Climate change has well-documented psychological consequences for society.However,the emotional experiences of frontline conservation professionals remain underexplored.As key knowledge producers and participants in d...Climate change has well-documented psychological consequences for society.However,the emotional experiences of frontline conservation professionals remain underexplored.As key knowledge producers and participants in decision-making processes,conservation researchers play a crucial role in shaping and implementing adaptation and mitigation efforts,which are pivotal for effective climate planning.Understanding their emotional responses is essential for enhancing the success of these strategies and supporting climate action.This study aims to identify the most prevalent emotions experienced by conservation researchers regarding climate change across various countries and to examine the qualitative and quantitative factors shaping these emotions.An online survey was conducted with 362 participants from 98 academic and research institutions,utilising both closed and open-ended questions to capture demographic data,climate knowledge,stances on mitigation and adaptation,and emotional responses.Data analysis revealed that feelings of powerlessness,guilt,and concern were most frequently reported,driven by a profound sense of inability to halt climate change,frustration with perceived inaction by governments and industries,and self-assessed personal shortcomings.Age and stances on climate adaptation were identified as primary factors influencing emotional responses,particularly among individuals aged 20–50 and 61–70,with opposition to adaptation correlating with stronger emotional reactions.Demographic factors such as region,place of residence,and mitigation stances played a minor role.These findings provide valuable insights into the psychological well-being of conservation researchers related to climate change.展开更多
Purpose:Diaspora researchers work in one country but have ancestral origins in another,either through moves during a research career(mobile diaspora researchers)or by starting research in the target country(embedded d...Purpose:Diaspora researchers work in one country but have ancestral origins in another,either through moves during a research career(mobile diaspora researchers)or by starting research in the target country(embedded diaspora researchers).Whilst mobile researchers might be tracked through affiliation changes in bibliometric databases,embedded researchers cannot.This article reports an evidence-based discussion of which countries’diaspora researchers can be partially tracked using first or last names,addressing this limitation.Design/methodology/approach:A frequency analysis of first and last names of authors of all Scopus journal articles 2001-2021 for 200 countries or regions.Findings:There are great variations in the extent to which first or last names are uniquely national,from Monserrat(no unique first names)to Thailand(81%unique last names).Nevertheless,most countries have a subset of first or last names that are relatively unique.For the 50 countries with the most researchers,authors with relatively national names are always more likely to research their name-associated country,suggesting a continued national association.Lists of researchers’first and last name frequencies and proportions are provided for 200 countries/regions.Research limitations:Only one period is tracked(2001-2021)and no attempt was made to validate the ancestral origins of any researcher.Practical implications:Simple name heuristics can be used to identify the international spread of a sample of most countries’diaspora researchers,but some manual checks of individual names are needed to weed out false matches.This can supplement mobile researcher data from bibliometric databases.Originality/value:This is the first attempt to list name associations for the authors of all countries and large regions,and to identify the countries for which diaspora researchers could be tracked by name.展开更多
Purpose:The ranking lists of highly cited researchers receive much public attention.In common interpretations,highly cited researchers are perceived to have made extraordinary contributions to science.Thus,the metrics...Purpose:The ranking lists of highly cited researchers receive much public attention.In common interpretations,highly cited researchers are perceived to have made extraordinary contributions to science.Thus,the metrics of highly cited researchers are often linked to notions of breakthroughs,scientific excellence,and lone geniuses.Design/methodology/approach:In this study,we analyze a sample of individuals who appear on Clarivate Analytics’Highly Cited Researchers list.The main purpose is to juxtapose the characteristics of their research performance against the claim that the list captures a small fraction of the researcher population that contributes disproportionately to extending the frontier and gaining—on behalf of society—knowledge and innovations that make the world healthier,richer,sustainable,and more secure.Findings:The study reveals that the highly cited articles of the selected individuals generally have a very large number of authors.Thus,these papers seldom represent individual contributions but rather are the result of large collective research efforts conducted in research consortia.This challenges the common perception of highly cited researchers as individual geniuses who can be singled out for their extraordinary contributions.Moreover,the study indicates that a few of the individuals have not even contributed to highly cited original research but rather to reviews or clinical guidelines.Finally,the large number of authors of the papers implies that the ranking list is very sensitive to the specific method used for allocating papers and citations to individuals.In the"whole count"methodology applied by Clarivate Analytics,each author gets full credit of the papers regardless of the number of additional co-authors.The study shows that the ranking list would look very different using an alternative fractionalised methodology.Research limitations:The study is based on a limited part of the total population of highly cited researchers.Practical implications:It is concluded that"excellence"understood as highly cited encompasses very different types of research and researchers of which many do not fit with dominant preconceptions.Originality/value:The study develops further knowledge on highly cited researchers,addressing questions such as who becomes highly cited and the type of research that benefits by defining excellence in terms of citation scores and specific counting methods.展开更多
Opening a new scientific frontier lying under the Antarctic ice, Russian researchers have drilled down and finally reached the surface of the gigantic freshwater lake, Lake Vostok. The mission chief likened the achiev...Opening a new scientific frontier lying under the Antarctic ice, Russian researchers have drilled down and finally reached the surface of the gigantic freshwater lake, Lake Vostok. The mission chief likened the achievement to placing a man on the moon. Drilling in the area of the lake began 22 years ago in 1990, but progressed slowly as a result of funding shortages, equipment breakdowns, difficulties of drilling in the ＂warm＂ ice, and environmental concerns. In 1996, six years after drilling was started, a group of Russian and British scientists discovered the lake believed to be one of the largest fresh water reservoirs on the planet. This lake is among the last unexplored places on Earth. Sealed from the Earth＇s atmosphere for millions of years, it may provide vital information about microbial evolution, the past climate of the Earth, and the formation of the Antarctic ice sheet. Russian experts waited several years for international approval of their drilling technology before proceeding. As anticipated, lake water under pressure rushed up the borehole, pushing the drilling fluid up and away, then froze, forming a protective plug that prevented contamination of the lake. In December of the next Antarctic season, 2012--2013, researchers plan to re-drill the frozen sample of subglacial water for analysis.展开更多
Gene deletion has been a valuable tool for unraveling the mysteries of molecular biology.Early approaches included gene trapping and gene targetting to disrupt or delete a gene randomly or at a specific location,respe...Gene deletion has been a valuable tool for unraveling the mysteries of molecular biology.Early approaches included gene trapping and gene targetting to disrupt or delete a gene randomly or at a specific location,respectively.Using these technologies in mouse embryos led to the generation of mouse knocko ut models and many scientific discoveries.The efficacy and specificity of these approaches have significantly increased with the advent of new technology such as cluste red regula rly inters paced short palindromic repeats for targetted gene deletion.However,several limitations including unwanted off-target gene deletion have hindered their widespread use in the field.Crerecombinase technology has provided additional capacity for cell-specific gene deletion.In this review,we provide a summary of currently available literature on the application of this system for targetted deletion of neuronal genes.This article has been constructed to provide some background info rmation for the new trainees on the mechanism and to provide necessary information for the design,and application of the Cre-recombinase system thro ugh reviewing the most f requent promoters that are currently available for genetic manipulation of neuro ns.We additionally will provide a summary of the latest technological developments that can be used for targeting neurons.This may also serve as a general guide for the selection of appropriate models for biomedical research.展开更多
Lanthanide(Ln^(3+))-doped photon avalanche(PA)upconversion nanoparticles(UCNPs)have great prospects in many frontier applications,such as super-resolution bioimaging,miniaturized lasers,single-molecule tracking,and qu...Lanthanide(Ln^(3+))-doped photon avalanche(PA)upconversion nanoparticles(UCNPs)have great prospects in many frontier applications,such as super-resolution bioimaging,miniaturized lasers,single-molecule tracking,and quantum optics.However,it remains challenging to realize PA in colloidal Ln^(3+)-doped UCNPs at room temperature(RT),due to the deleterious quenching effect associated with the surface and lattice OH^(-)defects.展开更多
This paper focuses on the remarkable contributions and achievements of Dr.Azar Andami(1926–1984),a renowned physician and specialist at the Pasteur Institute of Iran.Dr.Andami conducted extensive research on infectio...This paper focuses on the remarkable contributions and achievements of Dr.Azar Andami(1926–1984),a renowned physician and specialist at the Pasteur Institute of Iran.Dr.Andami conducted extensive research on infectious diseases,particularly cholera,utilizing her knowledge in medicine,bacteriology,and laboratory sciences.She played a crucial role in the mass production of the cholera vaccine at the Pasteur Institute of Iran and in controlling the spread of communicable diseases both locally and globally.This paper aims to highlight her remarkable works and accomplishments.展开更多
Purpose:This study was carried out to uncover the characteristics of information seeking behavior of researchers as faculty/student team members.Design/methodology/approach:An inventory encompassing 6 dimensions of in...Purpose:This study was carried out to uncover the characteristics of information seeking behavior of researchers as faculty/student team members.Design/methodology/approach:An inventory encompassing 6 dimensions of information seeking behavior was developed:Information awareness,information acquisition,information evaluation,information organization and management,information utilization and information ethics.Data was collected on 306 respondents from 52 faculty/student teams in Central South University in China and analyzed using SPSS 18.0 software.Findings:Significant differences were found among researchers with different genders in information awareness and in different academic disciplines in information acquisition and information utilization.The survey shows the characteristics of information seeking behavior of different gender groups and different teams:1) male participants got higher scores in all of the 6 dimensions of information seeking behavior;2) small teams performed best,followed by middle-sized teams and large teams;3) faculty/doctoral student teams possessed better information seeking skills than faculty/master’s student teams or faculty/doctoral and master’s student teams:4) medical teams achieved the highest level in all of the 6 dimensions of information seeking behavior,whereas natural science teams the lowest level.Medical and engineering teams were rated higher than other teams in information acquisition and information utilization.Research limitations:The small population size and doctoral students accounting for only a small portion of the respondents in the sample limit the generalization of our findings.Practical implications:The findings of this study have some implications for research and practice,especially for educational institutions,library science and information literacy training.Originality/value:This paper is the first to describe and analyze the characteristics of information seeking behavior of researchers as faculty/student team members.展开更多
为探究节水灌溉以及品种类型对再生稻产量和稻米品质的影响,2023年在湖北蕲春和浠水开展大田试验。以3个节水抗旱稻品种(旱优8200、旱优116和旱优73)和3个优质稻品种(箴两优郢香丝苗、荃优粤农丝苗和荃优607)为供试材料,以湖北省再生稻...为探究节水灌溉以及品种类型对再生稻产量和稻米品质的影响,2023年在湖北蕲春和浠水开展大田试验。以3个节水抗旱稻品种(旱优8200、旱优116和旱优73)和3个优质稻品种(箴两优郢香丝苗、荃优粤农丝苗和荃优607)为供试材料,以湖北省再生稻大面积种植的普通水稻品种(两优6326)为对照,设置常规灌溉和节水灌溉2种水分管理方式,分析再生稻模式下不同品种产量和稻米品质对水分管理的响应差异。结果表明,相较于常规灌溉,节水灌溉处理使头季和再生季灌水量分别平均减少76%和85%,但产量和稻米的加工、外观和蒸煮食味品质在水分处理间无显著差异,且这一结果在不同试验地点间保持一致。这表明,与常规灌溉相比,节水抗旱稻和优质稻品种在节水灌溉条件下均能保持较为稳定的头季和再生季产量和稻米品质。优质稻头季和再生季产量分别为8.54 t hm^(-2)和5.88 t hm^(-2),相较于普通水稻产量差异不显著;但头季和再生季整精米率分别显著提高13.5个百分点和20.6个百分点,垩白粒率和垩白度分别显著降低22.6个百分点和6.4个百分点、10.8个百分点和1.8个百分点。节水抗旱稻在头季的产量以及稻米加工、外观和蒸煮食味品质方面与普通水稻无显著差异,但在再生季,产量显著下降17%,整精米率显著提高17.0个百分点,垩白粒率和垩白度分别降低5.5个百分点和1.0个百分点。在同一品种类型中,再生稻产量和稻米品质存在显著的品种间差异。相关性分析表明,再生季稻米的加工、外观和蒸煮食味品质指标均与头季相应指标呈正相关。因此,在降水条件较好的地区,结合优良水稻品种,实施“以雨养为主、关键生育期适时灌溉”的节水灌溉策略,可有效降低水分消耗、提升水分利用效率,同时实现再生稻的高产与优质目标。展开更多
Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microgl...Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.展开更多
Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’...Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.展开更多
Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mecha...Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.展开更多
Space-Based Solar Power(SBSP) presents a promising solution for achieving carbon neutrality and Renewable Electricity 100%(RE100) goals by offering a stable and continuous energy supply. However, its commercialization...Space-Based Solar Power(SBSP) presents a promising solution for achieving carbon neutrality and Renewable Electricity 100%(RE100) goals by offering a stable and continuous energy supply. However, its commercialization faces significant obstacles due to the technical challenges of long-distance microwave Wireless Power Transmission(WPT) from geostationary orbit. Even ground-based kilometer-scale WPT experiments remain difficult because of limited testing infrastructure, high costs, and strict electromagnetic wave regulations. Since the 1975 NASA-Raytheon experiment, which successfully recovered 30 kW of power over 1.55 km, there has been little progress in extending the transmission distance or increasing the retrieved power. This study proposes a cost-effective methodology for conducting long-range WPT experiments in constrained environments by utilizing existing infrastructure. A deep space antenna operating at 2.08 GHz with an output power of 2.3 kW and a gain of 55.3 dBi was used as the transmitter. Two test configurations were implemented: a 1.81 km ground-to-air test using an aerostat to elevate the receiver and a 1.82 km ground-to-ground test using a ladder truck positioned on a plateau. The rectenna consists of a lightweight 3×3 patch antenna array(0.9 m × 0.9 m), accompanied by a steering device and LED indicators to verify power reception. The aerostat-based test achieved a power density of 154.6 mW/m2, which corresponds to approximately 6.2% of the theoretical maximum. The performance gap is primarily attributed to near-field interference, detuning of the patch antenna, rectifier mismatch, and alignment issues. These limitations are expected to be mitigated through improved patch antenna fabrication, a transition from GaN to GaAs rectifiers optimized for lower input power, and the implementation of an automated alignment system. With these enhancements, the recovered power is expected to improve by approximately four to five times. The results demonstrate a practical and scalable framework for long-range WPT experiments under constrained conditions and provide key insights for advancing SBSP technology.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
To mitigate the impact of interdiffusion reactions between the silicide slurry and Ta12W alloy substrate during vacuum sintering process on the oxidation resistance of the silicide coating,a micro-arc oxidation pretre...To mitigate the impact of interdiffusion reactions between the silicide slurry and Ta12W alloy substrate during vacuum sintering process on the oxidation resistance of the silicide coating,a micro-arc oxidation pretreatment was employed to construct a Ta_(2)O_(5)ceramic layer on the Ta12W alloy surface.Subsequently,a slurry spraying-vacuum sintering method was used to prepare a Si-Cr-Ti-Zr coating on the pretreated substrate.Comparative studies were conducted on the microstructure,phase composition,and isothermal oxidation resistance(at 1600℃)of the as-prepared coatings with and without the micro-arc oxidation ceramic layer.The results show that the Ta_(2)O_(5)layer prepared at 400 V is more continuous and has smaller pores than that prepared at 350 V.After microarc oxidation pretreatment,the Si-Cr-Ti-Zr coating on Ta12W alloy consists of three distinct layers:an upper layer dominated by Ti_(5)Si_(3),Ta_(5)Si_(3),and ZrSi;a middle layer dominated by TaSi_(2);a coating/substrate interfacial reaction layer dominated by Ta_(5)Si_(3).Both the Si-Cr-Ti-Zr coatings with and without the Ta_(2)O_(5)ceramic layer do not fail after isothermal oxidation at 1600℃for 5 h.Notably,the addition of the Ta2O5 ceramic layer reduces the high-temperature oxidation rate of the coating.展开更多
The influence of Hf on the precipitation behavior of γ'phase and the subsequent tensile properties of a Ni-Cr-Mo alloy after long-term thermal exposure was investigated.The results reveal that the addition of Hf ...The influence of Hf on the precipitation behavior of γ'phase and the subsequent tensile properties of a Ni-Cr-Mo alloy after long-term thermal exposure was investigated.The results reveal that the addition of Hf increases the average diameter ofγ'phases after thermal exposure at 700℃ for 5000 h,which enhances the critical resolved shear stress required for dislocations to shear the γ'phases in the Ni-Cr-Mo alloy.Simultaneously,element Hf incorporated into the γ'phases increases the lattice mismatch between the γ'and γ phase,thereby strengthening the coherency strengthening effect.These two factors collectively contribute to the enhanced strength of the alloy.Thus,Hf alloying effectively improves the yield strength of the Ni-Cr-Mo alloy after thermal exposure at 700℃.展开更多
Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone...Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.展开更多
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord,leading to muscle weakness,para...Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord,leading to muscle weakness,paralysis,and respiratory failure (Morgan and Orrell,2016).展开更多
The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,p...The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,particularly given the current lack of disease-modifying treatments.The glymphatic system,a recently identified perivascular fluid transport network,is crucial for clearing neurotoxic proteins.This review aims to synthesize current knowledge on the role of the glymphatic system inα-synuclein clearance and its implications for the pathology of Parkinson's disease while emphasizing potential therapeutic strategies and areas for future research.The review begins with an overview of the glymphatic system and details its anatomical structure and physiological functions that facilitate cerebrospinal fluid circulation and waste clearance.It summarizes emerging evidence from neuroimaging and experimental studies that highlight the close correlation between the glymphatic system and clinical symptom severity in patients with Parkinson's disease,as well as the effect of glymphatic dysfunction onα-synuclein accumulation in Parkinson's disease models.Subsequently,the review summarizes the mechanisms of glymphatic system impairment in Parkinson's disease,including sleep disturbances,aquaporin-4 impairment,and mitochondrial dysfunction,all of which diminish glymphatic system efficiency.This creates a vicious cycle that exacerbatesα-synuclein accumulation and worsens Parkinson's disease.The therapeutic perspectives section outlines strategies for enhancing glymphatic activity,such as improving sleep quality and pharmacologically targeting aquaporin-4 or its subcellular localization.Promising interventions include deep brain stimulation,melatonin supplementation,γ-aminobutyric acid modulation,and non-invasive methods(such as exercise and bright-light therapy),multisensoryγstimulation,and ultrasound therapy.Moreover,identifying neuroimaging biomarkers to assess glymphatic flow as an indicator ofα-synuclein burden could refine Parkinson's disease diagnosis and track disease progression.In conclusion,the review highlights the critical role of the glymphatic system inα-synuclein clearance and its potential as a therapeutic target in Parkinson's disease.It advocates for further research to elucidate the specific mechanisms by which the glymphatic system clears misfoldedα-synuclein and the development of imaging biomarkers to monitor glymphatic activity in patients with Parkinson's disease.Findings from this review suggest that enhancing glymphatic clearance is a promising strategy for reducingα-synuclein deposits and mitigating the progression of Parkinson's disease.展开更多
基金funded the Ecuadorian National Secretary of Higher Education,Science and Technology(SENESCYT),through the Scholarship Programme 2012.
文摘Climate change has well-documented psychological consequences for society.However,the emotional experiences of frontline conservation professionals remain underexplored.As key knowledge producers and participants in decision-making processes,conservation researchers play a crucial role in shaping and implementing adaptation and mitigation efforts,which are pivotal for effective climate planning.Understanding their emotional responses is essential for enhancing the success of these strategies and supporting climate action.This study aims to identify the most prevalent emotions experienced by conservation researchers regarding climate change across various countries and to examine the qualitative and quantitative factors shaping these emotions.An online survey was conducted with 362 participants from 98 academic and research institutions,utilising both closed and open-ended questions to capture demographic data,climate knowledge,stances on mitigation and adaptation,and emotional responses.Data analysis revealed that feelings of powerlessness,guilt,and concern were most frequently reported,driven by a profound sense of inability to halt climate change,frustration with perceived inaction by governments and industries,and self-assessed personal shortcomings.Age and stances on climate adaptation were identified as primary factors influencing emotional responses,particularly among individuals aged 20–50 and 61–70,with opposition to adaptation correlating with stronger emotional reactions.Demographic factors such as region,place of residence,and mitigation stances played a minor role.These findings provide valuable insights into the psychological well-being of conservation researchers related to climate change.
文摘Purpose:Diaspora researchers work in one country but have ancestral origins in another,either through moves during a research career(mobile diaspora researchers)or by starting research in the target country(embedded diaspora researchers).Whilst mobile researchers might be tracked through affiliation changes in bibliometric databases,embedded researchers cannot.This article reports an evidence-based discussion of which countries’diaspora researchers can be partially tracked using first or last names,addressing this limitation.Design/methodology/approach:A frequency analysis of first and last names of authors of all Scopus journal articles 2001-2021 for 200 countries or regions.Findings:There are great variations in the extent to which first or last names are uniquely national,from Monserrat(no unique first names)to Thailand(81%unique last names).Nevertheless,most countries have a subset of first or last names that are relatively unique.For the 50 countries with the most researchers,authors with relatively national names are always more likely to research their name-associated country,suggesting a continued national association.Lists of researchers’first and last name frequencies and proportions are provided for 200 countries/regions.Research limitations:Only one period is tracked(2001-2021)and no attempt was made to validate the ancestral origins of any researcher.Practical implications:Simple name heuristics can be used to identify the international spread of a sample of most countries’diaspora researchers,but some manual checks of individual names are needed to weed out false matches.This can supplement mobile researcher data from bibliometric databases.Originality/value:This is the first attempt to list name associations for the authors of all countries and large regions,and to identify the countries for which diaspora researchers could be tracked by name.
基金the Research Council of Norway,grant number 256223(the R-QUEST centre)。
文摘Purpose:The ranking lists of highly cited researchers receive much public attention.In common interpretations,highly cited researchers are perceived to have made extraordinary contributions to science.Thus,the metrics of highly cited researchers are often linked to notions of breakthroughs,scientific excellence,and lone geniuses.Design/methodology/approach:In this study,we analyze a sample of individuals who appear on Clarivate Analytics’Highly Cited Researchers list.The main purpose is to juxtapose the characteristics of their research performance against the claim that the list captures a small fraction of the researcher population that contributes disproportionately to extending the frontier and gaining—on behalf of society—knowledge and innovations that make the world healthier,richer,sustainable,and more secure.Findings:The study reveals that the highly cited articles of the selected individuals generally have a very large number of authors.Thus,these papers seldom represent individual contributions but rather are the result of large collective research efforts conducted in research consortia.This challenges the common perception of highly cited researchers as individual geniuses who can be singled out for their extraordinary contributions.Moreover,the study indicates that a few of the individuals have not even contributed to highly cited original research but rather to reviews or clinical guidelines.Finally,the large number of authors of the papers implies that the ranking list is very sensitive to the specific method used for allocating papers and citations to individuals.In the"whole count"methodology applied by Clarivate Analytics,each author gets full credit of the papers regardless of the number of additional co-authors.The study shows that the ranking list would look very different using an alternative fractionalised methodology.Research limitations:The study is based on a limited part of the total population of highly cited researchers.Practical implications:It is concluded that"excellence"understood as highly cited encompasses very different types of research and researchers of which many do not fit with dominant preconceptions.Originality/value:The study develops further knowledge on highly cited researchers,addressing questions such as who becomes highly cited and the type of research that benefits by defining excellence in terms of citation scores and specific counting methods.
文摘Opening a new scientific frontier lying under the Antarctic ice, Russian researchers have drilled down and finally reached the surface of the gigantic freshwater lake, Lake Vostok. The mission chief likened the achievement to placing a man on the moon. Drilling in the area of the lake began 22 years ago in 1990, but progressed slowly as a result of funding shortages, equipment breakdowns, difficulties of drilling in the ＂warm＂ ice, and environmental concerns. In 1996, six years after drilling was started, a group of Russian and British scientists discovered the lake believed to be one of the largest fresh water reservoirs on the planet. This lake is among the last unexplored places on Earth. Sealed from the Earth＇s atmosphere for millions of years, it may provide vital information about microbial evolution, the past climate of the Earth, and the formation of the Antarctic ice sheet. Russian experts waited several years for international approval of their drilling technology before proceeding. As anticipated, lake water under pressure rushed up the borehole, pushing the drilling fluid up and away, then froze, forming a protective plug that prevented contamination of the lake. In December of the next Antarctic season, 2012--2013, researchers plan to re-drill the frozen sample of subglacial water for analysis.
文摘Gene deletion has been a valuable tool for unraveling the mysteries of molecular biology.Early approaches included gene trapping and gene targetting to disrupt or delete a gene randomly or at a specific location,respectively.Using these technologies in mouse embryos led to the generation of mouse knocko ut models and many scientific discoveries.The efficacy and specificity of these approaches have significantly increased with the advent of new technology such as cluste red regula rly inters paced short palindromic repeats for targetted gene deletion.However,several limitations including unwanted off-target gene deletion have hindered their widespread use in the field.Crerecombinase technology has provided additional capacity for cell-specific gene deletion.In this review,we provide a summary of currently available literature on the application of this system for targetted deletion of neuronal genes.This article has been constructed to provide some background info rmation for the new trainees on the mechanism and to provide necessary information for the design,and application of the Cre-recombinase system thro ugh reviewing the most f requent promoters that are currently available for genetic manipulation of neuro ns.We additionally will provide a summary of the latest technological developments that can be used for targeting neurons.This may also serve as a general guide for the selection of appropriate models for biomedical research.
文摘Lanthanide(Ln^(3+))-doped photon avalanche(PA)upconversion nanoparticles(UCNPs)have great prospects in many frontier applications,such as super-resolution bioimaging,miniaturized lasers,single-molecule tracking,and quantum optics.However,it remains challenging to realize PA in colloidal Ln^(3+)-doped UCNPs at room temperature(RT),due to the deleterious quenching effect associated with the surface and lattice OH^(-)defects.
文摘This paper focuses on the remarkable contributions and achievements of Dr.Azar Andami(1926–1984),a renowned physician and specialist at the Pasteur Institute of Iran.Dr.Andami conducted extensive research on infectious diseases,particularly cholera,utilizing her knowledge in medicine,bacteriology,and laboratory sciences.She played a crucial role in the mass production of the cholera vaccine at the Pasteur Institute of Iran and in controlling the spread of communicable diseases both locally and globally.This paper aims to highlight her remarkable works and accomplishments.
基金supported by the National Social Science Foundation of China(Grant No.:11BTQ044)
文摘Purpose:This study was carried out to uncover the characteristics of information seeking behavior of researchers as faculty/student team members.Design/methodology/approach:An inventory encompassing 6 dimensions of information seeking behavior was developed:Information awareness,information acquisition,information evaluation,information organization and management,information utilization and information ethics.Data was collected on 306 respondents from 52 faculty/student teams in Central South University in China and analyzed using SPSS 18.0 software.Findings:Significant differences were found among researchers with different genders in information awareness and in different academic disciplines in information acquisition and information utilization.The survey shows the characteristics of information seeking behavior of different gender groups and different teams:1) male participants got higher scores in all of the 6 dimensions of information seeking behavior;2) small teams performed best,followed by middle-sized teams and large teams;3) faculty/doctoral student teams possessed better information seeking skills than faculty/master’s student teams or faculty/doctoral and master’s student teams:4) medical teams achieved the highest level in all of the 6 dimensions of information seeking behavior,whereas natural science teams the lowest level.Medical and engineering teams were rated higher than other teams in information acquisition and information utilization.Research limitations:The small population size and doctoral students accounting for only a small portion of the respondents in the sample limit the generalization of our findings.Practical implications:The findings of this study have some implications for research and practice,especially for educational institutions,library science and information literacy training.Originality/value:This paper is the first to describe and analyze the characteristics of information seeking behavior of researchers as faculty/student team members.
文摘为探究节水灌溉以及品种类型对再生稻产量和稻米品质的影响,2023年在湖北蕲春和浠水开展大田试验。以3个节水抗旱稻品种(旱优8200、旱优116和旱优73)和3个优质稻品种(箴两优郢香丝苗、荃优粤农丝苗和荃优607)为供试材料,以湖北省再生稻大面积种植的普通水稻品种(两优6326)为对照,设置常规灌溉和节水灌溉2种水分管理方式,分析再生稻模式下不同品种产量和稻米品质对水分管理的响应差异。结果表明,相较于常规灌溉,节水灌溉处理使头季和再生季灌水量分别平均减少76%和85%,但产量和稻米的加工、外观和蒸煮食味品质在水分处理间无显著差异,且这一结果在不同试验地点间保持一致。这表明,与常规灌溉相比,节水抗旱稻和优质稻品种在节水灌溉条件下均能保持较为稳定的头季和再生季产量和稻米品质。优质稻头季和再生季产量分别为8.54 t hm^(-2)和5.88 t hm^(-2),相较于普通水稻产量差异不显著;但头季和再生季整精米率分别显著提高13.5个百分点和20.6个百分点,垩白粒率和垩白度分别显著降低22.6个百分点和6.4个百分点、10.8个百分点和1.8个百分点。节水抗旱稻在头季的产量以及稻米加工、外观和蒸煮食味品质方面与普通水稻无显著差异,但在再生季,产量显著下降17%,整精米率显著提高17.0个百分点,垩白粒率和垩白度分别降低5.5个百分点和1.0个百分点。在同一品种类型中,再生稻产量和稻米品质存在显著的品种间差异。相关性分析表明,再生季稻米的加工、外观和蒸煮食味品质指标均与头季相应指标呈正相关。因此,在降水条件较好的地区,结合优良水稻品种,实施“以雨养为主、关键生育期适时灌溉”的节水灌溉策略,可有效降低水分消耗、提升水分利用效率,同时实现再生稻的高产与优质目标。
基金supported by the Natural Science Foundation of Yunnan Province,No.202401AS070086(to ZW)the National Key Research and Development Program of China,No.2018YFA0801403(to ZW)+1 种基金Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(to ZW)the Natural Science Foundation of China,No.31960120(to ZW)。
文摘Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.
基金supported by the National Key R&D Program of China,No.2021YFC2501200(to PC).
文摘Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.
基金supported by the National Science Foundation of China,Nos.82325031(to FX),82030059(to YC),82102290(to YG),U23A20485(to YC)Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0505504(to FX),2023ZD0505500(to YC)the Key R&D Program of Shandong Province,No.2022ZLGX03(to YC).
文摘Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.
文摘Space-Based Solar Power(SBSP) presents a promising solution for achieving carbon neutrality and Renewable Electricity 100%(RE100) goals by offering a stable and continuous energy supply. However, its commercialization faces significant obstacles due to the technical challenges of long-distance microwave Wireless Power Transmission(WPT) from geostationary orbit. Even ground-based kilometer-scale WPT experiments remain difficult because of limited testing infrastructure, high costs, and strict electromagnetic wave regulations. Since the 1975 NASA-Raytheon experiment, which successfully recovered 30 kW of power over 1.55 km, there has been little progress in extending the transmission distance or increasing the retrieved power. This study proposes a cost-effective methodology for conducting long-range WPT experiments in constrained environments by utilizing existing infrastructure. A deep space antenna operating at 2.08 GHz with an output power of 2.3 kW and a gain of 55.3 dBi was used as the transmitter. Two test configurations were implemented: a 1.81 km ground-to-air test using an aerostat to elevate the receiver and a 1.82 km ground-to-ground test using a ladder truck positioned on a plateau. The rectenna consists of a lightweight 3×3 patch antenna array(0.9 m × 0.9 m), accompanied by a steering device and LED indicators to verify power reception. The aerostat-based test achieved a power density of 154.6 mW/m2, which corresponds to approximately 6.2% of the theoretical maximum. The performance gap is primarily attributed to near-field interference, detuning of the patch antenna, rectifier mismatch, and alignment issues. These limitations are expected to be mitigated through improved patch antenna fabrication, a transition from GaN to GaAs rectifiers optimized for lower input power, and the implementation of an automated alignment system. With these enhancements, the recovered power is expected to improve by approximately four to five times. The results demonstrate a practical and scalable framework for long-range WPT experiments under constrained conditions and provide key insights for advancing SBSP technology.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金National Natural Science Foundation of China(52071274)Key Research and Development Projects of Shaanxi Province(2023-YBGY-442)Science and Technology Nova Project-Innovative Talent Promotion Program of Shaanxi Province(2020KJXX-062)。
文摘To mitigate the impact of interdiffusion reactions between the silicide slurry and Ta12W alloy substrate during vacuum sintering process on the oxidation resistance of the silicide coating,a micro-arc oxidation pretreatment was employed to construct a Ta_(2)O_(5)ceramic layer on the Ta12W alloy surface.Subsequently,a slurry spraying-vacuum sintering method was used to prepare a Si-Cr-Ti-Zr coating on the pretreated substrate.Comparative studies were conducted on the microstructure,phase composition,and isothermal oxidation resistance(at 1600℃)of the as-prepared coatings with and without the micro-arc oxidation ceramic layer.The results show that the Ta_(2)O_(5)layer prepared at 400 V is more continuous and has smaller pores than that prepared at 350 V.After microarc oxidation pretreatment,the Si-Cr-Ti-Zr coating on Ta12W alloy consists of three distinct layers:an upper layer dominated by Ti_(5)Si_(3),Ta_(5)Si_(3),and ZrSi;a middle layer dominated by TaSi_(2);a coating/substrate interfacial reaction layer dominated by Ta_(5)Si_(3).Both the Si-Cr-Ti-Zr coatings with and without the Ta_(2)O_(5)ceramic layer do not fail after isothermal oxidation at 1600℃for 5 h.Notably,the addition of the Ta2O5 ceramic layer reduces the high-temperature oxidation rate of the coating.
基金National Key Research and Development Program of China(2021YFB3704103)National Natural Science Foundation of China(51571191)。
文摘The influence of Hf on the precipitation behavior of γ'phase and the subsequent tensile properties of a Ni-Cr-Mo alloy after long-term thermal exposure was investigated.The results reveal that the addition of Hf increases the average diameter ofγ'phases after thermal exposure at 700℃ for 5000 h,which enhances the critical resolved shear stress required for dislocations to shear the γ'phases in the Ni-Cr-Mo alloy.Simultaneously,element Hf incorporated into the γ'phases increases the lattice mismatch between the γ'and γ phase,thereby strengthening the coherency strengthening effect.These two factors collectively contribute to the enhanced strength of the alloy.Thus,Hf alloying effectively improves the yield strength of the Ni-Cr-Mo alloy after thermal exposure at 700℃.
基金supported by the Ministry of Health National Medical Research Council (to JL)the National University of Singapore (to JJEC)
文摘Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.
文摘Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord,leading to muscle weakness,paralysis,and respiratory failure (Morgan and Orrell,2016).
基金partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
基金supported by the National Natural Science Foundation of China,No.81971031(to ZL)the National Key Research and Development Program of China,No.2022YFE0210100(to JFC)+7 种基金the National Natural Science Foundation of China(Original Exploration Project),No.82151308(to JFC)the National Natural Science Foundation of China(Research Fund for International Senior Scientists),No.82150710558(to JFC)Science&Technology Initiative STI2030-Major Projects,No.2021ZD0203400(to JFC)Key Research and Development Program of Zhejiang Province,No.2023C03079(to JFC)Scientific Research Starting Foundation of Oujiang Laboratory(Zhejiang Laboratory for Regenerative Medicine,Vision and Brain Health),No.OJQDSP2022007(to JFC)Project of State Key Laboratory of Ophthalmology,Optometry and Visual Science,Wenzhou Medical University,No.J01-20190101(to JFC)Scientific Research Starting Foundation of Wenzhou Medical University,No.QTJ12003(to JFC)Department of Science and Technology of Zhejiang Province,No.2023ZY1011(to JFC)。
文摘The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,particularly given the current lack of disease-modifying treatments.The glymphatic system,a recently identified perivascular fluid transport network,is crucial for clearing neurotoxic proteins.This review aims to synthesize current knowledge on the role of the glymphatic system inα-synuclein clearance and its implications for the pathology of Parkinson's disease while emphasizing potential therapeutic strategies and areas for future research.The review begins with an overview of the glymphatic system and details its anatomical structure and physiological functions that facilitate cerebrospinal fluid circulation and waste clearance.It summarizes emerging evidence from neuroimaging and experimental studies that highlight the close correlation between the glymphatic system and clinical symptom severity in patients with Parkinson's disease,as well as the effect of glymphatic dysfunction onα-synuclein accumulation in Parkinson's disease models.Subsequently,the review summarizes the mechanisms of glymphatic system impairment in Parkinson's disease,including sleep disturbances,aquaporin-4 impairment,and mitochondrial dysfunction,all of which diminish glymphatic system efficiency.This creates a vicious cycle that exacerbatesα-synuclein accumulation and worsens Parkinson's disease.The therapeutic perspectives section outlines strategies for enhancing glymphatic activity,such as improving sleep quality and pharmacologically targeting aquaporin-4 or its subcellular localization.Promising interventions include deep brain stimulation,melatonin supplementation,γ-aminobutyric acid modulation,and non-invasive methods(such as exercise and bright-light therapy),multisensoryγstimulation,and ultrasound therapy.Moreover,identifying neuroimaging biomarkers to assess glymphatic flow as an indicator ofα-synuclein burden could refine Parkinson's disease diagnosis and track disease progression.In conclusion,the review highlights the critical role of the glymphatic system inα-synuclein clearance and its potential as a therapeutic target in Parkinson's disease.It advocates for further research to elucidate the specific mechanisms by which the glymphatic system clears misfoldedα-synuclein and the development of imaging biomarkers to monitor glymphatic activity in patients with Parkinson's disease.Findings from this review suggest that enhancing glymphatic clearance is a promising strategy for reducingα-synuclein deposits and mitigating the progression of Parkinson's disease.
