The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centere...The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.展开更多
F_(10.7)指数是太阳活动的重要指标,准确预测F_(10.7)指数有助于预防和缓解太阳活动对无线电通信、导航和卫星通信等领域的影响.基于F_(10.7)射电流量的特性,在双向长短时记忆网络(Bidirectional Long Short-Term Memory Network,BiLSTM...F_(10.7)指数是太阳活动的重要指标,准确预测F_(10.7)指数有助于预防和缓解太阳活动对无线电通信、导航和卫星通信等领域的影响.基于F_(10.7)射电流量的特性,在双向长短时记忆网络(Bidirectional Long Short-Term Memory Network,BiLSTM)基础上融入注意力机制(Attention),提出了一种基于BiLSTM-Attention的F_(10.7)预报模型.在加拿大DRAO数据集上其平均绝对误差(MAE)为5.38,平均绝对百分比误差(MAPE)控制在5%以内,相关系数(R)高达0.987,与其他RNN模型相比拥有优越的预测性能.针对中国廊坊L&S望远镜观测的F_(10.7)数据集,提出了一种转换平均校准(Conversion Average Calibration,CAC)方法进行数据预处理,处理后的数据与DRAO数据集具有较高的相关性.基于该数据集对比分析了RNN系列模型的预报效果,实验结果表明,BiLSTM-Attention和BiLSTM两种模型在预测F_(10.7)指数方面具有较好的优势,表现出较好的预测性能和稳定性.展开更多
本文基于连续介质力学和理性扩展热力学分析流程,将L-S(Lord and Shulman)热弹性理论与声弹性理论相结合,建立L-S热声弹性理论的基本框架,包括运动学、力学与热力学、本构方程与演化方程、基本场方程四部分。在运动学部分,区分了Lagrang...本文基于连续介质力学和理性扩展热力学分析流程,将L-S(Lord and Shulman)热弹性理论与声弹性理论相结合,建立L-S热声弹性理论的基本框架,包括运动学、力学与热力学、本构方程与演化方程、基本场方程四部分。在运动学部分,区分了Lagrange描述和Euler描述,以及3种不同的状态和构形,同时针对热声弹性情况定义了两类从自然状态到初始状态的转变过程;在力学与热力学部分,给出了质量守恒定律、动量守恒定律、角动量守恒定律、能量守恒定律以及熵产不等式,从而引出经典不可逆热力学的局限性;在本构方程与演化方程部分,介绍了扩展不可逆热力学原理,并基于理性扩展热力学流程,推导了从自然状态到初始状态、从初始状态到最终状态的热声弹性本构方程与演化方程,将热流作为本构自变量并考虑了热流与应变和温度的相关性;在最后一部分给出了基本场方程的运动方程形式和适用于数值模拟的一阶速度-应力-热流-温度微分方程。展开更多
BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value...BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.展开更多
Mosquitoes are an interesting topic due to their medical importance, as they play an active role in the transmission of many pathogens and parasites, acting as vectors for various pathologies that are deadly to humans...Mosquitoes are an interesting topic due to their medical importance, as they play an active role in the transmission of many pathogens and parasites, acting as vectors for various pathologies that are deadly to humans, such as dengue, yellow fever, chikungunya, West Nile virus, encephalitis and malaria, among many others that are less common. In terms of morbidity and mortality caused by vector-borne diseases, mosquitoes are the most dangerous animals for humanity and, although they also play a role in the ecosystem as a food source for other organisms, their importance for public health cannot be overlooked. As highly efficient vectors, they put more than three billion people at risk, mainly in tropical and subtropical regions as well as in Europe, since heat waves and flooding are becoming more frequent and severe, and summers are getting longer and warmer, accelerating mosquito development, biting rates, and the incubation of the pathogens within their bodies. Female mosquitoes bite to acquire proteins for the development of their ovaries and eggs and, in the process, acquire pathogens and/or parasites from one vertebrate host and transmit them to another, usually after a short period of replication. Three of their four life stages are lived in still freshwater, so it is crucial to understand their range of action when they reach adulthood and leave the water, in order to plan and implement local prevention measures. A set of georeferenced abundance data collected in mainland Portugal over seven years was linked to cartographed water bodies in a geographic information system to estimate the distances at which Culex pipiens s.l. had a significant presence, with criteria based on the size of the catches. The result allows for an estimate of the fly range of those mosquitoes, which can be used to focus countermeasures.展开更多
Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation...Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used SGTF of TaqPath COVID-19 Combo Kit RT-qPCR as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The nested PCR amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed R203K, G204R and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: Sanger sequencing of a 445-base segment of the SARS-CoV-2 RBD is useful for accurate determination of emerging variants. The CDC may consider using Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.展开更多
目的评估在骨质疏松条件下,行L5/S1节段斜外侧椎间融合术(oblique lateral interbody fusion at L5/S1,OLIF51)及其联合双侧皮质骨轨迹螺钉(cortical bone trajectory screw,CBT)和双侧椎弓根螺钉(bilateral pedicle screw,BPS)的生物...目的评估在骨质疏松条件下,行L5/S1节段斜外侧椎间融合术(oblique lateral interbody fusion at L5/S1,OLIF51)及其联合双侧皮质骨轨迹螺钉(cortical bone trajectory screw,CBT)和双侧椎弓根螺钉(bilateral pedicle screw,BPS)的生物力学性能。方法招募1名健康青年男性作为志愿者,获得其腰骶椎三维CT数据,在有限元分析软件中完成L4~S1三维模型,采用前路钛板(titanium plate,TP)固定的OLIF51手术模型、OLIF51+CBT和OLIF51+BPS手术模型的构建,分别命名为A、B、C、D模型。通过赋值、设定条件、施加载荷,分析不同条件下的生物力学特性。结果顺利完成4种有限元模型的构建。4种模型在所有运动中的平均活动度(range of motion,ROM)变化趋势为A模型>B模型>C模型>D模型;其中,与A模型相比,B模型降幅为84.21%~94.42%,C模型降幅为88.12%~96.40%,D模型降幅为90.07%~96.49%(P均<0.05);与B模型相比,C模型降幅为7.41%~52.38%,D模型降幅为27.78%~58.33%(P均<0.05)。3种手术模型在所有运动中的融合器(Cage)平均最大应力变化趋势为B模型>C模型>D模型;其中,与B模型相比,C模型降幅为12.89%~57.62%,D模型降幅为36.43%~73.11%;D模型和C模型相比,除左侧弯外差异均有统计学意义(P均<0.05);D模型降幅为21.83%~37.67%。3种手术模型在所有运动中的内固定平均最大应力变化趋势为B模型>C模型>D模型;与B模型相比,C模型降幅为3.55%~65.47%,D模型降幅为18.58%~84.41%;CBT应力大于BPS应力(P<0.05)。结论在OLIF51手术中,补充后路内固定可以增强融合节段的稳定性并减轻TP上的应力。不建议对骨质疏松症患者单独进行OLIF51手术,使用BPS辅助固定可达到最佳生物力学特性。接受CBT辅助内固定的患者术后需要佩戴支具,并尽量避免融合部位的右侧弯曲运动。展开更多
文摘The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.
文摘F_(10.7)指数是太阳活动的重要指标,准确预测F_(10.7)指数有助于预防和缓解太阳活动对无线电通信、导航和卫星通信等领域的影响.基于F_(10.7)射电流量的特性,在双向长短时记忆网络(Bidirectional Long Short-Term Memory Network,BiLSTM)基础上融入注意力机制(Attention),提出了一种基于BiLSTM-Attention的F_(10.7)预报模型.在加拿大DRAO数据集上其平均绝对误差(MAE)为5.38,平均绝对百分比误差(MAPE)控制在5%以内,相关系数(R)高达0.987,与其他RNN模型相比拥有优越的预测性能.针对中国廊坊L&S望远镜观测的F_(10.7)数据集,提出了一种转换平均校准(Conversion Average Calibration,CAC)方法进行数据预处理,处理后的数据与DRAO数据集具有较高的相关性.基于该数据集对比分析了RNN系列模型的预报效果,实验结果表明,BiLSTM-Attention和BiLSTM两种模型在预测F_(10.7)指数方面具有较好的优势,表现出较好的预测性能和稳定性.
文摘本文基于连续介质力学和理性扩展热力学分析流程,将L-S(Lord and Shulman)热弹性理论与声弹性理论相结合,建立L-S热声弹性理论的基本框架,包括运动学、力学与热力学、本构方程与演化方程、基本场方程四部分。在运动学部分,区分了Lagrange描述和Euler描述,以及3种不同的状态和构形,同时针对热声弹性情况定义了两类从自然状态到初始状态的转变过程;在力学与热力学部分,给出了质量守恒定律、动量守恒定律、角动量守恒定律、能量守恒定律以及熵产不等式,从而引出经典不可逆热力学的局限性;在本构方程与演化方程部分,介绍了扩展不可逆热力学原理,并基于理性扩展热力学流程,推导了从自然状态到初始状态、从初始状态到最终状态的热声弹性本构方程与演化方程,将热流作为本构自变量并考虑了热流与应变和温度的相关性;在最后一部分给出了基本场方程的运动方程形式和适用于数值模拟的一阶速度-应力-热流-温度微分方程。
基金Supported by National Nature Science Foundation of China,No.82060450,No.82360517,No.81460374,and No.31460304Nature Science Foundation of Jiangxi Province of China,No.20232BAB206086,No.20192BAB205072,No.20203BBGL73206,No.2017BCB23086,No.2017BAB205062,and No.20181BAB205050.
文摘BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.
文摘Mosquitoes are an interesting topic due to their medical importance, as they play an active role in the transmission of many pathogens and parasites, acting as vectors for various pathologies that are deadly to humans, such as dengue, yellow fever, chikungunya, West Nile virus, encephalitis and malaria, among many others that are less common. In terms of morbidity and mortality caused by vector-borne diseases, mosquitoes are the most dangerous animals for humanity and, although they also play a role in the ecosystem as a food source for other organisms, their importance for public health cannot be overlooked. As highly efficient vectors, they put more than three billion people at risk, mainly in tropical and subtropical regions as well as in Europe, since heat waves and flooding are becoming more frequent and severe, and summers are getting longer and warmer, accelerating mosquito development, biting rates, and the incubation of the pathogens within their bodies. Female mosquitoes bite to acquire proteins for the development of their ovaries and eggs and, in the process, acquire pathogens and/or parasites from one vertebrate host and transmit them to another, usually after a short period of replication. Three of their four life stages are lived in still freshwater, so it is crucial to understand their range of action when they reach adulthood and leave the water, in order to plan and implement local prevention measures. A set of georeferenced abundance data collected in mainland Portugal over seven years was linked to cartographed water bodies in a geographic information system to estimate the distances at which Culex pipiens s.l. had a significant presence, with criteria based on the size of the catches. The result allows for an estimate of the fly range of those mosquitoes, which can be used to focus countermeasures.
文摘Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used SGTF of TaqPath COVID-19 Combo Kit RT-qPCR as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The nested PCR amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed R203K, G204R and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: Sanger sequencing of a 445-base segment of the SARS-CoV-2 RBD is useful for accurate determination of emerging variants. The CDC may consider using Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.
文摘目的评估在骨质疏松条件下,行L5/S1节段斜外侧椎间融合术(oblique lateral interbody fusion at L5/S1,OLIF51)及其联合双侧皮质骨轨迹螺钉(cortical bone trajectory screw,CBT)和双侧椎弓根螺钉(bilateral pedicle screw,BPS)的生物力学性能。方法招募1名健康青年男性作为志愿者,获得其腰骶椎三维CT数据,在有限元分析软件中完成L4~S1三维模型,采用前路钛板(titanium plate,TP)固定的OLIF51手术模型、OLIF51+CBT和OLIF51+BPS手术模型的构建,分别命名为A、B、C、D模型。通过赋值、设定条件、施加载荷,分析不同条件下的生物力学特性。结果顺利完成4种有限元模型的构建。4种模型在所有运动中的平均活动度(range of motion,ROM)变化趋势为A模型>B模型>C模型>D模型;其中,与A模型相比,B模型降幅为84.21%~94.42%,C模型降幅为88.12%~96.40%,D模型降幅为90.07%~96.49%(P均<0.05);与B模型相比,C模型降幅为7.41%~52.38%,D模型降幅为27.78%~58.33%(P均<0.05)。3种手术模型在所有运动中的融合器(Cage)平均最大应力变化趋势为B模型>C模型>D模型;其中,与B模型相比,C模型降幅为12.89%~57.62%,D模型降幅为36.43%~73.11%;D模型和C模型相比,除左侧弯外差异均有统计学意义(P均<0.05);D模型降幅为21.83%~37.67%。3种手术模型在所有运动中的内固定平均最大应力变化趋势为B模型>C模型>D模型;与B模型相比,C模型降幅为3.55%~65.47%,D模型降幅为18.58%~84.41%;CBT应力大于BPS应力(P<0.05)。结论在OLIF51手术中,补充后路内固定可以增强融合节段的稳定性并减轻TP上的应力。不建议对骨质疏松症患者单独进行OLIF51手术,使用BPS辅助固定可达到最佳生物力学特性。接受CBT辅助内固定的患者术后需要佩戴支具,并尽量避免融合部位的右侧弯曲运动。