Objective:Early sepsis can be treated if recognised early,but progression to severe sepsis and septic shock and multiple organ dysfunction syndrome substantially increases mortality.The objectives of our study were to...Objective:Early sepsis can be treated if recognised early,but progression to severe sepsis and septic shock and multiple organ dysfunction syndrome substantially increases mortality.The objectives of our study were to assess morbidity and mortality of patients with sepsis and to compare the effectiveness of a simple bedside satisfiable Quick Sequential Organ Failure Assessment(qSOFA)score with National Early Warning Score(NEWS)in prognosticating sepsis.Methods:This prospective observational study was conducted among patients>18 years old presenting with sepsis at B.J.Medical College.The SOFA,qSOFA and NEWS scores were calculated.The effectiveness in predicting mortality was evaluated using receiver operating characteristic curve analysis.Results:A total of 200 patients were evaluated(56%male)with a mean age of 51.7 years.The mortality rate was 23%.Patients categorized under high risk according to SOFA score>8,qSOFA score of 2-3 and NEWS>7 had a mortality rate of 33.3%,27.5%and 28.4%,respectively.AUC for mortality prediction was 0.695 using SOFA score,0.665 using qSOFA and 0.725 using NEWS.At a cut off of 7.50,NEWS demonstrated a sensitivity of 97.8%with a specificity of 28.0%and outperformed both SOFA and qSOFA which yielded a sensitivity of 43.5%and 91.3%and a specificity of 77.9%and 27.9%,respectively.Conclusions:The NEWS score outperforms SOFA and qSOFA in predicting mortality among sepsis patients.However,qSOFA is more helpful in identifying high risk patients and performs better in intensive care setting.展开更多
BACKGROUND:This study aims to develop and validate a machine learning-based in-hospital mortality predictive model for acute aortic syndrome(AAS)in the emergency department(ED)and to derive a simplifi ed version suita...BACKGROUND:This study aims to develop and validate a machine learning-based in-hospital mortality predictive model for acute aortic syndrome(AAS)in the emergency department(ED)and to derive a simplifi ed version suitable for rapid clinical application.METHODS:In this multi-center retrospective cohort study,AAS patient data from three hospitals were analyzed.The modeling cohort included data from the First Affiliated Hospital of Zhengzhou University and the People’s Hospital of Xinjiang Uygur Autonomous Region,with Peking University Third Hospital data serving as the external test set.Four machine learning algorithms—logistic regression(LR),multilayer perceptron(MLP),Gaussian naive Bayes(GNB),and random forest(RF)—were used to develop predictive models based on 34 early-accessible clinical variables.A simplifi ed model was then derived based on fi ve key variables(Stanford type,pericardial eff usion,asymmetric peripheral arterial pulsation,decreased bowel sounds,and dyspnea)via Least Absolute Shrinkage and Selection Operator(LASSO)regression to improve ED applicability.RESULTS:A total of 929 patients were included in the modeling cohort,and 210 were included in the external test set.Four machine learning models based on 34 clinical variables were developed,achieving internal and external validation AUCs of 0.85-0.90 and 0.73-0.85,respectively.The simplifi ed model incorporating fi ve key variables demonstrated internal and external validation AUCs of 0.71-0.86 and 0.75-0.78,respectively.Both models showed robust calibration and predictive stability across datasets.CONCLUSION:Both kinds of models were built based on machine learning tools,and proved to have certain prediction performance and extrapolation.展开更多
Knee osteoarthritis(KOA)represents one of the most common causes of chronic pain.The high prevalence and disability rates of KOA impose a severe burden on both individuals and society.In contrast to cutaneous pain,KOA...Knee osteoarthritis(KOA)represents one of the most common causes of chronic pain.The high prevalence and disability rates of KOA impose a severe burden on both individuals and society.In contrast to cutaneous pain,KOA-induced joint pain is characterized as a deep tissue pain that potentially involves distinct subgroups of peripheral sensory neurons and central processing mechanisms.Furthermore,KOA pain is closely related to locomotion activity.Impaired sensorimotor integration and pain mutually reinforce each other in KOA,forming a vicious cycle that exacerbates disease progression.In this review,we highlight the key differences between KOA pain and cutaneous pain,and the latter has been extensively studied in the pain field.We hope to offer new insights into the central mechanisms and development of new treatment strategies for KOA based on the interactions between impaired sensorimotor integration and chronic joint pain.展开更多
The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
This paper presents an Eulerian-Lagrangian algorithm for direct numerical simulation(DNS)of particle-laden flows.The algorithm is applicable to perform simulations of dilute suspensions of small inertial particles in ...This paper presents an Eulerian-Lagrangian algorithm for direct numerical simulation(DNS)of particle-laden flows.The algorithm is applicable to perform simulations of dilute suspensions of small inertial particles in turbulent carrier flow.The Eulerian framework numerically resolves turbulent carrier flow using a parallelized,finite-volume DNS solver on a staggered Cartesian grid.Particles are tracked using a point-particle method utilizing a Lagrangian particle tracking(LPT)algorithm.The proposed Eulerian-Lagrangian algorithm is validated using an inertial particle-laden turbulent channel flow for different Stokes number cases.The particle concentration profiles and higher-order statistics of the carrier and dispersed phases agree well with the benchmark results.We investigated the effect of fluid velocity interpolation and numerical integration schemes of particle tracking algorithms on particle dispersion statistics.The suitability of fluid velocity interpolation schemes for predicting the particle dispersion statistics is discussed in the framework of the particle tracking algorithm coupled to the finite-volume solver.In addition,we present parallelization strategies implemented in the algorithm and evaluate their parallel performance.展开更多
Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of ...Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.展开更多
In order to explore the reduction pathways of zinc oxide in LiCl molten salt and the optimal process,experiments were conducted in an alumina crucible using metallic lithium as the reducing agent and lithium chloride ...In order to explore the reduction pathways of zinc oxide in LiCl molten salt and the optimal process,experiments were conducted in an alumina crucible using metallic lithium as the reducing agent and lithium chloride molten salt as the reaction medium at 923 K.The study assessed the effects of lithium thermochemical reduction and electrolytic reduction of ZnO.The volatilization behavior of metal oxides in molten salts,the equivalent of a reducing agent,reduction time,amount of molten salt,stirring time,and the method of reduction feed were investigated for their impacts on the reduction yield and product composition.X-ray powder diffraction(XRD)analysis of the products showed that lithium reduction of ZnO not only produced metallic Zn but also formed a LiZn alloy.Electrolytic reduction can be used to obtain the metallic Zn product by controlling the potential below-2.2 V(vs Ag/Ag^(+)).Moreover,sintered oxides and higher electrode potentials could enhance the efficiency of electrolysis.Under the optimal reaction conditions determined experimentally,the lithium reduction experiment achieved a yield of 77.2%after a 12-h test,and the electrolytic reduction reached a yield of 85.4%after a 6-h test.展开更多
The poor electrical conductivity of metal-organic frameworks(MOFs)limits their electrocatalytic performance in the oxygen evolution reaction(OER).In this study,a Py@Co-MOF composite material based on pyrene(Py)molecul...The poor electrical conductivity of metal-organic frameworks(MOFs)limits their electrocatalytic performance in the oxygen evolution reaction(OER).In this study,a Py@Co-MOF composite material based on pyrene(Py)molecules and{[Co2(BINDI)(DMA)_(2)]·DMA}_(n)(Co-MOF,H4BINDI=N,N'-bis(5-isophthalic acid)naphthalenediimide,DMA=N,N-dimethylacetamide)was synthesized via a one-pot method,leveragingπ-πinteractions between pyrene and Co-MOF to modulate electrical conductivity.Results demonstrate that the Py@Co-MOF catalyst exhibited significantly enhanced OER performance compared to pure Co-MOF or pyrene-based electrodes,achieving an overpotential of 246 mV at a current density of 10 mA·cm^(-2) along with excellent stability.Density functional theory(DFT)calculations reveal that the formation of O*in the second step is the rate-determining step(RDS)during the OER process on Co-MOF,with an energy barrier of 0.85 eV due to the weak adsorption affinity of the OH*intermediate for Co sites.CCDC:2419276.展开更多
In this paper,we present a circuit model of single-quantum-well InGaN/GaN light-emitting diodes based on the standard rate equations.Two rate equations describe carrier transport processes occurring in sep-arate confi...In this paper,we present a circuit model of single-quantum-well InGaN/GaN light-emitting diodes based on the standard rate equations.Two rate equations describe carrier transport processes occurring in sep-arate confinement heterostructure and quantum well respectively,and the third equation describes the varied photons in quantum well.By using the presented model,impacts of quantum well thickness on the static and dynamic performances are investigated.Simulated results show that LED with 4 nm well exhibits better lightcurrent(L-I)performance,but LED with 3 nm well presents wider 3 dB modulation bandwidth.It reveals that high carrier density in quantum well is detrimental to the static performance,but beneficial to the dynamic performance.展开更多
In mammals,the litter size is approximately half the number of mammae,known as the‘one-half rule’,which has been recognized since the time of Aristotle in ancient Greece(Aristotle,1937)and applies to many species(Gi...In mammals,the litter size is approximately half the number of mammae,known as the‘one-half rule’,which has been recognized since the time of Aristotle in ancient Greece(Aristotle,1937)and applies to many species(Gilbert,1986;Diamond,1987).In contrast,arboreal squirrels,including flying squirrels,notably diverge from this norm by producing fewer offspring(Gilbert,1986).However,the reasons underlying this smaller litter size in arboreal squirrels have long remained elusive.展开更多
Among various architectures of polymers,end-group-free rings have attracted growing interests due to their distinct physicochemical performances over the linear counterparts which are exemplified by reduced hydrodynam...Among various architectures of polymers,end-group-free rings have attracted growing interests due to their distinct physicochemical performances over the linear counterparts which are exemplified by reduced hydrodynamic size and slower degradation.It is key to develop facile methods to large-scale synthesis of polymer rings with tunable compositions and microstructures.Recent progresses in large-scale synthesis of polymer rings against single-chain dynamic nanoparticles,and the example applications in synchronous enhancing toughness and strength of polymer nanocomposites are summarized.Once there is the breakthrough in rational design and effective large-scale synthesis of polymer rings and their functional derivatives,a family of cyclic functional hybrids would be available,thus providing a new paradigm in developing polymer science and engineering.展开更多
In light of the pressing global challenges of climate change,declining crop resilience,and hidden hunger,it is imperative to overcome the limitations of conventional crop breeding to enhance both the nutritional quali...In light of the pressing global challenges of climate change,declining crop resilience,and hidden hunger,it is imperative to overcome the limitations of conventional crop breeding to enhance both the nutritional quality and stress tolerance of crops.Synthetic metabolic engineering presents innovative strategies for the precision modification and de novo design of metabolic pathways.This approach generally encompasses three essential steps:identifying key metabolites through metabolomics,integrating multi-omics technologies to investigate the synthesis and regulation of these metabolites,and utilizing gene editing or de novo design to modify crop metabolic pathways associated with desirable agronomic traits.This review underscores the vital role of plant metabolite diversity in enhancing crop nutritional quality and stress resilience.Integrated multi-omics analyses facilitate the metabolic engineering by identifying key genes,transporters,and transcription factors that regulate metabolite biosynthesis.Precision modification strategies employ genome editing tools to reprogram endogenous metabolic networks,while de novo design reconstructs metabolic pathways through the introduction of exogenous biological elements—thereby both approaches enable the targeted enhancement of desired traits.These strategies have been effectively implemented in major food crops.However,simultaneously enhancing nutritional quality and stress resilience remains challenging due to inherent trade-offs and resource competition in distinct metabolic pathways within plants.Future research should integrate AI-driven predictive models with multi-omics datasets to decipher dynamic metabolic homeostasis and engineer climate-smart crops that maximize yield while preserving quality and environmental adaptability.展开更多
Background:Insufficient physical activity and prolonged sedentary behavior have emerged as major global public health challenges.Short bouts(≤10 min)of accumulated exercise(SBAE)throughout the day may be a promising ...Background:Insufficient physical activity and prolonged sedentary behavior have emerged as major global public health challenges.Short bouts(≤10 min)of accumulated exercise(SBAE)throughout the day may be a promising strategy to mitigate the adverse effects of prolonged sitting and promote physical activity,ultimately promoting overall health.However,previous ambiguity in defining this concept has resulted in a fragmented and inconsistent evidence base,impeding practical applications,the development of guidelines,and policymaking.The purpose of this study is to establish an operational definition of SBAE by synthesizing systematic reviews and research trials alongside an expert consensus.Additionally,it seeks to evaluate acute and long-term efficacy and feasibility,providing evidence-based recommendations for practice and future research directions.Methods:A literature search was performed across PubMed and Web of Science,followed by systematic screening and summarization of eligible studies based on predefined inclusion criteria.Inclusion criteria encompassed various modes/types of SBAE(bouts lasting≤10 min,performed multiple times daily with≥30 min intervals);both aerobic and resistance exercise were considered.Relevant systematic reviews and research trials were included.Methodological quality,risk of bias,and evidence certainty were assessed.Expert consensus was obtained through a survey to evaluate recommendations and agreement levels on findings.Results:After analyzing 27 systematic reviews,135 research studies,and an expert consensus involving 48 researchers from 11 countries,SBAE is defined as any exercise mode of activity,regardless of intensity,that is accumulated in either continuous or intermittent bouts lasting≤10 min per session(including multiple intermittent sets)that are performed multiple times(≥2 sessions/day)per day,with intervals of≥30 min between bouts or otherwise sufficient time for recovery.When used to interrupt prolonged periods of sedentary time,SBAE mitigates the acute adverse effects of sedentary behavior on more than 10 clinical biomarkers of endocrine,cardiovascular,and brain health/function among adults of diverse ages and conditions.Moreover,SBAE was superior for improving acute glycemic control compared to a single continuous exercise session.As a long-term intervention(average of 11 weeks),SBAE can improve over 20 health outcomes,including peak oxygen uptake,resting blood pressure,and metabolic health.Additionally,SBAE might be more effective than continuous exercise for improving longer-term glycemic control and body composition.Long-term completion rates for SBAE interventions are generally high(95%),with low dropout rates(12%)and high adherence rates even without supervision(85%),and its safety has been preliminarily validated.Conclusion:An operational definition of SBAE is provided along with its classification and acute and long-term efficacy.Practical exercise prescription recommendations and evidence-based strategies for various populations and contexts are provided.Future research should focus on generating high-quality evidence for SBAE in 5 key areas:quantification and monitoring,population-specific responses,optimization of exercise prescriptions,intervention efficacy,and practical implementation.Additionally,addressing policy,environmental,and promotional barriers is crucial for transitioning from expert consensus to public consensus,and for facilitating the application of this strategy in real-world environments.展开更多
Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as ...Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as deep brain stimulation and transcranial magnetic stimulation,show limitations such as invasiveness,restricted cortical targeting,and irreversible tissue effects.In this context,low-intensity transcranial ultrasound has emerged as a promising noninvasive alternative that can penetrate deep into the brain and modulate neuroplasticity.This review comprehensively assesses the therapeutic mechanisms,efficacy,and translational potential of low-intensity transcranial ultrasound in treating neurodegenerative diseases,with emphasis on its role in promoting neuronal regeneration,modulating neuroinflammation,and enhancing functional recovery.We summarize the findings of previous studies and systematically illustrate the potential of low-intensity transcranial ultrasound in regulating cell death mechanisms,enhancing neural repair and regeneration,and alleviating symptoms associated with neurodegenerative diseases.Preclinical findings indicate that low-intensity transcranial ultrasound can enhance the release of neurotrophic factors(e.g.,brain-derived neurotrophic factor),promote autophagy to clear protein aggregates,modulate microglial activation,and temporarily open the blood-brain barrier to facilitate targeted drug delivery.Existing clinical trial data show that low-intensity transcranial ultrasound can reduce amyloid-βplaques,improve motor and cognitive deficits,and promote remyelination in various disease models.Early clinical trials suggest that low-intensity transcranial ultrasound may enhance cognitive scores in Alzheimer’s disease and alleviate motor symptoms in Parkinson’s disease,all while demonstrating a favorable safety profile.Past studies support the notion that by integrating safety,precision,and reversibility,low-intensity transcranial ultrasound can transform the treatment landscape for neurodegenerative disease.However,more advancements are necessary for future clinical application of low-intensity transcranial ultrasound,including optimizing parameters such as frequency,intensity,and duty cycle;considering individual anatomical differences;and confirming long-term efficacy.We believe establishing standardized protocols,conducting larger trials,and investigating the underlying mechanisms to clarify dose-response relationships and refine personalized application strategies are essential in this regard.Future research should focus on translating preclinical findings into clinical practice,addressing technical challenges,and exploring combination therapies with pharmacological or gene interventions.展开更多
The complexes 1-4 of cyclobutanocucurbit[5]uril(CyB5Q[5])with Na^(+)/K^(+)have been synthesized and characterized by single-crystal X-ray diffraction.The results show that although the inorganic salts are used when th...The complexes 1-4 of cyclobutanocucurbit[5]uril(CyB5Q[5])with Na^(+)/K^(+)have been synthesized and characterized by single-crystal X-ray diffraction.The results show that although the inorganic salts are used when the cations are the same and the anions are different,in complex 1,Na^(+)closes one port of CyB5Q[5]through Na—O seven coordination bonds to form a molecular bowl;in complex 3,Na^(+)completely closes the two ports of CyB5Q[5]to form a molecular capsule with six Na—O coordination bonds;in complexes 2 and 4,the two ports of CyB5Q[5]are completely closed to form K—O coordinated molecular capsules,but the K^(+)of complex 2 is six-coordinated and that of complex 4 is eight-/nine-coordinated.and complex 4 are connected by three oxygen bridges to form a 1D molecular chain.CCDC:2457122,1;2457121,2;2457400,3;2457120,4.展开更多
Purpose-This paper provides a comprehensive analysis of the Brazilian freight railway system,examining the efficacy of the current concession renewal model in light of persistent structural problems such as market con...Purpose-This paper provides a comprehensive analysis of the Brazilian freight railway system,examining the efficacy of the current concession renewal model in light of persistent structural problems such as market concentration,cargo dependence on export commodities and underutilization of the network.Situating Brazil within the broader international debate on railway reforms,the paper evaluates whether the ongoing early renewal of concessions can deliver a more diversified and competitive freight system.Design/methodology/approach-The study adopts a sequential mixed-methods research design that integrates longitudinal quantitative analysis with qualitative institutional and policy evaluation.The quantitative component examines time-series indicators published by ANTT,DNIT and INFRA S.A.from 1999 to 2023 to identify structural patterns in traffic growth,investment,safety and market concentration.The qualitative component employs a process-tracing logic to reconstruct the evolution of concession renewals and the implementation of Railway Law 14.273/2021,drawing on concepts from regulatory economics,institutional theory and industrial organization.These empirical streams are synthesized through an analytical framework that connects three dimensions-regulatory design,market structure and system performance-allowing for a systematic assessment of how Brazil’s institutional configuration shapes incentives,competitive dynamics and network utilization.Findings-The analysis confirms that the early renewal of concessions has successfully secured substantial private investment for capacity expansion on existing trunk lines.However,it has perpetuated the vertically integrated model,reinforcing the market power of incumbent operators and failing to significantly promote intramodal competition or cargo diversification.The system remains dominated by iron ore and agricultural commodities,with general cargo representing a minuscule share.The new authorization regime and short-line railway policies present a viable pathway for market opening but face significant operational and institutional barriers to implementation.Originality/value-This research offers a timely and critical assessment of a pivotal moment in Brazilian railway policy.It moves beyond a simplistic evaluation of volume growth to a structural analysis of market failures and the interplay between concession renewal and regulatory innovation.The findings provide actionable insights for policymakers in Brazil and other emerging economies seeking to balance private investment with public interest goals in railway infrastructure,highlighting the necessity of complementary,pro-competitive measures alongside financial investment.展开更多
BACKGROUND Repeated application of the Pringle maneuver is a key obstacle to safe minimally invasive repeat liver resection(MISRLR).However,limited technical guidance is available.AIM To study the utility of newly dev...BACKGROUND Repeated application of the Pringle maneuver is a key obstacle to safe minimally invasive repeat liver resection(MISRLR).However,limited technical guidance is available.AIM To study the utility of newly developed Pringle taping method guided by liver surface in MISRLR.METHODS We retrospectively reviewed 72 cases of MISRLR performed by a single surgeon at two centers from August 2015 to July 2024.Beginning in October 2019,a liver surface-guided encirclement of hepatoduodenal ligament(LSEH)was used for repeat Pringle taping.Perioperative outcomes including Pringle taping success,operative time,blood loss,conversion rate,morbidity,and mortality were assessed.RESULTS Laparoscopic and robotic approaches were used in 63 patients and 9 patients,respectively.The median operative time,blood loss,and hospital stay were 331.5 minutes,70 mL,and 8 days,respectively.Open conversion occurred in two cases(2.8%)due to severe adhesions and right renal vein injury.Clavien-Dindo grade≥III complications occurred in 5.6%of cases with no mortality.Anti-adhesion barriers were used in 54 patients(75.0%).LSEH was attempted in 57 cases,improving Pringle taping success from 33.0%to 91.4%(P<0.001).LSEH succeeded in all patients with prior open liver resection(n=11).Among 6 patients in whom LSEH failed,3 patients(50.0%)had undergone a third liver resection,and 1 patient had a history of distal gastrectomy with choledochoduodenostomy.CONCLUSION The newly developed LSEH technique for Pringle taping in MISRLR was feasible,enhancing safety and reproducibility even in patients with a history of open liver resection.展开更多
Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors,rigidity,and slowed movements.A key feature of Parkinson's disease i...Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors,rigidity,and slowed movements.A key feature of Parkinson's disease is the accumulation of misfoldedα-synuclein,forming insoluble Lewy bodies in the substantia nigra pars compacta,which contributes to neurodegeneration.Theseα-synuclein aggregates may act as autoantigens,leading to T-cell-mediated neuroinflammation and contributing to dopaminergic cell death.Our perspective explores the hypothesis that Parkinson's disease may have an autoimmune component,highlighting research that connects peripheral immune responses with neurodegeneration.T cells derived from Parkinson's disease patients appear to have the potential to initiate an autoimmune response againstα-synuclein and its modified peptides,possibly leading to the formation of neo-epitopes.Recent evidence associates Parkinson's disease with abnormal immune responses,as indicated by increased levels of immune cells,such as CD4^(+)and CD8^(+)T cells,observed in both patients and mouse models.The convergence of T cells filtration increasing major histocompatibility complex molecules,and the susceptibility of dopaminergic neurons supports the hypothesis that Parkinson's disease may exhibit autoimmune characteristics.Understanding the immune mechanisms involved in Parkinson's disease will be crucial for developing therapeutic strategies that target the autoimmune aspects of the disease.Novel approaches,including precision medicine based on major histocompatibility complex/human leukocyte antigen typing and early biomarker identification,could pave the way for immune-based treatments aimed at slowing or halting disease progression.This perspective explores the relationship between autoimmunity and Parkinson's disease,suggesting that further research could deepen understanding and offer new therapeutic avenues.In this paper,it is organized to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease.It investigates critical areas such as the autoimmune response observed in Parkinson's disease patients and the role of autoimmune mechanisms targetingα-synuclein in Parkinson's disease.The paper also examines the impact of CD4~+T cells,specifically Th1 and Th17,on neurons through in vitro and ex vivo studies.Additionally,it explores howα-synuclein influences glia-induced neuroinflammation in Parkinson's disease.The discussion extends to the clinical implications and therapeutic landscape,offering insights into potential treatments.Consequently,we aim to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease,incorporating both supportive and opposing views on its classification as an autoimmune disorder and exploring implications for clinical applications.展开更多
Plantago major L.,commonly known as plantain,waybread,or dooryard plantain,is a versatile medicinal plant with multiple therapeutic applications.Traditionally,various parts of the plant have been formulated into syrup...Plantago major L.,commonly known as plantain,waybread,or dooryard plantain,is a versatile medicinal plant with multiple therapeutic applications.Traditionally,various parts of the plant have been formulated into syrups,drops,ointments,vaginal suppositories,gargles,and roasted preparations to treat diverse ailments,such as liver disorders,earaches,epilepsy,asthma,stomachaches,diarrhea,constipation,polymenorrhea,and uterine disorders.The plant contains clinically valuable bioactive compounds,including polysaccharides,flavonoids,lipids,iridoid glycosides,caffeic acid derivatives,terpenoids,alkaloids,and organic acids.These bioactive constituents are the primary contributors to the plant’s broad spectrum of biological activities,including antioxidant,anti-inflammatory,antibacterial,antidiarrheal,hepatoprotective,antiviral,antiphage,antinociceptive,antiulcerogenic,antigenotoxic,and immunomodulatory effects of the plant.This review comprehensively summarizes the phytochemical composition,traditional medicinal applications,and biological properties of this multifunctional medicinal plant.展开更多
The emergence of Medical Large Language Models has significantly transformed healthcare.Medical Large Language Models(Med-LLMs)serve as transformative tools that enhance clinical practice through applications in decis...The emergence of Medical Large Language Models has significantly transformed healthcare.Medical Large Language Models(Med-LLMs)serve as transformative tools that enhance clinical practice through applications in decision support,documentation,and diagnostics.This evaluation examines the performance of leading Med-LLMs,including GPT-4Med,Med-PaLM,MEDITRON,PubMedGPT,and MedAlpaca,across diverse medical datasets.It provides graphical comparisons of their effectiveness in distinct healthcare domains.The study introduces a domain-specific categorization system that aligns these models with optimal applications in clinical decision-making,documentation,drug discovery,research,patient interaction,and public health.The paper addresses deployment challenges of Medical-LLMs,emphasizing trustworthiness and explainability as essential requirements for healthcare AI.It presents current evaluation techniques that improve model transparency in high-stakes medical contexts and analyzes regulatory frameworks using benchmarking datasets such asMedQA,MedMCQA,PubMedQA,and MIMIC.By identifying ongoing challenges in biasmitigation,reliability,and ethical compliance,thiswork serves as a resource for selecting appropriate Med-LLMs and outlines future directions in the field.This analysis offers a roadmap for developing Med-LLMs that balance technological innovation with the trust and transparency required for clinical integration,a perspective often overlooked in existing literature.展开更多
文摘Objective:Early sepsis can be treated if recognised early,but progression to severe sepsis and septic shock and multiple organ dysfunction syndrome substantially increases mortality.The objectives of our study were to assess morbidity and mortality of patients with sepsis and to compare the effectiveness of a simple bedside satisfiable Quick Sequential Organ Failure Assessment(qSOFA)score with National Early Warning Score(NEWS)in prognosticating sepsis.Methods:This prospective observational study was conducted among patients>18 years old presenting with sepsis at B.J.Medical College.The SOFA,qSOFA and NEWS scores were calculated.The effectiveness in predicting mortality was evaluated using receiver operating characteristic curve analysis.Results:A total of 200 patients were evaluated(56%male)with a mean age of 51.7 years.The mortality rate was 23%.Patients categorized under high risk according to SOFA score>8,qSOFA score of 2-3 and NEWS>7 had a mortality rate of 33.3%,27.5%and 28.4%,respectively.AUC for mortality prediction was 0.695 using SOFA score,0.665 using qSOFA and 0.725 using NEWS.At a cut off of 7.50,NEWS demonstrated a sensitivity of 97.8%with a specificity of 28.0%and outperformed both SOFA and qSOFA which yielded a sensitivity of 43.5%and 91.3%and a specificity of 77.9%and 27.9%,respectively.Conclusions:The NEWS score outperforms SOFA and qSOFA in predicting mortality among sepsis patients.However,qSOFA is more helpful in identifying high risk patients and performs better in intensive care setting.
基金supported by the special fund of the National Clinical Key Specialty Construction Program[(2022)301-2305].
文摘BACKGROUND:This study aims to develop and validate a machine learning-based in-hospital mortality predictive model for acute aortic syndrome(AAS)in the emergency department(ED)and to derive a simplifi ed version suitable for rapid clinical application.METHODS:In this multi-center retrospective cohort study,AAS patient data from three hospitals were analyzed.The modeling cohort included data from the First Affiliated Hospital of Zhengzhou University and the People’s Hospital of Xinjiang Uygur Autonomous Region,with Peking University Third Hospital data serving as the external test set.Four machine learning algorithms—logistic regression(LR),multilayer perceptron(MLP),Gaussian naive Bayes(GNB),and random forest(RF)—were used to develop predictive models based on 34 early-accessible clinical variables.A simplifi ed model was then derived based on fi ve key variables(Stanford type,pericardial eff usion,asymmetric peripheral arterial pulsation,decreased bowel sounds,and dyspnea)via Least Absolute Shrinkage and Selection Operator(LASSO)regression to improve ED applicability.RESULTS:A total of 929 patients were included in the modeling cohort,and 210 were included in the external test set.Four machine learning models based on 34 clinical variables were developed,achieving internal and external validation AUCs of 0.85-0.90 and 0.73-0.85,respectively.The simplifi ed model incorporating fi ve key variables demonstrated internal and external validation AUCs of 0.71-0.86 and 0.75-0.78,respectively.Both models showed robust calibration and predictive stability across datasets.CONCLUSION:Both kinds of models were built based on machine learning tools,and proved to have certain prediction performance and extrapolation.
基金supported by the Natural Science Foundation of Beijing Municipality(No.F252065)the National Natural Science Foundation of China(No.32271190,32571323)the STI 2030 Major Project(No.2021ZD0203202)。
文摘Knee osteoarthritis(KOA)represents one of the most common causes of chronic pain.The high prevalence and disability rates of KOA impose a severe burden on both individuals and society.In contrast to cutaneous pain,KOA-induced joint pain is characterized as a deep tissue pain that potentially involves distinct subgroups of peripheral sensory neurons and central processing mechanisms.Furthermore,KOA pain is closely related to locomotion activity.Impaired sensorimotor integration and pain mutually reinforce each other in KOA,forming a vicious cycle that exacerbates disease progression.In this review,we highlight the key differences between KOA pain and cutaneous pain,and the latter has been extensively studied in the pain field.We hope to offer new insights into the central mechanisms and development of new treatment strategies for KOA based on the interactions between impaired sensorimotor integration and chronic joint pain.
基金partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
基金supported by the P.G.Senapathy Center for Computing Resources at IIT Madrasfunding provided by the Ministry of Education,Government of Indiasupported by the National Natural Science Foundation of China(Grant Nos.12388101,12472224 and 92252104).
文摘This paper presents an Eulerian-Lagrangian algorithm for direct numerical simulation(DNS)of particle-laden flows.The algorithm is applicable to perform simulations of dilute suspensions of small inertial particles in turbulent carrier flow.The Eulerian framework numerically resolves turbulent carrier flow using a parallelized,finite-volume DNS solver on a staggered Cartesian grid.Particles are tracked using a point-particle method utilizing a Lagrangian particle tracking(LPT)algorithm.The proposed Eulerian-Lagrangian algorithm is validated using an inertial particle-laden turbulent channel flow for different Stokes number cases.The particle concentration profiles and higher-order statistics of the carrier and dispersed phases agree well with the benchmark results.We investigated the effect of fluid velocity interpolation and numerical integration schemes of particle tracking algorithms on particle dispersion statistics.The suitability of fluid velocity interpolation schemes for predicting the particle dispersion statistics is discussed in the framework of the particle tracking algorithm coupled to the finite-volume solver.In addition,we present parallelization strategies implemented in the algorithm and evaluate their parallel performance.
文摘Cancer continues to pose a formidable challenge in global health,with conventional treatments such as chemotherapy and radiotherapy often resulting in severe toxicities that significantly degrade patients’quality of life and restrict therapeutic outcomes.Addressing this pressing issue,this review presents a thorough and systematic analysis of innovative and emerging strategies designed to minimize the toxicity induced by treatment,while maintaining or even enhancing antitumor efficacy.The focus is on six promising therapeutic approaches:combination therapies utilizing natural bioactive products,molecularly targeted therapies,immunotherapies,nanotechnology-mediated drug delivery systems,adjunct traditional Chinese medicine interventions,and low-dose spatiotemporally concerted regimens.Each approach employs unique mechanisms—such as enhanced targeting precision,immune system activation,tumor microenvironment reprogramming,and multi-component synergistic effects—to mitigate damage to normal tissues and reduce systemic adverse reactions.Despite promising preclinical and clinical advancements,several challenges persist,including drug resistance,high economic costs,a lack of reliable predictive biomarkers,and complexities in clinical translation and regulatory approval.Looking ahead,the incorporation of artificial intelligence,multi-omics profiling,and novel biomimetic nanotechnologies offers unprecedented opportunities for developing highly personalized,low-toxicity treatment frameworks.This review highlights a fundamental shift in oncology towards precision medicine that balances efficacy with safety,demonstrating the transformative potential of these strategies in shaping the future of cancer therapy and enhancing patient care globally.
文摘In order to explore the reduction pathways of zinc oxide in LiCl molten salt and the optimal process,experiments were conducted in an alumina crucible using metallic lithium as the reducing agent and lithium chloride molten salt as the reaction medium at 923 K.The study assessed the effects of lithium thermochemical reduction and electrolytic reduction of ZnO.The volatilization behavior of metal oxides in molten salts,the equivalent of a reducing agent,reduction time,amount of molten salt,stirring time,and the method of reduction feed were investigated for their impacts on the reduction yield and product composition.X-ray powder diffraction(XRD)analysis of the products showed that lithium reduction of ZnO not only produced metallic Zn but also formed a LiZn alloy.Electrolytic reduction can be used to obtain the metallic Zn product by controlling the potential below-2.2 V(vs Ag/Ag^(+)).Moreover,sintered oxides and higher electrode potentials could enhance the efficiency of electrolysis.Under the optimal reaction conditions determined experimentally,the lithium reduction experiment achieved a yield of 77.2%after a 12-h test,and the electrolytic reduction reached a yield of 85.4%after a 6-h test.
文摘The poor electrical conductivity of metal-organic frameworks(MOFs)limits their electrocatalytic performance in the oxygen evolution reaction(OER).In this study,a Py@Co-MOF composite material based on pyrene(Py)molecules and{[Co2(BINDI)(DMA)_(2)]·DMA}_(n)(Co-MOF,H4BINDI=N,N'-bis(5-isophthalic acid)naphthalenediimide,DMA=N,N-dimethylacetamide)was synthesized via a one-pot method,leveragingπ-πinteractions between pyrene and Co-MOF to modulate electrical conductivity.Results demonstrate that the Py@Co-MOF catalyst exhibited significantly enhanced OER performance compared to pure Co-MOF or pyrene-based electrodes,achieving an overpotential of 246 mV at a current density of 10 mA·cm^(-2) along with excellent stability.Density functional theory(DFT)calculations reveal that the formation of O*in the second step is the rate-determining step(RDS)during the OER process on Co-MOF,with an energy barrier of 0.85 eV due to the weak adsorption affinity of the OH*intermediate for Co sites.CCDC:2419276.
文摘In this paper,we present a circuit model of single-quantum-well InGaN/GaN light-emitting diodes based on the standard rate equations.Two rate equations describe carrier transport processes occurring in sep-arate confinement heterostructure and quantum well respectively,and the third equation describes the varied photons in quantum well.By using the presented model,impacts of quantum well thickness on the static and dynamic performances are investigated.Simulated results show that LED with 4 nm well exhibits better lightcurrent(L-I)performance,but LED with 3 nm well presents wider 3 dB modulation bandwidth.It reveals that high carrier density in quantum well is detrimental to the static performance,but beneficial to the dynamic performance.
文摘In mammals,the litter size is approximately half the number of mammae,known as the‘one-half rule’,which has been recognized since the time of Aristotle in ancient Greece(Aristotle,1937)and applies to many species(Gilbert,1986;Diamond,1987).In contrast,arboreal squirrels,including flying squirrels,notably diverge from this norm by producing fewer offspring(Gilbert,1986).However,the reasons underlying this smaller litter size in arboreal squirrels have long remained elusive.
基金Supported by the National Natural Science Foundation of China(Nos.52293472,22473096 and 22471164)。
文摘Among various architectures of polymers,end-group-free rings have attracted growing interests due to their distinct physicochemical performances over the linear counterparts which are exemplified by reduced hydrodynamic size and slower degradation.It is key to develop facile methods to large-scale synthesis of polymer rings with tunable compositions and microstructures.Recent progresses in large-scale synthesis of polymer rings against single-chain dynamic nanoparticles,and the example applications in synchronous enhancing toughness and strength of polymer nanocomposites are summarized.Once there is the breakthrough in rational design and effective large-scale synthesis of polymer rings and their functional derivatives,a family of cyclic functional hybrids would be available,thus providing a new paradigm in developing polymer science and engineering.
基金supported by the Project of Sanya Yazhou Bay Science and Technology City (SKJC-JYRC-2024-26)the National Natural Science Foundation of China (32460072)+4 种基金Hainan Provincial Natural Science Foundation of China (323RC421)the Hainan Province Science and Technology Special Fund (ZDYF2022XDNY144)the Hainan Provincial Academician Innovation Platform Project (HDYSZX-202004)the Collaborative Innovation Center of Nanfan and High-Efficiency Tropical Agriculture, Hainan University (XTCX2022NYB06)Hainan Postdoctoral Research Grant Project
文摘In light of the pressing global challenges of climate change,declining crop resilience,and hidden hunger,it is imperative to overcome the limitations of conventional crop breeding to enhance both the nutritional quality and stress tolerance of crops.Synthetic metabolic engineering presents innovative strategies for the precision modification and de novo design of metabolic pathways.This approach generally encompasses three essential steps:identifying key metabolites through metabolomics,integrating multi-omics technologies to investigate the synthesis and regulation of these metabolites,and utilizing gene editing or de novo design to modify crop metabolic pathways associated with desirable agronomic traits.This review underscores the vital role of plant metabolite diversity in enhancing crop nutritional quality and stress resilience.Integrated multi-omics analyses facilitate the metabolic engineering by identifying key genes,transporters,and transcription factors that regulate metabolite biosynthesis.Precision modification strategies employ genome editing tools to reprogram endogenous metabolic networks,while de novo design reconstructs metabolic pathways through the introduction of exogenous biological elements—thereby both approaches enable the targeted enhancement of desired traits.These strategies have been effectively implemented in major food crops.However,simultaneously enhancing nutritional quality and stress resilience remains challenging due to inherent trade-offs and resource competition in distinct metabolic pathways within plants.Future research should integrate AI-driven predictive models with multi-omics datasets to decipher dynamic metabolic homeostasis and engineer climate-smart crops that maximize yield while preserving quality and environmental adaptability.
文摘Background:Insufficient physical activity and prolonged sedentary behavior have emerged as major global public health challenges.Short bouts(≤10 min)of accumulated exercise(SBAE)throughout the day may be a promising strategy to mitigate the adverse effects of prolonged sitting and promote physical activity,ultimately promoting overall health.However,previous ambiguity in defining this concept has resulted in a fragmented and inconsistent evidence base,impeding practical applications,the development of guidelines,and policymaking.The purpose of this study is to establish an operational definition of SBAE by synthesizing systematic reviews and research trials alongside an expert consensus.Additionally,it seeks to evaluate acute and long-term efficacy and feasibility,providing evidence-based recommendations for practice and future research directions.Methods:A literature search was performed across PubMed and Web of Science,followed by systematic screening and summarization of eligible studies based on predefined inclusion criteria.Inclusion criteria encompassed various modes/types of SBAE(bouts lasting≤10 min,performed multiple times daily with≥30 min intervals);both aerobic and resistance exercise were considered.Relevant systematic reviews and research trials were included.Methodological quality,risk of bias,and evidence certainty were assessed.Expert consensus was obtained through a survey to evaluate recommendations and agreement levels on findings.Results:After analyzing 27 systematic reviews,135 research studies,and an expert consensus involving 48 researchers from 11 countries,SBAE is defined as any exercise mode of activity,regardless of intensity,that is accumulated in either continuous or intermittent bouts lasting≤10 min per session(including multiple intermittent sets)that are performed multiple times(≥2 sessions/day)per day,with intervals of≥30 min between bouts or otherwise sufficient time for recovery.When used to interrupt prolonged periods of sedentary time,SBAE mitigates the acute adverse effects of sedentary behavior on more than 10 clinical biomarkers of endocrine,cardiovascular,and brain health/function among adults of diverse ages and conditions.Moreover,SBAE was superior for improving acute glycemic control compared to a single continuous exercise session.As a long-term intervention(average of 11 weeks),SBAE can improve over 20 health outcomes,including peak oxygen uptake,resting blood pressure,and metabolic health.Additionally,SBAE might be more effective than continuous exercise for improving longer-term glycemic control and body composition.Long-term completion rates for SBAE interventions are generally high(95%),with low dropout rates(12%)and high adherence rates even without supervision(85%),and its safety has been preliminarily validated.Conclusion:An operational definition of SBAE is provided along with its classification and acute and long-term efficacy.Practical exercise prescription recommendations and evidence-based strategies for various populations and contexts are provided.Future research should focus on generating high-quality evidence for SBAE in 5 key areas:quantification and monitoring,population-specific responses,optimization of exercise prescriptions,intervention efficacy,and practical implementation.Additionally,addressing policy,environmental,and promotional barriers is crucial for transitioning from expert consensus to public consensus,and for facilitating the application of this strategy in real-world environments.
基金supported by STI2030-Major Project,No,2021ZD0204200(to LX).
文摘Neurodegenerative diseases,which are characterized by progressive neuronal loss and the lack of disease-modifying therapies,are becoming a major global health challenge.The existing neuromodulation techniques,such as deep brain stimulation and transcranial magnetic stimulation,show limitations such as invasiveness,restricted cortical targeting,and irreversible tissue effects.In this context,low-intensity transcranial ultrasound has emerged as a promising noninvasive alternative that can penetrate deep into the brain and modulate neuroplasticity.This review comprehensively assesses the therapeutic mechanisms,efficacy,and translational potential of low-intensity transcranial ultrasound in treating neurodegenerative diseases,with emphasis on its role in promoting neuronal regeneration,modulating neuroinflammation,and enhancing functional recovery.We summarize the findings of previous studies and systematically illustrate the potential of low-intensity transcranial ultrasound in regulating cell death mechanisms,enhancing neural repair and regeneration,and alleviating symptoms associated with neurodegenerative diseases.Preclinical findings indicate that low-intensity transcranial ultrasound can enhance the release of neurotrophic factors(e.g.,brain-derived neurotrophic factor),promote autophagy to clear protein aggregates,modulate microglial activation,and temporarily open the blood-brain barrier to facilitate targeted drug delivery.Existing clinical trial data show that low-intensity transcranial ultrasound can reduce amyloid-βplaques,improve motor and cognitive deficits,and promote remyelination in various disease models.Early clinical trials suggest that low-intensity transcranial ultrasound may enhance cognitive scores in Alzheimer’s disease and alleviate motor symptoms in Parkinson’s disease,all while demonstrating a favorable safety profile.Past studies support the notion that by integrating safety,precision,and reversibility,low-intensity transcranial ultrasound can transform the treatment landscape for neurodegenerative disease.However,more advancements are necessary for future clinical application of low-intensity transcranial ultrasound,including optimizing parameters such as frequency,intensity,and duty cycle;considering individual anatomical differences;and confirming long-term efficacy.We believe establishing standardized protocols,conducting larger trials,and investigating the underlying mechanisms to clarify dose-response relationships and refine personalized application strategies are essential in this regard.Future research should focus on translating preclinical findings into clinical practice,addressing technical challenges,and exploring combination therapies with pharmacological or gene interventions.
文摘The complexes 1-4 of cyclobutanocucurbit[5]uril(CyB5Q[5])with Na^(+)/K^(+)have been synthesized and characterized by single-crystal X-ray diffraction.The results show that although the inorganic salts are used when the cations are the same and the anions are different,in complex 1,Na^(+)closes one port of CyB5Q[5]through Na—O seven coordination bonds to form a molecular bowl;in complex 3,Na^(+)completely closes the two ports of CyB5Q[5]to form a molecular capsule with six Na—O coordination bonds;in complexes 2 and 4,the two ports of CyB5Q[5]are completely closed to form K—O coordinated molecular capsules,but the K^(+)of complex 2 is six-coordinated and that of complex 4 is eight-/nine-coordinated.and complex 4 are connected by three oxygen bridges to form a 1D molecular chain.CCDC:2457122,1;2457121,2;2457400,3;2457120,4.
文摘Purpose-This paper provides a comprehensive analysis of the Brazilian freight railway system,examining the efficacy of the current concession renewal model in light of persistent structural problems such as market concentration,cargo dependence on export commodities and underutilization of the network.Situating Brazil within the broader international debate on railway reforms,the paper evaluates whether the ongoing early renewal of concessions can deliver a more diversified and competitive freight system.Design/methodology/approach-The study adopts a sequential mixed-methods research design that integrates longitudinal quantitative analysis with qualitative institutional and policy evaluation.The quantitative component examines time-series indicators published by ANTT,DNIT and INFRA S.A.from 1999 to 2023 to identify structural patterns in traffic growth,investment,safety and market concentration.The qualitative component employs a process-tracing logic to reconstruct the evolution of concession renewals and the implementation of Railway Law 14.273/2021,drawing on concepts from regulatory economics,institutional theory and industrial organization.These empirical streams are synthesized through an analytical framework that connects three dimensions-regulatory design,market structure and system performance-allowing for a systematic assessment of how Brazil’s institutional configuration shapes incentives,competitive dynamics and network utilization.Findings-The analysis confirms that the early renewal of concessions has successfully secured substantial private investment for capacity expansion on existing trunk lines.However,it has perpetuated the vertically integrated model,reinforcing the market power of incumbent operators and failing to significantly promote intramodal competition or cargo diversification.The system remains dominated by iron ore and agricultural commodities,with general cargo representing a minuscule share.The new authorization regime and short-line railway policies present a viable pathway for market opening but face significant operational and institutional barriers to implementation.Originality/value-This research offers a timely and critical assessment of a pivotal moment in Brazilian railway policy.It moves beyond a simplistic evaluation of volume growth to a structural analysis of market failures and the interplay between concession renewal and regulatory innovation.The findings provide actionable insights for policymakers in Brazil and other emerging economies seeking to balance private investment with public interest goals in railway infrastructure,highlighting the necessity of complementary,pro-competitive measures alongside financial investment.
文摘BACKGROUND Repeated application of the Pringle maneuver is a key obstacle to safe minimally invasive repeat liver resection(MISRLR).However,limited technical guidance is available.AIM To study the utility of newly developed Pringle taping method guided by liver surface in MISRLR.METHODS We retrospectively reviewed 72 cases of MISRLR performed by a single surgeon at two centers from August 2015 to July 2024.Beginning in October 2019,a liver surface-guided encirclement of hepatoduodenal ligament(LSEH)was used for repeat Pringle taping.Perioperative outcomes including Pringle taping success,operative time,blood loss,conversion rate,morbidity,and mortality were assessed.RESULTS Laparoscopic and robotic approaches were used in 63 patients and 9 patients,respectively.The median operative time,blood loss,and hospital stay were 331.5 minutes,70 mL,and 8 days,respectively.Open conversion occurred in two cases(2.8%)due to severe adhesions and right renal vein injury.Clavien-Dindo grade≥III complications occurred in 5.6%of cases with no mortality.Anti-adhesion barriers were used in 54 patients(75.0%).LSEH was attempted in 57 cases,improving Pringle taping success from 33.0%to 91.4%(P<0.001).LSEH succeeded in all patients with prior open liver resection(n=11).Among 6 patients in whom LSEH failed,3 patients(50.0%)had undergone a third liver resection,and 1 patient had a history of distal gastrectomy with choledochoduodenostomy.CONCLUSION The newly developed LSEH technique for Pringle taping in MISRLR was feasible,enhancing safety and reproducibility even in patients with a history of open liver resection.
基金supported by the National Research Foundation of South Korea(2023R1A2C2004516,RS-2023-00219399 to SPY,and 2022R1I1A1A01063513 to MGJ)。
文摘Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors,rigidity,and slowed movements.A key feature of Parkinson's disease is the accumulation of misfoldedα-synuclein,forming insoluble Lewy bodies in the substantia nigra pars compacta,which contributes to neurodegeneration.Theseα-synuclein aggregates may act as autoantigens,leading to T-cell-mediated neuroinflammation and contributing to dopaminergic cell death.Our perspective explores the hypothesis that Parkinson's disease may have an autoimmune component,highlighting research that connects peripheral immune responses with neurodegeneration.T cells derived from Parkinson's disease patients appear to have the potential to initiate an autoimmune response againstα-synuclein and its modified peptides,possibly leading to the formation of neo-epitopes.Recent evidence associates Parkinson's disease with abnormal immune responses,as indicated by increased levels of immune cells,such as CD4^(+)and CD8^(+)T cells,observed in both patients and mouse models.The convergence of T cells filtration increasing major histocompatibility complex molecules,and the susceptibility of dopaminergic neurons supports the hypothesis that Parkinson's disease may exhibit autoimmune characteristics.Understanding the immune mechanisms involved in Parkinson's disease will be crucial for developing therapeutic strategies that target the autoimmune aspects of the disease.Novel approaches,including precision medicine based on major histocompatibility complex/human leukocyte antigen typing and early biomarker identification,could pave the way for immune-based treatments aimed at slowing or halting disease progression.This perspective explores the relationship between autoimmunity and Parkinson's disease,suggesting that further research could deepen understanding and offer new therapeutic avenues.In this paper,it is organized to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease.It investigates critical areas such as the autoimmune response observed in Parkinson's disease patients and the role of autoimmune mechanisms targetingα-synuclein in Parkinson's disease.The paper also examines the impact of CD4~+T cells,specifically Th1 and Th17,on neurons through in vitro and ex vivo studies.Additionally,it explores howα-synuclein influences glia-induced neuroinflammation in Parkinson's disease.The discussion extends to the clinical implications and therapeutic landscape,offering insights into potential treatments.Consequently,we aim to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease,incorporating both supportive and opposing views on its classification as an autoimmune disorder and exploring implications for clinical applications.
文摘Plantago major L.,commonly known as plantain,waybread,or dooryard plantain,is a versatile medicinal plant with multiple therapeutic applications.Traditionally,various parts of the plant have been formulated into syrups,drops,ointments,vaginal suppositories,gargles,and roasted preparations to treat diverse ailments,such as liver disorders,earaches,epilepsy,asthma,stomachaches,diarrhea,constipation,polymenorrhea,and uterine disorders.The plant contains clinically valuable bioactive compounds,including polysaccharides,flavonoids,lipids,iridoid glycosides,caffeic acid derivatives,terpenoids,alkaloids,and organic acids.These bioactive constituents are the primary contributors to the plant’s broad spectrum of biological activities,including antioxidant,anti-inflammatory,antibacterial,antidiarrheal,hepatoprotective,antiviral,antiphage,antinociceptive,antiulcerogenic,antigenotoxic,and immunomodulatory effects of the plant.This review comprehensively summarizes the phytochemical composition,traditional medicinal applications,and biological properties of this multifunctional medicinal plant.
文摘The emergence of Medical Large Language Models has significantly transformed healthcare.Medical Large Language Models(Med-LLMs)serve as transformative tools that enhance clinical practice through applications in decision support,documentation,and diagnostics.This evaluation examines the performance of leading Med-LLMs,including GPT-4Med,Med-PaLM,MEDITRON,PubMedGPT,and MedAlpaca,across diverse medical datasets.It provides graphical comparisons of their effectiveness in distinct healthcare domains.The study introduces a domain-specific categorization system that aligns these models with optimal applications in clinical decision-making,documentation,drug discovery,research,patient interaction,and public health.The paper addresses deployment challenges of Medical-LLMs,emphasizing trustworthiness and explainability as essential requirements for healthcare AI.It presents current evaluation techniques that improve model transparency in high-stakes medical contexts and analyzes regulatory frameworks using benchmarking datasets such asMedQA,MedMCQA,PubMedQA,and MIMIC.By identifying ongoing challenges in biasmitigation,reliability,and ethical compliance,thiswork serves as a resource for selecting appropriate Med-LLMs and outlines future directions in the field.This analysis offers a roadmap for developing Med-LLMs that balance technological innovation with the trust and transparency required for clinical integration,a perspective often overlooked in existing literature.
