft model.Results:KLC2-MT overexpression in BCR::ABL1-positive K562 and KU812 CML cells promoted cell proliferation and clonogenic potential,decreased imatinib sensitivity,and reduced apoptosis.Serial colony replating assays revealed that KLC2-MT and BCR::ABL1 co-expression enhanced the self-renewal ability of mouse BMCs with immature morphology.In the K562 xenograft model,KLC2-MT enhanced tumorigenic potential and diminished imatinib efficacy.Further studies reported that KLC2-MT augmented signal transducer and activator of transcription 3(STAT3)activation and nuclear accumulation in imatinib-treated CML cells.KLC2-WT and KLC2-MT interacted with mothers against decapentaplegic homolog 2(SMAD2);however,the latter impaired transforming growth factor-beta(TGF-β)–mediated SMAD2/3 activation while enhancing STAT3 phosphorylation.Conclusions:This study demonstrates the biological and functional importance of KLC2 mutation in CML cells,potentially enabling the development of better treatment strategies for CML patients carrying KLC2 mutations and providing enhanced understanding of the disease progression.
基金supported by Hebei Province Natural Science Foundation(H2023423037)The Government Funded Clinical Program of Hebei Province(No.ZF2025287)+1 种基金Special Project of Hebei Industrial Technology Institute for Traditional Chinese Medicine Preparation(No.YJY2024001)Chinese Medicine Scientific Research Program of Hebei Province(No.2025222).
文摘Background:Acute kidney injury(AKI),characterized by rapid renal dysfunction(KDIGO 2022 criteria:48-hour doubling of serum creatinine or<0.5 mL/kg/h urine output for>6 h),affects 13.3 million people annually with>20%mortality.Its progression involves metabolic imbalances,toxin accumulation,and multiorgan failure,often culminating in chronic kidney disease.Current therapies(fluid resuscitation,diuretics,renal replacement therapy)remain limited.Inflammation drives AKI pathogenesis:renal insults(ischemia,toxins)trigger tubular cell release of pro-inflammatory mediators(TNF-α,IL-1β,IL-6),activating neutrophil gelatinase-associated lipocalin(NGAL)and dysregulating P38 MAPK/ERK pathways.This cascade promotes leukocyte infiltration,oxidative stress,and apoptosis,exacerbating renal damage.Ononin,a flavonoid from Astragali Radix,shows multi-target potential by suppressing pro-inflammatory cytokines,modulating signaling,and mitigating oxidative stress.Its dual anti-inflammatory/antioxidant properties position it as a promising candidate for AKI intervention.Exploring the ameliorative effect of ononin on the inflammatory response Ameliorative effect of ononin on the inflammatory response in doxorubicin-induced AKI mice.Methods:We used network pharmacology to explore ononin’s target molecules and AKI-related disease molecules,identified their intersections,and predicted potential mechanisms via enrichment analysis,followed by molecular docking verification.For in-vivo validation,50 mice were randomly divided into five groups(n=10/group):Control,Model,Ononin-L(15 mg/kg),Ononin-H(60 mg/kg),and Dexamethasone(2.6 mg/kg).An AKI model was established by intravenous tail-vein injection of Doxorubicin(15 mg/kg).Samples were collected 12 h post-induction.We calculated the renal coefficient,examined renal histopathology using hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and Masson’s trichrome(MASSON)staining,and observed mitochondrial morphology by electron microscopy(EM).ELISA was used to measure NGAL,serum creatinine(Scr),and blood urea nitrogen(BUN)levels in serum.Immunofluorescence(IF)evaluated the expression of P-P38,P-ERK,NGAL,and KIM-1 in renal tissues.RT-qPCR assessed the gene expression of pro-inflammatory cytokines,MAPK pathway components,and renal injury markers in kidney tissues.Western Blot(WB)quantified P-P38,P38 MAPK,P-ERK,ERK,NGAL,and KIM-1 in renal tissues.Results:Network pharmacology analysis suggested that ononin could attenuate AKI through its anti-inflammatory properties and regulation of the MAPK signaling pathway.The Model group exhibited a significantly elevated renal coefficient(P<0.05),severe histopathological damage,and mitochondrial dysfunction compared to controls.Serum levels of NGAL,Scr,and BUN were markedly increased(P<0.05),indicating impaired renal function.Enhanced fluorescence signals of P-P38 MAPK,P-ERK,NGAL,and KIM-1 suggested activation of MAPK pathways and renal injury.Upregulation of pro-inflammatory cytokines(IL-1β,IL-6,TNF-α)and MAPK-related genes(P38 MAPK,ERK)alongside injury markers(NGAL,KIM-1)(P<0.05).Increased ratios of phosphorylated-to-total proteins(P-P38/P38,P-ERK/ERK)and elevated NGAL/KIM-1 protein levels confirmed pathway dysregulation.Treatment significantly reduced the renal coefficient(P<0.05),attenuated histological damage,and restored mitochondrial integrity.NGAL,Scr,and BUN levels were lowered,reflecting functional recovery.Diminished fluorescence intensities of P-P38,P-ERK,NGAL,and KIM-1 indicated suppression of injury pathways.Downregulation of inflammatory cytokines(IL-1β,IL-6,TNF-α),MAPK components(P38 MAPK,ERK),and injury markers(NGAL,KIM-1)(P<0.05).Reduced phosphorylation ratios(P-P38/P38,P-ERK/ERK)and decreased NGAL/KIM-1 protein expression demonstrated therapeutic efficacy.Conclusion:Ononin ameliorates inflammatory responses in AKI mice via the P38 MAPK/ERK pathway.
基金supported by the National Natural Science Foundation of China(No.51939009)Shenzhen Science and Technology Program(Nos.JCYJ20241202125905008 and GXWD20201231165807007-20200810165349001).
文摘A trace analytical method based on solid-phase extraction gas chromatography-tandem mass spectrometry(SPE–GC–MS/MS)was developed for the rapid detection of 256 semi-volatile organic compounds(SVOCs),including 25 polycyclic aromatic hydrocarbons(PAHs),70 polychlorinated biphenyls(PCBs),123 pesticides,20 phthalate esters(PAEs),4 organophosphate esters(OPEs),9 synthetic musks(SMs),and 5 UV filters(UVs)in water.No-tably,this method provided a decent linearity of calibration standards(R^(2)>0.999),excellent method limits of quantification(MLOQs)(0.12–11.41 ng/L),satisfactory matrix spiking recovery rates(60.4%–126%),and high precision(intra-day relative standard deviations(RSDs):1.0%–10.0%,inter-day RSDs:3.0%–15.0%,and inter-week RSDs:3.4%–15.7%),making it suitable for trace-level studies.Statistical analysis revealed that SVOCs with higher volatility exhibited enhanced recovery rates.Validation of the methodology involved analyzing SVOCs in real spring water and river water samples.Twenty-seven SVOCs were detected in spring water and 58 in river water,with an average concentration of 631.73 and 16,095 ng/L,respectively.Among the detected SVOCs,PAEs constituted the predominant proportion.This study underscored the presence of SVOCs contamination specifi-cally within the spring water,although SVOCs concentrations in river water were significantly greater than those found in spring water.In summary,this sensitive method based on SPE–GC–MS/MS was successfully developed and validated for the rapid analysis of a diverse array of 256 SVOCs at trace levels in water,including not only the traditional highly valued PAHs,PCBs,pesticides,and PAEs,but also the emerging OPEs,UVs,and SMs.
文摘Post-kidney transplant rejection is a critical factor influencing transplant success rates and the survival of transplanted organs.With the rapid advancement of artificial intelligence technologies,machine learning(ML)has emerged as a powerful data analysis tool,widely applied in the prediction,diagnosis,and mechanistic study of kidney transplant rejection.This mini-review systematically summarizes the recent applications of ML techniques in post-kidney transplant rejection,covering areas such as the construction of predictive models,identification of biomarkers,analysis of pathological images,assessment of immune cell infiltration,and formulation of personalized treatment strategies.By integrating multi-omics data and clinical information,ML has significantly enhanced the accuracy of early rejection diagnosis and the capability for prognostic evaluation,driving the development of precision medicine in the field of kidney transplantation.Furthermore,this article discusses the challenges faced in existing research and potential future directions,providing a theoretical basis and technical references for related studies.
基金supported by the Original Exploratory Program of the National Natural Science Foundation of China(No.52450012)。
文摘TiB_(2)coatings can significantly enhance the high-temperature oxidation resistance of molybdenum,which would broaden the application range of molybdenum and alloys thereof.However,traditional methods for preparing TiB_(2)coatings have disadvantages such as high equipment costs,complicated processes,and highly toxic gas emissions.This paper proposes an environmentally friendly method,which requires inexpensive equipment and simple processing,for preparing TiB_(2)coating on molybdenum via electrophoretic deposition within Na3AlF6-based molten salts.The produced TiB_(2)layer had an approximate thickness of 60μm and exhibited high density,outstanding hardness(38.2 GPa)and robust adhesion strength(51 N).Additionally,high-temperature oxidation experiments revealed that,at900℃,the TiB_(2)coating provided effective protection to the molybdenum substrate against oxidation for 3 h.This result indicates that the TiB_(2)coating prepared on molybdenum using molten salt electrophoretic deposition possesses good high-temperature oxidation resistance.
基金supported by the National Research Foundation of Korea(NRF),funded by the Ministry of Science and ICT(MSIT),Republic of Korea(grant numbers:RS-2022-NR070489 and RS-2023-00210847)the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health and Welfare,Republic of Korea(grant number HR21C1003).
文摘Hepatocellular carcinoma(HCC)remains one of the most prevalent and lethal malignancies worldwide.Long non-coding RNAs(lncRNAs)have emerged as crucial regulators of gene expression and cancer progression,yet the functional diversity of RP11-derived lncRNAs—originally mapped to bacterial artificial chromosome(BAC)clones from the Roswell Park Cancer Institute—has only recently begun to be appreciated.This mini-review aims to systematically synthesize current findings on RP11-derived lncRNAs in HCC,outlining their genomic origins,molecular mechanisms,and biological significance.We highlight their roles in metabolic reprogramming,microRNA network modulation,and tumor progression,as well as their diagnostic and prognostic value in tissue and serum-based analyses.Finally,we discuss therapeutic opportunities and propose future directions to translate RP11-derived lncRNAs into clinically actionable biomarkers and targets for precision liver cancer therapy.
基金the Chinese Academy of Sciences Pioneer Hundred Talents Program and the Second Tibetan Plateau Scientific Expedition and Research Program(Grant No.2019QZKK0708)supported by a MEXT(Ministry of Education,Culture,Sports,Science and Technology)KAKENHI(Grants-in-Aid for Scientific Research)grant(Grant No.21H05203)Kobe University Strategic International Collaborative Research Grant(Type B Fostering Joint Research).
文摘The intracontinental subduction of a>200-km-long section of the Tajik-Tarim lithosphere beneath the Pamir Mountains is proposed to explain nearly 30 km of shortening in the Tajik fold-thrust belt and the Pamir uplift.Seismic imaging revealed that the upper slab was scraped and that the lower slab had subducted to a depth of>150 km.These features constitute the tectonic complexity of the Pamirs,as well as the thermal subduction mechanism involved,which remains poorly understood.Hence,in this study,high-resolution three-dimensional(3D)kinematic modeling is applied to investigate the thermal structure and geometry of the subducting slab beneath the Pamirs.The modeled slab configuration reveals distinct along-strike variations,with a steeply dipping slab beneath the southern Pamirs,a more gently inclined slab beneath the northern Pamirs,and apparent upper slab termination at shallow depths beneath the Pamirs.The thermal field reveals a cold slab core after delamination,with temperatures ranging from 400℃to 800℃,enveloped by a hotter mantle reaching~1400℃.The occurrence of intermediate-depth earthquakes aligns primarily with colder slab regions,particularly near the slab tear-off below the southwestern Pamirs,indicating a strong correlation between slab temperature and seismicity.In contrast,the northern Pamirs exhibit reduced seismicity at depth,which is likely associated with thermal weakening and delamination.The central Pamirs show a significant thermal anomaly caused by a concave slab,where the coldest crust does not descend deeply,further suggesting crustal detachment or mechanical failure.The lateral asymmetry in slab temperature possibly explains the mechanism of lateral tearing and differential slab-mantle coupling.
基金supported by the Shanghai Sailing Program(No.21YF1418500)the Shanghai Chenguang Program(No.21CGA70)+1 种基金the three-year action plan for strengthening the construction of the public health system in Shanghai(No.GWVI-11.2-YQ12)Additionally,we would like to thank the Shanghai Oriental Talents Program-Youth Project(Education Platform)for its support of this study.
文摘Aging is a complex biological process characterized by nine hallmarks,including genomic instability,mitochondrial dysfunction,and chronic inflammation,which collectively drive the progression of age-related chronic non-communicable diseases.Phytonutrients,a class of bioactive secondary metabolites abundant in plants,have emerged as a promising research focus for intervening in the aging process due to their multifaceted biological activities.This review systematically elaborates on the molecular mechanisms,key signaling pathways,specifically SIRT1,Nrf2/ARE,and AMPK/mTOR,and the synergistic anti-aging effects of four typical phytonutrient categories:polyphenols(e.g.,resveratrol,quercetin),carotenoids(e.g.,lycopene,astaxanthin),sulfur compounds(e.g.,α-lipoic acid,ergothioneine),and phytoestrogens(e.g.,soybean isoflavones).The evidence indicates that these compounds combat aging through a multidimensional network involving direct antioxidant actions,free radical scavenging,metal chelation,promotion of autophagy,and modulation of inflammatory and epigenetic pathways.Crucially,the review highlights that synergistic interactions between different phytonutrients can significantly enhance their efficacy beyond the effect of any single compound.The aim is to consolidate the anti-aging evidence of phytonutrients and address the current translational challenges,such as bioavailability and a lack of robust human trials,thereby providing a comprehensive theoretical framework for developing effective,diet-centered strategies to promote healthy aging and reduce the global burden of non-communicable diseases.
基金funded by Ongoing Research Funding Program for Project number(ORF-2025-648),King Saud University,Riyadh,Saudi Arabia.
文摘Heart disease remains a leading cause of mortality worldwide,emphasizing the urgent need for reliable and interpretable predictive models to support early diagnosis and timely intervention.However,existing Deep Learning(DL)approaches often face several limitations,including inefficient feature extraction,class imbalance,suboptimal classification performance,and limited interpretability,which collectively hinder their deployment in clinical settings.To address these challenges,we propose a novel DL framework for heart disease prediction that integrates a comprehensive preprocessing pipeline with an advanced classification architecture.The preprocessing stage involves label encoding and feature scaling.To address the issue of class imbalance inherent in the personal key indicators of the heart disease dataset,the localized random affine shadowsampling technique is employed,which enhances minority class representation while minimizing overfitting.At the core of the framework lies the Deep Residual Network(DeepResNet),which employs hierarchical residual transformations to facilitate efficient feature extraction and capture complex,non-linear relationships in the data.Experimental results demonstrate that the proposed model significantly outperforms existing techniques,achieving improvements of 3.26%in accuracy,3.16%in area under the receiver operating characteristics,1.09%in recall,and 1.07%in F1-score.Furthermore,robustness is validated using 10-fold crossvalidation,confirming the model’s generalizability across diverse data distributions.Moreover,model interpretability is ensured through the integration of Shapley additive explanations and local interpretable model-agnostic explanations,offering valuable insights into the contribution of individual features to model predictions.Overall,the proposed DL framework presents a robust,interpretable,and clinically applicable solution for heart disease prediction.
文摘The effect of plasma and charged particle interaction with spacecraft in a low Earth orbit(LEO)environment leads to ion focusing and the formation of an ion void in the downstream region as a result of charging.Simulations and investigations using a fixed potential imposed on the spacecraft showed the nonsignificance of geophysical parameter changes to ion focusing.Variation of the temperature ratio(T_(r))contributed only to local ion focusing and manifested as two-ion streamers dispersed at the upper and lower edges of the spacecraft-the outermost layers of the satellite structure at the top and bottom,respectively.A simulation involving changing the ambient plasma density(N_(p))also showed the formation of local ion focusing,in which ions were more concentrated as the density increased.Furthermore,auroral electron density(N_(ae))variation had no clear impact on ion focusing,as indicated by static two-ion structures in the wake field.However,variation of the object potential(ϕ)strongly affected ion focusing formation,leading to distortion of the initial ion void region behind the spacecraft.The formation of ion focusing in this study was subject to the electric field produced by the object potential and the ambipolar electric field resulting from plasma expansion in the downstream region.
基金supported by the National Research Foundation of Korea,Nos.2021R1A2C2006110,2021M3E5D9021364,2019R1A5A2026045(to BGK)the Korea Initiative for Fostering University of Research and Innovation(KIURI)Program of the NRF funded by the MSIT(to HK),No.NRF2021M3H1A104892211(to HSK)。
文摘Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.
基金supported by a grant from the Japan Foundation for applied enzymology (to NT)the Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (26430059, 17K08272, and 20K07014 to NT)+1 种基金the establishment of university fellowships toward the creation of science technology innovation (JPMJFS2128)a Grant-in-Aid for JSPS Fellows (23KJ1603)(to MK)。
文摘The purpose of this perspective is to discuss the future development of a potential treatment of glial pathology in Alzheimer's disease(AD) and a new regulatory mechanism, nuclear lipids, which may be involved in the pathogenesis of the disease, based on the work of the authors(Takasugi et al., 2011;Komai et al., 2024).
基金Supported by the National Natural Science Foundation of China,No.81860843Guangxi Administration of Traditional Chinese Medicine Project,No.GZSY23-36 and No.GXZYA20240150。
文摘BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,has been shown to significantly improve clinical symptoms in patients with CAG,as demonstrated by a multicenter cohort study(overall effective rate:82.5%,P<0.01).However,the unclear molecular mechanisms and therapeutic targets of AWD limit its international acceptance.AIM To investigate the therapeutic mechanisms of AWD against CAG from an integrated perspective.METHODS In this study,N-methyl-N’-nitro-N-nitrosoguanidine was used to establish a CAG rat model.Serum-derived constituents transferred from AWD were first identified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry.The concentrations of inflammatory cytokines in serum samples were determined by enzyme-linked immunosorbent assay.Moreover,gastric mucosal tissues were analyzed by quantitative realtime polymerase chain reaction to measure messenger RNA(mRNA)levels of the NLRP3 inflammasome.Western blotting was used to detect the protein expression of NLRP3,caspase-1,and interleukin(IL)-1β.To elucidate the regulatory mechanisms underlying AWD treatment,structural alterations of the gut microbiota(GM)and associated metabolites were analyzed using integrated high-throughput sequencing(16S rRNA)and liquid chromatography-mass spectrometry based untargeted metabolomics.This comprehensive approach systematically clarified AWD’s multi-target therapeutic mechanisms against CAG.RESULTS AWD notably reduced serum levels of pro-inflammatory cytokines,such as IL-1β,IL-18,tumor necrosis factor-α,and lipopolysaccharide,demonstrating significant statistical differences(all P<0.01).Additionally,AWD substantially inhibited NLRP3 mRNA expression in gastric mucosal tissue(P<0.01)and concurrently decreased the protein abundance of NLRP3,IL-1β,and caspase-1(all P<0.01),thereby suppressing inflammasome signaling activation.GM analysis indicated that AWD intervention significantly increased the relative abundance of beneficial bacteria.Associated microbial metabolites likely inhibited the NLRP3 inflammasome pathway by modulating immune cell function.Non-targeted metabolomics further indicated that AWD exerted anti-inflammatory effects by regulating critical metabolic pathways,including the Kaposi’s sarcoma-associated herpesvirus infection pathway,autophagy processes,and glycosylphosphatidylinositol-anchor biosynthesis.CONCLUSION AWD alleviates the pathological progression of CAG through multi-target synergistic mechanisms.On one hand,AWD directly suppresses gastric mucosal inflammation by inhibiting NLRP3 inflammasome activation.On the other hand,AWD remodels intestinal microbiota-metabolite homeostasis,enhances intestinal barrier function,and regulates mucosal immune responses.
