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
Pseudounipolar neurons in the dorsal root ganglia(DRG),as the central nodes of primary sensory afferents,possess a distinctive T-junction that is not merely a morphological peculiarity but also performs complex roles ...Pseudounipolar neurons in the dorsal root ganglia(DRG),as the central nodes of primary sensory afferents,possess a distinctive T-junction that is not merely a morphological peculiarity but also performs complex roles in rapid,multiplexed shunting and regulation of sensory signals.This specialized geometry enables separation,filtering,and feedback regulation of neuronal signals,thereby coordinating peripheral and central responses at multiple levels.Recent advances,including spatial transcriptomics,single-cell sequencing,super-resolution microscopy,organoid models,and novel electrophysiological methods,have permitted more precise dissection of the T-junction's molecular composition,ion-channel distribution,and electrophysiological properties.Here,we review current knowledge of the T-junction's developmental regulation and multilayered molecular networks,and we detail its functional alterations in both physiological signaling and pathological pain states,with particular emphasis on ion-channel modulation,signal attenuation,and selective transmission mechanisms.Finally,we discuss contemporary pain-intervention approaches and prospects for precision-targeted therapies,aiming to provide a theoretical foundation for future studies in pain physiology and clinical translation.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
Persistent postsurgical pain is a major clinical concern,especially in the aging population,who represent a growing proportion of surgical patients.Although age is a known pain risk factor,the mechanisms driving age-r...Persistent postsurgical pain is a major clinical concern,especially in the aging population,who represent a growing proportion of surgical patients.Although age is a known pain risk factor,the mechanisms driving age-related vulnerability to chronic postoperative pain remain poorly understood.This study aims to investigate how aging influences the resolution of postoperative pain and to elucidate the roles of microglial activation and synaptic remodeling in the spinal dorsal horn.A plantar incision model in young(3-month-old)and aged(18-month-old)male and female mice was used to mimic postoperative pain conditions.Mechanical and thermal hypersensitivity at various postoperative intervals were assessed by von Frey and Hargreaves tests.Microglial activation and inhibitory/excitatory synaptic densities in the spinal dorsal horn were evaluated using immunofluorescence and 3D reconstruction with Imaris software.On postoperative day(POD)3,both age groups exhibited reduced pain thresholds on the ipsilateral side,along with microglial activation in the dorsal horn.On POD 7,pain thresholds in young mice had returned to baseline with no significant microglial activation,while aged mice showed sustained reduction in pain thresholds,continuous microglial activation,and significant loss of inhibitory synapses without detectable changes in excitatory synapse density.These findings are consistent across both sexes,with no sex-related differences.Collectively,these results suggest that aging is associated with persistent postoperative pain,which correlates with microglial activation and inhibitory synapse loss.These insights advance our understanding of age-related pain vulnerability and may inform the development of more effective,targeted,and age-specific therapeutic strategies to prevent or alleviate persistent postoperative pain in elderly patients.展开更多
3D laser scanning technology is widely used in underground openings for high-precision,rapid,and nondestructive structural evaluations.Segmenting large 3D point cloud datasets,particularly in coal mine roadways with m...3D laser scanning technology is widely used in underground openings for high-precision,rapid,and nondestructive structural evaluations.Segmenting large 3D point cloud datasets,particularly in coal mine roadways with multi-scale targets,remains challenging.This paper proposes an enhanced segmentation method integrating improved PointNet++with a coverage-voted strategy.The coverage-voted strategy reduces data while preserving multi-scale target topology.The segmentation is achieved using an enhanced PointNet++algorithm with a normalization preprocessing head,resulting in a 94%accuracy for common supporting components.Ablation experiments show that the preprocessing head and coverage strategies increase segmentation accuracy by 20%and 2%,respectively,and improve Intersection over Union(IoU)for bearing plate segmentation by 58%and 20%.The accuracy of the current pretraining segmentation model may be affected by variations in surface support components,but it can be readily enhanced through re-optimization with additional labeled point cloud data.This proposed method,combined with a previously developed machine learning model that links rock bolt load and the deformation field of its bearing plate,provides a robust technique for simultaneously measuring the load of multiple rock bolts in a single laser scan.展开更多
A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synth...A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synthetic metabolic engineering offers a method to modify and redesign metabolic pathways to increase the nutritional value of crops.We summarize recent advances in the biofortification of key nutrients including provitamin A,vitamin C,vitamin B9,iron,zinc,anthocyanins,flavonoids,and unsaturated fatty acids.We discuss the potential of multi-gene stacking,gene editing,enzyme engineering,and artificial intelligence in synthetic metabolic engineering.We propose future research directions and potential solutions centered on leveraging AI-driven systems biology,precision gene editing,enzyme engineering,agrobacterium-mediated genotype-independent transformation,and modular metabolic engineering strategies to develop next-generation nutritionally enhanced super crops and transform global food systems.展开更多
Neurodevelopmental and neurodegenerative illnesses constitute a global health issue and a foremost economic burden since they are a large cause of incapacity and death worldwide.Altogether,the burden of neurological d...Neurodevelopmental and neurodegenerative illnesses constitute a global health issue and a foremost economic burden since they are a large cause of incapacity and death worldwide.Altogether,the burden of neurological disorders has increased considerably over the past 30 years because of population aging.Overall,neurological diseases significantly impair cognitive and motor functions and their incidence will increase as societies age and the world's population continues to grow.Autism spectrum disorder,motor neuron disease,encephalopathy,epilepsy,stroke,ataxia,Alzheimer's disease,amyotrophic lateral sclerosis,Huntington's disease,and Parkinson's disease represent a non-exhaustive list of neurological illnesses.These affections are due to perturbations in cellular homeostasis leading to the progressive injury and death of neurons in the nervous system.Among the common features of neurological handicaps,we find protein aggregation,oxidative stress,neuroinflammation,and mitochondrial impairment in the target tissues,e.g.,the brain,cerebellum,and spinal cord.The high energy requirements of neurons and their inability to produce sufficient adenosine triphosphate by glycolysis,are responsible for their dependence on functional mitochondria for their integrity.Reactive oxygen species,produced along with the respiration process within mitochondria,can lead to oxidative stress,which compromises neuronal survival.Besides having an essential role in energy production and oxidative stress,mitochondria are indispensable for an array of cellular processes,such as amino acid metabolism,iron-sulfur cluster biosynthesis,calcium homeostasis,intrinsic programmed cell death(apoptosis),and intraorganellar signaling.Despite the progress made in the last decades in the understanding of a growing number of genetic and molecular causes of central nervous diseases,therapies that are effective to diminish or halt neuronal dysfunction/death are rare.Given the genetic complexity responsible for neurological disorders,the development of neuroprotective strategies seeking to preserve mitochondrial homeostasis is a realistic challenge to lastingly diminish the harmful evolution of these pathologies and so to recover quality of life.A promising candidate is the neuroglobin,a globin superfamily member of 151 amino acids,which is found at high levels in the brain,the eye,and the cerebellum.The protein,which localizes to mitochondria,is involved in electron transfer,oxygen storage and defence against oxidative stress;hence,possessing neuroprotective properties.This review surveys up-to-date knowledge and emphasizes on existing investigations regarding neuroglobin physiological functions,which remain since its discovery in 2000 under intense debate and the possibility of using neuroglobin either by gene therapy or its direct delivery into the brain to treat neurological disorders.展开更多
Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)mode...Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.展开更多
The uplift resistance of the soil overlying shield tunnels significantly impacts their anti-floating stability.However,research on uplift resistance concerning special-shaped shield tunnels is limited.This study combi...The uplift resistance of the soil overlying shield tunnels significantly impacts their anti-floating stability.However,research on uplift resistance concerning special-shaped shield tunnels is limited.This study combines numerical simulation with machine learning techniques to explore this issue.It presents a summary of special-shaped tunnel geometries and introduces a shape coefficient.Through the finite element software,Plaxis3D,the study simulates six key parameters—shape coefficient,burial depth ratio,tunnel’s longest horizontal length,internal friction angle,cohesion,and soil submerged bulk density—that impact uplift resistance across different conditions.Employing XGBoost and ANN methods,the feature importance of each parameter was analyzed based on the numerical simulation results.The findings demonstrate that a tunnel shape more closely resembling a circle leads to reduced uplift resistance in the overlying soil,whereas other parameters exhibit the contrary effects.Furthermore,the study reveals a diminishing trend in the feature importance of buried depth ratio,internal friction angle,tunnel longest horizontal length,cohesion,soil submerged bulk density,and shape coefficient in influencing uplift resistance.展开更多
Mytilus contain abundant antimicrobial peptides(AMPs)that play a key role in the innate immunity.However,heterologous production of these AMPs remains challenging due to their short sequences,multiple disulfide bonds,...Mytilus contain abundant antimicrobial peptides(AMPs)that play a key role in the innate immunity.However,heterologous production of these AMPs remains challenging due to their short sequences,multiple disulfide bonds,and high content of cationic amino acids,which hinder functional expression in prokaryotic systems such as Escherichia coli.To establish a eukaryotic recombinant expression system for the AMPs of mussel and obtain recombinant mussel AMPs for subsequent studies,we reported the successful recombinant expression of myticofensin B1,a novel defensin-like AMP identified previously in Mytiluscoruscus,using the eukaryotic host Pichia pastoris.The codon-optimized gene encoding the mature myticofensin-B1(composed of 65 amino acid residues,including 6 conserved cysteine residues)was cloned into a pPICZαA vector and expressed in P.pastoris GS115.Structural fidelity of the recombinant peptide was confirmed by liquid chromatography-tandem mass spectrometry(LC-MS/MS),showing a molecular weight of 8849.9 Da,which was consistent with the theoretical prediction.Functional assays demonstrated a broad-spectrum antimicrobial activity of the recombinant myticofensin-B1,with stronger inhibition against Gram-negative bacteria.Scanning electron microscopy revealed different effects of the recombinant myticofensin-B1 against different bacteria.In addition,the recombinant myticofensin-B1 exhibited a very low hemolytic activity against sheep red blood cells and weak cytotoxicity against human A549 lung cancer cells.This study establishes P.pastoris as a powerful platform to produce functional mussel AMP and highlights the potential of the recombinant myticofensin-B1 as a therapeutic agent for aquaculture pathogens and infections.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
Neutrophils,macrophages,CD3^(+),CD4^(+),and CD8^(+)T lymphocytes expressμ-,δ-,andκ-opioid receptors(ORs)with varying affinities for opioids.Mast cells express the atypical OR Mas-related G-protein-coupled receptor ...Neutrophils,macrophages,CD3^(+),CD4^(+),and CD8^(+)T lymphocytes expressμ-,δ-,andκ-opioid receptors(ORs)with varying affinities for opioids.Mast cells express the atypical OR Mas-related G-protein-coupled receptor X2(MRGPRX2),which has a low affinity for morphine.Neutrophils and macrophages can synthesize and release endogenous opioid peptides.Activation of ORs enhances the synthesis of proinflammatory cytokines and the production of reactive oxygen species(ROS)in unstimulated leukocytes.Conversely,OR activation reduces proinflammatory cytokine synthesis in stimulated neutrophils and macrophages.Morphine inhibits Toll-like receptor 4(TLR4)expression in macrophages,thereby attenuating inflammation,whereas methadone induces ROS production in mast cells through TLR4 activation.Stimulation of TLR4 triggersβ-endorphin synthesis in macrophages.The production of proinflammatory cytokines and ROS contributes to cardiac reperfusion injury.Importantly,activation ofκ1-andμ-ORs suppresses proinflammatory cytokine production by leukocytes,thereby mitigating inflammatory injury to the heart and other organs.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 grant from the National Key Technology Support Program of the Ministry of Science and Technology of China(No.2021ZD0203204)。
文摘Pseudounipolar neurons in the dorsal root ganglia(DRG),as the central nodes of primary sensory afferents,possess a distinctive T-junction that is not merely a morphological peculiarity but also performs complex roles in rapid,multiplexed shunting and regulation of sensory signals.This specialized geometry enables separation,filtering,and feedback regulation of neuronal signals,thereby coordinating peripheral and central responses at multiple levels.Recent advances,including spatial transcriptomics,single-cell sequencing,super-resolution microscopy,organoid models,and novel electrophysiological methods,have permitted more precise dissection of the T-junction's molecular composition,ion-channel distribution,and electrophysiological properties.Here,we review current knowledge of the T-junction's developmental regulation and multilayered molecular networks,and we detail its functional alterations in both physiological signaling and pathological pain states,with particular emphasis on ion-channel modulation,signal attenuation,and selective transmission mechanisms.Finally,we discuss contemporary pain-intervention approaches and prospects for precision-targeted therapies,aiming to provide a theoretical foundation for future studies in pain physiology and clinical translation.
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 Natural Science Foundation of China(No.82401445 and 82271249)the China Postdoctoral Science Foundation(No.2024M752251)+3 种基金the Postdoctoral Fellowship Program of CPSF(No.GZC20241141)the Sichuan Science and Technology Program(No.2024NSFSC1636 and 2025ZNSFSC1645)the Postdoctoral Research Fund of West China Hospital of Sichuan University(No.2024HXBH013)1-3-5 Project for Disciplines of Excellence of West China Hospital of Sichuan University(No.ZYYC23002)。
文摘Persistent postsurgical pain is a major clinical concern,especially in the aging population,who represent a growing proportion of surgical patients.Although age is a known pain risk factor,the mechanisms driving age-related vulnerability to chronic postoperative pain remain poorly understood.This study aims to investigate how aging influences the resolution of postoperative pain and to elucidate the roles of microglial activation and synaptic remodeling in the spinal dorsal horn.A plantar incision model in young(3-month-old)and aged(18-month-old)male and female mice was used to mimic postoperative pain conditions.Mechanical and thermal hypersensitivity at various postoperative intervals were assessed by von Frey and Hargreaves tests.Microglial activation and inhibitory/excitatory synaptic densities in the spinal dorsal horn were evaluated using immunofluorescence and 3D reconstruction with Imaris software.On postoperative day(POD)3,both age groups exhibited reduced pain thresholds on the ipsilateral side,along with microglial activation in the dorsal horn.On POD 7,pain thresholds in young mice had returned to baseline with no significant microglial activation,while aged mice showed sustained reduction in pain thresholds,continuous microglial activation,and significant loss of inhibitory synapses without detectable changes in excitatory synapse density.These findings are consistent across both sexes,with no sex-related differences.Collectively,these results suggest that aging is associated with persistent postoperative pain,which correlates with microglial activation and inhibitory synapse loss.These insights advance our understanding of age-related pain vulnerability and may inform the development of more effective,targeted,and age-specific therapeutic strategies to prevent or alleviate persistent postoperative pain in elderly patients.
基金supported by the National Natural Science Foundation of China(Grant Nos.52304139,52325403)the CCTEG Coal Mining Research Institute funding(Grant No.KCYJY-2024-MS-10).
文摘3D laser scanning technology is widely used in underground openings for high-precision,rapid,and nondestructive structural evaluations.Segmenting large 3D point cloud datasets,particularly in coal mine roadways with multi-scale targets,remains challenging.This paper proposes an enhanced segmentation method integrating improved PointNet++with a coverage-voted strategy.The coverage-voted strategy reduces data while preserving multi-scale target topology.The segmentation is achieved using an enhanced PointNet++algorithm with a normalization preprocessing head,resulting in a 94%accuracy for common supporting components.Ablation experiments show that the preprocessing head and coverage strategies increase segmentation accuracy by 20%and 2%,respectively,and improve Intersection over Union(IoU)for bearing plate segmentation by 58%and 20%.The accuracy of the current pretraining segmentation model may be affected by variations in surface support components,but it can be readily enhanced through re-optimization with additional labeled point cloud data.This proposed method,combined with a previously developed machine learning model that links rock bolt load and the deformation field of its bearing plate,provides a robust technique for simultaneously measuring the load of multiple rock bolts in a single laser scan.
基金supported by grants from the Guangxi Science and Technology Major Project(GKAA24206023)the Biological Breeding-National Science and Technology Major Project(2024ZD04077)+2 种基金the National Natural Science Foundation of China(32272120)the National Key Research and Development Program of China(2024YFF1000800)the Guangdong Basic Research Center of Excellence for Precise Breeding of Future Crops Major Project(FCBRCE-202502,FCBRCE-202504).
文摘A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synthetic metabolic engineering offers a method to modify and redesign metabolic pathways to increase the nutritional value of crops.We summarize recent advances in the biofortification of key nutrients including provitamin A,vitamin C,vitamin B9,iron,zinc,anthocyanins,flavonoids,and unsaturated fatty acids.We discuss the potential of multi-gene stacking,gene editing,enzyme engineering,and artificial intelligence in synthetic metabolic engineering.We propose future research directions and potential solutions centered on leveraging AI-driven systems biology,precision gene editing,enzyme engineering,agrobacterium-mediated genotype-independent transformation,and modular metabolic engineering strategies to develop next-generation nutritionally enhanced super crops and transform global food systems.
基金supported by AFM-Telethon grants N°21704 and 23264,Universite Paris Cite(Paris)the National Institute of Health and Medical Research(INSERM)+3 种基金the National Center for Scientific Research(CNRS)the French Association Connaître les Syndromes Cerebelleux(CSC)(to MCD)GV/2021/188 granted from Conselleria of Innovation,Universities,28 Science and Society digital of the Community of Valencia(Spain)(to ITC)Subprograma Atraccion de Talento-Contratos Postdoctorales de la Universitat de Valencia(to IMY).
文摘Neurodevelopmental and neurodegenerative illnesses constitute a global health issue and a foremost economic burden since they are a large cause of incapacity and death worldwide.Altogether,the burden of neurological disorders has increased considerably over the past 30 years because of population aging.Overall,neurological diseases significantly impair cognitive and motor functions and their incidence will increase as societies age and the world's population continues to grow.Autism spectrum disorder,motor neuron disease,encephalopathy,epilepsy,stroke,ataxia,Alzheimer's disease,amyotrophic lateral sclerosis,Huntington's disease,and Parkinson's disease represent a non-exhaustive list of neurological illnesses.These affections are due to perturbations in cellular homeostasis leading to the progressive injury and death of neurons in the nervous system.Among the common features of neurological handicaps,we find protein aggregation,oxidative stress,neuroinflammation,and mitochondrial impairment in the target tissues,e.g.,the brain,cerebellum,and spinal cord.The high energy requirements of neurons and their inability to produce sufficient adenosine triphosphate by glycolysis,are responsible for their dependence on functional mitochondria for their integrity.Reactive oxygen species,produced along with the respiration process within mitochondria,can lead to oxidative stress,which compromises neuronal survival.Besides having an essential role in energy production and oxidative stress,mitochondria are indispensable for an array of cellular processes,such as amino acid metabolism,iron-sulfur cluster biosynthesis,calcium homeostasis,intrinsic programmed cell death(apoptosis),and intraorganellar signaling.Despite the progress made in the last decades in the understanding of a growing number of genetic and molecular causes of central nervous diseases,therapies that are effective to diminish or halt neuronal dysfunction/death are rare.Given the genetic complexity responsible for neurological disorders,the development of neuroprotective strategies seeking to preserve mitochondrial homeostasis is a realistic challenge to lastingly diminish the harmful evolution of these pathologies and so to recover quality of life.A promising candidate is the neuroglobin,a globin superfamily member of 151 amino acids,which is found at high levels in the brain,the eye,and the cerebellum.The protein,which localizes to mitochondria,is involved in electron transfer,oxygen storage and defence against oxidative stress;hence,possessing neuroprotective properties.This review surveys up-to-date knowledge and emphasizes on existing investigations regarding neuroglobin physiological functions,which remain since its discovery in 2000 under intense debate and the possibility of using neuroglobin either by gene therapy or its direct delivery into the brain to treat neurological disorders.
基金supported by the National Natural Science Foundation of China(No.82471229)Science and Technology Collaborative Innovation Fund of Fujian Province(No.2021Y9172)the Natural Science Foundation of Fujian Province,China(No.2023J01169)。
文摘Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.
基金Guangzhou Metro Scientific Research Project(No.JT204-100111-23001)Chongqing Municipal Special Project for Technological Innovation and Application Development(No.CSTB2022TIAD-KPX0101)Science and Technology Research and Development Program of China State Railway Group Co.,Ltd.(No.N2023G045)。
文摘The uplift resistance of the soil overlying shield tunnels significantly impacts their anti-floating stability.However,research on uplift resistance concerning special-shaped shield tunnels is limited.This study combines numerical simulation with machine learning techniques to explore this issue.It presents a summary of special-shaped tunnel geometries and introduces a shape coefficient.Through the finite element software,Plaxis3D,the study simulates six key parameters—shape coefficient,burial depth ratio,tunnel’s longest horizontal length,internal friction angle,cohesion,and soil submerged bulk density—that impact uplift resistance across different conditions.Employing XGBoost and ANN methods,the feature importance of each parameter was analyzed based on the numerical simulation results.The findings demonstrate that a tunnel shape more closely resembling a circle leads to reduced uplift resistance in the overlying soil,whereas other parameters exhibit the contrary effects.Furthermore,the study reveals a diminishing trend in the feature importance of buried depth ratio,internal friction angle,tunnel longest horizontal length,cohesion,soil submerged bulk density,and shape coefficient in influencing uplift resistance.
基金supported by the National Natural Science Foundation of China(32271580,42020104009)the Fundamental Research Funds for Zhejiang Provincial Universities and Research Institutes(JX6311101923)。
文摘Mytilus contain abundant antimicrobial peptides(AMPs)that play a key role in the innate immunity.However,heterologous production of these AMPs remains challenging due to their short sequences,multiple disulfide bonds,and high content of cationic amino acids,which hinder functional expression in prokaryotic systems such as Escherichia coli.To establish a eukaryotic recombinant expression system for the AMPs of mussel and obtain recombinant mussel AMPs for subsequent studies,we reported the successful recombinant expression of myticofensin B1,a novel defensin-like AMP identified previously in Mytiluscoruscus,using the eukaryotic host Pichia pastoris.The codon-optimized gene encoding the mature myticofensin-B1(composed of 65 amino acid residues,including 6 conserved cysteine residues)was cloned into a pPICZαA vector and expressed in P.pastoris GS115.Structural fidelity of the recombinant peptide was confirmed by liquid chromatography-tandem mass spectrometry(LC-MS/MS),showing a molecular weight of 8849.9 Da,which was consistent with the theoretical prediction.Functional assays demonstrated a broad-spectrum antimicrobial activity of the recombinant myticofensin-B1,with stronger inhibition against Gram-negative bacteria.Scanning electron microscopy revealed different effects of the recombinant myticofensin-B1 against different bacteria.In addition,the recombinant myticofensin-B1 exhibited a very low hemolytic activity against sheep red blood cells and weak cytotoxicity against human A549 lung cancer cells.This study establishes P.pastoris as a powerful platform to produce functional mussel AMP and highlights the potential of the recombinant myticofensin-B1 as a therapeutic agent for aquaculture pathogens and infections.
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 Russian Science Foundation(Grant No.23-65-10017 to B.K.K.and M.K.)The Ministry of Science and Higher Education of the Russian Federation(Grant No.122020300042-4 to L.N.M.)supported the preparation of the minichapter titled"Opioids reduce inflammatory injury of the heart".
文摘Neutrophils,macrophages,CD3^(+),CD4^(+),and CD8^(+)T lymphocytes expressμ-,δ-,andκ-opioid receptors(ORs)with varying affinities for opioids.Mast cells express the atypical OR Mas-related G-protein-coupled receptor X2(MRGPRX2),which has a low affinity for morphine.Neutrophils and macrophages can synthesize and release endogenous opioid peptides.Activation of ORs enhances the synthesis of proinflammatory cytokines and the production of reactive oxygen species(ROS)in unstimulated leukocytes.Conversely,OR activation reduces proinflammatory cytokine synthesis in stimulated neutrophils and macrophages.Morphine inhibits Toll-like receptor 4(TLR4)expression in macrophages,thereby attenuating inflammation,whereas methadone induces ROS production in mast cells through TLR4 activation.Stimulation of TLR4 triggersβ-endorphin synthesis in macrophages.The production of proinflammatory cytokines and ROS contributes to cardiac reperfusion injury.Importantly,activation ofκ1-andμ-ORs suppresses proinflammatory cytokine production by leukocytes,thereby mitigating inflammatory injury to the heart and other organs.
