Mannan-oligosaccharides (MOS), as indigestible functional prebiotic, support intestinal health. Here, we engineered MOS to undergo linoleic acid (LA)-mediated self-assembly with quercetin, forming lipid bilayer nanoparticles (MOS-LA/LA-Q NPs). These nanoparticles achieved a high quercetin encapsulation efficiency (92.4%) and demonstrated superior stability in aqueous solution at 4 °C. The MOS outer layer effectively protected the quercetin core from gastrointestinal stress. Triggered by microbial enzymes, the system enabled a sustained quercetin release, up to 60% over 48 h, representing a novel microbe-specific delivery mechanism. In an Alzheimer’s disease (AD) mice models induced by AlCl3/D-galactose, MOS-LA/LA-Q NPs significantly enhanced gut microbiota diversity, restored gut microbiota balance, suppressed pathogenic bacteria, and regulated metabolites short-chain fatty acid (SCFA) and lactic acid levels. Compared with free quercetin, these nanoparticles (NPs) alleviated cognitive deficits, reduced inflammation and oxidative stress in both the colon and brain, improved gut-brain barrier integrity, and restored gut-brain function more significantly. Mechanistically, these effects were associated with modulation of the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathways, reducing tau phosphorylation and Aβ amyloid levels, thus demonstrating superior neuroprotection. This study proposes a novel strategy for addressing the complex pathology of AD through multi-target intervention, highlighting the potential of MOS-based NPs to enhance quercetin’s therapeutic efficacy.

Background: Gut-brain axis dysfunction contributes to Alzheimer’s disease (AD) beyond amyloid/tau pathology, yet it remains unclear whether oral melatonin (MT) alleviates AD and gut comorbidities by modulating gut microbiota. Objective: To investigate whether oral MT improves cognitive impairment, brain pathology, and gut comorbidities in AD mice and to elucidate microbiota-dependent mechanisms inhibiting oxidative stress and ferroptosis. Methods: AD was induced in mice using AlCl₃/D-gal, followed by 6 weeks of oral melatonin (10 mg/kg/day). Cognitive function, oxidative stress, gut microbiota (16S rRNA), ferroptosis-related proteins, and fecal metabolites were assessed. Antibiotic intervention and fecal microbiota transplantation (FMT) validated microbiota dependency. Results: Oral MT reshaped gut microbiota and metabolites, significantly improving cognitive deficits, reducing brain Aβ 1-42 and P-tau, alleviating colonic iron overload and dysfunction, and attenuating gut-brain oxidative stress (increased CAT/T-SOD, decreased MDA). MT repaired intestinal and blood-brain barriers and inhibited central ferroptosis via the Keap-1/Nrf-2/HO-1 axis. Antibiotic-induced dysbiosis exacerbated AD pathology. Notably, FMT from MT-treated donors partially recapitulated MT’s protective effects, confirming that MT’s anti-AD actions are partially microbiota-dependent. Conclusion: Gut microbiota plays a key mediating role in MT’s inhibition of ferroptosis against AD. Oral MT shows therapeutic potential for managing AD-related gut-brain comorbidity, supporting microbiota-based AD treatment strategies.

The increased use of nanosilica (SiO2 NPs) poses a safety risk to public health. Current research on the tissue distribution and microbiota-gut-liver crosstalk toxicity of orally ingested SiO2 NPs remains poorly understood. In this study, we examined the distribution of SiO2 NPs by gavage in major organs as well as liver senescence and fibrotic injury induced by microbiota-gut-liver crosstalk following the sub-chronic oral ingestion thereof. In addition, probiotics were administered to investigate their protective potential against SiO2 NPs-induced hepatotoxicity. Our results showed that C57BL/6J mice that received orally administered SiO2 NPs for 12 w exhibited gut dysbiosis, imbalance of metabolites (short-chain fatty acids and lactate), intestinal barrier damage, and disruption of gut homeostasis. Furthermore, ICP-OES revealed the silicon accumulation in the Liver, with 165

Silica nanoparticles (SiO2 NPs) are widely used in the food and pharmaceutical industries and dramatically increase the health risks associated with gastrointestinal exposure. However, the neurotoxicological effects and mechanisms of exposure to SiO2 NPs and their relationship with the gut microbiome require further in-depth investigation. Here, we performed a systematic assessment of the toxicity of gavage containing 20 nm SiO2 NPs to C57BL/6 J mice. After 14 weeks administration, we comprehensively discovered that gastrointestinal exposure to SiO2 NPs led to mice Alzheimer’s disease (AD)-like neurotoxicity, including Aβ accumulation, cognitive impairment, oxidative stress burden, and neuroinflammation, which was microbiota-gut-brain axis-dependent and proven using a low-load gut-bacteria experiment and antibiotic treatment. Mechanistically, gastrointestinal exposure to SiO2 NPs disrupted intestinal homeostasis. Specifically, the total faecal short-chain fatty acid (SCFA) levels were reduced as analysed by 16S rRNA gene sequencing and liquid chromatography mass-spectrometry (LC–MS) analysis. The reduced SCFA content damaged the integrity of gut-brain axis by increasing gut permeability, which may have caused metabolite redistribution, brain basement membrane dissolution, activated the neuroinflammation signalling pathway TLR4/NF-κB, and interfered with HDAC3 and HDAC1/OGG1 pathways. We showed for the first time that gastrointestinal exposure to SiO2 NPs depends on the gut microbiome and causes neurological and cognitive impairment via gut-brain axis information transmission. These findings suggest that the gut microbiota, as a mediator between intestinal and brain information communications, contributes to gastrointestinal exposure to SiO2 NPs-induced neurotoxicity. The health risks of exposure to SiO2 NPs should be recognised, and addressing strategies should be extensively reconsidered.

Background: Oligopeptides from sea cucumber eggs (SCEPs) are rarely studied for their neuroprotective effects. Methods: Therefore, we prepared SCEPs via simulated gastrointestinal digestion and then administered them to an Alzheimer’s disease (AD) mouse model via gavage. Behavior tests, gut–brain histopathology and fecal microbiota transplantation (FMT) experiments were conducted, and gut microbiota and metabolite short-chain fatty acids (SCFAs) were evaluated via 16sRNA gene sequencing and LC-MS. Results: The results showed that both the SCEP and FMT groups experienced improvements in the cognitive impairments of AD and showed reduced levels of Aβ, P-Tau, GFAP, and NFL in the brain, especially in the hippocampus. SCEP remodeled the gut microbiota, increasing the relative abundances of Turicibacter and Lactobacillus by 2.7- and 4.8-fold compared with the model at the genus level. In the SCEP and FMT treatments, four SCFA-producing bacteria obtained from gut microbiota profiling showed consistent trends, indicating that they may be involved in mediating the neuroprotective effects of SCEP. Mechanically, SCEP regulated the SCFA distribution in feces, blood, and the brain, greatly increased the content of SCFAs in the brain up to 2000 μg/mg, eased gut–brain barrier dysfunction, inhibited HDAC3 overexpression, and upregulated BDNF/NT3 levels. Conclusions: This study provides a promising candidate for preventing AD and a reference for applying SCEP.

BACKGROUND:Lingguizhugan (LGZG) decoction, an ancient Chinese herbal remedy originating from the Eastern Han Dynasty, consists of Poria cocos, Cinnamomi ramulus, Atractylodes macrocephala, and Glycyrrhiza, as described in the Golden Chamber Synopsis. It has a history spanning over 1600 years, in which it has been primarily used for the treatment of inflammation, injuries, and fluid retention; however, the potential of LGZG decoction to ameliorate Alzheimer's disease (AD) progression by modulating the gut-brain axis through attenuation of gut microbiota and their metabolites remains unknown. PURPOSE:To examine the in vivo anti-AD effects and mechanism of LGZG decoction in alleviating AD cognitive impairment. STUDY DESIGN:Two-part experiments in vivo were designed, one for behavior tests, intestinal and brain histopathology, intestinal microbiome and quantitative determination, and another one for metabolite supplementation study. METHODS:AlCl3/D-gal was used to establish an AD-like mouse model. Behavioral tests, such as the Morris water maze test, were used to assess the effect of LGZG decoction on cognitive dysfunction. The concentration of proinflammatory mediators was measured by ELISA. The protein content was detected by western blot analysis and immunohistochemistry. The content of short-chain fatty acids was measured by LC-MS/MS. Evaluation of 16S rRNA gene sequencing for species and strain-level gut microbiome analysis was performed. RESULTS:LGZG decoction mitigated cognitive impairment in an AD-like mouse model, and decreased the deposition of amyloid-β and the production of proinflammatory cytokines in the brain. LGZG decoction remodeled the intestinal microecology, enhanced the integrity of the intestinal and brain tissue barriers, and modulated Aβ transportation through gut microbiota metabolite SCFAs. The neuroprotective effect of SCFAs on the AD-like model mice may be manifested through the inhibition of pP38 of the MAPK signaling pathway. CONCLUSION:Our results suggest that LGZG decoction reshapes the gut microbiota. SCFAs derived from the gut microbiota ameliorate the cognitive decline induced by AlCl3/D-gal through the gut-brain axis and reduce brain Aβ aggregation. We propose LGZG decoction as a potential therapeutic option for AD.

Preserving perishable fruits during transportation and storage is a critical challenge in modern logistics and supply chains. This study developed an antibacterial and unidirectional water-permeable tri-layered polylactic acid/ZnO composite film using green biosynthesis and electrospinning technologies to protect highly perishable non-climacteric fruits. The composite film, with encapsulated ZnO nanoparticles, exhibited exceptional antibacterial properties, achieving a 99.999 % inhibition rate against Escherichia coli and Staphylococcus aureus. Additionally, the film's unidirectional water permeability allowed water droplets to penetrate its surface within 1.10 s, ensuring effective moisture retention. When used to package strawberries, cherries, and grapes, the film significantly reduced decay and moisture loss, keeping strawberries fresh for 8 days and cherries and grapes for 12 days at room temperature. This polylactic acid/ZnO composite film shows great potential for enhancing the preservation of perishable fruits in packaging applications.

以青岛地铁1号线胶州湾过海隧道为研究背景,选取了影响复合式衬砌外围水压力的9个主要影响因素,在利用Midas有限元数值分析软件的基础上,采用正交试验设计法分析了 2种测试水平下这9个因素对水压力折减系数的显著性影响水平.结果表明:影响二次衬砌外围水压力大小的显著性因素为二次衬砌外围半径和围岩渗透系数与二次衬砌渗透系数的比值;影响初期支护外围水压力大小的显著性因素为围岩渗透系数与注浆圈渗透系数的比值、注浆圈厚度、围岩渗透系数与二次衬砌渗透系数的比值及隧道半径.其中,围岩渗透系数与二次衬砌渗透系数的比值对二次衬砌、初期支护的外围水压力均有显著性影响.因此,在海底隧道设计和施工过程中,应重点关注衬砌的渗透性能,注意支护结构的参数设计和选取,以保障海底隧道的顺利开挖及运营安全.

Background Trypanosomiasis is a highly lethal infectious disease caused by trypanosome, leading to a severe social and economic burden worldwide. Due to the lack of mechanism research, application of the promising nanomaterials and nanotechnologies in treatment of trypanosomiasis is limited. Results Herein, the toxicological effects induced by graphene quantum dots (GQDs) on T. brucei and the underlying mechanism are investigated. First, the biological/cytotoxic effects are evaluated, including endotytosis, cell viability, apoptosis, ROS production and morphological defects of subcellular organelles. Considering the few experimentally-determined 3D structures of T. brucei proteins, next, a computed structure database of T. brucei genome-wide proteins is constructed from I-TASSER, AlphaFold2 and MD simulation. Then, the database is used for docking with GQDs, and two goups of potential target proteins with transporter activity and antioxidant activity are screened out. Last, TryR stands out as a vital target due to its high binding energy with GQDs at active site and its key role in the trypanothione-dependent antioxidant network of T. brucei , which is further verified by theoretical (MD simulation) and experimental (BLI, inhibition of enzyme activity) means. Conclusions Evidences from this study suggest that GQD-induced cytotoxicity on T. brucei results from interference of GQDs with the lineage-specific antioxidant network with TryR as a key target. These findings provide theoretical insights into the rational design of nanomedical materials for trypanosomiasis.

Graphyne, a newly discovered carbon nanomaterial, has received increasing attention as a potential biomedical material. Although beta-rich peptide scaffolds have been implicated in a range of neurodegenerative diseases, the mechanisms by which toxic peptides assemble and mediate neuropathic effects remain poorly understood. Modeling the interaction between graphyne and beta-rich peptide scaffolds is crucial for understanding nanobiological effects or potential nanotoxicity and the safe design of graphyne as a nanomedicine material. Herein, we investigate the potential effects of graphyne on the assembly of A beta(33-42) peptides by molecular dynamics (MD) simulations. The A beta(33-42) peptide is considered to be the primary assembling core in the natural abnormal assembly of amyloid beta (A beta) proteins. The results show that A beta(33-42) strands are easily adsorbed to the graphyne surface and spontaneously aggregate into a well-structured beta-chain-like monolayer assembly through chain straightening, nucleation, and assembly processes in turn. The sp(1) and sp(2) hybrid orbitals in the carbon electronic structure of graphyne dominate the alignment of A beta(33-42) strands along the C C bonds with a specific "armchair" direction. Our findings deepen the understanding of the interaction between graphyne and biological macromolecules and provide implications for biomedical applications of graphyne.

Colon cancer (CC) is one of the most common malignant tumors worldwide. As there are no effective biomarkers for the early diagnosis and intervention tracking, the incidence of CC is increasing every year. Cholesterol is an important component of cell membrane, and it has been shown to be associated with CC. Oxysterol is an oxidized derivative of cholesterol, which plays an important role in many malignant tumors. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine serum cholesterol and ten oxysterol metabolites related to cholesterol in CC patients and healthy controls, and qualitative and quantitative analyses were carried out. Raw data were processed and analyzed using GraphPad Prism 8.3.0 and the MetaboAnalyst 5.0 platform (https://www.metaboanalyst.ca/MetaboAnalyst/ModuleView.xhtml). To perform the independent sample t-test, it was necessary to ensure that all the sample data followed a normal distribution; therefore, the normal distribution test was performed in advance. The Mann-Whitney U test, which is a nonparametric test, was adopted for samples without a normal distribution. For the processed data, we used the statistical analysis function module of the MetaboAnalyst 5.0 platform to perform partial least-square discriminant analysis (PLS-DA) and orthogonal partial least-square discriminant analysis (OPLS-DA). Both PLS-DA and OPLS-DA are supervised discriminant analysis methods. The OPLS-DA model is based on the PLS-DA model and eliminates variables that are unrelated to the experiment. In both models, the samples from the two groups were well separated by the score plot. In the PLS-DA model, the horizontal and vertical coordinates of the score plot represent the interpretation rates of the principal components of the model. The horizontal coordinates show the differences between groups, and the vertical coordinates show the differences within groups. In addition to the score plot in the PLS-DA model, another crucial factor is variable importance in the projection (VIP). When VIP>1, the compound makes an important contribution to the model and is also used as a criterion for screening differential metabolites. Based on 10-fold cross-validation (CV) of the PLS-DA model, the performance of the model was the best when the number of components was three. To avoid overfitting of the data, three metabolic markers were selected by using not only the VIP values of metabolites of the PLS-DA model, but also the optimal compositions and K-mean clusters. The three biomarkers were 4β-hydroxycholesterol (4β-OHC), cholestane-3β,5α,6β-triol (Triol), and cholesterol. A receiver operating characteristic (ROC) curve was constructed. The area under the curve (AUC) was generally between 0.5 and 1.0. In the case of AUC>0.5, the closer the AUC is to 1, the better is the performance of the model. In this study, the area under the ROC curve constructed jointly by the three metabolic markers was 0.998, indicating that their combined ability to predict CC was strong and that the diagnostic performance was excellent. In addition, to understand the role of the three metabolic markers in the pathogenesis of CC, the genes associated with the metabolic markers were identified using GeneCards (https://www.genecards.org/). Finally, 110 genes were identified. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the biological processes, metabolic pathways, and possible roles in the body. GO enrichment showed that the three markers are mainly distributed in the endoplasmic reticulum lumen and coated vesicles, and they are mainly involved in biological processes such as cholesterol metabolism, transportation, and low-density lipoprotein particle remodeling. Their molecular functions are cholesterol transfer activity and low-density lipoprotein particle receptor binding. KEGG pathway analysis showed that biomarkers are enriched in steroid biosynthesis, PPAR (peroxisome proliferator-activated receptor) signaling pathways, and ABC (ATP-binding cassette) transport pathways. The results of this study are helpful to understand the role of cholesterol and oxysterol in the pathogenesis of CC and to elucidate the pathogenesis of CC.

为防范地铁深基坑开挖对紧邻运营中的轻轨桥桩产生影响,以大连市地铁5号线车站工程为依托,通过有限元软件Midas-GTS数值模拟与现场监测数据对比分析深基坑开挖对临近桩基产生的附加位移影响,并研究在不同基坑和桥桩距离、不同围护墙刚度及采取加固措施等情况下临近桥桩桩身侧移的变化规律.结果表明:基坑和桥桩距离越大及围护墙刚度越大时,桩身侧移越小;采取三重管高压旋喷桩加固措施使得桩身附加位移减小49.05％,最终降低至城市铁路桥梁规范要求以内.研究结论可为类似深基坑开挖过程中对紧邻桥桩产生的位移变化趋势提供价值.

氧固醇是在人体内形成或摄入饮食中的胆固醇的氧化衍生物,是当前分子流行病学和肿瘤学探索的目标之一.氧固醇具有多种功能,能够调节肝脏X受体(liver X receptor,LXR)、氧固醇结合蛋白(oxysterol binding protein,OSBP)及其相关蛋白(oxysterol binding protein-related proteins,ORPs)等受体的活性,进而参与胆固醇代谢、调节酶活性、介导细胞内信号传导途径.现有的证据表明,氧固醇及其结合蛋白与包括癌症在内的许多人类疾病有关,但氧固醇家族成员功能复杂,其在不同癌症病理发展中的作用尚未有定论.针对这一问题,本文总结了氧固醇家族及其OSBP/ORPs在主要癌症中的作用,为进一步研究氧固醇分子及其受体在癌症进展中的机理和针对性的诊断治疗提供基础.

为简化计算和分析围护墙的变形,以等厚度型钢混凝土搅拌墙为例,探索一种新的方法.该方法利用静力学中的力平衡原理,将TRD围护墙中的型钢以及混凝土这2种材料等效为1种规则截面的第3种材料.利用有限元软件建立不同墙厚、型钢间距及型钢规格下的4组模型,并对其进行对比分析后表明利用原始参数建立模型得到的结果与利用等效参数建立模型得到的结果相吻合.在进行TRD围护墙变形计算时,将该方法运用其中,可使计算更加简便.

硫酸化(Sulfation)是人体内主要的共轭途径之一,它们是由胞浆磺基转移酶(sulfotrans-ferase,SULT)超家族成员催化的重要Ⅱ期反应,在人体代谢中具有重要作用.本文总结了目前人体内存在的13种SULT的组织分布和功能的相关信息,并结合目前国内外相关报道,综述了SULT在几种临床药物代谢中的影响与作用,期待为今后的药物研发和临床研究提供一定的帮助.

本着进一步完善和优化分子生物学实验课程的教学内容,加强本科生实验操作技能,提高本科生生物学综合创新思维能力,该文总结设计了以实时荧光定量PCR(Real-time PCR,RT-PCR)为主题的"小综合"实验,以期通过课程的实施,激发学生的学习兴趣,提高教学质量,取得良好的教学效果.

生物技术专业发展方向分支众多,针对生物技术专业生物制药方向,其方向课程教学模式需多元化改革.本文以本校生物技术专业方向课生物制药工艺学为例,探讨当下可行的教学模式,旨在为相关专业方向课教学提供借鉴.

胆汁酸以其在吸收脂肪和脂溶性维生素方面的功能而闻名.然而,胆汁酸也是调节胆固醇、葡萄糖和能量稳态的重要信号分子,并且是人体与肠道微生物代谢之间的关键中间分子.胆汁酸循环的稳态与人体代谢和免疫功能密切相关.但胆汁酸家族成员的化学结构多样,并且在复杂生物基质的样品中以较低的浓度存在.因此,精确测量这些重要代谢物意义重大,尽管酶法测定总胆汁酸在临床实验室中最为普遍,但这些方法只提供了有限的胆汁酸信息.先进的分析方法,如气相色谱和液相色谱-质谱技术,是高度信息丰富的技术,有助于识别和量化复杂生物基质中的个别胆汁酸.本文对几种利用色谱技术定量分析胆汁酸的方法进行了综述.

硫酸化(sulfation)是人体内的主要共轭途径之一,它负责脱毒并从宿主体内清除有毒外源性化学物质和内源性小分子.人体内硫酸化反应主要由胞浆磺基转移酶(sulfotransferase,SULT)超家族成员催化的,此反应对于维持体内内源性小分子与外源性化合物的稳态具有重要作用.本文结合国内外关于SULT的报道,综述了SULT对癌症、脂质代谢紊乱等疾病的重要作用,最后对SULT的发展趋势和应用前景做出了展望.