In the present paper, one hundred cluster models NinBP （n = 1-6） have been designed and studied by density functional theory （DFT） to get an insight into the local structure, catalytic properties and sulfur resist...In the present paper, one hundred cluster models NinBP （n = 1-6） have been designed and studied by density functional theory （DFT） to get an insight into the local structure, catalytic properties and sulfur resistibility of amorphous alloy Ni-B-P. The configurations in triplet state are found more stable than those in the singlet state. It is found： that as the content of Ni in the clusters increases, the value of Fermi level in clusters fluctuated, which shows that the content of Ni can influence the Fermi level to a certain extent. Based on the Fermi level and DOS, we consider the activity of catalyst in hydrogenation reaction is the best in cluster Ni3BP. On the basis of the charge of clusters NinBP （n = 1 -6）, we conclude the amorphous alloy Ni-B-P with high Ni content has better sulfur resistibility and the best hydrogenation activity, strong sulfur resistibility appears in clusters Ni3BP, and the amorphous alloy Ni60B20P20 with similar proportion is expected to prepare in the future.展开更多
Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone...Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.展开更多
Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the ...Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies. Astrocytes, the largest group of nonneuronal cells in the central nervous system, play several crucial roles in maintaining ionic and energy metabolic homeostasis in neurons, regulating neurotransmitter levels, and modulating synaptic plasticity. This article briefly reviews the critical role of astrocytes in maintaining balance within the central nervous system. Building on previous research, we discuss how astrocyte dysfunction contributes to the onset and progression of epilepsy through four key aspects: the imbalance between excitatory and inhibitory neuronal signaling, dysregulation of metabolic homeostasis in the neuronal microenvironment, neuroinflammation, and the formation of abnormal neural circuits. We summarize relevant basic research conducted over the past 5 years that has focused on modulating astrocytes as a therapeutic approach for epilepsy. We categorize the therapeutic targets proposed by these studies into four areas: restoration of the excitation–inhibition balance, reestablishment of metabolic homeostasis, modulation of immune and inflammatory responses, and reconstruction of abnormal neural circuits. These targets correspond to the pathophysiological mechanisms by which astrocytes contribute to epilepsy. Additionally, we need to consider the potential challenges and limitations of translating these identified therapeutic targets into clinical treatments. These limitations arise from interspecies differences between humans and animal models, as well as the complex comorbidities associated with epilepsy in humans. We also highlight valuable future research directions worth exploring in the treatment of epilepsy and the regulation of astrocytes, such as gene therapy and imaging strategies. The findings presented in this review may help open new therapeutic avenues for patients with drugresistant epilepsy and for those suffering from other central nervous system disorders associated with astrocytic dysfunction.展开更多
Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,par...Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).展开更多
Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central com...Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.展开更多
The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evi...The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.展开更多
The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.Obesity-related conditions like type 2 d...The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.Obesity-related conditions like type 2 diabetes and non-alcoholic fatty liver disease exacerbate this relationship.Peripheral lipid accumulation,particularly in the liver,initiates a cascade of inflammatory processes that extend to the brain,influencing critical metabolic regulatory regions.Ceramide and palmitate,key lipid components,along with lipid transporters lipocalin-2 and apolipoprotein E,contribute to neuroinflammation by disrupting blood–brain barrier integrity and promoting gliosis.Peripheral insulin resistance further exacerbates brain insulin resistance and neuroinflammation.Preclinical interventions targeting peripheral lipid metabolism and insulin signaling pathways have shown promise in reducing neuroinflammation in animal models.However,translating these findings to clinical practice requires further investigation into human subjects.In conclusion,metabolic dysfunction,peripheral inflammation,and insulin resistance are integral to neuroinflammation and neurodegeneration.Understanding these complex mechanisms holds potential for identifying novel therapeutic targets and improving outcomes for neurodegenerative diseases.展开更多
With vigorous developments in nanotechnology,the elaborate regulation of microstructure shows attractive potential in the design of electromagnetic wave absorbers.Herein,a hierarchical porous structure and composite h...With vigorous developments in nanotechnology,the elaborate regulation of microstructure shows attractive potential in the design of electromagnetic wave absorbers.Herein,a hierarchical porous structure and composite heterogeneous interface are constructed successfully to optimize the electromagnetic loss capacity.The macro–micro-synergistic graphene aerogel formed by the ice template‑assisted 3D printing strategy is cut by silicon carbide nanowires(SiC_(nws))grown in situ,while boron nitride(BN)interfacial structure is introduced on graphene nanoplates.The unique composite structure forces multiple scattering of incident EMWs,ensuring the combined effects of interfacial polarization,conduction networks,and magnetic-dielectric synergy.Therefore,the as-prepared composites present a minimum reflection loss value of−37.8 dB and a wide effective absorption bandwidth(EAB)of 9.2 GHz(from 8.8 to 18.0 GHz)at 2.5 mm.Besides,relying on the intrinsic high-temperature resistance of SiC_(nws) and BN,the EAB also remains above 5.0 GHz after annealing in air environment at 600℃ for 10 h.展开更多
In-situ formed high Mn steel coating reinforced by carbides was formed by laser surface alloying(LSA).Laser alloyed layers on 1Cr18Ni9Ti steel with Mn+W_(2)C(specimen A),Mn+NiWC(specimen B)and Mn+SiC(specimen C)powder...In-situ formed high Mn steel coating reinforced by carbides was formed by laser surface alloying(LSA).Laser alloyed layers on 1Cr18Ni9Ti steel with Mn+W_(2)C(specimen A),Mn+NiWC(specimen B)and Mn+SiC(specimen C)powders were fabricated to improve the wear and corrosion behavior of 1Cr18Ni9Ti steel blades in high speed mixers.Microstructure evolution,phases,element distribution,microhardness,wear and corrosion behavior of the laser alloyed layers were investigated.Results indicated that high Mn steel matrix composites with undissolved W_(2)C,WC and other in-situ formed carbides were formed by LSA with Mn+W_(2)C and Mn+NiWC while SiC totally dissolved into the high Mn matrix when adding Mn+SiC.Ni as the binding phase in Ni-WC powder decreased the crack sensitivity of the alloyed layer as compared with the addition of W_(2)C powder.An improvement in average microhardness was achieved in the matrix in specimen A,B and C,with the value of 615,602 and 277 HV_(0.5),while that of the substrate was 212 HV_(0.5).The increase of microhardness,wear and corrosion resistance is highly corelated to microstructure,formed phases,type and content of carbides,micro-hardness and toughness of the alloyed layers.展开更多
BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring except...BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.展开更多
Powdery mildew negatively impacts wheat yield and quality.Emmer wheat(Triticum dicoccum),an ancestral species of common wheat,is a gene donor for wheat improvement.Cultivated emmer accession H1-707 exhibited all-stage...Powdery mildew negatively impacts wheat yield and quality.Emmer wheat(Triticum dicoccum),an ancestral species of common wheat,is a gene donor for wheat improvement.Cultivated emmer accession H1-707 exhibited all-stage resistance to powdery mildew over consecutive years.Genetic analysis of H1-707 at the seedling stage revealed a dominant monogenic inheritance pattern,and the underlying gene was designated Pm71.By employing bulked segregant exome sequencing(BSE-Seq)and using 2000 F2:3 families,Pm71 was fine mapped to a 336-kb interval on chromosome arm 6AS by referencing to the durum cv.Svevo RefSeq 1.0.Collinearity analysis revealed high homology in the candidate interval between Svevo and six Triticum species.Among six high-confidence genes annotated within this interval,TRITD6Av1G005050 encoding a GDSL esterase/lipase was identified as a key candidate for Pm71.展开更多
Proton exchange membrane water electrolysis(PEMWE)is one of the most promising strategies to pro-duce green hydrogen energy,and it is crucial to exploit highly conductive and good corrosion-resistant coatings on bipol...Proton exchange membrane water electrolysis(PEMWE)is one of the most promising strategies to pro-duce green hydrogen energy,and it is crucial to exploit highly conductive and good corrosion-resistant coatings on bipolar plates(BPs),one of the core components in PEMWE cells.In this work,NbN coatings are deposited on Ti BPs by magnetron sputtering to improve the corrosion resistance and conductivity,for which the critical process parameters,such as the working pressure,partial nitrogen pressure and de-position temperature are well optimized.It is found that the compact microstructure,highly conductive δ-NbN and uniform nanoparticles play a dominant role in the synergistic improvement of the corrosion resistance and electrical conductivity of NbN coatings.The optimized NbN coatings exhibit excellent cor-rosion resistance with the low corrosion current density of 1.1×10^(-8) A cm^(-2),a high potential value of-0.005 V vs.SCE and a low ICR value of 15.8 mΩcm2@1.5 MPa.Accordingly,NbN coatings can be a promising candidate for the development of the low-cost and high-anti-corrosion Ti BPs of PEMWE.展开更多
Triple-negative breast cancer(TNBC)is currently the most heterogeneous and aggressive breast cancer type.It has a high recurrence rate,poor clinical prospects,and lack of predictive markers and potential treatment opt...Triple-negative breast cancer(TNBC)is currently the most heterogeneous and aggressive breast cancer type.It has a high recurrence rate,poor clinical prospects,and lack of predictive markers and potential treatment options.Dysregulated microRNAs(miRNAs)are involved in various cellular processes in TNBC.Moreover,variations in the miRNA levels in TNBC may act as a dependable indicator for predicting the effectiveness and specificity of treatments.Currently,the application of miRNAs for breast cancer therapy is primarily in the preclinical stage,with a focus on identifying highly specific and sensitive miRNAs that could offer new possibilities for early diagnosis,clinical treat-ment,and prognostic monitoring of TNBC.展开更多
Exploring high-efficiency and broadband microwave absorption(MA)materials with corrosion resistance and low cost is ur-gently needed for wide practical applications.Herein,the natural porous attapulgite(ATP)nanorods e...Exploring high-efficiency and broadband microwave absorption(MA)materials with corrosion resistance and low cost is ur-gently needed for wide practical applications.Herein,the natural porous attapulgite(ATP)nanorods embedded with TiO_(2)and polyaniline(PANI)nanoparticles are synthesized via heterogeneous precipitation and in-situ polymerization.The obtained PANI-TiO_(2)-ATP one-di-mensional(1D)nanostructures can intertwine into three-dimensional(3D)conductive network,which favors energy dissipation.The min-imum reflection loss(RL_(min))of the PANI-TiO_(2)-ATP coating(20wt%)reaches-49.36 dB at 9.53 GHz,and the effective absorption band-width(EAB)can reach 6.53 GHz with a thickness of 2.1 mm.The excellent MA properties are attributed to interfacial polarization,mul-tiple loss mechanisms,and good impedance matching induced by the synergistic effect of PANI-TiO_(2)nanoparticle shells and ATP nanor-ods.In addition,salt spray and Tafel polarization curve tests reveal that the PANI-TiO_(2)-ATP coating shows outstanding corrosion resist-ance performance.This study provides a low-cost and high-efficiency strategy for constructing 1D nanonetwork composites for MA and corrosion resistance applications using natural porous ATP nanorods as carriers.展开更多
BACKGROUND Liver transplant(LT)recipients are susceptible to carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Comprehensive research addressing the incidence,timing,infection sites,resistance patterns,treatm...BACKGROUND Liver transplant(LT)recipients are susceptible to carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Comprehensive research addressing the incidence,timing,infection sites,resistance patterns,treatment options,and associated risk factors among LT recipients with CRKP is now lacking.AIM To assess the incidence,resistance,therapy,and risk factors of CRKP infections post-LT,and to evaluate the impact of them on prognosis.METHODS A retrospective study was conducted,including 430 consecutive patients who underwent LT between January 2015 and June 2023.This study aimed to investigate the risk factors for CRKP infections and their influence on outcomes using logistic regression analysis.RESULTS Among the 430 patients who underwent LT,20(4.7%)experienced at least one documented CRKP infection within 3 months post-transplantation.The median time from LT to the onset of CRKP infections was 6.5 days.The lungs and bloodstream were the most common sites of CRKP infections.CRKP isolates were relatively susceptible to ceftazidime/avibactam(93.7%),polymyxin B(90.6%),and tigecycline(75.0%)treatment.However,all isolates were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin treatment.Recipients with CRKP infections had a mortality rate of 35%,the rate was 12.5%for those receiving ceftazidime/avibactam therapy.Multivariate analysis identified female sex[odds ratio(OR)=3.306;95%confidence interval(CI):1.239-8.822;P=0.017],intraoperative bleeding≥3000 mL(OR=3.269;95%CI:1.018-10.490;P=0.047),alanine aminotransferase on day 1 post-LT≥1500 U/L(OR=4.370;95%CI:1.686-11.326;P=0.002),and post-LT mechanical ventilation(OR=2.772;95%CI:1.077-7.135;P=0.035)as significant variables associated with CRKP.CRKP infections were related to an intensive care unit length(ICU)of stay≥7 days and 6-month all-cause mortality post-LT.CONCLUSION CRKP infections were frequent complications following LT,with poor associated outcomes.Risk factors for post-LT CRKP infections included female sex,significant intraoperative bleeding,elevated alanine aminotransferase levels,and the need for mechanical ventilation.CRKP infections negatively impacted survival and led to prolonged ICU stays.展开更多
Antimicrobial resistance is a global health crisis and carbapenem-resistant Klebsiella pneumoniae(CRKp)is listed as one of the top high-priority pathogens by the World Health Organization.Meanwhile,hypervirulent K.pne...Antimicrobial resistance is a global health crisis and carbapenem-resistant Klebsiella pneumoniae(CRKp)is listed as one of the top high-priority pathogens by the World Health Organization.Meanwhile,hypervirulent K.pneumoniae(hvKp)causes severe community-associated infections,such as liver abscesses and meningitis,in otherwise healthy individuals.Both CRKp and hvKp infections are associated with high mortality rates.The convergence of carbapenem resistance and hypervirulence within a single bacterial strain may lead to significantly more severe clinical outcomes.展开更多
Silicide coatings have proven to be promising for improving the high-temperature oxidation resistance of niobium alloy.However,the long-term protective property of single silicide coating remains a long-time endeavor ...Silicide coatings have proven to be promising for improving the high-temperature oxidation resistance of niobium alloy.However,the long-term protective property of single silicide coating remains a long-time endeavor due to the deficiency of oxygen-consuming phases,as well as the self-healing ability of the protective layer.Herein,a silicide-based composite coating is constructed on niobium alloy by incor-poration of nano-SiC particles for enhancing the high-temperature oxidation resistance.Isothermal oxi-dation results at 1250℃ for 50 h indicate that NbSi_(2)/Nb_(2)O_(5)-SiO_(2)/SiC multilayer coated sample with a low mass gain of 2.49 mg/cm^(2) shows an improved oxidation resistance compared with NbSi_(2) coating(6.49 mg/cm^(2)).The enhanced high-temperature antioxidant performance of NbSi_(2)/Nb_(2)O_(5)-SiO_(2)/SiC multi-layer coating is mainly attributed to the formation of the protective SiO_(2) self-healing film and the high-temperature diffusion behavior of NbSi_(2)/substrate.展开更多
Reductive soil disinfestation(RSD)is commonly employed for soil remediation in greenhouse cultivation.However,its influence on antibiotic resistance genes(ARGs)in soil remains uncertain.This study investigated the dyn...Reductive soil disinfestation(RSD)is commonly employed for soil remediation in greenhouse cultivation.However,its influence on antibiotic resistance genes(ARGs)in soil remains uncertain.This study investigated the dynamic changes in soil communities,potential bacterial pathogens,and ARG profiles under various organicmaterial treatments during RSD,including distillers’grains,potato peel,peanut vine,and peanut vine combined with charcoal.Results revealed that applying diverse organic materials in RSD significantly altered bacterial community composition and diminished the relative abundance of potential bacterial pathogens(P<0.05).The relative abundance of high-risk ARGs decreased by 10.7%-30.6%after RSD treatments,the main decreased ARG subtypeswere AAC(3)_Via,dfrA1,ErmB,lnuB,aadA.Actinobacteria was the primary host of ARGs and was suppressed by RSD.Soil physicochemical properties,such as total nitrogen,soil pH,total carbon,were crucial factors affecting ARG profiles.Our findings demonstrated that RSD treatment inhibited pathogenic bacteria and could be an option for reducing high-risk ARG proliferation in soil.展开更多
Nosocomial pathogen carbapenem-resistant Klebsiella pneumoniae(CRKP)poses a heightened risk to public health through carbapenem resistance and virulence convergence,particularly in China’s dominant sequence type 11(S...Nosocomial pathogen carbapenem-resistant Klebsiella pneumoniae(CRKP)poses a heightened risk to public health through carbapenem resistance and virulence convergence,particularly in China’s dominant sequence type 11(ST11)clone[1,2].Monoclonal K.pneumoniae exhibits within-host diversity during prolonged infections[3–5],with certain variants surviving through adaptation[4,6].CRKP strains from the blood of a single patient are heterogeneous in terms of antibiotic susceptibility,capsular polysaccharide production,and mucoviscosity[3].Intra-host evolution drives novel resistance via cumulative mutations(e.g.,the transcriptional regulator gene ramR mutations and the outer membrane porin gene OmpK35 loss)[4].展开更多
Background:Under hypoxia,exaggerated compensatory responses may lead to acute mountain sickness.The excessive vasodilatory effect of nitric oxide(NO)can lower the hypoxic pulmonary vasoconstriction(HPV)and peripheral ...Background:Under hypoxia,exaggerated compensatory responses may lead to acute mountain sickness.The excessive vasodilatory effect of nitric oxide(NO)can lower the hypoxic pulmonary vasoconstriction(HPV)and peripheral blood pressure.While NO is catalyzed by various nitric oxide synthase(NOS)isoforms,the regulatory roles of these types in the hemodynamics of pulmonary and systemic circulation in living hypoxic animals remain unclear.Therefore,this study aims to investigate the regu-latory effects of different NOS isoforms on pulmonary and systemic circulation in hypoxic rats by employing selective NOS inhibitors and continuously monitoring hemodynamic parameters of both pulmonary and systemic circulation.Methods:Forty healthy male Sprague–Dawley(SD)rats were randomly divided into four groups:Control group(NG-nitro-D-arginine methyl ester,D-NAME),L-NAME group(non-selective NOS inhibitor,NG-nitro-L-arginine methyl ester),AG group(in-ducible NOS inhibitor group,aminoguanidine),and 7-NI group(neurological NOS in-hibitor,7-nitroindazole).Hemodynamic parameters of rats were monitored for 10 min after inhibitor administration and 5 min after induction of hypoxia[15%O2,2200 m a.sl.,582 mmHg(76.5 kPa),Xining,China]using the real-time dynamic monitoring model for pulmonary and systemic circulation hemodynamics in vivo.Serum NO concentra-tions and blood gas analysis were measured.Results:Under normoxia,mean arterial pressure and total peripheral vascular resist-ance were increased,and ascending aortic blood flow and serum NO concentration were decreased in the L-NAME and AG groups.During hypoxia,pulmonary arterial pressure and pulmonary vascular resistance were significantly increased in the L-NAME and AG groups.Conclusions:This compensatory mechanism activated by inducible NOS and en-dothelial NOS effectively counteracts the pulmonary hemodynamic changes induced by hypoxic stress.It plays a crucial role in alleviating hypoxia-induced pulmonary arte-rial hypertension.展开更多
基金University of Science and Technology Liaoning Research Project (No. 2003001)
文摘In the present paper, one hundred cluster models NinBP （n = 1-6） have been designed and studied by density functional theory （DFT） to get an insight into the local structure, catalytic properties and sulfur resistibility of amorphous alloy Ni-B-P. The configurations in triplet state are found more stable than those in the singlet state. It is found： that as the content of Ni in the clusters increases, the value of Fermi level in clusters fluctuated, which shows that the content of Ni can influence the Fermi level to a certain extent. Based on the Fermi level and DOS, we consider the activity of catalyst in hydrogenation reaction is the best in cluster Ni3BP. On the basis of the charge of clusters NinBP （n = 1 -6）, we conclude the amorphous alloy Ni-B-P with high Ni content has better sulfur resistibility and the best hydrogenation activity, strong sulfur resistibility appears in clusters Ni3BP, and the amorphous alloy Ni60B20P20 with similar proportion is expected to prepare in the future.
基金supported by the Ministry of Health National Medical Research Council (to JL)the National University of Singapore (to JJEC)
文摘Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.
基金supported by the National Key Research and Development Program of China,No. 2023YFF0714200 (to CW)the National Natural Science Foundation of China,Nos. 82472038 and 82202224 (both to CW)+3 种基金the Shanghai Rising-Star Program,No. 23QA1407700 (to CW)the Construction Project of Shanghai Key Laboratory of Molecular Imaging,No. 18DZ2260400 (to CW)the National Science Foundation for Distinguished Young Scholars,No. 82025019 (to CL)the Greater Bay Area Institute of Precision Medicine (Guangzhou)(to CW)。
文摘Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies. Astrocytes, the largest group of nonneuronal cells in the central nervous system, play several crucial roles in maintaining ionic and energy metabolic homeostasis in neurons, regulating neurotransmitter levels, and modulating synaptic plasticity. This article briefly reviews the critical role of astrocytes in maintaining balance within the central nervous system. Building on previous research, we discuss how astrocyte dysfunction contributes to the onset and progression of epilepsy through four key aspects: the imbalance between excitatory and inhibitory neuronal signaling, dysregulation of metabolic homeostasis in the neuronal microenvironment, neuroinflammation, and the formation of abnormal neural circuits. We summarize relevant basic research conducted over the past 5 years that has focused on modulating astrocytes as a therapeutic approach for epilepsy. We categorize the therapeutic targets proposed by these studies into four areas: restoration of the excitation–inhibition balance, reestablishment of metabolic homeostasis, modulation of immune and inflammatory responses, and reconstruction of abnormal neural circuits. These targets correspond to the pathophysiological mechanisms by which astrocytes contribute to epilepsy. Additionally, we need to consider the potential challenges and limitations of translating these identified therapeutic targets into clinical treatments. These limitations arise from interspecies differences between humans and animal models, as well as the complex comorbidities associated with epilepsy in humans. We also highlight valuable future research directions worth exploring in the treatment of epilepsy and the regulation of astrocytes, such as gene therapy and imaging strategies. The findings presented in this review may help open new therapeutic avenues for patients with drugresistant epilepsy and for those suffering from other central nervous system disorders associated with astrocytic dysfunction.
文摘Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC)+6 种基金STI2030-Major Projects(2021ZD0202700,to HY)the National Natural Science Foundation of China(32241004,to HY)the Natural Science Foundation of Zhejiang Province of China(LR24C090001,to HY)Key R&D Program of Zhejiang Province(2024SSYS0017,to HY)CAMS Innovation Fund for Medical Sciences(2019-12M-5-057,to HY)Fundamental Research Funds for the Central Universities(226-2022-00193,to HY)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT310-01,to HY)。
文摘Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC).
文摘The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.
基金supported by a Presidential Postdoctoral Fellowship (021229-00001) from Nanyang Technological University,Singapore (to JZ)a Lee Kong Chian School of Medicine Dean’s Postdoctoral Fellowship (021207-00001) from NTU Singaporea Mistletoe Research Fellowship (022522-00001) from the Momental Foundaton,USA (to CHL)
文摘The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.Obesity-related conditions like type 2 diabetes and non-alcoholic fatty liver disease exacerbate this relationship.Peripheral lipid accumulation,particularly in the liver,initiates a cascade of inflammatory processes that extend to the brain,influencing critical metabolic regulatory regions.Ceramide and palmitate,key lipid components,along with lipid transporters lipocalin-2 and apolipoprotein E,contribute to neuroinflammation by disrupting blood–brain barrier integrity and promoting gliosis.Peripheral insulin resistance further exacerbates brain insulin resistance and neuroinflammation.Preclinical interventions targeting peripheral lipid metabolism and insulin signaling pathways have shown promise in reducing neuroinflammation in animal models.However,translating these findings to clinical practice requires further investigation into human subjects.In conclusion,metabolic dysfunction,peripheral inflammation,and insulin resistance are integral to neuroinflammation and neurodegeneration.Understanding these complex mechanisms holds potential for identifying novel therapeutic targets and improving outcomes for neurodegenerative diseases.
基金sponsored by National Natural Science Foundation of China(No.52302121,No.52203386)Shanghai Sailing Program(No.23YF1454700)+1 种基金Shanghai Natural Science Foundation(No.23ZR1472700)Shanghai Post-doctoral Excellent Program(No.2022664).
文摘With vigorous developments in nanotechnology,the elaborate regulation of microstructure shows attractive potential in the design of electromagnetic wave absorbers.Herein,a hierarchical porous structure and composite heterogeneous interface are constructed successfully to optimize the electromagnetic loss capacity.The macro–micro-synergistic graphene aerogel formed by the ice template‑assisted 3D printing strategy is cut by silicon carbide nanowires(SiC_(nws))grown in situ,while boron nitride(BN)interfacial structure is introduced on graphene nanoplates.The unique composite structure forces multiple scattering of incident EMWs,ensuring the combined effects of interfacial polarization,conduction networks,and magnetic-dielectric synergy.Therefore,the as-prepared composites present a minimum reflection loss value of−37.8 dB and a wide effective absorption bandwidth(EAB)of 9.2 GHz(from 8.8 to 18.0 GHz)at 2.5 mm.Besides,relying on the intrinsic high-temperature resistance of SiC_(nws) and BN,the EAB also remains above 5.0 GHz after annealing in air environment at 600℃ for 10 h.
文摘In-situ formed high Mn steel coating reinforced by carbides was formed by laser surface alloying(LSA).Laser alloyed layers on 1Cr18Ni9Ti steel with Mn+W_(2)C(specimen A),Mn+NiWC(specimen B)and Mn+SiC(specimen C)powders were fabricated to improve the wear and corrosion behavior of 1Cr18Ni9Ti steel blades in high speed mixers.Microstructure evolution,phases,element distribution,microhardness,wear and corrosion behavior of the laser alloyed layers were investigated.Results indicated that high Mn steel matrix composites with undissolved W_(2)C,WC and other in-situ formed carbides were formed by LSA with Mn+W_(2)C and Mn+NiWC while SiC totally dissolved into the high Mn matrix when adding Mn+SiC.Ni as the binding phase in Ni-WC powder decreased the crack sensitivity of the alloyed layer as compared with the addition of W_(2)C powder.An improvement in average microhardness was achieved in the matrix in specimen A,B and C,with the value of 615,602 and 277 HV_(0.5),while that of the substrate was 212 HV_(0.5).The increase of microhardness,wear and corrosion resistance is highly corelated to microstructure,formed phases,type and content of carbides,micro-hardness and toughness of the alloyed layers.
文摘BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.
基金financially supported by National Natural Science Foundation of China(32301800,32301923 and 32072053)Wheat Industrial Technology System of Shandong Province(SDAIT-01-01)Key Research and Development Project of Shandong Province(2022LZG002-4,2023LZGC009-4-4).
文摘Powdery mildew negatively impacts wheat yield and quality.Emmer wheat(Triticum dicoccum),an ancestral species of common wheat,is a gene donor for wheat improvement.Cultivated emmer accession H1-707 exhibited all-stage resistance to powdery mildew over consecutive years.Genetic analysis of H1-707 at the seedling stage revealed a dominant monogenic inheritance pattern,and the underlying gene was designated Pm71.By employing bulked segregant exome sequencing(BSE-Seq)and using 2000 F2:3 families,Pm71 was fine mapped to a 336-kb interval on chromosome arm 6AS by referencing to the durum cv.Svevo RefSeq 1.0.Collinearity analysis revealed high homology in the candidate interval between Svevo and six Triticum species.Among six high-confidence genes annotated within this interval,TRITD6Av1G005050 encoding a GDSL esterase/lipase was identified as a key candidate for Pm71.
基金supported by the National Key Re-search and Development Program of China(No.2022YFB4002100)the National Natural Science Foundation of China(No.52271136)the Natural Science Foundation of Shaanxi Province(Nos.2019TD-020 and 2021JC-06).
文摘Proton exchange membrane water electrolysis(PEMWE)is one of the most promising strategies to pro-duce green hydrogen energy,and it is crucial to exploit highly conductive and good corrosion-resistant coatings on bipolar plates(BPs),one of the core components in PEMWE cells.In this work,NbN coatings are deposited on Ti BPs by magnetron sputtering to improve the corrosion resistance and conductivity,for which the critical process parameters,such as the working pressure,partial nitrogen pressure and de-position temperature are well optimized.It is found that the compact microstructure,highly conductive δ-NbN and uniform nanoparticles play a dominant role in the synergistic improvement of the corrosion resistance and electrical conductivity of NbN coatings.The optimized NbN coatings exhibit excellent cor-rosion resistance with the low corrosion current density of 1.1×10^(-8) A cm^(-2),a high potential value of-0.005 V vs.SCE and a low ICR value of 15.8 mΩcm2@1.5 MPa.Accordingly,NbN coatings can be a promising candidate for the development of the low-cost and high-anti-corrosion Ti BPs of PEMWE.
基金supported by Shandong Provincial Natural Science Foundation(no.ZR2020MH319).
文摘Triple-negative breast cancer(TNBC)is currently the most heterogeneous and aggressive breast cancer type.It has a high recurrence rate,poor clinical prospects,and lack of predictive markers and potential treatment options.Dysregulated microRNAs(miRNAs)are involved in various cellular processes in TNBC.Moreover,variations in the miRNA levels in TNBC may act as a dependable indicator for predicting the effectiveness and specificity of treatments.Currently,the application of miRNAs for breast cancer therapy is primarily in the preclinical stage,with a focus on identifying highly specific and sensitive miRNAs that could offer new possibilities for early diagnosis,clinical treat-ment,and prognostic monitoring of TNBC.
基金support from the National Key Research and Development Program of China(No.2021YFB3701503)the Key Research and Development Program of Ningbo,China(No.2023Z107)+1 种基金the Jiangsu Key R&D program,China(No.BE2019072)the special project of Gansu regional science and technology cooperation,China(No.20JR10 QA579).
文摘Exploring high-efficiency and broadband microwave absorption(MA)materials with corrosion resistance and low cost is ur-gently needed for wide practical applications.Herein,the natural porous attapulgite(ATP)nanorods embedded with TiO_(2)and polyaniline(PANI)nanoparticles are synthesized via heterogeneous precipitation and in-situ polymerization.The obtained PANI-TiO_(2)-ATP one-di-mensional(1D)nanostructures can intertwine into three-dimensional(3D)conductive network,which favors energy dissipation.The min-imum reflection loss(RL_(min))of the PANI-TiO_(2)-ATP coating(20wt%)reaches-49.36 dB at 9.53 GHz,and the effective absorption band-width(EAB)can reach 6.53 GHz with a thickness of 2.1 mm.The excellent MA properties are attributed to interfacial polarization,mul-tiple loss mechanisms,and good impedance matching induced by the synergistic effect of PANI-TiO_(2)nanoparticle shells and ATP nanor-ods.In addition,salt spray and Tafel polarization curve tests reveal that the PANI-TiO_(2)-ATP coating shows outstanding corrosion resist-ance performance.This study provides a low-cost and high-efficiency strategy for constructing 1D nanonetwork composites for MA and corrosion resistance applications using natural porous ATP nanorods as carriers.
文摘BACKGROUND Liver transplant(LT)recipients are susceptible to carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Comprehensive research addressing the incidence,timing,infection sites,resistance patterns,treatment options,and associated risk factors among LT recipients with CRKP is now lacking.AIM To assess the incidence,resistance,therapy,and risk factors of CRKP infections post-LT,and to evaluate the impact of them on prognosis.METHODS A retrospective study was conducted,including 430 consecutive patients who underwent LT between January 2015 and June 2023.This study aimed to investigate the risk factors for CRKP infections and their influence on outcomes using logistic regression analysis.RESULTS Among the 430 patients who underwent LT,20(4.7%)experienced at least one documented CRKP infection within 3 months post-transplantation.The median time from LT to the onset of CRKP infections was 6.5 days.The lungs and bloodstream were the most common sites of CRKP infections.CRKP isolates were relatively susceptible to ceftazidime/avibactam(93.7%),polymyxin B(90.6%),and tigecycline(75.0%)treatment.However,all isolates were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin treatment.Recipients with CRKP infections had a mortality rate of 35%,the rate was 12.5%for those receiving ceftazidime/avibactam therapy.Multivariate analysis identified female sex[odds ratio(OR)=3.306;95%confidence interval(CI):1.239-8.822;P=0.017],intraoperative bleeding≥3000 mL(OR=3.269;95%CI:1.018-10.490;P=0.047),alanine aminotransferase on day 1 post-LT≥1500 U/L(OR=4.370;95%CI:1.686-11.326;P=0.002),and post-LT mechanical ventilation(OR=2.772;95%CI:1.077-7.135;P=0.035)as significant variables associated with CRKP.CRKP infections were related to an intensive care unit length(ICU)of stay≥7 days and 6-month all-cause mortality post-LT.CONCLUSION CRKP infections were frequent complications following LT,with poor associated outcomes.Risk factors for post-LT CRKP infections included female sex,significant intraoperative bleeding,elevated alanine aminotransferase levels,and the need for mechanical ventilation.CRKP infections negatively impacted survival and led to prolonged ICU stays.
基金supported by the National Natural Science Foundation of China(grant numbers 81991531 to M.W.,82102440 to J.J.,and 32400149 to J.Z.).
文摘Antimicrobial resistance is a global health crisis and carbapenem-resistant Klebsiella pneumoniae(CRKp)is listed as one of the top high-priority pathogens by the World Health Organization.Meanwhile,hypervirulent K.pneumoniae(hvKp)causes severe community-associated infections,such as liver abscesses and meningitis,in otherwise healthy individuals.Both CRKp and hvKp infections are associated with high mortality rates.The convergence of carbapenem resistance and hypervirulence within a single bacterial strain may lead to significantly more severe clinical outcomes.
基金supported by the National Natural Science Foundation of China(Nos.U21B2053,52071114,52001100,and 523B2010)Outstanding Youth Project of Natural Science Foundation of Heilongjiang Province(No.YQ2023E008)+1 种基金Young Elite Scientists Sponsorship Program by CAST(NO.2021QNRC001)Heilongjiang Touyan Team Program.
文摘Silicide coatings have proven to be promising for improving the high-temperature oxidation resistance of niobium alloy.However,the long-term protective property of single silicide coating remains a long-time endeavor due to the deficiency of oxygen-consuming phases,as well as the self-healing ability of the protective layer.Herein,a silicide-based composite coating is constructed on niobium alloy by incor-poration of nano-SiC particles for enhancing the high-temperature oxidation resistance.Isothermal oxi-dation results at 1250℃ for 50 h indicate that NbSi_(2)/Nb_(2)O_(5)-SiO_(2)/SiC multilayer coated sample with a low mass gain of 2.49 mg/cm^(2) shows an improved oxidation resistance compared with NbSi_(2) coating(6.49 mg/cm^(2)).The enhanced high-temperature antioxidant performance of NbSi_(2)/Nb_(2)O_(5)-SiO_(2)/SiC multi-layer coating is mainly attributed to the formation of the protective SiO_(2) self-healing film and the high-temperature diffusion behavior of NbSi_(2)/substrate.
基金supported by the Key Research and Development Program of Shandong Province,China(No 2021CXGC010803)Pan’an County Chinese Medicine Industry Project(No.PZYF202103).
文摘Reductive soil disinfestation(RSD)is commonly employed for soil remediation in greenhouse cultivation.However,its influence on antibiotic resistance genes(ARGs)in soil remains uncertain.This study investigated the dynamic changes in soil communities,potential bacterial pathogens,and ARG profiles under various organicmaterial treatments during RSD,including distillers’grains,potato peel,peanut vine,and peanut vine combined with charcoal.Results revealed that applying diverse organic materials in RSD significantly altered bacterial community composition and diminished the relative abundance of potential bacterial pathogens(P<0.05).The relative abundance of high-risk ARGs decreased by 10.7%-30.6%after RSD treatments,the main decreased ARG subtypeswere AAC(3)_Via,dfrA1,ErmB,lnuB,aadA.Actinobacteria was the primary host of ARGs and was suppressed by RSD.Soil physicochemical properties,such as total nitrogen,soil pH,total carbon,were crucial factors affecting ARG profiles.Our findings demonstrated that RSD treatment inhibited pathogenic bacteria and could be an option for reducing high-risk ARG proliferation in soil.
基金Guangdong Basic and Applied Basic Research Foundation(grant number 2024A1515010319 to J.Q.)Science and Technology Program of Shenzhen(grant numbers KCXFZ20230731100901003 to J.Q.and L.L.,KJZD20230923115116032 to J.Q.,JCYJ20190809144005609 to J.Q.)+1 种基金Shenzhen Key Laboratory of Biochip(grant number ZDSYS201504301534057 to J.Q.)Shenzhen High-level Hospital Construction Fund(to J.Q.).
文摘Nosocomial pathogen carbapenem-resistant Klebsiella pneumoniae(CRKP)poses a heightened risk to public health through carbapenem resistance and virulence convergence,particularly in China’s dominant sequence type 11(ST11)clone[1,2].Monoclonal K.pneumoniae exhibits within-host diversity during prolonged infections[3–5],with certain variants surviving through adaptation[4,6].CRKP strains from the blood of a single patient are heterogeneous in terms of antibiotic susceptibility,capsular polysaccharide production,and mucoviscosity[3].Intra-host evolution drives novel resistance via cumulative mutations(e.g.,the transcriptional regulator gene ramR mutations and the outer membrane porin gene OmpK35 loss)[4].
基金This work was supported by the National Natural Science Foundation of China(grant numbers 81560301 and 81160012)the Natural Science Foundation of Qinghai Province(grant number 2022-ZJ-905)‘2022 Qinghai Province Kunlun Talents High-end Innovation and Entrepreneurship Talents’Outstanding Talent Project.
文摘Background:Under hypoxia,exaggerated compensatory responses may lead to acute mountain sickness.The excessive vasodilatory effect of nitric oxide(NO)can lower the hypoxic pulmonary vasoconstriction(HPV)and peripheral blood pressure.While NO is catalyzed by various nitric oxide synthase(NOS)isoforms,the regulatory roles of these types in the hemodynamics of pulmonary and systemic circulation in living hypoxic animals remain unclear.Therefore,this study aims to investigate the regu-latory effects of different NOS isoforms on pulmonary and systemic circulation in hypoxic rats by employing selective NOS inhibitors and continuously monitoring hemodynamic parameters of both pulmonary and systemic circulation.Methods:Forty healthy male Sprague–Dawley(SD)rats were randomly divided into four groups:Control group(NG-nitro-D-arginine methyl ester,D-NAME),L-NAME group(non-selective NOS inhibitor,NG-nitro-L-arginine methyl ester),AG group(in-ducible NOS inhibitor group,aminoguanidine),and 7-NI group(neurological NOS in-hibitor,7-nitroindazole).Hemodynamic parameters of rats were monitored for 10 min after inhibitor administration and 5 min after induction of hypoxia[15%O2,2200 m a.sl.,582 mmHg(76.5 kPa),Xining,China]using the real-time dynamic monitoring model for pulmonary and systemic circulation hemodynamics in vivo.Serum NO concentra-tions and blood gas analysis were measured.Results:Under normoxia,mean arterial pressure and total peripheral vascular resist-ance were increased,and ascending aortic blood flow and serum NO concentration were decreased in the L-NAME and AG groups.During hypoxia,pulmonary arterial pressure and pulmonary vascular resistance were significantly increased in the L-NAME and AG groups.Conclusions:This compensatory mechanism activated by inducible NOS and en-dothelial NOS effectively counteracts the pulmonary hemodynamic changes induced by hypoxic stress.It plays a crucial role in alleviating hypoxia-induced pulmonary arte-rial hypertension.
