Background The neurophysiological differences in cortical plasticity and cholinergic system function due to ageing and their correlation with cognitive function remain poorly understood.Aims To reveal the differences ...Background The neurophysiological differences in cortical plasticity and cholinergic system function due to ageing and their correlation with cognitive function remain poorly understood.Aims To reveal the differences in long-term potentiation(LTP)-like plasticity and short-latency afferent inhibition(SAl)between older and younger individuals,alongside their correlation with cognitive function using transcranial magnetic stimulation(TMS).Methods The cross-sectional study involved 31 younger adults aged 18-30 and 46 older adults aged 60-80.All participants underwent comprehensive cognitive assessments and a neurophysiological evaluation based on TMS.Cognitive function assessments included evaluations of global cognitive function,language,memory and executive function.The neurophysiological assessment included LTP-like plasticity and SAl.Results The findings of this study revealed a decline in LTP among the older adults compared with the younger adults(wald χ^(2)=3.98,p=0.046).Subgroup analysis further demonstrated a significant reduction in SAl level among individuals aged 70-80 years in comparison to both the younger adults(SAI(N20)):(t=-3.37,p=0.018);SAl(N20+4):(t=-3.13,p=0.038)and those aged 60-70(SAl(N20)):(t=3.26,p=0.025);SAl(N20+4):(t=-3.69,p=0.006).Conversely,there was no notable difference in SAl level between those aged 60-70 years and the younger group.Furthermore,after employing the Bonferroni correction,the correlation analysis revealed that only the positive correlation between LTP-like plasticity and language function(r=0.61,p<0.001)in the younger group remained statistically significant.Conclusions During the normal ageing process,a decline in synaptic plasticity may precede cholinergic system dysfunction.In individuals over 60 years of age,there is a reduction in LTP-like plasticity,while a decline in cholinergic system function is observed in those over 70.Thus,the cholinergic system may play a vital role in preventing cognitive decline during normal ageing.In younger individuals,LTP-like plasticity might represent a potential neurophysiological marker for language function.展开更多
NdNiO_(3) is a typical correlated material with temperature-driven metal–insulator transition. Resolving the local electronic phase is crucial in understanding the driving mechanism behind the phase transition. Here ...NdNiO_(3) is a typical correlated material with temperature-driven metal–insulator transition. Resolving the local electronic phase is crucial in understanding the driving mechanism behind the phase transition. Here we present a nano-infrared study of the metal–insulator transition in NdNiO_(3) films by a cryogenic scanning near-field optical microscope. The NdNiO_(3) films undergo a continuous transition without phase coexistence. The nano-infrared signal shows significant temperature dependence and a hysteresis loop. Stripe-like modulation of the optical conductivity is formed in the films and can be attributed to the epitaxial strain. These results provide valuable evidence to understand the coupled electronic and structural transformations in NdNiO_(3) films at the nano-scale.展开更多
In the context of next-generation optical access networks beyond 10 G, for high SE and flexible dynamic bandwidth allocation (DBA), the scheme of hybrid 64/16/4QAM-OFDM signal for downlink transmission and hybrid 16/8...In the context of next-generation optical access networks beyond 10 G, for high SE and flexible dynamic bandwidth allocation (DBA), the scheme of hybrid 64/16/4QAM-OFDM signal for downlink transmission and hybrid 16/8/QPSK-OFDM signal for uplink transmission is successfully proposed and experimentally presented in a full-duplex PON based on OFDM system. Here, for the uplink, in order to unit management of the optical line terminal (OLT) and reduce cost, the optical source functioned as the optical subcarrier at optical network units (ONUs) is from OLT in the central station. Moreover, there is an external cavity laser (ECL) with center frequency of 193.2 THz not only employed as optical modulated signal but also acted as LO signal. Our simulation results show that bit error ratio (BER) under hardware detection forward error correction has been successfully gained after 20 km of SSMF transmission. It is observed that the receiver sensitivity of multilevel PSK (M-PSK) is obviously larger than that of the M-QAM in this measurement scheme.展开更多
To the Editor,Previous studies have demonstrated close associations of specific immune cell profiles in the occurrence and development of COVID-19.[1,2]However,due to confounding factors and reverse causality in tradi...To the Editor,Previous studies have demonstrated close associations of specific immune cell profiles in the occurrence and development of COVID-19.[1,2]However,due to confounding factors and reverse causality in traditional observational studies,it remains unclear whether these associations reflect a causal link.Mendelian randomization(MR)is a reliable method of causal inferences that uses genetic variants(usually single-nucleotide polymorphisms[SNPs])as instrumental variables(IVs)to estimate the causal effect of exposure on outcome.展开更多
Background: Advances in organoid culture technology have provided a greater understanding of disease pathogenesis, which has been rarely studied in sepsis before. We aim to establish a suitable organoids-based intesti...Background: Advances in organoid culture technology have provided a greater understanding of disease pathogenesis, which has been rarely studied in sepsis before. We aim to establish a suitable organoids-based intestinal injury model for sepsis.Methods: Stable passaged organoids were constructed and pre-treated with lipopolysaccharide (LPS) to mimic sepsis-induced intestinal injury. The LPS-induced sepsis model was used as a reference. We used quantitative real-time polymerase chain reaction to evaluate the RNA levels of inflammatory factors and antimicrobial peptides. Enzyme-linked immunosorbent assay was used to evaluate the protein levels, hematoxylin and eosin staining was used to evaluate the pathology of the small intestine of mice, and immunohistochemistry and immunofluorescence were used to evaluate the intestinal epithelial barrier function. Perkin Elmer OperettaTM was used to obtain high-resolution images of three-dimensional organoids.Results: An LPS concentration >150 μg/mL after 24 h was identified to cause organoid growth restriction. The fluorescence intensity of zonula occludens-1 and occludins at LPS concentrations >100 μg/mL decreased significantly after 24 h. After LPS stimulation for 8 h, the RNA expression levels of interleukin (IL)-1α, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, IL-6, and regenerating islet-derived protein 3 alpha, beta, and gamma increased. These results resembled those of intestinal epithelial layer alterations in a mouse sepsis model. For IL-10, the RNA expression level increased only when the LPS level >200 μg/mL for 24 h.Conclusions: This study provides the primary intestinalin vitro model to study the effects of LPS-induced intestinal injury resembling sepsis. This model provides a platform for immune associated mechanism exploration and effective drug screening.展开更多
Background: Gut-resident macrophages (gMacs) supplemented by monocytes-to-gMacs differentiation play a critical role in maintaining intestinal homeostasis. Activating transcription factor 4 (ATF4) is involved in immun...Background: Gut-resident macrophages (gMacs) supplemented by monocytes-to-gMacs differentiation play a critical role in maintaining intestinal homeostasis. Activating transcription factor 4 (ATF4) is involved in immune cell differentiation. We therefore set out to investigate the role of ATF4-regulated monocytes-to-gMacs differentiation in sepsis-induced intestinal injury.Methods: Sepsis was induced in C57BL/6 wild type (WT) mice andAtf4-knockdown (Atf4+/-) mice by cecal ligation and puncture or administration of lipopolysaccharide (LPS). Colon, peripheral blood mononuclear cells, sera, lung, liver, and mesenteric lymph nodes were collected for flow cytometry, hematoxylin and eosin staining, immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively.Results: CD64, CD11b, Ly6C, major histocompatibility complex-II (MHC-II), CX3CR1, Ly6G, and SSC were identified as optimal primary markers for detecting the process of monocytes-to-gMacs differentiation in the colon of WT mice. Monocytes-to-gMacs differentiation was impaired in the colon during sepsis and was associated with decreased expression of ATF4 in P1 (Ly6Chi monocytes), the precursor cells of gMacs.Atf4 knockdown exacerbated the impairment of monocytes-to-gMacs differentiation in response to LPS, resulting in a significant reduction of gMacs in the colon. Furthermore, compared with WT mice,Atf4+/- mice exhibited higher pathology scores, increased expression of inflammatory factor genes (TNF-α, IL-1β), suppressed expression of CD31 and vascular endothelial-cadherin in the colon, and increased translocation of intestinal bacteria to lymph nodes and lungs following exposure to LPS. However, the aggravation of sepsis-induced intestinal injury resulting fromAtf4 knockdown was not caused by the enhanced inflammatory effect of Ly6Chi monocytes and gMacs.Conclusion: ATF4, as a novel regulator of monocytes-to-gMacs differentiation, plays a critical role in protecting mice against sepsis-induced intestinal injury, suggesting that ATF4 might be a potential therapeutic target for sepsis treatment.展开更多
Background:Novel coronavirus disease 2019(COVID-19)is an ongoing global pandemic with high mortality.Although several studies have reported different risk factors for mortality in patients based on traditional analyti...Background:Novel coronavirus disease 2019(COVID-19)is an ongoing global pandemic with high mortality.Although several studies have reported different risk factors for mortality in patients based on traditional analytics,few studies have used artificial intelligence(AI)algorithms.This study investigated prognostic factors for COVID-19 patients using AI methods.Methods:COVID-19 patients who were admitted in Wuhan Infectious Diseases Hospital from December 29,2019 to March 2,2020 were included.The whole cohort was randomly divided into training and testing sets at a 6:4 ratio.Demographic and clinical data were analyzed to identify predictors of mortality using least absolute shrinkage and selection operator(LASSO)regression and LASSO-based artificial neural network(ANN)models.The predictive performance of the models was evaluated using receiver operating characteristic(ROC)curve analysis.Results:A total of 1145 patients(610 male,53.3%)were included in the study.Of the 1145 patients,704 were assigned to the training set and 441 were assigned to the testing set.The median age of the patients was 57 years(range:47-66 years).Severity of illness,age,platelet count,leukocyte count,prealbumin,C-reactive protein(CRP),total bilirubin,Acute Physiology and Chronic Health Evaluation(APACHE)II score,and Sequential Organ Failure Assessment(SOFA)score were identified as independent prognostic factors for mortality.Incorporating these nine factors into the LASSO regression model yielded a correct classification rate of 0.98,with area under the ROC curve(AUC)values of 0.980 and 0.990 in the training and testing cohorts,respectively.Incorporating the same factors into the LASSO-based ANN model yielded a correct classification rate of 0.990,with an AUC of 0.980 in both the training and testing cohorts.Conclusions:Both the LASSO regression and LASSO-based ANN model accurately predicted the clinical outcome of patients with COVID-19.Severity of illness,age,platelet count,leukocyte count,prealbumin,CRP,total bilirubin,APACHE II score,and SOFA score were identified as prognostic factors for mortality in patients with COVID-19.展开更多
Regarding to the actual situation of the new coronavirus disease 2019 epidemic,social factors should be taken into account and the increasing growth trend of confirmed populations needs to be explained.A proper model ...Regarding to the actual situation of the new coronavirus disease 2019 epidemic,social factors should be taken into account and the increasing growth trend of confirmed populations needs to be explained.A proper model needs to be established,not only to simulate the epidemic,but also to evaluate the future epidemic situation and find a pilot indicator for the outbreak.The original susceptible-infectious-recover model is modified into the susceptible-infectious-quarantine-confirm-recover combined with social factors(SIDCRL)model,which combines the natural transmission with social factors such as external interventions and isolation.The numerical simulation method is used to imitate the change curve of the cumulative number of the confirmed cases and the number of cured patients.Furthermore,we investigate the relationship between the suspected close contacts(SCC)and the final outcome of the growth trend of confirmed cases with a simulation approach.This article selects four representative countries,that is,China,South Korea,Italy,and the United States,and gives separate numerical simulations.The simulation results of the model fit the actual situation of the epidemic development and reasonable predictions are made.In addition,it is analyzed that the increasing number of SCC contributes to the epidemic outbreak and the prediction of the United States based on the population of the SCC highlights the importance of external intervention and active prevention measures.The simulation of the model verifies its reliability and stresses that observable variable SCC can be taken as a pilot indicator of the coronavirus disease 2019 pandemic.展开更多
基金the National Key Research and Development Program of China(2022YFC2009700)the National Science Foundation of China(82372582)+1 种基金the Medical Applications Basic Research Project of Suzhou Science and Technology Bureau(SKY2023033)the Wujiang District Science,Education,Health and Promotion Project(WWK202021).
文摘Background The neurophysiological differences in cortical plasticity and cholinergic system function due to ageing and their correlation with cognitive function remain poorly understood.Aims To reveal the differences in long-term potentiation(LTP)-like plasticity and short-latency afferent inhibition(SAl)between older and younger individuals,alongside their correlation with cognitive function using transcranial magnetic stimulation(TMS).Methods The cross-sectional study involved 31 younger adults aged 18-30 and 46 older adults aged 60-80.All participants underwent comprehensive cognitive assessments and a neurophysiological evaluation based on TMS.Cognitive function assessments included evaluations of global cognitive function,language,memory and executive function.The neurophysiological assessment included LTP-like plasticity and SAl.Results The findings of this study revealed a decline in LTP among the older adults compared with the younger adults(wald χ^(2)=3.98,p=0.046).Subgroup analysis further demonstrated a significant reduction in SAl level among individuals aged 70-80 years in comparison to both the younger adults(SAI(N20)):(t=-3.37,p=0.018);SAl(N20+4):(t=-3.13,p=0.038)and those aged 60-70(SAl(N20)):(t=3.26,p=0.025);SAl(N20+4):(t=-3.69,p=0.006).Conversely,there was no notable difference in SAl level between those aged 60-70 years and the younger group.Furthermore,after employing the Bonferroni correction,the correlation analysis revealed that only the positive correlation between LTP-like plasticity and language function(r=0.61,p<0.001)in the younger group remained statistically significant.Conclusions During the normal ageing process,a decline in synaptic plasticity may precede cholinergic system dysfunction.In individuals over 60 years of age,there is a reduction in LTP-like plasticity,while a decline in cholinergic system function is observed in those over 70.Thus,the cholinergic system may play a vital role in preventing cognitive decline during normal ageing.In younger individuals,LTP-like plasticity might represent a potential neurophysiological marker for language function.
文摘NdNiO_(3) is a typical correlated material with temperature-driven metal–insulator transition. Resolving the local electronic phase is crucial in understanding the driving mechanism behind the phase transition. Here we present a nano-infrared study of the metal–insulator transition in NdNiO_(3) films by a cryogenic scanning near-field optical microscope. The NdNiO_(3) films undergo a continuous transition without phase coexistence. The nano-infrared signal shows significant temperature dependence and a hysteresis loop. Stripe-like modulation of the optical conductivity is formed in the films and can be attributed to the epitaxial strain. These results provide valuable evidence to understand the coupled electronic and structural transformations in NdNiO_(3) films at the nano-scale.
文摘In the context of next-generation optical access networks beyond 10 G, for high SE and flexible dynamic bandwidth allocation (DBA), the scheme of hybrid 64/16/4QAM-OFDM signal for downlink transmission and hybrid 16/8/QPSK-OFDM signal for uplink transmission is successfully proposed and experimentally presented in a full-duplex PON based on OFDM system. Here, for the uplink, in order to unit management of the optical line terminal (OLT) and reduce cost, the optical source functioned as the optical subcarrier at optical network units (ONUs) is from OLT in the central station. Moreover, there is an external cavity laser (ECL) with center frequency of 193.2 THz not only employed as optical modulated signal but also acted as LO signal. Our simulation results show that bit error ratio (BER) under hardware detection forward error correction has been successfully gained after 20 km of SSMF transmission. It is observed that the receiver sensitivity of multilevel PSK (M-PSK) is obviously larger than that of the M-QAM in this measurement scheme.
基金supported by the National Natural Science Foundation of China(grant numbers:82241044 and 82172152)the Science and Technology Commission of Shanghai(grant numbers:22692192200).
文摘To the Editor,Previous studies have demonstrated close associations of specific immune cell profiles in the occurrence and development of COVID-19.[1,2]However,due to confounding factors and reverse causality in traditional observational studies,it remains unclear whether these associations reflect a causal link.Mendelian randomization(MR)is a reliable method of causal inferences that uses genetic variants(usually single-nucleotide polymorphisms[SNPs])as instrumental variables(IVs)to estimate the causal effect of exposure on outcome.
基金supported by grants from the National Natural Science Foundation of China(Nos.81873944 and 81971869)the Shanghai Science and Technology Commission(No.20DZ2200500).
文摘Background: Advances in organoid culture technology have provided a greater understanding of disease pathogenesis, which has been rarely studied in sepsis before. We aim to establish a suitable organoids-based intestinal injury model for sepsis.Methods: Stable passaged organoids were constructed and pre-treated with lipopolysaccharide (LPS) to mimic sepsis-induced intestinal injury. The LPS-induced sepsis model was used as a reference. We used quantitative real-time polymerase chain reaction to evaluate the RNA levels of inflammatory factors and antimicrobial peptides. Enzyme-linked immunosorbent assay was used to evaluate the protein levels, hematoxylin and eosin staining was used to evaluate the pathology of the small intestine of mice, and immunohistochemistry and immunofluorescence were used to evaluate the intestinal epithelial barrier function. Perkin Elmer OperettaTM was used to obtain high-resolution images of three-dimensional organoids.Results: An LPS concentration >150 μg/mL after 24 h was identified to cause organoid growth restriction. The fluorescence intensity of zonula occludens-1 and occludins at LPS concentrations >100 μg/mL decreased significantly after 24 h. After LPS stimulation for 8 h, the RNA expression levels of interleukin (IL)-1α, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, IL-6, and regenerating islet-derived protein 3 alpha, beta, and gamma increased. These results resembled those of intestinal epithelial layer alterations in a mouse sepsis model. For IL-10, the RNA expression level increased only when the LPS level >200 μg/mL for 24 h.Conclusions: This study provides the primary intestinalin vitro model to study the effects of LPS-induced intestinal injury resembling sepsis. This model provides a platform for immune associated mechanism exploration and effective drug screening.
基金National Natural Science Foundation of China(Nos. 82172152, 81873944, 82172154, 81971869, 82171729)Natural Science Foundation of Shanghai(No.19ZR1442500)Research Fund of Ruijin Hospital North Affiliated to Shanghai Jiao Tong University School of Medicine(No.2020ZY11)
文摘Background: Gut-resident macrophages (gMacs) supplemented by monocytes-to-gMacs differentiation play a critical role in maintaining intestinal homeostasis. Activating transcription factor 4 (ATF4) is involved in immune cell differentiation. We therefore set out to investigate the role of ATF4-regulated monocytes-to-gMacs differentiation in sepsis-induced intestinal injury.Methods: Sepsis was induced in C57BL/6 wild type (WT) mice andAtf4-knockdown (Atf4+/-) mice by cecal ligation and puncture or administration of lipopolysaccharide (LPS). Colon, peripheral blood mononuclear cells, sera, lung, liver, and mesenteric lymph nodes were collected for flow cytometry, hematoxylin and eosin staining, immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively.Results: CD64, CD11b, Ly6C, major histocompatibility complex-II (MHC-II), CX3CR1, Ly6G, and SSC were identified as optimal primary markers for detecting the process of monocytes-to-gMacs differentiation in the colon of WT mice. Monocytes-to-gMacs differentiation was impaired in the colon during sepsis and was associated with decreased expression of ATF4 in P1 (Ly6Chi monocytes), the precursor cells of gMacs.Atf4 knockdown exacerbated the impairment of monocytes-to-gMacs differentiation in response to LPS, resulting in a significant reduction of gMacs in the colon. Furthermore, compared with WT mice,Atf4+/- mice exhibited higher pathology scores, increased expression of inflammatory factor genes (TNF-α, IL-1β), suppressed expression of CD31 and vascular endothelial-cadherin in the colon, and increased translocation of intestinal bacteria to lymph nodes and lungs following exposure to LPS. However, the aggravation of sepsis-induced intestinal injury resulting fromAtf4 knockdown was not caused by the enhanced inflammatory effect of Ly6Chi monocytes and gMacs.Conclusion: ATF4, as a novel regulator of monocytes-to-gMacs differentiation, plays a critical role in protecting mice against sepsis-induced intestinal injury, suggesting that ATF4 might be a potential therapeutic target for sepsis treatment.
基金supported by the National Natural Science Foundation of China(Grant No.81,873,944 and 81,971,869)the Shanghai Science and Technology Commission(Grant No.20DZ2200500).
文摘Background:Novel coronavirus disease 2019(COVID-19)is an ongoing global pandemic with high mortality.Although several studies have reported different risk factors for mortality in patients based on traditional analytics,few studies have used artificial intelligence(AI)algorithms.This study investigated prognostic factors for COVID-19 patients using AI methods.Methods:COVID-19 patients who were admitted in Wuhan Infectious Diseases Hospital from December 29,2019 to March 2,2020 were included.The whole cohort was randomly divided into training and testing sets at a 6:4 ratio.Demographic and clinical data were analyzed to identify predictors of mortality using least absolute shrinkage and selection operator(LASSO)regression and LASSO-based artificial neural network(ANN)models.The predictive performance of the models was evaluated using receiver operating characteristic(ROC)curve analysis.Results:A total of 1145 patients(610 male,53.3%)were included in the study.Of the 1145 patients,704 were assigned to the training set and 441 were assigned to the testing set.The median age of the patients was 57 years(range:47-66 years).Severity of illness,age,platelet count,leukocyte count,prealbumin,C-reactive protein(CRP),total bilirubin,Acute Physiology and Chronic Health Evaluation(APACHE)II score,and Sequential Organ Failure Assessment(SOFA)score were identified as independent prognostic factors for mortality.Incorporating these nine factors into the LASSO regression model yielded a correct classification rate of 0.98,with area under the ROC curve(AUC)values of 0.980 and 0.990 in the training and testing cohorts,respectively.Incorporating the same factors into the LASSO-based ANN model yielded a correct classification rate of 0.990,with an AUC of 0.980 in both the training and testing cohorts.Conclusions:Both the LASSO regression and LASSO-based ANN model accurately predicted the clinical outcome of patients with COVID-19.Severity of illness,age,platelet count,leukocyte count,prealbumin,CRP,total bilirubin,APACHE II score,and SOFA score were identified as prognostic factors for mortality in patients with COVID-19.
文摘Regarding to the actual situation of the new coronavirus disease 2019 epidemic,social factors should be taken into account and the increasing growth trend of confirmed populations needs to be explained.A proper model needs to be established,not only to simulate the epidemic,but also to evaluate the future epidemic situation and find a pilot indicator for the outbreak.The original susceptible-infectious-recover model is modified into the susceptible-infectious-quarantine-confirm-recover combined with social factors(SIDCRL)model,which combines the natural transmission with social factors such as external interventions and isolation.The numerical simulation method is used to imitate the change curve of the cumulative number of the confirmed cases and the number of cured patients.Furthermore,we investigate the relationship between the suspected close contacts(SCC)and the final outcome of the growth trend of confirmed cases with a simulation approach.This article selects four representative countries,that is,China,South Korea,Italy,and the United States,and gives separate numerical simulations.The simulation results of the model fit the actual situation of the epidemic development and reasonable predictions are made.In addition,it is analyzed that the increasing number of SCC contributes to the epidemic outbreak and the prediction of the United States based on the population of the SCC highlights the importance of external intervention and active prevention measures.The simulation of the model verifies its reliability and stresses that observable variable SCC can be taken as a pilot indicator of the coronavirus disease 2019 pandemic.
