The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia.

With an increase in global aging, the number of people affected by cerebrovascular diseases is also increasing, and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate. However, few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients. Similarly in Alzheimer's disease and other neurological disorders, synaptic dysfunction is recognized as the main reason for cognitive decline. Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system. Recently, nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia. This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction, neuroinflammation, oxidative stress, and blood-brain barrier dysfunction that underlie the progress of vascular dementia. Additionally, we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

Comparison of inferior vena cava puncture under continuous cardiac perfusion with cardiac puncture in blood acquisition of the laboratory mouse.

Obtaining sufficient blood volume from mice significantly facilitates experimental research. This study explored the inferior vena cava puncture under continuous cardiac perfusion (IVCP-UCCP) technique and evaluated its efficiency in comparison with conventional cardiac puncture (CP). In an initial dose-finding study, 50 mice were randomly assigned to one of 10 groups with escalating perfusion volume from 0.5 to 4.5 ml in 0.5-ml increments. The minimum perfusion volume was determined to be 2 ml in collecting whole circulating blood. In the next comparison using the conventional method, 40 mice were randomly assigned to one of two groups denoting different blood collection methods: Group 1: CP, Group 2: IVCP-UCCP. The results showed 1) that the cells and undiluted blood volume collected via IVCP-UCCP was over twofold higher than that by CP (p < 0.001), confirmed by the cell counts and hematoxylin-eosin staining of different tissues slides (p < 0.001); 2) the new technique did not alter the cellular composition or viability, which was verified by routine blood tests and flow cytometry (p > 0.05); 3) the blood collected via the novel technique was diluted 2.1 times: the hemato-biochemical indicator results multiplied by 2.1 were identical with the test results of blood from CP (p > 0.05). Together, the refined blood collection method of IVCP-UCCP completely extracted the limited blood resources in mice, significantly enhanced the utilization of each mouse, and thus offered scientific and ethical benefits. This technique may be also applicable for other small animal models.

Effect of psychological nursing intervention on anxiety level and quality of life in patients with gastrointestinal peptic ulcer.

BACKGROUND: Peptic ulcer is a common gastrointestinal disease, and psychological intervention has an important influence on its occurrence and development. AIM: To investigate the effect of psychological nursing intervention on the anxiety level and quality of life of patients with gastrointestinal peptic ulcers. METHODS: Two groups of patients with peptic ulcer were selected from January to December 2012, with 60 cases in each group, and psychological nursing intervention and routine treatment were respectively performed. Psychological nursing interventions include cognitive behavioral therapy, psychological support and relaxation training. Self-rating anxiety scale (SAS) and quality of life questionnaire were used to evaluate the anxiety level and quality of life of patients before, during and after treatment. RESULTS: The SAS scores of the experimental group significantly decreased over the course of treatment, from 52.3 before treatment to 30.5 after treatment, while SAS scores of the control group did not change significantly. Meanwhile, the experimental group's quality of life score (SF-36) significantly improved over the course of treatment, from 65.2 to 85.2, while the control group remained stable. Further analysis showed that sex and age had no significant influence on the effect of psychotherapy. Both men and women, young and old, showed similar trends in anxiety relief and improved quality of life after treatment. CONCLUSION: Psychological nursing-based intervention program has a positive effect on the anxiety level and quality of life of patients with gastrointestinal peptic ulcer.

Surface Coordination of Garnet Fillers Improves the Organic-Inorganic Interfacial Compatibility of Composite Solid Electrolyte.

Composite solid electrolytes (CSEs) have become one of the most promising solid-state electrolytes due to their favorable safety and flexibility. However, the weak interaction between inorganic fillers and polymer matrix leads to poor organic-inorganic interfacial compatibility, which degrades the electrochemical performance of CSEs. Herein, it is demonstrated that Li6.4La3Zr1.4Ta0.6O12 (LLZTO) can be chemically bonded to the polymer matrix by surface coordination of the 1,2-dithiolane group of lipoic acid (LA) with metal atoms on the surface of LLZTO through a combination of experimental investigations and theoretical calculations. The surface coordination not only enhances the interfacial compatibility between LLZTO and the polymer matrix, but also facilitates rapid Li+ transport, which leads to the ionic conductivity of the prepared CSE (P-V-M@LLZTO) as high as 6.1 × 10-4 S cm-1 at 30 °C. The excellent interface compatibility ensures a stable cycle of Li/P-V-M@LLZTO/Li symmetrical cell for more than 3500 h. As a result, LiFePO4/P-V-M@LLZTO/Li cell delivers the discharge capacity of 161 mAh g-1 after 5 cycles with a capacity retention of 81% after 500 cycles at 0.5C under 30 °C. This work demonstrates that surface coordination is an effective strategy to solve the inherent interfacial incompatibility problem in CSEs.

Impact of Temperature Elevation on Microbial Communities and Antibiotic Degradation in Cold Region Soils of Northeast China.

This study systematically investigated the effects of temperature changes on the degradation of antibiotics in soil, as well as the alterations in microbial community structure and aggregation, through a field warming experiment in a greenhouse. Compared to non-warming soil, the warming treatment significantly accelerated the degradation rate of tetracyclines during soil freezing and mitigated the impact of environmental fluctuations on soil microbial communities. The greenhouse environment promoted the growth and reproduction of a wide range of microbial taxa, but the abundance of Myxococcota was positively correlated with antibiotic concentrations in both treatments, suggesting a potential specific association with antibiotic degradation processes. Long-term warming in the greenhouse led to a shift in the assembly process of soil microbial communities, with a decrease in dispersal limitation and an increase in the drift process. Furthermore, co-occurrence network analysis revealed a more loosely structured microbial community in the greenhouse soil, along with the emergence of new characteristic taxa. Notably, more than 60% of the key taxa that connected the co-occurrence networks in both groups belonged to rare taxa, indicating that rare taxa play a crucial role in maintaining community structure and function.

Present and future use of exosomes containing proteins and RNAs in neurodegenerative diseases for synaptic function regulation: A comprehensive review.

Neurodegenerative diseases (NDDs) are increasingly prevalent with global aging, demanding effective treatments. Exosomes, which contain biological macromolecules such as RNA (including miRNAs) and proteins like α-synuclein, tau, and amyloid-beta, are gaining attention as innovative therapeutics. This comprehensive review systematically explores the potential roles of exosomes in NDDs, with a particular focus on their role in synaptic dysfunction. We present the synaptic pathophysiology of NDDs and discuss the mechanisms of exosome formation, secretion, and action. Subsequently, we review the roles of exosomes in different types of NDDs, such as Alzheimer's disease and Parkinson's disease, with a special focus on their regulation of synaptic function. In addition, we explore the potential use of exosomes as biomarkers, as well as the challenges and opportunities in their clinical application. We provide perspectives on future research directions and development trends to provide a more comprehensive understanding of and guidance for the application of exosomes in the treatment of NDDs. In conclusion, exosomes rich in biological macromolecules, as a novel therapeutic strategy, have opened up new possibilities for the treatment of NDDs and brought new hope to patients.

A self-healing composite solid electrolyte with dynamic three-dimensional inorganic/organic hybrid network for flexible all-solid-state lithium metal batteries.

Composite solid electrolytes (CSEs), which combine the advantages of solid polymer electrolytes and inorganic solid electrolytes, are considered to be promising electrolytes for all-solid-state lithium metal batteries. However, the current CSEs suffer from defects such as poor inorganic/organic interface compatibility, lithium dendrite growth, and easy damage of electrolyte membrane, which hinder the practical application of CSEs. Herein, a CSE (PBHL@LLZTO@DDB) with polyurethane (PBHL) as the polymer matrix and Li6.4La3Zr1.4Ta0.6O12 (LLZTO) modified by silane coupling agent (DDB) as inorganic fillers (LLZTO@DDB) has been prepared. Disulfide bond exchange reactions between PBHL and LLZTO@DDB enable PBHL@LLZTO@DDB to form a dynamic three-dimensional (3D) inorganic/organic hybrid network, which promotes the uniform dispersion of LLZTO in PBHL@LLZTO@DDB, improves the Li+ conductivity (1.24 ± 0.08 × 10-4 S cm-1 at 30 â„ƒ), and broadens the electrochemical stability window (5.16 V vs. Li+/Li). Moreover, a combination of hydrogen bonds and disulfide bonds endows PBHL@LLZTO@DDB with excellent self-healing properties. As such, both all-solid-state symmetric and full cells exhibit excellent cycle performance at ambient temperature. More importantly, the healed PBHL@LLZTO@DDB can almost completely restore its original electrochemical properties, indicating its application potential in flexible electronic products.

STING coordinates resolution of inflammation during wound repair by modulating macrophage trafficking through STAT3.

Efficient cutaneous wound healing requires a coordinated transition between inflammatory phases mediated by dynamic changes in leukocyte subset populations. Here, we identify STING as a key innate immune mediator governing timely resolution of inflammation by regulating macrophage dynamics during skin repair. Using a mouse model, we show STING deficiency caused delayed wound closure associated with abnormal persistence of TNF-α+ leukocytes. This resulted from the impaired macrophage recruitment. STING controlled the trafficking of bone marrow myeloid cells into blood and wounds, intrinsically enhancing macrophage migratory capacity through STAT3 activation. Specifically, STING modulated the production of monocyte chemokines and their receptors CCR2/CCR5 to enable efficient egress and wound infiltration. Consequently, disrupted systemic and local STING-STAT3-chemokine signaling combine to delay macrophage influx. This study elucidates STING as a critical rheostat tuning macrophage responses through STAT3 to orchestrate inflammatory resolution necessary for efficient wound healing. Our findings have broad implications for targeting STING therapeutically in both regenerative medicine and inflammatory disease contexts. STING regulates the macrophage trafficking through STAT3 in wound healing.

3MT-Net: A Multi-modal Multi-task Model for Breast Cancer and Pathological Subtype Classification Based on a Multicenter Study.

Breast cancer significantly impacts women's health, with ultrasound being crucial for lesion assessment. To enhance diagnostic accuracy, computer-aided detection (CAD) systems have attracted considerable interest. This study introduces a prospective deep learning architecture called "Multi-modal Multi-task Network" (3MT-Net). 3MT-Net utilizes a combination of clinical data, B-mode, and color Doppler ultrasound. We have designed the AM-CapsNet network, specifically tailored to extract crucial tumor features from ultrasound. To combine clinical data in 3MT-Net, we have employed a cascaded cross-attention to fuse information from three distinct sources. To ensure the preservation of pertinent information during the fusion of high-dimensional and low-dimensional data, we adopt the idea of ensemble learning and design an optimization algorithm to assign weights to different modalities. Eventually, 3MT-Net performs binary classification of benign and malignant lesions as well as pathological subtype classification. In addition, we retrospectively collected data from nine medical centers. To ensure the broad applicability of the 3MT-Net, we created two separate testsets and conducted extensive experiments. Furthermore, a comparative analysis was conducted between 3MT-Net and the industrial-grade CAD product S-detect. The AUC of 3MT-Net surpasses S-Detect by 1.4% to 3.8%.

Interface Engineering of VOx/Ni/Ni3N Heterostructures for Electrochemical Urea-Assisted Hydrogen Production.

Electrocatalytic hydrogen generation driven by renewable energy sources is severely limited by the slow oxygen evolution reaction (OER). Urea-assisted alkaline hydrogen production offers a perspective approach. However, the construction of efficient and robust anode catalysts is still challenging. Herein, an amorphous/crystalline VOx/Ni/Ni3N-heterostructured catalyst grown on carbon cloth was synthesized and used as a bifunctional electrocatalyst for the hydrogen evolution reaction (HER) and urea electrooxidation reaction (UOR). Benefiting from the electronic modification of intercomponents and abundant active sites, VOx/Ni/Ni3N exhibits an excellent electrochemical performance toward the HER and UOR. Theoretical calculations confirmed that the crystalline/amorphous VOx/Ni/Ni3N heterostructure has a suitable water dissociation energy and H* adsorption energy, thereby promoting the HER process. When the UOR and HER are integrated into an electrolytic device, VOx/Ni/Ni3N requires a potential of 1.40 V to achieve a current density of 10 mA cm-2.

Tungsten-needle intensifies microwave-sustained plasma accelerating direct H2S conversion to H2.

Direct sustainable conversion of hydrogen sulfide (H2S) enables collaborative recovery of H and S resources via a metal-enhanced microwave plasma strategy, avoiding the hydrogen waste in the traditional Claus process. However, the metal size effect on microwave plasma property, the optimal process parameters, and the enhancement mechanism remain unclear in H2S conversion. Herein, the optimal tungsten needle (diameter: 1 mm, length: 60 mm, and tip angle: 10°) is experimentally proven for intensifying microwave discharge in multi-mode cavities. Theoretical calculations and plasma distribution reveal that the optimized tungsten needle achieves the ideal coupling with the microwave field, exhibiting extreme electric field augmentation around the needle tip. Tungsten-needle intensifies microwave-sustained plasma, realizing 40.2 % (90.1 %) conversion of 100 % (10 %) concentration H2S to H2 at a low microwave power of 300 W with a good stability of 30 hrs. Low power, large flow rate, and high H2S concentration are beneficial for improving energy efficiency. The excitation of microwave plasma is accompanied by a massive generation of highly energetic electrons. The direct high-energy electron-H2S collision contributes a lot to H2S splitting, especially for high-concentration H2S. In-situ optical emission spectroscopy confirms the vital S and H radicals in the plasma. The free radical reactions triggered by electron collisions are responsible for the production of H2 and S. This work opens an avenue to sustainable and low-carbon hydrogen production from the direct conversion and utilization of H2S.

The Role of the Complement System in Synaptic Pruning after Stroke.

Stroke is a serious disease that can lead to local neurological dysfunction and cause great harm to the patient's health due to blood cerebral circulation disorder. Synaptic pruning is critical for the normal development of the human brain, which makes the synaptic circuit completer and more efficient by removing redundant synapses. The complement system is considered a key player in synaptic loss and cognitive impairment in neurodegenerative disease. After stroke, the complement system is over-activated, and complement proteins can be labeled on synapses. Microglia and astrocytes can recognize and engulf synapses through corresponding complement receptors. Complement-mediated excessive synaptic pruning can cause post-stroke cognitive impairment (PSCI) and secondary brain damage. This review summarizes the latest progress of complement-mediated synaptic pruning after stroke and the potential mechanisms. Targeting complement-mediated synaptic pruning may be essential for exploring therapeutic strategies for secondary brain injury (SBI) and neurological dysfunction after stroke.

"I will resume my research work when things settle down": A narrative inquiry of an EFL academic's emotions and identities in research experiences.

Despite a surge of studies on the construction of researcher identities among English as a Foreign Language (EFL) teachers, insufficient attention has been paid to their ongoing identity development after establishing a researcher identity. Using narrative inquiry, this study investigated how an EFL academic transitioned from being a rising star in research to becoming a teaching-focused academic midcareer with emotional flux in situated socio-institutional contexts. Data were collected from semi-structured interviews, narrative frame, institutional documents, and the participant's academic profile. The data analysis revealed that while the participant started her research journey as a confident novice researcher, she faced negative emotions arising from encounters with potential bias in academia, institutional managerial practices, and diminished self-agency with waned research motivation. Such negative emotions gradually escalated, posing severe impediments to her researcher identity. Eventually, these impediments resulted in her research stagnation and subsequent transformation of her identity into that of a teaching-focused EFL academic midcareer. The findings provide a nuanced understanding of the complexities involved in the continuous development of EFL academics' researcher identities in the changing landscape of higher education. The study also provides implications for supporting EFL teachers in constructing and maintaining a robust researcher identity to facilitate their ongoing professional development.

Bisphenol S causes excessive estrogen synthesis by activating FSHR and the downstream cAMP/PKA signaling pathway.

Estrogen excess in females has been linked to a diverse array of chronic and acute diseases. Emerging research shows that exposure to estrogen-like compounds such as bisphenol S leads to increases in 17ß-estradiol levels, but the mechanism of action is unclear. The aim of this study was to reveal the underlying signaling pathway-mediated mechanisms, target site and target molecule of action of bisphenol S causing excessive estrogen synthesis. Human ovarian granulosa cells SVOG were exposed to bisphenol S at environmentally relevant concentrations (1 µg/L, 10 µg/L, and 100 µg/L) for 48 h. The results confirms that bisphenol S accumulates mainly on the cell membrane, binds to follicle stimulating hormone receptor (FSHR) located on the cell membrane, and subsequently activates the downstream cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling pathway, leading to enhanced conversion of testosterone to 17ß-estradiol. This study deepens our knowledge of the mechanisms of environmental factors in pathogenesis of hyperestrogenism.

FOXM1 Upregulates O-GlcNAcylation Level Via The Hexosamine Biosynthesis Pathway to Promote Angiogenesis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) presents significant challenges in treatment and prognosis because of its aggressive nature and high metastatic potential. This study aims to investigate the role of the hexosamine biosynthesis pathway (HBP) and its association with HCC progression and prognosis. We identified SPP1 and FOXM1 as hub genes within the HBP pathway, showing their correlation with poor prognosis and late-stage progression. In addition, the analysis uncovered the complex participation of the HBP pathway in nutrients and oxygen reactions, PI3K-AKT signaling, AMPK activation, and angiogenesis regulation. The disruption of these pathways is pivotal in influencing the growth and progression of HCC. Targeting the HBP presents a promising therapeutic approach to modulate the tumor microenvironment, thereby enhancing the efficacy of immunotherapy. In addition, FOXM1 was identified as the HBP pathway regulator, influencing cellular O-GlcNAcylation level and VEGF secretion, thereby promoting angiogenesis in HCC. Inhibition of O-GlcNAcylation significantly hindered angiogenesis, which is suggested as a potential avenue for therapeutic intervention. Our research demonstrates the practicality of using the HBP-related gene as a prognostic marker in liver cancer patients and suggests targeting FOXM1 as a novel avenue for personalized therapy.

A novel signature constructed by cuproptosis-related RNA methylation regulators suggesting downregulation of YTHDC2 may induce cuproptosis resistance in colorectal cancer.

BACKGROUND: A newly identified type of cell death due to intracellular copper accumulation is known as cuproptosis and RNA methylation is a post-transcriptional modification mechanism, both of which perform vital roles in the immune microenvironment of colorectal cancer (CRC), but the link between the two needs more research. METHODS: TCGA database provided RNA-seq data and details clinically of CRC samples. Cuproptosis-related RNA methylation regulators (CRRMRs) were identified by correlation analysis. We screened 6 CRRMRs for prognostic model construction by employing LASSO-Cox regression analysis and calculated risk scores by CRRMRs (CuMS). GSE39582 and GSE38832 cohort were used as external validation sets. This research concentrated on the connection between the prognostic model and somatic mutation, anti-cancer drug sensitivity, immune infiltration, immune checkpoint expression. In addition, we investigated the differential expression of YTHDC2 in epithelial cell subpopulations by single-cell analysis with GSE166555, calculated cuproptosis scores and performed pathway enrichment. In vitro experiments were performed to explore the consequences of knockdown of YTHDC2 on CRC cell proliferation and migration, as well as changes in CRC cell viability in response to elesclomol after knockdown of YTHDC2. In vivo experiments, we constructed the cell line-derived xenograft model to further validate the results of the in vitro experiments. RESULTS: The prognosis of CRC can be predicted by CuMS, which GSE39582 and GSE38832 confirmed. Two CuMS groups showed different tumor mutation burden (TMB) and immune infiltration. CuMS was connected to emerging immune checkpoints CD47 and PVR, therefore, it can be clinically complementary to TMB and microsatellite instability (MSI) status. In single-cell analysis, a subpopulation of epithelial cells with high YTHDC2 expression had a high cuproptosis score. In vitro experiments, knocking down YTHDC2 promoted cell proliferation and migration in CRC, and weaken the inhibitory effect of elesclomol and elesclomol-Cu on cell viability, which in vivo experiments validated. CONCLUSION: We developed a prognostic model constructed by 6 CRRMRs to assess overall survival and immune microenvironment of CRC patients. YTHDC2 might regulate cuproptosis in multiple ways.

Enhanced removal of antibiotics and heavy metals in aquatic systems using spent mushroom substrate-derived biochar integrated with Herbaspirillum huttiense.

A novel integrated removal strategy was developed to enhance the concurrent elimination of copper (Cu), zinc (Zn), oxytetracycline (OTC), and enrofloxacin (ENR) from the aqueous environments. The underlying adsorption mechanisms of spent mushroom substrate (SMSB) and the Herbaspirillum huttiense strain (HHS1), and their efficacy in removing Cu, Zn, OTC, and ENR was also examined. Results showed that the SMSB-HHS1 composite stabilized 29.86% of Cu and 49.75% of Zn and achieved removal rates of 97.95% for OTC and 59.35% for ENR through a combination of chemisorption and biodegradation. Zinc did not affect Cu adsorption, and ENR did not impact the adsorption of OTC on SMSB. However, the co-presence of OTC and ENR modified the adsorption behaviors of both Cu and Zn. Copper and Zn enhanced the adsorption of OTC and ENR by serving as bridging agents, facilitating the interaction between the contaminants and SMSB. Conversely, OTC and ENR inhibited the adsorption process of Cu by obstructing its interaction with the SMSB and occupying the oxygen-containing functional groups. The ‒OH (3415 cm-1) and C-O-C (1059 cm-1) functional groups were identified as the principal active sites to form hydrogen bonds and interact with Cu and Zn, leading to the formation of CuP4O11 and Zn4CO3(OH)6H2O. HHS1 also enhanced antibiotic removal through biodegradation, as evidenced by the decrease of ‒C‒O and increase of ‒C = O groups. This study underscores the innovative potential of the SMSB-HHS1 composite, offering a sustainable approach to addressing multifaceted pollution challenges in the aquatic environments.

Deciphering the Genetic Variation: A Comparative Analysis of Parental and Attenuated Strains of the QXL87 Vaccine for Infectious Bronchitis.

The QXL87 live attenuated vaccine strain for infectious bronchitis represents the first approved QX type (GI-19 lineage) vaccine in China. This strain was derived from the parental strain CK/CH/JS/2010/12 through continuous passage in SPF chicken embryos. To elucidate the molecular mechanism behind its attenuation, whole-genome sequencing was conducted on both the parental and attenuated strains. Analysis revealed 145 nucleotide mutations in the attenuated strain, leading to 48 amino acid mutations in various proteins, including Nsp2 (26), Nsp3 (14), Nsp4 (1), S (4), 3a (1), E (1), and N (1). Additionally, a frameshift mutation caused by a single base insertion in the ORFX resulted in a six-amino-acid extension. Subsequent comparison of post-translational modification sites, protein structure, and protein-protein binding sites between the parental and attenuated strains identified three potential virulence genes: Nsp2, Nsp3, and S. The amino acid mutations in these proteins not only altered their conformation but also affected the distribution of post-translational modification sites and protein-protein interaction sites. Furthermore, three potential functional mutation sites-P106S, A352T, and L472F, all located in the Nsp2 protein-were identified through PROVEAN, PolyPhen, and I-Mutant. Overall, our findings suggest that Nsp2, Nsp3, and S proteins may play a role in modulating IBV pathogenicity, with a particular focus on the significance of the Nsp2 protein. This study contributes to our understanding of the molecular mechanisms underlying IBV attenuation and holds promise for the development of safer live attenuated IBV vaccines using reverse genetic approaches.

Orchestration of Macrophage Polarization Dynamics by Fibroblast-Secreted Exosomes during Skin Wound Healing.

Macrophages undertake pivotal yet dichotomous functions during skin wound healing, mediating both early proinflammatory immune activation and late anti-inflammatory tissue remodeling processes. The timely phenotypic transition of macrophages from inflammatory M1 to proresolving M2 activation states is essential for efficient healing. However, the endogenous mechanisms calibrating macrophage polarization in accordance with the evolving tissue milieu remain undefined. In this study, we reveal an indispensable immunomodulatory role for fibroblast-secreted exosomes in directing macrophage activation dynamics. Fibroblast-derived exosomes permitted spatiotemporal coordination of macrophage phenotypes independent of direct intercellular contact. Exosomes enhanced macrophage sensitivity to both M1 and M2 polarizing stimuli, yet they also accelerated timely switching from M1 to M2 phenotypes. Exosome inhibition dysregulated macrophage responses, resulting in aberrant inflammation and impaired healing, whereas provision of exogenous fibroblast-derived exosomes corrected defects. Topical application of fibroblast-derived exosomes onto chronic diabetic wounds normalized dysregulated macrophage activation to resolve inflammation and restore productive healing. Our findings elucidate fibroblast-secreted exosomes as remote programmers of macrophage polarization that calibrate immunological transitions essential for tissue repair. Harnessing exosomes represents a previously unreported approach to steer productive macrophage activation states with immense therapeutic potential for promoting healing in chronic inflammatory disorders.

Virological evaluation of natural and modified attapulgite against porcine epidemic diarrhoea virus.

BACKGROUND: The Porcine Epidemic Diarrhea Virus (PEDV) has caused significant economic losses in the global swine industry. As a potential drug for treating diarrhea, the antiviral properties of attapulgite deserve further study. METHODS: In this study, various methods such as RT-qPCR, Western blot, viral titer assay, Cytopathic Effect, immunofluorescence analysis and transmission electron microscopy were used to detect the antiviral activity of attapulgite and to assess its inhibitory effect on PEDV. RESULTS: When exposed to the same amount of virus, there was a significant decrease in the expression of the S protein, resulting in a viral titer reduction from 10-5.613 TCID50/mL to 10-2.90 TCID50/mL, which represents a decrease of approximately 102.6 folds. Results of cytopathic effect and indirect immunofluorescence also indicate a notable decrease in viral infectivity after attapulgite treatment. Additionally, it was observed that modified materials after acidification had weaker antiviral efficacy compared to powdered samples that underwent ultrasonic disintegration, which showed the strongest antiviral effects. CONCLUSION: As a result, Attapulgite powders can trap and adsorb viruses to inhibit PEDV in vitro, leading to loss of viral infectivity. This study provides new materials for the development of novel disinfectants and antiviral additives.