As a result of accumulating methylglyoxal and advanced glycation end products in the brains of patients with Alzheimer’s disease,it is considered a protein precipitation disease.The ubiquitin proteasome system is one...As a result of accumulating methylglyoxal and advanced glycation end products in the brains of patients with Alzheimer’s disease,it is considered a protein precipitation disease.The ubiquitin proteasome system is one of the most important mechanisms for cells to degrade proteins,and thus is very important for maintaining normal physiological function of the nervous system.This study recruited 48 individuals with Alzheimer’s disease(20 males and 28 females aged 75±6 years)and 50 healthy volunteers(21 males and 29 females aged 72±7 years)from the Affiliated Hospital of Youjiang Medical University for Nationalities(Baise,China)between 2014 and 2017.Plasma levels of malondialdehyde and H2O2 were measured by colorimetry,while glyoxalase 1 activity was detected by spectrophotometry.In addition,20S proteasome activity in erythrocytes was measured with a fluorescent substrate method.Ubiquitin and glyoxalase 1 protein expression in erythrocyte membranes was detected by western blot assay.The results demonstrated that compared with the control group,patients with Alzheimer’s disease exhibited increased plasma malondialdehyde and H2O2 levels,and decreased glyoxalase 1 activity;however,expression level of glyoxalase 1 protein remained unchanged.Moreover,activity of the 20S proteasome was decreased and expression of ubiquitin protein was increased in erythrocytes.These findings indicate that proteasomal and glyoxalase activities may be involved in the occurrence of Alzheimer’s disease,and erythrocytes may be a suitable tissue for Alzheimer’s disease studies.This study was approved by the Ethics Committee of Youjiang Medical University for Nationalities(approval No.YJ12017013)on May 3,2017.展开更多
During the pathogenesis of type 1 diabetes(T1D) and type 2 diabetes(T2D), pancreatic islets, especially the β cells, face significant challenges. These insulin-producing cells adopt a regeneration strategy to compens...During the pathogenesis of type 1 diabetes(T1D) and type 2 diabetes(T2D), pancreatic islets, especially the β cells, face significant challenges. These insulin-producing cells adopt a regeneration strategy to compensate for the shortage of insulin, but the exact mechanism needs to be defined. High-fat diet(HFD) and streptozotocin(STZ) treatment are well-established models to study islet damage in T2D and T1D respectively. Therefore, we applied these two diabetic mouse models, triggered at different ages, to pursue the cell fate transition of isletβ cells. Cre-LoxP systems were used to generate islet cell type-specific(α, β, or δ) green fluorescent protein(GFP)-labeled mice for genetic lineage tracing, thereinto β-cell GFP-labeled mice were tamoxifen induced. Single-cell RNA sequencing(scRNA-seq) was used to investigate the evolutionary trajectories and molecular mechanisms of the GFP-labeled β cells in STZ-treated mice. STZ-induced diabetes caused extensive dedifferentiation of β cells and some of which transdifferentiated into α or δ cells in both youth-and adulthood-initiated mice while this phenomenon was barely observed in HFD models. β cells in HFD mice were expanded via self-replication rather than via transdifferentiation from α or δ cells, in contrast, α or δ cells were induced to transdifferentiate into β cells in STZ-treated mice(both youthand adulthood-initiated). In addition to the re-dedifferentiation of β cells, it is also highly likely that these “α or δ” cells transdifferentiated from pre-existing β cells could also re-trans-differentiate into insulin-producing β cells and be beneficial to islet recovery. The analysis of ScRNA-seq revealed that several pathways including mitochondrial function, chromatin modification, and remodeling are crucial in the dynamic transition of β cells. Our findings shed light on how islet β cells overcome the deficit of insulin and the molecular mechanism of islet recovery in T1D and T2D pathogenesis.展开更多
DNA sequencers have become increasingly important research and diagnostic tools over the past 20 years.In this study,we developed a single-molecule desktop sequencer,GenoCare 1600(GenoCare),which utilizes amplificatio...DNA sequencers have become increasingly important research and diagnostic tools over the past 20 years.In this study,we developed a single-molecule desktop sequencer,GenoCare 1600(GenoCare),which utilizes amplification-free library preparation and two-color sequencing-by-synthesis chemistry,making it more user-friendly compared with previous single-molecule sequencing platforms for clinical use.Using the GenoCare platform,we sequenced an Escherichia coli standard sample and achieved a consensus accuracy exceeding 99.99%.We also evaluated the sequencing performance of this platform in microbial mixtures and coronavirus disease 2019(COVID-19)samples from throat swabs.Our findings indicate that the GenoCare platform allows for microbial quantitation,sensitive identification of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus,and accurate detection of virus mutations,as confirmed by Sanger sequencing,demonstrating its remarkable potential in clinical application.展开更多
Fluid intelligence is a cognitive domain that encompasses general reasoning, pattern recognition, and problem-solving abilities independent of task-specific experience. Understanding its genetic and neural underpinnin...Fluid intelligence is a cognitive domain that encompasses general reasoning, pattern recognition, and problem-solving abilities independent of task-specific experience. Understanding its genetic and neural underpinnings is critical yet challenging for predicting human development, lifelong health, and well-being. One approach to address this challenge is to map the network of correlations between intelligence and other constructs. In the current study, we performed a genome-wide association study using fluid intelligence quotient scores from the UK Biobank to explore the genetic architecture of the associations between obesity risk and fluid intelligence. Our results revealed novel common genetic loci (SH2B1, TUFM, ATP2A1, and FOXO3) underlying the association between fluid intelligence and body metabolism. Surprisingly, we demonstrated that SH2B1 variation influenced fluid intelligence independently of its effects on metabolism but partially mediated its association with bilateral hippocampal volume. Consistently, selective genetic ablation of Sh2b1 in the mouse hippocampus, particularly in inhibitory neurons, but not in excitatory neurons, significantly impaired working memory, short-term novel object recognition memory, and behavioral flexibility, but not spatial learning and memory, mirroring the human intellectual performance. Single-cell genetic profiling of Sh2B1-regulated molecular pathways revealed that Sh2b1 deletion resulted in aberrantly enhanced extracellular signal-regulated kinase (ERK) signaling, whereas pharmacological inhibition of ERK signaling reversed the associated behavioral impairment. Our cross-species study thus provides unprecedented insight into the role of SH2B1 in fluid intelligence and has implications for understanding the genetic and neural underpinnings of lifelong mental health and well-being.展开更多
Background To evaluate the effect of recombinant human thrombopoietin(rhTPO)on clinical prognosis by exploring changes in endothelial cell injury markers and inflammatory factors in patients with sepsis after treatmen...Background To evaluate the effect of recombinant human thrombopoietin(rhTPO)on clinical prognosis by exploring changes in endothelial cell injury markers and inflammatory factors in patients with sepsis after treatment with rhTPO.Methods This retrospective observational study involved patients with sepsis(diagnosed according to Sepsis 3.0)admitted to Shanghai General Hospital intensive care unit from January 1,2019 to December 31,2022.Patients were divided into two groups(control and rhTPO)according to whether they received rhTPO.Baseline information,clinical data,prognosis,and survival status of the patients,as well as inflammatory factors and immune function indicators were collected.The main monitoring indicators were endothelial cell-specific molecule(ESM-1),human heparin-binding protein(HBP),and CD31;secondary monitoring indicators were interleukin(IL)-6,tumor necrosis factor(TNF)-α,extravascular lung water index,platelet,antithrombin III,fibrinogen,and international normalized ratio.We used intraperitoneal injection of lipopolysaccharide(LPS)to establish a mouse model of sepsis.Mice were randomly divided into four groups:normal saline,LPS,LPS+rhTPO,and LPS+rhTPO+LY294002.Plasma indicators in mice were measured by enzyme-linked immunosorbent assay.Results A total of 84 patients were included in the study.After 7 days of treatment,ESM-1 decreased more significantly in the rhTPO group than in the control group compared with day 1(median=38.6[interquartile range,IQR:7.2 to 67.8]pg/mL vs.median=23.0[IQR:−15.7 to 51.5]pg/mL,P=0.008).HBP and CD31 also decreased significantly in the rhTPO group compared with the control group(median=59.6[IQR:−1.9 to 91.9]pg/mL vs.median=2.4[IQR:−23.2 to 43.2]pg/mL;median=2.4[IQR:0.4 to 3.5]pg/mL vs.median=−0.6[IQR:−2.2 to 0.8]pg/mL,P<0.001).Inflammatory markers IL-6 and TNF-αdecreased more significantly in the rhTPO group than in the control group compared with day 1(median=46.0[IQR:15.8 to 99.1]pg/mL vs.median=31.2[IQR:19.7 to 171.0]pg/mL,P<0.001;median=17.2[IQR:6.4 to 23.2]pg/mL vs.median=0.0[IQR:0.0 to 13.8]pg/mL,P=0.010).LPS+rhTPO-treated mice showed significantly lower vascular von Willebrand factor(P=0.003),vascular endothelial growth factor(P=0.002),IL-6(P<0.001),and TNF-α(P<0.001)than mice in the LPS group.Endothelial cell damage factors vascular von Willebrand factor(P=0.012),vascular endothelial growth factor(P=0.001),IL-6(P<0.001),and TNF-α(P=0.001)were significantly elevated by inhibiting the PI3K/Akt pathway.Conclusion rhTPO alleviates endothelial injury and inflammatory indices in sepsis,and may regulate septic endothelial cell injury through the PI3K/Akt pathway.展开更多
Ligand-mediated nickel-catalyzed asymmetric hydrogenation of alkynone imines has been achieved. By using Ni(OAc)_2·4H_2O/(S,S)-Ph-BPE complex as a catalyst, the chemo-and enantioselective hydrogenation of alkynon...Ligand-mediated nickel-catalyzed asymmetric hydrogenation of alkynone imines has been achieved. By using Ni(OAc)_2·4H_2O/(S,S)-Ph-BPE complex as a catalyst, the chemo-and enantioselective hydrogenation of alkynone imines occurred efficiently to afford chiral propargyl amines with high yields and excellent enantioselectivities(up to 99% yield, >99% ee), leaving the readily reducible alkynyl group intact. Both the C=N and C≡C bonds of alkynone imines were hydrogenated efficiently in the presence of Ni(OAc)_2·4H_2O and Josiphos SL-J011-1, furnishing unfunctionalized chiral imines efficiently(up to 99% yield, >99% ee).The(Z)-allylamines and(E)-allylamines were also efficiently prepared from alkynone imines by the combination of the different catalytic systems. The preliminary mechanism study revealed that the reduction of alkynone imines was a stepwise process and the C=N bonds were preferably hydrogenated in the complete reduction of alkynone imines. The synthetic utility of this method was demonstrated by its application in the late-stage modification of the antiviral drug Zidovudine and the concise synthesis of chiral dibenzoazepine.展开更多
Sentence Boundary Disambiguation(SBD)is a preprocessing step for natural language processing.Segmenting text into sentences is essential for Deep Learning(DL)and pretraining language models.Tibetan punctuation marks m...Sentence Boundary Disambiguation(SBD)is a preprocessing step for natural language processing.Segmenting text into sentences is essential for Deep Learning(DL)and pretraining language models.Tibetan punctuation marks may involve ambiguity about the sentences’beginnings and endings.Hence,the ambiguous punctuation marks must be distinguished,and the sentence structure must be correctly encoded in language models.This study proposed a component-level Tibetan SBD approach based on the DL model.The models can reduce the error amplification caused by word segmentation and part-of-speech tagging.Although most SBD methods have only considered text on the left side of punctuation marks,this study considers the text on both sides.In this study,465669 Tibetan sentences are adopted,and a Bidirectional Long Short-Term Memory(Bi-LSTM)model is used to perform SBD.The experimental results show that the F1-score of the Bi-LSTM model reached 96%,the most efficient among the six models.Experiments are performed on low-resource languages such as Turkish and Romanian,and high-resource languages such as English and German,to verify the models’generalization.展开更多
Background Since the beginning of the coronavirus disease 2019(COVID-19)pandemic,prone positioning has been widely applied for non-intubated,spontaneously breathing patients.However,the efficacy and safety of prone po...Background Since the beginning of the coronavirus disease 2019(COVID-19)pandemic,prone positioning has been widely applied for non-intubated,spontaneously breathing patients.However,the efficacy and safety of prone positioning in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure remain unclear.We aimed to systematically analyze the outcomes associated with awake prone positioning(APP).Methods We conducted a systematic literature search of PubMed/MEDLINE,Cochrane Library,Embase,and Web of Science from January 1,2020,to June 3,2022.This study included adult patients with acute respiratory failure caused by COVID-19.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines were followed,and the study quality was assessed using the Cochrane risk-of-bias tool.The primary outcome was the reported cumulative intubation risk across randomized controlled trials(RCTs),and the effect estimates were calculated as risk ratios(RRs;95%confidence interval[CI]).Results A total of 495 studies were identified,of which 10 fulfilled the selection criteria,and 2294 patients were included.In comparison to supine positioning,APP significantly reduced the need for intubation in the overall population(RR=0.84,95%CI:0.74–0.95).The two groups showed no significant differences in the incidence of adverse events(RR=1.16,95%CI:0.48–2.76).The meta-analysis revealed no difference in mortality between the groups(RR=0.93,95%CI:0.77–1.11).Conclusions APP was safe and reduced the need for intubation in patients with respiratory failure associated with COVID-19.However,it did not significantly reduce mortality in comparison to usual care without prone positioning.展开更多
Recent research about reconstruction methods mainly used the interpolation reconstruction of the fluctuating wind pressure field on the surface.However,to investigate wind pressure at the edge of the building,the work...Recent research about reconstruction methods mainly used the interpolation reconstruction of the fluctuating wind pressure field on the surface.However,to investigate wind pressure at the edge of the building,the work presented in this paper focuses on the extrapolation reconstruction of wind pressure fields.Here,we propose an improved proper orthogonal decomposition(POD)and Kriging method with a von Karman correlation function to resolve this issue.The studies show that it works well for not only interpolation reconstruction but also extrapolation reconstruction.The proposed method does require determination of the Hurst exponent and other parameters analysed from the original data.Hence,the fluctuating wind fields have been characterized by the von Karman correlation function,as an a priori function.Compared with the cubic spline method and different variogram,preliminary results suggest less time consumption and high efficiency in extrapolation reconstruction at the edge.展开更多
Nickel/(S)-t-Bu-PHOX complex catalyzed asymmetric arylative cyclization of N-alkynones has been achieved, delivering 1,2,3,6-tetrahydropyridines containing a chiral tertiary alcohol in high yields and excellent enanti...Nickel/(S)-t-Bu-PHOX complex catalyzed asymmetric arylative cyclization of N-alkynones has been achieved, delivering 1,2,3,6-tetrahydropyridines containing a chiral tertiary alcohol in high yields and excellent enantioselectivities, which provides efficient access to chiral tetrahydropyridine and piperidine analogues.展开更多
The method of fundamental solutions(MFS)and the Collocation Trefftz method have been known as two highly effective boundary-type methods for solving homogeneous equations.Despite many attractive features of these two ...The method of fundamental solutions(MFS)and the Collocation Trefftz method have been known as two highly effective boundary-type methods for solving homogeneous equations.Despite many attractive features of these two methods,they also experience different aspects of difficulty.Recent advances in the selection of source location of theMFS and the techniques in reducing the condition number of the Trefftz method have made significant improvement in the performance of these two methods which have been proven to be theoretically equivalent.In this paper we will compare the numerical performance of these two methods under various smoothness of the boundary and boundary conditions.展开更多
A combined model of the transmission-line laser model （TLLM） and the digital filter approach is developed to simulate the shuttering characteristic of a semiconductor optical amplifier （SOA）, which is inte- grated...A combined model of the transmission-line laser model （TLLM） and the digital filter approach is developed to simulate the shuttering characteristic of a semiconductor optical amplifier （SOA）, which is inte- grated with a sampled grating distributed Bragg reflector （SGDBR） laser, to create a so called SOA-SGDBR laser. The SOA section acts as a shutter to blank the laser output during wavelength switching events. Simulated results show that the turn-on edge of the SOA blanking process will oscillate when the facet reflection of SOA is relatively high. This phenomenon is also observed by experiments.展开更多
The first asymmetric hydrogenation of acyclic tetrasubstitutedα,β-unsaturated amides has been achieved by using Rh/DuanPhos complex as a catalyst,delivering chiralβ-amino amides with two contiguous chiral centers i...The first asymmetric hydrogenation of acyclic tetrasubstitutedα,β-unsaturated amides has been achieved by using Rh/DuanPhos complex as a catalyst,delivering chiralβ-amino amides with two contiguous chiral centers in excellent yields and high enantioselectivities(up to 99%yield,96%ee),which provides efficient and concise access to valuableβ-amino amide derivatives.The gram-scale reaction and efficient transformation ofβ-amino amide toβ-amino acid andβ-amino cyanide demonstrated the utility of this methodology.展开更多
基金supported by the National Natural Science Foundation of China,No.81860244the Natural Science Foundation of Guangxi Zhuang Autonomous Region of China,No.2018JJA140311 and 2018GXNSFAA281051the Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi Zhuang Autonomous Region of China,No.2017KY0516(all to CDJ)
文摘As a result of accumulating methylglyoxal and advanced glycation end products in the brains of patients with Alzheimer’s disease,it is considered a protein precipitation disease.The ubiquitin proteasome system is one of the most important mechanisms for cells to degrade proteins,and thus is very important for maintaining normal physiological function of the nervous system.This study recruited 48 individuals with Alzheimer’s disease(20 males and 28 females aged 75±6 years)and 50 healthy volunteers(21 males and 29 females aged 72±7 years)from the Affiliated Hospital of Youjiang Medical University for Nationalities(Baise,China)between 2014 and 2017.Plasma levels of malondialdehyde and H2O2 were measured by colorimetry,while glyoxalase 1 activity was detected by spectrophotometry.In addition,20S proteasome activity in erythrocytes was measured with a fluorescent substrate method.Ubiquitin and glyoxalase 1 protein expression in erythrocyte membranes was detected by western blot assay.The results demonstrated that compared with the control group,patients with Alzheimer’s disease exhibited increased plasma malondialdehyde and H2O2 levels,and decreased glyoxalase 1 activity;however,expression level of glyoxalase 1 protein remained unchanged.Moreover,activity of the 20S proteasome was decreased and expression of ubiquitin protein was increased in erythrocytes.These findings indicate that proteasomal and glyoxalase activities may be involved in the occurrence of Alzheimer’s disease,and erythrocytes may be a suitable tissue for Alzheimer’s disease studies.This study was approved by the Ethics Committee of Youjiang Medical University for Nationalities(approval No.YJ12017013)on May 3,2017.
基金supported by the National Natural Science Foundation of China(81830023,82070803,82100838,82100837,81900708)。
文摘During the pathogenesis of type 1 diabetes(T1D) and type 2 diabetes(T2D), pancreatic islets, especially the β cells, face significant challenges. These insulin-producing cells adopt a regeneration strategy to compensate for the shortage of insulin, but the exact mechanism needs to be defined. High-fat diet(HFD) and streptozotocin(STZ) treatment are well-established models to study islet damage in T2D and T1D respectively. Therefore, we applied these two diabetic mouse models, triggered at different ages, to pursue the cell fate transition of isletβ cells. Cre-LoxP systems were used to generate islet cell type-specific(α, β, or δ) green fluorescent protein(GFP)-labeled mice for genetic lineage tracing, thereinto β-cell GFP-labeled mice were tamoxifen induced. Single-cell RNA sequencing(scRNA-seq) was used to investigate the evolutionary trajectories and molecular mechanisms of the GFP-labeled β cells in STZ-treated mice. STZ-induced diabetes caused extensive dedifferentiation of β cells and some of which transdifferentiated into α or δ cells in both youth-and adulthood-initiated mice while this phenomenon was barely observed in HFD models. β cells in HFD mice were expanded via self-replication rather than via transdifferentiation from α or δ cells, in contrast, α or δ cells were induced to transdifferentiate into β cells in STZ-treated mice(both youthand adulthood-initiated). In addition to the re-dedifferentiation of β cells, it is also highly likely that these “α or δ” cells transdifferentiated from pre-existing β cells could also re-trans-differentiate into insulin-producing β cells and be beneficial to islet recovery. The analysis of ScRNA-seq revealed that several pathways including mitochondrial function, chromatin modification, and remodeling are crucial in the dynamic transition of β cells. Our findings shed light on how islet β cells overcome the deficit of insulin and the molecular mechanism of islet recovery in T1D and T2D pathogenesis.
文摘DNA sequencers have become increasingly important research and diagnostic tools over the past 20 years.In this study,we developed a single-molecule desktop sequencer,GenoCare 1600(GenoCare),which utilizes amplification-free library preparation and two-color sequencing-by-synthesis chemistry,making it more user-friendly compared with previous single-molecule sequencing platforms for clinical use.Using the GenoCare platform,we sequenced an Escherichia coli standard sample and achieved a consensus accuracy exceeding 99.99%.We also evaluated the sequencing performance of this platform in microbial mixtures and coronavirus disease 2019(COVID-19)samples from throat swabs.Our findings indicate that the GenoCare platform allows for microbial quantitation,sensitive identification of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus,and accurate detection of virus mutations,as confirmed by Sanger sequencing,demonstrating its remarkable potential in clinical application.
基金grants from the National Key Research and Development Program of China (2023YFE0109700)the National Natural Science Foundation of China (82125032, 81930095, 32071023, 82272079, and 32200967)+4 种基金the Science and Technology Commission of Shanghai Municipality (23Y21900500, 2018SHZDZX01, 22XD1420700, 23XD142300, and 23YF1425700)the Shanghai Municipal Commission of Health and Family Planning (GWV-11.1-34, 2020CXJQ01, 2018YJRC03, and 2022XD046)the Innovative research team of high-level local universities in Shanghai (SHSMU-ZDCX20211100)the Guangdong Key Project (2018B030335001)University of Sydney - Fudan University BISA Flagship Research Program. Y.Y. and T.Z. were awarded the fellowship of China Postdoctoral Science Foundation (2021M700851, 2023T160117, and 2022M712125).
文摘Fluid intelligence is a cognitive domain that encompasses general reasoning, pattern recognition, and problem-solving abilities independent of task-specific experience. Understanding its genetic and neural underpinnings is critical yet challenging for predicting human development, lifelong health, and well-being. One approach to address this challenge is to map the network of correlations between intelligence and other constructs. In the current study, we performed a genome-wide association study using fluid intelligence quotient scores from the UK Biobank to explore the genetic architecture of the associations between obesity risk and fluid intelligence. Our results revealed novel common genetic loci (SH2B1, TUFM, ATP2A1, and FOXO3) underlying the association between fluid intelligence and body metabolism. Surprisingly, we demonstrated that SH2B1 variation influenced fluid intelligence independently of its effects on metabolism but partially mediated its association with bilateral hippocampal volume. Consistently, selective genetic ablation of Sh2b1 in the mouse hippocampus, particularly in inhibitory neurons, but not in excitatory neurons, significantly impaired working memory, short-term novel object recognition memory, and behavioral flexibility, but not spatial learning and memory, mirroring the human intellectual performance. Single-cell genetic profiling of Sh2B1-regulated molecular pathways revealed that Sh2b1 deletion resulted in aberrantly enhanced extracellular signal-regulated kinase (ERK) signaling, whereas pharmacological inhibition of ERK signaling reversed the associated behavioral impairment. Our cross-species study thus provides unprecedented insight into the role of SH2B1 in fluid intelligence and has implications for understanding the genetic and neural underpinnings of lifelong mental health and well-being.
基金supported by grants from the Shenkang Municipal Hospital emerging Frontier technology joint project(grant no.SHDC12019131)the National Natural Science Foundation of China(grant no.82202423)+4 种基金the Clinical Research Innovation Plan of Shanghai General Hospital(grant no.CCTR-2022B04)the 3rd Sansheng TCP Young and Middleaged Scientific Research FundingShanghai Jiao Tong University“Medicine-Engineering Interdisciplinary Research Fund”(grant no.YG2021QN79)National Key Clinical Specialist Construction Project(grant no.Z155080000004)Shanghai Committee(grant no.23Y31900100).
文摘Background To evaluate the effect of recombinant human thrombopoietin(rhTPO)on clinical prognosis by exploring changes in endothelial cell injury markers and inflammatory factors in patients with sepsis after treatment with rhTPO.Methods This retrospective observational study involved patients with sepsis(diagnosed according to Sepsis 3.0)admitted to Shanghai General Hospital intensive care unit from January 1,2019 to December 31,2022.Patients were divided into two groups(control and rhTPO)according to whether they received rhTPO.Baseline information,clinical data,prognosis,and survival status of the patients,as well as inflammatory factors and immune function indicators were collected.The main monitoring indicators were endothelial cell-specific molecule(ESM-1),human heparin-binding protein(HBP),and CD31;secondary monitoring indicators were interleukin(IL)-6,tumor necrosis factor(TNF)-α,extravascular lung water index,platelet,antithrombin III,fibrinogen,and international normalized ratio.We used intraperitoneal injection of lipopolysaccharide(LPS)to establish a mouse model of sepsis.Mice were randomly divided into four groups:normal saline,LPS,LPS+rhTPO,and LPS+rhTPO+LY294002.Plasma indicators in mice were measured by enzyme-linked immunosorbent assay.Results A total of 84 patients were included in the study.After 7 days of treatment,ESM-1 decreased more significantly in the rhTPO group than in the control group compared with day 1(median=38.6[interquartile range,IQR:7.2 to 67.8]pg/mL vs.median=23.0[IQR:−15.7 to 51.5]pg/mL,P=0.008).HBP and CD31 also decreased significantly in the rhTPO group compared with the control group(median=59.6[IQR:−1.9 to 91.9]pg/mL vs.median=2.4[IQR:−23.2 to 43.2]pg/mL;median=2.4[IQR:0.4 to 3.5]pg/mL vs.median=−0.6[IQR:−2.2 to 0.8]pg/mL,P<0.001).Inflammatory markers IL-6 and TNF-αdecreased more significantly in the rhTPO group than in the control group compared with day 1(median=46.0[IQR:15.8 to 99.1]pg/mL vs.median=31.2[IQR:19.7 to 171.0]pg/mL,P<0.001;median=17.2[IQR:6.4 to 23.2]pg/mL vs.median=0.0[IQR:0.0 to 13.8]pg/mL,P=0.010).LPS+rhTPO-treated mice showed significantly lower vascular von Willebrand factor(P=0.003),vascular endothelial growth factor(P=0.002),IL-6(P<0.001),and TNF-α(P<0.001)than mice in the LPS group.Endothelial cell damage factors vascular von Willebrand factor(P=0.012),vascular endothelial growth factor(P=0.001),IL-6(P<0.001),and TNF-α(P=0.001)were significantly elevated by inhibiting the PI3K/Akt pathway.Conclusion rhTPO alleviates endothelial injury and inflammatory indices in sepsis,and may regulate septic endothelial cell injury through the PI3K/Akt pathway.
基金supported by the National Natural Science Foundation of China (22071188, 21871212)the Open Foundation of CAS Key Laboratory of Molecular Recognition and Functionthe “Double First-Class” Project of Shihezi University。
文摘Ligand-mediated nickel-catalyzed asymmetric hydrogenation of alkynone imines has been achieved. By using Ni(OAc)_2·4H_2O/(S,S)-Ph-BPE complex as a catalyst, the chemo-and enantioselective hydrogenation of alkynone imines occurred efficiently to afford chiral propargyl amines with high yields and excellent enantioselectivities(up to 99% yield, >99% ee), leaving the readily reducible alkynyl group intact. Both the C=N and C≡C bonds of alkynone imines were hydrogenated efficiently in the presence of Ni(OAc)_2·4H_2O and Josiphos SL-J011-1, furnishing unfunctionalized chiral imines efficiently(up to 99% yield, >99% ee).The(Z)-allylamines and(E)-allylamines were also efficiently prepared from alkynone imines by the combination of the different catalytic systems. The preliminary mechanism study revealed that the reduction of alkynone imines was a stepwise process and the C=N bonds were preferably hydrogenated in the complete reduction of alkynone imines. The synthetic utility of this method was demonstrated by its application in the late-stage modification of the antiviral drug Zidovudine and the concise synthesis of chiral dibenzoazepine.
基金This work was supported by the National Key R&D Program of China(No.2020YFC0832500)the Ministry of Education-China Mobile Research Foundation(No.MCM20170206)+5 种基金the Fundamental Research Funds for the Central Universities(Nos.lzujbky-2022-kb12,lzujbky-2021-sp43,lzujbky-2020-sp02,lzujbky-2019-kb51,and lzujbky-2018-k12)the National Natural Science Foundation of China(No.61402210)the Science and Technology Plan of Qinghai Province(No.2020-GX-164)the Google Research Awards and Google Faculty Award,the Provincial Science and Technology Plan(Major Science and Technology Projects-Open Solicitation)(No.22ZD6GA048)the Gansu Provincial Science and Technology Major Special Innovation Consortium Project(No.21ZD3GA002)the Gansu Province Green and Smart Highway Key Technology Research and Demonstration。
文摘Sentence Boundary Disambiguation(SBD)is a preprocessing step for natural language processing.Segmenting text into sentences is essential for Deep Learning(DL)and pretraining language models.Tibetan punctuation marks may involve ambiguity about the sentences’beginnings and endings.Hence,the ambiguous punctuation marks must be distinguished,and the sentence structure must be correctly encoded in language models.This study proposed a component-level Tibetan SBD approach based on the DL model.The models can reduce the error amplification caused by word segmentation and part-of-speech tagging.Although most SBD methods have only considered text on the left side of punctuation marks,this study considers the text on both sides.In this study,465669 Tibetan sentences are adopted,and a Bidirectional Long Short-Term Memory(Bi-LSTM)model is used to perform SBD.The experimental results show that the F1-score of the Bi-LSTM model reached 96%,the most efficient among the six models.Experiments are performed on low-resource languages such as Turkish and Romanian,and high-resource languages such as English and German,to verify the models’generalization.
基金supported by the Clinical Research Plan of SHDC (grant number:SHDC2020CR2013A)the Clinical Research Plan of SHDC (grant number:SHDC2020CR5010-003).
文摘Background Since the beginning of the coronavirus disease 2019(COVID-19)pandemic,prone positioning has been widely applied for non-intubated,spontaneously breathing patients.However,the efficacy and safety of prone positioning in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure remain unclear.We aimed to systematically analyze the outcomes associated with awake prone positioning(APP).Methods We conducted a systematic literature search of PubMed/MEDLINE,Cochrane Library,Embase,and Web of Science from January 1,2020,to June 3,2022.This study included adult patients with acute respiratory failure caused by COVID-19.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines were followed,and the study quality was assessed using the Cochrane risk-of-bias tool.The primary outcome was the reported cumulative intubation risk across randomized controlled trials(RCTs),and the effect estimates were calculated as risk ratios(RRs;95%confidence interval[CI]).Results A total of 495 studies were identified,of which 10 fulfilled the selection criteria,and 2294 patients were included.In comparison to supine positioning,APP significantly reduced the need for intubation in the overall population(RR=0.84,95%CI:0.74–0.95).The two groups showed no significant differences in the incidence of adverse events(RR=1.16,95%CI:0.48–2.76).The meta-analysis revealed no difference in mortality between the groups(RR=0.93,95%CI:0.77–1.11).Conclusions APP was safe and reduced the need for intubation in patients with respiratory failure associated with COVID-19.However,it did not significantly reduce mortality in comparison to usual care without prone positioning.
文摘Recent research about reconstruction methods mainly used the interpolation reconstruction of the fluctuating wind pressure field on the surface.However,to investigate wind pressure at the edge of the building,the work presented in this paper focuses on the extrapolation reconstruction of wind pressure fields.Here,we propose an improved proper orthogonal decomposition(POD)and Kriging method with a von Karman correlation function to resolve this issue.The studies show that it works well for not only interpolation reconstruction but also extrapolation reconstruction.The proposed method does require determination of the Hurst exponent and other parameters analysed from the original data.Hence,the fluctuating wind fields have been characterized by the von Karman correlation function,as an a priori function.Compared with the cubic spline method and different variogram,preliminary results suggest less time consumption and high efficiency in extrapolation reconstruction at the edge.
基金financial support from the National Natural Science Foundation of China (Nos. 22071188, 21871212)the open foundation of CAS Key Laboratory of Molecular Recognition and Function, the "Double First-Class" Project of Shihezi University。
文摘Nickel/(S)-t-Bu-PHOX complex catalyzed asymmetric arylative cyclization of N-alkynones has been achieved, delivering 1,2,3,6-tetrahydropyridines containing a chiral tertiary alcohol in high yields and excellent enantioselectivities, which provides efficient access to chiral tetrahydropyridine and piperidine analogues.
基金Authors acknowledge the support of the Soft Science Project of Shanxi Province of China(Project No.2016041029-5)the National Natural Science Foundation of China(Grant No.11472184)the National Youth Science Foundation of China(Grant No.11401423).
文摘The method of fundamental solutions(MFS)and the Collocation Trefftz method have been known as two highly effective boundary-type methods for solving homogeneous equations.Despite many attractive features of these two methods,they also experience different aspects of difficulty.Recent advances in the selection of source location of theMFS and the techniques in reducing the condition number of the Trefftz method have made significant improvement in the performance of these two methods which have been proven to be theoretically equivalent.In this paper we will compare the numerical performance of these two methods under various smoothness of the boundary and boundary conditions.
文摘A combined model of the transmission-line laser model （TLLM） and the digital filter approach is developed to simulate the shuttering characteristic of a semiconductor optical amplifier （SOA）, which is inte- grated with a sampled grating distributed Bragg reflector （SGDBR） laser, to create a so called SOA-SGDBR laser. The SOA section acts as a shutter to blank the laser output during wavelength switching events. Simulated results show that the turn-on edge of the SOA blanking process will oscillate when the facet reflection of SOA is relatively high. This phenomenon is also observed by experiments.
基金financial support from the National Natural Science Foundation of China(Grant Nos.22071188,22371217)Hubei Provincial Natural Science Foundation of China(2023AFA011).
文摘The first asymmetric hydrogenation of acyclic tetrasubstitutedα,β-unsaturated amides has been achieved by using Rh/DuanPhos complex as a catalyst,delivering chiralβ-amino amides with two contiguous chiral centers in excellent yields and high enantioselectivities(up to 99%yield,96%ee),which provides efficient and concise access to valuableβ-amino amide derivatives.The gram-scale reaction and efficient transformation ofβ-amino amide toβ-amino acid andβ-amino cyanide demonstrated the utility of this methodology.
