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Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD‐1)/programmed cell death 1 ligand 1 (PD‐L1) pathway have transformed urothelial cancer (UC) therapy. The correlation between PD‐L1 expression and ICI effectiveness is uncertain, leaving the role of PD‐L1 as a predictive marker for ICI efficacy unclear. Among several ways to enhance the efficacy of ICI, trials are exploring combining ICIs with serine/threonine‐protein kinase mTOR (mTOR) inhibitors in different tumor types. The potential interaction between mTOR inhibitors and PD‐L1 expression in UC has not been well characterized. In our study, we investigated how phosphoinositide 3‐kinase (PI3K)/AKT/mTOR pathway inhibitors (TAK‐228, everolimus and TAK‐117) affect PD‐L1 expression and function in preclinical bladder cancer cell models. TAK‐228 increased cell surface levels of glycosylated PD‐L1 in all but one of the seven cell lines, regardless of baseline levels. TAK‐228 promoted the secretion of epidermal growth factor (EGF) and interferon‐β (IFNβ), both linked to PD‐L1 protein induction. Blocking EGF and IFNβ receptors reversed the TAK‐228‐induced PD‐L1 increase. Additionally, TAK‐228 enhanced IFN‐γ‐induced PD‐L1 expression and intracellular HLA‐I levels in some cells. TAK‐228‐treated bladder cancer cells exhibited resistance to the cytotoxic effects of peripheral blood mononuclear cells (PBMCs) and cluster of differentiation 8 (CD8)+ T cells. The addition of an anti‐PD‐L1 antibody diminished this resistance in T24 cells. Increased expression of PD‐L1 under TAK‐228 exposure was confirmed in patient‐derived explants (PDEs) treated ex vivo. These preclinical findings suggest that mTOR inhibition with TAK‐228 can increase PD‐L1 levels, potentially impacting the specific immune response against UC cells. This highlights the rationale for exploring the combination of mTOR inhibitors with ICIs in patients with advanced UC. mTOR inhibition with TAK‐228 can increase PD‐L1 levels, potentially impacting the specific immune response against bladder cancer cell lines.

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD‐1)/programmed cell death 1 ligand 1 (PD‐L1) pathway have transformed urothelial cancer (UC) therapy. The correlation between PD‐L1 expression and ICI effectiveness is uncertain, leaving the role of PD‐L1 as a predictive marker for ICI efficacy unclear. Among several ways to enhance the efficacy of ICI, trials are exploring combining ICIs with serine/threonine‐protein kinase mTOR (mTOR) inhibitors in different tumor types. The potential interaction between mTOR inhibitors and PD‐L1 expression in UC has not been well characterized. In our study, we investigated how phosphoinositide 3‐kinase (PI3K)/AKT/mTOR pathway inhibitors (TAK‐228, everolimus and TAK‐117) affect PD‐L1 expression and function in preclinical bladder cancer cell models. TAK‐228 increased cell surface levels of glycosylated PD‐L1 in all but one of the seven cell lines, regardless of baseline levels. TAK‐228 promoted the secretion of epidermal growth factor (EGF) and interferon‐β (IFNβ), both linked to PD‐L1 protein induction. Blocking EGF and IFNβ receptors reversed the TAK‐228‐induced PD‐L1 increase. Additionally, TAK‐228 enhanced IFN‐γ‐induced PD‐L1 expression and intracellular HLA‐I levels in some cells. TAK‐228‐treated bladder cancer cells exhibited resistance to the cytotoxic effects of peripheral blood mononuclear cells (PBMCs) and cluster of differentiation 8 (CD8)+ T cells. The addition of an anti‐PD‐L1 antibody diminished this resistance in T24 cells. Increased expression of PD‐L1 under TAK‐228 exposure was confirmed in patient‐derived explants (PDEs) treated ex vivo . These preclinical findings suggest that mTOR inhibition with TAK‐228 can increase PD‐L1 levels, potentially impacting the specific immune response against UC cells. This highlights the rationale for exploring the combination of mTOR inhibitors with ICIs in patients with advanced UC.

Enveloped viruses encased within a lipid bilayer membrane are highly contagious and can cause many infectious diseases like influenza and COVID-19, thus calling for effective prevention and inactivation strategies. Here, we develop a diatomic iron nanozyme with lipoxidase-like (LOX-like) activity for the inactivation of enveloped virus. The diatomic iron sites can destruct the viral envelope via lipid peroxidation, thus displaying non-specific virucidal property. In contrast, natural LOX exhibits low antiviral performance, manifesting the advantage of nanozyme over the natural enzyme. Theoretical studies suggest that the Fe-O-Fe motif can match well the energy levels of Fe 2 minority β-spin d orbitals and pentadiene moiety π* orbitals, and thus significantly lower the activation barrier of cis , cis -1,4-pentadiene moiety in the vesicle membrane. We showcase that the diatomic iron nanozyme can be incorporated into air purifier to disinfect airborne flu virus. The present strategy promises a future application in comprehensive biosecurity control. Enveloped viruses encased within a lipid bilayer membrane are highly contagious and cause diseases like influenza and COVID-19, so strategies for their prevention and inactivation are needed. Here, the authors develop a diatomic iron nanozyme with lipoxidase-like activity for the inactivation of enveloped viruses, where the diatomic iron sites destroy the viral envelope via lipid peroxidation.

The preliminary structure, in vitro antioxidant and in vivo hepatoprotective activities of water-soluble polysaccharides (ORWP) and alkali-soluble polysaccharides (ORAP), prepared from the mushroom Oudemansiella radicata, were investigated. Both ORWP and ORAP were heteropolysaccharides with mannose, glucose and galactose being the main monosaccharide components. Regarding the antioxidant activities, ORWP and ORAP showed effective 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, hydrogen peroxide scavenging activity and lipid peroxidation inhibitory effects, as well as moderate reducing power and Fe2+ chelating activity. For the hepatoprotective activity, administration of ORWP and ORAP prevented the increase in serum alanine aminotransferase and aspartate aminotransferase activities in a carbon tetrachloride-induced acute liver damage model, suppressed hepatic malondialdehyde formation and stimulated the activities of hepatic superoxide dismutase and glutathione peroxidase. Thus, we speculate that ORWP and ORAP may protect the liver from CCl4-induced hepatic damage via antioxidant mechanisms.

The natural fermentation of cigar tobacco leaves usually utilizes natural temperature and humidity for fermentation. Cigars produced in China are often fermented in winter, and the low environmental temperatures can lead to slow heating of the tobacco stack, affecting the cigar tobacco leaves quality. This study aimed to determine the minimum chamber temperature required to initiate the process of fermentation for cigar tobacco leaves and to explore the impact of temperature on the microbial community of tobacco leaves. Here, the cigar variety “Dexue 1” were subjected to stacking fermentation under three temperature parameters (20 ℃, 27 ℃, 34 ℃). With an increase in environmental temperature, the temperature inside the stack of cigar leaves increased significantly, the protein, total sugar, starch, and total alkaloid content in fermented tobacco leaves decreased, and the aroma components and amino acid content increased. Microbial richness and community diversity associated with fermented tobacco were highest at chamber temperatures of above 27 ℃. The relative abundance of Chryseobacterium and Rhodococcus was significantly negatively correlated with protein, alkaloids, total sugar, and starch, and positively correlated with amino acids and aroma components. Chryseobacterium and Rhodococcus may be responsible for the degradation of macromolecular substances and the conversion of favorable aromatic substances, thus improving the tobacco leaves quality. This study demonstrated that increasing the fermentation chamber temperature above 27 ℃ was conductive to raising the inner-stack temperature, increased microbial diversity and aromatic quality, reduced the strength and irritation, and extremely enhanced the overall quality of fermented cigar tobacco leaves.Key points• The environmental temperature of the fermentation chamber has a significant impact on the quality of tobacco• Temperature > 27 ℃ can initiate the process of cigar tobacco leaves fermentation and increase inner-stack temperature and microbial diversity and abundance• Chryseobacterium and Rhodococcus may be related to the degradation of macromolecular substances and the transformation of aromatic substances, thereby improving the quality of tobacco leaves

Hepatocellular carcinoma (HCC) ranks as the third most common malignant tumor globally. Although hyperthermia has shown promise as a non-invasive treatment for tumors, its specific mechanisms and impact on HCC remain underexplored. This study aims to investigate the effects of hyperthermia on HCC proliferation and apoptosis and to elucidate the role of the Hippo signaling pathway in these processes. Huh7 and HepG2 HCC cells were cultured at various temperatures (37 °C, 40 °C, 43 °C, and 46 °C), with 37 °C as the control. Cell proliferation, apoptosis, and cell cycle distribution were assessed via CCK-8 assays and flow cytometry. A subcutaneous xenograft model in nude mice, treated with indocyanine green (ICG) and near-infrared (NIR) irradiation to achieve local hyperthermia, was used to evaluate in vivo tumor growth. RNA-seq and KEGG pathway analyses identified differentially expressed genes, and Western blotting and immunofluorescence were used to confirm the involvement of the Hippo signaling pathway. Hyperthermia at 43 °C significantly inhibited Huh7 and HepG2 cell proliferation and induced apoptosis, accompanied by cell cycle arrest. In vivo, local hyperthermia reduced tumor volume and weight in the ICG + NIR-treated group. RNA-seq and KEGG analyses revealed that the Hippo signaling pathway was activated under hyperthermic conditions, with YAP expression and nuclear translocation markedly downregulated. Further experiments showed that YAP overexpression mitigated hyperthermia-induced effects on cell proliferation and apoptosis, underscoring the role of the Hippo pathway. These findings demonstrate that hyperthermia inhibits HCC growth by regulating the Hippo signaling pathway, reducing cell proliferation, and promoting apoptosis. This study highlights the potential of hyperthermia as an effective therapeutic approach for HCC, with implications for developing targeted hyperthermic therapies.

Developing targeted therapeutic drugs for liver cancer remains a significant scientific and clinical challenge. Previous research by the authors showed that taraxasterol (TS) can enhance the antitumor immune response of T-lymphocytes, inhibiting the growth of liver cancer cells both in vivo and in vitro. To improve the targeting ability and efficacy of TS, the authors synthesized a novel compound, Bio-SS-TS, which utilizes the high expression of biotin receptors on tumor cell membranes to link biotin to TS for increased targeting to hepatocellular carcinoma cells, and its disulfide bond can be specifically hydrolyzed by high - level glutathione (GSH) in tumor cells to release the active component TS. In vitro, Bio-SS-TS reduced liver cancer cell (HepG2 and Huh7) proliferation, impaired mitochondrial membrane potential, decreased intracellular GSH content in tumor cells, increased the reactive oxygen species level, and promoted the release of cytochrome c. Endogenous GSH in cancer cells reduced the disulfide bond in Bio-SS-TS, releasing active TS components. In vivo, treatment with Bio-SS-TS caused no significant change in mouse body weight and no toxicity to the main organs. The present study comprehensively demonstrates that Bio-SS-TS exerts a potent anti - liver cancer effect by enhancing mitochondria-dependent apoptosis, which may provide a new candidate for targeted liver cancer therapy.

Current management of canine mammary tumors (CMTs) remains reliant on surgical resection and chemotherapy. However, these strategies are often limited by high recurrence rates and systemic toxicity. Addressing these limitations requires urgent development of safer and more effective therapeutics. Pseudolaric acid B (PAB), a bioactive compound extracted from the roots of the Gord., has garnered attention for its broad-spectrum antitumor activity and favorable pharmacokinetic profile, and it has shown promise in inhibiting the growth of a variety of tumors, including breast cancer. The aim of this study was to investigate the anticancer effects of PAB on canine mammary tumor U27 cells and its underlying mechanisms. analyses demonstrated that PAB dose dependently reduced cell viability, suppressed cell proliferation, and triggered caspase-mediated apoptosis. Transcriptomic profiling of PAB-treated tumor cells revealed significant enrichment of differentially expressed genes in pathways such as gap junction, cell cycle, and cellular senescence. Mechanistically, CDK1 suppression by PAB, achieved through binding that diminishes its expression and stability, induced G2/M phase arrest and halted mitotic progression. While these findings suggest the potential of PAB as a candidate for canine mammary tumor treatment, further investigations are warranted to delineate its precise targeting specificity and pharmacodynamic interactions. These findings not only expand the translational applicability of PAB in veterinary oncology but also identify CDK1 as a potential therapeutic vulnerability for combinatorial treatment strategies in CMTs.

CD3, a surface antigen critical for T cell activation and signal transduction, serves as a key diagnostic marker for T cell-associated malignancies and a therapeutic target in immunotherapy. With canine models gaining prominence in translational immunology and oncology, reliable tools to study T cell-mediated immunity are essential. In this study, recombinant canine CD3ε protein was generated via eukaryotic expression and used to immunize rabbits, yielding a novel rabbit anti-canine CD3ε monoclonal antibody (mAb), designated HORCF-CD3.1. Functional characterization confirmed its specificity through flow cytometry and Western blot, demonstrating robust binding to CD3 molecules. Furthermore, the mAb effectively induced T cell stimulation when applied as an anti-CD3 activator. These findings validate HORCF-CD3.1 as a versatile tool for ELISA, Western blot, and flow cytometry applications. The successful development of this species-specific antibody provides a foundation for advancing diagnostic and therapeutic strategies targeting T cell-related diseases in both humans and dogs.

This study proposes an Additive Wavelet Transform (AWT)-based method to fuse Multispectral UAV (MS UAV, 5 cm resolution) and Sentinel-2 satellite imagery (10–20 m resolution), generating 5 cm resolution fused images with a focus on near-infrared and shortwave infrared bands to enhance the accuracy of mango canopy water content monitoring. The fused Sentinel-2 and MS UAV data were validated and calibrated using field-collected hyperspectral data to construct vegetation indices, which were then used with five machine learning (ML) models to estimate Fuel Moisture Content (FMC), Equivalent Water Thickness (EWT), and canopy water content (CWC). The results indicate that the addition of fused Sentinel-2 data significantly improved the estimation accuracy of all parameters compared to using MS UAV data alone, with the Genetic Algorithm Backpropagation Neural Network (GABP) model performing best (R2 = 0.745, 0.859, and 0.702 for FMC, EWT, and CWC, respectively), achieving R2 improvements of 0.066, 0.179, and 0.210. Slope, canopy coverage, and human activities were identified as key factors influencing the spatial variability of FMC, EWT, and CWC, with CWC being the most sensitive to environmental changes, providing a reliable representation of mango canopy water status.