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Background Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive decline in cognitive ability. Exosomes derived from bone-marrow mesenchymal stem cells (BMSC-exos) are extracellular vesicles that can execute the function of bone-marrow mesenchymal stem cells (BMSCs). Given the versatile therapeutic potential of BMSC and BMSC-exos, especially their neuroprotective effect, the aim of this study was to investigate the potential effect of BMSC-exos on AD-like behavioral dysfunction in mice and explore the possible molecular mechanism. Methods BMSC-exos were extracted from the supernatant of cultured mouse BMSCs, which were isolated from the femur and tibia of adult C57BL/6 mice, purified and sorted via flow cytometry, and cultured in vitro. BMSC-exos were identified via transmission electron microscopy, and typical marker proteins of exosomes were also detected via Western blot. A sporadic AD mouse model was established by intracerebroventricular injection of streptozotocin (STZ). Six weeks later, BMSC-exos were administered via lateral ventricle injection or caudal vein injection lasting five consecutive days, and the control mice were intracerebroventricularly administered an equal volume of solvent. Behavioral performance was observed via the open field test (OFT), elevated plus maze test (EPM), novel object recognition test (NOR), Y maze test (Y-maze), and tail suspension test (TST). The mRNA and protein expression levels of IL-1β, IL-6, and TNF-α in the hippocampus were measured via quantitative polymerase chain reaction (qPCR) and Western blot, respectively. Moreover, the protein expression of Aβ 1-42 , BACE, IL-1β, IL-6, TNF-α, GFAP, p-Tau (Ser396), Tau5, synaptotagmin-1 (Syt-1), synapsin-1, and brain-derived neurotrophic factor (BDNF) in the hippocampus was detected using Western blot, and the expression of GFAP, IBA1, Aβ 1−42 and DCX in the hippocampus was measured via immunofluorescence staining. Results Lateral ventricle administration, but not caudal vein injection of BMSC-exos improved AD-like behaviors in the STZ-injected mouse model, as indicated by the increased number of rearing, increased frequency to the central area, and increased duration and distance traveled in the central area in the OFT, and improved preference index of the novel object in the NOR. Moreover, the hyperactivation of microglia and astrocytes in the hippocampus of the model mice was inhibited after treatment with BMSC-exos via lateral ventricle administration, accompanied by the reduced expression of IL-1β, IL-6, TNF-α, Aβ 1-42, and p-Tau and upregulated protein expression of synapse-related proteins and BDNF. Furthermore, the results of the Pearson test showed that the preference index of the novel object in the NOR was positively correlated with the hippocampal expression of BDNF, but negatively correlated with the expression of GFAP, IBA1, and IL-1β. Apart from a positive correlation between the hippocampal expression of BDNF and Syt-1, BDNF abundance was found to be negatively correlated with markers of glial activation and the expression of the inflammatory cytokines, Aβ 1-42 , and p-Tau, which are characteristic neuropathological features of AD. Conclusions Lateral ventricle administration, but not caudal vein injection of BMSC-exos, can improve AD-like behavioral performance in STZ-injected mice, the mechanism of which might be involved in the regulation of glial activation and its associated neuroinflammation and BDNF-related neuropathological changes in the hippocampus.

Ischemic stroke is one of the leading causes of mortality and disability worldwide. However, there is a current lack of effective therapies available. As the resident macrophages of the brain, microglia can monitor the microenvironment and initiate immune responses. In response to various brain injuries, such as ischemic stroke, microglia are activated and polarized into the proinflammatory M1 phenotype or the anti-inflammatory M2 phenotype. The immunomodulatory molecules, such as cytokines and chemokines, generated by these microglia are closely associated with secondary brain damage or repair, respectively, following ischemic stroke. It has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke. In addition, autophagy is also reportedly involved in the pathology of ischemic stroke through regulating the activation and function of microglia. Therefore, this review aimed to provide a comprehensive overview of microglia activation, their functions and changes, and the modulators of these processes, including transcription factors, membrane receptors, ion channel proteins and genes, in ischemic stroke. The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified.

This article discusses the use of distributed acoustic sensing (DAS) for monitoring gas–liquid two-phase slug flow in horizontal pipes, using standard telecommunication fiber optics connected to a DAS integrator for data acquisition. The experiments were performed in a 14 m long, 5 cm diameter transparent PVC pipe with a fiber cable helically wrapped around the pipe. Using mineral oil and compressed air, the system captured various flow rates and gas–oil ratios. New algorithms were developed to characterize slug flow using DAS data, including slug frequency, translational velocity, and the lengths of slug body, slug unit, and the liquid film region that had never been discussed previously. This study employed a high-speed camera next to the fiber cable sensing section for validation purposes and achieved a good correlation among the measurements under all conditions tested. Compared to traditional multiphase flow sensors, this technology is non-intrusive and offers continuous, real-time measurement across long distances and in harsh environments, such as subsurface or downhole conditions. It is cost-effective, particularly where multiple measurement points are required. Characterizing slug flow in real time is crucial to many industries that suffer slug-flow-related issues. This research demonstrated the DAS’s potential to characterize slug flow quantitively. It will offer the industry a more optimal solution for facility design and operation and ensure safer operational practices.

The therapeutic landscape for recurrent or metastatic cervical cancer remains limited, with few options available. According to National Comprehensive Cancer Network (NCCN) guidelines, pembrolizumab combined with chemotherapy, with or without bevacizumab, is recommended for affected patients. Despite these guidelines, recurrence rates remain elevated, and survival outcomes following standard interventions are unsatisfactory. Furthermore, real-world management of recurrent or metastatic cervical cancer presents inherent complexities, often requiring an integrative, multidimensional treatment approach to enhance long-term survival. The pressing need to refine and adopt multimodal therapeutic strategies is evident in addressing the persistent challenges associated with disease recurrence and progression. The case involved a 40-year-old female diagnosed with advanced cervical cancer who underwent radical hysterectomy. Postoperative pathology identified high-risk features, including lymph node involvement, necessitating adjuvant chemoradiotherapy. However, disease progression occurred during treatment, manifesting as metastases in the left supraclavicular and axillary lymph nodes. Subsequent local radiotherapy and systemic therapy led to a favorable response. By November 2024, overall survival (OS) had surpassed 72 months, with toripalimab administered for 65 months, during which no immunotherapy-related adverse events occurred. This case offers clinical insight into the efficacy and safety of integrating chemotherapy, immunotherapy, and radiotherapy in recurrent or metastatic cervical cancer. The multimodal approach contributes to prolonged survival in this patient. Further clinical trials are essential to substantiate the therapeutic benefits of this regimen in broader patient cohorts.

Wenshenyang decoction (WSY) has been shown to have a considerable effect on restoring renal function and improving kidney Yang deficiency syndrome in patients with CKD. However, its mechanism remains unclear. This study aimed to integrated metabolomics and network pharmacology analysis combined with experiments to reveal the mechanisms. Patients were selected from a clinical trial. LC-MS (Liquid chromatography-mass spectrometry) was used to investigate the differential metabolites and pathways. Spearman correlation analysis was performed between differential metabolites and clinical phenotypes. \"Drug-component-differential metabolite\" network was constructed to predict the core components and hub genes, and validated by molecular docking. On this basis, the effects of core components of WSY on the viability of Human Kidney-2 cells (HK-2) induced by doxorubicin (DOX) was detected by CCK-8, and RT-qPCR (Reverse transcription quantitative polymerase chain reaction) was used to detect the mRNA expression level of hub genes and related targets. LC-MS detected 54 differential metabolites, of which 35 metabolites showed up regulated, and 19 decreased. Spearman analysis showed that the differential metabolites were correlated with the clinical phenotype. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis showed that WSY mainly affected linoleic acid metabolism, FcεRI signaling pathway, and unsaturated fatty acid biosynthesis. The \"Drug-component-differential metabolite\" network showed that the core components of WSY were quercetin, luteolin and kaempferol, and the hub genes were PTGS2, AKT1, MMP9, EGFR and MMP2. Molecular docking showed that they had good biological binding capacity. cell experiments further showed that quercetin, luteolin and kaempferol could significantly activate the cells and reduce the mRNA levels of PTGS2, AKT1, MMP9, EGFR, MMP2, and ANGPTL4, and increase the level of FGFR1, SIRT3 and the glucocorticoid receptor (GR). WSY has multi-component and multi-target properties in the treatment of CKD kidney Yang deficiency syndrome, and its mechanism may be related to anti-inflammatory and anti-fibrotic effects. This study provides a methodological reference for the treatment of CKD.

The task of automatic document summarization aims at generating short summaries for originally long documents. A good summary should cover the most important information of the original document or a cluster of documents, while being coherent, non-redundant and grammatically readable. Numerous approaches for automatic summarization have been developed to date. In this paper we give a self-contained, broad overview of recent progress made for document summarization within the last 5 years. Specifically, we emphasize on significant contributions made in recent years that represent the state-of-the-art of document summarization, including progress on modern sentence extraction approaches that improve concept coverage, information diversity and content coherence, as well as attempts from summarization frameworks that integrate sentence compression, and more abstractive systems that are able to produce completely new sentences. In addition, we review progress made for document summarization in domains, genres and applications that are different from traditional settings. We also point out some of the latest trends and highlight a few possible future directions.

The development of next-generation sequencing technology has enabled researchers to explore and understand the gut microbiome from a broader and deeper perspective. However, the results of different studies on gut microbiota are highly variable even in the same disease, which makes it difficult to guide clinical diagnosis and treatment. The ideal sampling method should be non-invasive, involve little cross-contamination or bowel preparation, and collect gut microbiota at different sites. Currently, sequencing technologies are usually based on samples collected from feces, mucosal biopsy, intestinal fluid, etc. However, different parts of the gastrointestinal tract possess various physiological characteristics that are essential for particular species of living microbiota. Moreover, current sampling methods are somewhat defective. For example, fecal samples are just a proxy for intestinal microbiota, while biopsies are invasive for patients and not suitable for healthy controls. In this review, we summarize the current sampling methods and their advantages and shortcomings. New sampling technologies, such as the Brisbane Aseptic Biopsy Device and the intelligent capsule, are also mentioned to inspire the development of future precise description methods of the gut microbiome.

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug that leads to severe hepatotoxicity at excessive doses. Fucoidan, a sulfated polysaccharide derived from brown seaweeds, possesses a wide range of pharmacological properties. However, the impacts of fucoidan on APAP-induced liver injury have not been sufficiently addressed. In the present study, male Institute of Cancer Research (ICR) mice aged 6 weeks were subjected to a single APAP (500 mg/kg) intraperitoneal injection after 7 days of fucoidan (100 or 200 mg/kg/day) or bicyclol intragastric administration. The mice continued to be administered fucoidan or bicyclol once per day, and were sacrificed at an indicated time. The indexes evaluated included liver pathological changes, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum, levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) in the liver, and related proteins levels (CYP2E1, pJNK and Bax). Furthermore, human hepatocyte HL-7702 cell line was used to elucidate the potential molecular mechanism of fucoidan. The mitochondrial membrane potential (MMP) and nuclear factor-erythroid 2-related factor (Nrf2) translocation in HL-7702 cells were determined. The results showed that fucoidan pretreatment reduced the levels of ALT, AST, ROS, and MDA, while it enhanced the levels of GSH, SOD, and CAT activities. Additionally, oxidative stress-induced phosphorylated c-Jun N-terminal protein kinase (JNK) and decreased MMP were attenuated by fucoidan. Although the nuclear Nrf2 was induced after APAP incubation, fucoidan further enhanced Nrf2 in cell nuclei and total expression of Nrf2. These results indicated that fucoidan ameliorated APAP hepatotoxicity, and the mechanism might be related to Nrf2-mediated oxidative stress.

Arsenic exposure model of offspring mice was established and intervened with 6-chlorobenzo[d]isoxazol-3-ol (CBIO), a D-amino acid oxidase (DAAO) inhibitor, to explore the role of DAAO in cognitive impairment of offspring mice induced by arsenic during early developmental stage. Female mice and their pups treated with 0 or 60 mg/L sodium arsenite (NaAsO 2 ) via drinkable water from the first day of gestation till the end of lactation. On the 28th day after birth, the offspring mice in the drinking distilled water group were randomly divided into control and 1 mg/mL CBIO group. The offspring mice in the arsenic group were divided into 60 mg/L NaAsO 2 group and 60 mg/L NaAsO 2  + 1 mg/mL CBIO group, CBIO was administered to the lateral ventricle for one week. Additionally, D-serine and L-serine concentrations were detected by UHPLC-MS/MS, Real-time RT-PCR and Western blot were applied to measure DAAO, serine racemase (SR), N-methyl-D-aspartate receptor (NMDAR), synaptophysin (SYP) and postsynaptic density (PSD95) levels in the hippocampus. Results disclosed that arsenic could reduce the levels of D-serine, L-serine, SR and NMDAR, while upregulate DAAO levels, however, inhibiting DAAO levels could increase D-serine and NR1 levels. These findings indicated that DAAO might be involved in cognitive impairment of offspring mice induced by arsenic during early developmental stage by affecting D-serine metabolism.

Background: With the continuous large-scale development of the COVID-19 vaccine, the acceptance of vaccination and its influencing factors at the individual level have become crucial to stemming the pandemic. This study aims to explore the factors that influence the acceptance of the COVID-19 vaccine among international college students. Methods: The target population constituted international students pursuing various degrees in Jiangsu Province through an online cross-sectional study. A cluster random sampling was performed using a self-administered questionnaire. The Health Belief Model and Knowledge, Attitude/Beliefs, and Practice Theory served as the underlying theories to understanding the factors that influence vaccine acceptance. Results: We received 330 responses. About 36.4% intended to accept the vaccine. The acceptance varied across respondents’ place of residence, program of study, continent of origin, knowledge, susceptibility, severity, benefits, and cues to action (p < 0.05). A multivariable logistics regression revealed cues to action (p < 0.001), the perception of COVID-19 vaccination benefits (p = 0.002), and the perception of barriers (p < 0.001) that were associated with vaccine acceptance. Conclusions: The acceptance of the COVID-19 vaccine was low among international students. The correct and comprehensive beliefs of the target groups regarding the benefits and barriers of the vaccination must be raised. Various effective social strategies must be adopted to trigger the intention of COVID-19 vaccination. The study findings will inform the decisions of public health campaigners, aimed at reducing vaccine hesitation when the COVID-19 vaccine is widely available.