Edge devices,due to their limited computational and storage resources,often require the use of compilers for program optimization.Therefore,ensuring the security and reliability of these compilers is of paramount impo...Edge devices,due to their limited computational and storage resources,often require the use of compilers for program optimization.Therefore,ensuring the security and reliability of these compilers is of paramount importance in the emerging field of edge AI.One widely used testing method for this purpose is fuzz testing,which detects bugs by inputting random test cases into the target program.However,this process consumes significant time and resources.To improve the efficiency of compiler fuzz testing,it is common practice to utilize test case prioritization techniques.Some researchers use machine learning to predict the code coverage of test cases,aiming to maximize the test capability for the target compiler by increasing the overall predicted coverage of the test cases.Nevertheless,these methods can only forecast the code coverage of the compiler at a specific optimization level,potentially missing many optimization-related bugs.In this paper,we introduce C-CORE(short for Clustering by Code Representation),the first framework to prioritize test cases according to their code representations,which are derived directly from the source codes.This approach avoids being limited to specific compiler states and extends to a broader range of compiler bugs.Specifically,we first train a scaled pre-trained programming language model to capture as many common features as possible from the test cases generated by a fuzzer.Using this pre-trained model,we then train two downstream models:one for predicting the likelihood of triggering a bug and another for identifying code representations associated with bugs.Subsequently,we cluster the test cases according to their code representations and select the highest-scoring test case from each cluster as the high-quality test case.This reduction in redundant testing cases leads to time savings.Comprehensive evaluation results reveal that code representations are better at distinguishing test capabilities,and C-CORE significantly enhances testing efficiency.Across four datasets,C-CORE increases the average of the percentage of faults detected(APFD)value by 0.16 to 0.31 and reduces test time by over 50% in 46% of cases.When compared to the best results from approaches using predicted code coverage,C-CORE improves the APFD value by 1.1% to 12.3% and achieves an overall time-saving of 159.1%.展开更多
Based on the Wallerian degeneration in the spinal cord pathways,the changes in synaptic connections,and the spinal cord-related cellular responses that alter the cellular structure of the brain,we presumed that brain ...Based on the Wallerian degeneration in the spinal cord pathways,the changes in synaptic connections,and the spinal cord-related cellular responses that alter the cellular structure of the brain,we presumed that brain diffusion tensor imaging(DTI)parameters may change after spinal cord injury.However,the dynamic changes in DTI parameters remain unclear.We established a Beagle dog model of T10 spinal cord contusion and performed DTI of the injured spinal cord.We found dynamic changes in DTI parameters in the cerebral peduncle,posterior limb of the internal capsule,pre-and postcentral gyri of the brain within 12 weeks after spinal cord injury.We then performed immunohistochemistry to detect the expression of neurofilament heavy polypeptide(axonal marker),glial fibrillary acidic protein(glial cell marker),and NeuN(neuronal marker).We found that these pathological changes were consistent with DTI parameter changes.These findings suggest that DTI can display brain structure changes after spinal cord injury.展开更多
Background:Pathological angiogenesis and blood–brain barrier damage may play an important role in Alzheimer's disease(AD).ACE2 is mainly expressed on the surface of endothelial cells in brain.Recent studies have ...Background:Pathological angiogenesis and blood–brain barrier damage may play an important role in Alzheimer's disease(AD).ACE2 is mainly expressed on the surface of endothelial cells in brain.Recent studies have shown that the expression of ACE2 in AD is reduced,but its role in AD is still unclear.Method:We induced AD damage in endothelial cells using Aβ25-35 and overexpressed ACE2 in bEend.3 cells through lentiviral transfection.We detected the effect of Aβ25-35 on cell viability using the CCK-8 assay and examined the effect of overexpressing ACE2 on angiogenesis using an angiogenesis assay.We used western blot and cell immunofluorescence to detect changes in the expression of the VEGF/VEGFR2 pathway,tight junction protein,and NF-κB pathway.Results:Aβ25-35 treatment significantly decreased the expression of ACE2 and reduced cell viability.ACE2 overexpression(1)reduced the number of branches and junctions in tube formation,(2)inhibited the activation of the VEGF/VEGFR2 pathway induced by Aβ25-35,(3)increased the expression of TJPs,including ZO-1 and claudin-5,and(4)restored Aβ25-35-induced activation of the NF-κB pathway.Conclusion:Overexpression of ACE2 can improve pathological angiogenesis and blood–brain barrier damage in AD models in vitro by inhibiting NF-κB/VEGF/VEGFR2 pathway activity.ACE2 may therefore represent a therapeutic target for endothelial cell dysfunction in AD.展开更多
Autophagy is one of the degradation pathways to remove proteins or damaged or-ganelles in cells that plays an important role in neuroprotection.Different stages of autophagy are regulated by autophagy-related genes,an...Autophagy is one of the degradation pathways to remove proteins or damaged or-ganelles in cells that plays an important role in neuroprotection.Different stages of autophagy are regulated by autophagy-related genes,and many molecules such as transcription factor EB(TFEB)are involved.The complete autophagy process plays an important role in maintaining the dynamic balance of autophagy and is crucial to the homeostasis of intracellular substance and energy metabolism.Autophagy balance is disrupted in neurodegenerative diseases,accounting for a variety of degeneration dis-orders.These impairments can be alleviated or treated by the regulation of autophagy through molecules such as TFEB.展开更多
According to the traditional Chinese zodiac,2023 is the Year of the Rabbit,which holds the meaning of life and hope due to the rabbit's vigorous reproductive ability.Over the past 5 years AMEM has flourished,initi...According to the traditional Chinese zodiac,2023 is the Year of the Rabbit,which holds the meaning of life and hope due to the rabbit's vigorous reproductive ability.Over the past 5 years AMEM has flourished,initial hopes have been realized and the journal has gone from strength to strength.Following the gradual rise in submissions and the journal's increasing influence,in 2022 AMEM changed from quarterly to bimonthly,and successively launched seven themed sections-columns-includ-ing neurodegenerative disease,cardiovascular disease,and so on.展开更多
Singing,as a method of combining respiratory function exercise and vocal intonation therapy,provides a new direction for respiratory function exercise in patients with spinal cord injury.This randomized controlled tri...Singing,as a method of combining respiratory function exercise and vocal intonation therapy,provides a new direction for respiratory function exercise in patients with spinal cord injury.This randomized controlled trial investigated the effects of oral motor respiratory exercise and vocal intonation therapy on respiratory function and vocal quality in patients with spinal cord injury.Among 31 included patients with spinal cord injury,18 completed the treatment.These 18 patients were randomly assigned to undergo music therapy(intervention group,30 min/d,5 times a week,for a total of 12 weeks;n=9,7 males and 2 females;30.33±11.74 years old)or normal respiratory training(control group,n=9;8 males and 1 female;34.78±11.13 years old).Both patient groups received routine treatment concurrently.Before and at 6 and 12 weeks after intervention,a standard respiratory function test,a voice test,the St.George's Respiratory Questionnaire,and a quality of life questionnaire were administered.The results showed that the inspiratory capacity,forced expiratory volume in 1 second,forced vital capacity,maximal mid-expiratory flow rate,sing-loud pressure level,and sustained note length were significantly increased in the intervention group compared with the control group.The St.George's Respiratory Questionnaire and quality of life results of patients in the intervention group were significantly superior to those in the control group.These findings suggest that oral motor respiratory exercise and vocal intonation therapy,as respiratory training methods in music therapy,are effective and valuable for improving respiratory dysfunction and vocal quality in patients with spinal cord injury.This study was approved by the Ethics Committee of China Rehabilitation Research Center(approval No.2019-78-1)on May 27,2019 and was registered with the Chinese Clinical Trial Registry(registration number:Chi CTR1900026922)on October 26,2019.展开更多
Non-coding RNAs(ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs(tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cle...Non-coding RNAs(ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs(tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18–40 nucleotides, known as tRNA-derived small RNAs(tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points:(1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes.(2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress.(3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma.(4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.展开更多
Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of internatio...Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.展开更多
Objective To develop a model of SHIV-KB9/Chinese origin rhesus (Ch Rh) macaques for vaccine research and to compare the pathogenesis of SHIV-KB9 in Ch Rh macaques with that reported in Indian rhesus (Ind Rh) macaques....Objective To develop a model of SHIV-KB9/Chinese origin rhesus (Ch Rh) macaques for vaccine research and to compare the pathogenesis of SHIV-KB9 in Ch Rh macaques with that reported in Indian rhesus (Ind Rh) macaques. Methods Seven mamu-A*01 negative Ch Rh macaques were inoculated intravenously with 1-10000 MID50 of SHIV-KB9. The monkeys were monitored for viral load, CD4, CD8, SHIV-specific antibody and virus genetic variation. The results were compared with those previously observed in Ind Rh macaques. Results As compared to that observed in Ind Rh macaques, SHIV-KB9 in Ch Rh macaques displayed three identical disease progression patterns. However, the primary pattern was not identical between the two subspecies. The level of plasma viremia differed in SHIV-KB9-infected Ch Rh macaques which exhibited different outcomes from those in Ind Rh macaques. Generally, the values of viral load and the maintenance of CD4+ T cells were associated with humoral responses. Otherwise, the viral genetic distances (divergence, diversity) were larger in animals (M419, M425) with their CD4+ T cells profoundly depleted. Conclusion The model of SHIV-KB9/Ch Rh macaques displays a relatively slow progression to AIDS compared with Ind Rh macaques, which may more accurately reflect the potential of candidate vaccines in humans.展开更多
In this paper,we propose a novel coverless image steganographic scheme based on a generative model.In our scheme,the secret image is first fed to the generative model database,to generate a meaning-normal and independ...In this paper,we propose a novel coverless image steganographic scheme based on a generative model.In our scheme,the secret image is first fed to the generative model database,to generate a meaning-normal and independent image different from the secret image.The generated image is then transmitted to the receiver and fed to the generative model database to generate another image visually the same as the secret image.Thus,we only need to transmit the meaning-normal image which is not related to the secret image,and we can achieve the same effect as the transmission of the secret image.This is the first time to propose the coverless image information steganographic scheme based on generative model,compared with the traditional image steganography.The transmitted image is not embedded with any information of the secret image in this method,therefore,can effectively resist steganalysis tools.Experimental results show that our scheme has high capacity,security and reliability.展开更多
Background:Alzheimer's disease(AD)is an incurable and irreversible neurodegen-erative disease,without a clear pathogenesis.Therefore,identification of candidates before amyloid-βplaque(Aβ)deposition proceeds is ...Background:Alzheimer's disease(AD)is an incurable and irreversible neurodegen-erative disease,without a clear pathogenesis.Therefore,identification of candidates before amyloid-βplaque(Aβ)deposition proceeds is of major significance for earlier intervention in AD.Methods:To explore the potential noninvasive earlier biomarkers of AD in a 5XFAD mouse model,microRNAs(miRNAs)from urinary exosomes in 1-month-old pre-Aβaccumulation 5XFAD mice models and their littermate controls were profiled by mi-croarray analysis.The differentially expressed miRNAs were further analyzed via droplet digital PCR(ddPCR).Results:Microarray analysis demonstrated that 48 differentially expressed miRNAs(18 upregulated and 30 downregulated),of which six miRNAs-miR-196b-5p,miR-339-3p,miR-34a-5p,miR-376b-3p,miR-677-5p,and miR-721-were predicted to display gene targets and important signaling pathways closely associated with AD pathogenesis and verified by ddPCR.Conclusions:Urinary exosomal miRNAs showing differences in expression prior to Aβ-plaque deposition were identified.These exosomal miRNAs represent potential noninvasive biomarkers that may be used to prevent AD in clinical applications.展开更多
Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological pr...Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological processes, including immune, cancer, stress, development and differentiation at the transcriptional, epigenetic or post-transcriptional levels. Here, we review the role of lnc RNAs in the process of neurodevelopment, neural differentiation, synaptic function, and pathogenesis of Parkinson’s disease(PD). These pathomechanisms include protein misfolding and aggregation, disordered protein degradation, mitochondrial dysfunction, oxidative stress, autophagy, apoptosis, and neuroinflammation. This information will provide the basis of lnc RNA-based disease diagnosis and drug treatment for PD.展开更多
OBJECTIVE: To investigate the effects of myelotomy on locomotor recovery in rats subjected to spinal cord injury. DATA SOURCES: Electronic databases including Pub Med, Science Citation Index, Cochrane Library, China N...OBJECTIVE: To investigate the effects of myelotomy on locomotor recovery in rats subjected to spinal cord injury. DATA SOURCES: Electronic databases including Pub Med, Science Citation Index, Cochrane Library, China National Knowledge Infrastructure, Chinese Journals Full-text Database, China Biology Medicine disc, and Wanfang Database were searched to retrieve related studies published before September 2017. The Me SH terms(the Medical Subject Headings) such as "myelotomy", "spinal cord injuries", "rats", "randomized controlled trial" and all related entry terms were searched. DATA SELECTION: Randomized controlled trials using myelotomy for the treatment of acute spinal cord injury in rats were included. Basso, Beattie, and Bresnahan scores were adopted as the evaluation method. Rev Man Software(version 5.3) was used for data processing. The χ~2 and I^2 tests were used to assess heterogeneity. Using a random-effects model, a subgroup analysis was conducted to analyze the source of the heterogeneity. OUTCOME MEASURES: Basso, Beattie, and Bresnahan scores were observed 1–6 weeks after spinal cord injury.RESULTS: Six animal trials were included, using a total of 143 lab rats. The included trials were divided into two subgroups by injury degrees(moderate or severe). The pooled results showed that, 1–6 weeks after spinal cord injury, the overall Basso, Beattie, and Bresnahan score was significantly higher in the myelotomy group than in the contusion group(weighted mean difference(WMD) = 0.60; 95% confidence interval(CI): 0.23–0.97; P = 0.001; WMD = 2.10; 95% CI: 1.56–2.64; P < 0.001; WMD = 2.65; 95% CI: 1.73–3.57; P < 0.001; WMD = 1.66; 95% CI: 0.80–2.52; P < 0.001; WMD = 2.09; 95% CI: 0.92–3.26, P < 0.001; WMD = 2.25; 95% CI: 1.06–3.44, P < 0.001). The overall heterogeneity was high(I^2 = 85%; I^2 = 95%; I^2 = 94%; I^2 = 88%; I^2 = 91%; I^2 = 89%). The results in the moderate injury subgroup showed that Basso, Beattie, and Bresnahan scores were significantly higher in the myelotomy group than in the contusion group(WMD = 0.91, 95% CI: 0.52–1.3, P < 0.001; WMD = 2.10; 95% CI: 1.56–2.64, P < 0.001; WMD = 2.65; 95% CI: 1.73–3.57, P < 0.001; WMD = 2.50, 95% CI: 1.72–3.28, P < 0.001; WMD = 3.29, 95% CI: 2.21–4.38, P < 0.001; WMD = 3.27; 95% CI: 2.31–4.23, P < 0.001). The relevant heterogeneity was low. However, there were no significant differences in Basso, Beattie, and Bresnahan scores between the myelotomy and contusion groups in the severe injury subgroup at 2 and 3 weeks after the injury(P = 0.75; P = 0.92). CONCLUSION: To date, this is the first attempt to summarize the potential effect of myelotomy on locomotor recovery in rats with spinal cord injury. Our findings conclude that myelotomy promotes locomotor recovery in rats with spinal cord injury, especially in those with moderate injury.展开更多
Object:Early-life neglect has irreversible emotional effects on the central nervous system.In this work,we aimed to elucidate distinct functional neural changes in me-dial prefrontal cortex(mPFC)of model rats.Methods:...Object:Early-life neglect has irreversible emotional effects on the central nervous system.In this work,we aimed to elucidate distinct functional neural changes in me-dial prefrontal cortex(mPFC)of model rats.Methods:Maternal separation with early weaning was used as a rat model of early-life neglect.The excitation of glutamatergic and GABAergic neurons in rat mPFC was recorded and analyzed by whole-cell patch clamp.Results:Glutamatergic and GABAergic neurons of mPFC were distinguished by typi-cal electrophysiological properties.The excitation of mPFC glutamatergic neurons was significantly increased in male groups,while the excitation of mPFC GABAergic neurons was significant in both female and male groups,but mainly in terms of rest membrane potential and amplitude,respectively.Conclusions:Glutamatergic and GABAergic neurons in medial prefrontal cortex showed different excitability changes in a rat model of early-life neglect,which can contribute to distinct mechanisms for emotional and cognitive manifestations.展开更多
With the increasingly serious aging of the global population, dementia has already become a severe clinical challenge on a global scale. Dementia caused by Alzheimer’s disease(AD) is the most common form of dementia ...With the increasingly serious aging of the global population, dementia has already become a severe clinical challenge on a global scale. Dementia caused by Alzheimer’s disease(AD) is the most common form of dementia observed in the elderly, but its pathogenetic mechanism has still not been fully elucidated. Furthermore, no effective treatment strategy has been developed to date, despite considerable efforts. This can be mainly attributed to the paucity of animal models of AD that are sufficiently similar to humans. Among the presently established animal models, non-human primates share the closest relationship with humans, and their neural anatomy and neurobiology share highly similar characteristics with those of humans. Thus, there is no doubt that these play an irreplaceable role in AD research. Considering this, the present literature on non-human primate models of AD was reviewed to provide a theoretical basis for future research.展开更多
Alzheimer's disease(AD)is a neurodegenerative disorder.The pathology of AD is characterized by extracellular amyloid beta(Aβ)plaques,neurofibrillary tangles com-posed of hyperphosphorylated tau,neuronal death,syn...Alzheimer's disease(AD)is a neurodegenerative disorder.The pathology of AD is characterized by extracellular amyloid beta(Aβ)plaques,neurofibrillary tangles com-posed of hyperphosphorylated tau,neuronal death,synapse loss,and brain atrophy.Many therapies have been tested to improve or at least effectively modify the course of AD.Meaningful data indicate that the transplantation of stem cells can alleviate neuropathology and significantly ameliorate cognitive deficits in animal models with Alzheimer's disease.Transplanted stem cells have shown their inherent advantages in improving cognitive impairment and memory dysfunction,although certain weak-nesses or limitations need to be overcome.This review recapitulates rodent models for AD,the therapeutic efficacy of stem cells,influencing factors,and the underlying mechanisms behind these changes.Stem cell therapy provides perspective and chal-lenges for its clinical application in the future.展开更多
Background:Cardiovascular diseases(CVDs)and diabetes mellitus(DM)are top two chronic comorbidities that increase the severity and mortality of COVID-19.However,how SARS-CoV-2 alters the progression of chronic diseases...Background:Cardiovascular diseases(CVDs)and diabetes mellitus(DM)are top two chronic comorbidities that increase the severity and mortality of COVID-19.However,how SARS-CoV-2 alters the progression of chronic diseases remain unclear.Methods:We used adenovirus to deliver h-ACE2 to lung to enable SARS-CoV-2 infection in mice.SARS-CoV-2’s impacts on pathogenesis of chronic diseases were studied through histopathological,virologic and molecular biology analysis.Results:Pre-existing CVDs resulted in viral invasion,ROS elevation and activation of apoptosis pathways contribute myocardial injury during SARS-CoV-2 infection.Viral infection increased fasting blood glucose and reduced insulin response in DM model.Bone mineral density decreased shortly after infection,which associated with impaired PI3K/AKT/mTOR signaling.Conclusion:We established mouse models mimicked the complex pathological symptoms of COVID-19 patients with chronic diseases.Pre-existing diseases could impair the inflammatory responses to SARS-CoV-2 infection,which further aggravated the pre-existing diseases.This work provided valuable information to better understand the interplay between the primary diseases and SARS-CoV-2 infection.展开更多
Alzheimer's disease(AD) is an increasingly common neurodegenerative disease.Since the intestinal microbiome is closely related to nervous system diseases, alterations in the composition of intestinal microbiota co...Alzheimer's disease(AD) is an increasingly common neurodegenerative disease.Since the intestinal microbiome is closely related to nervous system diseases, alterations in the composition of intestinal microbiota could potentially contribute to the pathophysiology of AD. However, how the initial interactions with intestinal microbes alter events later in life, such as during neurodegenerative diseases, is still unclear. This review summarizes what is known about the relationship between the intestinal microbiome and AD.展开更多
The oxygenation constants(Ko_2)of cobalt(Ⅱ)hydroxamates(CoL_2~1-CoL_2~3)with benzo-15-crown-5(B15C5)pendants were measured over the range of-5 to+20℃,and the values of thermodynamic parameters(ΔH^0 andΔS^0)were ca...The oxygenation constants(Ko_2)of cobalt(Ⅱ)hydroxamates(CoL_2~1-CoL_2~3)with benzo-15-crown-5(B15C5)pendants were measured over the range of-5 to+20℃,and the values of thermodynamic parameters(ΔH^0 andΔS^0)were calculated based on these(No_2)values.Meanwhile,these crowned complexes were employed to the oxidation for p-xylene to p-toluic acid with air at 110Δunder normal atmospheric pressure.The effects of B15C5 pendant and the length of chain bonded to B15C5 in these complexes on the O_2-binding capabilities and oxidation for p-xylene were investigated with the comparison of crown-free analogues CoL_2~4.展开更多
文摘Edge devices,due to their limited computational and storage resources,often require the use of compilers for program optimization.Therefore,ensuring the security and reliability of these compilers is of paramount importance in the emerging field of edge AI.One widely used testing method for this purpose is fuzz testing,which detects bugs by inputting random test cases into the target program.However,this process consumes significant time and resources.To improve the efficiency of compiler fuzz testing,it is common practice to utilize test case prioritization techniques.Some researchers use machine learning to predict the code coverage of test cases,aiming to maximize the test capability for the target compiler by increasing the overall predicted coverage of the test cases.Nevertheless,these methods can only forecast the code coverage of the compiler at a specific optimization level,potentially missing many optimization-related bugs.In this paper,we introduce C-CORE(short for Clustering by Code Representation),the first framework to prioritize test cases according to their code representations,which are derived directly from the source codes.This approach avoids being limited to specific compiler states and extends to a broader range of compiler bugs.Specifically,we first train a scaled pre-trained programming language model to capture as many common features as possible from the test cases generated by a fuzzer.Using this pre-trained model,we then train two downstream models:one for predicting the likelihood of triggering a bug and another for identifying code representations associated with bugs.Subsequently,we cluster the test cases according to their code representations and select the highest-scoring test case from each cluster as the high-quality test case.This reduction in redundant testing cases leads to time savings.Comprehensive evaluation results reveal that code representations are better at distinguishing test capabilities,and C-CORE significantly enhances testing efficiency.Across four datasets,C-CORE increases the average of the percentage of faults detected(APFD)value by 0.16 to 0.31 and reduces test time by over 50% in 46% of cases.When compared to the best results from approaches using predicted code coverage,C-CORE improves the APFD value by 1.1% to 12.3% and achieves an overall time-saving of 159.1%.
基金supported by the National Natural Science Foundation of China, No. 82102676 (to CBL)a grant from Beijing Municipal Science & Technology Commission, No. Z171100001017076 (to JJL)+1 种基金National Key Research and Development Program, No. 2018YFF0301104 (to JJL)Research on Medical Protection Technology and Application of Induced Neural Stem Cells in the Treatment of Military Spinal Cord Injury, No. Z181100004118004 (to JL)
文摘Based on the Wallerian degeneration in the spinal cord pathways,the changes in synaptic connections,and the spinal cord-related cellular responses that alter the cellular structure of the brain,we presumed that brain diffusion tensor imaging(DTI)parameters may change after spinal cord injury.However,the dynamic changes in DTI parameters remain unclear.We established a Beagle dog model of T10 spinal cord contusion and performed DTI of the injured spinal cord.We found dynamic changes in DTI parameters in the cerebral peduncle,posterior limb of the internal capsule,pre-and postcentral gyri of the brain within 12 weeks after spinal cord injury.We then performed immunohistochemistry to detect the expression of neurofilament heavy polypeptide(axonal marker),glial fibrillary acidic protein(glial cell marker),and NeuN(neuronal marker).We found that these pathological changes were consistent with DTI parameter changes.These findings suggest that DTI can display brain structure changes after spinal cord injury.
基金Peking Union Medical CollegeCAMS initiative for Innovative Medicine of ChinaGrant/Award Number:2021-I2M-1-034
文摘Background:Pathological angiogenesis and blood–brain barrier damage may play an important role in Alzheimer's disease(AD).ACE2 is mainly expressed on the surface of endothelial cells in brain.Recent studies have shown that the expression of ACE2 in AD is reduced,but its role in AD is still unclear.Method:We induced AD damage in endothelial cells using Aβ25-35 and overexpressed ACE2 in bEend.3 cells through lentiviral transfection.We detected the effect of Aβ25-35 on cell viability using the CCK-8 assay and examined the effect of overexpressing ACE2 on angiogenesis using an angiogenesis assay.We used western blot and cell immunofluorescence to detect changes in the expression of the VEGF/VEGFR2 pathway,tight junction protein,and NF-κB pathway.Results:Aβ25-35 treatment significantly decreased the expression of ACE2 and reduced cell viability.ACE2 overexpression(1)reduced the number of branches and junctions in tube formation,(2)inhibited the activation of the VEGF/VEGFR2 pathway induced by Aβ25-35,(3)increased the expression of TJPs,including ZO-1 and claudin-5,and(4)restored Aβ25-35-induced activation of the NF-κB pathway.Conclusion:Overexpression of ACE2 can improve pathological angiogenesis and blood–brain barrier damage in AD models in vitro by inhibiting NF-κB/VEGF/VEGFR2 pathway activity.ACE2 may therefore represent a therapeutic target for endothelial cell dysfunction in AD.
基金National Natural Science Foundation of China grant(31970510,81941012)CAMS Innovation Fund for Medical Sciences(CIFMS)grant(2016-I2M-2-006,2016-I2M-1-010).
文摘Autophagy is one of the degradation pathways to remove proteins or damaged or-ganelles in cells that plays an important role in neuroprotection.Different stages of autophagy are regulated by autophagy-related genes,and many molecules such as transcription factor EB(TFEB)are involved.The complete autophagy process plays an important role in maintaining the dynamic balance of autophagy and is crucial to the homeostasis of intracellular substance and energy metabolism.Autophagy balance is disrupted in neurodegenerative diseases,accounting for a variety of degeneration dis-orders.These impairments can be alleviated or treated by the regulation of autophagy through molecules such as TFEB.
文摘According to the traditional Chinese zodiac,2023 is the Year of the Rabbit,which holds the meaning of life and hope due to the rabbit's vigorous reproductive ability.Over the past 5 years AMEM has flourished,initial hopes have been realized and the journal has gone from strength to strength.Following the gradual rise in submissions and the journal's increasing influence,in 2022 AMEM changed from quarterly to bimonthly,and successively launched seven themed sections-columns-includ-ing neurodegenerative disease,cardiovascular disease,and so on.
基金Scientific Research Foundation of China Rehabilitation Research Center,No.2019zx-23(to SHL)the Natural Science Foundation of Beijing of China,No.7192238。
文摘Singing,as a method of combining respiratory function exercise and vocal intonation therapy,provides a new direction for respiratory function exercise in patients with spinal cord injury.This randomized controlled trial investigated the effects of oral motor respiratory exercise and vocal intonation therapy on respiratory function and vocal quality in patients with spinal cord injury.Among 31 included patients with spinal cord injury,18 completed the treatment.These 18 patients were randomly assigned to undergo music therapy(intervention group,30 min/d,5 times a week,for a total of 12 weeks;n=9,7 males and 2 females;30.33±11.74 years old)or normal respiratory training(control group,n=9;8 males and 1 female;34.78±11.13 years old).Both patient groups received routine treatment concurrently.Before and at 6 and 12 weeks after intervention,a standard respiratory function test,a voice test,the St.George's Respiratory Questionnaire,and a quality of life questionnaire were administered.The results showed that the inspiratory capacity,forced expiratory volume in 1 second,forced vital capacity,maximal mid-expiratory flow rate,sing-loud pressure level,and sustained note length were significantly increased in the intervention group compared with the control group.The St.George's Respiratory Questionnaire and quality of life results of patients in the intervention group were significantly superior to those in the control group.These findings suggest that oral motor respiratory exercise and vocal intonation therapy,as respiratory training methods in music therapy,are effective and valuable for improving respiratory dysfunction and vocal quality in patients with spinal cord injury.This study was approved by the Ethics Committee of China Rehabilitation Research Center(approval No.2019-78-1)on May 27,2019 and was registered with the Chinese Clinical Trial Registry(registration number:Chi CTR1900026922)on October 26,2019.
基金supported by the National Natural Science Foundation of China,No.81870979(to JJL),No.81271366(to MLY)the National Key R&D Program of China,No.2018YFF0301104(to JJL)+4 种基金the Special Fund for Basic Scientific Research of Central Public Research Institutes of China,No.2018CZ-1(to JJL)the Basic Scientific Research Foundation of China Rehabilitation Research Center,No.2018ZX-30(to FG)the Scientific Research Foundation of CRRC,No.2012C-1(to JJL)the Major Science and Technology Project of Beijing of China,No.D161100002816004(to JJL)the Special Capital Health Research and Development of China,No.2018-1-6011(to JJL)
文摘Non-coding RNAs(ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs(tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18–40 nucleotides, known as tRNA-derived small RNAs(tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points:(1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes.(2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress.(3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma.(4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.
基金This work was supported by the National Research and Development Project of China(Grant No.2020YFC0841100)Fundamental Research Funds for CAMS of China(Grant No.2020HY320001)+3 种基金National Key Research and Development Project of China(Grant No.2016YFD0500304)CAMS initiative for Innovative Medicine of China(Grant No.2016-I2M-2-006)National Mega projects of China for Major Infectious Diseases(Grant No.2017ZX10304402)and National Key Research and Development Programme of China(2016YFD0500301,2020YFC0840800,2020YFC0840900).
文摘Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.
文摘Objective To develop a model of SHIV-KB9/Chinese origin rhesus (Ch Rh) macaques for vaccine research and to compare the pathogenesis of SHIV-KB9 in Ch Rh macaques with that reported in Indian rhesus (Ind Rh) macaques. Methods Seven mamu-A*01 negative Ch Rh macaques were inoculated intravenously with 1-10000 MID50 of SHIV-KB9. The monkeys were monitored for viral load, CD4, CD8, SHIV-specific antibody and virus genetic variation. The results were compared with those previously observed in Ind Rh macaques. Results As compared to that observed in Ind Rh macaques, SHIV-KB9 in Ch Rh macaques displayed three identical disease progression patterns. However, the primary pattern was not identical between the two subspecies. The level of plasma viremia differed in SHIV-KB9-infected Ch Rh macaques which exhibited different outcomes from those in Ind Rh macaques. Generally, the values of viral load and the maintenance of CD4+ T cells were associated with humoral responses. Otherwise, the viral genetic distances (divergence, diversity) were larger in animals (M419, M425) with their CD4+ T cells profoundly depleted. Conclusion The model of SHIV-KB9/Ch Rh macaques displays a relatively slow progression to AIDS compared with Ind Rh macaques, which may more accurately reflect the potential of candidate vaccines in humans.
基金This paper was supported by the National Natural Science Foundation of China(No.U1204606)the Key Programs for Science and Technology Development of Henan Province(No.172102210335)Key Scientific Research Projects in Henan Universities(No.16A520058).
文摘In this paper,we propose a novel coverless image steganographic scheme based on a generative model.In our scheme,the secret image is first fed to the generative model database,to generate a meaning-normal and independent image different from the secret image.The generated image is then transmitted to the receiver and fed to the generative model database to generate another image visually the same as the secret image.Thus,we only need to transmit the meaning-normal image which is not related to the secret image,and we can achieve the same effect as the transmission of the secret image.This is the first time to propose the coverless image information steganographic scheme based on generative model,compared with the traditional image steganography.The transmitted image is not embedded with any information of the secret image in this method,therefore,can effectively resist steganalysis tools.Experimental results show that our scheme has high capacity,security and reliability.
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2016-12M-2-006 and 2019-I2M-1-003Young Elite Scientists Sponsorship Program by CAST(YESS),Grant/Award Number:2019QNRC001+1 种基金National Natural Science Foundation of China,Grant/Award Number:81901114Fundamental Research Funds for the Central Universities,Grant/Award Number:3332019091。
文摘Background:Alzheimer's disease(AD)is an incurable and irreversible neurodegen-erative disease,without a clear pathogenesis.Therefore,identification of candidates before amyloid-βplaque(Aβ)deposition proceeds is of major significance for earlier intervention in AD.Methods:To explore the potential noninvasive earlier biomarkers of AD in a 5XFAD mouse model,microRNAs(miRNAs)from urinary exosomes in 1-month-old pre-Aβaccumulation 5XFAD mice models and their littermate controls were profiled by mi-croarray analysis.The differentially expressed miRNAs were further analyzed via droplet digital PCR(ddPCR).Results:Microarray analysis demonstrated that 48 differentially expressed miRNAs(18 upregulated and 30 downregulated),of which six miRNAs-miR-196b-5p,miR-339-3p,miR-34a-5p,miR-376b-3p,miR-677-5p,and miR-721-were predicted to display gene targets and important signaling pathways closely associated with AD pathogenesis and verified by ddPCR.Conclusions:Urinary exosomal miRNAs showing differences in expression prior to Aβ-plaque deposition were identified.These exosomal miRNAs represent potential noninvasive biomarkers that may be used to prevent AD in clinical applications.
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2017-I2M-2-005 and 2016-I2M-2-006Beijing Natural Science Foundation,Grant/Award Number:5171001
文摘Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological processes, including immune, cancer, stress, development and differentiation at the transcriptional, epigenetic or post-transcriptional levels. Here, we review the role of lnc RNAs in the process of neurodevelopment, neural differentiation, synaptic function, and pathogenesis of Parkinson’s disease(PD). These pathomechanisms include protein misfolding and aggregation, disordered protein degradation, mitochondrial dysfunction, oxidative stress, autophagy, apoptosis, and neuroinflammation. This information will provide the basis of lnc RNA-based disease diagnosis and drug treatment for PD.
基金supported by the Special Fund for Basic Scientific Research of Central Public Research Institutes of China,No.2015CZ-6,2016CZ-4a grant from the Beijing Institute for Brain Disorders,No.201601
文摘OBJECTIVE: To investigate the effects of myelotomy on locomotor recovery in rats subjected to spinal cord injury. DATA SOURCES: Electronic databases including Pub Med, Science Citation Index, Cochrane Library, China National Knowledge Infrastructure, Chinese Journals Full-text Database, China Biology Medicine disc, and Wanfang Database were searched to retrieve related studies published before September 2017. The Me SH terms(the Medical Subject Headings) such as "myelotomy", "spinal cord injuries", "rats", "randomized controlled trial" and all related entry terms were searched. DATA SELECTION: Randomized controlled trials using myelotomy for the treatment of acute spinal cord injury in rats were included. Basso, Beattie, and Bresnahan scores were adopted as the evaluation method. Rev Man Software(version 5.3) was used for data processing. The χ~2 and I^2 tests were used to assess heterogeneity. Using a random-effects model, a subgroup analysis was conducted to analyze the source of the heterogeneity. OUTCOME MEASURES: Basso, Beattie, and Bresnahan scores were observed 1–6 weeks after spinal cord injury.RESULTS: Six animal trials were included, using a total of 143 lab rats. The included trials were divided into two subgroups by injury degrees(moderate or severe). The pooled results showed that, 1–6 weeks after spinal cord injury, the overall Basso, Beattie, and Bresnahan score was significantly higher in the myelotomy group than in the contusion group(weighted mean difference(WMD) = 0.60; 95% confidence interval(CI): 0.23–0.97; P = 0.001; WMD = 2.10; 95% CI: 1.56–2.64; P < 0.001; WMD = 2.65; 95% CI: 1.73–3.57; P < 0.001; WMD = 1.66; 95% CI: 0.80–2.52; P < 0.001; WMD = 2.09; 95% CI: 0.92–3.26, P < 0.001; WMD = 2.25; 95% CI: 1.06–3.44, P < 0.001). The overall heterogeneity was high(I^2 = 85%; I^2 = 95%; I^2 = 94%; I^2 = 88%; I^2 = 91%; I^2 = 89%). The results in the moderate injury subgroup showed that Basso, Beattie, and Bresnahan scores were significantly higher in the myelotomy group than in the contusion group(WMD = 0.91, 95% CI: 0.52–1.3, P < 0.001; WMD = 2.10; 95% CI: 1.56–2.64, P < 0.001; WMD = 2.65; 95% CI: 1.73–3.57, P < 0.001; WMD = 2.50, 95% CI: 1.72–3.28, P < 0.001; WMD = 3.29, 95% CI: 2.21–4.38, P < 0.001; WMD = 3.27; 95% CI: 2.31–4.23, P < 0.001). The relevant heterogeneity was low. However, there were no significant differences in Basso, Beattie, and Bresnahan scores between the myelotomy and contusion groups in the severe injury subgroup at 2 and 3 weeks after the injury(P = 0.75; P = 0.92). CONCLUSION: To date, this is the first attempt to summarize the potential effect of myelotomy on locomotor recovery in rats with spinal cord injury. Our findings conclude that myelotomy promotes locomotor recovery in rats with spinal cord injury, especially in those with moderate injury.
基金CAMS Innovation Fund for Medical Sciences(CIFMS),Grant/Award Number:2021-I2M-1-034National Natural Science Foundation of China,Grant/Award Number:31970510Young Elite Scientist Sponsorship Program by CAST,Grant/Award Number:2019QNRC001。
文摘Object:Early-life neglect has irreversible emotional effects on the central nervous system.In this work,we aimed to elucidate distinct functional neural changes in me-dial prefrontal cortex(mPFC)of model rats.Methods:Maternal separation with early weaning was used as a rat model of early-life neglect.The excitation of glutamatergic and GABAergic neurons in rat mPFC was recorded and analyzed by whole-cell patch clamp.Results:Glutamatergic and GABAergic neurons of mPFC were distinguished by typi-cal electrophysiological properties.The excitation of mPFC glutamatergic neurons was significantly increased in male groups,while the excitation of mPFC GABAergic neurons was significant in both female and male groups,but mainly in terms of rest membrane potential and amplitude,respectively.Conclusions:Glutamatergic and GABAergic neurons in medial prefrontal cortex showed different excitability changes in a rat model of early-life neglect,which can contribute to distinct mechanisms for emotional and cognitive manifestations.
基金The CAMS Innovation Fund for Medical Science(2016-12M-2-006 and 2016-12M-1-10)the PUMC Innovation Fund for Graduate Students(Grant/Award number:2017-1001-07)
文摘With the increasingly serious aging of the global population, dementia has already become a severe clinical challenge on a global scale. Dementia caused by Alzheimer’s disease(AD) is the most common form of dementia observed in the elderly, but its pathogenetic mechanism has still not been fully elucidated. Furthermore, no effective treatment strategy has been developed to date, despite considerable efforts. This can be mainly attributed to the paucity of animal models of AD that are sufficiently similar to humans. Among the presently established animal models, non-human primates share the closest relationship with humans, and their neural anatomy and neurobiology share highly similar characteristics with those of humans. Thus, there is no doubt that these play an irreplaceable role in AD research. Considering this, the present literature on non-human primate models of AD was reviewed to provide a theoretical basis for future research.
基金National Natural Science Foundation of China Grant(81941012)CAMS initiative for Innovative Medicine of China(2021-I2 M-1-034)National Key Research and Development Project(2017YFA0105200).
文摘Alzheimer's disease(AD)is a neurodegenerative disorder.The pathology of AD is characterized by extracellular amyloid beta(Aβ)plaques,neurofibrillary tangles com-posed of hyperphosphorylated tau,neuronal death,synapse loss,and brain atrophy.Many therapies have been tested to improve or at least effectively modify the course of AD.Meaningful data indicate that the transplantation of stem cells can alleviate neuropathology and significantly ameliorate cognitive deficits in animal models with Alzheimer's disease.Transplanted stem cells have shown their inherent advantages in improving cognitive impairment and memory dysfunction,although certain weak-nesses or limitations need to be overcome.This review recapitulates rodent models for AD,the therapeutic efficacy of stem cells,influencing factors,and the underlying mechanisms behind these changes.Stem cell therapy provides perspective and chal-lenges for its clinical application in the future.
基金National Natural Science Foundation of China,Grant/Award Number:82041008 and 32070543National Mega Projects of China for Major Infectious Diseases,Grant/Award Number:2017ZX10304402+1 种基金CAMS Initiative for Innovative Medicine of China,Grant/Award Number:2016-12M-2-006 and 2017-12M-3-015Beijing Municipal Natural Science Foundation,Grant/Award Number:M21004。
文摘Background:Cardiovascular diseases(CVDs)and diabetes mellitus(DM)are top two chronic comorbidities that increase the severity and mortality of COVID-19.However,how SARS-CoV-2 alters the progression of chronic diseases remain unclear.Methods:We used adenovirus to deliver h-ACE2 to lung to enable SARS-CoV-2 infection in mice.SARS-CoV-2’s impacts on pathogenesis of chronic diseases were studied through histopathological,virologic and molecular biology analysis.Results:Pre-existing CVDs resulted in viral invasion,ROS elevation and activation of apoptosis pathways contribute myocardial injury during SARS-CoV-2 infection.Viral infection increased fasting blood glucose and reduced insulin response in DM model.Bone mineral density decreased shortly after infection,which associated with impaired PI3K/AKT/mTOR signaling.Conclusion:We established mouse models mimicked the complex pathological symptoms of COVID-19 patients with chronic diseases.Pre-existing diseases could impair the inflammatory responses to SARS-CoV-2 infection,which further aggravated the pre-existing diseases.This work provided valuable information to better understand the interplay between the primary diseases and SARS-CoV-2 infection.
基金CAMS Innovation Fund for Medical Science,Grant/Award Number:2016-12M-1-010,2017-12M-2-005National Science Fund for Young Scholars,Grant/Award Number:81500938International Science and Technology Cooperation Program of China,Grant/Award Number:2015DFG32230
文摘Alzheimer's disease(AD) is an increasingly common neurodegenerative disease.Since the intestinal microbiome is closely related to nervous system diseases, alterations in the composition of intestinal microbiota could potentially contribute to the pathophysiology of AD. However, how the initial interactions with intestinal microbes alter events later in life, such as during neurodegenerative diseases, is still unclear. This review summarizes what is known about the relationship between the intestinal microbiome and AD.
基金The authors gratefully acknowledge the grants from the National Natural Science Foundation of China(No.20072025)Education 0ffice Foundation of Sichuan Province(No.2005C012)Sichuan Provincial Department of Science&Technology(No.2006J13-143)in support of this work.
文摘The oxygenation constants(Ko_2)of cobalt(Ⅱ)hydroxamates(CoL_2~1-CoL_2~3)with benzo-15-crown-5(B15C5)pendants were measured over the range of-5 to+20℃,and the values of thermodynamic parameters(ΔH^0 andΔS^0)were calculated based on these(No_2)values.Meanwhile,these crowned complexes were employed to the oxidation for p-xylene to p-toluic acid with air at 110Δunder normal atmospheric pressure.The effects of B15C5 pendant and the length of chain bonded to B15C5 in these complexes on the O_2-binding capabilities and oxidation for p-xylene were investigated with the comparison of crown-free analogues CoL_2~4.
