Background:Glioblastoma(GBM)is one of the most malignant types of central nervous system tumors.Oxygen deprivation in the tumor microenvironment is thought to be an important factor in promoting GBM progression.Howeve...Background:Glioblastoma(GBM)is one of the most malignant types of central nervous system tumors.Oxygen deprivation in the tumor microenvironment is thought to be an important factor in promoting GBM progression.However,the mechanisms of hypoxia-promoted tumor progression remain elusive.Methods:Alternative splicing of diacylglycerol kinase gamma(DGKG)-Δexon13 was amplified and verified by PCR-Sanger sequencing.The functions of DGKG and DGKG-Δexon13 were analyzed by Cell counting kit-8(CCK-8),Transwell,Matrigeltranswell experiments,and in vivo orthotropic GBM animal models.Transcriptome analyses were done to find out the regulated genes.Results:In this study,we found that a new transcript DGKG-Δexon13 was generated in GBM under hypoxia via alternative splicing.Moreover,the results of CCK-8,Transwell,and Matrigel-transwell experiments showed that the proliferation,migration,and invasion abilities of U87-MG and T98G were decreased after DGKG knockdown.Compared to wild-type DGKG,DGKG-Δexon13 overexpression significantly promoted cellular proliferation,migration,and invasion abilities in GBM.Furthermore,in vivo,orthotropic GBM animal models analysis showed that the tumor volumes were much smaller in the DGKG knockdown group.However,the tumor sizes in the DGKG and DGKG-Δexon13 rescue groups were restored,especially in the DGKG-Δexon13 group.Transcriptome analysis revealed that MORC1,KLHDC7B,ATP1A2,INHBE,TMEM119,and FGD3 were altered significantly when DGKG was knocked down.IL-16,CCN2,and EFNB3 were specifically regulated by DGKG-Δexon13.Conclusions:Our study found that hypoxia-induced alternative splicing transcript DGKG-Δexon13 promotes GBM proliferation and infiltration,which might provide a new potential target for the clinical treatment and diagnosis of GBM.展开更多
In this study, 414 whole protein-coding sequences (238 004 codons) of alternatively spliced genes of human chromosome 1 have been employed to explore the patterns of codon usage bias among genes. Overall codon usage d...In this study, 414 whole protein-coding sequences (238 004 codons) of alternatively spliced genes of human chromosome 1 have been employed to explore the patterns of codon usage bias among genes. Overall codon usage data analysis indicates that G- and C-ending codons are predominant in the genes. The base usage in all three codon positions suggests a selection-mutation balance. Multivariate statistical analysis reveals that the codon usage variation has a strong positive correlation with the expressivities of the genes (r=0.5790, P<0.0001). All 27 codons identified as optimal are G- and C-ending codons. Correlation analysis shows a strong negative correlation between the gene length and codon adaptation index value (r=0.2252, P<0.0001), and a significantly positive correlation between the gene length and Nc values (r=0.1876, P<0.0001). These results suggest that the comparatively shorter genes in the genes have higher codon usage bias to maximize translational efficiency, and selection may also contribute to the reduction of highly expressed proteins.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
Environmental stresses profoundly altered accumulation of nonsense mRNAs including intron-retaining (IR) transcripts in Arabidopsis. Temporal patterns of stress-induced IR mRNAs were dissected using both oscillating...Environmental stresses profoundly altered accumulation of nonsense mRNAs including intron-retaining (IR) transcripts in Arabidopsis. Temporal patterns of stress-induced IR mRNAs were dissected using both oscillating and non-oscillating transcripts. Broad-range thermal cycles triggered a sharp increase in the long IR CCA1 isoforms and altered their phasing to different times of day. Both abiotic and biotic stresses such as drought or Pseudomonas syringae infection induced a similar increase. Thermal stress induced a time delay in accumulation of CCA1 14Rb transcripts, whereas functional mRNA showed steady oscillations. Our data favor a hypothesis that stress-induced instabilities of the central oscillator can be in part compensated through fluctuations in abundance and out-of-phase oscillations of CCA1 IR transcripts. Taken together, our results support a concept that mRNA abundance can be modulated through altering ratios between functional and nonsense/IR transcripts. SR45 protein specifically bound to the retained CCA1 intron in vitro, suggesting that this sp!icing factor could be involved in regulation of intron retention. Transcriptomes of nonsense-mediated mRNA decay (NMD)-impaired and heat-stressed plants shared a set of retained introns associated with stress- and defense-inducible transcripts. Constitutive activation of certain stress response networks in an NMD mutant could be linked to disequilibrium between functional and nonsense mRNAs.展开更多
Alternative splicing is a tightly regulated process that contributes to cancer development.CRNDE is a long noncoding RNA with alternative splicing and is implicated in the pathogenesis of several cancers.However,wheth...Alternative splicing is a tightly regulated process that contributes to cancer development.CRNDE is a long noncoding RNA with alternative splicing and is implicated in the pathogenesis of several cancers.However,whether deregulated expression of CRNDE is common and which isoforms are mainly involved in cancers remain unclear.In this study,we report that CRNDE is aberrantly expressed in the majority of solid and hematopoietic malignancies.The investigation of CRNDE expression in normal samples revealed that CRNDE was expressed in a tissue- and cell-specific manner.Further comparison of CRNDE expression in 2938 patient samples from 15 solid and hematopoietic tumors showed that CRNDE was significantly overexpressed in 11 malignancies,including 3 reported and 8 unreported,and also implicated that the overexpressed isoforms differed in various cancer types.Furthermore,anti-cancer drugs could efficiently repress CRNDE overexpression in cancer cell lines and primary samples,and even had different impacts on the expression of CRNDE isoforms.Finally,experimental profiles of 12 alternatively spliced isoforms demonstrated that the spliced variant CRNDE-g was the most highly expressed isoform in multiple cancer types.Collectively,our results emphasize the cancer-associated feature of CRNDE and its spliced isoforms,and may provide promising targets for cancer diagnosis and therapy.展开更多
Genes encoding proteins with PHD (plant homeodomain) finger motif (C4HC3) are highly conserved from Arabidopsis to Homo sapiens. One of the major functions of these genes is regulating the expression of homeotic genes...Genes encoding proteins with PHD (plant homeodomain) finger motif (C4HC3) are highly conserved from Arabidopsis to Homo sapiens. One of the major functions of these genes is regulating the expression of homeotic genes during the stage of embryonic development. They play a role in cell-cycle and cell differentiation and seem to be related with some human malignant diseases, such as leukemia. A human placenta cDNA library has been screened with cDNA probe amplified by PCR. The PGR primers have been designed according to the M96 (a mouse gene encoding a protein with PHD domain) homologous data in dbEST.A 2. 1 kb insert fragment in a positive cDNA clone has been isolated and sequenced. This new full-length cDNA is named PHF2 (GenBank Acc: AF052205). The putative protein composed of 567 aa has two typical PHD fingers at its N-terminus. Meanwhile it is identified that there are several alternatively spliced transcripts of PHF2 in different human tissues through the PCR amplification, Northern blot展开更多
All lymphocytes depend on the cytokine IL-7 for their development and homeostasis,and cell surface expression of the IL-7 receptor is a prerequisite for responses to IL-7.1 Notably,the IL-7 receptorα-chain(IL-7Rα)do...All lymphocytes depend on the cytokine IL-7 for their development and homeostasis,and cell surface expression of the IL-7 receptor is a prerequisite for responses to IL-7.1 Notably,the IL-7 receptorα-chain(IL-7Rα)does not only exist as a membranebound form but is also found as a soluble protein in human serum.2,3 The exact role of soluble IL-7Rα(sIL-7Rα)proteins remains to be determined.However,increased amounts of sIL-7Rαhave been associated with an increased risk of inflammation and autoimmunity.3,4 Mechanistically,sIL-7Rαproteins can be generated by alternative splicing of Il7r gene transcripts that encode IL-7Rα.Curiously,however,such Il7r splice isoforms have only been described in humans and have never been described in mice.5 Consequently,the importance of Il7r alternative splice products that are not conserved across species has remained questionable.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
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
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
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
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
基金funded by Guizhou Province Science and Technology Plan Project Qiankehe Foundation-ZK[2023]General 360,362Science and Technology Fund project of Guizhou Provincial Health Commission(gzwkj-2022-09,gzwkj-2023-035)+1 种基金National Natural Science Foundation Cultivation Project of Guizhou Medical University(21NSFCP14,gyfynsfc-2022-25)The PhD Scientific Research Launch Fund Project of the Affiliated Hospital of Guizhou Medical University(gyfybsky-2022-02).
文摘Background:Glioblastoma(GBM)is one of the most malignant types of central nervous system tumors.Oxygen deprivation in the tumor microenvironment is thought to be an important factor in promoting GBM progression.However,the mechanisms of hypoxia-promoted tumor progression remain elusive.Methods:Alternative splicing of diacylglycerol kinase gamma(DGKG)-Δexon13 was amplified and verified by PCR-Sanger sequencing.The functions of DGKG and DGKG-Δexon13 were analyzed by Cell counting kit-8(CCK-8),Transwell,Matrigeltranswell experiments,and in vivo orthotropic GBM animal models.Transcriptome analyses were done to find out the regulated genes.Results:In this study,we found that a new transcript DGKG-Δexon13 was generated in GBM under hypoxia via alternative splicing.Moreover,the results of CCK-8,Transwell,and Matrigel-transwell experiments showed that the proliferation,migration,and invasion abilities of U87-MG and T98G were decreased after DGKG knockdown.Compared to wild-type DGKG,DGKG-Δexon13 overexpression significantly promoted cellular proliferation,migration,and invasion abilities in GBM.Furthermore,in vivo,orthotropic GBM animal models analysis showed that the tumor volumes were much smaller in the DGKG knockdown group.However,the tumor sizes in the DGKG and DGKG-Δexon13 rescue groups were restored,especially in the DGKG-Δexon13 group.Transcriptome analysis revealed that MORC1,KLHDC7B,ATP1A2,INHBE,TMEM119,and FGD3 were altered significantly when DGKG was knocked down.IL-16,CCN2,and EFNB3 were specifically regulated by DGKG-Δexon13.Conclusions:Our study found that hypoxia-induced alternative splicing transcript DGKG-Δexon13 promotes GBM proliferation and infiltration,which might provide a new potential target for the clinical treatment and diagnosis of GBM.
基金the National Natural Science Foundation of China (No. 60171038) and the Science and Technology Ministry of China (No. 2001CCA01400)
文摘In this study, 414 whole protein-coding sequences (238 004 codons) of alternatively spliced genes of human chromosome 1 have been employed to explore the patterns of codon usage bias among genes. Overall codon usage data analysis indicates that G- and C-ending codons are predominant in the genes. The base usage in all three codon positions suggests a selection-mutation balance. Multivariate statistical analysis reveals that the codon usage variation has a strong positive correlation with the expressivities of the genes (r=0.5790, P<0.0001). All 27 codons identified as optimal are G- and C-ending codons. Correlation analysis shows a strong negative correlation between the gene length and codon adaptation index value (r=0.2252, P<0.0001), and a significantly positive correlation between the gene length and Nc values (r=0.1876, P<0.0001). These results suggest that the comparatively shorter genes in the genes have higher codon usage bias to maximize translational efficiency, and selection may also contribute to the reduction of highly expressed proteins.
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Environmental stresses profoundly altered accumulation of nonsense mRNAs including intron-retaining (IR) transcripts in Arabidopsis. Temporal patterns of stress-induced IR mRNAs were dissected using both oscillating and non-oscillating transcripts. Broad-range thermal cycles triggered a sharp increase in the long IR CCA1 isoforms and altered their phasing to different times of day. Both abiotic and biotic stresses such as drought or Pseudomonas syringae infection induced a similar increase. Thermal stress induced a time delay in accumulation of CCA1 14Rb transcripts, whereas functional mRNA showed steady oscillations. Our data favor a hypothesis that stress-induced instabilities of the central oscillator can be in part compensated through fluctuations in abundance and out-of-phase oscillations of CCA1 IR transcripts. Taken together, our results support a concept that mRNA abundance can be modulated through altering ratios between functional and nonsense/IR transcripts. SR45 protein specifically bound to the retained CCA1 intron in vitro, suggesting that this sp!icing factor could be involved in regulation of intron retention. Transcriptomes of nonsense-mediated mRNA decay (NMD)-impaired and heat-stressed plants shared a set of retained introns associated with stress- and defense-inducible transcripts. Constitutive activation of certain stress response networks in an NMD mutant could be linked to disequilibrium between functional and nonsense mRNAs.
基金National Natural Science Foundation of China (Nos.81530003,81300403,81770153 and 91440114)The National Key Research and Development Program (No.2016YFC0902800)+1 种基金Shanghai Leading Talent Projects (No.2015008)the Academic Leader Program of Shanghai Science and Technology Committee (No.2015137).
文摘Alternative splicing is a tightly regulated process that contributes to cancer development.CRNDE is a long noncoding RNA with alternative splicing and is implicated in the pathogenesis of several cancers.However,whether deregulated expression of CRNDE is common and which isoforms are mainly involved in cancers remain unclear.In this study,we report that CRNDE is aberrantly expressed in the majority of solid and hematopoietic malignancies.The investigation of CRNDE expression in normal samples revealed that CRNDE was expressed in a tissue- and cell-specific manner.Further comparison of CRNDE expression in 2938 patient samples from 15 solid and hematopoietic tumors showed that CRNDE was significantly overexpressed in 11 malignancies,including 3 reported and 8 unreported,and also implicated that the overexpressed isoforms differed in various cancer types.Furthermore,anti-cancer drugs could efficiently repress CRNDE overexpression in cancer cell lines and primary samples,and even had different impacts on the expression of CRNDE isoforms.Finally,experimental profiles of 12 alternatively spliced isoforms demonstrated that the spliced variant CRNDE-g was the most highly expressed isoform in multiple cancer types.Collectively,our results emphasize the cancer-associated feature of CRNDE and its spliced isoforms,and may provide promising targets for cancer diagnosis and therapy.
文摘Genes encoding proteins with PHD (plant homeodomain) finger motif (C4HC3) are highly conserved from Arabidopsis to Homo sapiens. One of the major functions of these genes is regulating the expression of homeotic genes during the stage of embryonic development. They play a role in cell-cycle and cell differentiation and seem to be related with some human malignant diseases, such as leukemia. A human placenta cDNA library has been screened with cDNA probe amplified by PCR. The PGR primers have been designed according to the M96 (a mouse gene encoding a protein with PHD domain) homologous data in dbEST.A 2. 1 kb insert fragment in a positive cDNA clone has been isolated and sequenced. This new full-length cDNA is named PHF2 (GenBank Acc: AF052205). The putative protein composed of 567 aa has two typical PHD fingers at its N-terminus. Meanwhile it is identified that there are several alternatively spliced transcripts of PHF2 in different human tissues through the PCR amplification, Northern blot
基金supported by the Intramural Research Program of the US National Institutes of Health,the National Cancer Institute,the Center for Cancer Researchthe Financial Support Project,Long-Term Overseas Dispatch,Tenure-Track Faculty,Pusan National University.
文摘All lymphocytes depend on the cytokine IL-7 for their development and homeostasis,and cell surface expression of the IL-7 receptor is a prerequisite for responses to IL-7.1 Notably,the IL-7 receptorα-chain(IL-7Rα)does not only exist as a membranebound form but is also found as a soluble protein in human serum.2,3 The exact role of soluble IL-7Rα(sIL-7Rα)proteins remains to be determined.However,increased amounts of sIL-7Rαhave been associated with an increased risk of inflammation and autoimmunity.3,4 Mechanistically,sIL-7Rαproteins can be generated by alternative splicing of Il7r gene transcripts that encode IL-7Rα.Curiously,however,such Il7r splice isoforms have only been described in humans and have never been described in mice.5 Consequently,the importance of Il7r alternative splice products that are not conserved across species has remained questionable.
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 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%.
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.
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.
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.