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Background Hypoxia is a major cause of beta cell death and dysfunction after transplantation. The aim of this study was to investigate the effect of exosomes derived from mesenchymal stem cells (MSCs) on beta cells under hypoxic conditions and the potential underlying mechanisms. Methods Exosomes were isolated from the conditioned medium of human umbilical cord MSCs and identified by WB, NTA, and transmission electron microscopy. Beta cells (βTC-6) were cultured in serum-free medium in the presence or absence of exosomes under 2% oxygen conditions. Cell viability and apoptosis were analysed with a CCK-8 assay and a flow cytometry-based annexin V-FITC/PI apoptosis detection kit, respectively. Endoplasmic reticulum stress (ER stress) proteins and apoptosis-related proteins were detected by the WB method. MiRNAs contained in MSC exosomes were determined by Illumina HiSeq, and treatment with specific miRNA mimics or inhibitors of the most abundant miRNAs was used to reveal the underlying mechanism of exosomes. Results Exosomes derived from MSC-conditioned culture medium were 40–100 nm in diameter and expressed the exosome markers CD9, CD63, CD81, HSP70, and Flotillin 1, as well as the MSC markers CD73, CD90, and CD105. Hypoxia significantly induced beta cell apoptosis, while MSC exosomes remarkably improved beta cell survival. The WB results showed that ER stress-related proteins, including GRP78, GRP94, p-eIF2α and CHOP, and the apoptosis-related proteins cleaved caspase 3 and PARP, were upregulated under hypoxic conditions but were inhibited by MSC exosomes. Moreover, the p38 MAPK signalling pathway was activated by hypoxia and was inhibited by MSC exosomes. The Illumina HiSeq results show that MSC exosomes were rich in miR-21, let-7 g, miR-1246, miR-381, and miR-100. After transfection with miRNA mimics, the viability of beta cells under hypoxia was increased significantly by miR-21 mimic, and the p38 MAPK and ER stress-related proteins in beta cells were downregulated. These changes were reversed after exosomes were pretreated with miR-21 inhibitor. Conclusions Exosomes derived from MSCs could protect beta cells against apoptosis induced by hypoxia, largely by carrying miR-21, alleviating ER stress and inhibiting p38 MAPK signalling. This result indicated that MSC exosomes might improve encapsulated islet survival and benefit diabetes patients.

Background USP51 is a deubiquitinase (DUB), that is involved in diverse cellular processes. Accumulating evidence has demonstrated that USP51 contributes to cancer development. However, its impact on non-small cell lung carcinoma (NSCLC) cell malignancy is largely unknown. Methods In this study, we performed bioinformatics analysis on a dataset from The Cancer Genome Atlas to determine the association between USP51 and cell stemness marker expression in NSCLC patients. RT‒qPCR, Western blotting, and flow cytometry were performed to examine the effects of USP51 depletion on stemness marker expression. Colony formation and tumor sphere formation assays were used to assess the stemness of NSCLC cells. A cycloheximide chase time-course assay and a polyubiquitination assay were carried out to analyze the effects of USP51 on the TWIST1 protein level. TWIST1 was overexpressed in USP51 knockdown NSCLC cells to determine whether TWIST1 is required. The effect of USP51 on the in vivo growth of NSCLC cells was tested through subcutaneous injections in mice. Results We found that USP51 deubiquitinates TWIST1, which is significantly upregulated in the tissues of patients with NSCLC and is closely associated with poor prognosis. USP51 expression was positively correlated with the expression of stemness marker CD44, SOX2, NANOG, and OCT4 in NSCLC patients. USP51 depletion attenuated mRNA, protein, and cell surface expression of stemness markers and the stemness of NSCLC cells. Ectopic USP51 expression potentiated the stability of the TWIST1 protein by attenuating its polyubiquitination. In addition, TWIST1 re-expression in NSCLC cells reversed the inhibitory effect of USP51 knockdown on cell stemness. Furthermore, the in vivo results confirmed the suppressive effect of USP51 depletion on NSCLC cell growth. Conclusions Our results show that USP51 maintains the stemness of NSCLC cells by deubiquitinating TWIST1. Knocking it down reduces both cell stemness and growth of NSCLC cells.

Bone marrow mesenchymal stromal cells (BMSCs) have been shown to enhance the function of pancreatic beta‐cells under hypoxic conditions. However, the precise mechanisms underlying this protective effect remain elusive. In this study, we established a hypoxic beta‐cell model using murine pancreatic beta‐TC‐6 cells to investigate the protective effect and mechanism of BMSCs and their secreted extracellular vesicles (BMSC‐EVs) on hypoxic β cells. Our findings reveal that coculture with BMSCs or BMSC‐EVs significantly enhances the viability and survival of hypoxic beta‐TC‐6 cells. Molecularly, hypoxic conditions trigger an upregulation of CD36 in beta‐TC‐6 cells, a response that is counteracted by BMSCs or BMSC‐EVs. Through a screening process for microRNAs (miRNAs) capable of degrading CD36 mRNA, we identified miR‐539‐3p as a potent suppressor of CD36 expression. The miR‐539‐3p mimic was found to bolster the viability of hypoxic beta‐TC‐6 cells, concurrently reducing CD36 mRNA levels by targeting its 3’ untranslated region (3’UTR). In contrast, the miR‐539‐3p inhibitor abrogates the protective effects of BMSCs and BMSC‐EVs on these cells. Additionally, knockdown of CD36 in hypoxic beta‐TC‐6 cells restores the protective function mitigated by miR‐539‐3p inhibition. In aggregate, these results suggest that BMSCs and BMSC‐EVs shield beta‐TC‐6 cells from hypoxia‐induced injury through miR‐539‐3p‐mediated downregulation of CD36, underscoring the therapeutic potential of targeting the miR‐539‐3p‐CD36 axis to enhance pancreatic beta‐cell function in diabetic patients.

Background Clear cell renal cell carcinoma (ccRCC) is the most common malignant urological tumor, and regrettably, and is insensitive to chemotherapy and radiotherapy, resulting in poor patient outcomes. DBF4 plays a critical role in DNA replication and participates in various biological functions, making it an attractive target for cancer treatment. However, its significance in ccRCC has not yet been explored. Methods We utilized external datasets and bioinformatics analyses to investigate the significance of DBF4 in ccRCC. We analysed its expression patterns, prognostic and diagnostic value, and potential mechanisms. We subsequently validated our findings through an immunohistochemistry (IHC) assay of ccRCC clinical samples. We further investigated the impact of DBF4 on the progression of ccRCC cells. Various assays, including assessments of cell proliferation, apoptosis, the cell cycle, cell migration and invasion, and colony formation, and xenograft tumor models were subsequently performed following to the knockdown of DBF4 expression via shRNA. Results Bioinformatics analyses revealed that DBF4 is significantly overexpressed in ccRCC tissues compared with adjacent normal tissues. This overexpression was confirmed by IHC analysis of 75 pairs of clinical ccRCC tumor and adjacent tissues. Kaplan-Meier analysis revealed that high DBF4 expression was associated with a significantly lower five-year overall survival rate. Moreover, DBF4 expression was identified as an independent risk factor in multivariate Cox regression analysis. GO and KEGG pathway enrichment analyses revealed a substantial enrichment of terms associated with cell division, whereas gene set enrichment analysis (GSEA) revealed correlations between increased DBF4 expression and the activation of cell cycle-related pathways. Subsequent in vitro and in vivo experiments demonstrated that DBF4 knockdown in ccRCC cells not only suppressed proliferation and migration in vitro but also significantly inhibited tumor growth in xenograft mice by arresting the cell cycle at the G1/G0 phase, which was mediated by the inhibition of MCM2 phosphorylation and cyclin D1 and CDK4 expression. Conclusion The current study revealed that DBF4 overexpression is a significant factor associated with malignant features and poor prognosis in patients with ccRCC. Therefore, it was proposed that DBF4 could serve as a novel potential prognostic biomarker and molecular target for ccRCC. Clinical trial number Not applicable.

Organohydrogels have demonstrated superior environmental adaptability and frost resistance compared to conventional hydrogels, thereby prompting considerable interests in the development and design of innovative organohydrogels. Herein, we report an effective one-pot method for fabricating MXene/polyacrylamide (MXene/PAM) composite organohydrogel (MAOH) by employing Ga liquid metals (Ga LMs) as a highly reactive component in the induced free radical polymerization reaction, without the need for additional heating or cross-linking agents. This synthetic protocol addresses the time-consuming and organic solvent waste concerns associated with traditional solvent displacement methods for organohydrogel preparation. The incorporation of MXene not only highly enhances the conductivity but also confers improved mechanical properties of MAOH. The MAOH exhibits excellent environmental adaptability (> 7 d), sustained moisture retention, remarkable self-healing capabilities, and outstanding mechanical properties under low temperatures (−20 °C). It demonstrates exceptional performance in micro-motion monitoring, rapid response time (125 ms), superior stretchability, and a broad range of strains (0.3%–600%). Therefore, the designed MAOH has great potential for applications in diverse fields such as prosthetics, electronic skin, human–machine interaction, and smart terminals.

The human microbiome is now recognized as a central regulator of cancer biology, intricately shaping tumor development, immune dynamics, and therapeutic response. This comprehensive review delineates the multifaceted roles of bacteria, viruses, and fungi in modulating the tumor microenvironment and systemic immunity across diverse cancer types. We synthesize current evidence on how microbial dysbiosis promotes carcinogenesis via chronic inflammation, metabolic reprogramming, genotoxic stress, immune evasion, and epigenetic remodeling. This review emphasizes organ‐specific microbiome signatures and highlights their potential as non‐invasive biomarkers for early detection, treatment stratification, and prognosis. Furthermore, we explore the impact of intratumoral microbiota on cancer therapies, uncovering how microbial metabolites and host–microbe interactions shape therapeutic efficacy and resistance. Finally, advances in microbiome‐targeted strategies, such as probiotics, fecal microbiota transplantation, and engineered microbes offer new avenues for adjunctive cancer therapy. This review provides a roadmap for future investigation and underscores the transformative promise of microbiome modulation in cancer prevention and treatment. This comprehensive review elucidates the transformative role of the human microbiome in cancer biology, revealing innovative mechanistic insights into the intricate tumor–microbe interactions across diverse organ systems. This work highlights the clinical and translational value of novel microbiome‐based biomarkers for early detection, prognosis, and therapeutic response prediction. Furthermore, this review examines breakthrough insights into how the microbiome modulates the tumor microenvironment and influences the efficacy of major cancer treatments, including chemotherapy, radiotherapy, immunotherapy, and targeted therapies. By integrating these findings, this review contributes to an advanced understanding of personalized, effective, and less‐toxic cancer management strategies. Highlights Microbiome dysbiosis drives carcinogenesis via multiple mechanisms. Microbiome‐targeted strategies offer novel therapeutic avenues. Organ‐specific microbiome signatures serve as non‐invasive biomarkers. Intratumoral microbiota modulate therapy efficacy and resistance. Microbial metabolites reprogram the tumor microenvironment.

Mesoporous silica materials have attracted great research interest for various applications ranging from (bio)catalysis and sensing to drug delivery. It remains challenging to prepare hollow mesoporous silica nanoparticles (HMSN) with large center-radial mesopores that could provide a more efficient transport channel through the cell for guest molecules. Here, we propose a novel strategy for the preparation of HMSN with large dendritic mesopores to achieve higher enzyme loading capacity and more efficient bioreactors. The materials were prepared by combining barium sulfate nanoparticles (BaSO4 NP) as a hard template and the in situ-formed 3-aminophenol/formaldehyde resin as a porogen for directing the dendritic mesopores’ formation. HMSNs with different particle sizes, shell thicknesses, and pore structures have been prepared by choosing BaSO4 NP of various sizes and adjusting the amount of tetraethyl orthosilicate added in synthesis. The obtained HMSN-1.1 possesses a high pore volume (1.07 cm3 g−1), a large average pore size (10.9 nm), and dendritic mesopores that penetrated through the shell. The advantages of HMSNs are also demonstrated for enzyme (catalase) immobilization and subsequent use of catalase-loaded HMSNs as bioreactors for catalyzing the H2O2 degradation reaction. The hollow and dendritic mesoporous shell features of HMSNs provide abundant tunnels for molecular transport and more accessible surfaces for molecular adsorption, showing great promise in developing efficient nanoreactors and drug delivery vehicles.

Cancer immunotherapy has emerged as a transformative therapeutic strategy that harnesses the immune system to combat malignant tumors, overcoming critical limitations such as the nonspecific cytotoxicity of conventional chemotherapy and radiotherapy and drug resistance arising from target mutations in targeted therapies. Growing evidence demonstrates that the human microbiome plays a pivotal role in modulating immune responses and influencing the efficacy of immunotherapeutic interventions. Although the impact is increasingly recognized, the molecular mechanisms and translational potential of microbiome‐based strategies remain incompletely explored. This review systematically elucidates how microorganisms from distinct anatomical sites (including bacteria, fungi, and viruses residing in the gut, oral cavity, skin, respiratory tract, and urogenital tract) and intratumoral microbes modulate the tumor immune microenvironment through metabolites, immune cell priming, and antigen mimicry. Furthermore, we discuss how specific microbial signatures predict responses to immune checkpoint inhibitors (ICIs) and CAR‐T cell therapy, and highlight emerging interventional strategies, including fecal microbiome transplantation (FMT), probiotics, and engineered bacteria, that demonstrate synergistic effects with immunotherapy in preclinical and clinical settings. By integrating mechanistic insights with translational advances, this review provides a comprehensive scientific foundation for microbiome‐based precision immunotherapy, aimed at improving patient survival outcomes and reducing treatment‐related adverse events. The microbiome is related to the efficacy of immunotherapy and can be utilized to predict the efficacy and adverse reactions of immunotherapy. Microbiome‐targeted intervention strategies can improve the efficacy of ICI, but necessitating more comprehensive exploration.

PurposeThe purpose of this paper is to examine how the emergent 3D interactive media technologies are used as a viable tool for enhancing visitors’ overall experiences at an exhibition entitled, 300 Years of Hakka Kungfu – Digital Vision of Its Legacy and Future (Hakka Kungfu Exhibition) – presented and co-organized by the Intangible Cultural Heritage Office of Hong Kong, International Guoshu Association and the School of Creative Media, City University of Hong Kong.Design/methodology/approachA questionnaire survey in both online and paper-based formats was used for identifying visitors’ experiences in the interactions with the multimedia technologies. For this research study, a questionnaire, consisting of 26 items, was set out to measure the visitors’ experiences at the Exhibition. Since the Exhibition was about presenting a centuries-old Chinese cultural heritage, Hakka Kungfu via the use multimedia technologies, in the context of establishing a dialogue between the past and present, the researchers included questionnaire items that were devoted to enquire about the level of understanding, knowledge and enjoyment, and visitors’ new knowledge about Hong Kong history and culture was successfully disseminated to the respondents at the end of the questionnaire.FindingsA total of 209 completed questionnaires were collected at this Hakka Kungfu Exhibition. The findings reveal that the exhibits did attract people at all ages. This Exhibition gave the visitors a sense of interest and wonder in the object and information presented in the Exhibition. Findings of this study also reveal that this Exhibition has successfully attracted a large number of female visitors, as well as visitors who have never taken any martial arts training. In addition, visitors’ Exhibition experience was found to be memorable, as well as enjoyable. Furthermore, visitors’ experience within the Exhibition suggested that it was entertaining, as well as educational. By creating a long-lasting impact on the minds of these Exhibition visitors about the connections between and relevance of traditional Chinese Kungfu, their collective cultural identity, as well as the contemporary society we live in. The Exhibition exemplified the successful integration of the presentation of Kungfu as a form of cultural heritage with engagement-creating technology, in which technology is unobtrusive but effective.Originality/valueAlthough it is already a global trend for the museums to integrate multimedia technologies into their exhibitions, research on the situation and feedback of multimedia technology used in the museum exhibitions in Hong Kong is scarce as well as scattered. Findings of this study could help identify various factors involved in audience participation, thereby exploring the possibility of building a contact point/space for traditional Chinese Kungfu as an intangible cultural heritage, via the integration of the latest media technologies. In particular, the development of multimedia technologies has become increasingly important to museums, and museum professionals have been exploring how digital and communication technologies can be developed to offer visitors a more interactive, personalized museum experience. In general, despite the growing interest in deploying digital technology as interpretation devices in museums and galleries, there are relatively few studies that examine how visitors, both alone and with others, use new technologies when exploring the museum contents.