High-precision estimation of lithium battery SOC can effectively optimize vehicle energy management,improve lithium battery safety protection,extend lithium battery cycle life,and reduce new energy vehicle costs.Based...High-precision estimation of lithium battery SOC can effectively optimize vehicle energy management,improve lithium battery safety protection,extend lithium battery cycle life,and reduce new energy vehicle costs.Based on the forgetting factor recursive least square method(FFRLS),Thevenin equivalent circuit model and Singular Value Decomposition-Unscented Kalman Filter(SVD-UKF),the SVD-UKF combined lithium battery SOC estimation algorithm with model capacity update is proposed,aiming at further improving the SOC estimation accuracy of lithium battery.The parameter identification of Thevenin model is studied by using the forgetting factor recursive least square method.To overcoming the shortcomings of Kalman filter linearization error and non-positive definite covariance matrix,the singular value decomposition unscented Kalman filter algorithm is proposed.It is worth mentioning that in order to consider the impact of battery available capacity attenuation on the estimation of lithium battery SOC,the model capacity update algorithm is used to optimize the model parameters and state joint estimation algorithm based on FFRLS&SVD-UKF.Verified by simulation and lithium battery test,the results show that the SVD-UKF algorithm based on model capacity update can accurately estimate the SOC of lithium battery in real time with the available capacity of lithium battery continuous attenuation.The purpose of improving the accuracy of SOC estimation of lithium batteries is achieved.展开更多
BACKGROUND Polycystic ovary syndrome(PCOS) is characterized by hyperandrogenism, hyperinsulinemia, ovarian polycystic changes, and irregular ovulation, often occurring in women of childbearing age for whom it can be a...BACKGROUND Polycystic ovary syndrome(PCOS) is characterized by hyperandrogenism, hyperinsulinemia, ovarian polycystic changes, and irregular ovulation, often occurring in women of childbearing age for whom it can be a cause of infertility. Hypothalamus-pituitary-ovarian axis dysregulation is important in the pathogenesis of PCOS and the associated chronic excess of sex hormones can lead to cardiovascular and cerebrovascular diseases, diabetes, and malignancies such as endometrial cancer, and breast cancer. At present, most scholars agree that lifestyle interventions in conjunction with drug treatment can help PCOS patients achieve their goals of successful pregnancy and childbirth.AIM To investigate the clinical effect of an online and offline(O2O) preventive health management model on PCOS with kidney deficiency and phlegm dampness.METHODS A total of 82 patients with PCOS of the kidney deficiency and phlegm dampness type who were admitted to Beijing Luhe Hospital Affiliated to Capital Medical University from April 2019 to June 2020 were randomly divided into two groups. The treatment group was treated with oral Diane-35 for 3 mo and received preventive O2O medical health management for 6 mo(including eating and living, exercise, drug management). The control group was treated with oral Diane-35 for 3 mo and completed outpatient health education. The traditional Chinese medicine(TCM) syndrome score, acne score, hair score, sex hormone level and clinical effects were compared between the two groups before and after the intervention. RESULTS After treatment, the TCM syndrome score, acne score, and serum luteinizing hormone/follicle stimulating hormone level were significantly lower in the treatment group than in the control group(P < 0.05). After 3 mo of treatment, the TCM syndrome curative effect index in the treatment group was 97.30% compared to 54.05% in the control group(P < 0.05), whereas the total treatment effect in the treatment group was 91.89%, compared to 54.05% in the control group(P < 0.05).CONCLUSION An integrated therapeutic approach incorporating medication, TCM methods and social media is more effective than standard treatment for PCOS.展开更多
AIM: To determine whether red blood cell(RBC)membrane and plasma lipids, particularly long-chain polyunsaturated fatty acids such as eicosapentaenoic acid(EPA), docosahexaenoic acid(DHA), arachidonic acid(AA) are sign...AIM: To determine whether red blood cell(RBC)membrane and plasma lipids, particularly long-chain polyunsaturated fatty acids such as eicosapentaenoic acid(EPA), docosahexaenoic acid(DHA), arachidonic acid(AA) are significantly correlated with severity of normal tension glaucoma(NTG).METHODS: This study included 35 patients with NTG and 12 healthy normal control subjects, matched for age and sex with the study group. The stage of glaucoma was determined according to the Hodapp-Parrish-Anderson classification. Lipids were extracted from RBC membranes and plasma, and fatty acid methyl esters prepared and analyzed by gas chromatography-mass spectrometry(GC-MS).RESULTS: When RBC lipids were analyzed, the levels of EPA, the levels of DHA and the ratio of n3 to n6 were positively associated with the Humphrey Perimetry mean Deviation(MD) score(r =0.617, P 【0.001; r =0.727, P 【0.001 and r =0.720, P 【0.001, respectively), while the level of AA was negatively associated with the MD score(r =-0.427, P =0.001). When plasma lipids were analyzed,there was a significant positive relationship between the levels of EPA and the MD score(r =0.648, P 【0.001), and the levels of AA were inversely correlated with the MD score(r =-0.638, P 【0.001). CONCLUSION: The levels of n3 and n6 polyunsaturated fatty acids in RBC membrane and plasma lipids were associated with severity of NTG.展开更多
目的:系统评价康柏西普和雷珠单抗治疗视网膜静脉阻塞(RVO)继发黄斑水肿(ME)的疗效、安全性、经济性。方法:分别在万方数据库、中国生物医学文献服务系统、中国知网、Pubmed、The Cochrane Library Central Register of Controlled Tria...目的:系统评价康柏西普和雷珠单抗治疗视网膜静脉阻塞(RVO)继发黄斑水肿(ME)的疗效、安全性、经济性。方法:分别在万方数据库、中国生物医学文献服务系统、中国知网、Pubmed、The Cochrane Library Central Register of Controlled Trials(CENTRAL)、Google scholar等数据库收集自建库至2020-02-20关于康柏西普和雷珠单抗治疗RVO继发ME的对照研究,提取最佳矫正视力、黄斑中心凹视网膜厚度、不良反应发生情况、注射次数等主要结局指标进行系统评价,比较二者的效果。采用RevMan 5.3统计软件进行数据的分析。结果:共纳入16项研究,合计患者1337例。Meta分析结果提示,与雷珠单抗相比,康柏西普在采用1+PRN注射方案和治疗视网膜分支静脉阻塞(BRVO)继发ME患者时,对黄斑水肿的消退效果更明显,但二者注射次数无明显差异;与雷珠单抗相比,康柏西普在采用3+PRN注射方案和治疗视网膜中央静脉阻塞(CRVO)继发ME患者时,注射次数更少;康柏西普和雷珠单抗在视力改善和不良反应的发生方面无明显差异。结论:与雷珠单抗相比,康柏西普在不同的注射方案和不同的静脉阻塞类型治疗中体现出更优的效果,即更少的注射次数或更好的黄斑水肿消退效果。展开更多
Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic ...Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.展开更多
Due to their tunable acidity,shape selectivity,and excellent stability,zeolites are of great importance as solid acid materials in industrial catalysis.Tuning the properties of the acid sites in zeolites allows for th...Due to their tunable acidity,shape selectivity,and excellent stability,zeolites are of great importance as solid acid materials in industrial catalysis.Tuning the properties of the acid sites in zeolites allows for the rational design and fabrication of catalysts for target reactions.Dimethyl ether(DME)carbonylation,a critical chain-growth reaction for C1 resource utilization,is selectively catalyzed by the Brønsted acid sites within the eight-membered rings(8-MRs)of mordenite(MOR).It is anticipated that strengthening the Brønsted acidity—particularly in 8-MRs—will improve the catalytic performance of MOR.In this work,density functional theory(DFT)calculations are first employed and the results used to design a modified MOR with stannum(Sn)and to predict the corresponding changes in acidity.Guided by the theoretical studies,a series of Sn-modified MOR are synthesized via a defect-engineering and subsequent heteroatom-substitution strategy.After partial desilication,isolated tetrahedral Sn species in an open configuration are successfully synthesized for the first time,within which tetrahedrally coordinated Al sites are preserved.An acidic characterization is used to confirm that the acidity of the Brønsted acid sites is enhanced by the introduction of the Sn species;as a result,the sample exhibits excellent activity in DME carbonylation reaction.Kinetic and DFT studies reveal that this strengthened acidity facilitates the adsorption of DME and reduces the activation barriers of DME dissociation and acetyl formation,accounting for the improved activity.The work demonstrates mechanistic insights into the promoting effects of strong acidity on DME carbonylation and offers a promising strategy to precisely control the acidic strength of zeolites.展开更多
AIM:To systematically understand the genetic association between methylenetetrahydrofolate reductase(MTHFR)C677 T polymorphism and primary open angle glaucoma(POAG).METHODS:A comprehensive literature search in Google ...AIM:To systematically understand the genetic association between methylenetetrahydrofolate reductase(MTHFR)C677 T polymorphism and primary open angle glaucoma(POAG).METHODS:A comprehensive literature search in Google Scholar,Pub Med,Science Citation Index,Foreign Medical Literature Retrieval Service,Chinese National Knowledge Infrastructure and Wanfang Databases was performed to collect all eligible studies up to August 2019.Study selection,data abstraction and study quality evaluation were performed by two independent investigators.Odds ratios(ORs)with 95%confidence intervals(CIs)were calculated to assess the association.RESULTS:Eighteen case-control studies including 2156 cases and 2201 controls were identified.There was no significant difference in the terms of MTHFR C677 T polymorphism and POAG in the Caucasian population(for T vs C OR=1.11,95%CI:0.88 to 1.39;for TT vs CC OR=1.01,95%CI:0.76 to 1.36;for TT+TC vs CC OR=1.15,95%CI:0.84 to 1.58 and for TT vs TC+CC OR=1.02,95%CI:0.78 to 1.33).However,a significant effect was revealed in the Asian population(for T vs C OR=1.34,95%CI:1.12 to 1.59;for TT+TC vs CC OR=1.41,95%CI:1.14 to 1.76).CONCLUSION:Based on 18 eligible studies,we provide a correlation between MTHFR C677 T polymorphism and POAG among the Asians subgroup indicating that the T allele or TT+TC genotype may play a critical role in POAG development in Asians.展开更多
The retinal pigment epithelium(RPE)and choroid are located behind the human retina and have multiple functions in the human visual system.Knowledge of the RPE and choroid cells and their gene expression profiles are f...The retinal pigment epithelium(RPE)and choroid are located behind the human retina and have multiple functions in the human visual system.Knowledge of the RPE and choroid cells and their gene expression profiles are fundamental for understanding retinal disease mechanisms and therapeutic strategies.Here,we sequenced the RNA of about 0.3 million single cells from human RPE and choroids across two regions and seven ages,revealing regional and age differences within the human RPE and choroid.Cell–cell interactions highlight the broad connectivity networks between the RPE and different choroid cell types.Moreover,the transcription factors and their target genes change during aging.The coding of somatic variations increases during aging in the human RPE and choroid at the single-cell level.Moreover,we identified ELN as a candidate for improving RPE degeneration and choroidal structure during aging.The mapping of the molecular architecture of the human RPE and choroid improves our understanding of the human vision support system and offers potential insights into the intervention targets for retinal diseases.展开更多
The human retina serves as a light detector and signals transmission tissue.Advanced insights into retinal disease mechanisms and therapeutic strategies require a deep understanding of healthy retina molecular events....The human retina serves as a light detector and signals transmission tissue.Advanced insights into retinal disease mechanisms and therapeutic strategies require a deep understanding of healthy retina molecular events.Here,we sequenced the m RNA of over 0.6 million single cells from human retinas across six regions at nine different ages.Sixty cell sub-types have been identified from the human mature retinas with unique markers.We revealed regional and age differences of gene expression profiles within the human retina.Cell-cell interaction analysis indicated a rich synaptic connection within the retinal cells.Gene expression regulon analysis revealed the specific expression of transcription factors and their regulated genes in human retina cell types.Some of the gene’s expression,such as DKK3,are elevated in aged retinas.A further functional investigation suggested that over expression of DKK3 could impact mitochondrial stability.Overall,decoding the molecular dynamic architecture of the human retina improves our understanding of the vision system.展开更多
Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1.ABCA1 is a key regulator of cholesterol efflux and the biogenesis of high-density lipoprotein(HDL) pa...Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1.ABCA1 is a key regulator of cholesterol efflux and the biogenesis of high-density lipoprotein(HDL) particles. Here, we showed that the POAG risk allele near ABCA1 attenuated ABCA1 expression in cultured cells. Consistently, POAG patients exhibited lower ABCA1 expression, reduced HDL, and higher cholesterol in white blood cells. Ablation of Abca1 in mice failed to form HDL, leading to elevated cholesterol levels in the retina. Counting retinal ganglion cells(RGCs) by using an artificial intelligence(AI) program revealed that Abca1-deficient mice progressively lost RGCs with age. Single-cell RNA sequencing(scRNA-seq) revealed aberrant oxidative phosphorylation in the Abca1-/-retina, as well as activation of the mTORC1 signaling pathway and suppression of autophagy. Treatment of Abca1-/-mice using atorvastatin reduced the cholesterol level in the retina,thereby improving metabolism and protecting RGCs from death. Collectively, we show that lower ABCA1 expression and lower HDL are risk factors for POAG. Accumulated cholesterol in the Abca1-/-retina causes profound aberrant metabolism, leading to a POAG-like phenotype that can be prevented by atorvastatin. Our findings establish statin use as a preventive treatment for POAG associated with lower ABCA1 expression.展开更多
The Revised International Staging System(R-ISS)is a simple and powerful prognostic tool for multiple myeloma(MM).However,heterogeneity in R-ISS stage is still poorly characterised,hampering improvement of treatments.W...The Revised International Staging System(R-ISS)is a simple and powerful prognostic tool for multiple myeloma(MM).However,heterogeneity in R-ISS stage is still poorly characterised,hampering improvement of treatments.We used single-cell RNA-seq to examine novel cellular heterogeneity and regular networks in nine MM patients stratified by R-ISS.Plasma cells were clustered into nine groups(P1–P9)based on gene expression,where P1–P5 were almost enriched in stage III.PDIA6 was significantly upregulated in P3 and LETM1was enriched in P1,and they were validated to be upregulated in the MM cell line and in 22 other patients’myeloma cells.Furthermore,in progression,PDIA6 was newly found and verified to be activated by UQCRB through oxidative phosphorylation,while LETM1 was activated by STAT1 via the C-type lectin receptor-signalling pathway.Finally,a subcluster of monocytes was exclusively found in stage III specifically expressed chemokines modulated by ATF3.A few ligand-receptor pairs(CCL3/CCL5/CCL3L1-CCR1)were obviously active in monocyte-plasma communications in stage III.Herein,this study identified novel molecules,networks and crosstalk pairs in different R-ISS stages of MM,providing significant insight for its prognosis and treatment.展开更多
CRISPR-mediated base editors have been widely used to correct defective alleles and create novel alleles by artificial evolution for the rapid genetic improvement of crops.The editing capabilities of base editors stri...CRISPR-mediated base editors have been widely used to correct defective alleles and create novel alleles by artificial evolution for the rapid genetic improvement of crops.The editing capabilities of base editors strictly rely on the performance of various nucleotide modification enzymes.Compared with the welldeveloped adenine base editors(ABEs),cytosine base editors(CBEs)and dual base editors suffer from unstable editing efficiency and patterns at different genomic loci in rice,significantly limiting their application.Here,we comprehensively examined the base editing activities of multiple evolved TadA8e variants in rice.We found that both TadA-CDd and TadA-E27R/N46L achieved more robust C-to-T editing than previously reported hyperactive hAID*D,and TadA-CDd outperformed TadA-E27R/N46L.A C-to-G base editor(CGBE)engineered with TadA-CDd and OsUNG performed highly efficient C-to-G editing in rice compared with that of TadA-N46P.In addition,a dual base editor constructed with a single protein,TadDE,enabled simultaneous,highly efficient C-to-T and A-to-G editing in rice.Collectively,our results demonstrate that TadA8e derivatives improve both CBEs and dual base editors in rice,providing a powerful way to induce diverse nucleotide substitutions for plant genome editing.展开更多
Erratum to:SCIENCE CHINA Life Sciences,Volume 66,Issue 2:211-225(2022),https://doi.org/10.1007/s11427-021-2126-2 This paper contains an error in Figure 4C,where the representative images of filipin staining of retinal...Erratum to:SCIENCE CHINA Life Sciences,Volume 66,Issue 2:211-225(2022),https://doi.org/10.1007/s11427-021-2126-2 This paper contains an error in Figure 4C,where the representative images of filipin staining of retinal sections from 6-month-old mice were misused.We provide the correct picture for Figure 4C as follows.The statistical result in Figure 4D was corrected as well.This new Figure 4 does not affect the conclusion of this article.展开更多
基金This research was funded by Natural Science Basic Research Program of Shaanxi(2020JQ-913)Key Research and Development Program of Shaanxi(2020ZDLGY16-01,2020ZDLGY16-02,2019ZDLGY15-01,2019ZDLGY15-02,2018ZDCXLGY-05-03-01)Key Laboratory Open Fund of Ministry of Communications(300102220503).
文摘High-precision estimation of lithium battery SOC can effectively optimize vehicle energy management,improve lithium battery safety protection,extend lithium battery cycle life,and reduce new energy vehicle costs.Based on the forgetting factor recursive least square method(FFRLS),Thevenin equivalent circuit model and Singular Value Decomposition-Unscented Kalman Filter(SVD-UKF),the SVD-UKF combined lithium battery SOC estimation algorithm with model capacity update is proposed,aiming at further improving the SOC estimation accuracy of lithium battery.The parameter identification of Thevenin model is studied by using the forgetting factor recursive least square method.To overcoming the shortcomings of Kalman filter linearization error and non-positive definite covariance matrix,the singular value decomposition unscented Kalman filter algorithm is proposed.It is worth mentioning that in order to consider the impact of battery available capacity attenuation on the estimation of lithium battery SOC,the model capacity update algorithm is used to optimize the model parameters and state joint estimation algorithm based on FFRLS&SVD-UKF.Verified by simulation and lithium battery test,the results show that the SVD-UKF algorithm based on model capacity update can accurately estimate the SOC of lithium battery in real time with the available capacity of lithium battery continuous attenuation.The purpose of improving the accuracy of SOC estimation of lithium batteries is achieved.
文摘BACKGROUND Polycystic ovary syndrome(PCOS) is characterized by hyperandrogenism, hyperinsulinemia, ovarian polycystic changes, and irregular ovulation, often occurring in women of childbearing age for whom it can be a cause of infertility. Hypothalamus-pituitary-ovarian axis dysregulation is important in the pathogenesis of PCOS and the associated chronic excess of sex hormones can lead to cardiovascular and cerebrovascular diseases, diabetes, and malignancies such as endometrial cancer, and breast cancer. At present, most scholars agree that lifestyle interventions in conjunction with drug treatment can help PCOS patients achieve their goals of successful pregnancy and childbirth.AIM To investigate the clinical effect of an online and offline(O2O) preventive health management model on PCOS with kidney deficiency and phlegm dampness.METHODS A total of 82 patients with PCOS of the kidney deficiency and phlegm dampness type who were admitted to Beijing Luhe Hospital Affiliated to Capital Medical University from April 2019 to June 2020 were randomly divided into two groups. The treatment group was treated with oral Diane-35 for 3 mo and received preventive O2O medical health management for 6 mo(including eating and living, exercise, drug management). The control group was treated with oral Diane-35 for 3 mo and completed outpatient health education. The traditional Chinese medicine(TCM) syndrome score, acne score, hair score, sex hormone level and clinical effects were compared between the two groups before and after the intervention. RESULTS After treatment, the TCM syndrome score, acne score, and serum luteinizing hormone/follicle stimulating hormone level were significantly lower in the treatment group than in the control group(P < 0.05). After 3 mo of treatment, the TCM syndrome curative effect index in the treatment group was 97.30% compared to 54.05% in the control group(P < 0.05), whereas the total treatment effect in the treatment group was 91.89%, compared to 54.05% in the control group(P < 0.05).CONCLUSION An integrated therapeutic approach incorporating medication, TCM methods and social media is more effective than standard treatment for PCOS.
基金supported by National Natural Science Foundation of China (No. 81000370)
文摘AIM: To determine whether red blood cell(RBC)membrane and plasma lipids, particularly long-chain polyunsaturated fatty acids such as eicosapentaenoic acid(EPA), docosahexaenoic acid(DHA), arachidonic acid(AA) are significantly correlated with severity of normal tension glaucoma(NTG).METHODS: This study included 35 patients with NTG and 12 healthy normal control subjects, matched for age and sex with the study group. The stage of glaucoma was determined according to the Hodapp-Parrish-Anderson classification. Lipids were extracted from RBC membranes and plasma, and fatty acid methyl esters prepared and analyzed by gas chromatography-mass spectrometry(GC-MS).RESULTS: When RBC lipids were analyzed, the levels of EPA, the levels of DHA and the ratio of n3 to n6 were positively associated with the Humphrey Perimetry mean Deviation(MD) score(r =0.617, P 【0.001; r =0.727, P 【0.001 and r =0.720, P 【0.001, respectively), while the level of AA was negatively associated with the MD score(r =-0.427, P =0.001). When plasma lipids were analyzed,there was a significant positive relationship between the levels of EPA and the MD score(r =0.648, P 【0.001), and the levels of AA were inversely correlated with the MD score(r =-0.638, P 【0.001). CONCLUSION: The levels of n3 and n6 polyunsaturated fatty acids in RBC membrane and plasma lipids were associated with severity of NTG.
文摘目的:系统评价康柏西普和雷珠单抗治疗视网膜静脉阻塞(RVO)继发黄斑水肿(ME)的疗效、安全性、经济性。方法:分别在万方数据库、中国生物医学文献服务系统、中国知网、Pubmed、The Cochrane Library Central Register of Controlled Trials(CENTRAL)、Google scholar等数据库收集自建库至2020-02-20关于康柏西普和雷珠单抗治疗RVO继发ME的对照研究,提取最佳矫正视力、黄斑中心凹视网膜厚度、不良反应发生情况、注射次数等主要结局指标进行系统评价,比较二者的效果。采用RevMan 5.3统计软件进行数据的分析。结果:共纳入16项研究,合计患者1337例。Meta分析结果提示,与雷珠单抗相比,康柏西普在采用1+PRN注射方案和治疗视网膜分支静脉阻塞(BRVO)继发ME患者时,对黄斑水肿的消退效果更明显,但二者注射次数无明显差异;与雷珠单抗相比,康柏西普在采用3+PRN注射方案和治疗视网膜中央静脉阻塞(CRVO)继发ME患者时,注射次数更少;康柏西普和雷珠单抗在视力改善和不良反应的发生方面无明显差异。结论:与雷珠单抗相比,康柏西普在不同的注射方案和不同的静脉阻塞类型治疗中体现出更优的效果,即更少的注射次数或更好的黄斑水肿消退效果。
基金supported by the National Natural Science Foundation of China,No.81971246 (to TM)Opening Foundation of Jiangsu Key Laboratory of Neurodegeneration,Nanjing Medical University,No.KF202204 (to LZ and SF)。
文摘Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.
基金the National Natural Science Foundation of China(21978209 and 22008177)the Royal Society International Collaboration Award(ICA\R1\180317).
文摘Due to their tunable acidity,shape selectivity,and excellent stability,zeolites are of great importance as solid acid materials in industrial catalysis.Tuning the properties of the acid sites in zeolites allows for the rational design and fabrication of catalysts for target reactions.Dimethyl ether(DME)carbonylation,a critical chain-growth reaction for C1 resource utilization,is selectively catalyzed by the Brønsted acid sites within the eight-membered rings(8-MRs)of mordenite(MOR).It is anticipated that strengthening the Brønsted acidity—particularly in 8-MRs—will improve the catalytic performance of MOR.In this work,density functional theory(DFT)calculations are first employed and the results used to design a modified MOR with stannum(Sn)and to predict the corresponding changes in acidity.Guided by the theoretical studies,a series of Sn-modified MOR are synthesized via a defect-engineering and subsequent heteroatom-substitution strategy.After partial desilication,isolated tetrahedral Sn species in an open configuration are successfully synthesized for the first time,within which tetrahedrally coordinated Al sites are preserved.An acidic characterization is used to confirm that the acidity of the Brønsted acid sites is enhanced by the introduction of the Sn species;as a result,the sample exhibits excellent activity in DME carbonylation reaction.Kinetic and DFT studies reveal that this strengthened acidity facilitates the adsorption of DME and reduces the activation barriers of DME dissociation and acetyl formation,accounting for the improved activity.The work demonstrates mechanistic insights into the promoting effects of strong acidity on DME carbonylation and offers a promising strategy to precisely control the acidic strength of zeolites.
基金National Key Research and Development Plan(No.2017YFC0113901)the Department of Science and Technology of Sichuan Province,China(No.2017JZ0039)+1 种基金the Science Research Project for Cadres’Health Care of Sichuan Province(No.2017-205)Science and Technology Department of Sichuan Province(No.2019JDJQ0031,No.2020ZYD035)。
文摘AIM:To systematically understand the genetic association between methylenetetrahydrofolate reductase(MTHFR)C677 T polymorphism and primary open angle glaucoma(POAG).METHODS:A comprehensive literature search in Google Scholar,Pub Med,Science Citation Index,Foreign Medical Literature Retrieval Service,Chinese National Knowledge Infrastructure and Wanfang Databases was performed to collect all eligible studies up to August 2019.Study selection,data abstraction and study quality evaluation were performed by two independent investigators.Odds ratios(ORs)with 95%confidence intervals(CIs)were calculated to assess the association.RESULTS:Eighteen case-control studies including 2156 cases and 2201 controls were identified.There was no significant difference in the terms of MTHFR C677 T polymorphism and POAG in the Caucasian population(for T vs C OR=1.11,95%CI:0.88 to 1.39;for TT vs CC OR=1.01,95%CI:0.76 to 1.36;for TT+TC vs CC OR=1.15,95%CI:0.84 to 1.58 and for TT vs TC+CC OR=1.02,95%CI:0.78 to 1.33).However,a significant effect was revealed in the Asian population(for T vs C OR=1.34,95%CI:1.12 to 1.59;for TT+TC vs CC OR=1.41,95%CI:1.14 to 1.76).CONCLUSION:Based on 18 eligible studies,we provide a correlation between MTHFR C677 T polymorphism and POAG among the Asians subgroup indicating that the T allele or TT+TC genotype may play a critical role in POAG development in Asians.
基金supported by the National Natural Science Foundation of China(No.81790643,81970839,82271105,and 82121003)the Sichuan Science and Technology Program(China)(No.2021YFS0033,2021YFS0404,2021YFS0369,and 2020ZYD037)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(China)(No.2019-I2M-5-032).
文摘The retinal pigment epithelium(RPE)and choroid are located behind the human retina and have multiple functions in the human visual system.Knowledge of the RPE and choroid cells and their gene expression profiles are fundamental for understanding retinal disease mechanisms and therapeutic strategies.Here,we sequenced the RNA of about 0.3 million single cells from human RPE and choroids across two regions and seven ages,revealing regional and age differences within the human RPE and choroid.Cell–cell interactions highlight the broad connectivity networks between the RPE and different choroid cell types.Moreover,the transcription factors and their target genes change during aging.The coding of somatic variations increases during aging in the human RPE and choroid at the single-cell level.Moreover,we identified ELN as a candidate for improving RPE degeneration and choroidal structure during aging.The mapping of the molecular architecture of the human RPE and choroid improves our understanding of the human vision support system and offers potential insights into the intervention targets for retinal diseases.
基金supported by the National Natural Science Foundation of China(81790643,81970839,82271105,82121003)the Sichuan Science and Technology Program(2021YFS0033,2021YFS0369,2021YFS0404,2021JDGD0036)the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2019I2M-5-032)。
文摘The human retina serves as a light detector and signals transmission tissue.Advanced insights into retinal disease mechanisms and therapeutic strategies require a deep understanding of healthy retina molecular events.Here,we sequenced the m RNA of over 0.6 million single cells from human retinas across six regions at nine different ages.Sixty cell sub-types have been identified from the human mature retinas with unique markers.We revealed regional and age differences of gene expression profiles within the human retina.Cell-cell interaction analysis indicated a rich synaptic connection within the retinal cells.Gene expression regulon analysis revealed the specific expression of transcription factors and their regulated genes in human retina cell types.Some of the gene’s expression,such as DKK3,are elevated in aged retinas.A further functional investigation suggested that over expression of DKK3 could impact mitochondrial stability.Overall,decoding the molecular dynamic architecture of the human retina improves our understanding of the vision system.
基金supported by the National Precision Medicine Project(2016YFC0905200)the National Natural Science Foundation of China(81790643,82121003,81570882,81770935,81670853,81271005)+1 种基金the grant from Chinese Academy of Medical Sciences(2019-I2M-5-032)the grant from the Department of Science and Technology of Sichuan Province(2021YFS0404,2021FS0369,2020YJ0445,2019JDJQ0031,2022JDTD0024)。
文摘Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1.ABCA1 is a key regulator of cholesterol efflux and the biogenesis of high-density lipoprotein(HDL) particles. Here, we showed that the POAG risk allele near ABCA1 attenuated ABCA1 expression in cultured cells. Consistently, POAG patients exhibited lower ABCA1 expression, reduced HDL, and higher cholesterol in white blood cells. Ablation of Abca1 in mice failed to form HDL, leading to elevated cholesterol levels in the retina. Counting retinal ganglion cells(RGCs) by using an artificial intelligence(AI) program revealed that Abca1-deficient mice progressively lost RGCs with age. Single-cell RNA sequencing(scRNA-seq) revealed aberrant oxidative phosphorylation in the Abca1-/-retina, as well as activation of the mTORC1 signaling pathway and suppression of autophagy. Treatment of Abca1-/-mice using atorvastatin reduced the cholesterol level in the retina,thereby improving metabolism and protecting RGCs from death. Collectively, we show that lower ABCA1 expression and lower HDL are risk factors for POAG. Accumulated cholesterol in the Abca1-/-retina causes profound aberrant metabolism, leading to a POAG-like phenotype that can be prevented by atorvastatin. Our findings establish statin use as a preventive treatment for POAG associated with lower ABCA1 expression.
基金This work was supported by the National Natural Science Foundation of China(82002212,81870683,82070928,81790643,82121003)the Science&Technology Department of Sichuan Province(19YJ0593,2020ZYD035,2020YJ0460,2020JDTD0028,2021JDGD0036,2021YFS0404,2021YFS0369,2022JDTD0024)+6 种基金Department of Sichuan Provincial Health(19PJ117)the Sichuan Provincial People’s Hospital(2018LY03)the Chengdu Science and Technology Bureau(2019-YF0500572-SN)the China Postdoctoral Science Foundation Grant(2019M663567)the foundation of Basic Scientific Research in Central Universities of University of Electronic Science and Technology(ZYGX2020J024)Medicine-engineering interdisciplinary grant of University of Electronic Science and Technology(ZYGX2021YGLH006)the CAMS Innovation Fund for Medical Sciences(2019-12M-5-032)。
文摘The Revised International Staging System(R-ISS)is a simple and powerful prognostic tool for multiple myeloma(MM).However,heterogeneity in R-ISS stage is still poorly characterised,hampering improvement of treatments.We used single-cell RNA-seq to examine novel cellular heterogeneity and regular networks in nine MM patients stratified by R-ISS.Plasma cells were clustered into nine groups(P1–P9)based on gene expression,where P1–P5 were almost enriched in stage III.PDIA6 was significantly upregulated in P3 and LETM1was enriched in P1,and they were validated to be upregulated in the MM cell line and in 22 other patients’myeloma cells.Furthermore,in progression,PDIA6 was newly found and verified to be activated by UQCRB through oxidative phosphorylation,while LETM1 was activated by STAT1 via the C-type lectin receptor-signalling pathway.Finally,a subcluster of monocytes was exclusively found in stage III specifically expressed chemokines modulated by ATF3.A few ligand-receptor pairs(CCL3/CCL5/CCL3L1-CCR1)were obviously active in monocyte-plasma communications in stage III.Herein,this study identified novel molecules,networks and crosstalk pairs in different R-ISS stages of MM,providing significant insight for its prognosis and treatment.
基金supported by the STI 2030-Major Projects(2023ZD04074)the National Key Research and Development Program of China(2023YFD1202900)+2 种基金the Nanfan special project of the Chinese Academy of Agricultural Sciences(YBXM2313)the Hainan Seed Industry Laboratory(project of B23CJ0208)the Agricultural Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences.
文摘CRISPR-mediated base editors have been widely used to correct defective alleles and create novel alleles by artificial evolution for the rapid genetic improvement of crops.The editing capabilities of base editors strictly rely on the performance of various nucleotide modification enzymes.Compared with the welldeveloped adenine base editors(ABEs),cytosine base editors(CBEs)and dual base editors suffer from unstable editing efficiency and patterns at different genomic loci in rice,significantly limiting their application.Here,we comprehensively examined the base editing activities of multiple evolved TadA8e variants in rice.We found that both TadA-CDd and TadA-E27R/N46L achieved more robust C-to-T editing than previously reported hyperactive hAID*D,and TadA-CDd outperformed TadA-E27R/N46L.A C-to-G base editor(CGBE)engineered with TadA-CDd and OsUNG performed highly efficient C-to-G editing in rice compared with that of TadA-N46P.In addition,a dual base editor constructed with a single protein,TadDE,enabled simultaneous,highly efficient C-to-T and A-to-G editing in rice.Collectively,our results demonstrate that TadA8e derivatives improve both CBEs and dual base editors in rice,providing a powerful way to induce diverse nucleotide substitutions for plant genome editing.
文摘Erratum to:SCIENCE CHINA Life Sciences,Volume 66,Issue 2:211-225(2022),https://doi.org/10.1007/s11427-021-2126-2 This paper contains an error in Figure 4C,where the representative images of filipin staining of retinal sections from 6-month-old mice were misused.We provide the correct picture for Figure 4C as follows.The statistical result in Figure 4D was corrected as well.This new Figure 4 does not affect the conclusion of this article.
