目的:在前期发现琐琐葡萄总黄酮(Flavones from Vitis vinifera L,VTF)可改善APP/PS-1双转基因(Alzheimer's disease,AD)小鼠认知功能的基础上,进一步验证“VTF是否通过重塑肠道菌群-肠-脑轴而发挥神经保护作用”,并阐明其潜在机制...目的:在前期发现琐琐葡萄总黄酮(Flavones from Vitis vinifera L,VTF)可改善APP/PS-1双转基因(Alzheimer's disease,AD)小鼠认知功能的基础上,进一步验证“VTF是否通过重塑肠道菌群-肠-脑轴而发挥神经保护作用”,并阐明其潜在机制。方法:本研究将从天然药物琐琐葡萄中提取活性成分总黄酮VTF,作用于APP/PS-1小鼠,VTF灌胃8周,通过Morris水迷宫实验评估小鼠空间学习能力;ELISA检测小鼠脑组织中IL-1β、IL-6、TNF-α因子,血清中5-HT、GABA因子的含量;苏木精-伊红(Hematoxylin and eosin staining,HE)染色法观察结肠组织形态,免疫组化法检测Occludin、Claudin、Zo-1、NLRP3蛋白表达;高通量测序检测小鼠粪便肠道菌群;结果:1)水迷宫实验结果显示:VTF低剂量组平均逃逸潜伏期缩短(P<0.05);VTF低、中剂量组有效区域运动距离,运动时间以及进入次数显著增多(P<0.01);2)结肠组织HE染色结果显示;AD模型小鼠肠粘膜膜层萎缩,隐窝丢失和绒毛断裂,而VTF干预之后小鼠上述情况均有所减轻;3)结肠组织免疫组化结果显示:VTF干预可以上调Occludin、Claudin、Zo-1等紧密连接蛋白阳性表达(P<0.01),减少NLRP3炎症相关蛋白的表达(P<0.01);4)ELISA结果:VTF各剂量组小鼠脑组织中IL-1β、IL-6、TNFα等炎症因子水平降低(P<0.01);VTF各剂量组中5-HT和GABA的含量增多(P<0.01);5)肠道菌群检测结果显示:VTF高剂量干预后的AD小鼠厚壁菌门相对丰度增多(P<0.05),与模型组小鼠相比,VTF中、高剂量组中乳杆菌科(Lactobacillaceae)相对丰度增多,VTF低剂量组中Muribaculaceae相对丰度增多,多奈哌齐组,VTF各剂量组中丹毒科(Erysipelotrichaceae)、瘤胃球菌科(Ruminococcaceae)相对丰度增多;而VTF各剂量组中毛螺菌科(Lachnospiraceae)、螺杆菌科(Helicobacteraceae),脱铁杆菌科(Deferribacteraceae)相对丰度减少。结论:这些结果表明,VTF调节肠道菌群可能具有治疗衰老过程中微生物导致脑轴和认知功能缺陷的潜力,其机制可能与改变肠道菌群组成,修复受损的肠道屏障,炎症反应和神经递质有关。因此,调节肠道微生物群可能是治疗AD相关神经疾病的一种潜在策略。展开更多
Tel Ad办公空间坐落于以色列卡法萨巴一栋翻新建筑内。因自然采光条件有限,设计团队引入中央人工照明中庭,重塑空间流线,并通过材料运用,明确空间界定与功能分区。该中庭既是空间锚点,亦是氛围焦点。鉴于建筑进深较大,难以持续获取自然...Tel Ad办公空间坐落于以色列卡法萨巴一栋翻新建筑内。因自然采光条件有限,设计团队引入中央人工照明中庭,重塑空间流线,并通过材料运用,明确空间界定与功能分区。该中庭既是空间锚点,亦是氛围焦点。鉴于建筑进深较大,难以持续获取自然光线,中庭采用全光谱农业照明系统,以确保绿植全年茂盛生长。同时,空间流线也经重新设计,形成环绕绿色核心的环形路径,既确保了与绿植的持续视觉联系,又使各工作区域间的流线直观且流畅。除满足空间功能需求外,中庭在提升员工福祉与工作效率方面亦扮演关键角色:研究显示,相较于传统无窗办公环境,接触绿植及动态照明等自然元素,可有效降低压力、增强专注力并缓解视疲劳。室内统一采用水磨石地面、不锈钢装饰及天然木饰面,实现了整体空间的连贯性。展开更多
In this paper,we propose a new privacy-aware transmission scheduling algorithm for 6G ad hoc networks.This system enables end nodes to select the optimum time and scheme to transmit private data safely.In 6G dynamic h...In this paper,we propose a new privacy-aware transmission scheduling algorithm for 6G ad hoc networks.This system enables end nodes to select the optimum time and scheme to transmit private data safely.In 6G dynamic heterogeneous infrastructures,unstable links and non-uniform hardware capabilities create critical issues regarding security and privacy.Traditional protocols are often too computationally heavy to allow 6G services to achieve their expected Quality-of-Service(QoS).As the transport network is built of ad hoc nodes,there is no guarantee about their trustworthiness or behavior,and transversal functionalities are delegated to the extreme nodes.However,while security can be guaranteed in extreme-to-extreme solutions,privacy cannot,as all intermediate nodes still have to handle the data packets they are transporting.Besides,traditional schemes for private anonymous ad hoc communications are vulnerable against modern intelligent attacks based on learning models.The proposed scheme fulfills this gap.Findings show the probability of a successful intelligent attack reduces by up to 65%compared to ad hoc networks with no privacy protection strategy when used the proposed technology.While congestion probability can remain below 0.001%,as required in 6G services.展开更多
Alzheimer’s disease(AD)is the most common form of dementia.In addition to the lack of effective treatments,there are limitations in diagnostic capabilities.The complexity of AD itself,together with a variety of other...Alzheimer’s disease(AD)is the most common form of dementia.In addition to the lack of effective treatments,there are limitations in diagnostic capabilities.The complexity of AD itself,together with a variety of other diseases often observed in a patient’s history in addition to their AD diagnosis,make deciphering the molecular mechanisms that underlie AD,even more important.Large datasets of single-cell RNA sequencing,single-nucleus RNA-sequencing(snRNA-seq),and spatial transcriptomics(ST)have become essential in guiding and supporting new investigations into the cellular and regional susceptibility of AD.However,with unique technology,software,and larger databases emerging;a lack of integration of these data can contribute to ineffective use of valuable knowledge.Importantly,there was no specialized database that concentrates on ST in AD that offers comprehensive differential analyses under various conditions,such as sex-specific,region-specific,and comparisons between AD and control groups until the new Single-cell and Spatial RNA-seq databasE for Alzheimer’s Disease(ssREAD)database(Wang et al.,2024)was introduced to meet the scientific community’s growing demand for comprehensive,integrated,and accessible data analysis.展开更多
AIM: To evaluate the association of β-2 adrenergic receptor(β2-AR) gene polymorphism with response of variceal pressure to propranolol in cirrhosis.METHODS: Sixty-four non-related cirrhotic patients participated in ...AIM: To evaluate the association of β-2 adrenergic receptor(β2-AR) gene polymorphism with response of variceal pressure to propranolol in cirrhosis.METHODS: Sixty-four non-related cirrhotic patients participated in this study and accepted variceal pressure measurement before and after propranolol administration. Polymorphism of the β 2-AR gene was determined by directly sequencing of the polymerase chain reaction products from the DNA samples that were prepared from the patients.RESULTS: The prevalence of Gly16-Glu/Gln27 and Arg16-Gln27 homozygotes, and compound heterozygotes was 29.7%, 10.9%, and 59.4%, respectively.Patients with cirrhosis with Gly16-Glu/Gln27 homozygotes had a greater decrease of variceal pressure after propranolol administration than those with Arg16-Gln27 homozygotes or with compound heterozygotes(22.4% ± 2.1%, 13.1% ± 2.7% and 12.5% ± 3.1%,respectively, P < 0.01).CONCLUSION: The variceal pressure response to propranolol was associated with polymorphism of β 2-AR gene. Patients with the Gly16-Glu/Gln27 homozygotes probably benefit from propranolol therapy.展开更多
AIM: To study the stereoselectivity of phase Ⅱ glucuronidation metabolism of side-chain propranolol in Chinese Han population. METHODS: Sixteen adult Chinese Han volunteers with an average age of 20 years were given ...AIM: To study the stereoselectivity of phase Ⅱ glucuronidation metabolism of side-chain propranolol in Chinese Han population. METHODS: Sixteen adult Chinese Han volunteers with an average age of 20 years were given a single oral dose of 20 mg racemic propranolol. Human urine at indicated time after administration was collected and S-(-)-propranolol glucuronide and R-(+)-propranolol glucuronide were determined simultaneously by using RP-HPLC. RESULTS: The mean values of k were 0.19±0.04 h-1 and 0.28±0.06 h-1, of t1/2 3.56±0.73 h and 2.45±0.50 h, of Tmax 2.21±0.45 and 1.75±0.33 h, and of Xu0-24 5.65±0.98 and 2.95±0.62 μmoL for S-(-)- and R-(+)-propranolol glucuronide, respectively. The cumulative excretion percentages in urine of closes were 14.7±2.46% and 7.68±1.60% for S-(-)-and R-(+)-propranolol glucuronide, respectively. The results showed the elimination rate constant k of S-(-)-propranolol glucuronide was less than that of R-(+)-propranolol glucuronide; and the elimination half-life (t1/2), Tmax and the cumulative excretion amount (Xu0-24) of R-(+)-propranolol glucuronide were significantly less than that of S-(-)-propranolol glucuronide. CONCLUSION: The propranolol glucuronidation of the side-chain undergoes stereoselective excretion in Chinese Han population after an oral administration of racemic propranolol.展开更多
The aims of this study were to prepare and characterize hydroxypropyl methylcellulose(HPMC)/polycarbophil(PC) mucoadhesive blend films saturated with propranolol hydrochloride(PNL)-loaded nanoparticles to improve perm...The aims of this study were to prepare and characterize hydroxypropyl methylcellulose(HPMC)/polycarbophil(PC) mucoadhesive blend films saturated with propranolol hydrochloride(PNL)-loaded nanoparticles to improve permeability of drugs that undergo firstpass metabolism. An ionic cross-linking method and film casting technique was used to prepare nanoparticles and mucoadhesive blend films, respectively. Increasing concentrations of PNL(70, 80, 90 mg/film) in HPMC/PC blend films containing PNL-loaded nanoparticles(PN-films) and HPMC/PC blend films containing PNL(80 mg/film) without nanoparticles(PPfilms) were prepared to test swelling, mucoadhesiveness, release, permeation and physicochemical properties. Scanning electron microscope(SEM) images showed a partially smooth surface with a wrinkled occurrence and spherically shaped, well-dispersed nanoparticles on the surface of PN-films containing PNL 80 mg/film(PN-films-80). The size of the nanoparticles on the surface of PN-films-80 was around 100 nm, which was similar to the nanoparticle size observed using light scattering technique. The swelling index(SI)of all PN-films and PP-films increased greatly in the first period time(10–20 min) and reached swelling equilibrium at 20 min and 30 min, respectively. For the PN-films, the concentration of PNL influenced the mucoadhesive properties and tended to be higher when the amount of PNL increased. Immediate release of all blend film formulations was found in early time points(10–30 min). After 120 min, the release of PN-films-70 was lower than the other PNfilms. Permeation studies using porcine buccal mucosa showed that inclusion of nanoparticles in the films increased the permeability of PNL compared to PP-films. Therefore, buccal administration of mucoadhesive blend films containing PNL-loaded nanoparticles could be a promising approach for drugs that undergo first-pass metabolism.展开更多
文摘目的:在前期发现琐琐葡萄总黄酮(Flavones from Vitis vinifera L,VTF)可改善APP/PS-1双转基因(Alzheimer's disease,AD)小鼠认知功能的基础上,进一步验证“VTF是否通过重塑肠道菌群-肠-脑轴而发挥神经保护作用”,并阐明其潜在机制。方法:本研究将从天然药物琐琐葡萄中提取活性成分总黄酮VTF,作用于APP/PS-1小鼠,VTF灌胃8周,通过Morris水迷宫实验评估小鼠空间学习能力;ELISA检测小鼠脑组织中IL-1β、IL-6、TNF-α因子,血清中5-HT、GABA因子的含量;苏木精-伊红(Hematoxylin and eosin staining,HE)染色法观察结肠组织形态,免疫组化法检测Occludin、Claudin、Zo-1、NLRP3蛋白表达;高通量测序检测小鼠粪便肠道菌群;结果:1)水迷宫实验结果显示:VTF低剂量组平均逃逸潜伏期缩短(P<0.05);VTF低、中剂量组有效区域运动距离,运动时间以及进入次数显著增多(P<0.01);2)结肠组织HE染色结果显示;AD模型小鼠肠粘膜膜层萎缩,隐窝丢失和绒毛断裂,而VTF干预之后小鼠上述情况均有所减轻;3)结肠组织免疫组化结果显示:VTF干预可以上调Occludin、Claudin、Zo-1等紧密连接蛋白阳性表达(P<0.01),减少NLRP3炎症相关蛋白的表达(P<0.01);4)ELISA结果:VTF各剂量组小鼠脑组织中IL-1β、IL-6、TNFα等炎症因子水平降低(P<0.01);VTF各剂量组中5-HT和GABA的含量增多(P<0.01);5)肠道菌群检测结果显示:VTF高剂量干预后的AD小鼠厚壁菌门相对丰度增多(P<0.05),与模型组小鼠相比,VTF中、高剂量组中乳杆菌科(Lactobacillaceae)相对丰度增多,VTF低剂量组中Muribaculaceae相对丰度增多,多奈哌齐组,VTF各剂量组中丹毒科(Erysipelotrichaceae)、瘤胃球菌科(Ruminococcaceae)相对丰度增多;而VTF各剂量组中毛螺菌科(Lachnospiraceae)、螺杆菌科(Helicobacteraceae),脱铁杆菌科(Deferribacteraceae)相对丰度减少。结论:这些结果表明,VTF调节肠道菌群可能具有治疗衰老过程中微生物导致脑轴和认知功能缺陷的潜力,其机制可能与改变肠道菌群组成,修复受损的肠道屏障,炎症反应和神经递质有关。因此,调节肠道微生物群可能是治疗AD相关神经疾病的一种潜在策略。
基金funding from the European Commission by the Ruralities project(grant agreement no.101060876).
文摘In this paper,we propose a new privacy-aware transmission scheduling algorithm for 6G ad hoc networks.This system enables end nodes to select the optimum time and scheme to transmit private data safely.In 6G dynamic heterogeneous infrastructures,unstable links and non-uniform hardware capabilities create critical issues regarding security and privacy.Traditional protocols are often too computationally heavy to allow 6G services to achieve their expected Quality-of-Service(QoS).As the transport network is built of ad hoc nodes,there is no guarantee about their trustworthiness or behavior,and transversal functionalities are delegated to the extreme nodes.However,while security can be guaranteed in extreme-to-extreme solutions,privacy cannot,as all intermediate nodes still have to handle the data packets they are transporting.Besides,traditional schemes for private anonymous ad hoc communications are vulnerable against modern intelligent attacks based on learning models.The proposed scheme fulfills this gap.Findings show the probability of a successful intelligent attack reduces by up to 65%compared to ad hoc networks with no privacy protection strategy when used the proposed technology.While congestion probability can remain below 0.001%,as required in 6G services.
文摘Alzheimer’s disease(AD)is the most common form of dementia.In addition to the lack of effective treatments,there are limitations in diagnostic capabilities.The complexity of AD itself,together with a variety of other diseases often observed in a patient’s history in addition to their AD diagnosis,make deciphering the molecular mechanisms that underlie AD,even more important.Large datasets of single-cell RNA sequencing,single-nucleus RNA-sequencing(snRNA-seq),and spatial transcriptomics(ST)have become essential in guiding and supporting new investigations into the cellular and regional susceptibility of AD.However,with unique technology,software,and larger databases emerging;a lack of integration of these data can contribute to ineffective use of valuable knowledge.Importantly,there was no specialized database that concentrates on ST in AD that offers comprehensive differential analyses under various conditions,such as sex-specific,region-specific,and comparisons between AD and control groups until the new Single-cell and Spatial RNA-seq databasE for Alzheimer’s Disease(ssREAD)database(Wang et al.,2024)was introduced to meet the scientific community’s growing demand for comprehensive,integrated,and accessible data analysis.
基金Supported by National Natural Science Foundation of China,No.81271736
文摘AIM: To evaluate the association of β-2 adrenergic receptor(β2-AR) gene polymorphism with response of variceal pressure to propranolol in cirrhosis.METHODS: Sixty-four non-related cirrhotic patients participated in this study and accepted variceal pressure measurement before and after propranolol administration. Polymorphism of the β 2-AR gene was determined by directly sequencing of the polymerase chain reaction products from the DNA samples that were prepared from the patients.RESULTS: The prevalence of Gly16-Glu/Gln27 and Arg16-Gln27 homozygotes, and compound heterozygotes was 29.7%, 10.9%, and 59.4%, respectively.Patients with cirrhosis with Gly16-Glu/Gln27 homozygotes had a greater decrease of variceal pressure after propranolol administration than those with Arg16-Gln27 homozygotes or with compound heterozygotes(22.4% ± 2.1%, 13.1% ± 2.7% and 12.5% ± 3.1%,respectively, P < 0.01).CONCLUSION: The variceal pressure response to propranolol was associated with polymorphism of β 2-AR gene. Patients with the Gly16-Glu/Gln27 homozygotes probably benefit from propranolol therapy.
基金Supported by the National Natural Science Foundation of China, No. 30225047
文摘AIM: To study the stereoselectivity of phase Ⅱ glucuronidation metabolism of side-chain propranolol in Chinese Han population. METHODS: Sixteen adult Chinese Han volunteers with an average age of 20 years were given a single oral dose of 20 mg racemic propranolol. Human urine at indicated time after administration was collected and S-(-)-propranolol glucuronide and R-(+)-propranolol glucuronide were determined simultaneously by using RP-HPLC. RESULTS: The mean values of k were 0.19±0.04 h-1 and 0.28±0.06 h-1, of t1/2 3.56±0.73 h and 2.45±0.50 h, of Tmax 2.21±0.45 and 1.75±0.33 h, and of Xu0-24 5.65±0.98 and 2.95±0.62 μmoL for S-(-)- and R-(+)-propranolol glucuronide, respectively. The cumulative excretion percentages in urine of closes were 14.7±2.46% and 7.68±1.60% for S-(-)-and R-(+)-propranolol glucuronide, respectively. The results showed the elimination rate constant k of S-(-)-propranolol glucuronide was less than that of R-(+)-propranolol glucuronide; and the elimination half-life (t1/2), Tmax and the cumulative excretion amount (Xu0-24) of R-(+)-propranolol glucuronide were significantly less than that of S-(-)-propranolol glucuronide. CONCLUSION: The propranolol glucuronidation of the side-chain undergoes stereoselective excretion in Chinese Han population after an oral administration of racemic propranolol.
基金the financial support provided by Thammasat University under the TU Research Scholar,Contract No.TP 2/68/2556
文摘The aims of this study were to prepare and characterize hydroxypropyl methylcellulose(HPMC)/polycarbophil(PC) mucoadhesive blend films saturated with propranolol hydrochloride(PNL)-loaded nanoparticles to improve permeability of drugs that undergo firstpass metabolism. An ionic cross-linking method and film casting technique was used to prepare nanoparticles and mucoadhesive blend films, respectively. Increasing concentrations of PNL(70, 80, 90 mg/film) in HPMC/PC blend films containing PNL-loaded nanoparticles(PN-films) and HPMC/PC blend films containing PNL(80 mg/film) without nanoparticles(PPfilms) were prepared to test swelling, mucoadhesiveness, release, permeation and physicochemical properties. Scanning electron microscope(SEM) images showed a partially smooth surface with a wrinkled occurrence and spherically shaped, well-dispersed nanoparticles on the surface of PN-films containing PNL 80 mg/film(PN-films-80). The size of the nanoparticles on the surface of PN-films-80 was around 100 nm, which was similar to the nanoparticle size observed using light scattering technique. The swelling index(SI)of all PN-films and PP-films increased greatly in the first period time(10–20 min) and reached swelling equilibrium at 20 min and 30 min, respectively. For the PN-films, the concentration of PNL influenced the mucoadhesive properties and tended to be higher when the amount of PNL increased. Immediate release of all blend film formulations was found in early time points(10–30 min). After 120 min, the release of PN-films-70 was lower than the other PNfilms. Permeation studies using porcine buccal mucosa showed that inclusion of nanoparticles in the films increased the permeability of PNL compared to PP-films. Therefore, buccal administration of mucoadhesive blend films containing PNL-loaded nanoparticles could be a promising approach for drugs that undergo first-pass metabolism.
