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Icaritin (ICT), a natural compound extracted from the dried leaves of the genus Epimedium, possesses antitumor and immunomodulatory properties. However, the mechanisms through which ICT modulates pyroptosis and immune response in hepatocellular carcinoma (HCC) remain unclear. This study demonstrated that ICT exhibits pyroptosis-inducing and anti-hepatocarcinoma effects. Specifically, the caspase1-GSDMD and caspase3-GSDME pathways were found to be involved in ICT-triggered pyroptosis. Furthermore, ICT promoted pyroptosis in co-cultivation of HepG2 cells and macrophages, regulating the release of inflammatory cytokines and the transformation of macrophages into a proinflammatory phenotype. In the Hepa1-6+Luc liver cancer model, ICT treatment significantly increased the expression of cleaved-caspase1, cleaved-caspase3, and granzyme B, modulated cytokine secretion, and stimulated CD8+ T cell infiltration, resulting in a reduction in tumor growth. In conclusion, the findings in this research suggested that ICT may modulate cell pyroptosis in HCC and subsequently regulate the immune microenvironment of the tumor. These observations may expand the understanding of the pharmacological mechanism of ICT, as well as the therapy of liver cancer. [ABSTRACT FROM AUTHOR]

Rapid and accurate diagnostic tests are fundamental for improving patient outcomes and combating infectious diseases. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas12a‐based detection system has emerged as a promising solution for on‐site nucleic acid testing. Nonetheless, the effective design of CRISPR RNA (crRNA) for Cas12a‐based detection remains challenging and time‐consuming. In this study, we propose an enhanced crRNA design system with deep learning for Cas12a‐mediated diagnostics, referred to as EasyDesign. This system employs an optimized convolutional neural network (CNN) prediction model, trained on a comprehensive data set comprising 11,496 experimentally validated Cas12a‐based detection cases, encompassing a wide spectrum of prevalent pathogens, achieving Spearman's ρ = 0.812. We further assessed the model performance in crRNA design for four pathogens not included in the training data: Monkeypox Virus, Enterovirus 71, Coxsackievirus A16, and Listeria monocytogenes. The results demonstrated superior prediction performance compared to the traditional experiment screening. Furthermore, we have developed an interactive web server (https://crispr.zhejianglab.com/) that integrates EasyDesign with recombinase polymerase amplification (RPA) primer design, enhancing user accessibility. Through this web‐based platform, we successfully designed optimal Cas12a crRNAs for six human papillomavirus (HPV) subtypes. Remarkably, all the top five predicted crRNAs for each HPV subtype exhibited robust fluorescent signals in CRISPR assays, thereby suggesting that the platform could effectively facilitate clinical sample testing. In conclusion, EasyDesign offers a rapid and reliable solution for crRNA design in Cas12a‐based detection, which could serve as a valuable tool for clinical diagnostics and research applications. Highlights: Advanced crRNA design system: Developed EasyDesign, utilizing a convolutional neural network (CNN) trained with over 11,000 diagnostic‐target pairs to enable the creation of highly sensitive crRNAs for Cas12a‐based nucleic acid diagnostics.Proven predictive capabilities: EasyDesign demonstrates superior predictive performance for crRNA‐mediated Cas12a detection, validated through its successful application in designing diagnostics for a variety of viruses in clinical settings.User‐friendly web platform: Features an intuitive web platform that streamlines the creation of CRISPR/Cas12a‐based diagnostic tools, thereby enhancing accessibility and usability for both researchers and clinicians. [ABSTRACT FROM AUTHOR]

Transition metal oxides (TMOs) have excellent electrochemical properties. However, they are commonly associated with short cycle lives, agglomeration, and lower electrical conductivity. To ameliorate these drawbacks, porous rod-shaped CuO@Co3O4 has been synthesized through calcination with optimized oxidation temperature by using CuCo-MOF-74 as a template. Due to the porous structure, the CuO@Co3O4 electrode significantly increases the contact area with the electrolyte and greatly improves the reaction kinetics. As a result, the CuO@Co3O4 electrode exhibits excellent electrochemical performance with a specific capacitance of 545.5 F g−1 at a current density of 1 A g−1. The capacitance retention at 10 A g−1 was 88.7% after 10 000 cycles. Furthermore, an asymmetric supercapacitor (SC) has been assembled with CuO@Co3O4 as the positive electrode and commercial reduced graphene oxide (RGO) as the negative electrode, and the device has exhibited an energy density of 38.2 W h kg−1 at a power density of 1268.3 W kg−1. Impressively, the capacitance retention remained 83.2% even after 10 000 cycles at a high current density of 10 A g−1. This performance has demonstrated the potential of CuO@Co3O4 as an anode material for SCs. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is the most aggressive breast cancer subtype and chemotherapy is the cornerstone treatment for TNBC. Regrettably, emerging findings suggest that chemotherapy facilitates pro‐metastatic changes in the tumour microenvironment. Extracellular vesicles (EVs) have been highly implicated in cancer drug resistance and metastasis. However, the effects of the EVs released from dying cancer cells on TNBC prognosis and corresponding therapeutic strategies have been poorly investigated. This study demonstrated that paclitaxel chemotherapy elicited CXCL1‐enriched EVs from apoptotic TNBC cells (EV‐Apo). EV‐Apo promoted the chemoresistance and invasion of co‐cultured TNBC cells by polarizing M2 macrophages through activating PD‐L1 signalling. However, baohuoside I (BHS) remarkably sensitized the co‐cultured TNBC cells to paclitaxel chemotherapy via modulating EV‐Apo signalling. Mechanistically, BHS remarkably decreased C‐X‐C motif chemokine ligand 1 (CXCL1) cargo within EV‐Apo and therefore attenuated macrophage M2 polarization by suppressing PD‐L1 activation. Additionally, BHS decreased EV‐Apo release by diminishing the biogenesis of intraluminal vesicles (ILVs) within multivesicular bodies (MVBs) of TNBC cells. Furthermore, BHS bound to the LEU104 residue of flotillin 2 (FLOT2) and interrupted its interaction with RAS oncogene family member 31 (RAB31), leading to the blockage of RAB31‐FLOT2 complex‐driven ILV biogenesis. Importantly, BHS remarkably chemosensitised paclitaxel to inhibit TNBC metastasis in vivo by suppressing EV‐ApoCXCL1‐induced PD‐L1 activation and M2 polarization of tumour‐associated macrophages (TAMs). This pioneering study sheds light on EV‐ApoCXCL1 as a novel therapeutic target to chemosensitise TNBC, and presents BHS as a promising chemotherapy adjuvant to improve TNBC chemosensitivity and prognosis by disturbing EV‐ApoCXCL1 biogenesis. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the second most common malignancy among men globally. The Fu-Zheng-Yi-Liu (FZYL) Formula has been widely utilized in the treatment of PCa. This study investigates whether the FZYL Formula can inhibit PCa by targeting the TAMs/CCL5 pathway. We conducted in vitro co-cultures and in vivo co-injections of PCa cells and TAMs to mimic their interaction. Results showed that the FZYL Formula significantly reduced the proliferation, colony formation, subpopulations of PCSCs, and sphere-formation efficacy of PCa cells, even in the presence of TAM co-culture. Additionally, the Formula markedly decreased the migration, invasion, and epithelial-mesenchymal transition (EMT) of PCa cells induced by TAMs. The FZYL Formula also reversed M2 phenotype polarization in TAMs and dose-dependently reduced their CCL5 expression and secretion, with minimal cytotoxicity observed. Mechanistic studies confirmed that the TAMs/CCL5 axis is a critical target of the FZYL Formula, as the addition of exogenous CCL5 partially reversed the formula's inhibitory effects on PCSCs self-renewal in the co-culture system. Importantly, the Formula also significantly inhibited the growth of PCa xenografts, bone metastasis, and PCSCs activity in vivo by targeting the TAMs/CCL5 pathway. Overall, this study not only elucidates the immunomodulatory mechanism of the FZYL Formula in PCa therapy but also highlights the TAMs/CCL5 axis as a promising therapeutic target. [ABSTRACT FROM AUTHOR]

The risk assessment of airborne bacteria and fungi between different-type buildings located in temperate climate zone is still unclear. We applied the culturable method to characterize the airborne bacteria and fungi in 10 residences, 1 school, 2 office buildings, 1 hospital, and 1 library during winter in Kunming, China. In a total of 79 rooms, 152 culturable microbial samples were investigated. Results showed that there were significant disparities in bacterial concentrations among various types of buildings. The highest culturable bacterial concentration was found in residences, while the lowest was in the library. In contrast, the fungal concentrations showed little difference. The risk assessment indicated that occupants in different types of buildings in Kunming had an acceptable exposure risk (hazard index < 1) for bioaerosols. The exposure risk for bacteria in residence was significantly higher than in the others, while the mean hazard index of fungi in residence was significantly higher than in schools, hospitals, and libraries. Ventilation could reduce the HI of bioaerosols in rooms. This study is helpful to give practical implications for assessing microbial characteristics in different types of buildings and highlight the significance of evaluating the microbial concentrations in residence in temperate climate zone in China.

With the rapid development of virtual reality technology, the field of physical education in colleges and universities has gradually focused on the development of the organic integration of virtual reality technology and sports skills. Aiming at the limitations of this field and the practical needs of college sports technology difficulty, this paper investigates the basic situation of the application of virtual reality technology in sports skills teaching in 7 colleges and universities in Shaanxi, China by means of questionnaire survey and statistical analysis. The actual demand of virtual reality technology in college sports skills, college sports students’ motivation to participate in virtual reality technology, use experience and demand sports items are statistically analyzed. Finally, in view of the challenges of using virtual reality technology in college sports skills, reasonable strategies are put forward, aiming to provide more effective and interesting auxiliary teaching methods for college sports technology teaching.