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is a significant source of natural fungal medicines and has been used for the treatment of various diseases for many years. However, the use of in cancer immunotherapy is poorly elucidated. In this study, we have analyzed 2,398 English-language papers and 6,968 Chinese-language papers published between 1987 and 2017 by using bibliometrics. A steady growth in the number of publications was observed before 2004, followed by an exponential increase between 2004 and 2017. The most common category for publications about was \"Pharmacology & Pharmacy,\" in which immunomodulation (25.60%) and cancer treatment (21.40%) were the most popular subcategories. Moreover, we have provided an overview of the bioactive components and combinatorial immunomodulatory effects for the use of in the treatment of cancer, including the major pathways of immune cells. Immunomodulatory protein and polysaccharides are the key bioactive factors responsible for cancer immunotherapy, and the NF-κB and MAPK pathways are the most comprehensively investigated major pathways. Our results indicate that has a broad-spectrum application for the treatment of cancer through the regulation of the immune system. This review provides guidance for future research into the role of in cancer immunotherapy.

The development of high‐performance solid‐state electrolytes (SSEs) is critical for advancing next‐generation energy storage systems. Traditional liquid electrolytes face safety risks such as flammability, while inorganic and polymeric SSEs suffer from brittleness, low ionic conductivity, and poor thermal stability. Covalent organic frameworks (COFs), with crystalline porosity, tunable functionality, and structural robustness, have emerged as promising candidates for SSEs. This review systematically explores COF‐based electrolytes through design strategies including backbone engineering, crystal arrangement optimization, and pore decoration, which aims to provide a roadmap for designing advanced COF electrolytes, emphasizing molecular‐level precision and multifunctional integration to overcome existing limitations in energy storage technologies. This review encapsulates the cutting‐edge research progress of covalent organic framework (COF)‐based electrolytes. The ingenious design of COFs, the meticulous regulation of crystalline structures, and strategic pore decorations are highlighted, which all chart new courses for innovative design strategies for advanced solid‐state electrolytes.

• Heat-stressed Arabidopsis plants release heterochromatin-associated transposable element (TE) silencing, yet it is not accompanied by major reductions of epigenetic repressive modifications. In this study, we explored the functional role of histone H1 in repressing heterochromatic TEs in response to heat stress. • We generated and analyzed RNA and bisulfite-sequencing data of wild-type and h1 mutant seedlings before and after heat stress. • Loss of H1 caused activation of pericentromeric Gypsy elements upon heat treatment, despite these elements remaining highly methylated. By contrast, nonpericentromeric Copia elements became activated concomitantly with loss of DNA methylation. The same Copia elements became activated in heat-treated chromomethylase 2 (cmt2) mutants, indicating that H1 represses Copia elements through maintaining DNA methylation under heat. • We discovered that H1 is required for TE repression in response to heat stress, but its functional role differs depending on TE location. Strikingly, H1-deficient plants treated with the DNA methyltransferase inhibitor zebularine were highly tolerant to heat stress, suggesting that both H1 and DNA methylation redundantly suppress the plant response to heat stress.

Background Lianhuaqingwen (LHQW) has been used in the treatment of chronic bronchitis, but the precise mechanism through which LHQW exhibits its anti-inflammatory effects in this context is not yet fully understood. The aim of this study was to investigate the active ingredients and signaling pathways responsible for LHQW's effectiveness in managing chronic bronchitis. Methods The research leveraged the TCMSP database to determine the active compounds and drug targets of LHQW. In parallel, the GeneCards, DrugBank, and PharmGkb databases were used to uncover targets pertinent to chronic bronchitis. To discern the potential mechanisms by which LHQW's active ingredients might treat chronic bronchitis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Network pharmacology facilitated the construction of a drug-active ingredient-disease target network, aiding in forecasting the core targets for chronic bronchitis treatment by LHQW. Subsequently, molecular docking techniques alongside in vitro experiments were applied to confirm the interactions between the active ingredients and the primary targets. Results A total of 157 active ingredients, 225 potential drug targets, and 594 bronchitis-related targets were derived from various databases. Following this, 76 potential gene targets were pinpointed by integrating drug and related targets. GO and KEGG enrichment analyses were employed to identify key pathways involved in LHQW's mechanism for treating chronic bronchitis. By constructing a protein–protein interaction (PPI) network for the 76 potential gene targets, four core targets (TNF, IL6, IFNG, and STAT3) were identified as primarily involved in responses to lipopolysaccharide, the TNF pathway, and the JAK-STAT pathway. Molecular docking results revealed a favorable affinity between multiple active ingredients of LHQW and the four core targets, suggesting that the therapeutic effects are mediated through the inhibition of inflammatory responses and signaling pathways. Interestingly, quercetin, an active ingredient of LHQW, was observed to bind to all four core targets simultaneously. Furthermore, cell experiment and western blot analysis indicated that both LHQW and quercetin exhibit anti-inflammatory effects by targeting the four core proteins and the JAK-STAT pathways. Conclusion This research emphasizes the diverse active ingredients, targets, channels, and pathways of LHQW in the treatment of chronic bronchitis, providing important perspectives for the creation of novel therapeutic drugs and clinical uses. Graphical Abstract

Background Stable gene repression is essential for normal growth and development. Polycomb repressive complexes 1 and 2 (PRC1&2) are involved in this process by establishing monoubiquitination of histone 2A (H2Aub1) and subsequent trimethylation of lysine 27 of histone 3 (H3K27me3). Previous work proposed that H2Aub1 removal by the ubiquitin-specific proteases 12 and 13 (UBP12 and UBP13) is part of the repressive PRC1&2 system, but its functional role remains elusive. Results We show that UBP12 and UBP13 work together with PRC1, PRC2, and EMF1 to repress genes involved in stimulus response. We find that PRC1-mediated H2Aub1 is associated with gene responsiveness, and its repressive function requires PRC2 recruitment. We further show that the requirement of PRC1 for PRC2 recruitment depends on the initial expression status of genes. Lastly, we demonstrate that removal of H2Aub1 by UBP12/13 prevents loss of H3K27me3, consistent with our finding that the H3K27me3 demethylase REF6 is positively associated with H2Aub1. Conclusions Our data allow us to propose a model in which deposition of H2Aub1 permits genes to switch between repression and activation by H3K27me3 deposition and removal. Removal of H2Aub1 by UBP12/13 is required to achieve stable PRC2-mediated repression.

The lack of tumor infiltration by CD8 + T cells is associated with poor patient response to anti-PD-1 therapy. Understanding how tumor infiltration is regulated is key to improving treatment efficacy. Here, we report that phosphorylation of HRS, a pivotal component of the ESCRT complex involved in exosome biogenesis, restricts tumor infiltration of cytolytic CD8 + T cells. Following ERK-mediated phosphorylation, HRS interacts with and mediates the selective loading of PD-L1 to exosomes, which inhibits the migration of CD8 + T cells into tumors. In tissue samples from patients with melanoma, CD8 + T cells are excluded from the regions where tumor cells contain high levels of phosphorylated HRS. In murine tumor models, overexpression of phosphorylated HRS increases resistance to anti-PD-1 treatment, whereas inhibition of HRS phosphorylation enhances treatment efficacy. Our study reveals a mechanism by which phosphorylation of HRS in tumor cells regulates anti-tumor immunity by inducing PD-L1 + immunosuppressive exosomes, and suggests HRS phosphorylation blockade as a potential strategy to improve the efficacy of cancer immunotherapy. Lack of CD8 + T-cell infiltration into solid tumors is associated with poor responsiveness to immune checkpoint therapy (ICT). Here, the authors show that blocking the phosphorylation of HRS to reduce the induction of immunosuppressive exosomes promotes CD8 + T-cell infiltration into tumors and enhances the efficacy of ICT in mouse melanoma models.

Epithelial stem cells (EpSCs) in the hair follicle bulge are required for hair follicle growth and cycling. The isolation and propagation of human EpSCs for tissue engineering purposes remains a challenge. Here we develop a strategy to differentiate human iPSCs (hiPSCs) into CD200 + /ITGA6 + EpSCs that can reconstitute the epithelial components of the hair follicle and interfollicular epidermis. The hiPSC-derived CD200 + /ITGA6 + cells show a similar gene expression signature as EpSCs directly isolated from human hair follicles. Human iPSC-derived CD200 + /ITGA6 + cells are capable of generating all hair follicle lineages including the hair shaft, and the inner and outer root sheaths in skin reconstitution assays. The regenerated hair follicles possess a KRT15 + stem cell population and produce hair shafts expressing hair-specific keratins. These results suggest an approach for generating large numbers of human EpSCs for tissue engineering and new treatments for hair loss, wound healing and other degenerative skin disorders. The hair follicle bulge contains epithelial stem cells that contribute to follicle formation during each hair cycle. Here the authors differentiate human induced pluripotent stem cells into folliculogenic epithelial stem cells, which can produce all hair follicle lineages including a stem cell population.

Background This study evaluates the effectiveness of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria, typically applied to singleton pregnancies, in managing gestational diabetes mellitus (GDM) in twin pregnancies. Focusing on a Chinese cohort, it contrasts the clinical outcomes and complications in twin pregnancies with and without GDM. Methods We conducted a retrospective cohort study at our hospital from January 2019 to December 2021, including all twin deliveries except those before 28 weeks of gestation, with prior diabetes, or unknown GDM status. GDM was diagnosed using a 75 g oral glucose tolerance test based on the IADPSG criteria, and management involved dietary or insulin interventions. We assessed outcomes such as hypertensive disorders (gestational hypertension, preeclampsia, and eclampsia), membrane rupture, preterm birth, small for gestational age (SGA), large for gestational age (LGA), and neonatal intensive care unit (NICU) admissions. Results Among 1003 twin pregnancies, 21.7% had GDM, with 11.5% receiving insulin. GDM was associated with older maternal age, higher BMI, and a family history of diabetes. Pregnant women with GDM had lower weekly weight gain (0.44 kg/week vs. 0.58 kg/week, p  < 0.001) and experienced a higher risk of SGA neonates (aOR = 1.68, 95% CI: 1.06–2.67) and increased NICU admissions (aOR = 1.30, 95% CI: 1.00-1.69) compared to those without GDM. Additionally, dichorionic twins with GDM showed higher risks of SGA and NICU admissions, while monochorionic twins had no significant differences. A U-shaped relationship was identified between weekly weight gain and the rates of SGA and NICU admissions, with the lowest risk observed at a weekly weight gain of 0.75 kg for SGA and 0.57 kg for NICU admissions. Conclusions Applying singleton-derived IADPSG criteria to twin pregnancies may mitigate some maternal risks but elevates the risk for SGA neonates, suggesting a need for tailored diagnostic and management strategies for twin pregnancies. Trial registration Retrospectively registered.

Insulin-like growth factor-binding protein 5 (IGFBP5) is associated with nonalcoholic fatty liver disease (NAFLD). IGFBP5 has a higher binding affinity to IGF1 and modulates its effects in serum. However, the effect of exercise on its expression remains unclear. Hence, this study investigated whether exercise regulated hepatic and circulating IGFBP5 levels to ameliorate NAFLD. The NAFLD mice were regularly trained for 12 weeks on a treadmill at a 0% grade. Serum levels of IGFBP5, total IGF1, and free IGF1 were detected using proteome analyses and ELISA. Critical cytokines, such as IRS1, Akt, and AMPKα, and their phosphorylation levels mediated by IGFBP5/IGF1 were confirmed via Western blotting. The results indicated that exercise remarkably alleviated HFD-induced NAFLD and insulin resistance. Although exercise lowered serum IGFBP5 levels and the IGFBP5/total IGF1 ratio in NAFLD mice, it had no effect on the hepatic expression of IGFBP5, IGF1, and IGF1R. Moreover, exercise increased serum levels of free IGF1 in NAFLD mice, which, when bound to IGF1R, accelerated the phosphorylation levels of hepatic IRS1, Akt, and AMPKα to ameliorate NAFLD. The present study confirmed that exercise activated the effects of IGF1 by reducing the serum IGFBP5/IGF1 ratio, consequently triggering the IRS1/Akt/AMPK pathway to ameliorate HFD-induced NAFLD.

Regulatory T cells (Tregs) are essential in the maintenance of immunity, and they are also a key to immune suppressive microenvironment in solid tumors. Many studies have revealed the biology of Tregs in various human pathologies. Here we review recent understandings of the immunophenotypes and suppressive functions of Tregs in melanoma, including Treg recruitment and expansion in a tumor. Tregs are frequently accumulated in melanoma and the ratio of CD8 + T cells versus Tregs in the melanoma is predictive for patient survival. Hence, depletion of Tregs is a promising strategy for the enhancement of anti-melanoma immunity. Many recent studies are aimed to target Tregs in melanoma. Distinguishing Tregs from other immune cells and understanding the function of different subsets of Tregs may contribute to better therapeutic efficacy. Depletion of functional Tregs from the tumor microenvironment has been tested to induce clinically relevant immune responses against melanomas. However, the lack of Treg specific therapeutic antibodies or Treg specific depleting strategies is a big hurdle that is yet to be overcome. Additional studies to fine-tune currently available therapies and more agents that specifically and selectively target tumor infiltrating Tregs in melanoma are urgently needed.