An optimization solution to roll shifting strategy for alternately rolling campaign is presented. All the strips in a rolling campaign are divided into narrow strips and wide ones, and shifting position of narrow stri...An optimization solution to roll shifting strategy for alternately rolling campaign is presented. All the strips in a rolling campaign are divided into narrow strips and wide ones, and shifting position of narrow strips is obtained by the recursive method, and then shifting position of wide strips is optimized by NSGA-II which is a multiobjective genetic algorithm. For wide strips, a multi-objective optimization model of roll shifting strategy is pro posed, which takes 3 wear contour factors including edge smoothness, body smoothness and edge drop as optimization objectives. The Pareto optimal front of roll shifting strategy can be gained quickly by NSGA-II, which suggests a series of alternative solutions to roll shifting strategy. Analysis shows that the conflict exists among the 3 objectives. The final optimal solution is selected from the Pareto optimal solutions by the weighted-sum decision-making method. Industrial production proves the validity of the solution, and it can improve strip profile of alternately rolling, reduce strip edge wave, and extend the rolling miles of rolling campaigns.展开更多
Presently,we develop a simplified corticothalamic(SCT)model and propose a single-pulse alternately resetting stimulation(SARS)with sequentially applying anodic(A,“+”)or cathodic(C,“−”)phase pulses to the thalamic ...Presently,we develop a simplified corticothalamic(SCT)model and propose a single-pulse alternately resetting stimulation(SARS)with sequentially applying anodic(A,“+”)or cathodic(C,“−”)phase pulses to the thalamic reticular(RE)nuclei,thalamus-cortex(TC)relay nuclei,and cortical excitatory(EX)neurons,respectively.Abatement effects of ACC-SARS of RE,TC,and EX for the 2 Hz-4 Hz spike and wave discharges(SWD)of absence seizures are then concerned.The m∶n on-off ACC-SARS protocol is shown to effectively reduce the SWD with the least current consumption.In particular,when its frequency is out of the 2 Hz-4 Hz SWD dominant rhythm,the desired seizure abatements can be obtained,which can be further improved by our proposed directional steering(DS)stimulation.The dynamical explanations for the SARS induced seizure abatements are lastly given by calculating the averaged mean firing rate(AMFR)of neurons and triggering averaged mean firing rates(TAMFRs)of 2 Hz-4 Hz SWD.展开更多
In this paper,according to the Shamanskii technology,an alternately linearized implicit(ALI)iteration method is proposed to compute the minimal nonnegative solution to the nonsymmetric coupled algebraic Riccati equati...In this paper,according to the Shamanskii technology,an alternately linearized implicit(ALI)iteration method is proposed to compute the minimal nonnegative solution to the nonsymmetric coupled algebraic Riccati equation.Based on the ALI iteration method,we propose two modified alternately linearized implicit(MALI)iteration methods with double parameters.Further,we prove the monotone convergence of these iteration methods.Numerical examples demonstrate the effectiveness of the presented iteration methods.展开更多
A numerical solution of the quadratic matrix equations associated with a nonsingular M-matrix by using the alternately linearized implicit iteration method is considered. An iteration method for computing a nonsingula...A numerical solution of the quadratic matrix equations associated with a nonsingular M-matrix by using the alternately linearized implicit iteration method is considered. An iteration method for computing a nonsingular M-matrix solution of the quadratic matrix equations is developed, and its corresponding theory is given. Some numerical examples are provided to show the efficiency of the new method.展开更多
Two-dimensional(2D)heterostructures hold great promise in designing integrated materials,while the current synthesis strategies still confront challenges for multilayer heterostructure construction and scale-up produc...Two-dimensional(2D)heterostructures hold great promise in designing integrated materials,while the current synthesis strategies still confront challenges for multilayer heterostructure construction and scale-up production.Here we report a generalized host-vip strategy based on nonexfoliated layered graphene oxide(LGO)to construct graphene-based heterostructures that consist of multilayered,alternately aligned graphene and metal oxide nanosheets.The 2D-aligned GOs and open interlayer spaces make LGO an ideal platform to create periodic 2D host frameworks.Polyetheramine oligomers covalently bond the adjacent GOs.The extended chain conformation endows the resulting accordionlike GO frameworks with high structural stability,periodicity and enlarged interlayer space.Owing to the high affinity of the open and well-arranged 2D channels toward vip precursors,a variety of high-quality heterostructures can be synthesized.Furthermore,a variety of exfoliated,ultrathin metal oxide nanosheets can also be prepared by removing the graphene skeleton.The flexible interlayer chemistry presented in this study paves a way toward the synthesis of a large family of graphene-inorganic/organic 2D heterostructures.展开更多
Glioblastoma(GBM)is an aggressive brain tumor with limited treatment options and a dismal prognosis.While immunotherapy has shown promise in treating some solid tumors,the treatment of GBM has been mostly unsuccessful...Glioblastoma(GBM)is an aggressive brain tumor with limited treatment options and a dismal prognosis.While immunotherapy has shown promise in treating some solid tumors,the treatment of GBM has been mostly unsuccessful because of a lack of targetable tumor antigens and high tumor heterogeneity.Here,we report RCAN1-4 as a novel tumor antigen derived from alternative splicing induced by the transcription factor C/EBPβ.Both C/EBPβand RCAN1-4 are highly expressed in GBM and glioma stem cells as mesenchymal subtype hallmarks.We report an immunogenic HLA-A24-specific splicing junction epitope within exon 4 and exon 5 that is unique to RCAN1-4.This epitope was validated for its ability to stimulate T cell responses in HLA-A24^(+)donors and GBM patients,leading us to identify RCAN1-4-reactive T cell receptors(TCRs)for the construction of TCR-engineered T cells(TCR-T cells).Functional studies of TCR-Ts demonstrated the in vitro and in vivo killing of RCAN1-4pos GBM tumor cells,highlighting its potential as an immunotherapeutic target in mesenchymal GBM.展开更多
Ship operations are crucial to global trade,and their decarbonization is essential to mitigate climate change.This study evaluates the economic viability of existing and emerging decarbonization technologies in mariti...Ship operations are crucial to global trade,and their decarbonization is essential to mitigate climate change.This study evaluates the economic viability of existing and emerging decarbonization technologies in maritime shipping using the levelized cost of energy methodology.It includes a detailed comparative analysis based on essential criteria and sensitivity assessments to highlight the economic impacts of technological advancements.Key factors influencing total costs include fuel costs,carbon pricing,and energy demands for carbon capture.The findings reveal that methanol is more cost-effective than heavy fuel oil(HFO)when priced below 3000 CNY/t,assuming HFO costs 4400 CNY/t.Additionally,methanol with post-combustion carbon capture is less expensive than pre-combustion carbon capture.When carbon prices rise above 480 CNY/t,carbon capture technologies prove more economical than purchasing carbon emission allowances for HFO and liquefied natural gas.Enhanc-ing the use of exhaust gas waste heat is recommended for cost savings.Post-combustion carbon capture also shows greater efficiency,requiring about 1.1 GJ/t less energy than pre-combustion methods,leading to lower overall costs.Future research should focus on market mechanisms to stabilize fuel prices and develop less energy-intensive carbon capture technologies.This study offers critical insights into effective decarbonization strategies for advancing global maritime trade in the present and future.展开更多
The main aim of this paper is a classification of non-trivial 2-(v,5,λ)designs admitting a block-transitive automorphism group.Let D=(P,B)be a non-trivial 2-(v,5,λ)design and G be a block-transitive automorphism gro...The main aim of this paper is a classification of non-trivial 2-(v,5,λ)designs admitting a block-transitive automorphism group.Let D=(P,B)be a non-trivial 2-(v,5,λ)design and G be a block-transitive automorphism group of D.In this paper,we prove that if Soc(G)is an alternating simple group,then the rank of G is at most 3.Moreover,we determine all pairs(D,G).展开更多
The preparation and functionalization of polymeric capsules attract intense attention due to their application in various areas.Herein we presented an amphiphilic alternating copolymer(ACP)-based microcapsule which is...The preparation and functionalization of polymeric capsules attract intense attention due to their application in various areas.Herein we presented an amphiphilic alternating copolymer(ACP)-based microcapsule which is both robust and readily-functionalized through interfacial click polymerization.A water-in-oil emulsion was constructed to act as the reaction medium,the hydrophilic 1,3-butadiene diepoxide(BDE)in water phase reacted with the oleophilic 1,4-dibutanedithiol(BDT)in oil phase at the water-oil interface to form the amphiphilic ACP named poly(2,3-dihydroxy butylene-alt-butylene dithioether)(abbreviated as P(DHB-a-BDT)below),which would deposite in situ to form the micro-sized capsules.Significantly,the dried capsules are robust enough to be rehydrated once the water was added and almost restored their original morphologies.Further elucidation showed that the Young's modulus of these capsules exceeded 1 GPa.As long as we know,it is the first time for the mechanical properties of the ACP-based microstructures being investigated.Besides,functionalization could be achieved simultaneously with the formation process.As a proof of concept,positive-charged capsules were successfully obtained through click copolymerization.Stemming from the unique characteristics of amphiphilic ACPs which combined both merits of click chemistry and interfacial reactions,all these features of the current method as well as the resultant capsules may promote the application of the polymeric capsules.展开更多
Background The rapid emergence of multidrug-resistant Salmonella in poultry demands alternative control strategies beyond conventional antibiotics.In this study,we evaluated a combination of lytic Salmonella-infecting...Background The rapid emergence of multidrug-resistant Salmonella in poultry demands alternative control strategies beyond conventional antibiotics.In this study,we evaluated a combination of lytic Salmonella-infecting bacteriophages(SLAM_phi ST45 and SLAM_phiST56)and a probiotic bacterium Limosilactobacillus reuteri(SLAM_LAR11)in a chick model challenged with Salmonella enterica serovar Typhimurium infection.Results Co-administration with two-phage cocktail and a probiotic showed markedly reduced Salmonella colonization in the gut and systemic organs of chicks,comparable to the effect of phage-only treatment.In contrast with phage-only treatment,the combined therapy significantly improved the rate of body-weight change from the day of infection to necropsy(P<0.0001)and alleviated infection-associated splenomegaly(P=0.028)and hepatomegaly(P=0.011).In the ileum,the villus height-to-crypt depth ratio(VH/CD)increased significantly(P=0.044).In the colon,expression of tight-junction genes OCLN(P=0.014),TJP1(P<0.0001),and MUC2(P=0.011)was elevated,whereas the pro-inflammatory cytokine IL6 was reduced(P=0.018).These improvements were accompanied,in the cecum,by trends toward decreases in Escherichia-Shigella(P=0.09)and Clostridium(P=0.16)and a trend toward an increase in Blautia(P=0.11);additionally,in the ileum,Lactobacillus(P=0.037)and Blautia(P=0.016)increased significantly,yielding a more balanced microbiota than with phage-only treatment.Consistently,levels of functional metabolites,including acetic acid(LDA=3.32)and lactic acid(LDA=5.29),were increased.Conclusion Taken together,these findings demonstrate that phage-probiotic co-administration not only enhances the clearance of multidrug-resistant Salmonella more effectively than phage treatment alone but also promotes intestinal health,highlighting its potential as an antibiotic-alternatives strategy to improve intestinal health and ensure food safety in poultry production systems.展开更多
Deep learning methods have achieved significant progress in solving partial differential equations.However,when applied to the widely used anisotropic scattering neutron transport equations in reactor engineering,thes...Deep learning methods have achieved significant progress in solving partial differential equations.However,when applied to the widely used anisotropic scattering neutron transport equations in reactor engineering,these encounter significant challenges.To address this issue,this study introduces a multi-antiderivative transformation alternating iterative deep learning method(M-AIM).This method transforms the integral terms of the scattering and fission sources in the transport equation into multiple antiderivative functions corresponding to the integrand,converts the differential-integral form of the transport equation into an exact differential equation,and establishes the necessary constraints for a unique solution.The M-AIM uses multiple deep neural networks to map the unknown angular flux density of transport equations and represents various forms of antiderivative functions.It constructs the corresponding weighted loss functions.By alternating iterative training with deep learning methods applied to these neural networks,the loss is reduced gradually.When the loss decreases to a preset minimum,the neural network approaches a numerical solution for both angular flux density and antiderivative functions.This paper presents a numerical verification of geometries such as flat plates and spheres.It verifies the validity of the theoretical framework and associated methods.The study contributes to the development of novel technical approaches for applying deep learning to solve anisotropic scattering neutron transport equations in reactor engineering.展开更多
Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammat...Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.展开更多
As silicon-based transistors face fundamental scaling limits,the search for breakthrough alternatives has led to innovations in 3D architectures,heterogeneous integration,and sub-3 nm semiconductor body thicknesses.Ho...As silicon-based transistors face fundamental scaling limits,the search for breakthrough alternatives has led to innovations in 3D architectures,heterogeneous integration,and sub-3 nm semiconductor body thicknesses.However,the true effectiveness of these advancements lies in the seamless integration of alternative semiconductors tailored for next-generation transistors.In this review,we highlight key advances that enhance both scalability and switching performance by leveraging emerging semiconductor materials.Among the most promising candidates are 2D van der Waals semiconductors,Mott insulators,and amorphous oxide semiconductors,which offer not only unique electrical properties but also low-power operation and high carrier mobility.Additionally,we explore the synergistic interactions between these novel semiconductors and advanced gate dielectrics,including high-K materials,ferroelectrics,and atomically thin hexagonal boron nitride layers.Beyond introducing these novel material configurations,we address critical challenges such as leakage current and long-term device reliability,which become increasingly crucial as transistors scale down to atomic dimensions.Through concrete examples showcasing the potential of these materials in transistors,we provide key insights into overcoming fundamental obstacles—such as device reliability,scaling down limitations,and extended applications in artificial intelligence—ultimately paving the way for the development of future transistor technologies.展开更多
Background:Cupping therapy(CT),an ancient practice revived in modern sports medicine,offers potential benefits for athlete recovery and performance.Distinctions between wet CT(WCT)and dry CT(DCT)in sports science focu...Background:Cupping therapy(CT),an ancient practice revived in modern sports medicine,offers potential benefits for athlete recovery and performance.Distinctions between wet CT(WCT)and dry CT(DCT)in sports science focus on their effects on recovery metrics,particularly how they influence sleep quality,perceived wellness,and athletic performance.Despite anecdotal evidence of its efficacy,rigorous comparative studies are scarce.Objective:This study aimed to evaluates and compare the effects of WCT and DCT on endurance,perceived wellness,exertion levels,and sleep quality among young,active males,addressing the gap in the literature regarding CT's efficacy in sports performance and recovery.Methods:Thirty-two amateur runners were randomly divided into two groups:one followed WCT sessions and the other followed DCT sessions.The study assessed the interventions'impacts on endurance performance(Yo-Yo intermittent recovery test),sleep quality(Pittsburgh Sleep Quality Index),and perceived exertion(Borg CR10 Scale).Heart rate was measured using a Polar H10 sensor to gauge physiological responses during physical tests.Results:Significant improvements were observed in the WCT group for sleep latency(%change=-82.31%;interaction group×time p=0.006;Cohen's d=0.74)and sleep disturbance(%change=-68.70%;interaction group×time p<0.001;Cohen's d=1.09),suggesting enhanced sleep quality(global score;%change=-52.81;interaction group×time p=0.004;Cohen's d=0.77).However,no significant differences were found in direct performance metrics(distance,maximal heart rate,maximal oxygen uptake)between WCT and DCT groups.These findings highlight WCT's potential as a recovery aid,particularly through improved sleep,without directly influencing endurance performance outcomes.Conclusion:WCT may serve as an effective ergogenic aid for athletes by potentially improving sleep quality and reducing perceived exertion,thus contributing indirectly to performance through enhanced recovery.展开更多
Limited adoption of solar energy in the Northwestern region of Russia is associated with insufficient data on annual solar radiation indicators and on the potential of solar collectors for water heating.The study aims...Limited adoption of solar energy in the Northwestern region of Russia is associated with insufficient data on annual solar radiation indicators and on the potential of solar collectors for water heating.The study aims to evaluate the potential of solar water heating for domestic use in Northwestern Russia,using Tyumen city as the case.In this region,the number of cloudy days ranges from 5% to 50%,with cloud cover increasing in winter.New data on the total solar radiation,availability duration,and cloud cover have been collected.Solar irradiance could reach 900 MJ/m^(2) during summer months,while decreasing to 50–150 MJ/m^(2) significantly in winter.Notably,the solar radiation demonstrates predictable and stable characteristics between the hours of 9 a.m.and 3 p.m.Consequently,the heating system is equipped with a gas-supplied boiler as the primary heat source,with the solar collector being the secondary clean energy source to meet the demand of a residential house.A is designed to compensate for the heat losses in the evening and at night.The results of unmatching energy demand and production highlight the need for a water tank for energy storage to facilitate a wider use of solar power.The peak thermal energy requirement for domestic hot water(DHW)occurs in January,amounting to 6046.8 MJ.In summer,from May to August,the thermal energy produced by solar collectors is not utilized due to the lack of heating load.The annual data indicate that the solar collectors contribute approximately 14%of the total heat required for DHW.展开更多
Mainstream medicine commonly categorizes acupuncture as“alternative and complementary,”a designation that reflects conceptual gaps in existing treatment classification systems.Integrating complementary medicine into...Mainstream medicine commonly categorizes acupuncture as“alternative and complementary,”a designation that reflects conceptual gaps in existing treatment classification systems.Integrating complementary medicine into the mainstream medical system requires a conceptual adjustment.Here,Ⅰ propose a mechanism-based 5R classification—Removing,Repairing,Replacing,Replenishing,Regulating—to systematically categorize therapies.Based on this classification,acupuncture and its related interventions fall under functional regulation therapy.This framework offers a unified,functional perspective that facilitates the integration of complementary medicine into mainstream medical taxonomy.展开更多
The ectomycorrhizal fungus Paxillus involutus was inoculated onto tissue-cultures of the hybrid poplar,Populus davidiana×P.bolleana,to evaluate the elemental defense effect to heavy metals copper and cadmium at d...The ectomycorrhizal fungus Paxillus involutus was inoculated onto tissue-cultures of the hybrid poplar,Populus davidiana×P.bolleana,to evaluate the elemental defense effect to heavy metals copper and cadmium at different concentrations by simulating Alternaria alternata fungus infection.The enrichment capacity of Populus davidiana×P.bolleana for Cu and Cd was closely associated with the degree of heavy metal stress.There was a significant positive interaction of applying Cu and Cd and the inoculation with P.involutus on A.alternata leaf blight disease index.The incidence rate and disease index of leaf blight underwent a significant reduction compared with the controls.Similarly,the ratio of the area of disease spot to leaf area,incidence rate,and disease index for Populus davidiana×P.bolleana leaves inoculated with Paxillus involutus(Batsch)Fr.were significantly lower than those of their nonmycorrhizal counterparts.With increasing the degree of Cu and Cd stress,a gradual increase in the average value of the membership function for the incidence rate and disease index was observed,indicating the weakened pathogen's ability to cause infection and the improved resistance of Populus davidiana×P.bolleana to leaf blight disease under Cu and Cd stress.Moreover,superoxide dismutase enzyme activity in Populus davidiana×P.bolleana increased significantly,reaching levels of 411.0 U/g FW and 421.6 U/g FW under Cu and Cd treatments,respectively.These changes in metabolic products and antioxidant enzyme activities suggest that P.involutus may enhance the resistance of Populus davidiana×P.bolleana to the fungus,Alternaria alternata Fr.Keissel under heavy metal stress by modulating these physiological indicators.展开更多
Accurately assessing the relationship between tree growth and climatic factors is of great importance in dendrochronology.This study evaluated the consistency between alternative climate datasets(including station and...Accurately assessing the relationship between tree growth and climatic factors is of great importance in dendrochronology.This study evaluated the consistency between alternative climate datasets(including station and gridded data)and actual climate data(fixed-point observations near the sampling sites),in northeastern China’s warm temperate zone and analyzed differences in their correlations with tree-ring width index.The results were:(1)Gridded temperature data,as well as precipitation and relative humidity data from the Huailai meteorological station,was more consistent with the actual climate data;in contrast,gridded soil moisture content data showed significant discrepancies.(2)Horizontal distance had a greater impact on the representativeness of actual climate conditions than vertical elevation differences.(3)Differences in consistency between alternative and actual climate data also affected their correlations with tree-ring width indices.In some growing season months,correlation coefficients,both in magnitude and sign,differed significantly from those based on actual data.The selection of different alternative climate datasets can lead to biased results in assessing forest responses to climate change,which is detrimental to the management of forest ecosystems in harsh environments.Therefore,the scientific and rational selection of alternative climate data is essential for dendroecological and climatological research.展开更多
Hans Zempel1,2 TAU,a microtubule-associated protein,encoded by the microtubule-associated protein tau(MAPT)gene,is a central regulator of microtubule stability and axonal function in the human brain,with its pathologi...Hans Zempel1,2 TAU,a microtubule-associated protein,encoded by the microtubule-associated protein tau(MAPT)gene,is a central regulator of microtubule stability and axonal function in the human brain,with its pathological aggregation representing a hallmark of Alzheimer’s disease and related tauopathies.Despite extensive research into the role of TAU in neurodegeneration,its essentiality for human brain development has remained unclear.This perspective synthesizes recent genetic,molecular,and cellular evidence to demonstrate that the human brain-specific TAU isoform 0N3R is indispensable for proper neurodevelopment,pointing to loss-of-function of this isoform as a novel paradigm for TAU-associated disease.Alternative splicing of MAPT generates six brain-specific TAU isoforms,with 0N3R being exclusively expressed during fetal brain development.Analysis of large-scale human genetic datasets(gnomAD v4.0.0)reveals a high probability of loss-of-function intolerance(pLI=0.96)for the 0N3R isoform.This is in stark contrast to the canonical Matched Annotation from the NCBI and EMBL-EBI(MANE)transcript and peripheral“Big TAU,”both of which are tolerant to loss-of-function mutations.This intolerance is further supported by the scarcity of loss-of-function mutations in 0N3R-encoding exons and high missense constraint scores,suggesting strong evolutionary selection against disruption of this isoform.Functional studies using human induced pluripotent stem cell-derived cortical neurons with CRISPR-Cas9-mediated MAPT knockout reveal that,unlike in murine models where compensation by other microtubule-associated proteins occurs,loss of TAU in human neurons leads to deficits in neurite outgrowth,axon initial segment shortening,and a trend toward hyperexcitability,accompanied by broad transcriptomic changes affecting genes involved in microtubule organization and synaptic structure.Remarkably,re-expression of any of the six human brain-specific TAU isoforms rescues these phenotypes,underscoring their functional redundancy during development.These findings position the 0N3R isoform as essential for human brain development and suggest that loss-of-function mutations affecting this isoform likely result in neurodevelopmental impairment,potentially manifesting as intellectual disability without overt dysmorphic features.This contrasts with the apparent tolerance to MAPT loss-of-function in mice and peripheral tissues,highlighting a critical species-and isoform-specific requirement for TAU in human neurodevelopment.The hypothesis of 0N3R-TAU loss-of-function intolerance opens new avenues for understanding neurodevelopmental disorders and refines the conceptual framework of TAU-associated disease mechanisms beyond toxic gain-of-function.展开更多
Alternate wetting and drying irrigation(AWD)significantly influences the cooking and eating quality of rice(Oryza sativa L.).However,the mechanisms by which AWD affects rice cooking and eating quality remain unclear.L...Alternate wetting and drying irrigation(AWD)significantly influences the cooking and eating quality of rice(Oryza sativa L.).However,the mechanisms by which AWD affects rice cooking and eating quality remain unclear.Lipid and free fatty acid contents in grains correlate positively with cooking and eating quality of rice.This study examined Yangdao 6(YD6,a conventional taste indica inbred)and Nanjing 9108(NJ9108,a superior taste japonica inbred)cultivated under conventional irrigation(CI),alternate wetting and moderate drying irrigation(AWMD),and alternate wetting and severe drying irrigation(AWSD)from 10 days after transplanting to maturity.The research investigated the relationship between lipid and free fatty acid biosynthesis in grains and the cooking and eating quality of rice.Compared to CI treatment,AWMD significantly enhanced the contents of lipid,total free fatty acids(TFFAs),free unsaturated fatty acids(FUFAs),linoleic acid,and oleic acid in milled rice by increasing activities of enzymes associated with lipid synthesis,while AWSD produced opposite effects.Correlation analysis revealed that elevated levels of lipid,TFFAs,FUFAs,linoleic acid,and oleic acid contribute to improved rice cooking and eating quality.The findings demonstrate that AWMD enhances cooking and eating quality of milled rice through optimization of lipid and fatty acid synthesis in rice grains.展开更多
基金Item Sponsored by National Natural Science Foundation of China(50974039)
文摘An optimization solution to roll shifting strategy for alternately rolling campaign is presented. All the strips in a rolling campaign are divided into narrow strips and wide ones, and shifting position of narrow strips is obtained by the recursive method, and then shifting position of wide strips is optimized by NSGA-II which is a multiobjective genetic algorithm. For wide strips, a multi-objective optimization model of roll shifting strategy is pro posed, which takes 3 wear contour factors including edge smoothness, body smoothness and edge drop as optimization objectives. The Pareto optimal front of roll shifting strategy can be gained quickly by NSGA-II, which suggests a series of alternative solutions to roll shifting strategy. Analysis shows that the conflict exists among the 3 objectives. The final optimal solution is selected from the Pareto optimal solutions by the weighted-sum decision-making method. Industrial production proves the validity of the solution, and it can improve strip profile of alternately rolling, reduce strip edge wave, and extend the rolling miles of rolling campaigns.
基金Project supported by the National Natural Science Foundation of China(Nos.11702018,11932003,and 11672074)。
文摘Presently,we develop a simplified corticothalamic(SCT)model and propose a single-pulse alternately resetting stimulation(SARS)with sequentially applying anodic(A,“+”)or cathodic(C,“−”)phase pulses to the thalamic reticular(RE)nuclei,thalamus-cortex(TC)relay nuclei,and cortical excitatory(EX)neurons,respectively.Abatement effects of ACC-SARS of RE,TC,and EX for the 2 Hz-4 Hz spike and wave discharges(SWD)of absence seizures are then concerned.The m∶n on-off ACC-SARS protocol is shown to effectively reduce the SWD with the least current consumption.In particular,when its frequency is out of the 2 Hz-4 Hz SWD dominant rhythm,the desired seizure abatements can be obtained,which can be further improved by our proposed directional steering(DS)stimulation.The dynamical explanations for the SARS induced seizure abatements are lastly given by calculating the averaged mean firing rate(AMFR)of neurons and triggering averaged mean firing rates(TAMFRs)of 2 Hz-4 Hz SWD.
基金National Natural Science Foundation for Youths of China(11801164)Youth Project of Hunan Provincial Education Department of China(22B0498).
文摘In this paper,according to the Shamanskii technology,an alternately linearized implicit(ALI)iteration method is proposed to compute the minimal nonnegative solution to the nonsymmetric coupled algebraic Riccati equation.Based on the ALI iteration method,we propose two modified alternately linearized implicit(MALI)iteration methods with double parameters.Further,we prove the monotone convergence of these iteration methods.Numerical examples demonstrate the effectiveness of the presented iteration methods.
基金This work was supported by the National Natural Science Foundation （No.11171337）, P. R. China.
文摘A numerical solution of the quadratic matrix equations associated with a nonsingular M-matrix by using the alternately linearized implicit iteration method is considered. An iteration method for computing a nonsingular M-matrix solution of the quadratic matrix equations is developed, and its corresponding theory is given. Some numerical examples are provided to show the efficiency of the new method.
基金This work was supported by Shanghai International Collaboration Research Project(19520713900).
文摘Two-dimensional(2D)heterostructures hold great promise in designing integrated materials,while the current synthesis strategies still confront challenges for multilayer heterostructure construction and scale-up production.Here we report a generalized host-vip strategy based on nonexfoliated layered graphene oxide(LGO)to construct graphene-based heterostructures that consist of multilayered,alternately aligned graphene and metal oxide nanosheets.The 2D-aligned GOs and open interlayer spaces make LGO an ideal platform to create periodic 2D host frameworks.Polyetheramine oligomers covalently bond the adjacent GOs.The extended chain conformation endows the resulting accordionlike GO frameworks with high structural stability,periodicity and enlarged interlayer space.Owing to the high affinity of the open and well-arranged 2D channels toward vip precursors,a variety of high-quality heterostructures can be synthesized.Furthermore,a variety of exfoliated,ultrathin metal oxide nanosheets can also be prepared by removing the graphene skeleton.The flexible interlayer chemistry presented in this study paves a way toward the synthesis of a large family of graphene-inorganic/organic 2D heterostructures.
基金supported by the Botha-Chan Research Fund,the Office of the Assistant Secretary of Defense for Health Affairs through award no.HT9425-24-1-0623(I.R.)the Brain Tumor Funders'Collaborative,the Ellie Kavalieros DIPG Research Fund+6 种基金the UPMC Children’s Hospital of Pittsburgh Foundation(G.K.,I.R.)the Children’s Brain Tumor Network(I.F.P.),a stipend from the Central South University Xiangya School of Medicine and University of Pittsburgh(Z.X.)by grant NS117742 from the National Institute of Health(T.G.F.)support from the Jesse H.&Mary Jones Gibbs Endowed Chair(T.G.F)supported in part by the University of Pittsburgh Center for Research Computing,RRID:SCR_022735through NIH award number S10OD028483Work performed in the UPMC Hillman Cancer Center Tissue and Research Pathology Services Shared Resource Facility and the services and instruments used in this project were supported,in part,by the University of Pittsburgh and the NCI of the NIH under Award Number P30CA047904.
文摘Glioblastoma(GBM)is an aggressive brain tumor with limited treatment options and a dismal prognosis.While immunotherapy has shown promise in treating some solid tumors,the treatment of GBM has been mostly unsuccessful because of a lack of targetable tumor antigens and high tumor heterogeneity.Here,we report RCAN1-4 as a novel tumor antigen derived from alternative splicing induced by the transcription factor C/EBPβ.Both C/EBPβand RCAN1-4 are highly expressed in GBM and glioma stem cells as mesenchymal subtype hallmarks.We report an immunogenic HLA-A24-specific splicing junction epitope within exon 4 and exon 5 that is unique to RCAN1-4.This epitope was validated for its ability to stimulate T cell responses in HLA-A24^(+)donors and GBM patients,leading us to identify RCAN1-4-reactive T cell receptors(TCRs)for the construction of TCR-engineered T cells(TCR-T cells).Functional studies of TCR-Ts demonstrated the in vitro and in vivo killing of RCAN1-4pos GBM tumor cells,highlighting its potential as an immunotherapeutic target in mesenchymal GBM.
基金supported by the National Key R&D Program of China(No.2022YFC3701500)the Key R&D Plan Projects of Zhejiang Province(No.2024SSYS0072)Zhejiang Provincial Natural Science Foundation(No.LDT23E0601).
文摘Ship operations are crucial to global trade,and their decarbonization is essential to mitigate climate change.This study evaluates the economic viability of existing and emerging decarbonization technologies in maritime shipping using the levelized cost of energy methodology.It includes a detailed comparative analysis based on essential criteria and sensitivity assessments to highlight the economic impacts of technological advancements.Key factors influencing total costs include fuel costs,carbon pricing,and energy demands for carbon capture.The findings reveal that methanol is more cost-effective than heavy fuel oil(HFO)when priced below 3000 CNY/t,assuming HFO costs 4400 CNY/t.Additionally,methanol with post-combustion carbon capture is less expensive than pre-combustion carbon capture.When carbon prices rise above 480 CNY/t,carbon capture technologies prove more economical than purchasing carbon emission allowances for HFO and liquefied natural gas.Enhanc-ing the use of exhaust gas waste heat is recommended for cost savings.Post-combustion carbon capture also shows greater efficiency,requiring about 1.1 GJ/t less energy than pre-combustion methods,leading to lower overall costs.Future research should focus on market mechanisms to stabilize fuel prices and develop less energy-intensive carbon capture technologies.This study offers critical insights into effective decarbonization strategies for advancing global maritime trade in the present and future.
基金Supported by the National Natural Science Foundation of China(Grant No.12361004)the Natural Science Foun-dation of Jiangxi Province(Grant Nos.20224BAB211005,20242BAB25005)the Natural Science Foundation of Henan Province(Grant No.242300421688).
文摘The main aim of this paper is a classification of non-trivial 2-(v,5,λ)designs admitting a block-transitive automorphism group.Let D=(P,B)be a non-trivial 2-(v,5,λ)design and G be a block-transitive automorphism group of D.In this paper,we prove that if Soc(G)is an alternating simple group,then the rank of G is at most 3.Moreover,we determine all pairs(D,G).
基金financially supported by the Fundamental Research Funds for Central Universities(No.24D110627)。
文摘The preparation and functionalization of polymeric capsules attract intense attention due to their application in various areas.Herein we presented an amphiphilic alternating copolymer(ACP)-based microcapsule which is both robust and readily-functionalized through interfacial click polymerization.A water-in-oil emulsion was constructed to act as the reaction medium,the hydrophilic 1,3-butadiene diepoxide(BDE)in water phase reacted with the oleophilic 1,4-dibutanedithiol(BDT)in oil phase at the water-oil interface to form the amphiphilic ACP named poly(2,3-dihydroxy butylene-alt-butylene dithioether)(abbreviated as P(DHB-a-BDT)below),which would deposite in situ to form the micro-sized capsules.Significantly,the dried capsules are robust enough to be rehydrated once the water was added and almost restored their original morphologies.Further elucidation showed that the Young's modulus of these capsules exceeded 1 GPa.As long as we know,it is the first time for the mechanical properties of the ACP-based microstructures being investigated.Besides,functionalization could be achieved simultaneously with the formation process.As a proof of concept,positive-charged capsules were successfully obtained through click copolymerization.Stemming from the unique characteristics of amphiphilic ACPs which combined both merits of click chemistry and interfacial reactions,all these features of the current method as well as the resultant capsules may promote the application of the polymeric capsules.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the National Research Foundation of Korea Grantfunded by the Korean government(MEST)(NRF-2021R1A2C3011051)by the Korea government(MSIT)(No.RS-2023-00218476)。
文摘Background The rapid emergence of multidrug-resistant Salmonella in poultry demands alternative control strategies beyond conventional antibiotics.In this study,we evaluated a combination of lytic Salmonella-infecting bacteriophages(SLAM_phi ST45 and SLAM_phiST56)and a probiotic bacterium Limosilactobacillus reuteri(SLAM_LAR11)in a chick model challenged with Salmonella enterica serovar Typhimurium infection.Results Co-administration with two-phage cocktail and a probiotic showed markedly reduced Salmonella colonization in the gut and systemic organs of chicks,comparable to the effect of phage-only treatment.In contrast with phage-only treatment,the combined therapy significantly improved the rate of body-weight change from the day of infection to necropsy(P<0.0001)and alleviated infection-associated splenomegaly(P=0.028)and hepatomegaly(P=0.011).In the ileum,the villus height-to-crypt depth ratio(VH/CD)increased significantly(P=0.044).In the colon,expression of tight-junction genes OCLN(P=0.014),TJP1(P<0.0001),and MUC2(P=0.011)was elevated,whereas the pro-inflammatory cytokine IL6 was reduced(P=0.018).These improvements were accompanied,in the cecum,by trends toward decreases in Escherichia-Shigella(P=0.09)and Clostridium(P=0.16)and a trend toward an increase in Blautia(P=0.11);additionally,in the ileum,Lactobacillus(P=0.037)and Blautia(P=0.016)increased significantly,yielding a more balanced microbiota than with phage-only treatment.Consistently,levels of functional metabolites,including acetic acid(LDA=3.32)and lactic acid(LDA=5.29),were increased.Conclusion Taken together,these findings demonstrate that phage-probiotic co-administration not only enhances the clearance of multidrug-resistant Salmonella more effectively than phage treatment alone but also promotes intestinal health,highlighting its potential as an antibiotic-alternatives strategy to improve intestinal health and ensure food safety in poultry production systems.
基金supported by the National Natural Science Foundation of China(No.12575189)。
文摘Deep learning methods have achieved significant progress in solving partial differential equations.However,when applied to the widely used anisotropic scattering neutron transport equations in reactor engineering,these encounter significant challenges.To address this issue,this study introduces a multi-antiderivative transformation alternating iterative deep learning method(M-AIM).This method transforms the integral terms of the scattering and fission sources in the transport equation into multiple antiderivative functions corresponding to the integrand,converts the differential-integral form of the transport equation into an exact differential equation,and establishes the necessary constraints for a unique solution.The M-AIM uses multiple deep neural networks to map the unknown angular flux density of transport equations and represents various forms of antiderivative functions.It constructs the corresponding weighted loss functions.By alternating iterative training with deep learning methods applied to these neural networks,the loss is reduced gradually.When the loss decreases to a preset minimum,the neural network approaches a numerical solution for both angular flux density and antiderivative functions.This paper presents a numerical verification of geometries such as flat plates and spheres.It verifies the validity of the theoretical framework and associated methods.The study contributes to the development of novel technical approaches for applying deep learning to solve anisotropic scattering neutron transport equations in reactor engineering.
基金supported by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil(CAPES)[Finance Code 001](to MGS)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico(CNPq)fellowship[research grants 309840/2022-8]。
文摘Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.
基金supported by the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(MSIT),South Korea(RS-2024-00421181)financially supported in part by National R&D Program(2021M3H4A3A02086430)through NRF(National Research Foundation of Korea)funded by Ministry of Science and ICT+2 种基金the National Research Council of Science&Technology(NST)grant by the Korea government(MSIT)(No.GTL25021-210)The Inter-University Semiconductor Research Center,Institute of Engineering Research,and Soft Foundry Institute at Seoul National University provided research facilities for this workhe grant by the National Research Foundation of Korea(NSF)supported by the Korea government(MIST)(RS-2025-16903034)。
文摘As silicon-based transistors face fundamental scaling limits,the search for breakthrough alternatives has led to innovations in 3D architectures,heterogeneous integration,and sub-3 nm semiconductor body thicknesses.However,the true effectiveness of these advancements lies in the seamless integration of alternative semiconductors tailored for next-generation transistors.In this review,we highlight key advances that enhance both scalability and switching performance by leveraging emerging semiconductor materials.Among the most promising candidates are 2D van der Waals semiconductors,Mott insulators,and amorphous oxide semiconductors,which offer not only unique electrical properties but also low-power operation and high carrier mobility.Additionally,we explore the synergistic interactions between these novel semiconductors and advanced gate dielectrics,including high-K materials,ferroelectrics,and atomically thin hexagonal boron nitride layers.Beyond introducing these novel material configurations,we address critical challenges such as leakage current and long-term device reliability,which become increasingly crucial as transistors scale down to atomic dimensions.Through concrete examples showcasing the potential of these materials in transistors,we provide key insights into overcoming fundamental obstacles—such as device reliability,scaling down limitations,and extended applications in artificial intelligence—ultimately paving the way for the development of future transistor technologies.
文摘Background:Cupping therapy(CT),an ancient practice revived in modern sports medicine,offers potential benefits for athlete recovery and performance.Distinctions between wet CT(WCT)and dry CT(DCT)in sports science focus on their effects on recovery metrics,particularly how they influence sleep quality,perceived wellness,and athletic performance.Despite anecdotal evidence of its efficacy,rigorous comparative studies are scarce.Objective:This study aimed to evaluates and compare the effects of WCT and DCT on endurance,perceived wellness,exertion levels,and sleep quality among young,active males,addressing the gap in the literature regarding CT's efficacy in sports performance and recovery.Methods:Thirty-two amateur runners were randomly divided into two groups:one followed WCT sessions and the other followed DCT sessions.The study assessed the interventions'impacts on endurance performance(Yo-Yo intermittent recovery test),sleep quality(Pittsburgh Sleep Quality Index),and perceived exertion(Borg CR10 Scale).Heart rate was measured using a Polar H10 sensor to gauge physiological responses during physical tests.Results:Significant improvements were observed in the WCT group for sleep latency(%change=-82.31%;interaction group×time p=0.006;Cohen's d=0.74)and sleep disturbance(%change=-68.70%;interaction group×time p<0.001;Cohen's d=1.09),suggesting enhanced sleep quality(global score;%change=-52.81;interaction group×time p=0.004;Cohen's d=0.77).However,no significant differences were found in direct performance metrics(distance,maximal heart rate,maximal oxygen uptake)between WCT and DCT groups.These findings highlight WCT's potential as a recovery aid,particularly through improved sleep,without directly influencing endurance performance outcomes.Conclusion:WCT may serve as an effective ergogenic aid for athletes by potentially improving sleep quality and reducing perceived exertion,thus contributing indirectly to performance through enhanced recovery.
文摘Limited adoption of solar energy in the Northwestern region of Russia is associated with insufficient data on annual solar radiation indicators and on the potential of solar collectors for water heating.The study aims to evaluate the potential of solar water heating for domestic use in Northwestern Russia,using Tyumen city as the case.In this region,the number of cloudy days ranges from 5% to 50%,with cloud cover increasing in winter.New data on the total solar radiation,availability duration,and cloud cover have been collected.Solar irradiance could reach 900 MJ/m^(2) during summer months,while decreasing to 50–150 MJ/m^(2) significantly in winter.Notably,the solar radiation demonstrates predictable and stable characteristics between the hours of 9 a.m.and 3 p.m.Consequently,the heating system is equipped with a gas-supplied boiler as the primary heat source,with the solar collector being the secondary clean energy source to meet the demand of a residential house.A is designed to compensate for the heat losses in the evening and at night.The results of unmatching energy demand and production highlight the need for a water tank for energy storage to facilitate a wider use of solar power.The peak thermal energy requirement for domestic hot water(DHW)occurs in January,amounting to 6046.8 MJ.In summer,from May to August,the thermal energy produced by solar collectors is not utilized due to the lack of heating load.The annual data indicate that the solar collectors contribute approximately 14%of the total heat required for DHW.
文摘Mainstream medicine commonly categorizes acupuncture as“alternative and complementary,”a designation that reflects conceptual gaps in existing treatment classification systems.Integrating complementary medicine into the mainstream medical system requires a conceptual adjustment.Here,Ⅰ propose a mechanism-based 5R classification—Removing,Repairing,Replacing,Replenishing,Regulating—to systematically categorize therapies.Based on this classification,acupuncture and its related interventions fall under functional regulation therapy.This framework offers a unified,functional perspective that facilitates the integration of complementary medicine into mainstream medical taxonomy.
基金supported by the National Natural Science Foundation of China(31800542)Natural Science Foundation of Heilongjiang Province(LH2023C105)Heilongjiang Research Institutes Basic Research Funding Project(LKSB2024-9)。
文摘The ectomycorrhizal fungus Paxillus involutus was inoculated onto tissue-cultures of the hybrid poplar,Populus davidiana×P.bolleana,to evaluate the elemental defense effect to heavy metals copper and cadmium at different concentrations by simulating Alternaria alternata fungus infection.The enrichment capacity of Populus davidiana×P.bolleana for Cu and Cd was closely associated with the degree of heavy metal stress.There was a significant positive interaction of applying Cu and Cd and the inoculation with P.involutus on A.alternata leaf blight disease index.The incidence rate and disease index of leaf blight underwent a significant reduction compared with the controls.Similarly,the ratio of the area of disease spot to leaf area,incidence rate,and disease index for Populus davidiana×P.bolleana leaves inoculated with Paxillus involutus(Batsch)Fr.were significantly lower than those of their nonmycorrhizal counterparts.With increasing the degree of Cu and Cd stress,a gradual increase in the average value of the membership function for the incidence rate and disease index was observed,indicating the weakened pathogen's ability to cause infection and the improved resistance of Populus davidiana×P.bolleana to leaf blight disease under Cu and Cd stress.Moreover,superoxide dismutase enzyme activity in Populus davidiana×P.bolleana increased significantly,reaching levels of 411.0 U/g FW and 421.6 U/g FW under Cu and Cd treatments,respectively.These changes in metabolic products and antioxidant enzyme activities suggest that P.involutus may enhance the resistance of Populus davidiana×P.bolleana to the fungus,Alternaria alternata Fr.Keissel under heavy metal stress by modulating these physiological indicators.
基金supported by the International Partnership program of the Chinese Academy of Sciences(170GJHZ2023074GC)National Natural Science Foundation of China(42425706 and 42488201)+1 种基金National Key Research and Development Program of China(2024YFF0807902)Beijing Natural Science Foundation(8242041),and China Postdoctoral Science Foundation(2025M770353).
文摘Accurately assessing the relationship between tree growth and climatic factors is of great importance in dendrochronology.This study evaluated the consistency between alternative climate datasets(including station and gridded data)and actual climate data(fixed-point observations near the sampling sites),in northeastern China’s warm temperate zone and analyzed differences in their correlations with tree-ring width index.The results were:(1)Gridded temperature data,as well as precipitation and relative humidity data from the Huailai meteorological station,was more consistent with the actual climate data;in contrast,gridded soil moisture content data showed significant discrepancies.(2)Horizontal distance had a greater impact on the representativeness of actual climate conditions than vertical elevation differences.(3)Differences in consistency between alternative and actual climate data also affected their correlations with tree-ring width indices.In some growing season months,correlation coefficients,both in magnitude and sign,differed significantly from those based on actual data.The selection of different alternative climate datasets can lead to biased results in assessing forest responses to climate change,which is detrimental to the management of forest ecosystems in harsh environments.Therefore,the scientific and rational selection of alternative climate data is essential for dendroecological and climatological research.
文摘Hans Zempel1,2 TAU,a microtubule-associated protein,encoded by the microtubule-associated protein tau(MAPT)gene,is a central regulator of microtubule stability and axonal function in the human brain,with its pathological aggregation representing a hallmark of Alzheimer’s disease and related tauopathies.Despite extensive research into the role of TAU in neurodegeneration,its essentiality for human brain development has remained unclear.This perspective synthesizes recent genetic,molecular,and cellular evidence to demonstrate that the human brain-specific TAU isoform 0N3R is indispensable for proper neurodevelopment,pointing to loss-of-function of this isoform as a novel paradigm for TAU-associated disease.Alternative splicing of MAPT generates six brain-specific TAU isoforms,with 0N3R being exclusively expressed during fetal brain development.Analysis of large-scale human genetic datasets(gnomAD v4.0.0)reveals a high probability of loss-of-function intolerance(pLI=0.96)for the 0N3R isoform.This is in stark contrast to the canonical Matched Annotation from the NCBI and EMBL-EBI(MANE)transcript and peripheral“Big TAU,”both of which are tolerant to loss-of-function mutations.This intolerance is further supported by the scarcity of loss-of-function mutations in 0N3R-encoding exons and high missense constraint scores,suggesting strong evolutionary selection against disruption of this isoform.Functional studies using human induced pluripotent stem cell-derived cortical neurons with CRISPR-Cas9-mediated MAPT knockout reveal that,unlike in murine models where compensation by other microtubule-associated proteins occurs,loss of TAU in human neurons leads to deficits in neurite outgrowth,axon initial segment shortening,and a trend toward hyperexcitability,accompanied by broad transcriptomic changes affecting genes involved in microtubule organization and synaptic structure.Remarkably,re-expression of any of the six human brain-specific TAU isoforms rescues these phenotypes,underscoring their functional redundancy during development.These findings position the 0N3R isoform as essential for human brain development and suggest that loss-of-function mutations affecting this isoform likely result in neurodevelopmental impairment,potentially manifesting as intellectual disability without overt dysmorphic features.This contrasts with the apparent tolerance to MAPT loss-of-function in mice and peripheral tissues,highlighting a critical species-and isoform-specific requirement for TAU in human neurodevelopment.The hypothesis of 0N3R-TAU loss-of-function intolerance opens new avenues for understanding neurodevelopmental disorders and refines the conceptual framework of TAU-associated disease mechanisms beyond toxic gain-of-function.
基金supported by the Natural Science Foundation of Jiangsu Province,China(BK20241931 and BK 20221371)the National Natural Science Foundation of China(32071943,32372214,and 31901444)the National Key Research and Development Program of China(2022YFD2300304)。
文摘Alternate wetting and drying irrigation(AWD)significantly influences the cooking and eating quality of rice(Oryza sativa L.).However,the mechanisms by which AWD affects rice cooking and eating quality remain unclear.Lipid and free fatty acid contents in grains correlate positively with cooking and eating quality of rice.This study examined Yangdao 6(YD6,a conventional taste indica inbred)and Nanjing 9108(NJ9108,a superior taste japonica inbred)cultivated under conventional irrigation(CI),alternate wetting and moderate drying irrigation(AWMD),and alternate wetting and severe drying irrigation(AWSD)from 10 days after transplanting to maturity.The research investigated the relationship between lipid and free fatty acid biosynthesis in grains and the cooking and eating quality of rice.Compared to CI treatment,AWMD significantly enhanced the contents of lipid,total free fatty acids(TFFAs),free unsaturated fatty acids(FUFAs),linoleic acid,and oleic acid in milled rice by increasing activities of enzymes associated with lipid synthesis,while AWSD produced opposite effects.Correlation analysis revealed that elevated levels of lipid,TFFAs,FUFAs,linoleic acid,and oleic acid contribute to improved rice cooking and eating quality.The findings demonstrate that AWMD enhances cooking and eating quality of milled rice through optimization of lipid and fatty acid synthesis in rice grains.
