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Chemoresistance of cancer cells is a major problem in treating cancer. Knowledge of how cancer cells may die or resist cancer drugs is critical to providing certain strategies to overcome tumour resistance to treatment. Paclitaxel is known as a chemotherapy drug that can suppress the proliferation of cancer cells by inducing cell cycle arrest and induction of mitotic catastrophe. However, today, it is well known that paclitaxel can induce multiple kinds of cell death in cancers. Besides the induction of mitotic catastrophe that occurs during mitosis, paclitaxel has been shown to induce the expression of several pro-apoptosis mediators. It also can modulate the activity of anti-apoptosis mediators. However, certain cell-killing mechanisms such as senescence and autophagy can increase resistance to paclitaxel. This review focuses on the mechanisms of cell death, including apoptosis, mitotic catastrophe, senescence, autophagic cell death, pyroptosis, etc., following paclitaxel treatment. In addition, mechanisms of resistance to cell death due to exposure to paclitaxel and the use of combinations to overcome drug resistance will be discussed.

Porcine reproductive and respiratory syndrome virus (PRRSV) has led to significant economic losses in the global swine industry. Type I interferon (IFN-I) plays a crucial role in the host’s resistance to PRRSV infection. Despite extensive research showing that PRRSV employs multiple strategies to antagonise IFN-I induction, the underlying mechanisms remain to be fully elucidated. In this study, we have discovered that PRRSV inhibits the production of IFN-I by degrading TANK-binding kinase 1 (TBK1) through chaperon-mediated autophagy (CMA). From a mechanistic standpoint, PRRSV nonstructural protein 2 (Nsp2) increases the interaction between the heat shock protein member 8 (HSPA8) and TBK1. This interaction leads to the translocation of TBK1 into lysosomes for degradation, mediated by lysosomal-associated membrane protein 2A (LAMP2A). As a result, the downstream activation of IFN regulatory factor 3 (IRF3) and the production of IFN-I are hindered. Together, these results reveal a new mechanism by which PRRSV suppresses host innate immunity and contribute to the development of new antiviral strategies against the virus.

Hashimoto’s thyroiditis (HT) is the most common autoimmune disease characterized by lymphocytic infiltration and thyrocyte destruction. Dissection of the interaction between the thyroidal stromal microenvironment and the infiltrating immune cells might lead to a better understanding of HT pathogenesis. Here we show, using single-cell RNA-sequencing, that three thyroidal stromal cell subsets, ACKR1 + endothelial cells and CCL21 + myofibroblasts and CCL21 + fibroblasts, contribute to the thyroidal tissue microenvironment in HT. These cell types occupy distinct histological locations within the thyroid gland. Our experiments suggest that they might facilitate lymphocyte trafficking from the blood to thyroid tissues, and T cell zone CCL21 + fibroblasts may also promote the formation of tertiary lymphoid organs characteristic to HT. Our study also demonstrates the presence of inflammatory macrophages and dendritic cells expressing high levels of IL-1β in the thyroid, which may contribute to thyrocyte destruction in HT patients. Our findings thus provide a deeper insight into the cellular interactions that might prompt the pathogenesis of HT. Hashimoto’s Thyroiditis is an autoimmune disease with a complex pathomechanism. Authors here show by single cell RNA sequencing that the thyroidal microenvironment in the disease is characterised by three stromal cell subtypes that are potentially responsible for the recruitment of infiltrating inflammatory immune cells, such as macrophages and dendritic cells.

The amino acid sequences of peptides determine their self-assembling properties. Accurate prediction of peptidic hydrogel formation, however, remains a challenging task. This work describes an interactive approach involving the mutual information exchange between experiment and machine learning for robust prediction and design of (tetra)peptide hydrogels. We chemically synthesize more than 160 natural tetrapeptides and evaluate their hydrogel-forming ability, and then employ machine learning-experiment iterative loops to improve the accuracy of the gelation prediction. We construct a score function coupling the aggregation propensity, hydrophobicity, and gelation corrector C g , and generate an 8,000-sequence library, within which the success rate of predicting hydrogel formation reaches 87.1%. Notably, the de novo-designed peptide hydrogel selected from this work boosts the immune response of the receptor binding domain of SARS-CoV-2 in the mice model. Our approach taps into the potential of machine learning for predicting peptide hydrogelator and significantly expands the scope of natural peptide hydrogels. Accurate prediction of peptidic hydrogels could prove useful for diverse biomedical applications. Here, the authors develop a “human-in-the-loop” approach that integrates coarse-grained molecular dynamics, machine learning, and experimentation to design natural peptide hydrogels.

Alternative RNA splicing plays an important role in cancer. To determine which factors involved in RNA processing are essential in prostate cancer, we performed a genome-wide CRISPR/Cas9 knockout screen to identify the genes that are required for prostate cancer growth. Functional annotation defined a set of essential spliceosome and RNA binding protein (RBP) genes, including most notably heterogeneous nuclear ribonucleoprotein L (HNRNPL). We defined the HNRNPL-bound RNA landscape by RNA immunoprecipitation coupled with next-generation sequencing and linked these RBP–RNA interactions to changes in RNA processing. HNRNPL directly regulates the alternative splicing of a set of RNAs, including those encoding the androgen receptor, the key lineage-specific prostate cancer oncogene. HNRNPL also regulates circular RNA formation via back splicing. Importantly, both HNRNPL and its RNA targets are aberrantly expressed in human prostate tumors, supporting their clinical relevance. Collectively, our data reveal HNRNPL and its RNA clients as players in prostate cancer growth and potential therapeutic targets.

As a promising alternative platform for cellular immunotherapy, natural killer cells (NK) have recently gained attention as an important type of innate immune regulatory cell. NK cells can rapidly kill multiple adjacent cancer cells through non-MHC-restrictive effects. Although tumors may develop multiple resistance mechanisms to endogenous NK cell attack, in vitro activation, expansion, and genetic modification of NK cells can greatly enhance their anti-tumor activity and give them the ability to overcome drug resistance. Some of these approaches have been translated into clinical applications, and clinical trials of NK cell infusion in patients with hematological malignancies and solid tumors have thus far yielded many encouraging clinical results. CAR-T cells have exhibited great success in treating hematological malignancies, but their drawbacks include high manufacturing costs and potentially fatal toxicity, such as cytokine release syndrome. To overcome these issues, CAR-NK cells were generated through genetic engineering and demonstrated significant clinical responses and lower adverse effects compared with CAR-T cell therapy. In this review, we summarize recent advances in NK cell immunotherapy, focusing on NK cell biology and function, the types of NK cell therapy, and clinical trials and future perspectives on NK cell therapy.

This study aimed to understand green finance’s impact on fertilizer use and agricultural carbon emissions. We selected the macro panel data of 30 provinces (cities) in China from 2000 to 2019. The main research methods are standardized test framework (cross-sectional dependence, unit root and cointegration test), the latest causal test, impulse response, and variance decomposition analysis. Examined the long-term equilibrium relationship between green finance, fertilizer use, and agricultural carbon emissions. The results show: fertilizer consumption and agricultural carbon emissions have a positive correlation. However, green finance can significantly reduce agricultural carbon emissions. The causal test confirmed the bidirectional causal relationship between agricultural carbon emissions and fertilizer use. At the same time, verified one-way causality from green finance to both of them. Interpret the results of impulse response and variance decomposition analysis: among the changes in agricultural carbon emissions, chemical fertilizers contributed 2.45%, green finance contributed 4.34%. In addition, the contribution rate of green finance to chemical fertilizer changes reached 11.37%. Green finance will make a huge contribution to reducing fertilizer use and agricultural carbon emissions within a decade. The research conclusions provide an important scientific basis for China’s provinces (cities) to formulate carbon emission reduction policies. China has initially formed a policy system and market environment to support the development of green finance, in 2020, the “dual carbon” goal was formally proposed. In 2021, the national “14th Five-Year Plan” and the 2035 Vision Goals emphasized the importance of green finance. It plays an important supporting role in carbon emission reduction goals, and green finance has become an important pillar of national strategic goals.

Metal-organic frameworks (MOFs) with high porosity and designable functionality make it possible to access the merits of high permeability and selectivity. However, scalable fabrication methods to produce mixed matrix membranes (MMMs) with good flexibility and ultrahigh MOF loading are urgently needed yet largely unmet. Herein, we report a thermally induced phase separation-hot pressing (TIPS-HoP) strategy to roll-to-roll produce 10 distinct MOF-membranes (loadings up to 86 wt%). Ultrahigh-molecular-weight polyethylene interweaving the MOF particles contributes to their mechanical strength. Rejections (99%) of organic dyes with a water flux of 125.7 L m –2  h –1  bar –1 under cross-flow filtration mode. The micron-sized channels between the MOF particles translate into fast water permeation, while the porous MOFs reject solutes through rapid adsorption. This strategy paves ways for developing high-performance membrane adsorbers for crucial separation processes. As a proof-of-concept, the abilities of the membrane adsorbers for separating racemates and proteins have been demonstrated. Mixed matrix membranes have shown great promise for separation applications, but low filler loading typically leads to low selectivity. Here the authors use a thermally induced phase separation-hot-pressing strategy to fabricate 10 distinct metal-organic framework-based membrane adsorbers with up to 86 wt% MOF-loading.

Ecosystem service value (ESV) constitutes the ecological value foundation for enhancing tourism economic resilience (TER), serving as the central catalytic mechanism that drives the synergistic evolution of system disturbance resistance, recovery efficiency, and transformative adaptability. This study conducts a comprehensive evaluation of the interrelation between ESV and TER while exploring the key influencing factors to optimize human-environment interactions within the tourism system. The Coupling Coordination Degree (CCD) model is utilized to examine the association between ESs and TER across China. Additionally, spatial evolution patterns and key driving factors are explored using Exploratory Spatial Data Analysis (ESDA) and Geographically Weighted Regression (GWR). The key findings are as follows: (1) ESV displayed an inverted “N” trend, declining from southeast to northwest. (2) The spatial distribution of TER showed a persistent pattern of “high in the south, low in the north,” indicating a sustained stage of coordination. (3) The CCD of TER revealed positive spatial clustering, characterized by a distinct “two poles” pattern. (4) Economic and tourism-related factors were the dominant forces enhancing the CCD of TER, while social factors imposed constraints. These insights can support regional tourism economic planning and ecosystem management strategies.

Five metabolites including two new ones, prochaetoviridin A (1) and chaetoindolin A (2), were isolated from the endophytic fungus Chaetomium globosum CDW7. Compounds 1 and 2 were characterized as an isocoumarin and an indole alkaloid derivative, respectively, with their structures elucidated by comprehensive spectroscopic analyses including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), NMR, and circular dichroism (CD) comparison. Compounds 3–5 were identified as chaetoviridin A, chaetoglobosin R, and chaetoglobosin T, respectively. Chaetoviridin A (3) exhibited antifungal activity against Sclerotinia sclerotiorum with an EC50 value of 1.97 μg/mL. In vivo test showed that 3 displayed a protective efficacy of 64.3% against rape Sclerotinia rot at the dosage of 200 μg/mL, comparable to that of carbendazim (69.2%).