E-learning platforms support education systems worldwide, transferring theoretical knowledge as well as soft skills. In the present study high-school pupils’, and adult students’ opinions were evaluated through a mo...E-learning platforms support education systems worldwide, transferring theoretical knowledge as well as soft skills. In the present study high-school pupils’, and adult students’ opinions were evaluated through a modern structured MOODLE interactive course, designed for the needs of the laboratory course “Automotive Systems”. The study concerns Greek secondary vocational education pupils aged 18 and vocational training adult students aged 20 to 50 years. The multistage, equal size simple random cluster sample was used as a sampling method. Pupils and adult students of each cluster completed structured 10-question questionnaires both before and after attending the course. A total of 120 questionnaires were collected. In general, our findings disclosed that the majority of pupils and adult students had significantly improved their knowledge and skills from using MOODLE. They reported strengthening conventional teaching, using the new MOODLE technology. The satisfaction indices improved quite, with the differences in their mean values being statistically significant.展开更多
To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we establishe...To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we established an in vitro transfection of human HO-1 gene into rat VSMC mediated by a retroviral vector. The results showed that the profound expression of HO-1 protein as well as HO activity was 1.8- and 2.0-fold increased respectively in the transfected cells compared to the non-transfected ones. The treatment of VSMC with different concentrations of H2O2 led to the remarkable cell damage as indicated by survival rate and LDH leakage. However, the resistance of the HO-1 transfected VSMC against H2O2 was significantly raised. This protective effect was dramatically diminished when the transfected VSMC were pretreated with ZnPP-IX, a specific inhibitor of HO, for 24 h. In addition, we found that the growth potential of the transfected cells was significantly inhibited directly by increased activity of HO-1, and this effect might be related to decreased phosphorylation of MAPK. These results suggest that the overexpression of introduced hHO-1 is potentially able to reduce the risk factors of atherosclerosis, partially due to its cellular protection against oxidative injury and to its inhibitory effect on cellular proliferation.展开更多
To address the critical gap in linking multi-compartmental transfer with risks of trace metals(Cd,Pb,As,Cr,Ni)in mining environments.This study systematically investigated the trans-media migration of Cd,Pb,As,Cr,and ...To address the critical gap in linking multi-compartmental transfer with risks of trace metals(Cd,Pb,As,Cr,Ni)in mining environments.This study systematically investigated the trans-media migration of Cd,Pb,As,Cr,and Ni in China’s Dexing copper mining district through paired sampling of water-amphibians,soil-earthworms,and air-lichens.Advanced methodologies were employed,including ICP-MS quantification for heavy metals,geochemical indices(Igeo,BCF,BAF)to assess bioavailability,NMDS for source apportionment,and HPLC to detect DNA methylation alterations.Aquatic systems exhibited severe Cd/Pb enrichment(16.25-24.42μg/L;11-15×WHO limits),while agricultural soils showed extreme Cd contamination(1.5 mg/kg;15×background).Biota displayed metal-specific accumulation:frogs achieved BCFs>1,000 for Pb/Cd,earthworms showed pH-modulated BAFs>2.5 for Cd/As,and lichens recorded 100-1,000×atmospheric Cr enrichment.NMDS resolved three contamination pathways:mining-derived Cd/Pb/As(MDS1=2.56),atmospheric Cr(PC2=1.84),and geogenic Ni.Cd dominated ecological risks(Eri=554.25;RI 300),while atmospheric Cr drove carcinogenic risks(TCR=4.11×10^(-5))exceeding safety thresholds.The source-media-biota-risk framework pioneers the integration of geochemical transport with epigenetic toxicity biomarkers,demonstrating that sub-lethal Cd/Pb exposure induces genome-wide DNA hypomethylation(2.4%-6.6%reduction;ρ=−0.71 to−0.91).This paradigm shift prioritizes bioavailability-informed regulations over concentration-based metrics,offering actionable strategies for sustainable development goals-aligned mining pollution control.展开更多
Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzhei...Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.展开更多
Metabolic syndrome-comprising central adiposity,dyslipidaemia,insulin resis-tance,and hypertension-is a major risk factor for cardiometabolic diseases such as ischaemic heart disease,stroke,and type 2 diabetes.Its glo...Metabolic syndrome-comprising central adiposity,dyslipidaemia,insulin resis-tance,and hypertension-is a major risk factor for cardiometabolic diseases such as ischaemic heart disease,stroke,and type 2 diabetes.Its global prevalence is rising,largely driven by urbanization,sedentary lifestyles,and dietary changes.These same factors are also associated with the increasing incidence of inflammatory bowel diseases(IBD),including Crohn’s disease and ulcerative colitis.Emerging evidence supports a potential biological link between chronic gastrointestinal inflammation and the later development of cardiometabolic disorders;a con-nection that is particularly relevant for patients with IBD.Comparative studies examining cardiometabolic risk associated with Crohn’s disease versus ulcerative colitis have reported inconsistent findings,likely due to confounding factors such as age,lifestyle,and comorbidities.This review summarizes current evidence linking IBD and cardiometabolic disorders,and highlights the need for clinicians to recognize cardiometabolic risk in patients with IBD.Future research should investigate whether treat-to-target strategies focused on controlling intestinal inflammation can simultaneously improve both long-term IBD and cardiometabolic outcomes.展开更多
The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions and metabolic levels.Mitochondria-associated endoplasmic reticulum membranes serve as ph...The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions and metabolic levels.Mitochondria-associated endoplasmic reticulum membranes serve as physical contact channels between the endoplasmic reticulum membrane and the mitochondrial outer membrane,formed by various proteins and protein complexes.This microstructural domain mediates several specialized functions,including calcium(Ca^(2+))signaling,autophagy,mitochondrial morphology,oxidative stress response,and apoptosis.Notably,the dysregulation of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes is a critical factor in the pathogenesis of neurological diseases.Certain proteins or protein complexes within these membranes directly or indirectly regulate the distance between the endoplasmic reticulum and mitochondria,as well as the transduction of Ca^(2+)signaling.Conversely,Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes influences other mitochondria-associated endoplasmic reticulum membraneassociated functions.These functions can vary significantly across different neurological diseases—such as ischemic stroke,traumatic brain injury,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,and Huntington's disease—and their respective stages of progression.Targeted modulation of these disease-related pathways and functional proteins can enhance neurological function and promote the regeneration and repair of damaged neurons.Therefore,mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling plays a pivotal role in the pathological progression of neurological diseases and represents a significant potential therapeutic target.This review focuses on the effects of protein complexes in mitochondria-associated endoplasmic reticulum membranes and the distinct roles of mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling in neurological diseases,specifically highlighting the early protective effects and neuronal damage that can result from prolonged mitochondrial Ca^(2+)overload or deficiency.This article provides a comprehensive analysis of the various mechanisms of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes in neurological diseases,contributing to the exploration of potential therapeutic targets for promoting neuroprotection and nerve repair.展开更多
Beginning with a 5D homogeneous universe [1], we have provided a plausible explanation of the self-rotation phenomenon of stellar objects previously with illustration of large number of star samples [2], via a 5D-4D p...Beginning with a 5D homogeneous universe [1], we have provided a plausible explanation of the self-rotation phenomenon of stellar objects previously with illustration of large number of star samples [2], via a 5D-4D projection. The origin of such rotation is the balance of the angular momenta of stars and that of positive and negative charged e-trino pairs, within a 3D ⊗1D?void of the stellar object, the existence of which is based on conservation/parity laws in physics if one starts with homogeneous 5D universe. While the in-phase e-trino pairs are proposed to be responsible for the generation of angular momentum, the anti-phase but oppositely charge pairs necessarily produce currents. In the 5D to 4D projection, one space variable in the 5D manifold was compacted to zero in most other 5D theories (including theories of Kaluza-Klein and Einstein [3] [4]). We have demonstrated, using the Fermat’s Last Theorem [5], that for validity of gauge invariance at the 4D-5D boundary, the 4th space variable in the 5D manifold is mapped into two current rings at both magnetic poles as required by Perelman entropy mapping;these loops are the origin of the dipolar magnetic field. One conclusion we draw is that there is no gravitational singularity, and hence no black holes in the universe, a result strongly supported by the recent discovery of many stars with masses well greater than 100 solar mass [6] [7] [8], without trace of phenomena observed (such as strong gamma and X ray emissions), which are supposed to be associated with black holes. We analyze the properties of such loop currents on the 4D-5D boundary, where Maxwell equations are valid. We derive explicit expressions for the dipolar fields over the whole temperature range. We then compare our prediction with measured surface magnetic fields of many stars. Since there is coupling in distribution between the in-phase and anti-phase pairs of e-trinos, the generated mag-netic field is directly related to the angular momentum, leading to the result that the magnetic field can be expressible in terms of only the mechanical variables (mass M, radius R, rotation period P)of a star, as if Maxwell equations are “hidden”. An explanation for the occurrence of this “un-expected result” is provided in Section (7.6). Therefore we provide satisfactory answers to a number of “mysteries” of magnetism in astrophysics such as the “Magnetic Bode’s Relation/Law” [9] and the experimental finding that B-P graph in the log-log plot is linear. Moreover, we have developed a new method for studying the relations among the data (M, R, P) during stellar evolution. Ten groups of stellar objects, effectively over 2000 samples are used in various parts of the analysis. We also explain the emergence of huge magnetic field in very old stars like White Dwarfs in terms of formation of 2D Semion state on stellar surface and release of magnetic flux as magnetic storms upon changing the 2D state back to 3D structure. Moreover, we provide an explanation, on the ground of the 5D theory, for the detection of extremely weak fields in Venus and Mars and the asymmetric distribution of magnetic field on the Martian surface. We predict the equatorial fields B of the newly discovered Trappist-1 star and the 6 nearest planets. The log B?−?log P graph for the 6 planets is linear and they satisfy the Magnetic Bode’s relation. Based on the above analysis, we have discovered several new laws of stellar magnetism, which are summarized in Section (7.6).展开更多
In this research we are going to define two new concepts: a) “The Potential of Events” (EP) and b) “The Catholic Information” (CI). The term CI derives from the ancient Greek language and declares all the Catholic...In this research we are going to define two new concepts: a) “The Potential of Events” (EP) and b) “The Catholic Information” (CI). The term CI derives from the ancient Greek language and declares all the Catholic (general) Logical Propositions (<img src="Edit_5f13a4a5-abc6-4bc5-9e4c-4ff981627b2a.png" width="33" height="21" alt="" />) which will true for every element of a set A. We will study the Riemann Hypothesis in two stages: a) By using the EP we will prove that the distribution of events e (even) and o (odd) of Square Free Numbers (SFN) on the axis Ax(N) of naturals is Heads-Tails (H-T) type. b) By using the CI we will explain the way that the distribution of prime numbers can be correlated with the non-trivial zeros of the function ζ(s) of Riemann. The Introduction and the Chapter 2 are necessary for understanding the solution. In the Chapter 3 we will present a simple method of forecasting in many very useful applications (e.g. financial, technological, medical, social, etc) developing a generalization of this new, proven here, theory which we finally apply to the solution of RH. The following Introduction as well the Results with the Discussion at the end shed light about the possibility of the proof of all the above. The article consists of 9 chapters that are numbered by 1, 2, …, 9.展开更多
Multiferroic tunnel junctions(MFTJs),which combine tunneling magnetoresistance(TMR)and electroresistance(TER)efects,have emerged as key candidates for data storage.Two-dimensional van der Waals(vdW)MFTJs,in particular...Multiferroic tunnel junctions(MFTJs),which combine tunneling magnetoresistance(TMR)and electroresistance(TER)efects,have emerged as key candidates for data storage.Two-dimensional van der Waals(vdW)MFTJs,in particular,are promising spintronic devices for the post-Moore era.However,these vdW MFTJs are typically based on multiferroics composed of ferromagnetic and ferroelectric materials or multilayer magnetic materials with sliding ferroelectricity,which increases device fabrication complexity.In this work,we design a vdW MFTJ using bilayer MoPtGe_(2)S_(6),a material with homologous multiferroicity in each monolayer,combined with symmetric PtTe_(2)electrodes.Using frst-principles calculations based on density functional theory and nonequilibrium Green's functions,we theoretically explore the spin-polarized electronic transport properties of this MFTJ.By controlling the ferroelectric and ferromagnetic polarization directions of bilayer MoPtGe_(2)S_(6),the MFTJ can exhibit six distinct non-volatile resistance states,with maximum TMR(137%)and TER(1943%)ratios.Under biaxial strain,TMR and TER can increase to 265%and 4210%,respectively.The TER ratio also increases to 2186%under a 0.1 V bias voltage.Remarkably,the MFTJ exhibits a pronounced spin-fltering and a signifcant negative diferential resistance efect.These fndings not only highlight the potential of monolayer multiferroic MoPtGe_(2)S_(6)for MFTJs but also ofer valuable theoretical insights for future experimental investigations.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
In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of A...In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.展开更多
AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines ...AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action. METHODS: Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS: NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG(53.7%, P 【 0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone (DEX)and iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x L(-1)) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol x L(-1)) under similar stimuli conditions (P【0.01). CONCLUSION: AG is a potent selective inhibitor of inducible isoform of NOS,and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.展开更多
With the gradual advancement of research methods and technologies,various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases.However,current descriptions of th...With the gradual advancement of research methods and technologies,various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases.However,current descriptions of these biological processes do not fully explain the onset,progression,and development of these conditions.Therefore,exploration of the pathogenesis of neurodegenerative diseases remains a valuable area of research.This review summarizes the potential common pathogeneses of Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,Huntington’s disease,frontotemporal lobar dementia,and Lewy body disease.Research findings have indicated that several common biological processes,including aging,genetic factors,progressive neuronal dysfunction,neuronal death and apoptosis,protein misfolding and aggregation,neuroinflammation,mitochondrial dysfunction,axonal transport defects,and gut microbiota dysbiosis,are involved in the pathogenesis of these six neurodegenerative diseases.Based on current information derived from diverse areas of research,these biological processes may form complex pathogenic networks that lead to distinctive types of neuronal death in neurodegenerative diseases.Furthermore,promoting the regeneration of damaged neurons may be achievable through the repair of affected neural cells if the underlying pathogenesis can be prevented or reversed.Hence,these potential common biological processes may represent only very small,limited elements within numerous intricate pathogenic networks associated with neurodegenerative diseases.In clinical treatment,interfering with any single biological process has proven insufficient to completely halt the progression of neurodegenerative diseases.Therefore,future research on the pathogenesis of neurodegenerative diseases should focus on uncovering the complex pathogenic networks,rather than isolating individual biological processes.Based on this,therapies that aim to block or reverse various targets involved in the potential pathogenic mechanisms of neurodegenerative diseases may be promising directions,as current treatment methods that focus on halting a single pathogenic factor have not achieved satisfactory efficacy.展开更多
In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,...In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,allowing them to target deep brain lesions.Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines,mRNAs,and disease-related proteins,thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects.However,exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells.This limitation can lead to side effects and toxicity when they interact with non-specific cells.Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases.In this review,we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases.Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases.We introduce the strategies being used to enhance exosome targeting,including genetic engineering,chemical modifications(both covalent,such as click chemistry and metabolic engineering,and non-covalent,such as polyvalent electrostatic and hydrophobic interactions,ligand-receptor binding,aptamer-based modifications,and the incorporation of CP05-anchored peptides),and nanomaterial modifications.Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases.However,several challenges remain in the clinical application of exosomes.Improvements are needed in preparation,characterization,and optimization methods,as well as in reducing the adverse reactions associated with their use.Additionally,the range of applications and the safety of exosomes require further research and evaluation.展开更多
The recent study published by Lee et al examined the discrepancies between endoscopic and histologic evaluations of mucosal inflammation in active ileal Crohn’s disease(CD).While this research contributes to our unde...The recent study published by Lee et al examined the discrepancies between endoscopic and histologic evaluations of mucosal inflammation in active ileal Crohn’s disease(CD).While this research contributes to our understanding of the limitations of current biopsy protocols,it raises several concerns about the generalizability of its findings,sample size,and methodology.One major limitation was the exclusion of patients with ileal strictures,ileostomies,or J-pouches,which reduced the applicability of the results to the wider CD population.Furthermore,the biopsy protocol's focus on single biopsies from specific locations may inadequately capture the patchy inflammation characteristic of CD.The study also uses histologic indices primarily developed for ulcerative colitis,which may not be suitable for assessing CD.It is recommended that multi-center studies be conducted and histologic indices specific to CD be developed to improve the relevance of future research.Additionally,researchers should consider the influence of treatment regimens on the findings.Addressing these limitations would enhance the clinical significance of the study and inform better diagnostic and therapeutic approaches for CD.展开更多
Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have ...Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging population.Posture and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous mechanisms.To effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory signals.The mechanisms which underpin the integration of these multisensory signals are the principal topic of the present work.Existing multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older adults.Insufficient emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and balance.In the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s disease.We also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older adults.Lastly,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.展开更多
Space was once a distant dream for African nations like Senegal.But that is changing fast.Today,space is emerging as a strategic frontier for the continent,with 22 countries including Senegal now operating national sp...Space was once a distant dream for African nations like Senegal.But that is changing fast.Today,space is emerging as a strategic frontier for the continent,with 22 countries including Senegal now operating national space agencies.Senegal launched its own agency,the Senegalese Space Study Agency(ASES),in March 2023.The recent inauguration of the African Space Agency’s headquarters in Cairo,Egypt,marks a new chapter in Africa’s rising ambitions beyond Earth.Tasked with coordinating national programmes,the agency seeks to drive economic and social development through space technologies while promoting scientific cooperation both within Africa and internationally.展开更多
AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human...AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.展开更多
The nucleotide sequence deduced from the amino acid sequence of the scorpion insectotoxin AaIT was chemically synthesized and was expressed in Escherichia coli. The authenticity of this in vitro expressed peptide was ...The nucleotide sequence deduced from the amino acid sequence of the scorpion insectotoxin AaIT was chemically synthesized and was expressed in Escherichia coli. The authenticity of this in vitro expressed peptide was confirmed by N-terminal peptide sequencing. Two groups of bioassays, artificial diet incorporation assay and contact insecticidal effect assay, were carried out separately to verify the toxicity of this recombinant toxin. At the end of a 24 h experimental period, more than 60% of the testing diamondback moth (Plutella xylostella) larvae were killed in both groups with LC50 value of 18.4 microM and 0.70 microM respectively. Cytotoxicity assay using cultured Sf9 insect cells and MCF-7 human cells demonstrated that the toxin AaIT had specific toxicity against insect cells but not human cells. Only 0.13 microM recombinant toxin was needed to kill 50% of cultured insect cells while as much as 1.3 microM toxin had absolutely no effect on human cells. Insect cells produced obvious intrusions from their plasma membrane before broken up. We infer that toxin AaIT bind to a putative sodium channel in these insect cells and open the channel persistently, which would result in Na+ influx and finally cause destruction of insect cells.展开更多
While celebrating 50 years of diplomatic ties,China and the EU are deepening their strategic partnership to counter U.S.-China tensions and Europe’s own geopolitical and economic challenges.
文摘E-learning platforms support education systems worldwide, transferring theoretical knowledge as well as soft skills. In the present study high-school pupils’, and adult students’ opinions were evaluated through a modern structured MOODLE interactive course, designed for the needs of the laboratory course “Automotive Systems”. The study concerns Greek secondary vocational education pupils aged 18 and vocational training adult students aged 20 to 50 years. The multistage, equal size simple random cluster sample was used as a sampling method. Pupils and adult students of each cluster completed structured 10-question questionnaires both before and after attending the course. A total of 120 questionnaires were collected. In general, our findings disclosed that the majority of pupils and adult students had significantly improved their knowledge and skills from using MOODLE. They reported strengthening conventional teaching, using the new MOODLE technology. The satisfaction indices improved quite, with the differences in their mean values being statistically significant.
基金This work was kindly supported by Na-tional Natural Science Foundation of China(No.39670308)
文摘To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we established an in vitro transfection of human HO-1 gene into rat VSMC mediated by a retroviral vector. The results showed that the profound expression of HO-1 protein as well as HO activity was 1.8- and 2.0-fold increased respectively in the transfected cells compared to the non-transfected ones. The treatment of VSMC with different concentrations of H2O2 led to the remarkable cell damage as indicated by survival rate and LDH leakage. However, the resistance of the HO-1 transfected VSMC against H2O2 was significantly raised. This protective effect was dramatically diminished when the transfected VSMC were pretreated with ZnPP-IX, a specific inhibitor of HO, for 24 h. In addition, we found that the growth potential of the transfected cells was significantly inhibited directly by increased activity of HO-1, and this effect might be related to decreased phosphorylation of MAPK. These results suggest that the overexpression of introduced hHO-1 is potentially able to reduce the risk factors of atherosclerosis, partially due to its cellular protection against oxidative injury and to its inhibitory effect on cellular proliferation.
基金financially supported by the Fundation of Key Laboratory of Ministry of Natural Resources for Eco-geochemistry (ZSDHJJ202202)Geological Investigation and Evaluation of Shale Gas in Complex Structural Areas of the Middle Yangtze plate(DD20250200604) of China Geological Survey+1 种基金the Natural Science Foundation of Guangdong Province,China(2023A1515140061)the Dongguan Science and Technology of Social Development Program(20231800935842, 20231800940562).
文摘To address the critical gap in linking multi-compartmental transfer with risks of trace metals(Cd,Pb,As,Cr,Ni)in mining environments.This study systematically investigated the trans-media migration of Cd,Pb,As,Cr,and Ni in China’s Dexing copper mining district through paired sampling of water-amphibians,soil-earthworms,and air-lichens.Advanced methodologies were employed,including ICP-MS quantification for heavy metals,geochemical indices(Igeo,BCF,BAF)to assess bioavailability,NMDS for source apportionment,and HPLC to detect DNA methylation alterations.Aquatic systems exhibited severe Cd/Pb enrichment(16.25-24.42μg/L;11-15×WHO limits),while agricultural soils showed extreme Cd contamination(1.5 mg/kg;15×background).Biota displayed metal-specific accumulation:frogs achieved BCFs>1,000 for Pb/Cd,earthworms showed pH-modulated BAFs>2.5 for Cd/As,and lichens recorded 100-1,000×atmospheric Cr enrichment.NMDS resolved three contamination pathways:mining-derived Cd/Pb/As(MDS1=2.56),atmospheric Cr(PC2=1.84),and geogenic Ni.Cd dominated ecological risks(Eri=554.25;RI 300),while atmospheric Cr drove carcinogenic risks(TCR=4.11×10^(-5))exceeding safety thresholds.The source-media-biota-risk framework pioneers the integration of geochemical transport with epigenetic toxicity biomarkers,demonstrating that sub-lethal Cd/Pb exposure induces genome-wide DNA hypomethylation(2.4%-6.6%reduction;ρ=−0.71 to−0.91).This paradigm shift prioritizes bioavailability-informed regulations over concentration-based metrics,offering actionable strategies for sustainable development goals-aligned mining pollution control.
基金financially supported by the National Natural Science Foundation of China,No.823 74552 (to WP)the Science and Technology Innovation Program of Hunan Province,No.2022RC1220 (to WP)+1 种基金the Natural Science Foundation of Hunan Province of China,Nos.2020JJ4803 (to WP),2022JJ40723 (to MY)the Scientific Research Launch Project for New Employees of the Second Xiangya Hospital of Central South University (to MY)
文摘Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.
文摘Metabolic syndrome-comprising central adiposity,dyslipidaemia,insulin resis-tance,and hypertension-is a major risk factor for cardiometabolic diseases such as ischaemic heart disease,stroke,and type 2 diabetes.Its global prevalence is rising,largely driven by urbanization,sedentary lifestyles,and dietary changes.These same factors are also associated with the increasing incidence of inflammatory bowel diseases(IBD),including Crohn’s disease and ulcerative colitis.Emerging evidence supports a potential biological link between chronic gastrointestinal inflammation and the later development of cardiometabolic disorders;a con-nection that is particularly relevant for patients with IBD.Comparative studies examining cardiometabolic risk associated with Crohn’s disease versus ulcerative colitis have reported inconsistent findings,likely due to confounding factors such as age,lifestyle,and comorbidities.This review summarizes current evidence linking IBD and cardiometabolic disorders,and highlights the need for clinicians to recognize cardiometabolic risk in patients with IBD.Future research should investigate whether treat-to-target strategies focused on controlling intestinal inflammation can simultaneously improve both long-term IBD and cardiometabolic outcomes.
基金supported by Yunnan Province Innovation Team of Prevention and Treatment for Brain Disease with Acupuncture and Tuina,No.202405AS350007Youth Top Talent Project of 10-thousand Talent Plan in Yunnan Province,No.YNWR-QNBJ-2018-345+3 种基金the National Natural Science Foundation of China,No.81960731Joint Special Project of Traditional Chinese Medicine in Science and Technology Department of Yunnan Province,Nos.2019FF002[-008],202001AZ070001-002 and 202001AZ070001-030Yunnan Province University Innovation Team Projects No.2019YGC04Yunnan Province Project Education Fund,Nos.2024Y406,2024Y414(all to PZ)。
文摘The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions and metabolic levels.Mitochondria-associated endoplasmic reticulum membranes serve as physical contact channels between the endoplasmic reticulum membrane and the mitochondrial outer membrane,formed by various proteins and protein complexes.This microstructural domain mediates several specialized functions,including calcium(Ca^(2+))signaling,autophagy,mitochondrial morphology,oxidative stress response,and apoptosis.Notably,the dysregulation of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes is a critical factor in the pathogenesis of neurological diseases.Certain proteins or protein complexes within these membranes directly or indirectly regulate the distance between the endoplasmic reticulum and mitochondria,as well as the transduction of Ca^(2+)signaling.Conversely,Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes influences other mitochondria-associated endoplasmic reticulum membraneassociated functions.These functions can vary significantly across different neurological diseases—such as ischemic stroke,traumatic brain injury,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,and Huntington's disease—and their respective stages of progression.Targeted modulation of these disease-related pathways and functional proteins can enhance neurological function and promote the regeneration and repair of damaged neurons.Therefore,mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling plays a pivotal role in the pathological progression of neurological diseases and represents a significant potential therapeutic target.This review focuses on the effects of protein complexes in mitochondria-associated endoplasmic reticulum membranes and the distinct roles of mitochondria-associated endoplasmic reticulum membranes-mediated Ca^(2+)signaling in neurological diseases,specifically highlighting the early protective effects and neuronal damage that can result from prolonged mitochondrial Ca^(2+)overload or deficiency.This article provides a comprehensive analysis of the various mechanisms of Ca^(2+)signaling mediated by mitochondria-associated endoplasmic reticulum membranes in neurological diseases,contributing to the exploration of potential therapeutic targets for promoting neuroprotection and nerve repair.
文摘Beginning with a 5D homogeneous universe [1], we have provided a plausible explanation of the self-rotation phenomenon of stellar objects previously with illustration of large number of star samples [2], via a 5D-4D projection. The origin of such rotation is the balance of the angular momenta of stars and that of positive and negative charged e-trino pairs, within a 3D ⊗1D?void of the stellar object, the existence of which is based on conservation/parity laws in physics if one starts with homogeneous 5D universe. While the in-phase e-trino pairs are proposed to be responsible for the generation of angular momentum, the anti-phase but oppositely charge pairs necessarily produce currents. In the 5D to 4D projection, one space variable in the 5D manifold was compacted to zero in most other 5D theories (including theories of Kaluza-Klein and Einstein [3] [4]). We have demonstrated, using the Fermat’s Last Theorem [5], that for validity of gauge invariance at the 4D-5D boundary, the 4th space variable in the 5D manifold is mapped into two current rings at both magnetic poles as required by Perelman entropy mapping;these loops are the origin of the dipolar magnetic field. One conclusion we draw is that there is no gravitational singularity, and hence no black holes in the universe, a result strongly supported by the recent discovery of many stars with masses well greater than 100 solar mass [6] [7] [8], without trace of phenomena observed (such as strong gamma and X ray emissions), which are supposed to be associated with black holes. We analyze the properties of such loop currents on the 4D-5D boundary, where Maxwell equations are valid. We derive explicit expressions for the dipolar fields over the whole temperature range. We then compare our prediction with measured surface magnetic fields of many stars. Since there is coupling in distribution between the in-phase and anti-phase pairs of e-trinos, the generated mag-netic field is directly related to the angular momentum, leading to the result that the magnetic field can be expressible in terms of only the mechanical variables (mass M, radius R, rotation period P)of a star, as if Maxwell equations are “hidden”. An explanation for the occurrence of this “un-expected result” is provided in Section (7.6). Therefore we provide satisfactory answers to a number of “mysteries” of magnetism in astrophysics such as the “Magnetic Bode’s Relation/Law” [9] and the experimental finding that B-P graph in the log-log plot is linear. Moreover, we have developed a new method for studying the relations among the data (M, R, P) during stellar evolution. Ten groups of stellar objects, effectively over 2000 samples are used in various parts of the analysis. We also explain the emergence of huge magnetic field in very old stars like White Dwarfs in terms of formation of 2D Semion state on stellar surface and release of magnetic flux as magnetic storms upon changing the 2D state back to 3D structure. Moreover, we provide an explanation, on the ground of the 5D theory, for the detection of extremely weak fields in Venus and Mars and the asymmetric distribution of magnetic field on the Martian surface. We predict the equatorial fields B of the newly discovered Trappist-1 star and the 6 nearest planets. The log B?−?log P graph for the 6 planets is linear and they satisfy the Magnetic Bode’s relation. Based on the above analysis, we have discovered several new laws of stellar magnetism, which are summarized in Section (7.6).
文摘In this research we are going to define two new concepts: a) “The Potential of Events” (EP) and b) “The Catholic Information” (CI). The term CI derives from the ancient Greek language and declares all the Catholic (general) Logical Propositions (<img src="Edit_5f13a4a5-abc6-4bc5-9e4c-4ff981627b2a.png" width="33" height="21" alt="" />) which will true for every element of a set A. We will study the Riemann Hypothesis in two stages: a) By using the EP we will prove that the distribution of events e (even) and o (odd) of Square Free Numbers (SFN) on the axis Ax(N) of naturals is Heads-Tails (H-T) type. b) By using the CI we will explain the way that the distribution of prime numbers can be correlated with the non-trivial zeros of the function ζ(s) of Riemann. The Introduction and the Chapter 2 are necessary for understanding the solution. In the Chapter 3 we will present a simple method of forecasting in many very useful applications (e.g. financial, technological, medical, social, etc) developing a generalization of this new, proven here, theory which we finally apply to the solution of RH. The following Introduction as well the Results with the Discussion at the end shed light about the possibility of the proof of all the above. The article consists of 9 chapters that are numbered by 1, 2, …, 9.
基金supported by the National Key R&D Program of China(Grant No.2022YFB3505301)the National Key R&D Program of Shanxi Province(Grant No.202302050201014)+1 种基金the National Natural Science Foundation of China(Grant No.12304148)the Natural Science Basic Research Program of Shanxi Province(Grant No.202203021222219)。
文摘Multiferroic tunnel junctions(MFTJs),which combine tunneling magnetoresistance(TMR)and electroresistance(TER)efects,have emerged as key candidates for data storage.Two-dimensional van der Waals(vdW)MFTJs,in particular,are promising spintronic devices for the post-Moore era.However,these vdW MFTJs are typically based on multiferroics composed of ferromagnetic and ferroelectric materials or multilayer magnetic materials with sliding ferroelectricity,which increases device fabrication complexity.In this work,we design a vdW MFTJ using bilayer MoPtGe_(2)S_(6),a material with homologous multiferroicity in each monolayer,combined with symmetric PtTe_(2)electrodes.Using frst-principles calculations based on density functional theory and nonequilibrium Green's functions,we theoretically explore the spin-polarized electronic transport properties of this MFTJ.By controlling the ferroelectric and ferromagnetic polarization directions of bilayer MoPtGe_(2)S_(6),the MFTJ can exhibit six distinct non-volatile resistance states,with maximum TMR(137%)and TER(1943%)ratios.Under biaxial strain,TMR and TER can increase to 265%and 4210%,respectively.The TER ratio also increases to 2186%under a 0.1 V bias voltage.Remarkably,the MFTJ exhibits a pronounced spin-fltering and a signifcant negative diferential resistance efect.These fndings not only highlight the potential of monolayer multiferroic MoPtGe_(2)S_(6)for MFTJs but also ofer valuable theoretical insights for future experimental investigations.
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 STI2030-Major Projects,No.2021ZD 0201801(to JG)Shanxi Province Basic Research Program,No.20210302123429(to QS).
文摘In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.
基金Project supported by the National Natural Science Foundation of China,No.39770861.and JANSSEN Science Research Foundation.
文摘AIM: To study the effects of aminoguanidine (AG) and two L-arginine analogues N(omega)-nitro-L-arginine methyl ester (L-NAME) and N(omega)-nitro-L-arginine (L-NNA) on nitric oxide (NO) production induced by cytokines (TNF-alpha, IL-1 beta, and IFN-gamma) and bacterial lipopolysaccharide (LPS) mixture (CM) in the cultured rat hepatocytes, and examine their mechanisms action. METHODS: Rat hepatocytes were incubated with AG, L-NAME, L-NNA, Actinomycin D (ActD) and dexamethasone in a medium containing CM (LPS plus TNF-alpha, IL-1 beta, and IFN-gamma) for 24h. NO production in the cultured supernatant was measured with the Griess reaction. Intracellular cGMP level was detected with radioimmunoassy. RESULTS: NO production was markedly blocked by AG and L-NAME in a dose-dependent manner under inflammatory stimuli condition triggered by CM in vitro. The rate of the maximum inhibitory effects of L-NAME (38.9%) was less potent than that obtained with AG(53.7%, P 【 0.05). There was no significant difference between the inhibitory effects of AG and two L-arginine analogues on intracellular cGMP accumulation in rat cultured hepatocytes. Non-specific NOS expression inhibitor dexamethasone (DEX)and iNOS mRNA transcriptional inhibitor ActD also significantly inhibited CM-induced NO production. AG(0.1 mmol x L(-1)) and ActD (0.2 ng x L(-1)) were equipotent in decreasing NO production induced by inflammatory stimuli in vitro, and both effects were more potent than that induced by non-selectivity NOS activity inhibitor L-NAME (0.1 mmol x L(-1)) under similar stimuli conditions (P【0.01). CONCLUSION: AG is a potent selective inhibitor of inducible isoform of NOS,and the mechanism of action may be not only competitive inhibition in the substrate level, but also the gene expression level in rat hepatocytes.
基金supported by the National Natural Science Foundation of China,No.82160255(to RX)the Natural Science Foundation of Jiangxi Province,No.20212BAB216026(to HL)+2 种基金Science and Technology Plan Project of Health Commission of Jiangxi Province,No.202110016(to HL)Science and Technology Plan Project of Jiangxi Provincial Administration of Traditional Chinese Medicine,No.2022B975(to HL)a grant from Jiangxi Province Key Laboratory of Neurology,No.2024SSY06081(to RX).
文摘With the gradual advancement of research methods and technologies,various biological processes have been identified as playing roles in the pathogenesis of neurodegenerative diseases.However,current descriptions of these biological processes do not fully explain the onset,progression,and development of these conditions.Therefore,exploration of the pathogenesis of neurodegenerative diseases remains a valuable area of research.This review summarizes the potential common pathogeneses of Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,Huntington’s disease,frontotemporal lobar dementia,and Lewy body disease.Research findings have indicated that several common biological processes,including aging,genetic factors,progressive neuronal dysfunction,neuronal death and apoptosis,protein misfolding and aggregation,neuroinflammation,mitochondrial dysfunction,axonal transport defects,and gut microbiota dysbiosis,are involved in the pathogenesis of these six neurodegenerative diseases.Based on current information derived from diverse areas of research,these biological processes may form complex pathogenic networks that lead to distinctive types of neuronal death in neurodegenerative diseases.Furthermore,promoting the regeneration of damaged neurons may be achievable through the repair of affected neural cells if the underlying pathogenesis can be prevented or reversed.Hence,these potential common biological processes may represent only very small,limited elements within numerous intricate pathogenic networks associated with neurodegenerative diseases.In clinical treatment,interfering with any single biological process has proven insufficient to completely halt the progression of neurodegenerative diseases.Therefore,future research on the pathogenesis of neurodegenerative diseases should focus on uncovering the complex pathogenic networks,rather than isolating individual biological processes.Based on this,therapies that aim to block or reverse various targets involved in the potential pathogenic mechanisms of neurodegenerative diseases may be promising directions,as current treatment methods that focus on halting a single pathogenic factor have not achieved satisfactory efficacy.
基金supported by the National Natural Science Foundation of China,No.22103055(to JG)the Natural Science Foundation of Hebei Province,No.F2024110001(to HC)Open Project of Tianjin Key Laboratory of Optoelectronic Detection Technology and System,Nos.2024LODTS215(to NL),2024LODTS216(to XS).
文摘In recent years,exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research.Exosomes are small and can effectively cross the blood-brain barrier,allowing them to target deep brain lesions.Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines,mRNAs,and disease-related proteins,thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects.However,exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells.This limitation can lead to side effects and toxicity when they interact with non-specific cells.Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases.In this review,we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases.Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases.We introduce the strategies being used to enhance exosome targeting,including genetic engineering,chemical modifications(both covalent,such as click chemistry and metabolic engineering,and non-covalent,such as polyvalent electrostatic and hydrophobic interactions,ligand-receptor binding,aptamer-based modifications,and the incorporation of CP05-anchored peptides),and nanomaterial modifications.Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases.However,several challenges remain in the clinical application of exosomes.Improvements are needed in preparation,characterization,and optimization methods,as well as in reducing the adverse reactions associated with their use.Additionally,the range of applications and the safety of exosomes require further research and evaluation.
文摘The recent study published by Lee et al examined the discrepancies between endoscopic and histologic evaluations of mucosal inflammation in active ileal Crohn’s disease(CD).While this research contributes to our understanding of the limitations of current biopsy protocols,it raises several concerns about the generalizability of its findings,sample size,and methodology.One major limitation was the exclusion of patients with ileal strictures,ileostomies,or J-pouches,which reduced the applicability of the results to the wider CD population.Furthermore,the biopsy protocol's focus on single biopsies from specific locations may inadequately capture the patchy inflammation characteristic of CD.The study also uses histologic indices primarily developed for ulcerative colitis,which may not be suitable for assessing CD.It is recommended that multi-center studies be conducted and histologic indices specific to CD be developed to improve the relevance of future research.Additionally,researchers should consider the influence of treatment regimens on the findings.Addressing these limitations would enhance the clinical significance of the study and inform better diagnostic and therapeutic approaches for CD.
文摘Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging population.Posture and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous mechanisms.To effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory signals.The mechanisms which underpin the integration of these multisensory signals are the principal topic of the present work.Existing multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older adults.Insufficient emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and balance.In the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s disease.We also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older adults.Lastly,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.
文摘Space was once a distant dream for African nations like Senegal.But that is changing fast.Today,space is emerging as a strategic frontier for the continent,with 22 countries including Senegal now operating national space agencies.Senegal launched its own agency,the Senegalese Space Study Agency(ASES),in March 2023.The recent inauguration of the African Space Agency’s headquarters in Cairo,Egypt,marks a new chapter in Africa’s rising ambitions beyond Earth.Tasked with coordinating national programmes,the agency seeks to drive economic and social development through space technologies while promoting scientific cooperation both within Africa and internationally.
文摘AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.
基金This work was supported by a grant from 863High Technology Program,Chinese Ministry of Sci-ence and Technology
文摘The nucleotide sequence deduced from the amino acid sequence of the scorpion insectotoxin AaIT was chemically synthesized and was expressed in Escherichia coli. The authenticity of this in vitro expressed peptide was confirmed by N-terminal peptide sequencing. Two groups of bioassays, artificial diet incorporation assay and contact insecticidal effect assay, were carried out separately to verify the toxicity of this recombinant toxin. At the end of a 24 h experimental period, more than 60% of the testing diamondback moth (Plutella xylostella) larvae were killed in both groups with LC50 value of 18.4 microM and 0.70 microM respectively. Cytotoxicity assay using cultured Sf9 insect cells and MCF-7 human cells demonstrated that the toxin AaIT had specific toxicity against insect cells but not human cells. Only 0.13 microM recombinant toxin was needed to kill 50% of cultured insect cells while as much as 1.3 microM toxin had absolutely no effect on human cells. Insect cells produced obvious intrusions from their plasma membrane before broken up. We infer that toxin AaIT bind to a putative sodium channel in these insect cells and open the channel persistently, which would result in Na+ influx and finally cause destruction of insect cells.
文摘While celebrating 50 years of diplomatic ties,China and the EU are deepening their strategic partnership to counter U.S.-China tensions and Europe’s own geopolitical and economic challenges.
