Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

Study of tree shrew biology and models: A booming and prosperous field for biomedical research

The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.

Two-dimensional ultrathin MoS2-modified black Ti^3+-TiO2 nanotubes for enhanced photocatalytic water splitting hydrogen production

Two-dimensional (2D) ultrathin MoS2-modified black Ti^3+-TiO2 nanotubes were fabricated using an electrospinning-hydrothermal treatment-reduction method.Bare TiO2 nanotubes were fabricated via electrospinning.Then,2D MoS2 lamellae were grown on the surface of the nanotubes and Ti^3+/Ov ions were introduced by reduction.The photocatalytic performance of the 2D MoS2/Ti^3+-TiO2 nanotubes was^15 times better than that of TiO2.The HER enhancement of the MoS2/Ti^3+-TiO2 nanotubes can be attributed to the Pt-like behavior of 2D MoS2 and the presence of Ti^3+-ions,which facilitated the quick diffusion of the photogenerated electrons to water,reducing the H2 activation barrier.The presence of Ov ions in the nanotubes and their hollow structure increased their solar utilization.

Effects of Bio-organic Fertilizer with Antagonistic Bacteria against Tobacco Bacterial Wilt on Soil Microbial Communities and Disease Resistance of Tobacco

In this study, the effects of bio-organic fertilizer with antagonistic bacteria against tobacco bacterial wilt on soil microbial communities and disease resist- ance of tobacco were investigated by field experiment. The results showed that the incidence of tobacco bacterial wilt in bio-organic fertilizer treatments （T3 and T4） decreased remarkably among four treatments in the field. Compared with the local conventional fertilization group, the incidence of tobacco bacterial wilt was re- duced by 21.9% and 25.0% in T3 and T4, respectively ; the yield of flue-cured tobacco was improved by 5.7% and 5.3%, respectively ; the proportion of mid- high grade tobacco leaves increased by 2.3% and 2.6%, respectively. After application of bio-organie fertilizer with antagonistic bacteria against tobacco bacterial wilt, rhizosphere soil microbial communities exhibited vast amount and abundant species ; the amount of rhizosphere soil bacteria of infected tobacco plants was im- proved by 218.5% with fewer species. It could be concluded that the application of bio-organic fertilizer with antagonistic bacteria against tobacco bacterial wilt could improve the ecological environment of tobacco field, inhibit the growth of pathogenic bacteria, decrease the incidence of tobacco bacterial wilt, and enhance the quality of flue-cured tobacco. This study laid the foundation for further ecological prevention and control of soil-borne diseases of tobacco.

Effects of shrub-grass patterns on soil detachment and hydraulic parameters of slope in the Pisha sandstone area of Inner Mongolia,China

The characteristics of soil holding capacity for different shrub-grass patterns are important to research the mechanisms regulating vegetation on slopes.The objective of this study was to describe the characteristics and mecha-nisms of soil erosion and hydraulic parameters under differ-ent vegetation patterns in the Pisha sandstone area of Inner Mongolia on lands of 8°slope gradient.We carried out field scouring experiments on five different shrub-grass patterns as treatments,viz no shrubs(GL),shrubs on the upper part of the slope(SU),middle part of the slope(SM)and lower part of the slope(SL).We designated bare slope(BL)as the control.We employed three different water flow rates(15,20,30 L·min^(−1)).Our results showed that the contribution of plant root systems to slope sediment reduction ranged from 64 to 84%.The root systems proved to be the main contributing factor to reduction of erosion by vegetation.The relationship between soil detachment rate,stream flow power,and flow unit stream power under different scouring discharge rates showed that soil detachment declined in rank order as:BL>GL>SU>SM>SL.The SL pat-tern had the lowest soil detachment rate(0.098 g·m^(−2)·s^(−1)),flow stream power(2.371 W·m^(−2)),flow unit stream power(0.165 m·s^(−1))and flow shear stress(16.986 Pa),and proved to be the best erosion combating pattern.The results of decision coefficient and path analysis showed that stream power was the most important hydraulic parameter for describing soil detachment rate.The combination of stream power and shear stress,namely Dr=0.1ω−0.03τ−0.56(R^(2)=0.924),most accurately simulated the soil detachment characteristics on slopes.Our study suggests that the risk of soil ero-sion can be reduced by planting shrub-grass mixes on these slopes.Under the conditions of limited water resources and economy,the benefit of sediment reduction can be maxi-mized by planting shrubbery on the lower parts of slopes.

青藏高原三江源和河湾区夏季降水变化特征及对高原夏季风的响应

本文利用1981~2020年观测数据和ERA5再分析资料,将青藏高原腹地三江源和东南重要水汽通道河湾区作为典型研究区域,分析了降水不同时间尺度变化特征及其典型强弱年对高原季风环流系统的响应,结果表明:(1)三江源和河湾区降水的季节变化均呈双峰型分布,峰值出现在7月初和8月下旬。夏季降水在21世纪初发生年代际转折,尤其是三江源降水量在近20年增加明显。两个高原季风指数DPMI(Dynamic Plateau Monsoon Index)和ZPMI(Zhou Plateau Monsoon Index)的夏季风爆发时间均超前于河湾区和三江源降水的明显增加期。三江源夏季降水年际变化与两个高原夏季风指数有较好的相关性。三江源与河湾区虽然相邻很近,但三江源夏季降水受高原季风影响程度远大于河湾区。当高原夏季风增强(减弱)时,三江源降水量偏多(少)。(2)三江源降水偏多年,南亚高压偏东偏强,低层高原主体低压异常,有利于西南风和东南风在三江源区域交汇,南方暖湿空气能够深入高原腹地导致水汽辐合偏强。河湾区降水偏多年,河湾区及整个高原主体附近高度场并没有明显异常,河湾区的水汽输送主要有两条路径,一条来自孟加拉湾沿高原南坡的西南路径,另一条来自中亚地区穿过高原上空的西北路径,两条路径在高原东侧汇合继续向东输送。

Application of a Three-dimensional Variational Method for Radar Reflectivity Data Correction in a Mudslide-inducing Rainstorm Simulation

Various types of radars with different horizontal and vertical detection ranges are deployed in China, particularly over complex terrain where radar blind zones are common. In this study, a new variational method is developed to correct threedimensional radar reflectivity data based on hourly ground precipitation observations. The aim of this method is to improve the quality of observations of various types of radar and effectively assimilate operational Doppler radar observations. A mudslide-inducing local rainstorm is simulated by the WRF model with assimilation of radar reflectivity and radial velocity data using LAPS（Local Analysis and Prediction System）. Experiments with different radar data assimilated by LAPS are performed. It is found that when radar reflectivity data are corrected using this variational method and assimilated by LAPS,the atmospheric conditions and cloud physics processes are reasonably described. The temporal evolution of radar reflectivity corrected by the variational method corresponds well to observed rainfall. It can better describe the cloud water distribution over the rainfall area and improve the cloud water analysis results over the central rainfall region. The LAPS cloud analysis system can update cloud microphysical variables and represent the hydrometeors associated with strong convective activities over the rainfall area well. Model performance is improved and the simulation of the dynamical processes and moisture transport is more consistent with observation.

新时代背景下分析化学微课的构建——以滴定突跃为例

伴随着信息化技术的发展及不可抗力因素的影响等,传统的课堂教学模式已不能满足分析化学的现代化教学。微课是一种新兴的、依托于互联网的优良数字化教学资源。本文以分析化学滴定分析中的滴定突跃为主题,阐述了微课的设计、构思、内容和形式等,展示了微课在分析化学教学中的应用,为传统教学提供了新思路。

Galectin-3在非小细胞肺癌患者血清中的表达及其临床意义

背景与目的肺癌是对人类健康威胁最大的疾病之一,发病率高,死亡率高。早期肺癌可以通过外科手术得到根治,因此,肺癌的早期发现及早期治疗尤其重要。血清肿瘤标志物是发现及诊断肺癌的一个重要手段。目前已知,半乳糖凝集素3(Galectin-3)在多种恶性肿瘤中均有表达。该研究旨在探讨Galectin-3在非小细胞肺癌患者血清中的表达水平及其临床意义。方法采用酶联免疫吸附法检测并比较69例非小细胞肺癌患者与77例健康人群外周血血清Galectin-3浓度,并分析其表达水平与肺癌临床特征之间的关系。结果 Galectin-3在非小细胞肺癌患者外周血血清中的表达水平高于健康人群,差异具有显著统计学意义(P<0.01);有淋巴结转移的非小细胞肺癌患者,Galectin-3表达水平显著高于无淋巴结转移患者,差异有显著统计学意义(P<0.01);N2淋巴结转移的患者Galectin-3表达水平显著高于N1淋巴结转移的患者,差异有显著统计学意义(P<0.01);临床III期+IV期患者Galectin-3表达水平显著高于临床I期+II期患者,差异有统计学意义(P<0.05)。结论非小细胞肺癌患者血清Galectin-3水平呈现高表达,与肺癌转移相关,可能是一种潜在的肺癌肿瘤标志物。

肺癌患者恶病质的药物治疗与营养支持研究进展

恶病质是肺癌患者的一种常见并发症,它会加重化疗毒副作用、阻碍治疗计划、削弱化疗反应性、降低生活质量,增加并发症及死亡率,严重危害肺癌患者的生理、心理健康。肿瘤恶病质的发病原因与发病机制都极为复杂,使其治疗具有艰巨性与复杂性。控制肺癌患者的恶病质需要采取抗肿瘤治疗、抑制炎症反应、营养支持、体育锻炼、缓解症状等多种手段,发挥多模式治疗的协同作用对抗肿瘤恶病质的多种机制。迄今为止,学科内已就任何单一疗法都不能控制恶病质的发生发展达成了一致共识。有些疗法取得了一定的研究进展,但需要在充分评估肺癌患者个体特征后结合多模式治疗实施。本文重点综述了肿瘤恶病质的药物治疗与营养支持等干预方法在肺癌患者人群中的应用,并对肺癌患者恶病质控制的研究方向进行展望。

伴血管变异的腹腔镜右半结肠癌根治术个体化手术入路的多学科临床探讨

目的:探讨中结肠动脉(middle colic artery,MCA)和回结肠静脉(ileocolic vein,ICV)血管变异及对腹腔镜右半结肠癌根治术手术入路选择的多学科协作体系(multidisciplinary treatment,MDT)的诊治流程。方法:分析2018年3月天津医科大学肿瘤医院收治1例MCA和ICV血管变异的右半结肠癌患者的MDT诊疗过程。患者经MDT讨论后接受有限中间入路腹腔镜右半结肠癌根治术。观察指标:1)手术和术后恢复情况;2)术后病理学检查情况;3)随访情况。结果:1)手术和术后恢复情况:患者顺利完成有限中间入路腹腔镜右半结肠癌根治术,无术中和术后并发症发生。术后住院时间为11 d。2)术后病理学检查情况:淋巴结清扫数目为39枚。病理学分期为pT3N0,病理学类型为中分化腺癌。3)随访情况:术后随访时间为10个月,无瘤生存。结论:个体化手术是结肠外科未来的发展趋势。采取MDT有利于制定规范化、个体化的手术方案,探索更安全和精准的手术入路,从而让更多患者获益。

Cell cycle-related genes p57kip2, Cdk5 and Spin in the pathogenesis of neural tube defects

In the field of developmental neurobiology, accurate and ordered regulation of the cell cycle and apoptosis are crucial factors contributing to the normal formation of the neural tube. Preliminary studies identified several genes involved in the development of neural tube defects. In this study, we established a model of developmental neural tube defects by administration of retinoic acid to pregnant rats. Gene chip hybridization analysis showed that genes related to the cell cycle and apoptosis, signal transduction, transcription and translation regulation, energy and metabolism, heat shock, and matrix and cytoskeletal proteins were all involved in the formation of developmental neural tube defects. Among these, cell cycle-related genes were predominant. Retinoic acid treat-ment caused differential expression of three cell cycle-related genes p57kip2, Cdk5 and Spin, the expression levels of which were downregulated by retinoic acid and upregulated during normal neural tube formation. The results of this study indicate that cell cycle-related genes play an im-portant role in the formation of neural tube defects. P57kip2, Cdk5 and Spin may be critical genes in the pathogenesis of neural tube defects.

A Single Species Model with Symmetric Bidirectional Impulsive Diffusion and Dispersal Delay

In the natural ecosystem, impulsive diffusion provides a more natural description for population dynamics. In addition, dispersal processes often involve with time delay. In view of these facts, a single species model with impulsive diffusion and dispersal delay is formulated. By the stroboscopic map of the discrete dynamical system and other analysis methods, the permanence of the system is investigated. Moreover, sufficient conditions on the existence and uniqueness of a positive periodic solution for the system are derived from the intermediate value theorem. We also demonstrate the global stability of the positive periodic solution by the theory of discrete dynamical system. Finally, numerical simulations and discussion are presented to validate our theoretical results.

Imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 may contribute to hemorrhage in cerebellar arteriovenous malformations

In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cerebellar arteriovenous malformations or primary epilepsy （control group）. Immunohistochemistry and enzyme-linked immunosorbent assay revealed that the expression of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with cerebellar arteriovenous malformations than in patients with primary epilepsy. The ratio of matrix metalloproteinase-9 to matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with hemorrhagic cerebellar arteriovenous malformations compared with those with non-hemorrhagic malformations. Matrix metalloproteinase-2 and matrix metalloproteinase tissue inhibitor-2 levels were not significantly changed. These findings indicate that an imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-I, resulting in a relative overabundance of matrix metalloproteinase-9, might be the underlying mechanism of hemorrhage of cerebellar arteriovenous malformations.

Retinoic acid induction of genes associated with neural tube developmental defects

To date, little information has been available regarding genes involved in the regulation of embryonic cell development, which participate in retinoic acid-induced neural tube defects in mice. Previous studies have revealed seven differentially expressed genes involved in neural tube developmental defects. However, gene expression and regulation is a complex process. Therefore, gene expression differences between normal and defective neural tubes at 9.5 and 10.5 days were compared. A total of eight differentially expressed genes exhibited coincident alterations at embryonic 9.5 and 10.5 days. In mice with retinoic acid-induced neural tube defects, NeK7, IGFBP5 ZW10, Csf3r, PSMC6, Cdk5, and Rbl expressions were downregulated, but Apoa-4 expression was upregulated. These results were confirmed by Northern blot hybridization. Results suggested that NeK7, IGFBP5, ZW10, Csf3r, PSMC6, Cdk5, Rb1, and Apoa-4 are important regulatory factors involved in neural tube defects.

Gene expression in retinoic acid-induced neural tube defects A cDNA microarray analysis

BACKGROUND： Neural tube defects can be induced by abnormal factors in vivo or in vitro during development. However, the molecular mechanisms of neural tube defect induction, and the related gene expression and regulation are still unknown. OBJECTIVE： To compare the differences in gene expression between normal embryos and those with neural tube defects. DESIGN, TIME AND SETTING： A neural development study was performed at the Department of Neurobiology, Third Military Medical University of Chinese PLA between January 2006 and October 2007. MATERIALS： Among 120 adult Kunming mice, 60 pregnant mice were randomly and evenly divided into a retinoic acid group （n = 30） and a normal control group （n =30）. The retinoic acid was produced by Sigma, USA, the gene microarray by the Amersham Pharmacia Company, Hong Kong, and the gene sequence was provided by the Incyte database, USA. METHODS： Retinoic acid was administered to prepare models of neural tube defects, and corn oil was similarly administered to the normal control group. Total RNA was extracted from embryonic tissue of the two groups using a Trizol kit, and a cDNA microarray containing 1 100 known genes was used to compare differences in gene expression between the normal control group and the retinoic acid group on embryonic （E） day 10.5 and 11.5. Several differentially expressed genes were randomly selected from the two groups for Northern blotting, to verify the results of the cDNA microarray. MAIN OUTCOME MEASURES： Morphological changes and differential gene expression between the normal control group and the retinoic acid group. RESULTS： Anatomical microscopy demonstrated that an intact closure of the brain was formed in the normal mouse embryos by days E10.5 and E11.5. The cerebral appearance was full and smooth, and the surface of the spine was intact. However, in the retinoic acid group on days E10.5 and E11.5, there were more dead embryos. Morphological malformations typically included non-closure at the top of the cranium and abnormal changes of the metencephalon and face. cDNA microarray analysis suggested that the changes in expression of seven different genes were similar on both days E10.5 and E11.5. These were downregulation of NekT, Igfbp5, Zw10, Csf3r, Psmc6 and Rb 1, and upregulation of Apoa-4. This study also indicated that Cdk5 expression was downregulated in the retinoic acid group on day E11.5. The results of the cDNA microarray analysis were partly confirmed by Northern blotting. CONCLUSION： Cdk5, Nek7, Igfbp5, Zw10, Csf3r, Psmc6, Rb1 and Apoa-4 may be key factors in retinoic acid-induced neural tube defects.

Longitudinal assessment of peripheral organ metabolism and the gut microbiota in an APP/PS1 transgenic mouse model of Alzheimer’s disease

Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.

Quantification of perfluorinated compounds in atmospheric particulate shows potential connection with environmental event

A method of quantification of perfluorinated compounds(PFCs)from atmospheric particulate matter(APM)is described.A single step pretreatment method,selective pressurized liquid extraction(SPLE),was developed to reduce the high matrix background and avoid contamination from commonly used multiple sample pretreatment steps.An effective sorbent was selected to purify the PFCs during SPLE,followed by liquid chromatography-tandem mass spectrometry(LC–MS/MS),for quantification of PFCs.Conditions affecting the SPLE efficiency,including temperature,static extraction time,and number of extraction cycles used,were studied.The optimum conditions were found to be 120℃,10 min,and 3 cycles,respectively.LC-MS/MS method was developed to obtain the optimal sensitivity specific to PFCs.The method detection limits(MDLs)were 0.006 to 0.48 ng/g for the PFCs studied and the linear response range was from 0.1 to 100 ng/g.To ensure accurate values were obtained,each step of the experiment was evaluated and controlled to prevent contamination.The optimized method was tested by performing spiking experiments in natural particulate matter matrices and good rates of recovery and reproducibility were obtained for all target compounds.Finally,the method was successfully used to measure 16 PFCs in the APM samples collected in Beijing over five years from 2015 to 2019.It is observed that some PFCs follow the trend of total PFC changes,and can be attributed to the environment influencing events and policy enforcement,while others don't seem to change as much with time of the year or from year to year.

Applications of virus-induced gene silencing for identification of gene function in fruit

With the development of bioinformatics,it is easy to obtain information and data about thousands of genes,but the determi nation of the functions of these genes depends on methods for rapid and effective functi on al identification.Virus-induced gene sile ncing(VIGS)is a mature method of gene functional identification developed over the last 20 years,which has been widely used in many research fields involving many species.Fruit quality formation is a complex biological process,which is closely related to ripening.Here,we review the progress and contribution of VIGS to our understanding of fruit biology and its advantages and disadvantages in determining gene function.

Regulated adsorption sites using atomically single cluster over biochar for efficient elemental mercury uptake

Carbon-based materials have been widely used in gaseous pollutant removal because of their sufficient surface functional groups;however,its removal efficiency for elemental mercury(Hg^(0))is low.In this study,we fabricated biomass using a chelated coupled pyrolysis strategy and further constructed the regulated adsorption sites for gaseous Hg^(0) uptake.A series of Mnδ-N_(2)O_(2)/BC with different manganese cluster sizes demonstrated that manganese clusters anchored on biochar acted as highly active and durable adsorbents for Hg^(0) immobilization,which increased the adsorption efficiency of Hg^(0) by up to 50%.Shrimp-and crab-based biochar adsorbents exhibited excellent Hg^(0) removal because of their chitosan-like structure.In particular,small Mn clusters and oxygen species around the defect led to a boost in the Hg^(0) adsorption by carbon.The results of density functional theory calculation revealed that the presence of oxygen in the carbon skeleton can tune the electrons of small-sized Mn clusters,thereby promoting the affinity of mercury atoms.The newly developed Mnδ-N_(2)O_(2)/BC_(shrimp) had an adsorption capacity of 7.98-11.52 mg g^(−1) over a broad temperature range(50-200℃)and showed a high tolerance to different industrial flue gases(H_(2)O,NO,HCl,and SO_(2)).These results provide novel green and low-carbon disposal methods for biomass resource utilization and industrial Hg^(0) emission control.