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The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. This review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors.

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BACKGROUND: Psychiatric disorders, including attention-deficit hyperactivity disorder (ADHD), depression, anxiety disorders, and dementia, manifest differently across life stages, impacting cognitive, emotional, and behavioral health. Understanding the causal relationships between various types of physical activity and these disorders is crucial for developing targeted interventions. METHODS: The summary level data from GWAS was utilized to conduct a two-sample Mendelian Randomization (MR) analysis. We assessed the potential causal relationships between different types of physical activity including light do it yourself (DIY) activities, heavy DIY activities, strenuous sports, and aerobic exercises/other exercises and the prevalence of psychiatric disorders (ADHD, depression, anxiety disorders, and dementia) across different life stages. RESULTS: The MR analysis showed no causal relationship between light DIY activities and any of the psychiatric disorders studied. Heavy DIY activities showed a significant negative association with anxiety disorders but no links with ADHD, depression, or dementia. Strenuous sports did not demonstrate any causal relationship with the psychiatric disorders examined. Aerobic exercises were notably correlated with a reduced risk of depression, although no significant associations were found with ADHD, anxiety disorders, or dementia. CONCLUSIONS: The findings indicate that heavy DIY activities might contribute to reducing anxiety disorders, while aerobic exercises potentially lower the risk of depression. These results emphasize the potential benefits of promoting specific types of physical activity to improve mental health outcomes across different life stages. Future research could further investigate the mechanisms underlying these relationships and consider diverse populations and objective measures of physical activity.

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Elevated levels of various cellular inflammatory markers have been observed in patients with endometriosis (EMs). However, a causal relationship between these markers and EMS has not been firmly established. This study aimed to assess the causality between cellular inflammatory markers and the onset of EMS using a bidirectional Mendelian randomization approach. Genetic associations for EMs were derived from the largest and most recent genome-wide association study (GWAS) involving 1937 EMS cases and 245,603 controls of European ancestry. Single nucleotide polymorphisms associated with 41 cellular cytokines and other systemic inflammatory regulators were identified from 8293 Finnish participants. Estimates were obtained using inverse-variance weighted, with sensitivity analyses conducted using MR-Egger, weighted median, and MR-PRESSO. Among the 41 systemic inflammatory regulators included in the analysis, none were associated with the risk of EMs. Elevated levels of IL-6 were associated with an increased risk of EMs (OR = 1.351, 95%CI = 1.015-1.797). Conversely, genetically predicted elevated levels of platelet-derived growth factor (PDGF-BB) were associated with a reduced risk of EMs (OR = 0.856, 95%CI = 0.742-0.987). Genetically predicted elevations in IL-6 may contribute to an increased risk of EMs, while elevated PDGF-BB levels appear protective, suggesting potential therapeutic targets for EMs. Other systemic inflammatory regulators seem unrelated to EMs risk, potentially representing downstream effects or consequences of shared factors between inflammation and EMs.

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BACKGROUND: Previous studies have hinted at a significant link between lung cancer and the gut microbiome, yet their causal relationship remains to be elucidated. METHODS: GWAS data for small cell lung cancer (SCLC) was extracted from the FinnGen consortium, comprising 179 cases and 218 613 controls. Genetic variation data for 211 gut microbiota were obtained as instrumental variables from MiBioGen. Mendelian randomization (MR) was employed to determine the causal relationship between the two, with inverse variance weighting (IVW) being the primary method for causal analysis. The MR results were validated through several sensitivity analyses. RESULTS: The study identified a protective effect against SCLC for the genus Eubacterium ruminantium group (OR = 0.413, 95% CI: 0.223-0.767, p = 0.00513), genus Barnesiella (OR = 0.208, 95% CI: 0.0640-0.678, p = 0.00919), family Lachnospiraceae (OR = 0.319, 95% CI: 0.107-0.948, p = 0.03979), and genus Butyricimonas (OR = 0.376, 95% CI: 0.144-0.984, p = 0.04634). Conversely, genus Intestinibacter (OR = 3.214, 95% CI: 1.303-7.926, p = 0.01125), genus Eubacterium oxidoreducens group (OR = 3.391, 95% CI: 1.215-9.467, p = 0.01973), genus Bilophila (OR = 3.547, 95% CI: 1.106-11.371, p = 0.03315), and order Bacillales (OR = 1.860, 95% CI: 1.034-3.347, p = 0.03842) were found to potentially promote the onset of SCLC. CONCLUSION: We identified potential causal relationships between certain gut microbiota and SCLC, offering new insights into microbiome-mediated mechanisms of SCLC pathogenesis, resistance, mutations, and more.

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Endometriosis is a prevalent condition with notable impacts on fertility. Recent studies have implicated gut microbiota in the development of endometriosis associated infertility (EAI). This study employs Mendelian randomization (MR) to elucidate the causal relationship between specific gut microbes and EAI. Using MR, we selected single nucleotide polymorphisms associated with 211 gut microbiota taxa from large-scale genome-wide association studies summary data. We applied statistical methods including inverse variance weighting, weighted median, and MR-Egger for analysis. Outliers were identified through the leave-one-out method. MR-Egger intercept tests were conducted to address horizontal pleiotropy, while Cochran Q and P values assessed heterogeneity. The false discovery rate method was used for multiple testing correction. Sensitivity analysis and F statistics evaluated the reliability and potential biases of our results. The inverse variance weighting method indicated a significant association of the genus Actinomyces (OR = 1.657, 95% CI: 1.187-2.312, P = .00298) with an increased risk of EAI. Conversely, genera Holdemania (OR = 0.630, 95% CI: 0.444-0.894, P = .00969) and Ruminococcaceae NK4A214 group (OR = 0.689, 95% CI: 0.481-0.999, P = .0439) appeared as protective factors. MR-PRESSO global test and MR-Egger regression indicated no significant horizontal pleiotropy (P > .05). Leave-one-out analysis confirmed the robustness of these findings. Our study provides evidence of a causal relationship between specific gut microbiome taxa and EAI. These findings offer novel insights and may guide the development of new preventive and therapeutic strategies for managing EAI.

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Background: Psychiatric disorders (PD) pose a significant burden, with vast prevalence and mortality, inflicting substantial costs on individuals and society. Despite its widespread prevalence, the complex pathogenesis of PD remains elusive, leading to limited and challenging therapeutic development. An emerging risk factor for chronic diseases, prolonged sedentary behavior, contrasts with the therapeutic potential of exercise, regardless of its intensity, for various ailments, including PD. Yet, the diversity in exercise modalities and intensities may offer varied impacts on health. This study, leveraging Mendelian Randomization (MR), seeks to investigate the causal relationship between exercise and PD, aiming to elucidate the optimal exercise modality and intensity for PD mitigation while addressing potential confounders. Methods: This study employed a Mendelian randomization analysis using the genome-wide association study (GWAS) database to investigate the causal relationship between types of physical activity and psychiatric disorders. Sensitivity analysis was conducted to demonstrate the reliability and robustness of the results. Results: In the past 4 weeks, engaging in a substantial amount of DIY physical activity was found to have a causal relationship with psychiatric disorders (IVW: OR = 0.228, 95% CI: 0.113-0.461, P = 0.000038). As for the types of exercises, there may be a potential causal association between aerobic training (including swimming, cycling, fitness, and bowling) and psychiatric disorders (IVW: OR = 0.322, 95% CI = 0.148-0.704, P = 0.004). However, there was no causal relationship found between mild DIY physical activity and psychiatric disorders (IVW: OR = 0.918, 95% CI = 0.417-2.021, P = 0.831). Furthermore, it seems that there is no causal relationship between vigorous exercise and psychiatric disorders (IVW: OR = 2.705, 95% CI = 0.081-3.419, P = 0.578). Conclusion: Our study confirms that only a certain level of training activity can have a protective effect on psychiatric disorders, while mild physical activity or vigorous training does not have an impact on psychiatric disorders.

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Members of the WRKY transcription factor (TF) family are unique to plants and serve as important regulators of diverse physiological processes, including the ability of plants to manage biotic and abiotic stressors. However, the functions of specific WRKY family members in the context of maize responses to fungal pathogens remain poorly understood, particularly in response to Ustilago maydis (DC.) Corda (U. maydis), which is responsible for the devastating disease known as corn smut. A systematic bioinformatic approach was herein employed for the characterization of the maize WRKY TF family, leading to the identification of 120 ZmWRKY genes encoded on 10 chromosomes. Further structural and phylogenetic analyses of these TFs enabled their classification into seven different subgroups. Segmental duplication was established as a major driver of ZmWRKY family expansion in gene duplication analyses, while the Ka/Ks ratio suggested that these ZmWRKY genes had experienced strong purifying selection. When the transcriptional responses of these genes to pathogen inoculation were evaluated, seven U. maydis-inducible ZmWRKY genes were identified, as validated using a quantitative real-time PCR approach. All seven of these WKRY proteins were subsequently tested using a yeast one-hybrid assay approach, which revealed their ability to directly bind the ZmSWEET4b W-box element, thereby controlling the U. maydis-inducible upregulation of ZmSWEET4b. These results suggest that these WRKY TFs can control sugar transport in the context of fungal infection. Overall, these data offer novel insight into the evolution, transcriptional regulation, and functional characteristics of the maize WRKY family, providing a basis for future research aimed at exploring the mechanisms through which these TFs control host plant responses to common smut and other fungal pathogens.

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Aging and metabolic disorders feedback and promote each other and are closely related to the occurrence and development of cardiovascular disease, type 2 diabetes, neurodegeneration and other degenerative diseases. Liupao tea is a geographical indication product of Chinese dark tea, with a "red, concentrated, aged and mellow" flavor quality. In this study, the aqueous extract of aged Liupao tea (ALPT) administered by continuous gavage significantly inhibited the increase of visceral fat and damage to the intestinal-liver-microbial axis in high-fat modeling of SAMP8 (P8+HFD) mice. Its potential mechanism is that ALPT significantly inhibited the inflammation and aggregation formation pathway caused by P8+HFD, increased the abundance of short-chain fatty acid producing bacteria Alistipes, Alloprevotella and Bacteroides, and had a calorie restriction effect. The results of the whole target metabolome network pharmacological analysis showed that there were 139 potential active components in the ALPT aqueous extract, and the core targets of their actions were SRC, TP53, AKT1, MAPK3, VEGFA, EP300, EGFR, HSP90AA1, CASP3, etc. These target genes were mainly enriched in cancer, neurodegenerative diseases, glucose and lipid metabolism and other pathways of degenerative changes. Molecular docking further verified the reliability of network pharmacology. The above results indicate that Liupao tea can effectively delay the body's degenerative changes through various mechanisms and multi-target effects. This study revealed that dark tea such as Liupao tea has significant drinking value in a modern and aging society.

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Background: Endometriosis (EMs) is a benign chronic condition that tends to recur in women of childbearing age, with an incidence of approximately 10%. It is a multifactorial disease for which the pathogenesis is currently unclear. This study is aimed at investigating the expression and clinical significance of tRNA-derived small RNA (tsRNA), a novel noncoding small RNA with potential regulatory functions, in endometriosis. Methods: The tRF/tiRNA expression profiles in endometrial tissues from three pairs of endometriosis patients and controls were detected by tRF&tiRNA PCR microarray technology and then verified by quantitative real-time polymerase chain reaction (qPCR). The target genes and target sites of TRF396, tiRNA-5030-GlnTTG-3, TRF308, and TRF320 were predicted by miRanda, and the network diagram of their interaction with miRNA was drawn. The impact of tRNA-derived fragments on the pathogenesis of endometriosis was analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: Two upregulated and 19 downregulated tRNA-derived fragments were identified. The qRT-PCR results of 2 upregulated and 2 downregulated RNA-derived fragments were consistent with the RNA Seq data. The OR2B4 gene related to TRF396, the DGAT1 gene related to tiRNA-5030-GlnTTG-3, the KLF16 gene of TRF308, and the RNF213 gene of TRF320 had significant correlations. Gene Ontology and pathway analysis showed that the target genes of TRF396 and tiRNA-5030-GlnTTG-3 were mainly involved in the intrinsic components of the membrane and the overall composition of the membrane in cell components; molecular functions mainly involve olfactory conduction and G protein-coupled receptor activity. In the biological process, it was mainly involved in the detection of sensory stimuli. The target genes of TRF308 and TRF320 were mainly involved in the intracellular part; molecular functions are mainly related to DNA binding transcription factor activity and protein binding and mainly related to biological regulation of biological processes. Pathway analysis showed that the RAP1 signaling pathway and the AXON GUIDANCE signaling pathway may participate in the progression of endometriosis. Conclusion: The differential expression of tRF/tiRNA in endometriosis may be related to the pathogenesis of endometriosis. Furthermore, tRF/tiRNA may be a biomarker for the diagnosis and treatment of EMs in the future.

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