Amyloidosis is a multisystem disease that is characterized by deposition of fibrils in extracellular tissue,which mainly involves the kidney,heart,and autonomic nervous system.Two types of amyloidosis typically infilt...Amyloidosis is a multisystem disease that is characterized by deposition of fibrils in extracellular tissue,which mainly involves the kidney,heart,and autonomic nervous system.Two types of amyloidosis typically infiltrate the heart,including immunoglobulin light-chain(AL)and amyloid transthyretin(ATTR).ATTR is further subdivided into wild-type ATTR and variant ATTR caused by point mutations in the TTR gene.[1]Wild-type ATTR is considered as not uncommon in older patients with heart failure.Recently,a comprehensive set of consensus recommendations for the suspicion and diagnosis of ATTR was published,with particular focus on the combined application of noninvasive methods.[2]We present here a case of wild-type TTR cardiac amyloidosis(ATTRwt-CA),which was diagnosed by noninvasive modalities,and provide an overview of the recommended diagnostic approach of CA.Furthermore,to the best of our knowledge,this is the first Chinese case of ATTRwt-CA reported to date.展开更多
The health status of the floating elderly population and the need of community management services are complex and important problems.Owing to the change of living environment and the insecure medical care,the mobile ...The health status of the floating elderly population and the need of community management services are complex and important problems.Owing to the change of living environment and the insecure medical care,the mobile elderly people have more health and psy-chological problems compared to the rest of the elderly population.Therefore,the community should take a variety of measures to meet their needs and help them to better adapt to the new living environment,and maintain their physical and mental health.This paper aims to summarize recent studies on the physical and emotional health problems of mobile elderly people and related community management service needs.展开更多
Background Sarcopenia is a progressive and generalized skeletal muscle disorder that is associated with an increased likelihood of adverse outcomes, including falls, fractures, physical disability, and mortality. Howe...Background Sarcopenia is a progressive and generalized skeletal muscle disorder that is associated with an increased likelihood of adverse outcomes, including falls, fractures, physical disability, and mortality. However, there have been few systematic studies of the prevalence and prognostic values of sarcopenia in older patients with coronary heart disease(CHD). This study aimed to investigate the prevalence of sarcopenia in hospitalized older patients with CHD, and to prospectively evaluate the effect of sarcopenia on the short-term prognosis of these patients. Methods Patients aged ≥ 65 years, with the diagnosis of CHD from Peking Union Medical College Hospital between December 2017 and November 2018, were included. Sarcopenia was diagnosed according to consensus of the Asian Working Group for Sarcopenia in 2014. Follow-up items included unscheduled return visits, occurrence of major adverse cardiac and cerebral events (MACCE), and all-cause mortality. The MACCE-free survival curve of sarcopenic and non-sarcopenic older patients with CHD was estimated by the Kaplan-Meier method. Cox regression analysis was used to analyze the association between sarcopenia and an unscheduled return visits, MACCE, and all-cause mortality. Results A total of 345 older patients with CHD were enrolled in the study, with a median age of 74 years. Among the patients, 78 (22.6%) were diagnosed with sarcopenia. During the follow-up time, there were significantly more unscheduled return visits in sarcopenic patients than in non-sarcopenic patients (34.2% vs. 21.8%,χ^2 = 4.418, P = 0.036), while there was no significant difference in the occurrence of MACCE (χ^2 = 2.869, P = 0.09) or all-cause mortality (χ^2 = 1.673, P = 0.196) between these patient groups. The Kaplan-Meier curve showed that the MACCE-free survival time of sarcopenic patients was significantly shorter than that in non-sarcopenic patients (χ^2 = 4.102, P = 0.043). After adjusting for sex, age, and the Charlson comorbidity index, sarcopenia was not an independent risk factor of unscheduled return visits (HR = 1.002, 95% CI: 0.556–1.807). However, the complication of anxiety and depression was an independent risk factor (HR = 1.876, 95% CI: 1.012–3.477, P = 0.046) for unscheduled return visits in older patients with CHD. Conclusions There is a high prevalence of sarcopenia among hospitalized older adults with CHD. A shorter MACCE-free survival time and more unscheduled return visits are found in sarcopenic older patients with CHD. Clinicians should pay more attention to the functional status of older patients with CHD, as well as identification and management of geriatric syndromes.展开更多
Many mammals risk damage from oxidative stress stemming from frequent dives(i.e., cycles of ischemia/reperfusion and hypoxia/reoxygenation),high altitude and subterranean environments, or powered flight. Purine metabo...Many mammals risk damage from oxidative stress stemming from frequent dives(i.e., cycles of ischemia/reperfusion and hypoxia/reoxygenation),high altitude and subterranean environments, or powered flight. Purine metabolism is an essential response to oxidative stress, and an imbalance between purine salvage and de novo biosynthesis pathways can generate damaging reactive oxygen species(ROS). Here, we examined the evolution of 117 purine metabolism-related genes to explore the accompanying molecular mechanisms of enhanced purine metabolism in mammals under high oxidative stress. We found that positively selected genes,convergent changes, and nonparallel amino acid substitutions are possibly associated with adaptation to oxidative stress in mammals. In particular, the evolution of convergent genes with c AMP and c GMP regulation roles may protect mammals from oxidative damage. Additionally, 32 genes were identified as under positive selection in cetaceans, including key purine salvage enzymes(i.e., HPRT1), suggesting improved re-utilization of non-recyclable purines avoid hypoxanthine accumulation and reduce oxidative stress. Most intriguingly, we found that six unique substitutions in cetacean xanthine dehydrogenase(XDH), an enzyme that regulates the generation of the ROS precursor xanthine oxidase(XO) during ischemic/hypoxic conditions, show enhanced enzyme activity and thermal stability and diminished XO conversion activity. These functional adaptations are likely beneficial for cetaceans by reducing radical oxygen species production during diving. In summary, our findings offer insights into the molecular and functional evolution of purine metabolism genes in mammalian oxidative stress adaptations.展开更多
A 22-year-old Chinese man presented with fever, cough, hoarseness, neck pain, acute heart failure and hemoptysis. Pulmonary tuberculosis was proved by sputum culture. Chest imaging showed an aortic arch pseudoaneurysm...A 22-year-old Chinese man presented with fever, cough, hoarseness, neck pain, acute heart failure and hemoptysis. Pulmonary tuberculosis was proved by sputum culture. Chest imaging showed an aortic arch pseudoaneurysm and bilateral ground glass opacities. Echocardiography confirmed cardiomyopathy. With anti-TB drugs, high-dose prednisone and surgery, the life of this patient was successfully prolonged for more than four months. The concomitant disorders of aortic pseudoaneurysm, alveolar hemorrhage and cardiomyopathy in pulmonary tuberculosis are intriguing. We postulate that immune-mediated small vessel vasculitis triggered by pathogens plays an important role in the pathogenesis of this disease, rather than a direct TB infection.展开更多
Objective To investigate the role of tyrosine 23 （Tyr23） phosphorylation of Annexin A2 （Anxa2） in regulating the proliferation and invasion of human breast cancer SK-BR-3 cells. Methods A panel of lentivirus plasm...Objective To investigate the role of tyrosine 23 （Tyr23） phosphorylation of Annexin A2 （Anxa2） in regulating the proliferation and invasion of human breast cancer SK-BR-3 cells. Methods A panel of lentivirus plasmids expressing Anxa2-wide type （Ana2-WT）, Anxa2-Y23A, and Anxa2-Y23D was generated and infected with SK-BR-3 cells. The monoclonal strains were screened. The expression of Anxa2-WT, Anxa2-Y23A, and Anxa2-Y23D was determined by Western blot analysis. The ability of the cells to proliferate was detected through an MTT [3-（4,5-Dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide] test. Boyden chamber assays were employed to examine migration and invasion abilities. The interaction between Anxa2 and Stat3 was analyzed by immunoprecipitation analyses. Nucleoprotein and cytosolic protein were extracted from SK-BR-3, Anxa2-WT, Anxa2-Y23A, and Anxa2-Y23D cells to analyze the expression and localization of Stat3 phosphorylation. Results The monoclonal strains constitutively expressing Anxa2-WT, Anxa2-Y23A, and Anxa2-Y23D were screened. Both Anxa2-WT and Anxa2-Y23D enhanced the proliferation, migration and invasion abilities of SK-BR-3 cells （P〈0.05）. Immunoprecipitation analysis revealed that Anxa2 and Stat3 interacted with each other, and the expression of Stat3 phosphorylation in the nucleus was enhanced by Anxa2-Y23D. Conclusions Tyr23 phosphorylation of Anxa2 promotes the proliferation and invasion of human breast cancer SK-BR-3 cells and the phosphorylation of Stat3 in the nucleus.展开更多
The clinical efficacy and safety of proprietary Chinese medicine has become a more prevailing public health concern.The China Food and Drug Administration has pushed drug companies to conduct post-marketing reappraisa...The clinical efficacy and safety of proprietary Chinese medicine has become a more prevailing public health concern.The China Food and Drug Administration has pushed drug companies to conduct post-marketing reappraisal for proprietary Chinese medicine to provide additional evidence supporting the efficacy and safety of these medicine.In this paper,we propose a reappraisal protocol called“precise proprietary Chinese medicine”to precisely i)define the therapeutic aim;ii)design the protocol;iii)control the quality of proprietary Chinese medicine;iv)implement the protocol in the trial;v)study the mechanism-of-action of the proprietary Chinese medicine and vi)describe the indications of the proprietary Chinese medicine.We hope that these steps facilitate the post-marketing reappraisal of proprietary Chinese medicine.展开更多
The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer treatment.Herein,a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to ...The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer treatment.Herein,a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to treat breast cancer via accurate tumor elimination,on-demand adipose tissue regeneration and effective infection inhibition.The hydrogel consisted of thiol groups ended polyethylene glycol(SH-PEG-SH)and doxorubicin encapsulated mesoporous silica nanocarriers(DOX@MSNs)double crosslinked hyaluronic acid(HA)after loading of antibacterial peptides(AP)and adipose-derived stem cells(ADSCs).A pH-cleavable unsaturated amide bond was pre-introduced between MSNs and HA frame to perform the tumor-specific acidic environment dependent DOX@MSNs release,meanwhile an esterase degradable glyceryl dimethacrylate cap was grafted on MSNs,which contributed to the selective chemotherapy in tumor cells with over-expressed esterase.The bond cleavage between MSNs and HA would also cause the swelling of the hydrogel,which not only provide sufficient space for the growth of ADSCs,but allows the hydrogel to fully fill the irregular defects generated by surgery and residual tumor atrophy,resulting in the on-demand regeneration of adipose tissue.Moreover,the sustained release of AP could be simultaneously triggered along with the size change of hydrogel,which further avoided bacterial infection to promote tissue regeneration.展开更多
As one of the essential tools for spatio‒temporal traffic data mining,vehicle trajectory clustering is widely used to mine the behavior patterns of vehicles.However,uploading original vehicle trajectory data to the se...As one of the essential tools for spatio‒temporal traffic data mining,vehicle trajectory clustering is widely used to mine the behavior patterns of vehicles.However,uploading original vehicle trajectory data to the server and clustering carry the risk of privacy leakage.Therefore,one of the current challenges is determining how to perform vehicle trajectory clustering while protecting user privacy.We propose a privacy-preserving vehicle trajectory clustering framework and construct a vehicle trajectory clustering model(IKV)based on the variational autoencoder(VAE)and an improved K-means algorithm.In the framework,the client calculates the hidden variables of the vehicle trajectory and uploads the variables to the server;the server uses the hidden variables for clustering analysis and delivers the analysis results to the client.The IKV’workflow is as follows:first,we train the VAE with historical vehicle trajectory data(when VAE’s decoder can approximate the original data,the encoder is deployed to the edge computing device);second,the edge device transmits the hidden variables to the server;finally,clustering is performed using improved K-means,which prevents the leakage of the vehicle trajectory.IKV is compared to numerous clustering methods on three datasets.In the nine performance comparison experiments,IKV achieves optimal or sub-optimal performance in six of the experiments.Furthermore,in the nine sensitivity analysis experiments,IKV not only demonstrates significant stability in seven experiments but also shows good robustness to hyperparameter variations.These results validate that the framework proposed in this paper is not only suitable for privacy-conscious production environments,such as carpooling tasks,but also adapts to clustering tasks of different magnitudes due to the low sensitivity to the number of cluster centers.展开更多
To the Editor:The global burden of premature coronary artery disease(CAD)is increasing among the young population.Premature CAD generally refers to the occurrence of obstructive coronary atherothrombotic lesions in me...To the Editor:The global burden of premature coronary artery disease(CAD)is increasing among the young population.Premature CAD generally refers to the occurrence of obstructive coronary atherothrombotic lesions in men and women aged<55 years and<65 years,respectively,and particularly in those aged<45 years.[1]The incidence of CAD in the younger population has remained stable or has increased,despite the declining incidence in older adults.Patients with premature CAD have a poor long-term prognosis,experiencing a high rate of recurrent ischemic events,rapid progression to multivessel disease,and frequent premature death.[1]Thus,it is crucial to identify the underlying causes of premature CAD that are distinct from those of age-related CAD and improve patient outcomes through precise diagnosis and treatment.展开更多
Wild animals and plants have developed a variety of adaptive traits driven by adaptive evolution,an important strategy for species survival and persistence.Uncovering the molecular mechanisms of adaptive evolution is ...Wild animals and plants have developed a variety of adaptive traits driven by adaptive evolution,an important strategy for species survival and persistence.Uncovering the molecular mechanisms of adaptive evolution is the key to understanding species diversification,phenotypic convergence,and inter-species interaction.As the genome sequences of more and more non-model organisms are becoming available,the focus of studies on molecular mechanisms of adaptive evolution has shifted from the candidate gene method to genetic mapping based on genome-wide scanning.In this study,we reviewed the latest research advances in wild animals and plants,focusing on adaptive traits,convergent evolution,and coevolution.Firstly,we focused on the adaptive evolution of morphological,behavioral,and physiological traits.Secondly,we reviewed the phenotypic convergences of life history traits and responding to environmental pressures,and the underlying molecular convergence mechanisms.Thirdly,we summarized the advances of coevolution,including the four main types:mutualism,parasitism,predation and competition.Overall,these latest advances greatly increase our understanding of the underlying molecular mechanisms for diverse adaptive traits and species interaction,demonstrating that the development of evolutionary biology has been greatly accelerated by multi-omics technologies.Finally,we highlighted the emerging trends and future prospects around the above three aspects of adaptive evolution.展开更多
Accurate long-term power forecasting is important in the decision-making operation of the power grid and power consumption management of customers to ensure the power system’s reliable power supply and the grid econ...Accurate long-term power forecasting is important in the decision-making operation of the power grid and power consumption management of customers to ensure the power system’s reliable power supply and the grid economy’s reliable operation.However,most time-series forecasting models do not perform well in dealing with long-time-series prediction tasks with a large amount of data.To address this challenge,we propose a parallel time-series prediction model called LDformer.First,we combine Informer with long short-term memory(LSTM)to obtain deep representation abilities in the time series.Then,we propose a parallel encoder module to improve the robustness of the model and combine convolutional layers with an attention mechanism to avoid value redundancy in the attention mechanism.Finally,we propose a probabilistic sparse(ProbSparse)self-attention mechanism combined with UniDrop to reduce the computational overhead and mitigate the risk of losing some key connections in the sequence.Experimental results on five datasets show that LDformer outperforms the state-of-the-art methods for most of the cases when handling the different long-time-series prediction tasks.展开更多
Logs contain runtime information for both systems and users.As many of them use natural language,a typical log-based analysis needs to parse logs into the structured format first.Existing parsing approaches often take...Logs contain runtime information for both systems and users.As many of them use natural language,a typical log-based analysis needs to parse logs into the structured format first.Existing parsing approaches often take two steps.The first step is to find similar words(tokens)or sentences.Second,parsers extract log templates by replacing different tokens with variable placeholders.However,we observe that most parsers concentrate on precisely grouping similar tokens or logs.But they do not have a well-designed template extraction process,which leads to inconsistent accuracy on particular datasets.The root cause is the ambiguous definition of variable placeholders and similar templates.The consequences include abuse of variable placeholders,incorrectly divided templates,and an excessive number of templates over time.In this paper,we propose our online log parsing approach Cognition.It redefines variable placeholders via a strict lower bound to avoid ambiguity first.Then,it applies our template correction technique to merge and absorb similar templates.It eliminates the interference of commonly used parameters and thus isolates template quantity.Evaluation through 16 public datasets shows that Cognition has better accuracy and consistency than the state-of-the-art approaches.It also saves up to 52.1%of time cost on average than the others.展开更多
Lactic acid bacteria(LAB)are a representative probiotic.As the dominant flora in the human intestinal tract,LAB can regulate the balance of human intestinal flora and improve host health.The purpose of this study was ...Lactic acid bacteria(LAB)are a representative probiotic.As the dominant flora in the human intestinal tract,LAB can regulate the balance of human intestinal flora and improve host health.The purpose of this study was to isolate and screen LAB that are well suited to the intestinal characteristics of the Chinese population,with excellent probiotics and high antibacterial activity.After 16S ribosomal RNA(rRNA)homology and phylogenetic tree analysis,potential probiotics were tested for their antibacterial activity,resistance to artificial gastrointestinal fluid and drugs,surface hydrophobicity,and safety.Three strains of LAB with acid resistance,bile salt resistance,epithelial cell adhesion,and no multidrug resistance were selected:Lactobacillus salivarius,Leuconostoc lactis,and Lactobacillus paracasei.Analysis of the antibacterial active substances in the three strains and their fermentation broths revealed that the main antibacterial substances of L.lactis were organic acids,whereas those of L.salivarius and L.paracasei were organic acids and bacteriocins with broad-spectrum antibacterial activity.These three strains of probiotic LAB with high antibacterial activity were identified as bacterial resources that could potentially be used to develop probiotic preparations for the prevention and treatment of intestinal diseases caused by intestinal pathogens.展开更多
Inflammatory response plays a critical role in myocardial infarction(MI)repair.The neutrophil apoptosis and subsequent macrophage ingestion can result in inflammation resolution and initiate regeneration,while the the...Inflammatory response plays a critical role in myocardial infarction(MI)repair.The neutrophil apoptosis and subsequent macrophage ingestion can result in inflammation resolution and initiate regeneration,while the therapeutic strategy that simulates and enhances this natural process has not been established.Here,we constructed engineered neutrophil apoptotic bodies(eNABs)to simulate natural neutrophil apoptosis,which regulated inflammation response and enhanced MI repair.The eNABs were fabricated by combining natural neutrophil apoptotic body membrane which has excellent inflammation-tropism and immunoregulatory properties,and mesoporous silica nanoparticles loaded with hexyl 5-aminolevulinate hydrochloride(HAL).The eNABs actively targeted to macrophages and the encapsulated HAL simultaneously initiated the biosynthesis pathway of heme to produce anti-inflammatory bilirubin after intracellular release,thereby further enhancing the anti-inflammation effects.In in vivo studies,the eNABs efficiently modulated inflammation responses in the infarcted region to ameliorate cardiac function.This study demonstrates an effective biomimetic construction strategy to regulate macrophage functions for MI repair.展开更多
基金the National Key Research and Development Program of China(2016YFC0901500).
文摘Amyloidosis is a multisystem disease that is characterized by deposition of fibrils in extracellular tissue,which mainly involves the kidney,heart,and autonomic nervous system.Two types of amyloidosis typically infiltrate the heart,including immunoglobulin light-chain(AL)and amyloid transthyretin(ATTR).ATTR is further subdivided into wild-type ATTR and variant ATTR caused by point mutations in the TTR gene.[1]Wild-type ATTR is considered as not uncommon in older patients with heart failure.Recently,a comprehensive set of consensus recommendations for the suspicion and diagnosis of ATTR was published,with particular focus on the combined application of noninvasive methods.[2]We present here a case of wild-type TTR cardiac amyloidosis(ATTRwt-CA),which was diagnosed by noninvasive modalities,and provide an overview of the recommended diagnostic approach of CA.Furthermore,to the best of our knowledge,this is the first Chinese case of ATTRwt-CA reported to date.
文摘The health status of the floating elderly population and the need of community management services are complex and important problems.Owing to the change of living environment and the insecure medical care,the mobile elderly people have more health and psy-chological problems compared to the rest of the elderly population.Therefore,the community should take a variety of measures to meet their needs and help them to better adapt to the new living environment,and maintain their physical and mental health.This paper aims to summarize recent studies on the physical and emotional health problems of mobile elderly people and related community management service needs.
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS #2018-I2M-1-002)
文摘Background Sarcopenia is a progressive and generalized skeletal muscle disorder that is associated with an increased likelihood of adverse outcomes, including falls, fractures, physical disability, and mortality. However, there have been few systematic studies of the prevalence and prognostic values of sarcopenia in older patients with coronary heart disease(CHD). This study aimed to investigate the prevalence of sarcopenia in hospitalized older patients with CHD, and to prospectively evaluate the effect of sarcopenia on the short-term prognosis of these patients. Methods Patients aged ≥ 65 years, with the diagnosis of CHD from Peking Union Medical College Hospital between December 2017 and November 2018, were included. Sarcopenia was diagnosed according to consensus of the Asian Working Group for Sarcopenia in 2014. Follow-up items included unscheduled return visits, occurrence of major adverse cardiac and cerebral events (MACCE), and all-cause mortality. The MACCE-free survival curve of sarcopenic and non-sarcopenic older patients with CHD was estimated by the Kaplan-Meier method. Cox regression analysis was used to analyze the association between sarcopenia and an unscheduled return visits, MACCE, and all-cause mortality. Results A total of 345 older patients with CHD were enrolled in the study, with a median age of 74 years. Among the patients, 78 (22.6%) were diagnosed with sarcopenia. During the follow-up time, there were significantly more unscheduled return visits in sarcopenic patients than in non-sarcopenic patients (34.2% vs. 21.8%,χ^2 = 4.418, P = 0.036), while there was no significant difference in the occurrence of MACCE (χ^2 = 2.869, P = 0.09) or all-cause mortality (χ^2 = 1.673, P = 0.196) between these patient groups. The Kaplan-Meier curve showed that the MACCE-free survival time of sarcopenic patients was significantly shorter than that in non-sarcopenic patients (χ^2 = 4.102, P = 0.043). After adjusting for sex, age, and the Charlson comorbidity index, sarcopenia was not an independent risk factor of unscheduled return visits (HR = 1.002, 95% CI: 0.556–1.807). However, the complication of anxiety and depression was an independent risk factor (HR = 1.876, 95% CI: 1.012–3.477, P = 0.046) for unscheduled return visits in older patients with CHD. Conclusions There is a high prevalence of sarcopenia among hospitalized older adults with CHD. A shorter MACCE-free survival time and more unscheduled return visits are found in sarcopenic older patients with CHD. Clinicians should pay more attention to the functional status of older patients with CHD, as well as identification and management of geriatric syndromes.
基金supported by the National Natural Science Foundation of China(NSFC)(31900310 to R.T.)Key Project of the NSFC(32030011 and 31630071 to G.Y.)+2 种基金NSFC(31950410545 to I.S.)Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Jiangsu Specially-Appointed Professors Program(to I.S.)。
文摘Many mammals risk damage from oxidative stress stemming from frequent dives(i.e., cycles of ischemia/reperfusion and hypoxia/reoxygenation),high altitude and subterranean environments, or powered flight. Purine metabolism is an essential response to oxidative stress, and an imbalance between purine salvage and de novo biosynthesis pathways can generate damaging reactive oxygen species(ROS). Here, we examined the evolution of 117 purine metabolism-related genes to explore the accompanying molecular mechanisms of enhanced purine metabolism in mammals under high oxidative stress. We found that positively selected genes,convergent changes, and nonparallel amino acid substitutions are possibly associated with adaptation to oxidative stress in mammals. In particular, the evolution of convergent genes with c AMP and c GMP regulation roles may protect mammals from oxidative damage. Additionally, 32 genes were identified as under positive selection in cetaceans, including key purine salvage enzymes(i.e., HPRT1), suggesting improved re-utilization of non-recyclable purines avoid hypoxanthine accumulation and reduce oxidative stress. Most intriguingly, we found that six unique substitutions in cetacean xanthine dehydrogenase(XDH), an enzyme that regulates the generation of the ROS precursor xanthine oxidase(XO) during ischemic/hypoxic conditions, show enhanced enzyme activity and thermal stability and diminished XO conversion activity. These functional adaptations are likely beneficial for cetaceans by reducing radical oxygen species production during diving. In summary, our findings offer insights into the molecular and functional evolution of purine metabolism genes in mammalian oxidative stress adaptations.
文摘A 22-year-old Chinese man presented with fever, cough, hoarseness, neck pain, acute heart failure and hemoptysis. Pulmonary tuberculosis was proved by sputum culture. Chest imaging showed an aortic arch pseudoaneurysm and bilateral ground glass opacities. Echocardiography confirmed cardiomyopathy. With anti-TB drugs, high-dose prednisone and surgery, the life of this patient was successfully prolonged for more than four months. The concomitant disorders of aortic pseudoaneurysm, alveolar hemorrhage and cardiomyopathy in pulmonary tuberculosis are intriguing. We postulate that immune-mediated small vessel vasculitis triggered by pathogens plays an important role in the pathogenesis of this disease, rather than a direct TB infection.
基金supported by grants from the Changjiang Scholars and Innovative Research Team of the University in China(No.IRT1076)the National Natural Science Foundation of China(No.81071731)the Tianjin Science and Technology Commission Key Project(No. 12JCZDJC24500)
文摘Objective To investigate the role of tyrosine 23 （Tyr23） phosphorylation of Annexin A2 （Anxa2） in regulating the proliferation and invasion of human breast cancer SK-BR-3 cells. Methods A panel of lentivirus plasmids expressing Anxa2-wide type （Ana2-WT）, Anxa2-Y23A, and Anxa2-Y23D was generated and infected with SK-BR-3 cells. The monoclonal strains were screened. The expression of Anxa2-WT, Anxa2-Y23A, and Anxa2-Y23D was determined by Western blot analysis. The ability of the cells to proliferate was detected through an MTT [3-（4,5-Dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide] test. Boyden chamber assays were employed to examine migration and invasion abilities. The interaction between Anxa2 and Stat3 was analyzed by immunoprecipitation analyses. Nucleoprotein and cytosolic protein were extracted from SK-BR-3, Anxa2-WT, Anxa2-Y23A, and Anxa2-Y23D cells to analyze the expression and localization of Stat3 phosphorylation. Results The monoclonal strains constitutively expressing Anxa2-WT, Anxa2-Y23A, and Anxa2-Y23D were screened. Both Anxa2-WT and Anxa2-Y23D enhanced the proliferation, migration and invasion abilities of SK-BR-3 cells （P〈0.05）. Immunoprecipitation analysis revealed that Anxa2 and Stat3 interacted with each other, and the expression of Stat3 phosphorylation in the nucleus was enhanced by Anxa2-Y23D. Conclusions Tyr23 phosphorylation of Anxa2 promotes the proliferation and invasion of human breast cancer SK-BR-3 cells and the phosphorylation of Stat3 in the nucleus.
文摘The clinical efficacy and safety of proprietary Chinese medicine has become a more prevailing public health concern.The China Food and Drug Administration has pushed drug companies to conduct post-marketing reappraisal for proprietary Chinese medicine to provide additional evidence supporting the efficacy and safety of these medicine.In this paper,we propose a reappraisal protocol called“precise proprietary Chinese medicine”to precisely i)define the therapeutic aim;ii)design the protocol;iii)control the quality of proprietary Chinese medicine;iv)implement the protocol in the trial;v)study the mechanism-of-action of the proprietary Chinese medicine and vi)describe the indications of the proprietary Chinese medicine.We hope that these steps facilitate the post-marketing reappraisal of proprietary Chinese medicine.
基金the National High Level Talents Special Support Plan(X.C.)the“Young Talent Support Plan”of Xi'an Jiaotong University(X.C.)+2 种基金the Natural Science Foundation of Shaanxi Province(No.2022JZ-48 to X.C.)the National Natural Science Foundation of China(No.82272141 to X.C.)the Shaanxi Provincial Key Research and Development Plan Project(No.2023-JC-QN-0260 to X.Q.).
文摘The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer treatment.Herein,a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to treat breast cancer via accurate tumor elimination,on-demand adipose tissue regeneration and effective infection inhibition.The hydrogel consisted of thiol groups ended polyethylene glycol(SH-PEG-SH)and doxorubicin encapsulated mesoporous silica nanocarriers(DOX@MSNs)double crosslinked hyaluronic acid(HA)after loading of antibacterial peptides(AP)and adipose-derived stem cells(ADSCs).A pH-cleavable unsaturated amide bond was pre-introduced between MSNs and HA frame to perform the tumor-specific acidic environment dependent DOX@MSNs release,meanwhile an esterase degradable glyceryl dimethacrylate cap was grafted on MSNs,which contributed to the selective chemotherapy in tumor cells with over-expressed esterase.The bond cleavage between MSNs and HA would also cause the swelling of the hydrogel,which not only provide sufficient space for the growth of ADSCs,but allows the hydrogel to fully fill the irregular defects generated by surgery and residual tumor atrophy,resulting in the on-demand regeneration of adipose tissue.Moreover,the sustained release of AP could be simultaneously triggered along with the size change of hydrogel,which further avoided bacterial infection to promote tissue regeneration.
基金the National Natural Science Foundation of China(No.71961028)the Key Research and Development Program of Gansu Province,China(No.22YF7GA171)+3 种基金the University Industry Support Program of Gansu Province,China(No.2023QB-115)the Innovation Fund for Science and Technology-Based Small and Medium Enterprises of Gansu Province,China(No.23CXGA0136)the Traditional Chinese Medicine Industry Innovation Consortium Project of Gansu Province,China(No.22ZD6FA021-5)the Scientific Research Project of the Lanzhou Science and Technology Program,China(No.2018-01-58)。
文摘As one of the essential tools for spatio‒temporal traffic data mining,vehicle trajectory clustering is widely used to mine the behavior patterns of vehicles.However,uploading original vehicle trajectory data to the server and clustering carry the risk of privacy leakage.Therefore,one of the current challenges is determining how to perform vehicle trajectory clustering while protecting user privacy.We propose a privacy-preserving vehicle trajectory clustering framework and construct a vehicle trajectory clustering model(IKV)based on the variational autoencoder(VAE)and an improved K-means algorithm.In the framework,the client calculates the hidden variables of the vehicle trajectory and uploads the variables to the server;the server uses the hidden variables for clustering analysis and delivers the analysis results to the client.The IKV’workflow is as follows:first,we train the VAE with historical vehicle trajectory data(when VAE’s decoder can approximate the original data,the encoder is deployed to the edge computing device);second,the edge device transmits the hidden variables to the server;finally,clustering is performed using improved K-means,which prevents the leakage of the vehicle trajectory.IKV is compared to numerous clustering methods on three datasets.In the nine performance comparison experiments,IKV achieves optimal or sub-optimal performance in six of the experiments.Furthermore,in the nine sensitivity analysis experiments,IKV not only demonstrates significant stability in seven experiments but also shows good robustness to hyperparameter variations.These results validate that the framework proposed in this paper is not only suitable for privacy-conscious production environments,such as carpooling tasks,but also adapts to clustering tasks of different magnitudes due to the low sensitivity to the number of cluster centers.
基金supported by grants from the National Key Research and Development Program of China(Nos.2022YFC2703100,2020YFC0861000,and 2016YFC0901500)National Natural Science Foundation(No.82170486)+1 种基金Beijing Natural Science Foundation(No.L202046)CAMS Innovation Fund for Medical Sciences(Nos.2021-I2M-1-003 and 2017-I2M-2-001),and Center for Rare Diseases Research,Chinese Academy of Medical Sciences,Beijing,China.
文摘To the Editor:The global burden of premature coronary artery disease(CAD)is increasing among the young population.Premature CAD generally refers to the occurrence of obstructive coronary atherothrombotic lesions in men and women aged<55 years and<65 years,respectively,and particularly in those aged<45 years.[1]The incidence of CAD in the younger population has remained stable or has increased,despite the declining incidence in older adults.Patients with premature CAD have a poor long-term prognosis,experiencing a high rate of recurrent ischemic events,rapid progression to multivessel disease,and frequent premature death.[1]Thus,it is crucial to identify the underlying causes of premature CAD that are distinct from those of age-related CAD and improve patient outcomes through precise diagnosis and treatment.
基金supported by the National Natural Science Foundation of China (31821001)the Strategic Priority Research Program of Chinese Academy of Sciences (XDB31000000)。
文摘Wild animals and plants have developed a variety of adaptive traits driven by adaptive evolution,an important strategy for species survival and persistence.Uncovering the molecular mechanisms of adaptive evolution is the key to understanding species diversification,phenotypic convergence,and inter-species interaction.As the genome sequences of more and more non-model organisms are becoming available,the focus of studies on molecular mechanisms of adaptive evolution has shifted from the candidate gene method to genetic mapping based on genome-wide scanning.In this study,we reviewed the latest research advances in wild animals and plants,focusing on adaptive traits,convergent evolution,and coevolution.Firstly,we focused on the adaptive evolution of morphological,behavioral,and physiological traits.Secondly,we reviewed the phenotypic convergences of life history traits and responding to environmental pressures,and the underlying molecular convergence mechanisms.Thirdly,we summarized the advances of coevolution,including the four main types:mutualism,parasitism,predation and competition.Overall,these latest advances greatly increase our understanding of the underlying molecular mechanisms for diverse adaptive traits and species interaction,demonstrating that the development of evolutionary biology has been greatly accelerated by multi-omics technologies.Finally,we highlighted the emerging trends and future prospects around the above three aspects of adaptive evolution.
基金Project supported by the National Natural Science Foundation of China(No.71961028)the Key Research and Development Program of Gansu Province,China(No.22YF7GA171)+2 种基金the University Industry Support Program of Gansu Province,China(No.2023QB-115)the Innovation Fund for Science and Technology-based Small and Medium Enterprises of Gansu Province,China(No.23CXGA0136)the Scientific Research Project of the Lanzhou Science and Technology Program,China(No.2018-01-58)。
文摘Accurate long-term power forecasting is important in the decision-making operation of the power grid and power consumption management of customers to ensure the power system’s reliable power supply and the grid economy’s reliable operation.However,most time-series forecasting models do not perform well in dealing with long-time-series prediction tasks with a large amount of data.To address this challenge,we propose a parallel time-series prediction model called LDformer.First,we combine Informer with long short-term memory(LSTM)to obtain deep representation abilities in the time series.Then,we propose a parallel encoder module to improve the robustness of the model and combine convolutional layers with an attention mechanism to avoid value redundancy in the attention mechanism.Finally,we propose a probabilistic sparse(ProbSparse)self-attention mechanism combined with UniDrop to reduce the computational overhead and mitigate the risk of losing some key connections in the sequence.Experimental results on five datasets show that LDformer outperforms the state-of-the-art methods for most of the cases when handling the different long-time-series prediction tasks.
基金supported by the National Key Research and Development Program of China under Grant No.2019YFB1802800the National Science Fund for Distinguished Young Scholars of China under Grant No.61725206。
文摘Logs contain runtime information for both systems and users.As many of them use natural language,a typical log-based analysis needs to parse logs into the structured format first.Existing parsing approaches often take two steps.The first step is to find similar words(tokens)or sentences.Second,parsers extract log templates by replacing different tokens with variable placeholders.However,we observe that most parsers concentrate on precisely grouping similar tokens or logs.But they do not have a well-designed template extraction process,which leads to inconsistent accuracy on particular datasets.The root cause is the ambiguous definition of variable placeholders and similar templates.The consequences include abuse of variable placeholders,incorrectly divided templates,and an excessive number of templates over time.In this paper,we propose our online log parsing approach Cognition.It redefines variable placeholders via a strict lower bound to avoid ambiguity first.Then,it applies our template correction technique to merge and absorb similar templates.It eliminates the interference of commonly used parameters and thus isolates template quantity.Evaluation through 16 public datasets shows that Cognition has better accuracy and consistency than the state-of-the-art approaches.It also saves up to 52.1%of time cost on average than the others.
基金the National Key Research and Development Program of China(No.2016YFD0400605)。
文摘Lactic acid bacteria(LAB)are a representative probiotic.As the dominant flora in the human intestinal tract,LAB can regulate the balance of human intestinal flora and improve host health.The purpose of this study was to isolate and screen LAB that are well suited to the intestinal characteristics of the Chinese population,with excellent probiotics and high antibacterial activity.After 16S ribosomal RNA(rRNA)homology and phylogenetic tree analysis,potential probiotics were tested for their antibacterial activity,resistance to artificial gastrointestinal fluid and drugs,surface hydrophobicity,and safety.Three strains of LAB with acid resistance,bile salt resistance,epithelial cell adhesion,and no multidrug resistance were selected:Lactobacillus salivarius,Leuconostoc lactis,and Lactobacillus paracasei.Analysis of the antibacterial active substances in the three strains and their fermentation broths revealed that the main antibacterial substances of L.lactis were organic acids,whereas those of L.salivarius and L.paracasei were organic acids and bacteriocins with broad-spectrum antibacterial activity.These three strains of probiotic LAB with high antibacterial activity were identified as bacterial resources that could potentially be used to develop probiotic preparations for the prevention and treatment of intestinal diseases caused by intestinal pathogens.
基金This work was supported by National Key Research and Development Program of China(2016YFC1101400)National Natural Science Foundation of China(31800817)+4 种基金Innovative Talent Project of Shaanxi province(2020KJXX-057)National Natural Science Foundation of China(31870970)National Natural Science Foundation of China(81991504)Key Research and Development Program of Shaanxi Province(2019SF-073)Young Talent Support Program of Stomatology of FMMU(41741835-MZ2020D5).
文摘Inflammatory response plays a critical role in myocardial infarction(MI)repair.The neutrophil apoptosis and subsequent macrophage ingestion can result in inflammation resolution and initiate regeneration,while the therapeutic strategy that simulates and enhances this natural process has not been established.Here,we constructed engineered neutrophil apoptotic bodies(eNABs)to simulate natural neutrophil apoptosis,which regulated inflammation response and enhanced MI repair.The eNABs were fabricated by combining natural neutrophil apoptotic body membrane which has excellent inflammation-tropism and immunoregulatory properties,and mesoporous silica nanoparticles loaded with hexyl 5-aminolevulinate hydrochloride(HAL).The eNABs actively targeted to macrophages and the encapsulated HAL simultaneously initiated the biosynthesis pathway of heme to produce anti-inflammatory bilirubin after intracellular release,thereby further enhancing the anti-inflammation effects.In in vivo studies,the eNABs efficiently modulated inflammation responses in the infarcted region to ameliorate cardiac function.This study demonstrates an effective biomimetic construction strategy to regulate macrophage functions for MI repair.
