Pathological cardiac hypertrophy contributes to the development of heart failure(HF).NOL1/NOP2/Sun domain family member 2(NSUN2)is implicated in pathophysiological processes of many diseases.However,the function and o...Pathological cardiac hypertrophy contributes to the development of heart failure(HF).NOL1/NOP2/Sun domain family member 2(NSUN2)is implicated in pathophysiological processes of many diseases.However,the function and operation of NSUN2 in cardiac hypertrophy and HF remain unclear.Here,we observed a significant increase in the levels of NSUN2 expression in both human hearts with HF and in mouse hearts with hypertrophy induced by transverse aortic constriction(TAC)and angiotensin II(Ang II)treatment.Cardiomyocyte-specific knockout of NSUN2 attenuated the reduced cardiac ejection fraction(EF)and fractional shortening(FS)and the increased heart weight to tibial length(HW/TL)upon either TAC or Ang II infusion.Conversely,cardiac-specific overexpression of NSUN2 resulted in cardiac remodeling as indicated by a prominent increase in hypertrophic growth and cardiac fibrosis and a robust decline in cardiac EF and FS.Mechanistically,NSUN2 induces 5-methylcytosine(m5C)modification of La-related protein 1(LARP1)to enhance its messenger RNA(mRNA)stability,which is mediated by Y-box binding protein 1(YBX1).Increased LARP1 further interacts with GATA binding protein 4(GATA4)mRNA and prevents its degradation.LARP1 silencing partially attenuates TAC and NSUN2 induced cardiac hypertrophy and HF.Collectively,this study provides a new insight into the central role of NSUN2 in cardiac hypertrophy,indicating that NSUN2 may serve as a novel therapeutic target for HF.展开更多
Wheat-maize(WM)and wheat-soybean(WS)double-cropping rotation systems are predominant in the North China Plain,with implications for national agricultural output and sustainability.As rotation systems exert legacy effe...Wheat-maize(WM)and wheat-soybean(WS)double-cropping rotation systems are predominant in the North China Plain,with implications for national agricultural output and sustainability.As rotation systems exert legacy effects on soil health and crop productivity,the role of crop rotation in shaping the root-associated microbiome of the succeeding crops has emerged as a pivotal aspect of crop management research.Here,the effects of the preceding two cycles of WM and WS rotations on the recruitment and filtering of wheat root-associated bacterial communities across wheat developmental stages were investigated.Our results revealed that bacterial community diversity and composition were primarily influenced by compartment and developmental stage,while the preceding rotation systems had a slight but significant effect on wheat root-associated bacterial communities.The co-occurrence networks under WM were more complex in the wheat rhizosphere and rhizoplane,with the operational taxonomic units(OTUs)related to cellulolysis showing greater connectivity.The co-occurrence networks under WS were simple but stable in the rhizosphere and complex in the rhizoplane and endosphere,with the OTUs related to ureolysis and nitrogen fixation showing greater connectivity.While both stochastic and deterministic processes contributed to the assembly of wheat root-associated bacterial communities,the contributions of deterministic processes under WS were 19.4-38.5%higher than those under the WM rotation across the root-associated compartments,indicating the substantial impact of a soybean legacy effect on wheat root selection of microbes.Plant growthpromoting rhizobacteria with the potential to fix nitrogen,produce indole-3-acetic acid,and inhibit diseases such as Betaproteobacteriales,Azospirillales and Dyella sp.,were identified within the OTUs that were consistently enriched across all the wheat root-associated compartments and developmental stages,which were also important predictors of wheat yield.This study elucidates the role of crop rotation in modulating the dynamics of crop root-associated bacterial communities,and underscores the potential of targeted microbiome manipulation for optimizing wheat production and enhancing soil health.展开更多
Menopause is characterized by the cessation of menstruation and a decline in reproductive function,which is an intrinsic component of the aging process.However,it has been a frequently overlooked field of women’s hea...Menopause is characterized by the cessation of menstruation and a decline in reproductive function,which is an intrinsic component of the aging process.However,it has been a frequently overlooked field of women’s health.The oral and gut microbiota,constituting the largest ecosystem within the human body,are important for maintaining human health and notably contribute to the healthy aging of menopausal women.Therefore,a comprehensive review elucidating the impact of the gut and oral microbiota on menopause for healthy aging is of paramount importance.This paper presents the current understanding of the microbiome during menopause,with a particular focus on alterations in the oral and gut microbiota.Our study elucidates the complex interplay between the microbiome and sex hormone levels,explores microbial crosstalk dynamics,and investigates the associations between the microbiome and diseases linked to menopause.Additionally,this review explores the potential of microbiome-targeting therapies for managing menopause-related diseases.Given that menopause can last for approximately 30 years,gaining insights into how the microbiome and menopause interact could pave the way for innovative interventions,which may result in symptomatic relief from menopause and an increase in quality of life in women.展开更多
[Objectives] This study was conducted to clarify the evolution characteristics of foxtail millet varieties in different ages and provide a basis for the breeding of new varieties. [Methods] A field experiment was carr...[Objectives] This study was conducted to clarify the evolution characteristics of foxtail millet varieties in different ages and provide a basis for the breeding of new varieties. [Methods] A field experiment was carried out on 20 main foxtail millet varieties promoted in North China developed from the 1980 s to 2000 s. The physiological and biochemical indexes of different foxtail millet varieties in four ages were compared, including chlorophyll content, soluble protein content, glutamine synthetase(GS) activity and glutamate synthase(GOGAT) activity, and the correlation between enzyme activity and yield was analyzed. [Results] The chlorophyll SPAD values of the flag leaf and functional leaves of foxtail millet varieties decreased with the filling process. The SPAD values of the flag leaf, top second leaf and top third leaf were higher in the varieties developed in the 1990 s and 2000 s than those in the 1980 s and 2010 s. The activity of glutamine synthetase(GS) and glutamate synthase(GOGAT) showed a single-peak curve in different foxtail millet varieties developed in the recent 30 years, and the peaks of the two were at 7 d and at 7 or 14 d, respectively. The activity of GS and GOGAT increased with the breeding age. In the period from 7 d after anthesis to the mature period, the decreases in the soluble protein content followed an order of 2010 s, 2000 s, 1990 s and 1980 s from small to large, indicating that the degradation rate of various enzyme sources and metabolic regulators in foxtail millet plants decreased during the improvement process. At 35 d after anthesis, the correlation coefficient between GS activity and yield was-0.247, that is, there was a negative correlation with yield. And there was a significant positive correlation between GOGAT activity and yield, and the correlation coefficient was as high as 0.455 at 7 d after anthesis. [Conclusions] Changes in the GS activity, GOGAT activity and soluble protein content in the flag leaf of foxtail millet varieties developed in recent years have a certain impact on yield.展开更多
Acute myeloid leukemia(AML)is an aging-related malignancy,with patients aged≥60 years old facing significantly poorer prognosis.Umbilical cord blood(UCB)has emerged as a promising source with effective anti-aging rol...Acute myeloid leukemia(AML)is an aging-related malignancy,with patients aged≥60 years old facing significantly poorer prognosis.Umbilical cord blood(UCB)has emerged as a promising source with effective anti-aging roles.Here,we conducted a prospective,phase 2,single-arm trial of UCB infusion as an adjuvant consolidation therapy in elderly AML patients(ChiCTR-OPC15006492).A total of 51 patients were enrolled(median age 66 years;range,60-75)and received two cycles of consolidation chemotherapy combined with UCB infusion.At a median follow-up of 27.3 months(range,9.3-100),the median overall survival(OS)was not yet reached and the median event-free survival(EFS)was 72.2 months(range,5.4-100).The 2-year OS and EFS rates were 76.9%and 62.8%,respectively.No acute graft-versus-host disease(aGVHD)or toxicity-related death occurred in any patient.The median times to platelet and neutrophil recovery were 11.5 days(range,6-17)and 12.2 days(range,0-21),respectively.Singlecell RNA sequencing(scRNA-seq)identified enhanced anti-tumor and anti-aging properties of UCB,manifested through activation of immune responses and telomere synthesis/maintenance.Thesefindings suggest that UCB infusion is an effective and safe postremission adjuvant therapy for elderly AML patients.This study provides evidence that anti-aging therapy may serve as a new and promising dimension in combined cancer treatment.展开更多
With the development of higher education and social changes,college English courses no longer only focus on the cultivation of language skills,but also pay more attention to the comprehensive quality cultivation of st...With the development of higher education and social changes,college English courses no longer only focus on the cultivation of language skills,but also pay more attention to the comprehensive quality cultivation of students.As an important educational tool,the construction and practice of ideological and political education in college English classrooms are of great importance and challenge.This article aims to explore the construction and practice of ideological and political education in college English classrooms,analyzing the construction of teaching staff,curriculum design,textbook selection,teaching methods and means,and other aspects.Firstly,the cultivation of teaching staff is the key to ensuring the quality of ideological and political education,and it is necessary to improve teachers'ideological and political literacy and abilities.Secondly,the curriculum and textbook selection should focus on ideological and political related topics and texts to stimulate students'thinking on social ethics,politics,and other issues.At the same time,teaching objectives should focus on cultivating students'correct political concepts and values.Finally,the textbook content and courseware should have an ideological and political orientation,incorporating in-depth analysis and exploration of social issues.Through the above measures,we can effectively construct ideological and political education in college English classrooms,and achieve the cultivation of students'comprehensive qualities.展开更多
Heart failure(HF)patients in general have a higher risk of developing cancer.Several animal studies have indicated that cardiac remodeling and HF remarkably accelerate tumor progression,highlighting a cause-and-effect...Heart failure(HF)patients in general have a higher risk of developing cancer.Several animal studies have indicated that cardiac remodeling and HF remarkably accelerate tumor progression,highlighting a cause-and-effect relationship between these two disease entities.Targeting ferroptosis,a prevailing form of non-apoptotic cell death,has been considered a promising therapeutic strategy for human cancers.Exosomes critically contribute to proximal and distant organ-organ communications and play crucial roles in regulating diseases in a paracrine manner.However,whether exosomes control the sensitivity of cancer to ferroptosis via regulating the cardiomyocyte-tumor cell crosstalk in ischemic HF has not yet been explored.Here,we demonstrate that myocardial infarction(MI)decreased the sensitivity of cancer cells to the canonical ferroptosis activator erastin or imidazole ketone erastin in a mouse model of xenograft tumor.Post-MI plasma exosomes potently blunted the sensitivity of tumor cells to ferroptosis inducers both in vitro in mouse Lewis lung carcinoma cell line LLC and osteosarcoma cell line K7M2 and in vivo with xenograft tumorigenesis model.The expression of miR-22-3p in cardiomyocytes and plasma-exosomes was significantly upregulated in the failing hearts of mice with chronic MI and of HF patients as well.Incubation of tumor cells with the exosomes isolated from post-MI mouse plasma or overexpression of miR-22-3p alone abrogated erastin-induced ferroptotic cell death in vitro.Cardiomyocyte-enriched miR-22-3p was packaged in exosomes and transferred into tumor cells.Inhibition of cardiomyocyte-specific miR-22-3p by AAV9 sponge increased the sensitivity of cancer cells to ferroptosis.ACSL4,a pro-ferroptotic gene,was experimentally established as a target of miR-22-3p in tumor cells.Taken together,our findings uncovered for the first time that MI suppresses erastin-induced ferroptosis through releasing miR-22-3p-enriched exosomes derived from cardiomyocytes.Therefore,targeting exosome-mediated cardiomyocyte/tumor pathological communication may offer a novel approach for the ferroptosis-based antitumor therapy.展开更多
With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures,there have been widespread SARS-CoV-2 infections in Chinese mainland.Here we have analyzed 369 viral genome...With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures,there have been widespread SARS-CoV-2 infections in Chinese mainland.Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai,identifying a large number of sublineages of the SARS-CoV-2 Omicron family.Phylogenetic analysis,coupled with contact history tracing,revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China(BA.5.2 mainly in Guangzhou and Shanghai,and BF.7 mainly in Beijing)and two highly infectious sublineages recently imported from abroad(XBB and BQ.1).Publicly available data from August 31 to November 29,2022 indicated an overall severe/critical case rate of 0.035%nationwide,while analysis of 5706 symptomatic patients treated at the Shanghai Public Health Center between September 1 and December 26,2022 showed that 20 cases(0.35%)without comorbidities progressed into severe/critical conditions and 153 cases(2.68%)with COVID-19-exacerbated comorbidities progressed into severe/critical conditions.These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases.Furthermore,mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year,whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023,and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival(January 21,2023).Altogether,these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population,especially in the rural areas,to ensure the country’s smooth exit from the ongoing pandemic and accelerate socio-economic recovery.展开更多
The cause–effect relationship between meso-γ-scale rotation and extreme short-term precipitation events remains elusive in mesoscale meteorological research.We aimed to elucidate this relationship by analyzing a rai...The cause–effect relationship between meso-γ-scale rotation and extreme short-term precipitation events remains elusive in mesoscale meteorological research.We aimed to elucidate this relationship by analyzing a rainstorm over the Pearl River Delta during the nocturnal hours of 15 May 2017 based on 6-min radar observations and 1-min rain gauge data.This rainstorm had a maximum hourly rainfall of 100.1 mm,with 26 stations recording hourly rainfall>60 mm h^(−1) in 5 h.Extreme heavy precipitation was produced in association with a convergence zone along the southern side of a synoptic low-level shear line,where southwesterly warm,humid airflows with precipitable water of>60 mm,little convection inhibition(<10 J kg^(−1)),and a low lifting condensation level(about 300 m)dominated.A meso-γ-scale vortex was quantitatively identified during the hour with the largest number of gauges observing extreme hourly rainfall.The vortex had a mean diameter of 6.1 km and a peak intensity of 3.1×10^(−3) s^(−1) during its lifetime of 54 min.The vortex initialized and remained inside the region of extreme rain rates(radar-retrieved rain rates>100 mm h^(−1)),reached its peak intensity after the peak of the collocated 6-min rainfall accumulation,and then weakened rapidly after the extreme rainfall region moved away.The radar-retrieved liquid water path was about five to seven times the ice water path and the specific differential phase(Kdp)below 0°C increased sharply downward during the lifetime of the vortex,suggesting the presence of active warm rain microphysical processes.These results indicate that the release of the latent heat of condensation induced by extreme rainfall could have contributed to the formation of the vortex in an environment with a weak 0–1-km vertical wind shear(about 4–5 m s^(−1))through enhanced lowlevel convergence,although the strengthening of low-level updrafts by rotational dynamic effects and short-term rainfall cannot be ruled out.展开更多
The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic.Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earl...The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic.Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022.Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020,BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood.In particular,severe/critical cases of COVID19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment.Importantly,the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototypeinactivated vaccines,supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records.Furthermore,even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection,vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged≥60 years old.Together,our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.展开更多
Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases.Here,to explore the role of the gut microbiome in the host immune responses in COVID-19,we conducted s...Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases.Here,to explore the role of the gut microbiome in the host immune responses in COVID-19,we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples.We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones.We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity,such as Enterococcus faecium,Coprococcus comes,Roseburia intestinalis,Akkermansia ntuciniphila,Bacteroides cellulosilyticus and Blautia obeum.We further analyzed the correlation between the abundance of gut microbes and host responses,and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe,including Coprococcus comes that was positively correlated with CD3^(+)/CD4^(+)/CD8^(+)lymphocyte counts.In addition,an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells(PBMCs)showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples.Moreover,a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases,including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19.Together,our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.展开更多
Ischemic heart failure(HF)remains a leading cause of morbidity and mortality.Maintaining homeostasis of cardiac function and preventing cardiac remodeling deterioration are critical to halting HF progression.Methyltra...Ischemic heart failure(HF)remains a leading cause of morbidity and mortality.Maintaining homeostasis of cardiac function and preventing cardiac remodeling deterioration are critical to halting HF progression.Methyltransferase-like protein 13(Mettl13)has been shown to regulate protein translation efficiency by acting as a protein lysine methyltransferase,but its role in cardiac pathology remains unexplored.This study aims to characterize the roles and mechanisms of Mettl13 in cardiac contractile function and HF.We found that Mettl13 was downregulated in the failing hearts of mice post-myocardial infarction(MI)and in a cellular model of oxidative stress.Cardiomyocyte-specific overexpression of Mettl13 mediated by AAV9-Mettl13 attenuated cardiac contractile dysfunction and fibrosis in response to MI,while silencing of Mettl13 impaired cardiac function in normal mice.Moreover,Mettl13 overexpression abrogated the reduction in cell shortening,Ca^(2+)transient amplitude and SERCA2a protein levels in the cardiomyocytes of adult mice with MI.Conversely,knockdown of Mettl13 impaired the contractility of cardiomyocytes,and decreased Ca^(2+)transient amplitude and SERCA2a protein expression in vivo and in vitro.Mechanistically,Mettl13 impaired the stability of c-Cbl by inducing lysine methylation of c-Cbl,which in turn inhibited ubiquitination-dependent degradation of SERCA2a.Furthermore,the inhibitory effects of knocking down Mettl13 on SERCA2a protein expression and Ca^(2+)transients were partially rescued by silencing c-Cbl in H_(2)O_(2)-treated cardiomyocytes.In conclusion,our study uncovers a novel mechanism that involves the Mettl13/c-Cbl/SERCA2a axis in regulating cardiac contractile function and remodeling,and identifies Mettl13 as a novel therapeutic target for ischemic HF.展开更多
The attainment of both high strength and high ductility is always the goal for structure materials,because the two properties generally are mutually competing,called strength-ductility trade-off.Nowadays,the data-driv...The attainment of both high strength and high ductility is always the goal for structure materials,because the two properties generally are mutually competing,called strength-ductility trade-off.Nowadays,the data-driven paradigm combined with expert domain knowledge provides the state-of-the-art methodology to design and discovery for structure materials with high strength and high ductility.To enhance both strength and ductility,a joint feature is proposed here to be the product of strength multiplying ductility.The strategy of“divide and conquer”is developed to solve the contradictory problem,that material experimental data of mechanical behaviors are,in general,small in size and big in noise,while the design space is huge,by a newly developed data preprocessing algorithm,named the Tree-Classifier for Gaussian Process Regression(TCGPR).The TCGPR effectively divides an original dataset in a huge design space into three appropriate sub-domains and then three Machine Learning(ML)models conquer the three sub-domains,achieving significantly improved prediction accuracy and generality.After that the Bayesian sampling is applied to design next experiments by balancing exploitation and exploration.Finally,the experiment results confirm the ML predictions,exhibiting novel lead-free solder alloys with high strength high ductility.Various material characterizations were also conducted to explore the mechanism of high strength and high ductility of the alloys.展开更多
基金supported by grants from the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2024ZD0537909)the National Natural Science Foundation of China(82273928,82473919,82330011,82161148007)+2 种基金the Distinguished Young Scholars of Natural Science Foundation of Heilongjiang Province(JQ2024H002)the Chunyan Programme of Heilongjiang Province(CYQN2403)the CAMS Innovation Fund for Medical Sciences(CIFMS,2020-I2M-5-003).
文摘Pathological cardiac hypertrophy contributes to the development of heart failure(HF).NOL1/NOP2/Sun domain family member 2(NSUN2)is implicated in pathophysiological processes of many diseases.However,the function and operation of NSUN2 in cardiac hypertrophy and HF remain unclear.Here,we observed a significant increase in the levels of NSUN2 expression in both human hearts with HF and in mouse hearts with hypertrophy induced by transverse aortic constriction(TAC)and angiotensin II(Ang II)treatment.Cardiomyocyte-specific knockout of NSUN2 attenuated the reduced cardiac ejection fraction(EF)and fractional shortening(FS)and the increased heart weight to tibial length(HW/TL)upon either TAC or Ang II infusion.Conversely,cardiac-specific overexpression of NSUN2 resulted in cardiac remodeling as indicated by a prominent increase in hypertrophic growth and cardiac fibrosis and a robust decline in cardiac EF and FS.Mechanistically,NSUN2 induces 5-methylcytosine(m5C)modification of La-related protein 1(LARP1)to enhance its messenger RNA(mRNA)stability,which is mediated by Y-box binding protein 1(YBX1).Increased LARP1 further interacts with GATA binding protein 4(GATA4)mRNA and prevents its degradation.LARP1 silencing partially attenuates TAC and NSUN2 induced cardiac hypertrophy and HF.Collectively,this study provides a new insight into the central role of NSUN2 in cardiac hypertrophy,indicating that NSUN2 may serve as a novel therapeutic target for HF.
基金the National Natural Science Foundation of China(42107339)the China Agriculture Research System(CARS-04)。
文摘Wheat-maize(WM)and wheat-soybean(WS)double-cropping rotation systems are predominant in the North China Plain,with implications for national agricultural output and sustainability.As rotation systems exert legacy effects on soil health and crop productivity,the role of crop rotation in shaping the root-associated microbiome of the succeeding crops has emerged as a pivotal aspect of crop management research.Here,the effects of the preceding two cycles of WM and WS rotations on the recruitment and filtering of wheat root-associated bacterial communities across wheat developmental stages were investigated.Our results revealed that bacterial community diversity and composition were primarily influenced by compartment and developmental stage,while the preceding rotation systems had a slight but significant effect on wheat root-associated bacterial communities.The co-occurrence networks under WM were more complex in the wheat rhizosphere and rhizoplane,with the operational taxonomic units(OTUs)related to cellulolysis showing greater connectivity.The co-occurrence networks under WS were simple but stable in the rhizosphere and complex in the rhizoplane and endosphere,with the OTUs related to ureolysis and nitrogen fixation showing greater connectivity.While both stochastic and deterministic processes contributed to the assembly of wheat root-associated bacterial communities,the contributions of deterministic processes under WS were 19.4-38.5%higher than those under the WM rotation across the root-associated compartments,indicating the substantial impact of a soybean legacy effect on wheat root selection of microbes.Plant growthpromoting rhizobacteria with the potential to fix nitrogen,produce indole-3-acetic acid,and inhibit diseases such as Betaproteobacteriales,Azospirillales and Dyella sp.,were identified within the OTUs that were consistently enriched across all the wheat root-associated compartments and developmental stages,which were also important predictors of wheat yield.This study elucidates the role of crop rotation in modulating the dynamics of crop root-associated bacterial communities,and underscores the potential of targeted microbiome manipulation for optimizing wheat production and enhancing soil health.
基金supported by Science&Technology Fundamental Resources Investigation Program(2022FY100800)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-12M-1-023/2023-12M-C&T-B-005)+1 种基金Funding for Reform and Development of Beijing Municipal Health Commissionthe National High Level Hospital Clinical Research Funding(2022-PUMCH-B-094).
文摘Menopause is characterized by the cessation of menstruation and a decline in reproductive function,which is an intrinsic component of the aging process.However,it has been a frequently overlooked field of women’s health.The oral and gut microbiota,constituting the largest ecosystem within the human body,are important for maintaining human health and notably contribute to the healthy aging of menopausal women.Therefore,a comprehensive review elucidating the impact of the gut and oral microbiota on menopause for healthy aging is of paramount importance.This paper presents the current understanding of the microbiome during menopause,with a particular focus on alterations in the oral and gut microbiota.Our study elucidates the complex interplay between the microbiome and sex hormone levels,explores microbial crosstalk dynamics,and investigates the associations between the microbiome and diseases linked to menopause.Additionally,this review explores the potential of microbiome-targeting therapies for managing menopause-related diseases.Given that menopause can last for approximately 30 years,gaining insights into how the microbiome and menopause interact could pave the way for innovative interventions,which may result in symptomatic relief from menopause and an increase in quality of life in women.
基金Supported by The Earmarked Fund for Modern Agro-industry Technology Research System(CARS-06-13.5-A19)Agricultural Scientific and Technological Innovation Project of Shandong Academy of Agricultural Sciences(GXGC2018D02)Shandong Key R&D Program(2018GNC113016)
文摘[Objectives] This study was conducted to clarify the evolution characteristics of foxtail millet varieties in different ages and provide a basis for the breeding of new varieties. [Methods] A field experiment was carried out on 20 main foxtail millet varieties promoted in North China developed from the 1980 s to 2000 s. The physiological and biochemical indexes of different foxtail millet varieties in four ages were compared, including chlorophyll content, soluble protein content, glutamine synthetase(GS) activity and glutamate synthase(GOGAT) activity, and the correlation between enzyme activity and yield was analyzed. [Results] The chlorophyll SPAD values of the flag leaf and functional leaves of foxtail millet varieties decreased with the filling process. The SPAD values of the flag leaf, top second leaf and top third leaf were higher in the varieties developed in the 1990 s and 2000 s than those in the 1980 s and 2010 s. The activity of glutamine synthetase(GS) and glutamate synthase(GOGAT) showed a single-peak curve in different foxtail millet varieties developed in the recent 30 years, and the peaks of the two were at 7 d and at 7 or 14 d, respectively. The activity of GS and GOGAT increased with the breeding age. In the period from 7 d after anthesis to the mature period, the decreases in the soluble protein content followed an order of 2010 s, 2000 s, 1990 s and 1980 s from small to large, indicating that the degradation rate of various enzyme sources and metabolic regulators in foxtail millet plants decreased during the improvement process. At 35 d after anthesis, the correlation coefficient between GS activity and yield was-0.247, that is, there was a negative correlation with yield. And there was a significant positive correlation between GOGAT activity and yield, and the correlation coefficient was as high as 0.455 at 7 d after anthesis. [Conclusions] Changes in the GS activity, GOGAT activity and soluble protein content in the flag leaf of foxtail millet varieties developed in recent years have a certain impact on yield.
基金supported by the Shanghai Science and Technology Development Funds(No.20Z11900200 to R.R.)Key Project of National Natural Science Foundation of China(No.82230088 to R.R.)+5 种基金National Key Research and Development Program of China(No.2019YFA0905900 to J.L.No.2019YFA0905902 to S.W.),National Natural Science Foundation of China(No.82170147 to R.R.No.82370157 to J.L.No.81970134 and 82170111 to P.L.)Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(No.2019CXJQ01 to R.R.)the Samuel Waxman Cancer Research Foundation(to R.R.).
文摘Acute myeloid leukemia(AML)is an aging-related malignancy,with patients aged≥60 years old facing significantly poorer prognosis.Umbilical cord blood(UCB)has emerged as a promising source with effective anti-aging roles.Here,we conducted a prospective,phase 2,single-arm trial of UCB infusion as an adjuvant consolidation therapy in elderly AML patients(ChiCTR-OPC15006492).A total of 51 patients were enrolled(median age 66 years;range,60-75)and received two cycles of consolidation chemotherapy combined with UCB infusion.At a median follow-up of 27.3 months(range,9.3-100),the median overall survival(OS)was not yet reached and the median event-free survival(EFS)was 72.2 months(range,5.4-100).The 2-year OS and EFS rates were 76.9%and 62.8%,respectively.No acute graft-versus-host disease(aGVHD)or toxicity-related death occurred in any patient.The median times to platelet and neutrophil recovery were 11.5 days(range,6-17)and 12.2 days(range,0-21),respectively.Singlecell RNA sequencing(scRNA-seq)identified enhanced anti-tumor and anti-aging properties of UCB,manifested through activation of immune responses and telomere synthesis/maintenance.Thesefindings suggest that UCB infusion is an effective and safe postremission adjuvant therapy for elderly AML patients.This study provides evidence that anti-aging therapy may serve as a new and promising dimension in combined cancer treatment.
文摘With the development of higher education and social changes,college English courses no longer only focus on the cultivation of language skills,but also pay more attention to the comprehensive quality cultivation of students.As an important educational tool,the construction and practice of ideological and political education in college English classrooms are of great importance and challenge.This article aims to explore the construction and practice of ideological and political education in college English classrooms,analyzing the construction of teaching staff,curriculum design,textbook selection,teaching methods and means,and other aspects.Firstly,the cultivation of teaching staff is the key to ensuring the quality of ideological and political education,and it is necessary to improve teachers'ideological and political literacy and abilities.Secondly,the curriculum and textbook selection should focus on ideological and political related topics and texts to stimulate students'thinking on social ethics,politics,and other issues.At the same time,teaching objectives should focus on cultivating students'correct political concepts and values.Finally,the textbook content and courseware should have an ideological and political orientation,incorporating in-depth analysis and exploration of social issues.Through the above measures,we can effectively construct ideological and political education in college English classrooms,and achieve the cultivation of students'comprehensive qualities.
基金the National Natural Science Fund of China(U21A20339,82273928,82273026)CAMS Innovation Fund for Medical Sciences(CIFMS)2019-I2M-5-078+2 种基金Outstanding Youth Project of Natural Science Fund of Heilongjiang Province(YQ2020H010,YQ2020H019)Heilongjiang Innovative Talent Training Fund for Young Teachers(to Ye Yuan in 2020)College of Pharmacy,Harbin Medical University,Excellent Young Talents Funding(2019-YQ-13).
文摘Heart failure(HF)patients in general have a higher risk of developing cancer.Several animal studies have indicated that cardiac remodeling and HF remarkably accelerate tumor progression,highlighting a cause-and-effect relationship between these two disease entities.Targeting ferroptosis,a prevailing form of non-apoptotic cell death,has been considered a promising therapeutic strategy for human cancers.Exosomes critically contribute to proximal and distant organ-organ communications and play crucial roles in regulating diseases in a paracrine manner.However,whether exosomes control the sensitivity of cancer to ferroptosis via regulating the cardiomyocyte-tumor cell crosstalk in ischemic HF has not yet been explored.Here,we demonstrate that myocardial infarction(MI)decreased the sensitivity of cancer cells to the canonical ferroptosis activator erastin or imidazole ketone erastin in a mouse model of xenograft tumor.Post-MI plasma exosomes potently blunted the sensitivity of tumor cells to ferroptosis inducers both in vitro in mouse Lewis lung carcinoma cell line LLC and osteosarcoma cell line K7M2 and in vivo with xenograft tumorigenesis model.The expression of miR-22-3p in cardiomyocytes and plasma-exosomes was significantly upregulated in the failing hearts of mice with chronic MI and of HF patients as well.Incubation of tumor cells with the exosomes isolated from post-MI mouse plasma or overexpression of miR-22-3p alone abrogated erastin-induced ferroptotic cell death in vitro.Cardiomyocyte-enriched miR-22-3p was packaged in exosomes and transferred into tumor cells.Inhibition of cardiomyocyte-specific miR-22-3p by AAV9 sponge increased the sensitivity of cancer cells to ferroptosis.ACSL4,a pro-ferroptotic gene,was experimentally established as a target of miR-22-3p in tumor cells.Taken together,our findings uncovered for the first time that MI suppresses erastin-induced ferroptosis through releasing miR-22-3p-enriched exosomes derived from cardiomyocytes.Therefore,targeting exosome-mediated cardiomyocyte/tumor pathological communication may offer a novel approach for the ferroptosis-based antitumor therapy.
基金supported by grants from the National Natural Science Foundation of China(Nos.82100158,81890994,81770143,81970130,and 81861148030)Double First-Class Project(No.WF510162602)from the Ministry of Education+8 种基金State Key Laboratory of Medical Genomics,Overseas Expertise Introduction Project for Discipline Innovation(111 Project,No.B17029)National Key R&D Program of China(Nos.2019YFA0905902 and 2018YFA0107802)Natural Science Foundation of Shanghai(Nos.20JC1410600,21ZR1480900,and 21YF1427900)Shanghai Clinical Research Center for Hematologic Disease(No.19MC1910700)Shanghai Major Project for Clinical Medicine(No.2017ZZ01002)Shanghai Shenkang Hospital Development Center(No.SHDC2020CR5002)Innovative Research Team of High-level Local Universities in Shanghai,Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(No.2019CXJQ01)Shanghai Jiao Tong University(No.YG2021QN19)Shanghai Guangci Translational Medical Research Development Foundation.
文摘With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures,there have been widespread SARS-CoV-2 infections in Chinese mainland.Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai,identifying a large number of sublineages of the SARS-CoV-2 Omicron family.Phylogenetic analysis,coupled with contact history tracing,revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China(BA.5.2 mainly in Guangzhou and Shanghai,and BF.7 mainly in Beijing)and two highly infectious sublineages recently imported from abroad(XBB and BQ.1).Publicly available data from August 31 to November 29,2022 indicated an overall severe/critical case rate of 0.035%nationwide,while analysis of 5706 symptomatic patients treated at the Shanghai Public Health Center between September 1 and December 26,2022 showed that 20 cases(0.35%)without comorbidities progressed into severe/critical conditions and 153 cases(2.68%)with COVID-19-exacerbated comorbidities progressed into severe/critical conditions.These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases.Furthermore,mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year,whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023,and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival(January 21,2023).Altogether,these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population,especially in the rural areas,to ensure the country’s smooth exit from the ongoing pandemic and accelerate socio-economic recovery.
基金Supported by the National Natural Science Foundation of China(42030610)National Key Research and Development Program of China for Intergovernmental Cooperation(2019YFE0110100).
文摘The cause–effect relationship between meso-γ-scale rotation and extreme short-term precipitation events remains elusive in mesoscale meteorological research.We aimed to elucidate this relationship by analyzing a rainstorm over the Pearl River Delta during the nocturnal hours of 15 May 2017 based on 6-min radar observations and 1-min rain gauge data.This rainstorm had a maximum hourly rainfall of 100.1 mm,with 26 stations recording hourly rainfall>60 mm h^(−1) in 5 h.Extreme heavy precipitation was produced in association with a convergence zone along the southern side of a synoptic low-level shear line,where southwesterly warm,humid airflows with precipitable water of>60 mm,little convection inhibition(<10 J kg^(−1)),and a low lifting condensation level(about 300 m)dominated.A meso-γ-scale vortex was quantitatively identified during the hour with the largest number of gauges observing extreme hourly rainfall.The vortex had a mean diameter of 6.1 km and a peak intensity of 3.1×10^(−3) s^(−1) during its lifetime of 54 min.The vortex initialized and remained inside the region of extreme rain rates(radar-retrieved rain rates>100 mm h^(−1)),reached its peak intensity after the peak of the collocated 6-min rainfall accumulation,and then weakened rapidly after the extreme rainfall region moved away.The radar-retrieved liquid water path was about five to seven times the ice water path and the specific differential phase(Kdp)below 0°C increased sharply downward during the lifetime of the vortex,suggesting the presence of active warm rain microphysical processes.These results indicate that the release of the latent heat of condensation induced by extreme rainfall could have contributed to the formation of the vortex in an environment with a weak 0–1-km vertical wind shear(about 4–5 m s^(−1))through enhanced lowlevel convergence,although the strengthening of low-level updrafts by rotational dynamic effects and short-term rainfall cannot be ruled out.
基金support from the National Natural Science Foundation of China(Nos.82100158 and 81861148030)the Natural Science Foundation of Shanghai(Nos.21ZR1480900 and 21YF1427900)+4 种基金Shanghai Clinical Research Center for Hematologic Disease(No.119MC1910700)ShanghaiMajor Project for Clinical Medicine(No.2017ZZ01002)Shanghai Shenkang Hospital Development Center(No.SHDC2020CR5002)Innovative Research Team of High-level Local Universities in Shanghai,and Shanghai Collaborative Innovation Program on Regenerative Medicineand StemCell Research(No.2019CXJQ01)support from the ASTRA computing platform in the National Research Center for Translational Medicine(Shanghai)and the Pi computing platform in the Center for High-Performance Computing at Shanghai Jiao Tong University.
文摘The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic.Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022.Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020,BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood.In particular,severe/critical cases of COVID19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment.Importantly,the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototypeinactivated vaccines,supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records.Furthermore,even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection,vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged≥60 years old.Together,our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
基金This work was supported by grants from National Natural Science Foundation of China(Nos.8210010124,81890994,and 81861148030)Double First-Class Project(No.WF510162602)from the Ministry of Education+7 种基金State Key Laboratory of Medical Genomics,Overseas Expertise Introduction Project for Discipline Innovation(111 Project,No.B17029)National Key R&D Program of China(No.2019YFA0905902)Natural Science Foundation of Shanghai(Nos.21ZR1480900 and 21YF1427900)Shanghai Clinical Research Center for Hematologic Disease(No.19MC1910700)Shanghai Major Project for Clinical Medicine(No.2017ZZ01002)Shanghai Shenkang Hospital Development Center(No.SHDC2020CR5002)Innovative Research Team of High-level Local Universities in Shanghai,Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(No.2019CXJQ01)Shanghai Jiao Tong University(No.YG2021QN19),Shanghai Guangci Translational Medical Research Development Foundation.
文摘Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases.Here,to explore the role of the gut microbiome in the host immune responses in COVID-19,we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples.We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones.We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity,such as Enterococcus faecium,Coprococcus comes,Roseburia intestinalis,Akkermansia ntuciniphila,Bacteroides cellulosilyticus and Blautia obeum.We further analyzed the correlation between the abundance of gut microbes and host responses,and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe,including Coprococcus comes that was positively correlated with CD3^(+)/CD4^(+)/CD8^(+)lymphocyte counts.In addition,an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells(PBMCs)showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples.Moreover,a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases,including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19.Together,our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.
基金supported by the National Natural Science Foundation of China (82273928,U21A20339)the Outstanding Youth Project of Natural Science Foundation of Heilongjiang Province (YQ2020H010)+2 种基金Youth Project of Scientific Research Institution of Heilongjiang Province (CZKYF2023-1-C047)CAMS Innovation Fund for Medical Sciences (CIFMS) (2019-I2M-5-078)Harbin Medical University Youth Talents Start-up Funding (2019-YQ-03)。
文摘Ischemic heart failure(HF)remains a leading cause of morbidity and mortality.Maintaining homeostasis of cardiac function and preventing cardiac remodeling deterioration are critical to halting HF progression.Methyltransferase-like protein 13(Mettl13)has been shown to regulate protein translation efficiency by acting as a protein lysine methyltransferase,but its role in cardiac pathology remains unexplored.This study aims to characterize the roles and mechanisms of Mettl13 in cardiac contractile function and HF.We found that Mettl13 was downregulated in the failing hearts of mice post-myocardial infarction(MI)and in a cellular model of oxidative stress.Cardiomyocyte-specific overexpression of Mettl13 mediated by AAV9-Mettl13 attenuated cardiac contractile dysfunction and fibrosis in response to MI,while silencing of Mettl13 impaired cardiac function in normal mice.Moreover,Mettl13 overexpression abrogated the reduction in cell shortening,Ca^(2+)transient amplitude and SERCA2a protein levels in the cardiomyocytes of adult mice with MI.Conversely,knockdown of Mettl13 impaired the contractility of cardiomyocytes,and decreased Ca^(2+)transient amplitude and SERCA2a protein expression in vivo and in vitro.Mechanistically,Mettl13 impaired the stability of c-Cbl by inducing lysine methylation of c-Cbl,which in turn inhibited ubiquitination-dependent degradation of SERCA2a.Furthermore,the inhibitory effects of knocking down Mettl13 on SERCA2a protein expression and Ca^(2+)transients were partially rescued by silencing c-Cbl in H_(2)O_(2)-treated cardiomyocytes.In conclusion,our study uncovers a novel mechanism that involves the Mettl13/c-Cbl/SERCA2a axis in regulating cardiac contractile function and remodeling,and identifies Mettl13 as a novel therapeutic target for ischemic HF.
基金This work was sponsored by the National Key Research and Development Program of China(No.2018YFB0704400)Key Program of Science and Technology of Yunnan Province(No.202002AB080001-2)+2 种基金Key Research Project of Zhejiang Laboratory(No.2021PE0AC02)Shanghai Pujiang Program(Grant No.20PJ1403700)Guangzhou Municipal Science and Technology Project(No.2023A03J0003).We would like to acknowledge the support from Yunnan Tin Group(Holding)Co.Ltd,China.We also acknowledge the support from the Shanghai Engineering Research Center for Integrated Circuits and Advanced Display Materials.
文摘The attainment of both high strength and high ductility is always the goal for structure materials,because the two properties generally are mutually competing,called strength-ductility trade-off.Nowadays,the data-driven paradigm combined with expert domain knowledge provides the state-of-the-art methodology to design and discovery for structure materials with high strength and high ductility.To enhance both strength and ductility,a joint feature is proposed here to be the product of strength multiplying ductility.The strategy of“divide and conquer”is developed to solve the contradictory problem,that material experimental data of mechanical behaviors are,in general,small in size and big in noise,while the design space is huge,by a newly developed data preprocessing algorithm,named the Tree-Classifier for Gaussian Process Regression(TCGPR).The TCGPR effectively divides an original dataset in a huge design space into three appropriate sub-domains and then three Machine Learning(ML)models conquer the three sub-domains,achieving significantly improved prediction accuracy and generality.After that the Bayesian sampling is applied to design next experiments by balancing exploitation and exploration.Finally,the experiment results confirm the ML predictions,exhibiting novel lead-free solder alloys with high strength high ductility.Various material characterizations were also conducted to explore the mechanism of high strength and high ductility of the alloys.
