Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its im...Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its implications for carbon sequestration.A large number of experiments have proved that CO_(2) interaction time(T),saturation pressure(P)and other parameters have significant effects on coal strength.However,accurate evaluation of CO_(2)-induced alterations in coal strength is still a difficult problem,so it is particularly important to establish accurate and efficient prediction models.This study explored the application of advancedmachine learning(ML)algorithms and Gene Expression Programming(GEP)techniques to predict CO_(2)-induced alterations in coal strength.Sixmodels were developed,including three metaheuristic-optimized XGBoost models(GWO-XGBoost,SSA-XGBoost,PO-XGBoost)and three GEP models(GEP-1,GEP-2,GEP-3).Comprehensive evaluations using multiple metrics revealed that all models demonstrated high predictive accuracy,with the SSA-XGBoost model achieving the best performance(R2—Coefficient of determination=0.99396,RMSE—Root Mean Square Error=0.62102,MAE—Mean Absolute Error=0.36164,MAPE—Mean Absolute Percentage Error=4.8101%,RPD—Residual Predictive Deviation=13.4741).Model interpretability analyses using SHAP(Shapley Additive exPlanations),ICE(Individual Conditional Expectation),and PDP(Partial Dependence Plot)techniques highlighted the dominant role of fixed carbon content(FC)and significant interactions between FC and CO_(2) saturation pressure(P).Theresults demonstrated that the proposedmodels effectively address the challenges of CO_(2)-induced strength prediction,providing valuable insights for geological storage safety and environmental applications.展开更多
Background: Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses...Background: Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra-and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy.This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules.Methods: In primary tumors and metastatic as well as non-metastatic lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma, we detected PD-L1 and PD-L2 expression with immunohistochemistry. CD8(+)T-cell density in primary tumors and PD-1 expression on CD8(+)T cells were detected with immunofluorescence. Univariate analysis was used to determine the prognostic values of them. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival and disease-free survival.Results: Among 119 eligible patients who had undergone surgical resection, the positive rate of PD-L1 was higher in metastatic lymph nodes than in primary tumors(45.4% vs. 38.7%, P = 0.005); the positive rate of PD-1 on CD8(+)T cells was significantly higher in primary tumors and metastatic lymph nodes than in tumor-free lymph nodes(both P < 0.001). The intensity of PD-1 expression on CD8(+) T cells in primary tumors and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes from the same patient. Beside, the positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression,PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis.Conclusion: The expression of PD-L1 is heterogeneous in primary tumors and in metastatic lymph nodes from patients with stageT1-4 N+M0 gastric adenocarcinoma, which might explain the inconsistent results in assessing the prognostic value of PD-L1 expression in previous studies.展开更多
AIM: To assess the effectiveness of the Chronic Disease Self-Management Program(CDSMP) on glycated hemoglobin A1c(HbA1c) and selected self-reported measures.METHODS: We compared patients who received a diabetes self-c...AIM: To assess the effectiveness of the Chronic Disease Self-Management Program(CDSMP) on glycated hemoglobin A1c(HbA1c) and selected self-reported measures.METHODS: We compared patients who received a diabetes self-care behavioral intervention, the CDSMP developed at the Stanford University, with controls whoreceived usual care on their HbA1c and selected self-reported measures, including diabetes self-care activities, health-related quality of life(HRQOL), pain and fatigue. The subjects were a subset of participants enrolled in a randomized controlled trial that took place at seven regional clinics of a university-affiliated integrated healthcare system of a multi-specialty group practice between January 2009 and June 2011. The primary outcome was change in HbA1c from randomization to 12 mo. Data were analyzed using multilevel statistical models and linear mixed models to provide unbiased estimates of intervention effects.RESULTS: Demographic and baseline clinical characteristics were generally comparable between the two groups. The average baseline HbA1c values in the CDSMP and control groups were 9.4% and 9.2%, respectively. Significant reductions in HbA1c were seen at 12 mo for the two groups, with adjusted changes around 0.6%(P < 0.0001), but the reductions did not differ significantly between the two groups(P = 0.885). Few significant differences were observed in participants' diabetes self-care activities. No significant differences were observed in the participants' HRQOL, pain, or fatigue measures.CONCLUSION: The CDSMP intervention may not lower HbA1c any better than good routine care in an integrated healthcare system. More research is needed to understand the benefits of self-management programs in primary care in different settings and populations.展开更多
Diabetes has become a growing concern in Japan, both medically and financially. The medical cost of diabetes was estimated at 1215 billion yen for fiscal year 2011. We analyzed the length of stay (LOS) in a hospital f...Diabetes has become a growing concern in Japan, both medically and financially. The medical cost of diabetes was estimated at 1215 billion yen for fiscal year 2011. We analyzed the length of stay (LOS) in a hospital for type 2 diabetes mellitus patients who participated in educational programs to determine factors affecting LOS. Data on 991 patients obtained from 28 Red Cross hospitals in 2008 were used. For the analysis, we used the Box-Cox transformation model and Hausman test. The results revealed that patients aged 75 years and above and those with comorbidities and complications were prone to longer LOS. The analysis also revealed significant differences in LOS across the hospitals, even after controlling for patient characteristics. Finally, we applied the least squares method to determine the effects of hospital and regional factors and revealed that patients’ LOS was affected by the region’s average LOS. Regional corporations and networks appeared to be important in improving educational programs.展开更多
BACKGROUND The exact regulation network of programmed death 1(PD-1), programmed death ligand 1(PD-L1), and programmed death ligand 2(PD-L2) signaling in immune escape is largely unknown. We aimed to describe the gene ...BACKGROUND The exact regulation network of programmed death 1(PD-1), programmed death ligand 1(PD-L1), and programmed death ligand 2(PD-L2) signaling in immune escape is largely unknown. We aimed to describe the gene expression profiles related to PD-1 as well as its ligands PD-L1 and PD-L2, thus deciphering their possible biological processes in hepatocellular carcinoma(HCC).AIM To find the possible mechanism of function of PD-1, PD-L1, and PD-L2 in HCC.METHODS Based on the expression data of HCC from The Cancer Genome Atlas, the PD-1/PD-L1/PD-L2 related genes were screened by weighted correlation network analysis method and the biological processes of certain genes were enriched. Relation of PD1/PD-L1/PD-L2 with immune infiltration and checkpoints was investigated by co-expression analysis. The roles of PD-1/PD-L1/PD-L2 in determination of clinical outcome were also analyzed.RESULTS Mutations of calcium voltage-gated channel subunit alpha1 E, catenin beta 1, ryanodine receptor 2, tumor suppressor protein p53, and Titin altered PD-1/PDL1/PD-L2 expression profiles in HCC. PD-1, PD-L1, and PD-L2 related genes were mainly enriched in biological procedures of T cell activation, cell adhesion, and other important lymphocyte effects. In addition, PD-1/PD-L1/PD-L2 was related with immune infiltration of CD8 T cells, cytotoxic lymphocytes,fibroblasts, and myeloid dendritic cells. Immune checkpoints of CTLA4, CD27, CD80, CD86, and CD28 were significantly related to the PD-1/PD-L1/PD-L2 axis. Clinically, PD-1 and PD-L2 expression was correlated with recurrence(P = 0.005 for both), but there was no significant correlation between their expression and HCC patient survival.CONCLUSION Mutations of key genes influence PD-1, PD-L1, and PD-L2 expression. PD-1, PDL1, and PD-L2 related genes participate in T cell activation, cell adhesion, and other important lymphocyte effects. The finding that PD-1/PD-L1/PD-L2 is related to immune infiltration and other immune checkpoints would expand our understanding of promising anti-PD-1 immunotherapy.展开更多
目的探讨乙醛脱氢酶2(aldehyde dehydrogenase 2,ALDH2)基因型多态性与急性缺血性脑卒中严重程度的关系。方法选取2022年3月至2023年9月于北京市昌平区医院神经内科住院的224例急性缺血性脑卒中患者作为研究对象,所有患者均行ALDH2基因...目的探讨乙醛脱氢酶2(aldehyde dehydrogenase 2,ALDH2)基因型多态性与急性缺血性脑卒中严重程度的关系。方法选取2022年3月至2023年9月于北京市昌平区医院神经内科住院的224例急性缺血性脑卒中患者作为研究对象,所有患者均行ALDH2基因型检测,根据检测结果分为GG组(n=136)与GA/AA组(n=88),GG组基因型为野生型(ALDH2*1/*1),GA/AA组基因型为基因突变杂合子型(ALDH2*1/*2)与纯合子型(ALDH2*2/*2)。比较两组临床资料Alberta卒中操作早期急性卒中分级CT(Alberta stroke program early CT score,ASPECT)评分、美国国立研究院卒中量表(National Institutes of Health Stroke scale,NIHSS)评分及Barthel指数(Barthel index,BI)。结果两组性别、年龄、体重指数、同型半胱氨酸、总胆固醇、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇及高血压病史、吸烟史、饮酒史占比比较差异均无统计学意义。GG组ASPECT评分、BI均高于GA/AA组,NIHSS评分低于GA/AA组,差异有统计学意义(P<0.05)。结论ALDH2基因型与急性缺血性脑卒中严重程度有关,ALDH2基因突变型患者急性缺血性脑卒中严重程度更严重。展开更多
BACKGROUND Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is a global pandemic that is associated with a high risk of morbidity and mortality among recipients of solid organ transplantation.In th...BACKGROUND Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is a global pandemic that is associated with a high risk of morbidity and mortality among recipients of solid organ transplantation.In the course of acute SARS-CoV-2 infection,various laboratory markers have been identified as predictors for high risk of mortality.AIM To risk stratify renal transplant recipients(RTxR)using general demographic parameters,comorbidities and routine laboratory markers for the severity of the disease and its outcomes.We believe that learning about these routinely monitored parameters can help us plan better strategies for the RTxR follow-up program.METHODS This present study includes RTxR who acquired SARS-CoV-2 infection from March 2020 to February 2021.We recorded the basic demographics,comorbidities and routine laboratory markers.We investigated the impact of SARS-CoV-2 infection on RTxRs and risk-stratified the progression of disease severity and outcomes in terms of recovery or mortality.RESULTS From 505 RTxRs in our renal transplant follow-up program,29(7.75%)RTxRs had PCR-positive SARS-CoV-2 infection.We recorded 8 deaths from SARS-CoV-2 infection giving an overall mortality rate of 1.6%but a significant 27.6%mortality in SARS-CoV-2 positive recipients.Age more than 68 years,non-Caucasian ethnicity and male gender were associated with a significant drop in survival probability;P≤0.001.<0.001 and<0.0001 respectively.87.5%of the deceased were diabetic;P≤0.0.0001.Estimated glomerular filtration rate of less than 26 mL/min/1.73 m2,serum albumin less than 20 g/L,Hemoglobin less than 9.6 g/L and serum calcium less than 1.70 mmol/L were all associated with significantly increased risk of mortality;P=0.0128,<0.001,<0.0001 and 0.0061 respectively.CONCLUSION This study has identified some routinely used modifiable parameters in predicting a higher risk of mortality and morbidity.This knowledge can be used in RTxR follow-up programs by addressing these parameters early to help reduce the morbidity and mortality in RTxRs.展开更多
This paper estimates the macroeconornic costs of CO2 emission reduction in China employing the input-output analysis with the multi-objective programming approach. The results show that the effect of reducing CO2 emis...This paper estimates the macroeconornic costs of CO2 emission reduction in China employing the input-output analysis with the multi-objective programming approach. The results show that the effect of reducing CO2 emissions on China＇s economy is significant. Under the present conditions, the estimated macroeconomic costs of CO2 emission reduction in 2010 for China are approximately 3,100-4,024 RMB t-1. The stronger the abatement actions, the higher the macroeconomic costs of per unit emission reduction would be. Excavation industry, oil industry, chemical industry, and metal smelting industry have high potential to abate their CO2 emissions.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in th...BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.展开更多
Investing in projects that support environmental benefits,such as tree harvesting,has the potential to reduce air pollution levels in the atmosphere in the future.However,this kind of investment may increase the curre...Investing in projects that support environmental benefits,such as tree harvesting,has the potential to reduce air pollution levels in the atmosphere in the future.However,this kind of investment may increase the current level of emissions.Therefore,it is necessary to estimate how much the policy affects the current level of CO_(2) emissions.This makes sure the policy doesn’t increase the level of CO_(2) emis-sions.This study aims to analyze the effect of the One Bil-lion Trees program on CO_(2) emissions in New Zealand by employing the 2020 input–output table analysis.This inves-tigation examines the direct and indirect effects of policy on both the demand and supply sides across six regions of New Zealand.The results of this study for the first year of plantation suggest that the policy increases the level of CO_(2) emissions in all regions,especially in the Waikato region.The direct and indirect impact of the policy leads to 64 kt of CO_(2) emissions on the demand side and 270 kt of CO_(2) emis-sions on the supply side.These lead to 0.19 and 0.74%of total CO_(2) emissions being attributed to investment shocks.Continuing the policy is recommended,as it has a low effect on CO_(2) emissions.However,it is crucial to prioritize the use of low-carbon machinery that uses fossil fuels during the plantation process.展开更多
Maternal nutrition is found to be the key factor that determines fetal health in utero and metabolic health during adulthood.Metabolic diseases have been primarily attributed to impaired maternal nutrition during preg...Maternal nutrition is found to be the key factor that determines fetal health in utero and metabolic health during adulthood.Metabolic diseases have been primarily attributed to impaired maternal nutrition during pregnancy,and impaired nutrition has been an immense issue across the globe.In recent years,type 2 diabetes(T2D)has reached epidemic proportion and is a severe public health problem in many countries.Although plenty of research has already been conducted to tackle T2D which is associated with obesity,little is known regarding the etiology and pathophysiology of lean T2D,a variant of T2D.Recent studies have focused on the effects of epigenetic variation on the contribution of in utero origins of lean T2D,although other mechanisms might also contribute to the pathology.Observational studies in humans and experiments in animals strongly suggest an association between maternal low protein diet and lean T2D phenotype.In addition,clear sex-specific disease prevalence was observed in different studies.Consequently,more research is essential for the understanding of the etiology and pathophysiology of lean T2D,which might help to develop better disease prevention and treatment strategies.This review examines the role of protein insufficiency in the maternal diet as the central driver of the developmental programming of lean T2D.展开更多
基金partially supported by the National Natural Science Foundation of China(42177164,52474121)the Outstanding Youth Project of Hunan Provincial Department of Education(23B0008).
文摘Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its implications for carbon sequestration.A large number of experiments have proved that CO_(2) interaction time(T),saturation pressure(P)and other parameters have significant effects on coal strength.However,accurate evaluation of CO_(2)-induced alterations in coal strength is still a difficult problem,so it is particularly important to establish accurate and efficient prediction models.This study explored the application of advancedmachine learning(ML)algorithms and Gene Expression Programming(GEP)techniques to predict CO_(2)-induced alterations in coal strength.Sixmodels were developed,including three metaheuristic-optimized XGBoost models(GWO-XGBoost,SSA-XGBoost,PO-XGBoost)and three GEP models(GEP-1,GEP-2,GEP-3).Comprehensive evaluations using multiple metrics revealed that all models demonstrated high predictive accuracy,with the SSA-XGBoost model achieving the best performance(R2—Coefficient of determination=0.99396,RMSE—Root Mean Square Error=0.62102,MAE—Mean Absolute Error=0.36164,MAPE—Mean Absolute Percentage Error=4.8101%,RPD—Residual Predictive Deviation=13.4741).Model interpretability analyses using SHAP(Shapley Additive exPlanations),ICE(Individual Conditional Expectation),and PDP(Partial Dependence Plot)techniques highlighted the dominant role of fixed carbon content(FC)and significant interactions between FC and CO_(2) saturation pressure(P).Theresults demonstrated that the proposedmodels effectively address the challenges of CO_(2)-induced strength prediction,providing valuable insights for geological storage safety and environmental applications.
文摘Background: Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra-and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy.This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules.Methods: In primary tumors and metastatic as well as non-metastatic lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma, we detected PD-L1 and PD-L2 expression with immunohistochemistry. CD8(+)T-cell density in primary tumors and PD-1 expression on CD8(+)T cells were detected with immunofluorescence. Univariate analysis was used to determine the prognostic values of them. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival and disease-free survival.Results: Among 119 eligible patients who had undergone surgical resection, the positive rate of PD-L1 was higher in metastatic lymph nodes than in primary tumors(45.4% vs. 38.7%, P = 0.005); the positive rate of PD-1 on CD8(+)T cells was significantly higher in primary tumors and metastatic lymph nodes than in tumor-free lymph nodes(both P < 0.001). The intensity of PD-1 expression on CD8(+) T cells in primary tumors and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes from the same patient. Beside, the positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression,PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis.Conclusion: The expression of PD-L1 is heterogeneous in primary tumors and in metastatic lymph nodes from patients with stageT1-4 N+M0 gastric adenocarcinoma, which might explain the inconsistent results in assessing the prognostic value of PD-L1 expression in previous studies.
基金Supported by The National Institutes of Health’s National Institute on Minority Health and Health Disparities,No.#1P20MD002295
文摘AIM: To assess the effectiveness of the Chronic Disease Self-Management Program(CDSMP) on glycated hemoglobin A1c(HbA1c) and selected self-reported measures.METHODS: We compared patients who received a diabetes self-care behavioral intervention, the CDSMP developed at the Stanford University, with controls whoreceived usual care on their HbA1c and selected self-reported measures, including diabetes self-care activities, health-related quality of life(HRQOL), pain and fatigue. The subjects were a subset of participants enrolled in a randomized controlled trial that took place at seven regional clinics of a university-affiliated integrated healthcare system of a multi-specialty group practice between January 2009 and June 2011. The primary outcome was change in HbA1c from randomization to 12 mo. Data were analyzed using multilevel statistical models and linear mixed models to provide unbiased estimates of intervention effects.RESULTS: Demographic and baseline clinical characteristics were generally comparable between the two groups. The average baseline HbA1c values in the CDSMP and control groups were 9.4% and 9.2%, respectively. Significant reductions in HbA1c were seen at 12 mo for the two groups, with adjusted changes around 0.6%(P < 0.0001), but the reductions did not differ significantly between the two groups(P = 0.885). Few significant differences were observed in participants' diabetes self-care activities. No significant differences were observed in the participants' HRQOL, pain, or fatigue measures.CONCLUSION: The CDSMP intervention may not lower HbA1c any better than good routine care in an integrated healthcare system. More research is needed to understand the benefits of self-management programs in primary care in different settings and populations.
文摘Diabetes has become a growing concern in Japan, both medically and financially. The medical cost of diabetes was estimated at 1215 billion yen for fiscal year 2011. We analyzed the length of stay (LOS) in a hospital for type 2 diabetes mellitus patients who participated in educational programs to determine factors affecting LOS. Data on 991 patients obtained from 28 Red Cross hospitals in 2008 were used. For the analysis, we used the Box-Cox transformation model and Hausman test. The results revealed that patients aged 75 years and above and those with comorbidities and complications were prone to longer LOS. The analysis also revealed significant differences in LOS across the hospitals, even after controlling for patient characteristics. Finally, we applied the least squares method to determine the effects of hospital and regional factors and revealed that patients’ LOS was affected by the region’s average LOS. Regional corporations and networks appeared to be important in improving educational programs.
基金National Science and Technology Major Project,No. 2017ZX10201201 and No. 2017ZX10202202Liaoning Province Natural Science Foundation,No. 20180550096。
文摘BACKGROUND The exact regulation network of programmed death 1(PD-1), programmed death ligand 1(PD-L1), and programmed death ligand 2(PD-L2) signaling in immune escape is largely unknown. We aimed to describe the gene expression profiles related to PD-1 as well as its ligands PD-L1 and PD-L2, thus deciphering their possible biological processes in hepatocellular carcinoma(HCC).AIM To find the possible mechanism of function of PD-1, PD-L1, and PD-L2 in HCC.METHODS Based on the expression data of HCC from The Cancer Genome Atlas, the PD-1/PD-L1/PD-L2 related genes were screened by weighted correlation network analysis method and the biological processes of certain genes were enriched. Relation of PD1/PD-L1/PD-L2 with immune infiltration and checkpoints was investigated by co-expression analysis. The roles of PD-1/PD-L1/PD-L2 in determination of clinical outcome were also analyzed.RESULTS Mutations of calcium voltage-gated channel subunit alpha1 E, catenin beta 1, ryanodine receptor 2, tumor suppressor protein p53, and Titin altered PD-1/PDL1/PD-L2 expression profiles in HCC. PD-1, PD-L1, and PD-L2 related genes were mainly enriched in biological procedures of T cell activation, cell adhesion, and other important lymphocyte effects. In addition, PD-1/PD-L1/PD-L2 was related with immune infiltration of CD8 T cells, cytotoxic lymphocytes,fibroblasts, and myeloid dendritic cells. Immune checkpoints of CTLA4, CD27, CD80, CD86, and CD28 were significantly related to the PD-1/PD-L1/PD-L2 axis. Clinically, PD-1 and PD-L2 expression was correlated with recurrence(P = 0.005 for both), but there was no significant correlation between their expression and HCC patient survival.CONCLUSION Mutations of key genes influence PD-1, PD-L1, and PD-L2 expression. PD-1, PDL1, and PD-L2 related genes participate in T cell activation, cell adhesion, and other important lymphocyte effects. The finding that PD-1/PD-L1/PD-L2 is related to immune infiltration and other immune checkpoints would expand our understanding of promising anti-PD-1 immunotherapy.
文摘目的探讨乙醛脱氢酶2(aldehyde dehydrogenase 2,ALDH2)基因型多态性与急性缺血性脑卒中严重程度的关系。方法选取2022年3月至2023年9月于北京市昌平区医院神经内科住院的224例急性缺血性脑卒中患者作为研究对象,所有患者均行ALDH2基因型检测,根据检测结果分为GG组(n=136)与GA/AA组(n=88),GG组基因型为野生型(ALDH2*1/*1),GA/AA组基因型为基因突变杂合子型(ALDH2*1/*2)与纯合子型(ALDH2*2/*2)。比较两组临床资料Alberta卒中操作早期急性卒中分级CT(Alberta stroke program early CT score,ASPECT)评分、美国国立研究院卒中量表(National Institutes of Health Stroke scale,NIHSS)评分及Barthel指数(Barthel index,BI)。结果两组性别、年龄、体重指数、同型半胱氨酸、总胆固醇、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇及高血压病史、吸烟史、饮酒史占比比较差异均无统计学意义。GG组ASPECT评分、BI均高于GA/AA组,NIHSS评分低于GA/AA组,差异有统计学意义(P<0.05)。结论ALDH2基因型与急性缺血性脑卒中严重程度有关,ALDH2基因突变型患者急性缺血性脑卒中严重程度更严重。
基金Compliance with local ethical and data protection policies.Registered with St Georges University Hospitals NHS Foundation Trust Quality Assurance Department.Registration no AUD1000854。
文摘BACKGROUND Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection is a global pandemic that is associated with a high risk of morbidity and mortality among recipients of solid organ transplantation.In the course of acute SARS-CoV-2 infection,various laboratory markers have been identified as predictors for high risk of mortality.AIM To risk stratify renal transplant recipients(RTxR)using general demographic parameters,comorbidities and routine laboratory markers for the severity of the disease and its outcomes.We believe that learning about these routinely monitored parameters can help us plan better strategies for the RTxR follow-up program.METHODS This present study includes RTxR who acquired SARS-CoV-2 infection from March 2020 to February 2021.We recorded the basic demographics,comorbidities and routine laboratory markers.We investigated the impact of SARS-CoV-2 infection on RTxRs and risk-stratified the progression of disease severity and outcomes in terms of recovery or mortality.RESULTS From 505 RTxRs in our renal transplant follow-up program,29(7.75%)RTxRs had PCR-positive SARS-CoV-2 infection.We recorded 8 deaths from SARS-CoV-2 infection giving an overall mortality rate of 1.6%but a significant 27.6%mortality in SARS-CoV-2 positive recipients.Age more than 68 years,non-Caucasian ethnicity and male gender were associated with a significant drop in survival probability;P≤0.001.<0.001 and<0.0001 respectively.87.5%of the deceased were diabetic;P≤0.0.0001.Estimated glomerular filtration rate of less than 26 mL/min/1.73 m2,serum albumin less than 20 g/L,Hemoglobin less than 9.6 g/L and serum calcium less than 1.70 mmol/L were all associated with significantly increased risk of mortality;P=0.0128,<0.001,<0.0001 and 0.0061 respectively.CONCLUSION This study has identified some routinely used modifiable parameters in predicting a higher risk of mortality and morbidity.This knowledge can be used in RTxR follow-up programs by addressing these parameters early to help reduce the morbidity and mortality in RTxRs.
基金supported by the National Natural Science Foundation of China under Grant Nos. 70825001 and 70941039
文摘This paper estimates the macroeconornic costs of CO2 emission reduction in China employing the input-output analysis with the multi-objective programming approach. The results show that the effect of reducing CO2 emissions on China＇s economy is significant. Under the present conditions, the estimated macroeconomic costs of CO2 emission reduction in 2010 for China are approximately 3,100-4,024 RMB t-1. The stronger the abatement actions, the higher the macroeconomic costs of per unit emission reduction would be. Excavation industry, oil industry, chemical industry, and metal smelting industry have high potential to abate their CO2 emissions.
基金Supported by the Natural Science Foundation of Gansu Province,No.21JR7RA373 and No.24JRRA295.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.
基金Open Access funding enabled and organized by CAUL and its Member Institutions
文摘Investing in projects that support environmental benefits,such as tree harvesting,has the potential to reduce air pollution levels in the atmosphere in the future.However,this kind of investment may increase the current level of emissions.Therefore,it is necessary to estimate how much the policy affects the current level of CO_(2) emissions.This makes sure the policy doesn’t increase the level of CO_(2) emis-sions.This study aims to analyze the effect of the One Bil-lion Trees program on CO_(2) emissions in New Zealand by employing the 2020 input–output table analysis.This inves-tigation examines the direct and indirect effects of policy on both the demand and supply sides across six regions of New Zealand.The results of this study for the first year of plantation suggest that the policy increases the level of CO_(2) emissions in all regions,especially in the Waikato region.The direct and indirect impact of the policy leads to 64 kt of CO_(2) emissions on the demand side and 270 kt of CO_(2) emis-sions on the supply side.These lead to 0.19 and 0.74%of total CO_(2) emissions being attributed to investment shocks.Continuing the policy is recommended,as it has a low effect on CO_(2) emissions.However,it is crucial to prioritize the use of low-carbon machinery that uses fossil fuels during the plantation process.
基金Supported by the National Institutes of Health Grants,No. HL102866, HL58144 and DK114689
文摘Maternal nutrition is found to be the key factor that determines fetal health in utero and metabolic health during adulthood.Metabolic diseases have been primarily attributed to impaired maternal nutrition during pregnancy,and impaired nutrition has been an immense issue across the globe.In recent years,type 2 diabetes(T2D)has reached epidemic proportion and is a severe public health problem in many countries.Although plenty of research has already been conducted to tackle T2D which is associated with obesity,little is known regarding the etiology and pathophysiology of lean T2D,a variant of T2D.Recent studies have focused on the effects of epigenetic variation on the contribution of in utero origins of lean T2D,although other mechanisms might also contribute to the pathology.Observational studies in humans and experiments in animals strongly suggest an association between maternal low protein diet and lean T2D phenotype.In addition,clear sex-specific disease prevalence was observed in different studies.Consequently,more research is essential for the understanding of the etiology and pathophysiology of lean T2D,which might help to develop better disease prevention and treatment strategies.This review examines the role of protein insufficiency in the maternal diet as the central driver of the developmental programming of lean T2D.
