The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions l...The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.展开更多
BACKGROUND Sorafenib has been the conventional treatment for advanced hepatocellular carcinoma(HCC)since 2008.While radiological complete responses are extremely rare,improved supportive care and multidisciplinary app...BACKGROUND Sorafenib has been the conventional treatment for advanced hepatocellular carcinoma(HCC)since 2008.While radiological complete responses are extremely rare,improved supportive care and multidisciplinary approaches in clinical practice may explain the recent increase in case reports and retrospective series documenting such responses.CASE SUMMARY This case series describes 3 patients with advanced HCC who achieved durable complete responses using first-line sorafenib therapy,even in the presence of portal vein thrombosis or extrahepatic spread,and highlights the potential for sustained remission in selected patients.Dermatologic toxicity and non-viral etiology may correlate with favorable outcomes;however,reliable predictive biomarkers for sorafenib response are lacking.CONCLUSION Future research into the etiology and molecular differences in HCC is necessary to develop more personalized therapy options.展开更多
Field-effect nanofluidic transistors(FENTs),biomimicking the structure and functionality of neuron,act as biological transistors with the ability to gate switching responses to external stimuli.The switching ratio has...Field-effect nanofluidic transistors(FENTs),biomimicking the structure and functionality of neuron,act as biological transistors with the ability to gate switching responses to external stimuli.The switching ratio has been verified to evaluate the performance of FENTs,but until recently,the response time,another crucial indicator,has been ignored.Employing finite-element method,we investigated the relationship among gate charge,switching ratio and response time by divisionally manipulating gate charge,including entrance surface and the surface of confinement space,for ion transport to optimize switching capability.The dual-split gate charge on FENTs exhibits synergistic effect on switching response.Based on the two regional gate charge on FENTs,multivalence ions in lower concentration,high aspect ratio and single channel show higher switching ratio but longer response time compared to monovalent ions.The findings highlight the necessity of balancing these two signals in FENTs and offer insights for optimizing their design and expanding applications to dual-signal-detection iontronics.展开更多
This study examines the dynamic response of two adjacent 9-and 20-story benchmark steel buildings subjected to six near-fault earthquake records.Two-dimensional numerical models were employed to account for the comple...This study examines the dynamic response of two adjacent 9-and 20-story benchmark steel buildings subjected to six near-fault earthquake records.Two-dimensional numerical models were employed to account for the complexities of structure-soil-structure interaction(SSSI).The research focuses on the separation gap between the buildings and the effects of pounding while considering Fixed Base(FB)and SSSI models,evaluated according to UBC 94 and ASCE 7-16 seismic codes.Key findings reveal that pounding occurs with the UBC 94 separation gap when earthquake frequency aligns with system frequency,leading to increased column stresses in the 9-story building.In contrast,the ASCE 7-16 standard effectively prevents pounding in both the FB and SSSI models.Additionally,drifts and displacements of lower floors in SSSI models exceed the allowable limits of ASCE 7-16,underscoring the impact of soil-structure interaction on seismic response.展开更多
As sessile organisms,plants must adapt various stresses.Accordingly,they have evolved several plant-specific growth and developmental processes.WRKY53 is a member of the WRKY transcription factor family,which plays a ...As sessile organisms,plants must adapt various stresses.Accordingly,they have evolved several plant-specific growth and developmental processes.WRKY53 is a member of the WRKY transcription factor family,which plays a crucial role in rice growth and development,stress response,and hormone signal transduction.This review discusses the role of WRKY53 in stress response,focusing on its functions in cold tolerance,salt tolerance,disease resistance,and pest defense,and explores its role in regulating rice leaf senescence and seed germination.This article also proposes future research directions,including functional genomics studies,protein interaction network analyses,hormone signal transduction pathways,genetic improvement strategies,applications of gene editing technologies,molecular basis of stress responses,cross-species functional conservation,and bioinformatics and comparative genomics research.This review highlights the importance of WRKY53 in rice biology and provides new perspectives and strategies for future research and genetic improvement of rice.展开更多
To achieve the goals of sustainable development of the energy system and the construction of a lowcarbon society,this study proposes a multi-energy storage collaborative optimization strategy for industrial park that ...To achieve the goals of sustainable development of the energy system and the construction of a lowcarbon society,this study proposes a multi-energy storage collaborative optimization strategy for industrial park that integrates the laddered carbon trading mechanism with demand response.Firstly,a dual dimensional DR model is constructed based on the characteristics of load elasticity.The alternativeDRenables flexible substitution of energy loads through complementary conversion of electricity/heat/cold multi-energy sources,while the price DR relies on timeof-use electricity price signals to guide load spatiotemporal migration;Secondly,the LCT mechanism is introduced to achieve optimal carbon emission costs through a tiered carbon quota allocation mechanism.On this basis,an optimization decision model is established with the core objective of maximizing the annual net profit of the park.The objective function takes into account energy sales revenue,generator unit costs,and investment and operation costs of multiple types of energy storage facilities.Themodel constraint system covers three key dimensions:dynamic operation constraints of power generation units,including unit output limits,ramping capability,and minimum start-stop time;the physical boundary of an electric/hot/cold multi-energy storage system involves energy storage capacity and charge/discharge efficiency;The multi-energy network coupling balance equation ensures that the energy conversion and transmission process satisfies the law of conservation of energy.Using CPLEX mathematical programming solver for simulation verification,construct an energy storage capacity configuration decision process that includes LCT-DR synergistic effect.The research results show that compared with the traditional single energy storage configuration mode,this strategy effectively enhances the economic feasibility and engineering practicality of industrial park operation by coordinating demand side resource scheduling and finely controlling carbon costs,while maintaining stable system operation.Its methodological framework provides a technical path that combines theoretical rigor and practical operability for the low-carbon transformation of regional integrated energy systems.展开更多
Foliar uptake of airborne metal(loid)s plays a crucial role in metal(loid)accumulation in plant organs and is influ-enced by the size and emission sources of aerosols.Given the high enrichment of toxic metal(loid)s in...Foliar uptake of airborne metal(loid)s plays a crucial role in metal(loid)accumulation in plant organs and is influ-enced by the size and emission sources of aerosols.Given the high enrichment of toxic metal(loid)s in submicron-scale particulates(PM1),this study established a PM1 exposure system to examine airborne metal(loid)accu-mulation and foliar physiological responses in Oryza sativa L.The results showed that the concentrations of Cu,Zn,As,Pb,and Cd in the leaves and grains were influenced not only by the airborne metal(loid)levels but also by the specific nature of the PM1 particles.The quantitative model for PM1-associated Pb entry into leaf tissue indicated that foliar Pb accumulation was primarily driven by particle adhesion,followed by hydrophilic pene-tration and trans-stomatal liquid film migration,accounting for 87%–89%of the total accumulation.The strong hygroscopicity and high Pb activity of PM1 emitted from waste incineration(WI)increased the Pb absorption coefficient via the hydrophilic and liquid film migration pathway.In contrast,the high hydrophobicity of PM1 from coal burning(CB)led to greater retention of Pb on leaf surfaces.Both foliar reactive oxygen metabolism and photosynthesis indices were sensitive to air pollution.Foliar metal(loid)accumulation and airborne PM1 concentration accounted for the variance in physiological responses in rice leaves.Our results also indicated that Pb was the key element in PM1 emissions from both coal burning(CB)and waste incineration(WI)responsible for significant physiological changes in rice leaves.展开更多
Microwave roasting self-leaching is an innovative method for recovering gold from high-sulfur refractory gold concentrates,without using deadly toxic cyanide reagents.However,the mechanism of gold self-leaching,which ...Microwave roasting self-leaching is an innovative method for recovering gold from high-sulfur refractory gold concentrates,without using deadly toxic cyanide reagents.However,the mechanism of gold self-leaching,which relies on lixiviants prepared using volatilized sulfur obtained from roasting,has not been fully elucidated.This study employs the response surface methodology to optimize processing parameters,resulting in an increased gold extraction rate of 96.18%.Analytical factorization and the Tafel curve indicate that CuSO_(4) and NH_(3)·H_(2)O significantly influence the self-leaching process.Furthermore,X-ray photoelectron spectroscopy(XPS)analysis reveals that S^(2−),S_(2)^(2−),polysulfides(S_(n)^(2−)),and thiosulfate(S_(2)O_(3)^(2−))are involved in the gold leaching reaction,with S^(2−),S_(2)^(2−),and S_(n)^(2−) serving as primary ligands for gold complexation.The role of S_(2)O_(3)^(2−) in the early stages of the gold-leaching reaction is also noteworthy.The copper–ammonia complex catalyzes the self-leaching gold reaction;however,an improper addition ratio can lead to copper-sulfur compound precipitates,reducing the extraction rate.展开更多
Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immun...Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.展开更多
Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues...Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues,their role in spinal cord injury has yet to be determined.In this study,we investigated the role and mechanisms of spinal cord tissue exosomes in the inflammatory response following spinal cord injury.We found morphological,concentration,and functional differences between exosomes extracted from injured and normal spinal cord tissues,and identified proinflammatory effects associated with spinal cord injury-generated tissue exosomes but not with exosomes derived from normal spinal cord tissue.Our in vivo and in vitro analyses showed that spinal cord injury-generated tissue exosomes promoted microglial M1 polarization and inflammatory cytokine expression,thereby exacerbating tissue and neuronal injury in the spinal cord.In addition,the combination of exosomal miRNA sequencing and experimental verification showed that the miR-155-5p level was higher in spinal cord injury-generated tissue exosomes than in spinal cord tissue.We further found that spinal cord injury-generated tissue exosomes-derived miR-155-5p induced a significant inhibition of forkhead box O3a phosphorylation and activated the nuclear factor-kappa B pathway,thereby promoting microglial M1 polarization and inflammatory cytokine expression.These findings suggest that injury-induced miR-155-5p-containing exosomes exacerbate spinal cord injury via the promotion of microglial M1 polarization and inflammatory responses.Thus,targeting miR-155-5p expression or exosome secretion could be a novel strategy for attenuating inflammation and reducing secondary injury post-spinal cord injury.展开更多
Owing to the inherent limitation of the internal pulse ionization chamber within the AlphaGUARD PQ2000 radon monitor,that is,its inability to discriminate the energy levels of α particles,the ingress of^(220)Rn from ...Owing to the inherent limitation of the internal pulse ionization chamber within the AlphaGUARD PQ2000 radon monitor,that is,its inability to discriminate the energy levels of α particles,the ingress of^(220)Rn from the surrounding environment,along with its decay progeny,poses a substantive challenge in accurately determining the^(222)Rn concentration in the measurement outcomes.Among these,the protracted influence primarily stems from the two enduring decay progenies,namely^(212)Pb with a half-life of 10.64 h and^(212)Bi with a half-life of 60.54 min.This study explored the influence of^(220)Rn progeny on the measurement results of an AlphaGUARD PQ2000 radon monitor by developing a theoretical calculation model.The response coefficient related to the residual^(220)Rn progeny within the AlphaGUARD PQ2000 radon monitor was experimentally validated.In addition,this study investigated the effects of temperature and wind speed on the sensitivity of the instrument to^(220)Rn gas.The research findings revealed commendable agreement between the experimentally measured response coefficients of the residual^(220)Rn progeny and the corresponding values derived from the theoretical model.Notably,both the response coefficients of the AlphaGUARD PQ2000 radon monitor to^(220)Rn gas and its internal residual^(220)Rn progeny increased with elevated temperatures and increased wind speeds,providing a reference for correcting the impact of^(220)Rn and its progeny on the measurement results of^(222)Rn concentration obtained using the AlphaGUARD PQ2000 radon monitor.展开更多
Stem cell fate decisions are increasingly understood through the dynamic interplay of two fundamental stress-adaptive programs:the integrated stress response(ISR)and the senescence-associated secretory phenotype(SASP)...Stem cell fate decisions are increasingly understood through the dynamic interplay of two fundamental stress-adaptive programs:the integrated stress response(ISR)and the senescence-associated secretory phenotype(SASP).These pathways act as a Yin-Yang system,balancing beneficial and detrimental outcomes across development,tissue homeostasis,and disease.On the yin(protective)side,transient ISR activation and acute SASP signaling foster adaptation,embryonic patterning,wound healing,and regeneration.On the yang(maladaptive)side,chronic ISR signaling and unresolved SASP output drive stem cell exhaustion,fibrosis,inflammation,and tumorigenesis.This duality highlights their roles as both guardians and disruptors of stem cell integrity.Mechanistically,ISR regulates translational control via eukaryotic initiation factor 2 alpha(eIF2α)phosphorylation and activating transcription factor 4(ATF4)-dependent transcription,while SASP reprograms the extracellular milieu through cytokines,growth factors,and proteases.Their crosstalk creates feedback loops that shape tissue niches and long-termstemcell potential.Framing ISR-SASP interactions through a Yin-Yang lens underscores the balance between resilience and decline,to offer new insights into regenerative medicine,anti-aging interventions,and cancer therapeutics.展开更多
This paper presents a new type of triangular Sharp Eagle wave energy converter(WEC)platform.On the basis of the linear potential flow theory and the finite element analysis method,the hydrodynamic performance and stru...This paper presents a new type of triangular Sharp Eagle wave energy converter(WEC)platform.On the basis of the linear potential flow theory and the finite element analysis method,the hydrodynamic performance and structural response of the platform are studied,considering the actual platform motion and free surface rise under extreme sea states.First,the effects of the wave frequency and direction on the wave-induced loads and dynamic responses were examined.The motion at a wave direction angle of 0°is relatively low.On this basis,the angle constrained by the two sides of the Sharp Eagle floaters should be aligned with the main wave direction to avoid significant platform motion under extreme sea states.Additionally,the structural response of the platform,including the wave-absorbing floaters,is investigated.The results highlighted that the conditions or locations where yielding,buckling,and fatigue failures occur were different.In this context,the connection area of the Sharp Eagle floaters and platform is prone to yielding failure under oblique wave action,whereas the pontoon and side of the Sharp Eagle floaters are prone to buckling failure during significant vertical motion.Additionally,fatigue damage is most likely to occur at the connection between the middle column on both sides of the Sharp Eagle floaters and the pontoons.The findings of this paper revealed an intrinsic connection between wave-induced loads and the dynamic and structural responses of the platform,which provides a useful reference for the improved design of WECs.展开更多
The occurrence of top-down(TD)cracking has gradually become a prevalent issue in semi-rigid base asphalt pavements after prolonged service.A coupled simulation model integrating the finite difference method(FDM)and di...The occurrence of top-down(TD)cracking has gradually become a prevalent issue in semi-rigid base asphalt pavements after prolonged service.A coupled simulation model integrating the finite difference method(FDM)and discrete element method(DEM)was employed to investigate the mechanical behavior of asphalt pavement containing a pre-existing TD crack.The mesoscopic parameters of the model were calibrated based on the mixture modulus and the static mechanical response on the MLS66 test road.Finally,an analysis was performed to assess how variations in TD crack depth and longitudinal length affect the distribution patterns of transverse tensile stress,vertical shear stress,and vertical compressive stress.The results indicate that the vertical propagation of TD crack significantly increases both the tensile stress value and range on the middle surface,while the longitudinal development of TD crack has minimal impact.This phenomenon may result in more severe fatigue failure on the middle surface.With the vertical and longitudinal development of TD crack,the vertical shear stress and compressive stress show obvious"two-stage"characteristics.When the crack's vertical length reaches 40 mm,there is a sharp increase in stress on the upper surface.As the crack continues to propagate vertically,the growth of stress on the upper surface becomes negligible,while the stress in the middle and lower layers increased significantly.Conversely,for longitudinal development of TD crack,any changes in stress are insignificant when their length is less than 180 mm;however,as they continue to develop longitudinally beyond this threshold,there is a sharp increase in stress levels.These findings hold great significance for understanding pavement structure deterioration and maintenance behavior associated with TD crack.展开更多
BACKGROUND Although the 2021 Chinese Clinical Practice Guidelines for Enhanced Recovery after Surgery(ERAS)provide recommendations for ERAS in gastrointestinal surgery,the clinical application of standard ERAS nursing...BACKGROUND Although the 2021 Chinese Clinical Practice Guidelines for Enhanced Recovery after Surgery(ERAS)provide recommendations for ERAS in gastrointestinal surgery,the clinical application of standard ERAS nursing models is challenging due to the variety of diseases involved in gastrointestinal surgery and the com-plex factors contributing to patient stress responses.Moreover,stress responses are more severe in older adult patients.Therefore,precision medicine is required to improve the quality of nursing care and promote postoperative recovery in gastrointestinal surgery.and demonstrate nursing benefits through clinical practice.METHODS This randomized clinical trial first established an evidence-based nursing ERAS protocol in older adult patients based on literature related to perioperative nursing measures for gastrointestinal surgery stress response.Next,392 older adult patients who underwent gastrointestinal surgery and were admitted to our hospital between December 2021 and June 2023 were categorized into two groups to receive evidence-based(study group)or conventional(control group)ERAS nursing models,respectively.Intraoperative physiological parameters during surgery and postoperative recovery indicators were compared between the groups.RESULTS Among 64 domestic and international studies,the stress responses of older adult patients mainly included emotional anxiety,sleep disorders,gastrointestinal discomfort,physical weakness,pain,and swelling.The appropriate nursing interventions included comprehensive psychological counseling,pre-and postoperative nutritional support,temperature control,pain management,and rehabilitation training.Compared with the control group,the study group showed lower heart rate,mean arterial pressure,blood glucose level,and adrenaline level;shorter duration of drainage tube placement,time to first flatus,time to first ambulation,and postoperative hospital stay;lower anxiety scores on postoperative day 3;and lower incidences of postoperative infection,obstruction,poor wound healing,and gastrointestinal reactions were lower in the study group(all P<0.05).CONCLUSION The evidence-based nursing measures targeting stress responses based on the conventional ERAS nursing model resulted in stable intraoperative physiological parameters during surgery,promoted postoperative recovery,and reduced the incidence of complications.展开更多
The DDR(DNA damage response)is an essential cellular mechanism that detects and repairs DNA lesions to maintain genomic stability.Dysregulation of DDR pathways is frequently observed in human tumors,leading to increas...The DDR(DNA damage response)is an essential cellular mechanism that detects and repairs DNA lesions to maintain genomic stability.Dysregulation of DDR pathways is frequently observed in human tumors,leading to increased genomic instability and promoting tumor progression.Consequently,targeting DDR mechanisms has emerged as a promising therapeutic strategy in oncology.This review provides an overview of the major DDR pathways,highlighting the roles of key proteins involved in various DDR processes.A detailed understanding of these molecular mechanisms has paved the way for the development of targeted antitumor agents,including inhibitors of PARP1,ATM,ATR,CHK1,CHK2,DNA-PK,and WEE1.Additionally,the significant challenges in the development of DDR inhibitors are examined,including tumor microenvironment heterogeneity,resistance mechanisms,issues with selectivity and toxicity,and the complexities associated with clinical trial design.Finally,future directions and emerging strategies to improve DDR-targeted therapies are discussed.These strategies include biomarker-driven precision medicine,novel combination therapies,advanced drug delivery systems,and the potential application of artificial intelligence to optimize treatment outcomes.展开更多
The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with...The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with a hard combination,a numerical model is developed in this study.The indoor model test verified the accuracy of the numerical model.The influence laws of different hard combinations,train operating speeds and modes were studied and evaluated accordingly.The results show that the frequency corresponding to the peak vibration acceleration level of each floor of the superstructure property is concentrated at 10–20 Hz.The vibration response decreases in the high-frequency parts and increases in the lowfrequency parts with increasing distance from the source.Furthermore,the factors,such as train operating speed,operating mode,and hard combination type,will affect the vibration of the superstructure.The vibration response under the reversible operation of the train is greater than that of the unidirectional operation.The operating speed of the train is proportional to its vibration response.The vibration amplification area appears between the middle and the top of the superstructure at a higher train speed.Its vibration acceleration level will exceed the limit value of relevant regulations,and vibration-damping measures are required.Within the scope of application,this study provides some suggestions for constructing subway stations and superstructures.展开更多
Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in re...Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in recent years.However,the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients.We present a novel disentangled synthesis transfer network(DiSyn)for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients.DiSyn uses a domain separation network(DSN)to disentangle drug response related features,employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement.DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets,The Cancer Genome Atlas(TCGA),Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2(I-SPY2)and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia(NIBR PDXE),achieving competitive performance with the state-of-the-art methods on cancer patients and mice.Furthermore,the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.展开更多
Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative processes.The biocompatible and wound-healing properties of decellularized amniotic m...Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative processes.The biocompatible and wound-healing properties of decellularized amniotic membrane(d AM)make it a subject of exploration for its potential impact on the anti-inflammatory response of macrophages.Experimental findings unequivocally demonstrate that d AM promotes anti-inflammatory M2 polarization of macrophage,with its cytokine-rich content posited as a potential mediator.The application of RNA sequencing unveils differential gene expression,implicating the hypoxia inducible factor-1α(HIF-1α)signaling pathway in this intricate interplay.Subsequent investigation further demonstrates that d AM facilitates anti-inflammatory M2 polarization of macrophage through the upregulation of epidermal growth factor(EGF),which,in turn,activates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway and stabilizes HIF-1α.This cascade results in a noteworthy augmentation of anti-inflammatory gene expression.This study significantly contributes to advancing our comprehension of d AM's immunomodulatory role in tissue repair,thereby suggesting promising therapeutic potential.展开更多
There is limited research reported on the multiple loss mechanism of electromagnetic waves(EMW)and the development of interface models.Dielectric loss and magnetic loss,as the two primary attenuation mechanisms in EMW...There is limited research reported on the multiple loss mechanism of electromagnetic waves(EMW)and the development of interface models.Dielectric loss and magnetic loss,as the two primary attenuation mechanisms in EMW absorbers,still pose challenges,especially in elucidating the correlation between composition,morphology,interface,and performance.Here,we construct 3D hierarchical porous conducting network structures and Schottky heterojunctions(MoNi_(4)@NC-NiFe_(2)O_(4)@NC)with a high density of defects,using trimetallic NiMoFe-MOFs.Synergistic enhancement of the dielectric and magnetic losses is realized through manipulation of the defects,interfaces,phase engineering,and magnetic resonance.In particular,the even dispersion of magnetic MoNi_(4) and NiFe_(2)O_(4)nanoparticles(NPs)within the carbon matrix triggers the creation of multiple heterogeneous interfaces.These inseparable interfaces,along with oxygen vacancies,play a role in enhancing dielectric polarization,while the closely spaced interactions among magnetic units contribute to magnetic loss.After optimizing the interfacial structure,NiFe_(2)O_(4)/MoNi_(4)-NC exhibits remarkable EMW absorption properties.A reflection loss(RL)value of-67.91 dB can be achieved at an ultra-thin thickness of 1.95 mm,and the effective absorption bandwidth(EAB,RL≤-10 dB)is as high as 5.76 GHz.Furthermore,we conducted radar scattering cross-section(RCS)simulations using computer simulation technology(CST)software,which revealed that NiFe_(2)O_(4)/MoNi_(4)-NC exhibits an RCS reduction value of 39.1 dB m^(2).Hence,this work provides comprehensive guidance for the construction of Schottky heterojunctions for lightweight EMW absorbers from a mechanistic point of view.展开更多
基金financial support from the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20230718)。
文摘The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.
文摘BACKGROUND Sorafenib has been the conventional treatment for advanced hepatocellular carcinoma(HCC)since 2008.While radiological complete responses are extremely rare,improved supportive care and multidisciplinary approaches in clinical practice may explain the recent increase in case reports and retrospective series documenting such responses.CASE SUMMARY This case series describes 3 patients with advanced HCC who achieved durable complete responses using first-line sorafenib therapy,even in the presence of portal vein thrombosis or extrahepatic spread,and highlights the potential for sustained remission in selected patients.Dermatologic toxicity and non-viral etiology may correlate with favorable outcomes;however,reliable predictive biomarkers for sorafenib response are lacking.CONCLUSION Future research into the etiology and molecular differences in HCC is necessary to develop more personalized therapy options.
基金supported by the Natural Science Foundation of Guangdong Province,China (No.2025A1515011654)the National Natural Science Foundation of China (No.22090053)+3 种基金the Fundamental Research Funds for National Universities,China University of Geosciences (Wuhan)support from the program of China Scholarships Council (No.202406410155)Young Elite Scientists Sponsorship Program by CAST-Doctoral Student Special Plansupport from the S&T Special Program of Huzhou (No.2024GZ07)。
文摘Field-effect nanofluidic transistors(FENTs),biomimicking the structure and functionality of neuron,act as biological transistors with the ability to gate switching responses to external stimuli.The switching ratio has been verified to evaluate the performance of FENTs,but until recently,the response time,another crucial indicator,has been ignored.Employing finite-element method,we investigated the relationship among gate charge,switching ratio and response time by divisionally manipulating gate charge,including entrance surface and the surface of confinement space,for ion transport to optimize switching capability.The dual-split gate charge on FENTs exhibits synergistic effect on switching response.Based on the two regional gate charge on FENTs,multivalence ions in lower concentration,high aspect ratio and single channel show higher switching ratio but longer response time compared to monovalent ions.The findings highlight the necessity of balancing these two signals in FENTs and offer insights for optimizing their design and expanding applications to dual-signal-detection iontronics.
文摘This study examines the dynamic response of two adjacent 9-and 20-story benchmark steel buildings subjected to six near-fault earthquake records.Two-dimensional numerical models were employed to account for the complexities of structure-soil-structure interaction(SSSI).The research focuses on the separation gap between the buildings and the effects of pounding while considering Fixed Base(FB)and SSSI models,evaluated according to UBC 94 and ASCE 7-16 seismic codes.Key findings reveal that pounding occurs with the UBC 94 separation gap when earthquake frequency aligns with system frequency,leading to increased column stresses in the 9-story building.In contrast,the ASCE 7-16 standard effectively prevents pounding in both the FB and SSSI models.Additionally,drifts and displacements of lower floors in SSSI models exceed the allowable limits of ASCE 7-16,underscoring the impact of soil-structure interaction on seismic response.
基金supported by the Hubei Provincial Natural Science Foundation,China(Grant No.2024AFB917).
文摘As sessile organisms,plants must adapt various stresses.Accordingly,they have evolved several plant-specific growth and developmental processes.WRKY53 is a member of the WRKY transcription factor family,which plays a crucial role in rice growth and development,stress response,and hormone signal transduction.This review discusses the role of WRKY53 in stress response,focusing on its functions in cold tolerance,salt tolerance,disease resistance,and pest defense,and explores its role in regulating rice leaf senescence and seed germination.This article also proposes future research directions,including functional genomics studies,protein interaction network analyses,hormone signal transduction pathways,genetic improvement strategies,applications of gene editing technologies,molecular basis of stress responses,cross-species functional conservation,and bioinformatics and comparative genomics research.This review highlights the importance of WRKY53 in rice biology and provides new perspectives and strategies for future research and genetic improvement of rice.
基金funded by Science and Technology Projects from State Grid Corporation of China,(Research on Adaptive Balance Optimization and Simulation Technology of Industrial community Energy System with High Proportion of Distributed Energy,No.:5100-202355752A-3-4-SY).
文摘To achieve the goals of sustainable development of the energy system and the construction of a lowcarbon society,this study proposes a multi-energy storage collaborative optimization strategy for industrial park that integrates the laddered carbon trading mechanism with demand response.Firstly,a dual dimensional DR model is constructed based on the characteristics of load elasticity.The alternativeDRenables flexible substitution of energy loads through complementary conversion of electricity/heat/cold multi-energy sources,while the price DR relies on timeof-use electricity price signals to guide load spatiotemporal migration;Secondly,the LCT mechanism is introduced to achieve optimal carbon emission costs through a tiered carbon quota allocation mechanism.On this basis,an optimization decision model is established with the core objective of maximizing the annual net profit of the park.The objective function takes into account energy sales revenue,generator unit costs,and investment and operation costs of multiple types of energy storage facilities.Themodel constraint system covers three key dimensions:dynamic operation constraints of power generation units,including unit output limits,ramping capability,and minimum start-stop time;the physical boundary of an electric/hot/cold multi-energy storage system involves energy storage capacity and charge/discharge efficiency;The multi-energy network coupling balance equation ensures that the energy conversion and transmission process satisfies the law of conservation of energy.Using CPLEX mathematical programming solver for simulation verification,construct an energy storage capacity configuration decision process that includes LCT-DR synergistic effect.The research results show that compared with the traditional single energy storage configuration mode,this strategy effectively enhances the economic feasibility and engineering practicality of industrial park operation by coordinating demand side resource scheduling and finely controlling carbon costs,while maintaining stable system operation.Its methodological framework provides a technical path that combines theoretical rigor and practical operability for the low-carbon transformation of regional integrated energy systems.
基金supported by the National Natural Science Foundation of China(Nos.42077367 and 21677123).
文摘Foliar uptake of airborne metal(loid)s plays a crucial role in metal(loid)accumulation in plant organs and is influ-enced by the size and emission sources of aerosols.Given the high enrichment of toxic metal(loid)s in submicron-scale particulates(PM1),this study established a PM1 exposure system to examine airborne metal(loid)accu-mulation and foliar physiological responses in Oryza sativa L.The results showed that the concentrations of Cu,Zn,As,Pb,and Cd in the leaves and grains were influenced not only by the airborne metal(loid)levels but also by the specific nature of the PM1 particles.The quantitative model for PM1-associated Pb entry into leaf tissue indicated that foliar Pb accumulation was primarily driven by particle adhesion,followed by hydrophilic pene-tration and trans-stomatal liquid film migration,accounting for 87%–89%of the total accumulation.The strong hygroscopicity and high Pb activity of PM1 emitted from waste incineration(WI)increased the Pb absorption coefficient via the hydrophilic and liquid film migration pathway.In contrast,the high hydrophobicity of PM1 from coal burning(CB)led to greater retention of Pb on leaf surfaces.Both foliar reactive oxygen metabolism and photosynthesis indices were sensitive to air pollution.Foliar metal(loid)accumulation and airborne PM1 concentration accounted for the variance in physiological responses in rice leaves.Our results also indicated that Pb was the key element in PM1 emissions from both coal burning(CB)and waste incineration(WI)responsible for significant physiological changes in rice leaves.
基金supported by the National Natural Science Foundation of China(No.51974016).
文摘Microwave roasting self-leaching is an innovative method for recovering gold from high-sulfur refractory gold concentrates,without using deadly toxic cyanide reagents.However,the mechanism of gold self-leaching,which relies on lixiviants prepared using volatilized sulfur obtained from roasting,has not been fully elucidated.This study employs the response surface methodology to optimize processing parameters,resulting in an increased gold extraction rate of 96.18%.Analytical factorization and the Tafel curve indicate that CuSO_(4) and NH_(3)·H_(2)O significantly influence the self-leaching process.Furthermore,X-ray photoelectron spectroscopy(XPS)analysis reveals that S^(2−),S_(2)^(2−),polysulfides(S_(n)^(2−)),and thiosulfate(S_(2)O_(3)^(2−))are involved in the gold leaching reaction,with S^(2−),S_(2)^(2−),and S_(n)^(2−) serving as primary ligands for gold complexation.The role of S_(2)O_(3)^(2−) in the early stages of the gold-leaching reaction is also noteworthy.The copper–ammonia complex catalyzes the self-leaching gold reaction;however,an improper addition ratio can lead to copper-sulfur compound precipitates,reducing the extraction rate.
基金supported by the National Natural Science Foundation of China(Nos.82573045,82460602,82560459)the Hainan Provincial Graduate Student Innovative Research Project(No.Qhys2024-440).
文摘Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.
基金supported by the Joint Funds for the Innovation of Science and Technology,Fujian Province,No.2023Y9233(to HH)the QuanzhouScience and Technology Project,No.2022C036R(to HH)+1 种基金the Science and Technology Bureau of Quanzhou,No.2020CT003(to SL)the Quanzhou MunicipalMedical and Health Guiding Science and Technology Project,No.2023N066S(to YZhou).
文摘Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues,their role in spinal cord injury has yet to be determined.In this study,we investigated the role and mechanisms of spinal cord tissue exosomes in the inflammatory response following spinal cord injury.We found morphological,concentration,and functional differences between exosomes extracted from injured and normal spinal cord tissues,and identified proinflammatory effects associated with spinal cord injury-generated tissue exosomes but not with exosomes derived from normal spinal cord tissue.Our in vivo and in vitro analyses showed that spinal cord injury-generated tissue exosomes promoted microglial M1 polarization and inflammatory cytokine expression,thereby exacerbating tissue and neuronal injury in the spinal cord.In addition,the combination of exosomal miRNA sequencing and experimental verification showed that the miR-155-5p level was higher in spinal cord injury-generated tissue exosomes than in spinal cord tissue.We further found that spinal cord injury-generated tissue exosomes-derived miR-155-5p induced a significant inhibition of forkhead box O3a phosphorylation and activated the nuclear factor-kappa B pathway,thereby promoting microglial M1 polarization and inflammatory cytokine expression.These findings suggest that injury-induced miR-155-5p-containing exosomes exacerbate spinal cord injury via the promotion of microglial M1 polarization and inflammatory responses.Thus,targeting miR-155-5p expression or exosome secretion could be a novel strategy for attenuating inflammation and reducing secondary injury post-spinal cord injury.
基金supported by the National Natural Science Foundation of China(No.12175102)Hunan Provincial Natural Science Foundation(No.2022JJ40346)the 2022 Hunan Provincial University Student Innovation and Entrepreneurship Training Program(No.S202210555144).
文摘Owing to the inherent limitation of the internal pulse ionization chamber within the AlphaGUARD PQ2000 radon monitor,that is,its inability to discriminate the energy levels of α particles,the ingress of^(220)Rn from the surrounding environment,along with its decay progeny,poses a substantive challenge in accurately determining the^(222)Rn concentration in the measurement outcomes.Among these,the protracted influence primarily stems from the two enduring decay progenies,namely^(212)Pb with a half-life of 10.64 h and^(212)Bi with a half-life of 60.54 min.This study explored the influence of^(220)Rn progeny on the measurement results of an AlphaGUARD PQ2000 radon monitor by developing a theoretical calculation model.The response coefficient related to the residual^(220)Rn progeny within the AlphaGUARD PQ2000 radon monitor was experimentally validated.In addition,this study investigated the effects of temperature and wind speed on the sensitivity of the instrument to^(220)Rn gas.The research findings revealed commendable agreement between the experimentally measured response coefficients of the residual^(220)Rn progeny and the corresponding values derived from the theoretical model.Notably,both the response coefficients of the AlphaGUARD PQ2000 radon monitor to^(220)Rn gas and its internal residual^(220)Rn progeny increased with elevated temperatures and increased wind speeds,providing a reference for correcting the impact of^(220)Rn and its progeny on the measurement results of^(222)Rn concentration obtained using the AlphaGUARD PQ2000 radon monitor.
基金funded by the National Institutes of Health,grant numbers UG3OD023285,P42ES030991,and P30ES036084.
文摘Stem cell fate decisions are increasingly understood through the dynamic interplay of two fundamental stress-adaptive programs:the integrated stress response(ISR)and the senescence-associated secretory phenotype(SASP).These pathways act as a Yin-Yang system,balancing beneficial and detrimental outcomes across development,tissue homeostasis,and disease.On the yin(protective)side,transient ISR activation and acute SASP signaling foster adaptation,embryonic patterning,wound healing,and regeneration.On the yang(maladaptive)side,chronic ISR signaling and unresolved SASP output drive stem cell exhaustion,fibrosis,inflammation,and tumorigenesis.This duality highlights their roles as both guardians and disruptors of stem cell integrity.Mechanistically,ISR regulates translational control via eukaryotic initiation factor 2 alpha(eIF2α)phosphorylation and activating transcription factor 4(ATF4)-dependent transcription,while SASP reprograms the extracellular milieu through cytokines,growth factors,and proteases.Their crosstalk creates feedback loops that shape tissue niches and long-termstemcell potential.Framing ISR-SASP interactions through a Yin-Yang lens underscores the balance between resilience and decline,to offer new insights into regenerative medicine,anti-aging interventions,and cancer therapeutics.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFC3003805)Youth Innovation Promotion Association of the Chinese Academy of Sciences(Grant No.2022356)Guangzhou Basic and Applied Basic Research Project(Grant No.2023A04J0955).
文摘This paper presents a new type of triangular Sharp Eagle wave energy converter(WEC)platform.On the basis of the linear potential flow theory and the finite element analysis method,the hydrodynamic performance and structural response of the platform are studied,considering the actual platform motion and free surface rise under extreme sea states.First,the effects of the wave frequency and direction on the wave-induced loads and dynamic responses were examined.The motion at a wave direction angle of 0°is relatively low.On this basis,the angle constrained by the two sides of the Sharp Eagle floaters should be aligned with the main wave direction to avoid significant platform motion under extreme sea states.Additionally,the structural response of the platform,including the wave-absorbing floaters,is investigated.The results highlighted that the conditions or locations where yielding,buckling,and fatigue failures occur were different.In this context,the connection area of the Sharp Eagle floaters and platform is prone to yielding failure under oblique wave action,whereas the pontoon and side of the Sharp Eagle floaters are prone to buckling failure during significant vertical motion.Additionally,fatigue damage is most likely to occur at the connection between the middle column on both sides of the Sharp Eagle floaters and the pontoons.The findings of this paper revealed an intrinsic connection between wave-induced loads and the dynamic and structural responses of the platform,which provides a useful reference for the improved design of WECs.
基金supported by National Key R&D Program of China(Grant No.2021YFB2601200)Open Fund of National Engineering Research Center of Highway Maintenance Technology(Changsha University of Science&Technology)(No.kfj230207).
文摘The occurrence of top-down(TD)cracking has gradually become a prevalent issue in semi-rigid base asphalt pavements after prolonged service.A coupled simulation model integrating the finite difference method(FDM)and discrete element method(DEM)was employed to investigate the mechanical behavior of asphalt pavement containing a pre-existing TD crack.The mesoscopic parameters of the model were calibrated based on the mixture modulus and the static mechanical response on the MLS66 test road.Finally,an analysis was performed to assess how variations in TD crack depth and longitudinal length affect the distribution patterns of transverse tensile stress,vertical shear stress,and vertical compressive stress.The results indicate that the vertical propagation of TD crack significantly increases both the tensile stress value and range on the middle surface,while the longitudinal development of TD crack has minimal impact.This phenomenon may result in more severe fatigue failure on the middle surface.With the vertical and longitudinal development of TD crack,the vertical shear stress and compressive stress show obvious"two-stage"characteristics.When the crack's vertical length reaches 40 mm,there is a sharp increase in stress on the upper surface.As the crack continues to propagate vertically,the growth of stress on the upper surface becomes negligible,while the stress in the middle and lower layers increased significantly.Conversely,for longitudinal development of TD crack,any changes in stress are insignificant when their length is less than 180 mm;however,as they continue to develop longitudinally beyond this threshold,there is a sharp increase in stress levels.These findings hold great significance for understanding pavement structure deterioration and maintenance behavior associated with TD crack.
文摘BACKGROUND Although the 2021 Chinese Clinical Practice Guidelines for Enhanced Recovery after Surgery(ERAS)provide recommendations for ERAS in gastrointestinal surgery,the clinical application of standard ERAS nursing models is challenging due to the variety of diseases involved in gastrointestinal surgery and the com-plex factors contributing to patient stress responses.Moreover,stress responses are more severe in older adult patients.Therefore,precision medicine is required to improve the quality of nursing care and promote postoperative recovery in gastrointestinal surgery.and demonstrate nursing benefits through clinical practice.METHODS This randomized clinical trial first established an evidence-based nursing ERAS protocol in older adult patients based on literature related to perioperative nursing measures for gastrointestinal surgery stress response.Next,392 older adult patients who underwent gastrointestinal surgery and were admitted to our hospital between December 2021 and June 2023 were categorized into two groups to receive evidence-based(study group)or conventional(control group)ERAS nursing models,respectively.Intraoperative physiological parameters during surgery and postoperative recovery indicators were compared between the groups.RESULTS Among 64 domestic and international studies,the stress responses of older adult patients mainly included emotional anxiety,sleep disorders,gastrointestinal discomfort,physical weakness,pain,and swelling.The appropriate nursing interventions included comprehensive psychological counseling,pre-and postoperative nutritional support,temperature control,pain management,and rehabilitation training.Compared with the control group,the study group showed lower heart rate,mean arterial pressure,blood glucose level,and adrenaline level;shorter duration of drainage tube placement,time to first flatus,time to first ambulation,and postoperative hospital stay;lower anxiety scores on postoperative day 3;and lower incidences of postoperative infection,obstruction,poor wound healing,and gastrointestinal reactions were lower in the study group(all P<0.05).CONCLUSION The evidence-based nursing measures targeting stress responses based on the conventional ERAS nursing model resulted in stable intraoperative physiological parameters during surgery,promoted postoperative recovery,and reduced the incidence of complications.
文摘The DDR(DNA damage response)is an essential cellular mechanism that detects and repairs DNA lesions to maintain genomic stability.Dysregulation of DDR pathways is frequently observed in human tumors,leading to increased genomic instability and promoting tumor progression.Consequently,targeting DDR mechanisms has emerged as a promising therapeutic strategy in oncology.This review provides an overview of the major DDR pathways,highlighting the roles of key proteins involved in various DDR processes.A detailed understanding of these molecular mechanisms has paved the way for the development of targeted antitumor agents,including inhibitors of PARP1,ATM,ATR,CHK1,CHK2,DNA-PK,and WEE1.Additionally,the significant challenges in the development of DDR inhibitors are examined,including tumor microenvironment heterogeneity,resistance mechanisms,issues with selectivity and toxicity,and the complexities associated with clinical trial design.Finally,future directions and emerging strategies to improve DDR-targeted therapies are discussed.These strategies include biomarker-driven precision medicine,novel combination therapies,advanced drug delivery systems,and the potential application of artificial intelligence to optimize treatment outcomes.
基金National Natural Science Foundation of China under Grant No.51578463。
文摘The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with a hard combination,a numerical model is developed in this study.The indoor model test verified the accuracy of the numerical model.The influence laws of different hard combinations,train operating speeds and modes were studied and evaluated accordingly.The results show that the frequency corresponding to the peak vibration acceleration level of each floor of the superstructure property is concentrated at 10–20 Hz.The vibration response decreases in the high-frequency parts and increases in the lowfrequency parts with increasing distance from the source.Furthermore,the factors,such as train operating speed,operating mode,and hard combination type,will affect the vibration of the superstructure.The vibration response under the reversible operation of the train is greater than that of the unidirectional operation.The operating speed of the train is proportional to its vibration response.The vibration amplification area appears between the middle and the top of the superstructure at a higher train speed.Its vibration acceleration level will exceed the limit value of relevant regulations,and vibration-damping measures are required.Within the scope of application,this study provides some suggestions for constructing subway stations and superstructures.
基金supported by the National Natural Science Foun-dation of China(Grant Nos.:32170680 and T2122018)the Natural Science Foundation of Shanghai,China(Grant No.:21ZR1476000)the CAS Youth Innovation Promotion Association,China(Grant No.:Y2022076).
文摘Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in recent years.However,the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients.We present a novel disentangled synthesis transfer network(DiSyn)for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients.DiSyn uses a domain separation network(DSN)to disentangle drug response related features,employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement.DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets,The Cancer Genome Atlas(TCGA),Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2(I-SPY2)and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia(NIBR PDXE),achieving competitive performance with the state-of-the-art methods on cancer patients and mice.Furthermore,the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.
基金supported by the National Natural Science Foundation of China(No.82302772)Guizhou Basic Research Project(No.ZK[2023]General 201)partially supported by Wuhan Kangchuang Biotechnology Co.,Ltd。
文摘Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative processes.The biocompatible and wound-healing properties of decellularized amniotic membrane(d AM)make it a subject of exploration for its potential impact on the anti-inflammatory response of macrophages.Experimental findings unequivocally demonstrate that d AM promotes anti-inflammatory M2 polarization of macrophage,with its cytokine-rich content posited as a potential mediator.The application of RNA sequencing unveils differential gene expression,implicating the hypoxia inducible factor-1α(HIF-1α)signaling pathway in this intricate interplay.Subsequent investigation further demonstrates that d AM facilitates anti-inflammatory M2 polarization of macrophage through the upregulation of epidermal growth factor(EGF),which,in turn,activates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway and stabilizes HIF-1α.This cascade results in a noteworthy augmentation of anti-inflammatory gene expression.This study significantly contributes to advancing our comprehension of d AM's immunomodulatory role in tissue repair,thereby suggesting promising therapeutic potential.
基金supported by the National Natural Science Foundation of China(No.22269010)the Jiangxi Provincial Natural Science Foundation(No.20224BAB214021).
文摘There is limited research reported on the multiple loss mechanism of electromagnetic waves(EMW)and the development of interface models.Dielectric loss and magnetic loss,as the two primary attenuation mechanisms in EMW absorbers,still pose challenges,especially in elucidating the correlation between composition,morphology,interface,and performance.Here,we construct 3D hierarchical porous conducting network structures and Schottky heterojunctions(MoNi_(4)@NC-NiFe_(2)O_(4)@NC)with a high density of defects,using trimetallic NiMoFe-MOFs.Synergistic enhancement of the dielectric and magnetic losses is realized through manipulation of the defects,interfaces,phase engineering,and magnetic resonance.In particular,the even dispersion of magnetic MoNi_(4) and NiFe_(2)O_(4)nanoparticles(NPs)within the carbon matrix triggers the creation of multiple heterogeneous interfaces.These inseparable interfaces,along with oxygen vacancies,play a role in enhancing dielectric polarization,while the closely spaced interactions among magnetic units contribute to magnetic loss.After optimizing the interfacial structure,NiFe_(2)O_(4)/MoNi_(4)-NC exhibits remarkable EMW absorption properties.A reflection loss(RL)value of-67.91 dB can be achieved at an ultra-thin thickness of 1.95 mm,and the effective absorption bandwidth(EAB,RL≤-10 dB)is as high as 5.76 GHz.Furthermore,we conducted radar scattering cross-section(RCS)simulations using computer simulation technology(CST)software,which revealed that NiFe_(2)O_(4)/MoNi_(4)-NC exhibits an RCS reduction value of 39.1 dB m^(2).Hence,this work provides comprehensive guidance for the construction of Schottky heterojunctions for lightweight EMW absorbers from a mechanistic point of view.
