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
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
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
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
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
Single-pixel imaging(SPI)enables efficient sensing in challenging conditions.However,the requirement for numerous samplings constrains its practicality.We address the challenge of high-quality SPI reconstruction at ul...Single-pixel imaging(SPI)enables efficient sensing in challenging conditions.However,the requirement for numerous samplings constrains its practicality.We address the challenge of high-quality SPI reconstruction at ultra-low sampling rates.We develop an alternative optimization with physics and a data-driven diffusion network(APD-Net).It features alternative optimization driven by the learned task-agnostic natural image prior and the task-specific physics prior.During the training stage,APD-Net harnesses the power of diffusion models to capture data-driven statistics of natural signals.In the inference stage,the physics prior is introduced as corrective guidance to ensure consistency between the physics imaging model and the natural image probability distribution.Through alternative optimization,APD-Net reconstructs data-efficient,high-fidelity images that are statistically and physically compliant.To accelerate reconstruction,initializing images with the inverse SPI physical model reduces the need for reconstruction inference from 100 to 30 steps.Through both numerical simulations and real prototype experiments,APD-Net achieves high-quality,full-color reconstructions of complex natural images at a low sampling rate of 1%.In addition,APD-Net’s tuning-free nature ensures robustness across various imaging setups and sampling rates.Our research offers a broadly applicable approach for various applications,including but not limited to medical imaging and industrial inspection.展开更多
While biochar amendment enhances plant productivity and water-use efficiency(WUE),particularly under waterlimited conditions,the specific mechanisms driving these benefits remain unclear.Thus,the present study aims to...While biochar amendment enhances plant productivity and water-use efficiency(WUE),particularly under waterlimited conditions,the specific mechanisms driving these benefits remain unclear.Thus,the present study aims to elucidate the synergistic effects of biochar and reduced irrigation on maize(Zea mays L.)plants,focusing on xylem composition,root-to-shoot signaling,stomatal behavior,and WUE.Maize plants were cultivated in splitroot pots filled with clay loam soil,amended by either wheat-straw biochar(WSB)or softwood biochar(SWB)at 2%(w/w).Plants received full irrigation(FI),deficit irrigation(DI),or partial root-zone drying rrigation(PRD)from the 4-leaf to the grain-filling stage.Our results revealed that the WSB amendment significantly enhanced plant water status,biomass accumulation,and WUE under reduced irrigation,particularly when combined with PRD.Although reduced irrigation inhibited photosynthesis,it enhanced WUE by modulating stomatal morphology and conductance.Biochar amendment combined with reduced rrigation significantly increased xylem K^(+),Ca^(2+),Mg^(2+),NO_(3)^(-),Cl^(-),PO_(4)^(3-),and SO_(4)^(2-)-but decreased Na+,which in turn lowered xylem pH.Moreover,biochar amendment and especially WSB amendment further increased abscisic acid(ABA)contents in both leaf and xylem sap under reduced irrigation conditions due to changes in xylem ionic constituents and pH.The synergistic interactions between xylem components and ABA led to refined adjustments in stomatal size and density,thereby affecting stomatal conductance and ultimately improving the WUE of maize plants at different scales.The combined application of WSB and PRD can,therefore,emerge as a promising approach for improving the overall plant performance of maize plants with increased stomatal adaptations and WUE,especially under water-limited conditions.展开更多
As the development of new power systems accelerates and the impacts of high renewable energy integration and extreme weather intensify,grid-alternative energy storage is garnering increasing attention for its grid-int...As the development of new power systems accelerates and the impacts of high renewable energy integration and extreme weather intensify,grid-alternative energy storage is garnering increasing attention for its grid-interaction benefits and clear business models.Consequently,assessing the value of grid-alternative energy storage in the systemtransition has become critically important.Considering the performance characteristics of storage,we propose a value assessment frame-work for grid-alternative energy storage,quantifying its non-wires-alternative effects from both cost and benefit perspectives.Building on this,we developed a collaborative planning model for energy storage and transmission grids,aimed at maximizing the economic benefits of storage systems while balancing investment and operational costs.The model considers regional grid interconnections and their interactions with system operation.By participating in system operations,grid-alternative energy storage not only maximizes its own economic benefits but also generates social welfare transfer effects.Furthermore,based on multi-regional interconnected planning,grid-alternative energy storage can reduce system costs by approximately 35%,with the most significant changes observed in generation costs.Multi-regional coordinated planning significantly enhances the sys-tem’s flexibility in regulation.However,when the load factor of interconnection lines between regions remains constant,system operational flexibility tends to decrease,leading to a roughly 28.9%increase in storage investment.Additionally,under regional coordinated planning,the greater the disparity in wind power integration across interconnected regions,the more noticeable the reduction in system costs.展开更多
Testosterone affects several organs in the body and is very important for male well-being.Aging men with late-onset hypogonadism(LOH)experience physiologic,psychiatric,and sexual symptoms related to a decline in the s...Testosterone affects several organs in the body and is very important for male well-being.Aging men with late-onset hypogonadism(LOH)experience physiologic,psychiatric,and sexual symptoms related to a decline in the serum concentration of testosterone with age.However,it is well-known that the extent of the decline in testosterone concentration does not correlate with the severity of LOH-related symptoms.Therefore,it is difficult to diagnose and treat patients with LOH.In addition,the symptoms,response to testosterone replacement therapy(TRT),and medical insurance coverage differ among ethnicities and countries.The evaluation of testosterone is essential for the diagnosis and treatment of LOH.The effects of testosterone are determined not only by the serum testosterone concentration but also by the androgen receptor sensitivity.A low number of glutamine repeats is indicative of high androgenic activity,and the number shows ethnicity-related differences(fewer in African American than in Caucasian people and more in East Asian people).The diagnosis of LOH is typically made using subjective symptoms and the serum testosterone concentration.The Aging Male Symptoms scale is widely used to evaluate the symptoms.The normal range of total testosterone concentration varies around the world;therefore,clinicians should follow the guidelines of their regional academic society.The principal treatment for LOH is TRT.There are many types of TRT and other treatment strategies are also available.Thus,physicians should treat LOH according to each patient’s situation,considering related disorders,such as diabetes,osteoporosis,metabolic syndrome,and depression.展开更多
Background Post-weaning diarrhea(PWD)in piglets,often caused by F4^(+)enterotoxigenic Escherichia coli(ETEC),poses significant challenges in pig production.Traditional solutions like antibiotics and zinc oxide face in...Background Post-weaning diarrhea(PWD)in piglets,often caused by F4^(+)enterotoxigenic Escherichia coli(ETEC),poses significant challenges in pig production.Traditional solutions like antibiotics and zinc oxide face increasing restrictions due to growing concerns over antibiotic resistance and environmental sustainability.This study investigates the application of bivalent heavy chain variable domain(V_(H)H)constructs(BL1.2 and BL2.2)targeting ETEC virulence factors,administered in feed to mitigate ETEC-induced PWD in weaned piglets.Results The supplementation of BL1.2 and BL2.2 in both mash and pelleted feed significantly reduced the diarrhea incidence and fecal shedding of F4^(+)ETEC in challenged piglets.Pelleted feed containing V_(H)H constructs helped to preserve gut barrier integrity by maintaining levels of the tight junction protein occludin in the small intestine.Additionally,the constructs maintained blood granulocyte counts at a similar level to the non-challenged control group,including neutrophils,and ameliorated the acute phase protein response after challenge.Notably,even at low feed intake immediately after weaning,V_(H)H constructs helped maintain piglet health by mitigating ETEC-induced inflammation and the resulting diarrhea.Conclusions Our findings demonstrated that using V_(H)H constructs as feed additives could serve as an effective strategy to help manage ETEC-associated PWD,by reducing F4^(+)ETEC gut colonization and supporting gut barrier function of weaned piglets.The high stability of these V_(H)H constructs supports their incorporation into industrial feed manufacturing processes,offering a more sustainable preventive strategy compared to traditional antimicrobial interventions,which could contribute to sustainable farming practices.展开更多
This editorial critically evaluates the application of foot reflexology as a treatment for sensorineural hearing loss(SNHL)in infants,as proposed in a case report published in the World of Clinical Cases.SNHL is a con...This editorial critically evaluates the application of foot reflexology as a treatment for sensorineural hearing loss(SNHL)in infants,as proposed in a case report published in the World of Clinical Cases.SNHL is a condition characterized by damage to the cochlea or the neural pathways that transmit auditory information to the brain.The etiology of SNHL is often complex,involving genetic mutations,prenatal factors,or perinatal insults.Reflexology,an alternative therapy involving the application of pressure to specific points on the feet,is based on the hypothesis that these points correspond to different organs and systems in the body,including the auditory system.However,the biological plausibility and clinical efficacy of foot reflexology in addressing SNHL lack empirical support.This editorial examines the pathophysiology of SNHL,assesses the clinical claims of reflexology practitioners,and emphasizes the necessity of evidence-based approaches in treating infant hearing loss.While complementary therapies may provide ancillary benefits,they should not supplant validated medical treatments in managing SNHL in infants.Further research is needed to evaluate the safety and efficacy of foot reflexology and other alternative therapies in pediatric audiology.展开更多
The ring-opening alternating copolymerization(ROAC)of 3,4-dihydrocoumarin(DHC)/epoxides has been successfully developed using an imidazolium salt of 1-ethyl-3-methylimidazolium chloride(EMIMCl)as a catalyst.The result...The ring-opening alternating copolymerization(ROAC)of 3,4-dihydrocoumarin(DHC)/epoxides has been successfully developed using an imidazolium salt of 1-ethyl-3-methylimidazolium chloride(EMIMCl)as a catalyst.The resulting copolymer has a molecular weight of 13.7kg·mol^(-1),a narrow molecular weight distribution of 1.03 and a strictly alternating structure.The MALDI-TOF MS characterization and DFT calculations including electrostatic potential(ESP),hydrogen-atom abstraction(HAA),independent gradient model based on hirshfeld partition(IGMH)and atoms-in-molecules(AIM)analysis were used to investigate the metal-free catalytic process.The synergistic effect of anions and cations of EMIMCl for ROAC of DHC and epoxides was demonstrated.This study provides a metal-free catalytic system for the facile synthesis of alternating polyesters from DHC.展开更多
The widespread ban on in-feed antibiotics in many regions has driven the search for natural alternatives to maintain health and production efficiency in swine and poultry.Phytogenic feed additives(PFAs)derived from he...The widespread ban on in-feed antibiotics in many regions has driven the search for natural alternatives to maintain health and production efficiency in swine and poultry.Phytogenic feed additives(PFAs)derived from herbs and plant extracts have emerged as promising candidates owing to their antioxidant,anti-inflammatory,and antimicrobial properties.Among these,silymarin—a flavonolignan complex extracted from milk thistle(Silybum marianum)—has attracted particular attention due to its hepatoprotective and growth-promoting activities.This review summarizes the chemical characteristics and mechanisms of action of silymarin/silybin.Also,evidence from both experimental and field studies shows that silymarin improves growth performance,nutrient digestibility,gut health,and reproductive outcomes.Advances in formulation technologies,such as micellization,have been addressed for improved bioavailability of silymarin.Despite these promising results,further long-term field studies and economic evaluations are needed to fully integrate silymarin into commercial animal production systems.展开更多
Prefabricated twinning represents an effective strategy for optimizing the microstructure of extruded forming components and facilitating changes in texture.The study examines the incorporation of[10-12]twins into an ...Prefabricated twinning represents an effective strategy for optimizing the microstructure of extruded forming components and facilitating changes in texture.The study examines the incorporation of[10-12]twins into an AZ31 magnesium alloy billet via cold pre-upsetting deformation before alternating forward extrusion(CUAFE).The experimental results indicate that the initial presence of[10-12]twins is advantageous for the development of[10-10]and[11-20]texture components during the extrusion process.In addition,different DRX mechanisms have different influences on the evolution of basal texture.The CDRX grains tend to preferentially select the[11-20]texture orientation,weakening the[10-10]texture and enhancing the[11-20]texture.However,most DDRX grains deviate significantly from the orientation of their surrounding original grain and do not have a preferred orientation.This is reflected in the mechanical properties of the CUAFE part.The tensile strength is 323.5 MPa,while the elongation is as high as 20.1%.展开更多
Changes in food production,often driven by distant demand,have a significant influence on sustainable man agement and use of land and water,and are in turn a driving factor of biodiversity change.While the connection ...Changes in food production,often driven by distant demand,have a significant influence on sustainable man agement and use of land and water,and are in turn a driving factor of biodiversity change.While the connection between land use and demand through value chains is increasingly understood,there is no comprehensive concep tualisation of this relationship.To address this gap,we propose a conceptual framework and use it as a basis for a systematic review to characterise value-chain connection and explore its influence on land-use and-cover change.Our search in June 2022 onWeb of Science and Scopus yielded 198 documents,describing studies completed after the year 2000 that provide information on both value-chain connection and land-use or-cover change.In total,we used 531 distinct cases to assess how frequently particular types of land-use or-cover change and value-chain connections co-occurred,and synthesized findings on their relations.Our findings confirm that 1)market inte gration is associated with intensification;2)land managers with environmental standards more frequently adopt environmentally friendly practices;3)physical and value-chain distances to consumers play a crucial role,with shorter distances associated with environmentally friendly practices and global chains linked to intensification and expansion.Incorporating these characteristics in existing theories of land-system change,would significantly advance understanding of land managers’decision-making,ultimately guiding more environmentally responsible production systems and contributing to global sustainability goals.展开更多
Background:Hippocratic medicine is routinely presented as the origin of rational,observational practice.Yet much of what is now called“Hippocratic principles”is a reception history-filtered through Galen,the Alexand...Background:Hippocratic medicine is routinely presented as the origin of rational,observational practice.Yet much of what is now called“Hippocratic principles”is a reception history-filtered through Galen,the Alexandrian medical school,and especially Islamic scholars such as Rhazes,Avicenna,and Masawaiyh.To reassess the enduring influence of Hippocratic medicine on contemporary practice and ethics by(i)distinguishing Hippocratic origins from later systematizations,and(ii)thematizing the philosophical stakes of the 21st-century“Hippocratic revival”(holism,patient-centrism,and the surge of non-science-based alternative medicine).Methods:Textual analysis of the Hippocratic Corpus is integrated with a reception-historical review(Galenic,Alexandrian,and Islamic commentators)and with historiographical framing(Porter,Temkin,Nutton).A conceptual analysis contrasts the Koan holistic and Knidian disease-entity approaches and examines their modern legacies.Results:Core Hippocratic themes-clinical observation,individualization,and ethical commitment-persist,but largely via later reinterpretations.The Koan/Knidian split illuminates today’s tensions between evidence-based standardization and person-centred holism.Modern invocations of Hippocrates often uncritically legitimate“holism”in ways that can blur boundaries between epistemically disciplined person-centred care and non-science-based alternative medicine.Conclusion:Hippocratic principles endure,but only when historically situated and normatively constrained.A philosophically robust“Hippocratic revival”in the 21st century must(a)acknowledge its Galenic-Islamic mediations,(b)preserve evidence standards,and(c)articulate an ethically grounded,epistemically responsible holism rather than a carte blanche for post-truth medical pluralism.展开更多
Male infertility constitutes a major global public health concern,with the underlying etiology remaining unidentified in nearly half of the diagnosed cases.Protein kinase CK1α(CK1α)functions as a pivotal regulator o...Male infertility constitutes a major global public health concern,with the underlying etiology remaining unidentified in nearly half of the diagnosed cases.Protein kinase CK1α(CK1α)functions as a pivotal regulator of cell cycle progression,pre-mRNA processing,and spliceosome-associated pathways through interactions with specific splicing factors.Comprehensive analyses revealed CK1αexpression in both germ cells and somatic cells of mouse testes,implicating its involvement in spermatogenic regulation.However,the physiological roles and mechanistic basis of CK1αfunction in Sertoli cells remain unclear.In this study,CK1αwas highly expressed in Sertoli cells,and conditional knockout of CK1αin murine Sertoli cells induced profound testicular atrophy and complete infertility.This phenotype was characterized by rapid depletion of Sertoli cells and spermatogenic dysfunction.Subsequent analyses demonstrated that CK1αregulated the fate determination of fetal and neonatal Sertoli cells in mice.At the molecular level,CK1αpromoted Sertoli cell survival through interaction with the splicing factor ZRSR1 to modulate apoptosis.Collectively,these findings establish CK1αas a key regulator of alternative splicing and male reproduction,providing critical insights into the molecular mechanisms underlying testicular development and reproductive function.展开更多
Caspases,which play key roles in cell apoptosis,undergo alternative splicing to form different splicing variants that can regulate the apoptotic process.Lepidopteran insect caspases undergo alternative splicing,althou...Caspases,which play key roles in cell apoptosis,undergo alternative splicing to form different splicing variants that can regulate the apoptotic process.Lepidopteran insect caspases undergo alternative splicing,although the functions of their splicing variants are still unclear.The Spodoptera exigua caspase-5(SeCaspase-5)gene was cloned and found to produce four different splicing variants with different gene sequences and protein functional domains,which were named SeCaspase-5a,SeCaspase-5b,SeCaspase-5c and SeCaspase-5d.Overexpression of these variants in S.exigua cells(Se-3)showed that SeCaspase-5a had a proapoptotic function,whereas SeCaspase-5b,SeCaspase-5c and SeCaspase-5d did not.Semi-qPCR analysis revealed that the expression of the SeCaspase-5 variants significantly differed during Autographa californica multiple nucleopolyhedrovirus(AcMNPV)infection.Furthermore,the SeCaspase-5 variants were constructed into the AcMNPV bacmid and transfected into Se-3 cells,which revealed that SeCaspase-5a promoted cell apoptosis and reduced virus production,whereas SeCaspase-5b,SeCaspase-5c and SeCaspase-5d did not promote cell apoptosis but instead increased virus production.Moreover,an analysis of the interactions between the SeCaspase-5 variants revealed that SeCaspase-5a directly interacted with SeCaspase-5b,SeCaspase-5c and SeCaspase-5d.Coexpression of these variants in Se-3 cells also revealed that SeCaspase-5b,SeCaspase-5c and SeCaspase-5d inhibited the proapoptotic function of SeCaspase-5a,resulting in a reduction in the percentage of apoptotic cells by about 20%.These results indicate that SeCaspase-5 undergoes alternative splicing and is involved in regulating the apoptosis induced by baculovirus infection.These findings increase our understanding of the functions of lepidopteran insect caspases and provide new insights into the mechanism of host-cell apoptosis induced by baculoviruses.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 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 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.
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upported by the National Natural Science Foundation of China(Grant No.62305184)the Major Key Project of Pengcheng Laboratory(Grant No.PCL2024A1)+1 种基金the Basic and Applied Basic Research Foundation of Guangdong Province(Grant No.2023A1515012932)the Science,Technology and Innovation Commission of Shenzhen Municipality(Grant No.WDZC20220818100259004).
文摘Single-pixel imaging(SPI)enables efficient sensing in challenging conditions.However,the requirement for numerous samplings constrains its practicality.We address the challenge of high-quality SPI reconstruction at ultra-low sampling rates.We develop an alternative optimization with physics and a data-driven diffusion network(APD-Net).It features alternative optimization driven by the learned task-agnostic natural image prior and the task-specific physics prior.During the training stage,APD-Net harnesses the power of diffusion models to capture data-driven statistics of natural signals.In the inference stage,the physics prior is introduced as corrective guidance to ensure consistency between the physics imaging model and the natural image probability distribution.Through alternative optimization,APD-Net reconstructs data-efficient,high-fidelity images that are statistically and physically compliant.To accelerate reconstruction,initializing images with the inverse SPI physical model reduces the need for reconstruction inference from 100 to 30 steps.Through both numerical simulations and real prototype experiments,APD-Net achieves high-quality,full-color reconstructions of complex natural images at a low sampling rate of 1%.In addition,APD-Net’s tuning-free nature ensures robustness across various imaging setups and sampling rates.Our research offers a broadly applicable approach for various applications,including but not limited to medical imaging and industrial inspection.
基金supported by the Natural Science Basic Research Program of Shaanxi Province,China(2024JCYBQN-0491)Heng Wan would like to thank the Chinese Scholarship Council(CsC)(202206300064)。
文摘While biochar amendment enhances plant productivity and water-use efficiency(WUE),particularly under waterlimited conditions,the specific mechanisms driving these benefits remain unclear.Thus,the present study aims to elucidate the synergistic effects of biochar and reduced irrigation on maize(Zea mays L.)plants,focusing on xylem composition,root-to-shoot signaling,stomatal behavior,and WUE.Maize plants were cultivated in splitroot pots filled with clay loam soil,amended by either wheat-straw biochar(WSB)or softwood biochar(SWB)at 2%(w/w).Plants received full irrigation(FI),deficit irrigation(DI),or partial root-zone drying rrigation(PRD)from the 4-leaf to the grain-filling stage.Our results revealed that the WSB amendment significantly enhanced plant water status,biomass accumulation,and WUE under reduced irrigation,particularly when combined with PRD.Although reduced irrigation inhibited photosynthesis,it enhanced WUE by modulating stomatal morphology and conductance.Biochar amendment combined with reduced rrigation significantly increased xylem K^(+),Ca^(2+),Mg^(2+),NO_(3)^(-),Cl^(-),PO_(4)^(3-),and SO_(4)^(2-)-but decreased Na+,which in turn lowered xylem pH.Moreover,biochar amendment and especially WSB amendment further increased abscisic acid(ABA)contents in both leaf and xylem sap under reduced irrigation conditions due to changes in xylem ionic constituents and pH.The synergistic interactions between xylem components and ABA led to refined adjustments in stomatal size and density,thereby affecting stomatal conductance and ultimately improving the WUE of maize plants at different scales.The combined application of WSB and PRD can,therefore,emerge as a promising approach for improving the overall plant performance of maize plants with increased stomatal adaptations and WUE,especially under water-limited conditions.
基金funded by the Technology Project of State Grid Jibei Electric Power Supply Co.,Ltd.(Grant Number:52018F240001).
文摘As the development of new power systems accelerates and the impacts of high renewable energy integration and extreme weather intensify,grid-alternative energy storage is garnering increasing attention for its grid-interaction benefits and clear business models.Consequently,assessing the value of grid-alternative energy storage in the systemtransition has become critically important.Considering the performance characteristics of storage,we propose a value assessment frame-work for grid-alternative energy storage,quantifying its non-wires-alternative effects from both cost and benefit perspectives.Building on this,we developed a collaborative planning model for energy storage and transmission grids,aimed at maximizing the economic benefits of storage systems while balancing investment and operational costs.The model considers regional grid interconnections and their interactions with system operation.By participating in system operations,grid-alternative energy storage not only maximizes its own economic benefits but also generates social welfare transfer effects.Furthermore,based on multi-regional interconnected planning,grid-alternative energy storage can reduce system costs by approximately 35%,with the most significant changes observed in generation costs.Multi-regional coordinated planning significantly enhances the sys-tem’s flexibility in regulation.However,when the load factor of interconnection lines between regions remains constant,system operational flexibility tends to decrease,leading to a roughly 28.9%increase in storage investment.Additionally,under regional coordinated planning,the greater the disparity in wind power integration across interconnected regions,the more noticeable the reduction in system costs.
文摘Testosterone affects several organs in the body and is very important for male well-being.Aging men with late-onset hypogonadism(LOH)experience physiologic,psychiatric,and sexual symptoms related to a decline in the serum concentration of testosterone with age.However,it is well-known that the extent of the decline in testosterone concentration does not correlate with the severity of LOH-related symptoms.Therefore,it is difficult to diagnose and treat patients with LOH.In addition,the symptoms,response to testosterone replacement therapy(TRT),and medical insurance coverage differ among ethnicities and countries.The evaluation of testosterone is essential for the diagnosis and treatment of LOH.The effects of testosterone are determined not only by the serum testosterone concentration but also by the androgen receptor sensitivity.A low number of glutamine repeats is indicative of high androgenic activity,and the number shows ethnicity-related differences(fewer in African American than in Caucasian people and more in East Asian people).The diagnosis of LOH is typically made using subjective symptoms and the serum testosterone concentration.The Aging Male Symptoms scale is widely used to evaluate the symptoms.The normal range of total testosterone concentration varies around the world;therefore,clinicians should follow the guidelines of their regional academic society.The principal treatment for LOH is TRT.There are many types of TRT and other treatment strategies are also available.Thus,physicians should treat LOH according to each patient’s situation,considering related disorders,such as diabetes,osteoporosis,metabolic syndrome,and depression.
基金financially supported by the Green Development and Demonstration Programme(GUDP)(case number 34009-19-1585)。
文摘Background Post-weaning diarrhea(PWD)in piglets,often caused by F4^(+)enterotoxigenic Escherichia coli(ETEC),poses significant challenges in pig production.Traditional solutions like antibiotics and zinc oxide face increasing restrictions due to growing concerns over antibiotic resistance and environmental sustainability.This study investigates the application of bivalent heavy chain variable domain(V_(H)H)constructs(BL1.2 and BL2.2)targeting ETEC virulence factors,administered in feed to mitigate ETEC-induced PWD in weaned piglets.Results The supplementation of BL1.2 and BL2.2 in both mash and pelleted feed significantly reduced the diarrhea incidence and fecal shedding of F4^(+)ETEC in challenged piglets.Pelleted feed containing V_(H)H constructs helped to preserve gut barrier integrity by maintaining levels of the tight junction protein occludin in the small intestine.Additionally,the constructs maintained blood granulocyte counts at a similar level to the non-challenged control group,including neutrophils,and ameliorated the acute phase protein response after challenge.Notably,even at low feed intake immediately after weaning,V_(H)H constructs helped maintain piglet health by mitigating ETEC-induced inflammation and the resulting diarrhea.Conclusions Our findings demonstrated that using V_(H)H constructs as feed additives could serve as an effective strategy to help manage ETEC-associated PWD,by reducing F4^(+)ETEC gut colonization and supporting gut barrier function of weaned piglets.The high stability of these V_(H)H constructs supports their incorporation into industrial feed manufacturing processes,offering a more sustainable preventive strategy compared to traditional antimicrobial interventions,which could contribute to sustainable farming practices.
文摘This editorial critically evaluates the application of foot reflexology as a treatment for sensorineural hearing loss(SNHL)in infants,as proposed in a case report published in the World of Clinical Cases.SNHL is a condition characterized by damage to the cochlea or the neural pathways that transmit auditory information to the brain.The etiology of SNHL is often complex,involving genetic mutations,prenatal factors,or perinatal insults.Reflexology,an alternative therapy involving the application of pressure to specific points on the feet,is based on the hypothesis that these points correspond to different organs and systems in the body,including the auditory system.However,the biological plausibility and clinical efficacy of foot reflexology in addressing SNHL lack empirical support.This editorial examines the pathophysiology of SNHL,assesses the clinical claims of reflexology practitioners,and emphasizes the necessity of evidence-based approaches in treating infant hearing loss.While complementary therapies may provide ancillary benefits,they should not supplant validated medical treatments in managing SNHL in infants.Further research is needed to evaluate the safety and efficacy of foot reflexology and other alternative therapies in pediatric audiology.
基金financially supported by the National Natural Science Foundation of China(No.22161040)Natural Science Foundation of Gansu(No.24JRRA125)Science Research Project of Northwest Normal University(No.NWNU-LKZD2021-3)。
文摘The ring-opening alternating copolymerization(ROAC)of 3,4-dihydrocoumarin(DHC)/epoxides has been successfully developed using an imidazolium salt of 1-ethyl-3-methylimidazolium chloride(EMIMCl)as a catalyst.The resulting copolymer has a molecular weight of 13.7kg·mol^(-1),a narrow molecular weight distribution of 1.03 and a strictly alternating structure.The MALDI-TOF MS characterization and DFT calculations including electrostatic potential(ESP),hydrogen-atom abstraction(HAA),independent gradient model based on hirshfeld partition(IGMH)and atoms-in-molecules(AIM)analysis were used to investigate the metal-free catalytic process.The synergistic effect of anions and cations of EMIMCl for ROAC of DHC and epoxides was demonstrated.This study provides a metal-free catalytic system for the facile synthesis of alternating polyesters from DHC.
基金supported by the research fund of Dankook University in 2025.
文摘The widespread ban on in-feed antibiotics in many regions has driven the search for natural alternatives to maintain health and production efficiency in swine and poultry.Phytogenic feed additives(PFAs)derived from herbs and plant extracts have emerged as promising candidates owing to their antioxidant,anti-inflammatory,and antimicrobial properties.Among these,silymarin—a flavonolignan complex extracted from milk thistle(Silybum marianum)—has attracted particular attention due to its hepatoprotective and growth-promoting activities.This review summarizes the chemical characteristics and mechanisms of action of silymarin/silybin.Also,evidence from both experimental and field studies shows that silymarin improves growth performance,nutrient digestibility,gut health,and reproductive outcomes.Advances in formulation technologies,such as micellization,have been addressed for improved bioavailability of silymarin.Despite these promising results,further long-term field studies and economic evaluations are needed to fully integrate silymarin into commercial animal production systems.
基金supported by the National Natural Science Foundation of China(No.52475341).
文摘Prefabricated twinning represents an effective strategy for optimizing the microstructure of extruded forming components and facilitating changes in texture.The study examines the incorporation of[10-12]twins into an AZ31 magnesium alloy billet via cold pre-upsetting deformation before alternating forward extrusion(CUAFE).The experimental results indicate that the initial presence of[10-12]twins is advantageous for the development of[10-10]and[11-20]texture components during the extrusion process.In addition,different DRX mechanisms have different influences on the evolution of basal texture.The CDRX grains tend to preferentially select the[11-20]texture orientation,weakening the[10-10]texture and enhancing the[11-20]texture.However,most DDRX grains deviate significantly from the orientation of their surrounding original grain and do not have a preferred orientation.This is reflected in the mechanical properties of the CUAFE part.The tensile strength is 323.5 MPa,while the elongation is as high as 20.1%.
文摘Changes in food production,often driven by distant demand,have a significant influence on sustainable man agement and use of land and water,and are in turn a driving factor of biodiversity change.While the connection between land use and demand through value chains is increasingly understood,there is no comprehensive concep tualisation of this relationship.To address this gap,we propose a conceptual framework and use it as a basis for a systematic review to characterise value-chain connection and explore its influence on land-use and-cover change.Our search in June 2022 onWeb of Science and Scopus yielded 198 documents,describing studies completed after the year 2000 that provide information on both value-chain connection and land-use or-cover change.In total,we used 531 distinct cases to assess how frequently particular types of land-use or-cover change and value-chain connections co-occurred,and synthesized findings on their relations.Our findings confirm that 1)market inte gration is associated with intensification;2)land managers with environmental standards more frequently adopt environmentally friendly practices;3)physical and value-chain distances to consumers play a crucial role,with shorter distances associated with environmentally friendly practices and global chains linked to intensification and expansion.Incorporating these characteristics in existing theories of land-system change,would significantly advance understanding of land managers’decision-making,ultimately guiding more environmentally responsible production systems and contributing to global sustainability goals.
文摘Background:Hippocratic medicine is routinely presented as the origin of rational,observational practice.Yet much of what is now called“Hippocratic principles”is a reception history-filtered through Galen,the Alexandrian medical school,and especially Islamic scholars such as Rhazes,Avicenna,and Masawaiyh.To reassess the enduring influence of Hippocratic medicine on contemporary practice and ethics by(i)distinguishing Hippocratic origins from later systematizations,and(ii)thematizing the philosophical stakes of the 21st-century“Hippocratic revival”(holism,patient-centrism,and the surge of non-science-based alternative medicine).Methods:Textual analysis of the Hippocratic Corpus is integrated with a reception-historical review(Galenic,Alexandrian,and Islamic commentators)and with historiographical framing(Porter,Temkin,Nutton).A conceptual analysis contrasts the Koan holistic and Knidian disease-entity approaches and examines their modern legacies.Results:Core Hippocratic themes-clinical observation,individualization,and ethical commitment-persist,but largely via later reinterpretations.The Koan/Knidian split illuminates today’s tensions between evidence-based standardization and person-centred holism.Modern invocations of Hippocrates often uncritically legitimate“holism”in ways that can blur boundaries between epistemically disciplined person-centred care and non-science-based alternative medicine.Conclusion:Hippocratic principles endure,but only when historically situated and normatively constrained.A philosophically robust“Hippocratic revival”in the 21st century must(a)acknowledge its Galenic-Islamic mediations,(b)preserve evidence standards,and(c)articulate an ethically grounded,epistemically responsible holism rather than a carte blanche for post-truth medical pluralism.
基金supported by the National Natural Science Foundation of China(32130098)。
文摘Male infertility constitutes a major global public health concern,with the underlying etiology remaining unidentified in nearly half of the diagnosed cases.Protein kinase CK1α(CK1α)functions as a pivotal regulator of cell cycle progression,pre-mRNA processing,and spliceosome-associated pathways through interactions with specific splicing factors.Comprehensive analyses revealed CK1αexpression in both germ cells and somatic cells of mouse testes,implicating its involvement in spermatogenic regulation.However,the physiological roles and mechanistic basis of CK1αfunction in Sertoli cells remain unclear.In this study,CK1αwas highly expressed in Sertoli cells,and conditional knockout of CK1αin murine Sertoli cells induced profound testicular atrophy and complete infertility.This phenotype was characterized by rapid depletion of Sertoli cells and spermatogenic dysfunction.Subsequent analyses demonstrated that CK1αregulated the fate determination of fetal and neonatal Sertoli cells in mice.At the molecular level,CK1αpromoted Sertoli cell survival through interaction with the splicing factor ZRSR1 to modulate apoptosis.Collectively,these findings establish CK1αas a key regulator of alternative splicing and male reproduction,providing critical insights into the molecular mechanisms underlying testicular development and reproductive function.
基金funded by the National Natural Science Foundation of China(32202393)the Natural Science Foundation of Shandong Province,China(ZR2021QC190)+1 种基金the Science and Technology Benefiting the People Demonstration Project of Qingdao,China(24-1-8-xdny-10-nsh)the Qingdao Agricultural University High-level Talent Fund,China(663/1120101)。
文摘Caspases,which play key roles in cell apoptosis,undergo alternative splicing to form different splicing variants that can regulate the apoptotic process.Lepidopteran insect caspases undergo alternative splicing,although the functions of their splicing variants are still unclear.The Spodoptera exigua caspase-5(SeCaspase-5)gene was cloned and found to produce four different splicing variants with different gene sequences and protein functional domains,which were named SeCaspase-5a,SeCaspase-5b,SeCaspase-5c and SeCaspase-5d.Overexpression of these variants in S.exigua cells(Se-3)showed that SeCaspase-5a had a proapoptotic function,whereas SeCaspase-5b,SeCaspase-5c and SeCaspase-5d did not.Semi-qPCR analysis revealed that the expression of the SeCaspase-5 variants significantly differed during Autographa californica multiple nucleopolyhedrovirus(AcMNPV)infection.Furthermore,the SeCaspase-5 variants were constructed into the AcMNPV bacmid and transfected into Se-3 cells,which revealed that SeCaspase-5a promoted cell apoptosis and reduced virus production,whereas SeCaspase-5b,SeCaspase-5c and SeCaspase-5d did not promote cell apoptosis but instead increased virus production.Moreover,an analysis of the interactions between the SeCaspase-5 variants revealed that SeCaspase-5a directly interacted with SeCaspase-5b,SeCaspase-5c and SeCaspase-5d.Coexpression of these variants in Se-3 cells also revealed that SeCaspase-5b,SeCaspase-5c and SeCaspase-5d inhibited the proapoptotic function of SeCaspase-5a,resulting in a reduction in the percentage of apoptotic cells by about 20%.These results indicate that SeCaspase-5 undergoes alternative splicing and is involved in regulating the apoptosis induced by baculovirus infection.These findings increase our understanding of the functions of lepidopteran insect caspases and provide new insights into the mechanism of host-cell apoptosis induced by baculoviruses.
