Efficacy of virtual reality exercise in knee osteoarthritis rehabilitation: a systematic review and meta-analysis.

Background: This systematic review and meta-analysis aims to investigate the effects of virtual reality (VR) exercise compared to traditional rehabilitation on pain, function, and muscle strength in patients with knee osteoarthritis (KOA). Additionally, the study explores the mechanisms by which VR exercise contributes to the rehabilitation of KOA patients. Methods: We systematically searched PubMed, the Cochrane Library, Embase, Web of Science, Scopus, and PEDro according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our search spanned from the library construction to 24 May 2024, focusing on randomized controlled trials Primary outcomes included pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and muscle strength. Meta-analysis was conducted using RevMan (version 5.4) and Stata (version 14.0). The bias risk of included studies was assessed using the Cochrane RoB 2.0 tool, while the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: This meta-analysis and systematic review included nine studies involving 456 KOA patients. The results indicated that VR exercise significantly improved pain scores (SMD, -1.53; 95% CI: -2.50 to -0.55; p = 0.002), WOMAC total score (MD, -14.79; 95% CI: -28.26 to -1.33; p = 0.03), WOMAC pain score (MD, -0.93; 95% CI: -1.52 to -0.34; p = 0.002), knee extensor strength (SMD, 0.51; 95% CI: 0.14 to 0.87; p = 0.006), and knee flexor strength (SMD, 0.65; 95% CI: 0.28 to 1.01; p = 0.0005), but not significantly for WOMAC stiffness (MD, -0.01; 95% CI: -1.21 to 1.19; p = 0.99) and physical function (MD, -0.35; 95% CI: -0.79 to -0.09; p = 0.12). Conclusion: VR exercise significantly alleviates pain, enhances muscle strength and WOMAC total score in KOA patients, but improvements in joint stiffness and physical function are not significant. However, the current number of studies is limited, necessitating further research to expand on the present findings. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024540061, identifier CRD42024540061.

Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening.

Mitochondria are key regulators of hematopoietic stem cell (HSC) homeostasis. Our research identifies the transcription factor Nynrin as a crucial regulator of HSC maintenance by modulating mitochondrial function. Nynrin is highly expressed in HSCs under both steady-state and stress conditions. The knockout Nynrin diminishes HSC frequency, dormancy, and self-renewal, with increased mitochondrial dysfunction indicated by abnormal mPTP opening, mitochondrial swelling, and elevated ROS levels. These changes reduce HSC radiation tolerance and promote necrosis-like phenotypes. By contrast, Nynrin overexpression in HSCs diminishes irradiation (IR)-induced lethality. The deletion of Nynrin activates Ppif, leading to overexpression of cyclophilin D (CypD) and further mitochondrial dysfunction. Strategies such as Ppif haploinsufficiency or pharmacological inhibition of CypD significantly mitigate these effects, restoring HSC function in Nynrin-deficient mice. This study identifies Nynrin as a critical regulator of mitochondrial function in HSCs, highlighting potential therapeutic targets for preserving stem cell viability during cancer treatment.

The choroid plexus maintains adult brain ventricles and subventricular zone neuroblast pool, which facilitates poststroke neurogenesis.

The brain's neuroreparative capacity after injuries such as ischemic stroke is partly contained in the brain's neurogenic niches, primarily the subventricular zone (SVZ), which lies in close contact with the cerebrospinal fluid (CSF) produced by the choroid plexus (ChP). Despite the wide range of their proposed functions, the ChP/CSF remain among the most understudied compartments of the central nervous system (CNS). Here, we report a mouse genetic tool (the ROSA26iDTR mouse line) for noninvasive, specific, and temporally controllable ablation of CSF-producing ChP epithelial cells to assess the roles of the ChP and CSF in brain homeostasis and injury. Using this model, we demonstrate that ChP ablation causes rapid and permanent CSF volume loss in both aged and young adult brains, accompanied by disruption of ependymal cilia bundles. Surprisingly, ChP ablation did not result in overt neurological deficits at 1 mo postablation. However, we observed a pronounced decrease in the pool of SVZ neuroblasts (NBs) following ChP ablation, which occurs due to their enhanced migration into the olfactory bulb. In the middle cerebral artery occlusion model of ischemic stroke, NB migration into the lesion site was also reduced in the CSF-depleted mice. Thus, our study establishes an important role of ChP/CSF in regulating the regenerative capacity of the adult brain under normal conditions and after ischemic stroke.

The influence of maternal and paternal parenting on adolescent brain structure.

BACKGROUND: Adolescents raised in families with different maternal and paternal parenting combinations exhibit variations in neurocognition and psychopathology; however, whether neural differences exist remains unexplored. This study used a longitudinal twin sample to delineate how different parenting combinations influence adolescent brain structure and to elucidate the genetic contribution. METHODS: A cohort of 216 twins participated in parenting assessments during early adolescence and underwent MRI scanning during middle adolescence. We utilized latent profile analysis to distinguish between various maternal and paternal parenting profiles and subsequently investigated their influences on brain anatomy. Biometric analysis was applied to assess the genetic influences on brain structure, and associations with internalizing symptoms were explored. RESULTS: In early adolescence, four parenting profiles emerged characterized by levels of harshness and hostility in one or both parents. Compared to adolescents in "catparent" families (low harshness/hostility in both parents), those raised in "tigermom" families (harsh/hostile mother only) exhibited smaller nucleus accumbens volume and larger temporal cortex surface area; those in "tigerdad" families demonstrated larger thalamus volumes; those in "tigerparent" families displayed smaller volumes in the mid-anterior corpus callosum. Genetic risk factors contributed significantly to the observed brain structural heterogeneity and internalizing symptoms. However, the influences of parenting profiles and brain structure on internalizing symptoms were not significant. CONCLUSIONS: The findings underscore distinct brain structural features linked to maternal and paternal parenting combinations, particularly in terms of subcortical volume and cortical surface area. This study suggests an interdependent role of maternal and paternal parenting in shaping adolescent neurodevelopment.

A new subtype of artificial cell-derived vesicles from dental pulp stem cells with the bioequivalence and higher acquisition efficiency compared to extracellular vesicles.

Extracellular vesicles (EVs) derived from dental pulp stem cells (DPSC) have been shown an excellent efficacy in a variety of disease models. However, current production methods fail to meet the needs of clinical treatment. In this study, we present an innovative approach to substantially enhance the production of 'Artificial Cell-Derived Vesicles (ACDVs)' by extracting and purifying the contents released by the DPSC lysate, namely intracellular vesicles. Comparative analysis was performed between ACDVs and those obtained through ultracentrifugation. The ACDVs extracted from the cell lysate meet the general standard of EVs and have similar protein secretion profile. The new ACDVs also significantly promoted wound healing, increased or decreased collagen regeneration, and reduced the production of inflammatory factors as the EVs. More importantly, the extraction efficiency is improved by 16 times compared with the EVs extracted using ultracentrifuge method. With its impressive attributes, this new subtype of ACDVs emerge as a prospective candidate for the future clinical applications in regenerative medicine.

Causal inference and mechanism for unraveling the removal of four pesticides from lettuce (Lactuca sativa L.) via ultrasonic processing and various immersion solutions.

This study explores the reduction of carbamates (CAs) and pyrethroids (PYs) - commonly used pesticides - in lettuce using various immersion solutions and ultrasonic processing. It also examines the role of machine learning and molecular docking in understanding the mechanisms of pesticide reduction. The results revealed that the highest reduction of both CAs and PYs exceeded 80 % on lettuce leaves. In most samples, the reduction increased with the power of ultrasonic processing and processing time. The results of machine learning models (XGBoost and SHAP) showed that during the immersion cleaning of CAs and PYs, as well as during both immersion cleaning and ultrasonic processing of CAs + PYs, the reduction was most influenced by the initial pesticide levels and immersion time. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of lettuce's wax layer identified 24 compounds, including fatty alcohols, fatty acids, fatty acid esters, and triterpenoids. Despite the absence of active sites, the lipophilic nature of long-chain aliphatic compounds aids in pesticide binding, while triterpenoids form strong hydrogen bonds with pesticides, indicating a robust adsorption on the lettuce surface. This study aims to offer insights into the efficient removal of chemical pesticide residues from fruits and vegetables, addressing critical concerns for food safety and human health.

Platinum single atom on CsPbBr3 nanocrystals as electrocatalyst boosts electrochemical sensing of ascorbic acid.

Monitoring ascorbic acid (AA) levels in human body can provide valuable clues for disease diagnosis. Anchoring noble metal single atoms on perovskite substrate is a promising strategy to design electrocatalysts with outstanding electrocatalytic performance. Herein, we design an electrochemical method for detecting AA by utilizing Pt single atoms-doped CsPbBr3 nanocrystals (Pt SA/CsPbBr3 NCs) fixed on a glassy carbon electrode as an electrochemical catalyst. The uncharged 3,5,3',5'-tetramethylbenzidine (TMB) undergoes oxidation to form the positively charged oxidized TMB (oxTMB) owing to the exceptional electrochemical catalytic performance of Pt SA/CsPbBr3 NCs. Subsequently, the target AA reduces oxTMB to TMB, which is then electrocatalytically oxidized to oxTMB, producing significant oxidation current. In this way, such characteristic provides a sensitive electrochemical strategy for AA detection, achieving a concentration range of 50-fold with the detection limit of 0.0369 µM. The developed electrochemical method also successfully generates accurate detection response of AA in complex sample media (urine). Overall, this approach is expected to offer a novel way for early disease diagnosis.

Impact of mobile application and outpatient follow-up on renal endpoints and physiological indices in patients with chronic kidney disease: a retrospective cohort study in Southwest China.

BACKGROUND: Chronic kidney disease (CKD) is a significant public health concern, and patient self-management is an effective approach to manage the condition. Mobile applications have been used as tools to assist in improving patient self-management, but their effectiveness in long-term outpatient follow-up management of patients with CKD remains to be validated. This study aimed to investigate whether using a mobile application combined with traditional outpatient follow-up can improve health outcomes of patients with CKD . METHODS: This retrospective cohort study recruited CKD patients with stage 1-5 who were not receiving renal replacement therapy from a CKD management center. Two groups were established: the APP + outpatient follow-up group and the traditional outpatient follow-up group. Baseline data was collected from January 2015 to December 2019, followed by a three-year long-term follow-up until December 2022. Laboratory data, all-cause mortality, and renal replacement treatment were then collected and compared between the two groups. RESULTS: 5326 patients were included in the study, including 2492 in the APP + outpatient group and 2834 in the traditional outpatient group. After IPTW virtualization matching, the final matched the APP + outpatient group consisted of 2489 cases (IQR, 33-55) and 2850 (IQR, 33-55) in the traditional outpatient group. By the end of the study, it was observed that the laboratory data of Phosphorus, Sodium, Triglyceride, Hemoglobin showed significant improvements, Furthermore the APP + outpatient group demonstrated superior results compared to the traditional outpatient group (P < .05). And it was observed that there were 34 deaths (1.4%) in the APP + outpatient group and 46 deaths (1.6%) in the traditional outpatient group(P = .49). After matching for renal replacement therapy outcomes, the two groups were found to be comparable (95% CI [0.72-1.08], P = .23), with no significant difference. However, it was noted that the traditional outpatient group had a lower incidence of using temporary catheters during initial hemodialysis (95% CI [8.4-29.8%], P < .001). CONCLUSION: The development and application of an app combined with outpatient follow-up management can improve patient health outcomes. However, to ensure optimal preparation for kidney replacement therapy, patients in CKD stages 4-5 may require more frequent traditional outpatient follow-ups, and further develop an information-based decision-making support tool for renal replacement therapy.

Maize straw increases while its biochar decreases native organic carbon mineralization in a subtropical forest soil.

Organic soil amendments have been widely adopted to enhance soil organic carbon (SOC) stocks in agroforestry ecosystems. However, the contrasting impacts of pyrogenic and fresh organic matter on native SOC mineralization and the underlying mechanisms mediating those processes remain poorly understood. Here, an 80-day experiment was conducted to compare the effects of maize straw and its derived biochar on native SOC mineralization within a Moso bamboo (Phyllostachys edulis) forest soil. The quantity and quality of SOC, the expression of microbial functional genes concerning soil C cycling, and the activity of associated enzymes were determined. Maize straw enhanced while its biochar decreased the emissions of native SOC-derived CO2. The addition of maize straw (cf. control) enhanced the O-alkyl C proportion, activities of ß-glucosidase (BG), cellobiohydrolase (CBH) and dehydrogenase (DH), and abundances of GH48 and cbhI genes, while lowered aromatic C proportion, RubisCO enzyme activity, and cbbL abundance; the application of biochar induced the opposite effects. In all treatments, the cumulative native SOC-derived CO2 efflux increased with enhanced O-alkyl C proportion, activities of BG, CBH, and DH, and abundances of GH48 and cbhI genes, and with decreases in aromatic C, RubisCO enzyme activity and cbbL gene abundance. The enhanced emissions of native SOC-derived CO2 by the maize straw were associated with a higher O-alkyl C proportion, activities of BG and CBH, and abundance of GH48 and cbhI genes, as well as a lower aromatic C proportion and cbbL gene abundance, while biochar induced the opposite effects. We concluded that maize straw induced positive priming, while its biochar induced negative priming within a subtropical forest soil, due to the contrasting microbial responses resulted from changes in SOC speciation and compositions. Our findings highlight that biochar application is an effective approach for enhancing soil C stocks in subtropical forests.

TL1A Promotes Fibrogenesis in Colonic Fibroblasts via the TGF-ß1/Smad3 Signaling Pathway.

OBJECTIVE: Intestinal fibrosis is a refractory complication of inflammatory bowel disease (IBD). Tumor necrosis factor ligand-related molecule-1A (TL1A) is important for IBD-related intestinal fibrosis in a dextran sodium sulfate (DSS)-induced experimental colitis model. This study aimed to explore the effects of TL1A on human colonic fibroblasts. METHODS: A trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic (Tg) or wild-type (WT) mice was established to determine the effect and mechanism of TL1A on intestinal fibrosis. The human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell (PBMC) supernatant. The proliferation and activation of CCD-18Co cells were detected by BrdU assays, flow cytometry, immunocytochemistry and Western blotting. Collagen metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The level of collagen metabolism in the TNBS+ethyl alcohol (EtOH)/Tg group was greater than that in the TNBS+EtOH/WT group. Transforming growth factor-ß1 (TGF-ß1) and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT group. The proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A, and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4% at 24 h. TL1A promoted cell activation and increased the levels of COL1A2, COL3A1, and TIMP-1 in CCD-18Co cells. Treatment of CCD-18Co cells with TL1A increased the expression of TGF-ß1 and p-Smad3. CONCLUSION: TL1A promotes TGF-ß1-mediated intestinal fibroblast activation, proliferation, and collagen deposition and is likely related to an increase in the TGF-ß1/Smad3 signaling pathway.

Effect of Implementing an Informatization Case Management Model on the Management of Chronic Respiratory Diseases in a General Hospital: Retrospective Controlled Study.

Background: The use of chronic disease information systems in hospitals and communities plays a significant role in disease prevention, control, and monitoring. However, there are several limitations to these systems, including that the platforms are generally isolated, the patient health information and medical resources are not effectively integrated, and the "Internet Plus Healthcare" technology model is not implemented throughout the patient consultation process. Objective: The aim of this study was to evaluate the efficiency of the application of a hospital case management information system in a general hospital in the context of chronic respiratory diseases as a model case. Methods: A chronic disease management information system was developed for use in general hospitals based on internet technology, a chronic disease case management model, and an overall quality management model. Using this system, the case managers provided sophisticated inpatient, outpatient, and home medical services for patients with chronic respiratory diseases. Chronic respiratory disease case management quality indicators (number of managed cases, number of patients accepting routine follow-up services, follow-up visit rate, pulmonary function test rate, admission rate for acute exacerbations, chronic respiratory diseases knowledge awareness rate, and patient satisfaction) were evaluated before (2019-2020) and after (2021-2022) implementation of the chronic disease management information system. Results: Before implementation of the chronic disease management information system, 1808 cases were managed in the general hospital, and an average of 603 (SD 137) people were provided with routine follow-up services. After use of the information system, 5868 cases were managed and 2056 (SD 211) patients were routinely followed-up, representing a significant increase of 3.2 and 3.4 times the respective values before use (U=342.779; P<.001). With respect to the quality of case management, compared to the indicators measured before use, the achievement rate of follow-up examination increased by 50.2%, the achievement rate of the pulmonary function test increased by 26.2%, the awareness rate of chronic respiratory disease knowledge increased by 20.1%, the retention rate increased by 16.3%, and the patient satisfaction rate increased by 9.6% (all P<.001), while the admission rate of acute exacerbation decreased by 42.4% (P<.001) after use of the chronic disease management information system. Conclusions: Use of a chronic disease management information system improves the quality of chronic respiratory disease case management and reduces the admission rate of patients owing to acute exacerbations of their diseases.

Integrated multi-omics analyses revealed the association between rheumatoid arthritis and colorectal cancer: MYO9A as a shared gene signature and an immune-related therapeutic target.

BACKGROUND: Our study aims to explore the relationship, shared gene signature, and the underlying mechanisms that connect rheumatoid arthritis (RA) to colorectal cancer (CRC). METHODS: Mendelian randomization (MR) analysis was conducted to assess the causality between RA and CRC. Summary statistic data-based Mendelian randomization (SMR) leveraging eQTL data was employed to identify the CRC-related causal genes. Integrated analyses of single-cell RNA sequencing and bulk RNA sequencing were employed to comprehensively investigate the shared gene signature and potential mechanisms underlying the pathogenesis of both RA and CRC. Predictive analysis of the shared hub gene in CRC immunotherapy response was performed. Pan-cancer analyses were conducted to explore the potential role of MYO9A in 33 types of human tumors. RESULTS: MR analysis suggested that RA might be associated with a slight increased risk of CRC (Odds Ratio = 1.04, 95% Confidence Interval = 1.01-1.07, P = 0.005). SMR analysis combining transcriptome analyses identified MYO9A as a causal gene in CRC and a shared gene signature in both RA and CRC. MYO9A may contribute to tumor suppression, while downregulation of MYO9A may impact CRC tumorigenesis by disrupting epithelial polarity and architecture, resulting in a worse prognosis in CRC. Additionally, MYO9A shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Pan-cancer analyses demonstrated MYO9A may have a protective role in the occurrence and progression of various human cancers. CONCLUSION: RA might be associated with a slight increased risk of CRC. MYO9A is a shared gene signature and a potential immune-related therapeutic target for both CRC and RA. Targeting the MYO9A-mediated loss of polarity and epithelial architecture could be a novel therapeutic approach for CRC.

Induction of CX3CL1 expression by LPS and its impact on invasion and migration in oral squamous cell carcinoma.

Purpose: This study aimed to explore the expression of CX3CL1 induced by lipopolysaccharide (LPS) in oral squamous cell carcinoma (OSCC) and its impact on biological characteristics such as invasion and migration, taking the foundation for new targets for the treatment and prognosis of OSCC. Methods: This study utilized a variety of techniques, including bioinformatics, molecular biology, and cell experiments, to investigate the expression of CX3CL1 and its receptor CX3CR1 in OSCC patients' cancer tissues or OSCC cell lines. Extracting, organizing, and analyzing the TCGA database on the expression of CX3CL1 and its receptor CX3CR1 in cancer tissues and corresponding paracancerous normal tissues of OSCC patients by bioinformatics methods. The expression of CX3CL1 in cancerous and normal tissues of OSCC patients was verified by IHC, and the changes in mRNA and protein expression of CX3CL1 and its receptor CX3CR1 in OSCC cell lines were detected before and after lipopolysaccharide LPS stimulation by RT-PCR, ELISA, and WB. Changes in cell biological behavior by overexpression of CX3CL1 in OSCC cell lines were detected by CCK-8, Transwell, scratch healing assay, and cloning assay. The effects of overexpressing cell lines on the AKT pathway and Epithelial-mesenchymal Transition (EMT)-related protein expression before and after LPS stimulation were detected by Western Blot. Results: (1) CX3CL1 and its receptor CX3CR1 were found to be downregulated in OSCC tissues of patients or OSCC cell lines. (2) After LPS stimulation, CX3CL1 gene expression increased in both OSCC cell lines, while CX3CR1 expression remained unchanged. (3) OSCC cell lines overexpressing CX3CL1 showed changes in cell biological characteristics, including decreased proliferation, invasion, migration, and stemness, which were more pronounced after LPS stimulation. (4) Overexpression of CX3CL1 in OSCC cell lines decreased EMT-related protein expression and AKT phosphorylation. On the contrary were promoted by LPS stimulation. Conclusion: CX3CL1 and CX3CR1 are downregulated in OSCC cancer tissues and cell lines compared to adjacent normal tissues and cells. LPS stimulation increases CX3CL1 expression in OSCC cell lines, suggesting that inflammation may induce CX3CL1 expression and that the CX3CL1 gene may play an important role in OSCC progression. Overexpression of CX3CL1 inhibits OSCC cell proliferation, migration, invasion, and stemness, suggesting that CX3CL1 plays a critical role in suppressing OSCC development. CX3CL1 suppresses OSCC invasion and migration by affecting EMT progression and AKT phosphorylation, and partially reverse the process that LPS causes and affects the development of OSCC.

Saline-alkali land reclamation boosts topsoil carbon storage by preferentially accumulating plant-derived carbon.

Saline-alkali land is an important cultivated land reserve resource for tackling global climate change and ensuring food security, partly because it can store large amounts of carbon (C). However, it is unclear how saline-alkali land reclamation (converting saline-alkali land into cultivated land) affects soil C storage. We collected 189 adjacent pairs of salt-affected and cultivated soil samples (0-30 cm deep) from the Songnen Plain, eastern coastal area, Hetao Plain, and northwestern arid area in China. Various soil properties, the soil inorganic C (SIC), organic C (SOC), particulate organic C (POC), and mineral-associated organic C (MAOC) densities, and plant- and microbial-derived C accumulation were determined. Saline-alkali land reclamation inconsistently affected the SIC density but significantly (P < 0.001) increased the SOC density. The SOC, POC, and MAOC densities were predicted well by the integrative soil amelioration index. Saline-alkali land reclamation significantly increased plant-derived C accumulation and the plant-derived C to microbial-derived C ratios in all saline-alkali areas, and less microbial transformation of plant-derived C (i.e., less lignin degradation or oxidation) occurred in cultivated soils than salt-affected soils. The results indicated that saline-alkali land reclamation leads to plant-derived C becoming the dominant contributor of SOC storage. POC storage and MAOC storage were strongly linked to plant- and microbial-derived C accumulation, respectively, caused by saline-alkali land reclamation. Our findings suggest that saline-alkali land reclamation increases C storage in topsoil by preferentially promoting plant-derived C accumulation.

Verapamil inhibits respiratory syncytial virus infection by regulating Ca2+ influx.

AIMS: The study evaluated the antiviral effect of Verapamil against respiratory syncytial virus (RSV) and investigated its underlying mechanism. MATERIALS AND METHODS: RSV-infected BALB/c mice were treated with Verapamil. Body weight, survival rates, viral load, lung damage, inflammatory factors, and the expression of RSV fusion (F) protein were analyzed. In cellular studies, intracellular Ca2+ and viral titers were measured in the presence of Verapamil, Calcium Chloride, and EGTA. A time-of-addition assay assessed the antiviral effect of Verapamil. KEY FINDINGS: Mice infected with RSV and treated with Verapamil exhibited a significant decrease in weight loss, an increase in survival rates, and reductions in viral titers, RSV F protein expression, inflammatory responses, and lung tissue injury. Verapamil reduced intracellular calcium levels, which correlated with reduced viral titers. The addition of calcium chloride reversed the anti-viral effects mediated by Verapamil, while EGTA potentiated them. The antiviral activity of Verapamil was observed during the early phase of RSV infection, likely by blocking Ca2+ channels and inhibiting virus replication. SIGNIFICANCE: Verapamil effectively inhibits RSV infection by blocking calcium channels and reducing intracellular calcium levels, thereby impeding viral replication. Thus, Verapamil shows promise as a treatment for RSV.

A label-free and rapid fluorometric strategy for microRNA detection using CRISPR-Cas12a coupled with copper nanoparticles.

CRISPR-Cas12a with robust trans-cleavage activity were employed to mitigate background fluorescence signal, achieving sensitive detection of miRNA-21. The activation of trans-cleavage activity of Cas12a was achieved by utilizing cDNA as a trigger. Upon the presence of target miRNA-21, cDNA hybridizes with it forming a DNA/RNA double-stranded structure. Exonuclease III (ExoIII) facilitates the degradation of cDNA, releasing the target for subsequent cycles. Due to cDNA degradation, the trans-cleavage activity of Cas12a remains unactivated and does not disrupt the synthesis template of copper nanoparticles. Addition of Cu2+ and AA leads to the formation of highly fluorescent copper nanoparticles. Conversely, in absence of miRNA-21, intact cDNA activates trans-cleavage activity of Cas12a, resulting in degradation of the synthesis template and failure in synthesizing fluorescent copper nanoparticles. This method exhibits excellent selectivity with a low limit of detection (LOD) at 5 pM. Furthermore, we successfully applied this approach to determine miRNA-21 in cell lysates and human serum samples, providing a new approach for sensitive determination of biomarkers in biochemical research and disease diagnosis.

Adult microglial TGFß1 is required for microglia homeostasis via an autocrine mechanism to maintain cognitive function in mice.

While TGF-ß signaling is essential for microglial function, the cellular source of TGF-ß1 ligand and its spatial regulation remains unclear in the adult CNS. Our data supports that microglia but not astrocytes or neurons are the primary producers of TGF-ß1 ligands needed for microglial homeostasis. Microglia-Tgfb1 KO leads to the activation of microglia featuring a dyshomeostatic transcriptome that resembles disease-associated, injury-associated, and aged microglia, suggesting microglial self-produced TGF-ß1 ligands are important in the adult CNS. Astrocytes in MG-Tgfb1 inducible (i)KO mice show a transcriptome profile that is closely aligned with an LPS-associated astrocyte profile. Additionally, using sparse mosaic single-cell microglia KO of TGF-ß1 ligand we established an autocrine mechanism for signaling. Here we show that MG-Tgfb1 iKO mice present cognitive deficits, supporting that precise spatial regulation of TGF-ß1 ligand derived from microglia is required for the maintenance of brain homeostasis and normal cognitive function in the adult brain.

Structure Elucidation of a Novel Polysaccharide Isolated from Euonymus fortunei and Establishing Its Antioxidant and Anticancer Properties.

Euonymusfortunei polysaccharides (EFPs) have not been extensively investigated yet in terms of their extraction and biological activity. The orthogonal experimental design was employed in this study to evaluate the optimum yield of EFPs. A maximum yield of 2.63 ± 0.23% was attained using material-liquid ratios of 60 mL/g, extraction temperature of 80°C, ultrasonic power of 144 W, and extraction time of 75 mins. The polysaccharide content reached 53.47 ± 0.31% when deproteinized thrice. An analysis of monosaccharide composition revealed that these polysaccharides consist of Gal, Glc, Man, Fuc, and Rha with a molar ratio of 7.14 ∶ 23.99 ∶ 6.29 ∶ 6.55 ∶ 1.00, respectively, in EFPs. Subsequently, the in vitro scavenging capacities of 2,2-diphenylpicrylhydrazyl (DPPH) and ·OH and superoxide anion radicals, along with the reducing power of EFPs, were studied. Results revealed that EFPs have higher antioxidant activity, particularly ·OH scavenging, as well as reducing power, as compared to Astragalus polysaccharides (ASPs) and Lycium barbarum polysaccharides (LBPs). The Cell Counting Kit-8 (CCK-8) method was used to evaluate the effects of different concentrations of polysaccharides on SKOV3 cell proliferation, and the results revealed their inhibition at concentrations in the range of 200-800 µg/mL. In addition, findings from flow cytometry further confirmed that EFPs blocked the cell cycle at G0/G1 and S phases and induced SKOV3 cell apoptosis. In a word, EFPs could be exploited and used further based on the experimental results from this study.

Accelerating the Rate-Determining Steps of Sulfur Conversion Reaction for Lithium-Sulfur Batteries Working at an Ultrawide Temperature Range.

Wide operation temperature is the crucial objective for an energy storage system that can be applied under harsh environmental conditions. For lithium-sulfur batteries, the "shuttle effect" of polysulfide intermediates will aggravate with the temperature increasing, while the reaction kinetics decreases sharply as the temperature decreasing. In particular, sulfur reaction mechanism at low temperatures seems to be quite different from that at room temperature. Here, through in situ Raman and electrochemical impedance spectroscopy studies, the newly emerged platform at cryogenic temperature corresponds to the reduction process of Li2S8 to Li2S4, which will be another rate-determining step of sulfur conversion reaction, in addition to the solid-phase conversion process of Li2S4 to Li2S2/Li2S at low temperatures. Porous bismuth vanadate (BiVO4) spheres are designed as sulfur host material, which achieve the rapid snap-transfer-catalytic process by shortening lithium-ion transport pathway and accelerating the targeted rate-determining steps. Such promoting effect greatly inhibits severe "shuttle effect" at high temperatures and simultaneously improves sulfur conversion efficiency in the cryogenic environment. The cell with the porous BiVO4 spheres as the host exhibits excellent rate capability and cycle performance under wide working temperatures.