Background Supplementation of choline chloride in culture medium programs the preimplantation bovine embryo to increase weaning weight of the resultant calf.Here,it was hypothesized that similar programming actions of...Background Supplementation of choline chloride in culture medium programs the preimplantation bovine embryo to increase weaning weight of the resultant calf.Here,it was hypothesized that similar programming actions of choline can be induced by feeding rumen-protected choline(RPC)to beef cows during the periconceptional period.Results A preliminary experiment was conducted to determine changes in circulating concentrations of choline and its metabolites after RPC supplementation.Suckled beef cows were individually fed 0,30,60,and 90 g of RPC(i.e.,0,8.6,17.3 and 25.9 g choline chloride)and blood samples were collected at random times after feeding.There were no differences in plasma concentrations of choline or its metabolites between groups.In the second experiment,effects of feeding 60 g/d RPC from d-1 to 7 relative to timed artificial insemination were examined for suckled beef cows.Feeding RPC did not affect pregnancy or calving rates,pregnancy losses,plasma concentrations of pregnancy-associated glycoproteins,gestation length or calf birth weight.Calves from RPC fed dams were lighter than control calves at~118 days of age(range 75–150;age included in the statistical model)and at weaning at~248 days of age.There was no effect of treatment on hip height at~118 days of age although there was a trend for RPC calves to be shorter at weaning.Weight/height ratio was lower for RPC than control at both 118 and 248 days of age.Treatment did not affect testis weight at~118 days of age.Conclusions Supplementation of RPC during the periconceptional period programmed development to alter calf phenotype in the postnatal period.The net result,reduced body weight,was the opposite of the phenotype caused by the addition of choline to embryo culture medium.展开更多
Gastric cancer(GC)remains one of the most common cancers and leading causes of cancer deaths globally1with 60.0%of cases and 56.6%of deaths occurring in East Asia.South Korea and Japan have conducted nationwide GC scr...Gastric cancer(GC)remains one of the most common cancers and leading causes of cancer deaths globally1with 60.0%of cases and 56.6%of deaths occurring in East Asia.South Korea and Japan have conducted nationwide GC screening programs for decades but with essential differences in strategies,organization,and coverage2.展开更多
Severe aortic stenosis has increased exponentially as a result of the aging of the population.Transcatheter aortic valve replacement(TAVR)procedures increase by 20%-30%per year in Spain.Referred patients are increasin...Severe aortic stenosis has increased exponentially as a result of the aging of the population.Transcatheter aortic valve replacement(TAVR)procedures increase by 20%-30%per year in Spain.Referred patients are increasingly older,have comorbidities,and frailty.TAVR cardiac rehabilitation(CR)programs significantly improve both functional capacity and quality of life of patients.However,there are no guidelines on how to carry out them and few elderly patients are referred to CR.Furthermore,mortality in women who undergo TAVR is higher than in men and even fewer are referred to CR programs.Multidisciplinary patient care,including comorbidities and frailty,is essential.It is necessary to ensure exquisite continuity of care during TAVR,CR,and the rest of the patient's life.Telerehabilitation could be an option in some lower-risk patients to include more patients in CR programs after TAVR,given the high demand.This article reviews the evidence on why CR should be performed in post-TAVR patients and proposes a practical and novel approach to the care process and the recommended aspects and components of the CR program.展开更多
交替方向乘子法(Alternating Direction Method of Multiplier,ADMM)因具有线性规划(Linear Programming,LP)译码条件约束的几何结构,同时利用了消息传递机制,被认为是一种第5代移动通信技术(5th Generation Mobile Communication Techn...交替方向乘子法(Alternating Direction Method of Multiplier,ADMM)因具有线性规划(Linear Programming,LP)译码条件约束的几何结构,同时利用了消息传递机制,被认为是一种第5代移动通信技术(5th Generation Mobile Communication Technology,5G)低密度校验(Low Density Parity Check,LDPC)码新型优化译码算法。通过在LP译码模型的目标函数中引入惩罚项,基于ADMM的变量节点惩罚译码有效地减轻了非积分解,从而提高了误帧率(Frame Error Rate,FER)性能。尽管ADMM在许多实际应用中表现出色,其收敛速度较慢以及对初始条件和参数设置敏感的问题仍然限制了其在高维、实时性要求高的场景中的进一步应用。特别是在LDPC线性规划译码过程中,ADMM的交替更新机制容易导致优化路径振荡,且在处理非精确约束时表现不佳。针对ADMM算法收敛速度慢的问题,我们提出了一种新的优化算法,该算法将Nesterov动量加速方法与ADMM相结合,以解决ADMM对LDPC译码器错误修正能力和收敛效率的影响。算法通过动量项减少迭代次数将一个Nesterov加速格式从无约束复合优化问题推广到ADMM惩罚函数模型,利用ADMM算法将原问题的约束条件有效转化为目标函数的一部分,从而构造出无约束优化子问题;在此基础上,进一步采用Nesterov加速技术对梯度下降迭代过程进行改进,以提高收敛速度和求解精度。仿真实验使用了三种不同码率的5G LDPC短码。结果表明,相对于现有ADMM惩罚译码算法,所提出的基于动量加速的ADMM译码算法不仅有大约0.2 dB的信噪比增益,而且平均迭代次数也降低了20%左右,加快了收敛速度。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
BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a ...BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment.While HP infection and PD-L1 expression in GC may be linked,the relationship between them remains unclear,in part because there have been conflicting results reported from various studies.AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.METHODS A systematic literature review was conducted using PubMed,Embase,Cochrane Library,and Web of Science databases.Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included.Odds ratios and 95%confidence intervals were calculated to estimate the association.Heterogeneity was assessed using Cochrane’s Q test and I²statistic.A random-effects model was used due to significant heterogeneity across studies.RESULTS Fourteen studies involving a total of 3069 patients with GC were included.The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues(odd ratio=1.69,95%confidence interval:1.24-2.29,P<0.001,I^(2)=59%).Sensitivity analyses confirmed the robustness of these findings.Subgroup analyses did not show significant variation based on geographic region,sample size,or method of PD-L1 assessment.Publication bias was minimal,as shown by funnel plots and Egger’s regression test.CONCLUSION HP infection is associated with increased PD-L1 expression in GC,suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.展开更多
Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells c...Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.展开更多
基金supported by the L.E.“Red”Larson Endowment and grants number 2020-67015-30821 and 2023-67015-40730 from the Agriculture and Food Research Initiative of USDA-NIFAsupported by the Higher Education Commission of Pakistan。
文摘Background Supplementation of choline chloride in culture medium programs the preimplantation bovine embryo to increase weaning weight of the resultant calf.Here,it was hypothesized that similar programming actions of choline can be induced by feeding rumen-protected choline(RPC)to beef cows during the periconceptional period.Results A preliminary experiment was conducted to determine changes in circulating concentrations of choline and its metabolites after RPC supplementation.Suckled beef cows were individually fed 0,30,60,and 90 g of RPC(i.e.,0,8.6,17.3 and 25.9 g choline chloride)and blood samples were collected at random times after feeding.There were no differences in plasma concentrations of choline or its metabolites between groups.In the second experiment,effects of feeding 60 g/d RPC from d-1 to 7 relative to timed artificial insemination were examined for suckled beef cows.Feeding RPC did not affect pregnancy or calving rates,pregnancy losses,plasma concentrations of pregnancy-associated glycoproteins,gestation length or calf birth weight.Calves from RPC fed dams were lighter than control calves at~118 days of age(range 75–150;age included in the statistical model)and at weaning at~248 days of age.There was no effect of treatment on hip height at~118 days of age although there was a trend for RPC calves to be shorter at weaning.Weight/height ratio was lower for RPC than control at both 118 and 248 days of age.Treatment did not affect testis weight at~118 days of age.Conclusions Supplementation of RPC during the periconceptional period programmed development to alter calf phenotype in the postnatal period.The net result,reduced body weight,was the opposite of the phenotype caused by the addition of choline to embryo culture medium.
基金supported by grants from the Shanghai Key Disciplines of Public Health(2023-2025)for New Threeyear Action Plan(Grant Nos.GWVI-11.1-22 and GWVI-11.1-23)the Fudan School of Public Health-Jiading CDC key disciplines for the high-quality development of public health(Grant No.GWGZLXK-2023-02)the Fudan Undergraduate Research Opportunities Program(Grant No.FDUROP-24647)。
文摘Gastric cancer(GC)remains one of the most common cancers and leading causes of cancer deaths globally1with 60.0%of cases and 56.6%of deaths occurring in East Asia.South Korea and Japan have conducted nationwide GC screening programs for decades but with essential differences in strategies,organization,and coverage2.
文摘Severe aortic stenosis has increased exponentially as a result of the aging of the population.Transcatheter aortic valve replacement(TAVR)procedures increase by 20%-30%per year in Spain.Referred patients are increasingly older,have comorbidities,and frailty.TAVR cardiac rehabilitation(CR)programs significantly improve both functional capacity and quality of life of patients.However,there are no guidelines on how to carry out them and few elderly patients are referred to CR.Furthermore,mortality in women who undergo TAVR is higher than in men and even fewer are referred to CR programs.Multidisciplinary patient care,including comorbidities and frailty,is essential.It is necessary to ensure exquisite continuity of care during TAVR,CR,and the rest of the patient's life.Telerehabilitation could be an option in some lower-risk patients to include more patients in CR programs after TAVR,given the high demand.This article reviews the evidence on why CR should be performed in post-TAVR patients and proposes a practical and novel approach to the care process and the recommended aspects and components of the CR program.
文摘交替方向乘子法(Alternating Direction Method of Multiplier,ADMM)因具有线性规划(Linear Programming,LP)译码条件约束的几何结构,同时利用了消息传递机制,被认为是一种第5代移动通信技术(5th Generation Mobile Communication Technology,5G)低密度校验(Low Density Parity Check,LDPC)码新型优化译码算法。通过在LP译码模型的目标函数中引入惩罚项,基于ADMM的变量节点惩罚译码有效地减轻了非积分解,从而提高了误帧率(Frame Error Rate,FER)性能。尽管ADMM在许多实际应用中表现出色,其收敛速度较慢以及对初始条件和参数设置敏感的问题仍然限制了其在高维、实时性要求高的场景中的进一步应用。特别是在LDPC线性规划译码过程中,ADMM的交替更新机制容易导致优化路径振荡,且在处理非精确约束时表现不佳。针对ADMM算法收敛速度慢的问题,我们提出了一种新的优化算法,该算法将Nesterov动量加速方法与ADMM相结合,以解决ADMM对LDPC译码器错误修正能力和收敛效率的影响。算法通过动量项减少迭代次数将一个Nesterov加速格式从无约束复合优化问题推广到ADMM惩罚函数模型,利用ADMM算法将原问题的约束条件有效转化为目标函数的一部分,从而构造出无约束优化子问题;在此基础上,进一步采用Nesterov加速技术对梯度下降迭代过程进行改进,以提高收敛速度和求解精度。仿真实验使用了三种不同码率的5G LDPC短码。结果表明,相对于现有ADMM惩罚译码算法,所提出的基于动量加速的ADMM译码算法不仅有大约0.2 dB的信噪比增益,而且平均迭代次数也降低了20%左右,加快了收敛速度。
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.
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment.While HP infection and PD-L1 expression in GC may be linked,the relationship between them remains unclear,in part because there have been conflicting results reported from various studies.AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.METHODS A systematic literature review was conducted using PubMed,Embase,Cochrane Library,and Web of Science databases.Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included.Odds ratios and 95%confidence intervals were calculated to estimate the association.Heterogeneity was assessed using Cochrane’s Q test and I²statistic.A random-effects model was used due to significant heterogeneity across studies.RESULTS Fourteen studies involving a total of 3069 patients with GC were included.The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues(odd ratio=1.69,95%confidence interval:1.24-2.29,P<0.001,I^(2)=59%).Sensitivity analyses confirmed the robustness of these findings.Subgroup analyses did not show significant variation based on geographic region,sample size,or method of PD-L1 assessment.Publication bias was minimal,as shown by funnel plots and Egger’s regression test.CONCLUSION HP infection is associated with increased PD-L1 expression in GC,suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.
基金supported by Canada First Research Excellence Fund,Medicine by Design(to CMM)。
文摘Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.
