Body size control is fundamental to development and requires proper energy engagement.One of the key energy sensing factors is AMP-activated protein kinase(AMPK),which regulates glucose uptake to ensure ATP production...Body size control is fundamental to development and requires proper energy engagement.One of the key energy sensing factors is AMP-activated protein kinase(AMPK),which regulates glucose uptake to ensure ATP production and nutrition supply during development.Here,we identify that the mutation of xgr,a gene encoding an ATPase,results in a reduced body size in Drosophila.Xgr is primarily expressed in the epithelial cells of the Malpighian tubules and the midguts.Loss of xgr leads to the inactivation of the AMPK signaling due to an increased ATP level.Glucose reabsorption in the Malpighian tubules is significantly reduced,as the Glut1 translocation to the plasma membrane is significantly disrupted in the absence of Xgr function.Our results suggest that Xgr function in the Malpighian tubules is essential to systemic glucose supply and energy homeostasis at the organismal level,thereby impacting body size.Our findings provide a mechanistic connection between energy homeostasis and animal size control during development.展开更多
AIM:To determine whether paeonol(Pae),a naturally occurring phenolic compound,can serve as an effective pharmacological inhibitor of posterior capsular opacification(PCO).METHODS:A rat model of cataract surgery—induc...AIM:To determine whether paeonol(Pae),a naturally occurring phenolic compound,can serve as an effective pharmacological inhibitor of posterior capsular opacification(PCO).METHODS:A rat model of cataract surgery—induced PCO was established,and Pae was administered via anterior chamber injection to evaluate its preventive effect on capsular opacification and fibrotic remodeling.Histological and immunohistochemical analyses were performed to assess epithelial-mesenchymal transition(EMT)—related changes in lens epithelial cells(LECs).Ex vivo lens capsule cultures were employed to examine the expression of Vimentin and Zonula Occludens-1(ZO-1)by immunofluorescence and immunohistochemistry.In the human LEC line SRA01/04,EMT marker expression at both mRNA and protein levels was analyzed following transforming growth factor beta 2(TGF-β2)stimulation,with Pae treatment.Western blotting and immunofluorescence were used to investigate the effect of Pae on TGF-β/Smad signaling and AMP-activated protein kinase(AMPK)activation.Molecular docking was performed to predict Pae–AMPK binding,and rescue experiments with AMPK inhibition were conducted to validate the mechanistic pathway.RESULTS:Pae significantly reduced capsular opacification and fibrotic remodeling in the rat PCO model compared with controls.In LECs,Pae markedly suppressed TGF-β2–induced EMT,evidenced by decreased expression of mesenchymal markers,such as Vimentin,Fibronectin,Collagen 1A1,α-SMA and preserved epithelial junctional protein ZO-1.Mechanistically,Pae was predicted to directly interact with the catalytic pocket of AMPK,which was experimentally confirmed by enhanced AMPK phosphorylation and nuclear translocation(P<0.05).This activation disrupted canonical TGF-β/Smad signaling,leading to suppression of EMT.Rescue experiments using AMPK inhibition abrogated the anti-EMT effect of Pae,further validating the AMPK-dependent mechanism.CONCLUSION:Pae exerts a potent inhibitory effect on PCO formation by blocking EMT of LECs through direct activation of AMPK and subsequent disruption of TGF-β/Smad signaling.展开更多
Aligning natural language with operating system(OS)commands allows users to performcomplex computer tasks through simple natural language descriptions.However,due to the complex nature of natural language,it still rem...Aligning natural language with operating system(OS)commands allows users to performcomplex computer tasks through simple natural language descriptions.However,due to the complex nature of natural language,it still remains challenging to achieve precise alignment.In this paper,we present ComAlign,a Chinese benchmark dataset that pairs Chinese natural language descriptions with corresponding OS commands.ComAlign covers a broad range of 82 distinct OS command types with a total of 1811 natural language descriptions.We elaborate on the construction of ComAlign and construct three baselines to evaluate the alignment accuracy on ComAlign.Experimental results show that even advanced large language models struggle with certain ambiguously phrased OS commands.Specifically,the best performing baseline achieves 46.9%alignment accuracy.We demonstrate that ComAlign is collected from realworld application scenarios,making it particularly suitable for developing and benchmarking intelligent OS and agent systems that support user-machine interactions through natural language.展开更多
The decarbonization of urban water systems is critical for achieving global climate goals,and reducing the carbon intensity of urban water systems necessitates a paradigm shift from traditional end-of-pipe treatment a...The decarbonization of urban water systems is critical for achieving global climate goals,and reducing the carbon intensity of urban water systems necessitates a paradigm shift from traditional end-of-pipe treatment approaches to alternative technological solutions and holistic planning.This study explores a comprehensive strategy for achieving sustainable urban water management that integrates a decentral-ized water system(DWS),source separation,and low-carbon water treatment technologies.DWS is fun-damental to implementing a sustainable urban water system.This study addresses the social contexts,costs,approaches,and benefits associated with DWS implementation,emphasizing the importance of its construction.Subsequently,the analysis focuses on the on-site source separation of grey water,feces,and yellow water in the DWS,which serves as the primary approach for wastewater reuse and N/P recov-ery for a sustainable urban water system.Following source separation,low-carbon water treatment tech-nologies based on resource conservation and recovery are thoroughly discussed.Specifically,resource conservation can be achieved through rainwater control,efficiency improvements,and low energy con-sumption,while resource recovery can be attained through carbon capturing and energy/nutrient recov-ery.Overall,in response to the challenges in current urban water management,this study proposes a comprehensive strategy that supports a sustainable urban water system,providing theoretical guidance for reducing carbon emissions.展开更多
1.Introduction Nasopharyngeal carcinoma(NPC)has an imbalanced geographical and ethnic distribution,with notably high incidence rates in Southeastern Asia and China.China accounted for 42.4%of the newly diagnosed cases...1.Introduction Nasopharyngeal carcinoma(NPC)has an imbalanced geographical and ethnic distribution,with notably high incidence rates in Southeastern Asia and China.China accounted for 42.4%of the newly diagnosed cases worldwide in 2022.1NPC is sensitive to irradiation,and radiotherapy is the mainstay curative treatment modality.2The widespread use of intensity-modulated radiation therapy(IMRT)and image-guided radiotherapy(IGRT)has achieved great advances in survival outcomes and toxicity profiles among NPC patients.1In radiotherapy of NPC,the tumor’s proximity to critical structures demands accuracy in tumor delineation in order to avoid radiation-induced toxicities.However,tumor target delineation for radiotherapy of NPC is labor-intensive and radiation oncologists’proficiency varied considerably.3In recent years,the advent of big data analytics and artificial intelligence(AI)has opened up new avenues for improving the precision and efficacy of radiotherapy and individualized treatment in NPC management.3-6In this article,we explored how big data,AI-assisted delineation,radiotherapy planning,and adaptive radiotherapy(ART)are transforming clinical decision-making in NPC treatment.We also provided an outlook on the historical development of AI and big data,their current dominance in oncological radiotherapy,and their projected impact on future clinical practice(Figure 1).展开更多
Objective: Rheumatoid arthritis (RA) is an autoimmune disease in which angiogenesis represents a critical early event of synovial inflammation. The present study aimed to reveal the potential molecular mechanisms of S...Objective: Rheumatoid arthritis (RA) is an autoimmune disease in which angiogenesis represents a critical early event of synovial inflammation. The present study aimed to reveal the potential molecular mechanisms of SAA/TLR4 induction of angiogenesis through NETs in RA. Materials and methods: Firstly, immunohistochemistry and immunofluorescence were used to determinate TLR4 and NETs expression in synovial tissue, respectively. ELISA was used to detect the content of SAA, MPO and NE in serum and synovial fluid of patients. DNA quantification was done by fluorescence. DNA fluorescence staining was used to compare NETs formation in RA and HC sera, and to investigate the mechanism of NETs formation induced by SAA stimulation. PicoGreen DNA testing was used to characterize the DNA in the supernatants. Also, DNA fluorescence staining to explore whether NETs formation induced by SAA was dependent or independent on NADPH oxidase pathway. MTT assay, Wound healing assay, Tube formation assay were performed to analyze human veins umbilical cells (HUVECs) proliferation, migration, and tube vessels formation, respectively under NETs or NETs + DNase stimulants. Results: Firstly, we demonstrated that TLR4 was predominantly and widely expressed in synovial tissues with elevated serum levels of SAA, compared to osteoarthritis (OA) patients, and the similar results were observed for NETs formation. Afterwards, in a series of in vitro experiments, we reported an increased MPO and NE levels, and a relatively decreased DNA level in the sera of RA patients. Set apart, the levels of MPO and NE in RA were correlated to the disease activity. Moreover, an increased spontaneous NETs formation was observed in RA patients, enhanced under SAA stimulation and regulated by TLR4 activation. And the total DNA expressed in RA patients was partly composed of NET-DNA. Also, SAA induced NETs formation dependent on NADPH pathway. Finally, our results indicated that extracted SAA-induced NETs promoted endothelial cells (ECs) migration, proliferation, and vascular tube formation. Conclusion: Our current study highlighted the role of SAA/TLR4 interaction in the induction of angiogenesis through formed NETs. Therefore, this study offers new perspectives in the understanding of RA pathogenicity and its management.展开更多
Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
This paper reports the effects of fiber breakage defects and waviness defects on the compressive fatigue behavior and the progressive damage evolution process of 3D Multiaxial Braided Composites (3DMBCs). Combined wit...This paper reports the effects of fiber breakage defects and waviness defects on the compressive fatigue behavior and the progressive damage evolution process of 3D Multiaxial Braided Composites (3DMBCs). Combined with finite element compression simulation and ultra-depth microscope, the internal defect content of composites with different braiding angles was determined. The results demonstrate that the weakening effect of waviness and fiber breakage defects is greater than the strengthening effect of the braiding angle. This causes the fatigue resistance of 3DMBCs with the 31° braiding angle being better in both directions of 0° and 90°. The increase of 4° waviness and 10% fiber breakage defect results in the average fatigue life of composites being shortened by 48% and the energy consumption rate increased by 10% at 85% stress level in 90° compression direction. The alteration in loading direction modifies the included angle corresponding to the stress component. The stress component parallel to the fiber direction under compressive fatigue load leads to interfacial debonding in the composites, whereas the stress component perpendicular to the fiber direction results in pronounced shear failure.展开更多
Halogenated aromatic disinfection byproducts(DBPs)are gradually receiving attention due to their high detection frequency and usually higher toxicity than regulated DBPs.In this study,we established a solid phase extr...Halogenated aromatic disinfection byproducts(DBPs)are gradually receiving attention due to their high detection frequency and usually higher toxicity than regulated DBPs.In this study,we established a solid phase extraction(SPE)-LC-MS/MS method to simultaneously trace analyze 59 halogenated aromatic DBPs.The limits of detection and limits of quantification of halogenated aromatic DBPs ranged from 0.03 to 135.23 ng/L and from 0.1 to 450.76 ng/L,respectively.The range of recoveries and relative standard deviation(RSD)in river water were between 72.41%to 119.54%and 1.86%to 16.03%,respectively.Therefore,this method can be used to accurately analyze trace levels of halogenated aromatic DBPs in drinking water.The occurrence and transformation of halogenated aromatic DBPs were explored based on this method.In the chlorinated simulated source water and chlorinated river water,20 and 45 halogenated aromatic DBPs were determined,respectively.The active halogen species(HOCl,HOBr,and HOI)first reacted with natural organic matter(NOM)to form halogenated aromatic DBPs.Then,chlorine further reacted with the halogenated aromatic DBPs to convert them into small-molecule halogenated aliphatic DBPs through oxidation,electrophilic substitution,and hydrolysis reaction,etc.In the chlorinated simulated source water,chlorinated river water,and tap water,the toxicity contribution of bromoacetic acids(Br-HAAs)accounted for themajority(>71.16%).Given that halogenated aromatic DBPs are intermediate products of halogenated aliphatic DBPs,controlling the formation of halogenated aromatic DBPs is beneficial in decreasing the formation of halogenated aliphatic DBPs,thereby diminishing the toxicity of drinking water.展开更多
With the global advancement of the circular economy,integrating reverse osmosis(RO)or forward osmosis(FO)with anaerobic membrane bioreactor(AnMBR)offers a promising approach to simultaneously generate high-grade recla...With the global advancement of the circular economy,integrating reverse osmosis(RO)or forward osmosis(FO)with anaerobic membrane bioreactor(AnMBR)offers a promising approach to simultaneously generate high-grade reclaimed water,produce energy,and preserve valuable nutrients from municipal wastewater.However,the selectivity of these osmotic membranes towards ammonia nitrogen,a major component in municipal wastewater and anaerobic effluent,remains unsatisfactory due to its similar polarity and hydraulic radius to water molecules.Therefore,enhancing the ammonia nitrogen rejection of osmotic membranes is imperative to maximize the quality of reclaimed water and minimize the loss of ammonia nitrogen resources.Unfortunately,the current understanding of the mapping relationship between ammonia nitrogen transmembrane diffusion and the micro/nano-structure of osmotic membranes is not systematic,making precise optimization of the membranes challenging.Hence,this review comprehensively analyzed the diffusion behavior of ammonia nitrogen through osmotic membranes to lay the foundation for targeted regulation of membrane fine structure.Initially,the desire for ammonia/ammonium-rejecting membranes was highlighted by introducing current and promising osmotic membrane-based applications in municipal wastewater reclamation processes.Subsequently,the connection between the micro/nano-structure of osmotic membranes and the transmembrane diffusion behavior of ammonia nitrogen was explored by analyzing the effects of membrane characteristics on ammonia nitrogen transport using the DSPM-DE model.Finally,precise methods for modifying membranes to enhance ammonia nitrogen rejection were proposed.This review aims to offer theoretical insights guiding the development of RO and FO membranes with superior ammonia nitrogen rejection for efficient reclamation of municipal wastewater.展开更多
Background:Published clinical trials have yielded controversial findings regarding the effects of sex on the benefits of immune checkpoint inhibitors(ICIs).Sex-associated differences in the efficacy of immunotherapy r...Background:Published clinical trials have yielded controversial findings regarding the effects of sex on the benefits of immune checkpoint inhibitors(ICIs).Sex-associated differences in the efficacy of immunotherapy remain an important,unresolved question.Methods:We investigated sex-biased molecular profiles across a multitude of biomarkers linked to immunotherapy responses.Multiomics data from major solid tumors in The Cancer Genome Atlas,with sufficient sample sizes(≥50 patients of each sex),were analyzed.Ninety-five molecular markers characterizing 4 distinct aspects of the tumor immune system were summarized and compared.The inverse probability of weights algorithm was used to generate well-balanced sex subgroups.Results:Our results showed that lung squamous cell carcinoma(LUSC),pancreatic adenocarcinoma,and liver hepatocellular carcinoma were the top 3 cancer types with extensive sex-biased biomarker profiles(31/95,15/95,and 14/95,respectively).Notably,although both were categorized as non–small cell lung carcinoma,LUSC harbored significantly more sex-biased immunological features than those of lung adenocarcinoma(p<0.01).We further explored the validity of this finding by analyzing ICI-responsive signatures and individual patient-level data for non–small cell lung carcinoma and found that sex had significant interaction effects on immunotherapy outcomes in LUSC(p_(interaction)<0.05),with women tending to derive greater benefits from ICIs than men.However,this difference was not apparent in the lung adenocarcinoma group(p_(interaction)=0.66),with men and women deriving comparable benefits.Conclusions:We systematically characterized sex-biased profiles of key molecular biomarkers predicting immunotherapy responses across solid tumors,which could pave the way for individualized therapeutic approaches for men and women.展开更多
This study examines the integration of narrative medicine(NM)into primary healthcare(PHC)settings,evaluating its role in enhancing medical humanities education within grassroots healthcare institutions.Through a compr...This study examines the integration of narrative medicine(NM)into primary healthcare(PHC)settings,evaluating its role in enhancing medical humanities education within grassroots healthcare institutions.Through a comprehensive literature review and case analysis,the research investigates the current state,challenges,and practical barriers to embedding NM into PHC systems,while proposing targeted strategies for improvement.The findings suggest that NM fosters stronger doctor-patient trust,enhances healthcare quality,and promotes humanistic care.However,primary hospitals face numerous challenges in advancing medical humanities,including a lack of trust between doctors and patients,tensions arising from the commercialization of healthcare,institutional limitations,unequal distribution of resources,and issues related to physicians'professional competencies and stress management.These interrelated obstacles detract from the quality of PHC services and the overall patient experience.Drawing on successful case studies from primary hospitals,the paper outlines effective strategies for overcoming these challenges.The study provides both theoretical and practical insights for advancing medical humanities in PHC,contributing to improvements in healthcare service quality and supporting the development of high standards in the healthcare sector.Ultimately,the findings aim to promote the broader adoption and ongoing refinement of NM within PHC institutions.展开更多
The catalyst's structural dynamics under reaction conditions critically determine their performance.We proved this indication by studying Ni nanoparticles supported on Mo_(2)CT_(x) MXene,where the average size dur...The catalyst's structural dynamics under reaction conditions critically determine their performance.We proved this indication by studying Ni nanoparticles supported on Mo_(2)CT_(x) MXene,where the average size during CO_(2) hydrogenation changed from 12.9 to 3.1 nm.A parallel increase of CO selectivity from 21.1%to 92.6%at 400℃ was observed,while the CO_(2) conversion rate remained at about 84.0 mmol·g_(cat)^(-1)·h^(-1).This transformation involved partial removal of Mo_(2)CT_(x) terminal groups,allowing direct interaction between Ni and Mo atoms instead of indirect coupling through-O terminations.The shift from a Ni-O-Mo to a Ni-Mo interaction enhanced electron transfer from Ni to Mo_(2)CT_(x),strengthening the metal-support interaction and driving Ni nanoparticle dispersion.In-situ mechanistic analysis and kinetic isotope studies revealed that Ni dispersion suppresses the formate and carboxyl pathway,promotes direct CO_(2) dissociation,and inhibits CO hydrogenation,shifting the primary product from CH_(4) to CO.These findings provide a strategy for designing highly selective and stable MXene-based catalysts through engineered metal-support interactions.展开更多
Biological neurons can be excited to maintain certain firing patterns following different external stimuli,and similar changes in electrical activities can be reproduced in some neural circuits by applying an external...Biological neurons can be excited to maintain certain firing patterns following different external stimuli,and similar changes in electrical activities can be reproduced in some neural circuits by applying an external voltage.Generic neural circuits are composed of capacitors,induction coils,resistors,and nonlinear resistors,and continuous energy exchange between the capacitive and inductive components is crucial for preserving output voltages.Incorporating nonlinear elements causes interactions between the charge flow across the capacitor and the induced electromotive force on the inductor.It is a challenge to explore the occurrence of nonlinear oscillation and coherence resonance in a neural circuit without using a capacitor and nonlinear resistor,and it considers the case lack of electric field energy.In this paper,a simple neural circuit is proposed that combines two inductors,one magnetic flux-controlled memristor(MFCM),and three resistors,with two constant voltage sources in the branch circuits used as reverse potentials in the ion channels.The field energy has an exact form,and it is stored in the circuit components as a magnetic field.Scale transformation is applied on the circuit equations and field energy function to obtain equivalent dimensionless forms of the memristive neuron and Hamilton energy.The reference values for the physical time and capacitance are represented by an appropriate combination of resistance and inductance,because the capacitance value is unavailable.The memristive neuron without capacitive effect still shows similar firing patterns,and coherence resonance is induced under noisy excitation.The emergence of coherence resonance can be predicted by calculating the distribution of the average energy<H>versus noise intensity,and the value for<H>reaches a maximum under coherence resonance.Finally,an adaptive law for parameter growth under energy control is proposed to control mode transitions in the electrical activity.The methodology and results of this work offer insights into the oscillatory mechanism of neural circuits,and showcase how magnetic field control can be used to manage neural activations.展开更多
According to the International Cancer Research Institute of the World Health Organization data,nasopharyngeal carcinoma(NPC)remains a significant health concern,particularly in regions such as Southeast Asia and south...According to the International Cancer Research Institute of the World Health Organization data,nasopharyngeal carcinoma(NPC)remains a significant health concern,particularly in regions such as Southeast Asia and southern China.Recently,substantial progress has been made in the field of basic and translational research on NPC,enhancing our understanding of the molecular mechanisms underlying the disease and paving the way for precise therapeutic approaches.This review summarizes the advances in NPC research,focusing on key areas that include radiotherapy and chemotherapy resistance and tumor metastasis,microenvironment,metabolism,microbiome,and biomarkers.Additionally,future research directions in NPC are discussed to provide valuable insights to advance the field further.展开更多
The aerospace and aviation industry has long been at the forefront of materials and processing technologies,driven by its ongoing demand for lightweight,highly reliable,and durable components.Precision manufacturing i...The aerospace and aviation industry has long been at the forefront of materials and processing technologies,driven by its ongoing demand for lightweight,highly reliable,and durable components.Precision manufacturing is a critical discipline that directly affects the performance,functionality,and safety of aircraft and aerospace vehicles.To meet the above-mentioned stringent requirements,advanced materials and cutting-edge processing technologies have evolved alongside aerospace innovations.展开更多
BACKGROUND Solid fuel use for cooking and heating is a major environmental risk factor,yet its association with new-onset heart disease(HD)remains unclear.The aim of this study was to investigate the relationship betw...BACKGROUND Solid fuel use for cooking and heating is a major environmental risk factor,yet its association with new-onset heart disease(HD)remains unclear.The aim of this study was to investigate the relationship between solid fuel exposure and new-onset HD in a large cohort.METHODS Multivariable logistic regression models assessed associations between cooking/heating fuel types(coal,crop residue/wood,liquefied petroleum gas,natural gas,and others)and new-onset HD.Subgroup analyses explored effect modification by age,sex,education,smoking,alcohol use,and region.RESULTS A prospective cohort study included 5915 participants,with 781 participants(13.2%)developing new-onset HD.Coal use for cooking showed an initial association with new-onset HD risk(OR=1.41,95%CI:1.06–1.86,P=0.02),which attenuated after full adjustment(OR=1.28,95%CI:0.96–1.72,P=0.10).Coal use for heating demonstrated robust associations across all models(OR=1.86,95%CI:1.42–2.43,P<0.001).Crop residue/wood burning for heating was also significant(Model 2:OR=1.40,95%CI:1.06–1.86,P=0.02).Subgroup analyses revealed stronger associations among females,non-smokers,non-drinkers,and less-educated participants.Geographic stratification showed significant associations in southern but not northern regions.CONCLUSIONS Solid fuel use,particularly coal for heating,is associated with increased new-onset HD risk.Reducing solid fuel exposure is crucial for HD prevention in low-resource settings.展开更多
基金funded by the National Key R&D Program of China(2021YFA0805800,2023YFE0107700,and 2020YFA0803202 to R.J.),the 111 Project(D18010 to R.J.)the Guangzhou Medical University Discipline Construction Funds(Basic Medicine)(JCXKJS2022A02 to R.J.)+1 种基金Guangdong Basic and Applied Basic Research Foundation(2024A1515010752 to C.W.)the Special Innovation Projects of Universities in Guangdong Province(2022KTSCx096 to C.W.).
文摘Body size control is fundamental to development and requires proper energy engagement.One of the key energy sensing factors is AMP-activated protein kinase(AMPK),which regulates glucose uptake to ensure ATP production and nutrition supply during development.Here,we identify that the mutation of xgr,a gene encoding an ATPase,results in a reduced body size in Drosophila.Xgr is primarily expressed in the epithelial cells of the Malpighian tubules and the midguts.Loss of xgr leads to the inactivation of the AMPK signaling due to an increased ATP level.Glucose reabsorption in the Malpighian tubules is significantly reduced,as the Glut1 translocation to the plasma membrane is significantly disrupted in the absence of Xgr function.Our results suggest that Xgr function in the Malpighian tubules is essential to systemic glucose supply and energy homeostasis at the organismal level,thereby impacting body size.Our findings provide a mechanistic connection between energy homeostasis and animal size control during development.
基金Supported by the Projects of Medical and Health Technology Development Program in Shandong Province(No.202107021009)Shandong Provincial Traditional Chinese Medicine Science and Technology Project(No.M-2023118).
文摘AIM:To determine whether paeonol(Pae),a naturally occurring phenolic compound,can serve as an effective pharmacological inhibitor of posterior capsular opacification(PCO).METHODS:A rat model of cataract surgery—induced PCO was established,and Pae was administered via anterior chamber injection to evaluate its preventive effect on capsular opacification and fibrotic remodeling.Histological and immunohistochemical analyses were performed to assess epithelial-mesenchymal transition(EMT)—related changes in lens epithelial cells(LECs).Ex vivo lens capsule cultures were employed to examine the expression of Vimentin and Zonula Occludens-1(ZO-1)by immunofluorescence and immunohistochemistry.In the human LEC line SRA01/04,EMT marker expression at both mRNA and protein levels was analyzed following transforming growth factor beta 2(TGF-β2)stimulation,with Pae treatment.Western blotting and immunofluorescence were used to investigate the effect of Pae on TGF-β/Smad signaling and AMP-activated protein kinase(AMPK)activation.Molecular docking was performed to predict Pae–AMPK binding,and rescue experiments with AMPK inhibition were conducted to validate the mechanistic pathway.RESULTS:Pae significantly reduced capsular opacification and fibrotic remodeling in the rat PCO model compared with controls.In LECs,Pae markedly suppressed TGF-β2–induced EMT,evidenced by decreased expression of mesenchymal markers,such as Vimentin,Fibronectin,Collagen 1A1,α-SMA and preserved epithelial junctional protein ZO-1.Mechanistically,Pae was predicted to directly interact with the catalytic pocket of AMPK,which was experimentally confirmed by enhanced AMPK phosphorylation and nuclear translocation(P<0.05).This activation disrupted canonical TGF-β/Smad signaling,leading to suppression of EMT.Rescue experiments using AMPK inhibition abrogated the anti-EMT effect of Pae,further validating the AMPK-dependent mechanism.CONCLUSION:Pae exerts a potent inhibitory effect on PCO formation by blocking EMT of LECs through direct activation of AMPK and subsequent disruption of TGF-β/Smad signaling.
基金supported by the National Key Research and Development Program under Grant 2024YFB4506200the Science and Technology Innovation Program of Hunan Province under Grant 2024RC1048the National Key Laboratory Foundation Project under Grant 2024-KJWPDL-14.
文摘Aligning natural language with operating system(OS)commands allows users to performcomplex computer tasks through simple natural language descriptions.However,due to the complex nature of natural language,it still remains challenging to achieve precise alignment.In this paper,we present ComAlign,a Chinese benchmark dataset that pairs Chinese natural language descriptions with corresponding OS commands.ComAlign covers a broad range of 82 distinct OS command types with a total of 1811 natural language descriptions.We elaborate on the construction of ComAlign and construct three baselines to evaluate the alignment accuracy on ComAlign.Experimental results show that even advanced large language models struggle with certain ambiguously phrased OS commands.Specifically,the best performing baseline achieves 46.9%alignment accuracy.We demonstrate that ComAlign is collected from realworld application scenarios,making it particularly suitable for developing and benchmarking intelligent OS and agent systems that support user-machine interactions through natural language.
基金supported by the National Natural Science Foun-dation of China(52200008 and 52270043)the Young Elite Scien-tists Sponsorship Program by CAST,National Key Research and Developing Program of China(2023YFE0113800)+1 种基金the China Post-doctoral Science Foundation(2022M710034)the Chengde National Sustainable Development Agenda Innovation Demonstra-tion Zone Construction Technology Special Project(202202F003).
文摘The decarbonization of urban water systems is critical for achieving global climate goals,and reducing the carbon intensity of urban water systems necessitates a paradigm shift from traditional end-of-pipe treatment approaches to alternative technological solutions and holistic planning.This study explores a comprehensive strategy for achieving sustainable urban water management that integrates a decentral-ized water system(DWS),source separation,and low-carbon water treatment technologies.DWS is fun-damental to implementing a sustainable urban water system.This study addresses the social contexts,costs,approaches,and benefits associated with DWS implementation,emphasizing the importance of its construction.Subsequently,the analysis focuses on the on-site source separation of grey water,feces,and yellow water in the DWS,which serves as the primary approach for wastewater reuse and N/P recov-ery for a sustainable urban water system.Following source separation,low-carbon water treatment tech-nologies based on resource conservation and recovery are thoroughly discussed.Specifically,resource conservation can be achieved through rainwater control,efficiency improvements,and low energy con-sumption,while resource recovery can be attained through carbon capturing and energy/nutrient recov-ery.Overall,in response to the challenges in current urban water management,this study proposes a comprehensive strategy that supports a sustainable urban water system,providing theoretical guidance for reducing carbon emissions.
基金supported in part by the National Natural Science Foundation of China(92259202)the Guangzhou Municipal Health Commission(2023P-GX02)+2 种基金the Science and Technology Projects in Guangzhou(2024B01J1301)the Fundamental Research Funds for the Central Universities,Sun Yat-sen University Clinical Research 5010 Program(2024001)the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center(CIRP-SYSUCC-0010).
文摘1.Introduction Nasopharyngeal carcinoma(NPC)has an imbalanced geographical and ethnic distribution,with notably high incidence rates in Southeastern Asia and China.China accounted for 42.4%of the newly diagnosed cases worldwide in 2022.1NPC is sensitive to irradiation,and radiotherapy is the mainstay curative treatment modality.2The widespread use of intensity-modulated radiation therapy(IMRT)and image-guided radiotherapy(IGRT)has achieved great advances in survival outcomes and toxicity profiles among NPC patients.1In radiotherapy of NPC,the tumor’s proximity to critical structures demands accuracy in tumor delineation in order to avoid radiation-induced toxicities.However,tumor target delineation for radiotherapy of NPC is labor-intensive and radiation oncologists’proficiency varied considerably.3In recent years,the advent of big data analytics and artificial intelligence(AI)has opened up new avenues for improving the precision and efficacy of radiotherapy and individualized treatment in NPC management.3-6In this article,we explored how big data,AI-assisted delineation,radiotherapy planning,and adaptive radiotherapy(ART)are transforming clinical decision-making in NPC treatment.We also provided an outlook on the historical development of AI and big data,their current dominance in oncological radiotherapy,and their projected impact on future clinical practice(Figure 1).
文摘Objective: Rheumatoid arthritis (RA) is an autoimmune disease in which angiogenesis represents a critical early event of synovial inflammation. The present study aimed to reveal the potential molecular mechanisms of SAA/TLR4 induction of angiogenesis through NETs in RA. Materials and methods: Firstly, immunohistochemistry and immunofluorescence were used to determinate TLR4 and NETs expression in synovial tissue, respectively. ELISA was used to detect the content of SAA, MPO and NE in serum and synovial fluid of patients. DNA quantification was done by fluorescence. DNA fluorescence staining was used to compare NETs formation in RA and HC sera, and to investigate the mechanism of NETs formation induced by SAA stimulation. PicoGreen DNA testing was used to characterize the DNA in the supernatants. Also, DNA fluorescence staining to explore whether NETs formation induced by SAA was dependent or independent on NADPH oxidase pathway. MTT assay, Wound healing assay, Tube formation assay were performed to analyze human veins umbilical cells (HUVECs) proliferation, migration, and tube vessels formation, respectively under NETs or NETs + DNase stimulants. Results: Firstly, we demonstrated that TLR4 was predominantly and widely expressed in synovial tissues with elevated serum levels of SAA, compared to osteoarthritis (OA) patients, and the similar results were observed for NETs formation. Afterwards, in a series of in vitro experiments, we reported an increased MPO and NE levels, and a relatively decreased DNA level in the sera of RA patients. Set apart, the levels of MPO and NE in RA were correlated to the disease activity. Moreover, an increased spontaneous NETs formation was observed in RA patients, enhanced under SAA stimulation and regulated by TLR4 activation. And the total DNA expressed in RA patients was partly composed of NET-DNA. Also, SAA induced NETs formation dependent on NADPH pathway. Finally, our results indicated that extracted SAA-induced NETs promoted endothelial cells (ECs) migration, proliferation, and vascular tube formation. Conclusion: Our current study highlighted the role of SAA/TLR4 interaction in the induction of angiogenesis through formed NETs. Therefore, this study offers new perspectives in the understanding of RA pathogenicity and its management.
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
基金supported by the National Natural Science Foundation,China(Nos.52073224,12472141 and 12002248)the Natural Science Foundation of Shaanxi Province,China(Nos.2023KXJ-034 and 2023KXJ-005)+3 种基金Xi’an Science and Technology Plan Project,China(No.2022JH-ZCZC-0004)the Young Talent Fund of University Association for Science and Technology in Shaanxi,China(No.20210509)the Scientific Research Project of Shaanxi Provincial Education Department,China(No.22JC035)Shaanxi Outstanding Youth Science Fund Project,China(No.2024JC-JCQN-03).
文摘This paper reports the effects of fiber breakage defects and waviness defects on the compressive fatigue behavior and the progressive damage evolution process of 3D Multiaxial Braided Composites (3DMBCs). Combined with finite element compression simulation and ultra-depth microscope, the internal defect content of composites with different braiding angles was determined. The results demonstrate that the weakening effect of waviness and fiber breakage defects is greater than the strengthening effect of the braiding angle. This causes the fatigue resistance of 3DMBCs with the 31° braiding angle being better in both directions of 0° and 90°. The increase of 4° waviness and 10% fiber breakage defect results in the average fatigue life of composites being shortened by 48% and the energy consumption rate increased by 10% at 85% stress level in 90° compression direction. The alteration in loading direction modifies the included angle corresponding to the stress component. The stress component parallel to the fiber direction under compressive fatigue load leads to interfacial debonding in the composites, whereas the stress component perpendicular to the fiber direction results in pronounced shear failure.
基金supported by the National Natural Science Foundation of China(No.52300005)China Postdoctoral Science Foundation(No.2023TQ0098)+5 种基金Heilongjiang Postdoctoral Fund(No.LBH-Z23175)Heilongjiang Touyan Innovation Team Program(No.HIT-SE-01)the Crossover Fund of Medical Engineering Science of Harbin Institute of Technology(No.IR2021107)the National Natural Science Foundation of International(Regional)Cooperation and Exchange Project(No.51961125104)the State Key Laboratory of Urban Water Resource and Environment(Harbin Institute of Technology)(No.2022TS15)the Ecological and Environmental Protection Research Project of Heilongjiang Province(No.HST2022ST006).
文摘Halogenated aromatic disinfection byproducts(DBPs)are gradually receiving attention due to their high detection frequency and usually higher toxicity than regulated DBPs.In this study,we established a solid phase extraction(SPE)-LC-MS/MS method to simultaneously trace analyze 59 halogenated aromatic DBPs.The limits of detection and limits of quantification of halogenated aromatic DBPs ranged from 0.03 to 135.23 ng/L and from 0.1 to 450.76 ng/L,respectively.The range of recoveries and relative standard deviation(RSD)in river water were between 72.41%to 119.54%and 1.86%to 16.03%,respectively.Therefore,this method can be used to accurately analyze trace levels of halogenated aromatic DBPs in drinking water.The occurrence and transformation of halogenated aromatic DBPs were explored based on this method.In the chlorinated simulated source water and chlorinated river water,20 and 45 halogenated aromatic DBPs were determined,respectively.The active halogen species(HOCl,HOBr,and HOI)first reacted with natural organic matter(NOM)to form halogenated aromatic DBPs.Then,chlorine further reacted with the halogenated aromatic DBPs to convert them into small-molecule halogenated aliphatic DBPs through oxidation,electrophilic substitution,and hydrolysis reaction,etc.In the chlorinated simulated source water,chlorinated river water,and tap water,the toxicity contribution of bromoacetic acids(Br-HAAs)accounted for themajority(>71.16%).Given that halogenated aromatic DBPs are intermediate products of halogenated aliphatic DBPs,controlling the formation of halogenated aromatic DBPs is beneficial in decreasing the formation of halogenated aliphatic DBPs,thereby diminishing the toxicity of drinking water.
基金supported by National Natural Science Foundation of China(No.52200051)Harbin Institute of Technology(No.HC202236)Outstanding Youth Fund of Heilongjiang Natural Science Foundation(No.YQ2023E021)。
文摘With the global advancement of the circular economy,integrating reverse osmosis(RO)or forward osmosis(FO)with anaerobic membrane bioreactor(AnMBR)offers a promising approach to simultaneously generate high-grade reclaimed water,produce energy,and preserve valuable nutrients from municipal wastewater.However,the selectivity of these osmotic membranes towards ammonia nitrogen,a major component in municipal wastewater and anaerobic effluent,remains unsatisfactory due to its similar polarity and hydraulic radius to water molecules.Therefore,enhancing the ammonia nitrogen rejection of osmotic membranes is imperative to maximize the quality of reclaimed water and minimize the loss of ammonia nitrogen resources.Unfortunately,the current understanding of the mapping relationship between ammonia nitrogen transmembrane diffusion and the micro/nano-structure of osmotic membranes is not systematic,making precise optimization of the membranes challenging.Hence,this review comprehensively analyzed the diffusion behavior of ammonia nitrogen through osmotic membranes to lay the foundation for targeted regulation of membrane fine structure.Initially,the desire for ammonia/ammonium-rejecting membranes was highlighted by introducing current and promising osmotic membrane-based applications in municipal wastewater reclamation processes.Subsequently,the connection between the micro/nano-structure of osmotic membranes and the transmembrane diffusion behavior of ammonia nitrogen was explored by analyzing the effects of membrane characteristics on ammonia nitrogen transport using the DSPM-DE model.Finally,precise methods for modifying membranes to enhance ammonia nitrogen rejection were proposed.This review aims to offer theoretical insights guiding the development of RO and FO membranes with superior ammonia nitrogen rejection for efficient reclamation of municipal wastewater.
基金supported by grants from the Special Funding of China Postdoctoral Science Foundation(No.2022TQ0389)the National Natural Science Foundation of China(No.82303693)the National Postdoctoral Program for Innovative Talents(No.BX2021386)。
文摘Background:Published clinical trials have yielded controversial findings regarding the effects of sex on the benefits of immune checkpoint inhibitors(ICIs).Sex-associated differences in the efficacy of immunotherapy remain an important,unresolved question.Methods:We investigated sex-biased molecular profiles across a multitude of biomarkers linked to immunotherapy responses.Multiomics data from major solid tumors in The Cancer Genome Atlas,with sufficient sample sizes(≥50 patients of each sex),were analyzed.Ninety-five molecular markers characterizing 4 distinct aspects of the tumor immune system were summarized and compared.The inverse probability of weights algorithm was used to generate well-balanced sex subgroups.Results:Our results showed that lung squamous cell carcinoma(LUSC),pancreatic adenocarcinoma,and liver hepatocellular carcinoma were the top 3 cancer types with extensive sex-biased biomarker profiles(31/95,15/95,and 14/95,respectively).Notably,although both were categorized as non–small cell lung carcinoma,LUSC harbored significantly more sex-biased immunological features than those of lung adenocarcinoma(p<0.01).We further explored the validity of this finding by analyzing ICI-responsive signatures and individual patient-level data for non–small cell lung carcinoma and found that sex had significant interaction effects on immunotherapy outcomes in LUSC(p_(interaction)<0.05),with women tending to derive greater benefits from ICIs than men.However,this difference was not apparent in the lung adenocarcinoma group(p_(interaction)=0.66),with men and women deriving comparable benefits.Conclusions:We systematically characterized sex-biased profiles of key molecular biomarkers predicting immunotherapy responses across solid tumors,which could pave the way for individualized therapeutic approaches for men and women.
基金Supported by National Natural Science Foundation of China,No.82272204 and No.824721882022 Key Clinical Specialty of Zhejiang Province(Critical Care Medicine)+4 种基金“Pioneer”and“Leading Goose”R&D Program of Zhejiang,No.2023C03084Wenzhou Major Science and Technology Innovation Project,No.ZY2023005Central Guiding Local Technology Development,No.2024ZY01012Zhejiang Provincial College Students'Science and Technology Innovation Activity Program,No.2024R413A037National Innovation and Entrepreneurship Training Program for College Students,No.202410343030.
文摘This study examines the integration of narrative medicine(NM)into primary healthcare(PHC)settings,evaluating its role in enhancing medical humanities education within grassroots healthcare institutions.Through a comprehensive literature review and case analysis,the research investigates the current state,challenges,and practical barriers to embedding NM into PHC systems,while proposing targeted strategies for improvement.The findings suggest that NM fosters stronger doctor-patient trust,enhances healthcare quality,and promotes humanistic care.However,primary hospitals face numerous challenges in advancing medical humanities,including a lack of trust between doctors and patients,tensions arising from the commercialization of healthcare,institutional limitations,unequal distribution of resources,and issues related to physicians'professional competencies and stress management.These interrelated obstacles detract from the quality of PHC services and the overall patient experience.Drawing on successful case studies from primary hospitals,the paper outlines effective strategies for overcoming these challenges.The study provides both theoretical and practical insights for advancing medical humanities in PHC,contributing to improvements in healthcare service quality and supporting the development of high standards in the healthcare sector.Ultimately,the findings aim to promote the broader adoption and ongoing refinement of NM within PHC institutions.
文摘The catalyst's structural dynamics under reaction conditions critically determine their performance.We proved this indication by studying Ni nanoparticles supported on Mo_(2)CT_(x) MXene,where the average size during CO_(2) hydrogenation changed from 12.9 to 3.1 nm.A parallel increase of CO selectivity from 21.1%to 92.6%at 400℃ was observed,while the CO_(2) conversion rate remained at about 84.0 mmol·g_(cat)^(-1)·h^(-1).This transformation involved partial removal of Mo_(2)CT_(x) terminal groups,allowing direct interaction between Ni and Mo atoms instead of indirect coupling through-O terminations.The shift from a Ni-O-Mo to a Ni-Mo interaction enhanced electron transfer from Ni to Mo_(2)CT_(x),strengthening the metal-support interaction and driving Ni nanoparticle dispersion.In-situ mechanistic analysis and kinetic isotope studies revealed that Ni dispersion suppresses the formate and carboxyl pathway,promotes direct CO_(2) dissociation,and inhibits CO hydrogenation,shifting the primary product from CH_(4) to CO.These findings provide a strategy for designing highly selective and stable MXene-based catalysts through engineered metal-support interactions.
基金supported by the National Natural Science Foundation of China(No.62361037).
文摘Biological neurons can be excited to maintain certain firing patterns following different external stimuli,and similar changes in electrical activities can be reproduced in some neural circuits by applying an external voltage.Generic neural circuits are composed of capacitors,induction coils,resistors,and nonlinear resistors,and continuous energy exchange between the capacitive and inductive components is crucial for preserving output voltages.Incorporating nonlinear elements causes interactions between the charge flow across the capacitor and the induced electromotive force on the inductor.It is a challenge to explore the occurrence of nonlinear oscillation and coherence resonance in a neural circuit without using a capacitor and nonlinear resistor,and it considers the case lack of electric field energy.In this paper,a simple neural circuit is proposed that combines two inductors,one magnetic flux-controlled memristor(MFCM),and three resistors,with two constant voltage sources in the branch circuits used as reverse potentials in the ion channels.The field energy has an exact form,and it is stored in the circuit components as a magnetic field.Scale transformation is applied on the circuit equations and field energy function to obtain equivalent dimensionless forms of the memristive neuron and Hamilton energy.The reference values for the physical time and capacitance are represented by an appropriate combination of resistance and inductance,because the capacitance value is unavailable.The memristive neuron without capacitive effect still shows similar firing patterns,and coherence resonance is induced under noisy excitation.The emergence of coherence resonance can be predicted by calculating the distribution of the average energy<H>versus noise intensity,and the value for<H>reaches a maximum under coherence resonance.Finally,an adaptive law for parameter growth under energy control is proposed to control mode transitions in the electrical activity.The methodology and results of this work offer insights into the oscillatory mechanism of neural circuits,and showcase how magnetic field control can be used to manage neural activations.
基金supported by the National Natural Science Foundation of China(no.81930072 and no.82172870 to J.Ma)by the Key-Area Research and Development Program of Guangdong Province(no.2019B020230002 to J.Ma).
文摘According to the International Cancer Research Institute of the World Health Organization data,nasopharyngeal carcinoma(NPC)remains a significant health concern,particularly in regions such as Southeast Asia and southern China.Recently,substantial progress has been made in the field of basic and translational research on NPC,enhancing our understanding of the molecular mechanisms underlying the disease and paving the way for precise therapeutic approaches.This review summarizes the advances in NPC research,focusing on key areas that include radiotherapy and chemotherapy resistance and tumor metastasis,microenvironment,metabolism,microbiome,and biomarkers.Additionally,future research directions in NPC are discussed to provide valuable insights to advance the field further.
文摘The aerospace and aviation industry has long been at the forefront of materials and processing technologies,driven by its ongoing demand for lightweight,highly reliable,and durable components.Precision manufacturing is a critical discipline that directly affects the performance,functionality,and safety of aircraft and aerospace vehicles.To meet the above-mentioned stringent requirements,advanced materials and cutting-edge processing technologies have evolved alongside aerospace innovations.
基金supported by the Sichuan Provincial Cadre Health Research Project(ZH2024-101)the Key Natural Science Foundation of Sichuan Province(No.2025 ZNSFSC0053)。
文摘BACKGROUND Solid fuel use for cooking and heating is a major environmental risk factor,yet its association with new-onset heart disease(HD)remains unclear.The aim of this study was to investigate the relationship between solid fuel exposure and new-onset HD in a large cohort.METHODS Multivariable logistic regression models assessed associations between cooking/heating fuel types(coal,crop residue/wood,liquefied petroleum gas,natural gas,and others)and new-onset HD.Subgroup analyses explored effect modification by age,sex,education,smoking,alcohol use,and region.RESULTS A prospective cohort study included 5915 participants,with 781 participants(13.2%)developing new-onset HD.Coal use for cooking showed an initial association with new-onset HD risk(OR=1.41,95%CI:1.06–1.86,P=0.02),which attenuated after full adjustment(OR=1.28,95%CI:0.96–1.72,P=0.10).Coal use for heating demonstrated robust associations across all models(OR=1.86,95%CI:1.42–2.43,P<0.001).Crop residue/wood burning for heating was also significant(Model 2:OR=1.40,95%CI:1.06–1.86,P=0.02).Subgroup analyses revealed stronger associations among females,non-smokers,non-drinkers,and less-educated participants.Geographic stratification showed significant associations in southern but not northern regions.CONCLUSIONS Solid fuel use,particularly coal for heating,is associated with increased new-onset HD risk.Reducing solid fuel exposure is crucial for HD prevention in low-resource settings.
