How different face mask types affect interpersonal distance perception and threat feeling in social interaction.

Due to the easing of the pandemic, public policies no longer mandated people to wear masks. People can choose to no wear or wear different types of masks based on personal preferences and safety perceptions during daily interaction. Available information about the influence of face mask type on interpersonal distance (IPD) by different aging populations is still lacking. Thus, this study aimed to investigate the face mask type (no wear, cloth, medical and N95 mask) and age group effect of avatars (children, adults and older adults) on IPD perception, threat feeling and physiological skin conductance response under active and passive approaching. One hundred participants with a range from 20 to 35 years old were recruited for this study. Twelve avatars (three age groups*four face mask conditions) were created and applied in a virtual reality environment. The results showed that age group, mask type and approach mode had significant effects on IPD and subjective threat feeling. A non-significant effect was found on skin conductance responses. Participants maintained a significantly longer IPD when facing the older adults, followed by adults and then children. In the passive approach condition, people tended to maintain a significantly greater comfort distance than during the active approach. For the mask type effect, people kept a significantly largest and shortest IPD when facing an avatar with no mask or the N95 mask, respectively. A non-significant IPD difference was found between the N95 and medical mask. Additionally, based on the subjective threat feeling, facing an avatar wearing a medical mask generated the lowest threat feeling compared to the others. The findings of this study indicated that wearing medical masks provided a benefit in bringing people closer for interaction during specific situations. Understanding that mask-wearing, especially medical one, brought to shortest IPD when compared to the unmasked condition can be utilized to enhance safety measures in crowded public spaces and health-care settings. This information could guide the development of physical distancing recommendations, taking into account both the type of mask and the age groups involved, to ensure the maintenance of appropriate distances.

Postural balance disorders in sarcopenia based on surface electromyography.

Background: Sarcopenia is an intrinsic factor that leads to balance disorders and falls in older adults. However, the characterization of sarcopenia-related postural balance deficits remains unclear. Aims: This study aimed to explore the balance performance and postural control strategy in older adults with sarcopenia during static stance tasks using force platforms and surface electromyography. Methods: Older adults with right-sided dominance were recruited, including 27 adults with sarcopenia and 27 healthy counterparts. Postural sway was measured with eyes open/closed on rigid/compliant surfaces. The time- and frequency-domain indexes of bilateral lower extremity muscle activity were simultaneously recorded. Results: The postural sway and activity of multiple lower extremity muscles in the sarcopenia group were increased (P < 0.05). The amplitude contribution ratio of the right tibialis anterior muscle (larger in sarcopenia), co-contraction ratio of right ankle dorsiflexion (smaller in sarcopenia), and mean power frequency and median frequency of the left gluteus maximus muscle (smaller in sarcopenia) had main effects of grouping (P < 0.001, η2p = 0.06-0.10). All of them had discrimination for sarcopenia (area under the curve = 0.639-0.657, P < 0.001) and were correlated with balance function measurement in sarcopenia (|rs| = 0.22-0.44, P < 0.05). Conclusion: The results of this study suggest that older adults with sarcopenia have decreased balance function and increased cost of electrophysiology. They were found to prefer the postural strategy of dominant ankle dorsiflexion and demonstrated overactivity of the dominant tibialis anterior muscles and fatigue vulnerability of the nondominant gluteus maximus. Improvements in these postural features may have balance benefits.

MOSGAT: Uniting Specificity-Aware GATs and Cross Modal-Attention to Integrate Multi-Omics Data for Disease Diagnosis.

With the advancement of sequencing methodologies, the acquisition of vast amounts of multi-omics data presents a significant opportunity for comprehending the intricate biological mechanisms underlying diseases and achieving precise diagnosis and treatment for complex disorders. However, as diverse omics data are integrated, extracting sample-specific features within each omics modality and exploring potential correlations among different modalities while avoiding mutual interference becomes a critical challenge in multi-omics data integration research. In the context of this study, we proposed a framework that unites specificity-aware GATs and cross-modal attention to integrate different omics data (MOSGAT). To be specific, we devise Graph Attention Networks (GATs) tailored for each omics modality data to perform feature extraction on samples. Additionally, an adaptive confidence attention weighting technique is incorporated to enhance the confidence in the extracted features. Finally, a cross-modal attention mechanism was devised based on multi-head self-attention, thoroughly uncovering potential correlations between different omics data. Extensive experiments were conducted on four publicly available medical datasets, highlighting the superiority of the proposed framework when compared to state-of-the-art methodologies, particularly in the realm of classification tasks. The experimental results underscore MOSGAT's effectiveness in extracting features and exploring potential inter-omics associations.

Targeted exosome-based nanoplatform for new-generation therapeutic strategies.

Exosomes, typically 30-150 nm in size, are lipid-bilayered small-membrane vesicles originating in endosomes. Exosome biogenesis is regulated by the coordination of various mechanisms whereby different cargoes (e.g. proteins, nucleic acids, and lipids) are sorted into exosomes. These components endow exosomes with bioregulatory functions related to signal transmission and intercellular communication. Exosomes exhibit substantial potential as drug-delivery nanoplatforms owing to their excellent biocompatibility and low immunogenicity. Proteins, miRNA, siRNA, mRNA, and drugs have been successfully loaded into exosomes, and these exosome-based delivery systems show satisfactory therapeutic effects in different disease models. To enable targeted drug delivery, genetic engineering and chemical modification of the lipid bilayer of exosomes are performed. Stimuli-responsive delivery nanoplatforms designed with appropriate modifications based on various stimuli allow precise control of on-demand drug delivery and can be utilized in clinical treatment. In this review, we summarize the general properties, isolation methods, characterization, biological functions, and the potential role of exosomes in therapeutic delivery systems. Moreover, the effective combination of the intrinsic advantages of exosomes and advanced bioengineering, materials science, and clinical translational technologies are required to accelerate the development of exosome-based delivery nanoplatforms.

Emerging strategies for nerve repair and regeneration in ischemic stroke: neural stem cell therapy.

Ischemic stroke is a major cause of mortality and disability worldwide, with limited treatment options available in clinical practice. The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function. Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect. Neural stem cells regulate multiple physiological responses, including nerve repair, endogenous regeneration, immune function, and blood-brain barrier permeability, through the secretion of bioactive substances, including extracellular vesicles/exosomes. However, due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation, limitations in the treatment effect remain unresolved. In this paper, we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke, review current neural stem cell therapeutic strategies and clinical trial results, and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells. We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.

Multi-kingdom microbial signatures in excess body weight colorectal cancer based on global metagenomic analysis.

Excess body weight (EBW) increases the risk of colorectal cancer (CRC) and is linked to lower colonoscopy compliance. Here, we extensively analyzed 981 metagenome samples from multiple cohorts to pinpoint the specific microbial signatures and their potential capability distinguishing EBW patients with CRC. The gut microbiome displayed considerable variations between EBW and lean CRC. We identify 44 and 37 distinct multi-kingdom microbial species differentiating CRC and controls in EBW and lean populations, respectively. Unique bacterial-fungal associations are also observed between EBW-CRC and lean-CRC. Our analysis revealed specific microbial functions in EBW-CRC, including D-Arginine and D-ornithine metabolism, and lipopolysaccharide biosynthesis. The best-performing classifier for EBW-CRC, comprising 12 bacterial and three fungal species, achieved an AUROC of 0.90, which was robustly validated across three independent cohorts (AUROC = 0.96, 0.94, and 0.80). Pathogenic microbial species, Anaerobutyricum hallii, Clostridioides difficile and Fusobacterium nucleatum, are EBW-CRC specific signatures. This work unearths the specific multi-kingdom microbial signatures for EBW-CRC and lean CRC, which may contribute to precision diagnosis and treatment of CRC.

Enhanced osteochondral regeneration with a 3D-Printed biomimetic scaffold featuring a calcified interfacial layer.

The integrative regeneration of both articular cartilage and subchondral bone remains an unmet clinical need due to the difficulties of mimicking spatial complexity in native osteochondral tissues for artificial implants. Layer-by-layer fabrication strategies, such as 3D printing, have emerged as a promising technology replicating the stratified zonal architecture and varying microstructures and mechanical properties. However, the dynamic and circulating physiological environments, such as mass transportation or cell migration, usually distort the pre-confined biological properties in the layered implants, leading to undistinguished spatial variations and subsequently inefficient regenerations. This study introduced a biomimetic calcified interfacial layer into the scaffold as a compact barrier between a cartilage layer and a subchondral bone layer to facilitate osteogenic-chondrogenic repair. The calcified interfacial layer consisting of compact polycaprolactone (PCL), nano-hydroxyapatite, and tasquinimod (TA) can physically and biologically separate the cartilage layer (TA-mixed, chondrocytes-load gelatin methacrylate) from the subchondral bond layer (porous PCL). This introduction preserved the as-designed independent biological environment in each layer for both cartilage and bone regeneration, successfully inhibiting vascular invasion into the cartilage layer and preventing hyaluronic cartilage calcification owing to devascularization of TA. The improved integrative regeneration of cartilage and subchondral bone was validated through gross examination, micro-computed tomography (micro-CT), and histological and immunohistochemical analyses based on an in vivo rat model. Moreover, gene and protein expression studies identified a key role of Caveolin (CAV-1) in promoting angiogenesis through the Wnt/ß-catenin pathway and indicated that TA in the calcified layer blocked angiogenesis by inhibiting CAV-1.

Spatiotemporal orchestration of macrophage activation trajectories by Vγ4 T cells during skin wound healing.

Dysregulated macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotypes underlies impaired cutaneous wound healing. This study reveals Vγ4+ γδ T cells spatiotemporally calibrate macrophage trajectories during skin repair via sophisticated interferon-γ (IFN-γ) conditioning across multiple interconnected tissues. Locally within wound beds, infiltrating Vγ4+ γδ T cells directly potentiate M1 activation and suppress M2 polarization thereby prolonging local inflammation. In draining lymph nodes, infiltrated Vγ4+ γδ T cells expand populations of IFN-γ-competent lymphocytes which disseminate systemically and infiltrate into wound tissues, further enforcing M1 macrophages programming. Moreover, Vγ4+γδ T cells flushed into bone marrow stimulate increased IFN-γ production, which elevates the output of pro-inflammatory Ly6C+monocytes. Mobilization of these monocytes continually replenishes the M1 macrophage pool in wounds, preventing phenotypic conversion to M2 activation. Thus, multi-axis coordination of macrophage activation trajectories by trafficking Vγ4+ γδ T cells provides a sophisticated immunological mechanism regulating inflammation timing and resolution during skin repair.

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.

Identification and validation of microbial biomarkers from cross-cohort datasets using xMarkerFinder.

Microbial signatures have emerged as promising biomarkers for disease diagnostics and prognostics, yet their variability across different studies calls for a standardized approach to biomarker research. Therefore, we introduce xMarkerFinder, a four-stage computational framework for microbial biomarker identification with comprehensive validations from cross-cohort datasets, including differential signature identification, model construction, model validation and biomarker interpretation. xMarkerFinder enables the identification and validation of reproducible biomarkers for cross-cohort studies, along with the establishment of classification models and potential microbiome-induced mechanisms. Originally developed for gut microbiome research, xMarkerFinder's adaptable design makes it applicable to various microbial habitats and data types. Distinct from existing biomarker research tools that typically concentrate on a singular aspect, xMarkerFinder uniquely incorporates a sophisticated feature selection process, specifically designed to address the heterogeneity between different cohorts, extensive internal and external validations, and detailed specificity assessments. Execution time varies depending on the sample size, selected algorithm and computational resource. Accessible via GitHub ( https://github.com/tjcadd2020/xMarkerFinder ), xMarkerFinder supports users with diverse expertise levels through different execution options, including step-to-step scripts with detailed tutorials and frequently asked questions, a single-command execution script, a ready-to-use Docker image and a user-friendly web server ( https://www.biosino.org/xmarkerfinder ).

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.

Exosomes: the next-generation therapeutic platform for ischemic stroke.

Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery. Therefore, there is an urgent need to develop new methods for the treatment of this condition. Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions. They have low immunogenicity, good stability, high delivery efficiency, and the ability to cross the blood-brain barrier. These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke. The rapid development of nanotechnology has advanced the application of engineered exosomes, which can effectively improve targeting ability, enhance therapeutic efficacy, and minimize the dosages needed. Advances in technology have also driven clinical translational research on exosomes. In this review, we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke, including their anti-inflammation, anti-apoptosis, autophagy-regulation, angiogenesis, neurogenesis, and glial scar formation reduction effects. However, it is worth noting that, despite their significant therapeutic potential, there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes. Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke. Ultimately, our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.