Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0...Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.展开更多
In this study,a framework for predicting the gas-sensitive properties of gas-sensitive materials by combining machine learning and density functional theory(DFT)has been proposed.The framework rapidly predicts the gas...In this study,a framework for predicting the gas-sensitive properties of gas-sensitive materials by combining machine learning and density functional theory(DFT)has been proposed.The framework rapidly predicts the gas response of materials by establishing relationships between multisource physical parameters and gas-sensitive properties.In order to prove its effectiveness,the perovskite Cs_(3)Cu_(2)I_(5) has been selected as the representative material.The physical parameters before and after the adsorption of various gases have been calculated using DFT,and then a machine learning model has been trained based on these parameters.Previous studies have shown that a single physical parameter alone is not enough to accurately predict the gas sensitivity of materials.Therefore,a variety of physical parameters have been selected for machine learning,and the final machine learning model achieved 92%accuracy in predicting gas sensitivity.It is important to note that although there have been no previous reports on the response of Cs_(3)Cu_(2)I_(5) to hydrogen sulfide,the resulting model predicts the gas response of H2S;it is subsequently confirmed experimentally.This method not only enhances the understanding of the gas sensing mechanism,but also has a universal nature,making it suitable for the development of various new gas-sensitive materials.展开更多
This paper examines an epidemic predator-prey model with prey dispersal and Holling type-II functional response. In this model, it is assumed that the predator population suffers a transmissible disease. By analyzing ...This paper examines an epidemic predator-prey model with prey dispersal and Holling type-II functional response. In this model, it is assumed that the predator population suffers a transmissible disease. By analyzing the corresponding characteristic equations, the local stability of each of feasible equilibria and the existence of Hopf bifurcations at the coexistence equilibrium is addressed. Using Lyapunov functionals and LaSalle's invariance principle, we obtained the sufficient conditions for the global stability of the trivial equilibrium, the predator-extinction equilibrium, the disease-free equilibrium and the coexistence equilibrium, respectively. The paper also includes numerical simulations to illustrate the analytical results.展开更多
Here we complete our work on the asymptotics of Hankel determinants studying the case wherein the entries are “ultrarapidly”-varying functions in the sense that their logarithms are rapidly varying. Moreover, the la...Here we complete our work on the asymptotics of Hankel determinants studying the case wherein the entries are “ultrarapidly”-varying functions in the sense that their logarithms are rapidly varying. Moreover, the last results in the paper highlight analogies between algebraic identities for Hankelians with special entries and asymptotic relations valid for large classes of entries.展开更多
Objective:To study the clinical value of combined detection of blood lipids,blood glucose,and liver function in non-alcoholic fatty liver disease.Methods:105 patients with non-alcoholic fatty liver disease treated in ...Objective:To study the clinical value of combined detection of blood lipids,blood glucose,and liver function in non-alcoholic fatty liver disease.Methods:105 patients with non-alcoholic fatty liver disease treated in our hospital from May 2022 to July 2024 were selected as the research subjects.All patients underwent a B-ultrasound examination.According to the severity of the disease,they were divided into group A(mild,n=35),group B(moderate,n=44),and group C(severe,n=26).Another 30 healthy residents who came to the hospital for physical examination during the same period were selected as group D.The differences in blood lipids,blood glucose,and liver function indicators between groups were compared.Results:The triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL)levels in groups A,B,and C were higher than those in group D,while the high-density lipoprotein cholesterol(HDL)level was lower(P<0.05).The fasting plasma glucose(FPG)levels in groups B and C were higher than those in group D(P<0.05).The TG,LDL,and FPG levels in groups B and C were higher than those in group A(P<0.05).The TC level in group C was higher than that in group A,while the HDL level was lower(P<0.05).The TC and FPG levels in group C were higher than those in group B(P<0.05).The total bilirubin(TBil),aspartate aminotransferase(AST),and alanine aminotransferase(ALT)levels in groups A,B,and C were higher than those in group D(P<0.05).The TBil and ALT levels in groups B and C were higher than those in group A(P<0.05).The AST level in group C was higher than that in group A(P<0.05).The AST and ALT levels in group C were higher than those in group B(P<0.05).Conclusion:Patients with non-alcoholic fatty liver disease have disordered glucose and lipid metabolism.Blood lipids,blood glucose,and liver function are closely related to the severity of the disease.Strengthening exercise and dietary intervention early on can help control the progression of simple fatty liver disease and reduce the risk of severe liver diseases such as steatohepatitis and cirrhosis.展开更多
BACKGROUND Appendicitis is a common acute abdominal pain disorder.Laparoscopic appendectomy,a commonly used modality,is associated with less trauma and faster recovery than traditional open appendectomy.However,postop...BACKGROUND Appendicitis is a common acute abdominal pain disorder.Laparoscopic appendectomy,a commonly used modality,is associated with less trauma and faster recovery than traditional open appendectomy.However,postoperative recovery remains an important issue that affects rehabilitation quality and surgical results.AIM To explore the effects of rapid rehabilitation and surgical nursing care on gastrointestinal function recovery and sleep quality among patients undergoing laparoscopic appendectomy.METHODS A total of 120 patients who underwent laparoscopic appendectomy at our hospital between January 2019 and March 2024 and for whom complete clinical data were available were selected.Patients were randomly assigned to two groups(n=60 each)using the random number table method.The control group received routine nursing care,while the experimental group received rapid rehabilitation surgical nursing care;all patients continued to receive nursing care until discharge.The recovery of gastrointestinal function,length of hospital stay,complications,Pittsburgh sleep quality index,and nursing satisfaction were compared between groups.RESULTS Following the implementation of effective nursing measures,the times to bowel sound recovery,first exhaust,first defecation,and first feeding were notably shorter in the study vs control group(P<0.05).Additionally,the duration of the first postoperative activity and the length of hospital stay were significantly shorter in the study vs control group(P<0.05).Furthermore,the study group exhibited better sleep quality than the control group(P<0.05).The postoperative complication rate was significantly lower and the nursing satisfaction rate significantly higher in the study vs control group(P<0.05).CONCLUSION Rapid rehabilitation surgical nursing interventions provided to patients after laparoscopic appendectomy can accelerate their postoperative recovery,reduce the occurrence of complications,and improve their sleep quality and nursing satisfaction.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
The mechanisms of mushroom polysaccharides on immune functions and lipid metabolism of aged mammals have not been fully elucidated.In the present study,after assessing the impacts of one type of Lentinula edodes-deriv...The mechanisms of mushroom polysaccharides on immune functions and lipid metabolism of aged mammals have not been fully elucidated.In the present study,after assessing the impacts of one type of Lentinula edodes-derived polysaccharides,named L2,on immune functions and blood lipid profiles,isobaric tags for relative and absolute quantification(iTRAQ)-based proteomic profiling of the small intestinal tissues from aged mice treated with L2 was performed.L2 reversed immune function declines and modulated the lipid metabolism of aged mice evidenced by increased levels of serum TC,HDL-C,and LDL-C,and reduced levels of serum TG.Moreover,a total of 95 differentially regulated proteins(DRPs) were identified,of which75 were up-regulated and 20 were down-regulated.Most of the DRPs were involved in intracellular and extracellular structure organization,and cellular and metabolic regulation.Particularly,approximately 16 and 9 DRPs participated in the regulation of immune functions and lipid metabolism,respectively.Furthermore,protein-protein interaction analysis highlighted that cadherin-1,plectin,cadherin-17,Ras GTPase-activating-like protein IQGAP2,and ezrin might be key proteins in response to L2 treatment.These findings provide new insights into the biological mechanisms of mushroom polysaccharides in anti-aging from a proteomic perspective.展开更多
Spinal cord injury(SCI) often results in permanent dysfunction of locomotion,sensation,and autonomic regulation,imposing a substantial burden on both individuals and society(Anjum et al.,2020).SCI has a complex pathop...Spinal cord injury(SCI) often results in permanent dysfunction of locomotion,sensation,and autonomic regulation,imposing a substantial burden on both individuals and society(Anjum et al.,2020).SCI has a complex pathophysiology:an initial primary injury(mechanical trauma,axonal disruption,and hemorrhage) is followed by a progressive secondary injury cascade that involves ischemia,neuronal loss,and inflammation.Given the challenges in achieving regeneration of the injured spinal cord,neuroprotection has been at the forefront of clinical research.展开更多
Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after inju...Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.展开更多
The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they ...The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they exhibit dense interconnectivity(Braitenburg and Schüz,1998;Campagnola et al.,2022).The strength and probability of connectivity depend on cell type,inter-neuronal distance,and species.Still,every cortical neuron receives input from thousands of other neurons while transmitting output to a similar number of neurons.Second,communication between neurons occurs primarily via chemical or electrical synapses.展开更多
Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography...Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography and microelectrode arrays.The challenges of these mentioned approaches are characterized by the bandwidth of the spatiotemporal resolution,which in turn is essential for large-area neuron recordings(Abiri et al.,2019).展开更多
In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tum...In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.展开更多
The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzh...The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzheimer's or Parkinson's disease)or traumatic injuries(such as spinal cord lesions).In the last 20 years,the field has made significant progress in unlocking axon regrowth.展开更多
Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological s...Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.展开更多
Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functio...Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functional recovery after brain injury.Neuromodulation technologies represent one of the fastest-growing fields in medicine.These techniques utilize electricity,magnetism,sound,and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury.Therefore,this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury.Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury.However,studies report negative findings,potentially due to variations in stimulation protocols,differences in observation periods,and the severity of functional impairments among participants across different clinical trials.Additionally,we observed that different neuromodulation techniques share remarkably similar mechanisms,including promoting neuroplasticity,enhancing neurotrophic factor release,improving cerebral blood flow,suppressing neuroinflammation,and providing neuroprotection.Finally,considering the advantages and disadvantages of various neuromodulation techniques,we propose that future development should focus on closed-loop neural circuit stimulation,personalized treatment,interdisciplinary collaboration,and precision stimulation.展开更多
Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission ...Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.展开更多
Freezing of gait is a significant and debilitating motor symptom often observed in individuals with Parkinson's disease.Resting-state functional magnetic resonance imaging,along with its multi-level feature indice...Freezing of gait is a significant and debilitating motor symptom often observed in individuals with Parkinson's disease.Resting-state functional magnetic resonance imaging,along with its multi-level feature indices,has provided a fresh perspective and valuable insight into the study of freezing of gait in Parkinson's disease.It has been revealed that Parkinson's disease is accompanied by widespread irregularities in inherent brain network activity.However,the effective integration of the multi-level indices of resting-state functional magnetic resonance imaging into clinical settings for the diagnosis of freezing of gait in Parkinson's disease remains a challenge.Although previous studies have demonstrated that radiomics can extract optimal features as biomarkers to identify or predict diseases,a knowledge gap still exists in the field of freezing of gait in Parkinson's disease.This cross-sectional study aimed to evaluate the ability of radiomics features based on multi-level indices of resting-state functional magnetic resonance imaging,along with clinical features,to distinguish between Parkinson's disease patients with and without freezing of gait.We recruited 28 patients with Parkinson's disease who had freezing of gait(15 men and 13 women,average age 63 years)and 30 patients with Parkinson's disease who had no freezing of gait(16 men and 14 women,average age 64 years).Magnetic resonance imaging scans were obtained using a 3.0T scanner to extract the mean amplitude of low-frequency fluctuations,mean regional homogeneity,and degree centrality.Neurological and clinical characteristics were also evaluated.We used the least absolute shrinkage and selection operator algorithm to extract features and established feedforward neural network models based solely on resting-state functional magnetic resonance imaging indicators.We then performed predictive analysis of three distinct groups based on resting-state functional magnetic resonance imaging indicators indicators combined with clinical features.Subsequently,we conducted 100 additional five-fold cross-validations to determine the most effective model for each classification task and evaluated the performance of the model using the area under the receiver operating characteristic curve.The results showed that when differentiating patients with Parkinson's disease who had freezing of gait from those who did not have freezing of gait,or from healthy controls,the models using only the mean regional homogeneity values achieved the highest area under the receiver operating characteristic curve values of 0.750(with an accuracy of 70.9%)and 0.759(with an accuracy of 65.3%),respectively.When classifying patients with Parkinson's disease who had freezing of gait from those who had no freezing of gait,the model using the mean amplitude of low-frequency fluctuation values combined with two clinical features achieved the highest area under the receiver operating characteristic curve of 0.847(with an accuracy of 74.3%).The most significant features for patients with Parkinson's disease who had freezing of gait were amplitude of low-frequency fluctuation alterations in the left parahippocampal gyrus and two clinical characteristics:Montreal Cognitive Assessment and Hamilton Depression Scale scores.Our findings suggest that radiomics features derived from resting-state functional magnetic resonance imaging indices and clinical information can serve as valuable indices for the identification of freezing of gait in Parkinson's disease.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82204360(to HM)and 82270411(to GW)National Science and Technology Innovation 2030 Major Program,No.2021ZD0200900(to YL)。
文摘Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.
基金supported by Natural Science Foundation of Jiangsu Province(No.BK20210494)National Natural Science Foundation of China(No.52303356).
文摘In this study,a framework for predicting the gas-sensitive properties of gas-sensitive materials by combining machine learning and density functional theory(DFT)has been proposed.The framework rapidly predicts the gas response of materials by establishing relationships between multisource physical parameters and gas-sensitive properties.In order to prove its effectiveness,the perovskite Cs_(3)Cu_(2)I_(5) has been selected as the representative material.The physical parameters before and after the adsorption of various gases have been calculated using DFT,and then a machine learning model has been trained based on these parameters.Previous studies have shown that a single physical parameter alone is not enough to accurately predict the gas sensitivity of materials.Therefore,a variety of physical parameters have been selected for machine learning,and the final machine learning model achieved 92%accuracy in predicting gas sensitivity.It is important to note that although there have been no previous reports on the response of Cs_(3)Cu_(2)I_(5) to hydrogen sulfide,the resulting model predicts the gas response of H2S;it is subsequently confirmed experimentally.This method not only enhances the understanding of the gas sensing mechanism,but also has a universal nature,making it suitable for the development of various new gas-sensitive materials.
基金Supported by the Social Science Foundation of Hebei Province(Grant No.HB23TJ003)the Science Research Project of Hebei Education Department(Grant No.BJK2024197)。
文摘This paper examines an epidemic predator-prey model with prey dispersal and Holling type-II functional response. In this model, it is assumed that the predator population suffers a transmissible disease. By analyzing the corresponding characteristic equations, the local stability of each of feasible equilibria and the existence of Hopf bifurcations at the coexistence equilibrium is addressed. Using Lyapunov functionals and LaSalle's invariance principle, we obtained the sufficient conditions for the global stability of the trivial equilibrium, the predator-extinction equilibrium, the disease-free equilibrium and the coexistence equilibrium, respectively. The paper also includes numerical simulations to illustrate the analytical results.
文摘Here we complete our work on the asymptotics of Hankel determinants studying the case wherein the entries are “ultrarapidly”-varying functions in the sense that their logarithms are rapidly varying. Moreover, the last results in the paper highlight analogies between algebraic identities for Hankelians with special entries and asymptotic relations valid for large classes of entries.
文摘Objective:To study the clinical value of combined detection of blood lipids,blood glucose,and liver function in non-alcoholic fatty liver disease.Methods:105 patients with non-alcoholic fatty liver disease treated in our hospital from May 2022 to July 2024 were selected as the research subjects.All patients underwent a B-ultrasound examination.According to the severity of the disease,they were divided into group A(mild,n=35),group B(moderate,n=44),and group C(severe,n=26).Another 30 healthy residents who came to the hospital for physical examination during the same period were selected as group D.The differences in blood lipids,blood glucose,and liver function indicators between groups were compared.Results:The triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL)levels in groups A,B,and C were higher than those in group D,while the high-density lipoprotein cholesterol(HDL)level was lower(P<0.05).The fasting plasma glucose(FPG)levels in groups B and C were higher than those in group D(P<0.05).The TG,LDL,and FPG levels in groups B and C were higher than those in group A(P<0.05).The TC level in group C was higher than that in group A,while the HDL level was lower(P<0.05).The TC and FPG levels in group C were higher than those in group B(P<0.05).The total bilirubin(TBil),aspartate aminotransferase(AST),and alanine aminotransferase(ALT)levels in groups A,B,and C were higher than those in group D(P<0.05).The TBil and ALT levels in groups B and C were higher than those in group A(P<0.05).The AST level in group C was higher than that in group A(P<0.05).The AST and ALT levels in group C were higher than those in group B(P<0.05).Conclusion:Patients with non-alcoholic fatty liver disease have disordered glucose and lipid metabolism.Blood lipids,blood glucose,and liver function are closely related to the severity of the disease.Strengthening exercise and dietary intervention early on can help control the progression of simple fatty liver disease and reduce the risk of severe liver diseases such as steatohepatitis and cirrhosis.
文摘BACKGROUND Appendicitis is a common acute abdominal pain disorder.Laparoscopic appendectomy,a commonly used modality,is associated with less trauma and faster recovery than traditional open appendectomy.However,postoperative recovery remains an important issue that affects rehabilitation quality and surgical results.AIM To explore the effects of rapid rehabilitation and surgical nursing care on gastrointestinal function recovery and sleep quality among patients undergoing laparoscopic appendectomy.METHODS A total of 120 patients who underwent laparoscopic appendectomy at our hospital between January 2019 and March 2024 and for whom complete clinical data were available were selected.Patients were randomly assigned to two groups(n=60 each)using the random number table method.The control group received routine nursing care,while the experimental group received rapid rehabilitation surgical nursing care;all patients continued to receive nursing care until discharge.The recovery of gastrointestinal function,length of hospital stay,complications,Pittsburgh sleep quality index,and nursing satisfaction were compared between groups.RESULTS Following the implementation of effective nursing measures,the times to bowel sound recovery,first exhaust,first defecation,and first feeding were notably shorter in the study vs control group(P<0.05).Additionally,the duration of the first postoperative activity and the length of hospital stay were significantly shorter in the study vs control group(P<0.05).Furthermore,the study group exhibited better sleep quality than the control group(P<0.05).The postoperative complication rate was significantly lower and the nursing satisfaction rate significantly higher in the study vs control group(P<0.05).CONCLUSION Rapid rehabilitation surgical nursing interventions provided to patients after laparoscopic appendectomy can accelerate their postoperative recovery,reduce the occurrence of complications,and improve their sleep quality and nursing satisfaction.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by the Key-Area Research and Development Program of Guangdong Province (2021B0707060001)the Program for Scientific Research Start-Up Funds of Guangdong Ocean UniversityChina Postdoctoral Science Foundation (2016T90787)。
文摘The mechanisms of mushroom polysaccharides on immune functions and lipid metabolism of aged mammals have not been fully elucidated.In the present study,after assessing the impacts of one type of Lentinula edodes-derived polysaccharides,named L2,on immune functions and blood lipid profiles,isobaric tags for relative and absolute quantification(iTRAQ)-based proteomic profiling of the small intestinal tissues from aged mice treated with L2 was performed.L2 reversed immune function declines and modulated the lipid metabolism of aged mice evidenced by increased levels of serum TC,HDL-C,and LDL-C,and reduced levels of serum TG.Moreover,a total of 95 differentially regulated proteins(DRPs) were identified,of which75 were up-regulated and 20 were down-regulated.Most of the DRPs were involved in intracellular and extracellular structure organization,and cellular and metabolic regulation.Particularly,approximately 16 and 9 DRPs participated in the regulation of immune functions and lipid metabolism,respectively.Furthermore,protein-protein interaction analysis highlighted that cadherin-1,plectin,cadherin-17,Ras GTPase-activating-like protein IQGAP2,and ezrin might be key proteins in response to L2 treatment.These findings provide new insights into the biological mechanisms of mushroom polysaccharides in anti-aging from a proteomic perspective.
文摘Spinal cord injury(SCI) often results in permanent dysfunction of locomotion,sensation,and autonomic regulation,imposing a substantial burden on both individuals and society(Anjum et al.,2020).SCI has a complex pathophysiology:an initial primary injury(mechanical trauma,axonal disruption,and hemorrhage) is followed by a progressive secondary injury cascade that involves ischemia,neuronal loss,and inflammation.Given the challenges in achieving regeneration of the injured spinal cord,neuroprotection has been at the forefront of clinical research.
文摘Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.
基金supported in part by the Rosetrees Trust(#CF-2023-I-2_113)by the Israel Ministry of Innovation,Science,and Technology(#7393)(to ES).
文摘The organization of biological neuronal networks into functional modules has intrigued scientists and inspired engineers to develop artificial systems.These networks are characterized by two key properties.First,they exhibit dense interconnectivity(Braitenburg and Schüz,1998;Campagnola et al.,2022).The strength and probability of connectivity depend on cell type,inter-neuronal distance,and species.Still,every cortical neuron receives input from thousands of other neurons while transmitting output to a similar number of neurons.Second,communication between neurons occurs primarily via chemical or electrical synapses.
文摘Invasive as well as non-invasive neurotechnologies conceptualized to interface the central and peripheral nervous system have been probed for the past decades,which refer to electroencephalography,electrocorticography and microelectrode arrays.The challenges of these mentioned approaches are characterized by the bandwidth of the spatiotemporal resolution,which in turn is essential for large-area neuron recordings(Abiri et al.,2019).
文摘In the words of the late Sir Colin Blakemore,neurologists have historically sought to infer brain functions in a manner akin to to king a hammer to a computeranalyzing localized anatomical lesions caused by trauma,tumors,or strokes,noting deficits,and inferring what functions certain brain regions may be responsible for.This approach exemplifies a deletion heuristic,where the absence of a specific function reveals insights about the underlying structures or mechanisms responsible for it.By observing what is lost when a particular brain region is damaged,throughout the history of the field,neurologists have pieced together the intricate relationship between anatomy and function.
基金supported by ANR(ANR-21CE16-0008-01)ANR(ANR-21-CE16-0008-02 and ANR-23CE52-0007)+1 种基金UNADEV(A22018CS)(to HN)UNADEV(A22020CS)(to SB)。
文摘The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzheimer's or Parkinson's disease)or traumatic injuries(such as spinal cord lesions).In the last 20 years,the field has made significant progress in unlocking axon regrowth.
基金supported by Deutsche Forschungsgemeinschaft,German Research Foundation grant GA 654/13-2 to OG.
文摘Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.
基金supported by the National Natural Science Foundation of China,No.82371399(to YY)the Natural Science Foundation of Jiangsu Province,No.BK20221206(to YY)+1 种基金the Young Elite Scientists Sponsorship Program of Jiangsu Province,No.TJ-2022-028(to YY)the Scientific Research Program of Wuxi Health Commission,No.Z202302(to LY)。
文摘Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited.This limited plasticity serves as a primary barrier to functional recovery after brain injury.Neuromodulation technologies represent one of the fastest-growing fields in medicine.These techniques utilize electricity,magnetism,sound,and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury.Therefore,this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury.Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury.However,studies report negative findings,potentially due to variations in stimulation protocols,differences in observation periods,and the severity of functional impairments among participants across different clinical trials.Additionally,we observed that different neuromodulation techniques share remarkably similar mechanisms,including promoting neuroplasticity,enhancing neurotrophic factor release,improving cerebral blood flow,suppressing neuroinflammation,and providing neuroprotection.Finally,considering the advantages and disadvantages of various neuromodulation techniques,we propose that future development should focus on closed-loop neural circuit stimulation,personalized treatment,interdisciplinary collaboration,and precision stimulation.
基金supported by the National Natural Science Foundation of China,Nos.32070989(to YMZ),31872766(to YMZ),81790640(to XLY),and 82070993(to SJW)the grant from Sanming Project of Medicine in Shenzhen,No.SZSM202011015(to XLY)。
文摘Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.
基金supported by the National Natural Science Foundation of China,No.82071909(to GF)the Natural Science Foundation of Liaoning Province,No.2023-MS-07(to HL)。
文摘Freezing of gait is a significant and debilitating motor symptom often observed in individuals with Parkinson's disease.Resting-state functional magnetic resonance imaging,along with its multi-level feature indices,has provided a fresh perspective and valuable insight into the study of freezing of gait in Parkinson's disease.It has been revealed that Parkinson's disease is accompanied by widespread irregularities in inherent brain network activity.However,the effective integration of the multi-level indices of resting-state functional magnetic resonance imaging into clinical settings for the diagnosis of freezing of gait in Parkinson's disease remains a challenge.Although previous studies have demonstrated that radiomics can extract optimal features as biomarkers to identify or predict diseases,a knowledge gap still exists in the field of freezing of gait in Parkinson's disease.This cross-sectional study aimed to evaluate the ability of radiomics features based on multi-level indices of resting-state functional magnetic resonance imaging,along with clinical features,to distinguish between Parkinson's disease patients with and without freezing of gait.We recruited 28 patients with Parkinson's disease who had freezing of gait(15 men and 13 women,average age 63 years)and 30 patients with Parkinson's disease who had no freezing of gait(16 men and 14 women,average age 64 years).Magnetic resonance imaging scans were obtained using a 3.0T scanner to extract the mean amplitude of low-frequency fluctuations,mean regional homogeneity,and degree centrality.Neurological and clinical characteristics were also evaluated.We used the least absolute shrinkage and selection operator algorithm to extract features and established feedforward neural network models based solely on resting-state functional magnetic resonance imaging indicators.We then performed predictive analysis of three distinct groups based on resting-state functional magnetic resonance imaging indicators indicators combined with clinical features.Subsequently,we conducted 100 additional five-fold cross-validations to determine the most effective model for each classification task and evaluated the performance of the model using the area under the receiver operating characteristic curve.The results showed that when differentiating patients with Parkinson's disease who had freezing of gait from those who did not have freezing of gait,or from healthy controls,the models using only the mean regional homogeneity values achieved the highest area under the receiver operating characteristic curve values of 0.750(with an accuracy of 70.9%)and 0.759(with an accuracy of 65.3%),respectively.When classifying patients with Parkinson's disease who had freezing of gait from those who had no freezing of gait,the model using the mean amplitude of low-frequency fluctuation values combined with two clinical features achieved the highest area under the receiver operating characteristic curve of 0.847(with an accuracy of 74.3%).The most significant features for patients with Parkinson's disease who had freezing of gait were amplitude of low-frequency fluctuation alterations in the left parahippocampal gyrus and two clinical characteristics:Montreal Cognitive Assessment and Hamilton Depression Scale scores.Our findings suggest that radiomics features derived from resting-state functional magnetic resonance imaging indices and clinical information can serve as valuable indices for the identification of freezing of gait in Parkinson's disease.
