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Recent studies suggest that cuproptosis, a novel mode of cell death, may be associated with the development of cancer. However, no studies are showing its role in tumorigenesis, progression, and prognosis. In the present study, we comprehensively analyzed the expression difference, gene variation and methylation modification of cuproptosis-related genes (CRGs) in pan-cancer. Then, Single sample gene set enrichment analysis (ssGSEA) was used to calculate individual cuproptosis scores (CS). The association of CS with copy number variation, clinical features, immune-related genes, TMB, MSI, and tumor immune dysfunction and exclusion (TIDE) was comprehensively assessed. Single-cell transcriptome sequencing (scRNA-seq) to analyze the activation of cuproptosis in the tumor microenvironment. Immunohistochemistry (IHC) were used to validate the expression of cuproptosis hub-gene. Our study shows that CRGs were significantly expressed in a variety of tumors, and CDKN2A had the highest mutation frequency (49%) in all tumors. A significant increase in the CS was observed in most cancers and were associated with poor prognosis in the majority of tumors. CS was significantly negatively correlated with tumor microenvironment scores in more than 10 tumors and positively correlated with PD-L1 in 11 tumors, suggesting involvement in tumor immune escape. scRNA-seq suggests that CRG scores significantly increased in the cancer cells. This study opens avenues for further research on the role of cuproptosis in the occurrence and development of cancer and the development of targeted therapies based on cuproptosis.

As a crucial industrial process for the production of bulk and fine chemicals, semi-hydrogenation of alkynes faces the trade-off between activity and selectivity due to undesirable over-hydrogenation. By breaking the energy linear scaling relationships, we report an efficient additive-free WO 3 -based single-atom Pd catalytic system with a vertical size effect of hydrogen spillover. Hydrogen spillover induced hydrophilic polar layer (HPL) with limited thickness on WO 3 -based support exhibits unconventional size effect to Pd site, in which over-hydrogenation is greatly suppressed on Pd 1 site due to the polar repulsive interaction between HPL and nonpolar C=C bonds, whereas this is invalid for Pd nanoparticles with higher altitudes. By further enhancing the HPL through Mo doping, activated Pd 1 /MoWO 3 achieves recorded performance of 98.4% selectivity and 10200 h −1 activity for semi-hydrogenation of 2-methyl-3-butyn-2-ol, 26-fold increase in activity of Lindlar catalyst. This observed vertical size effect of hydrogen spillover offers broad potential in catalytic performance regulation. The semi-hydrogenation of alkynes faces the trade-off between activity and selectivity due to undesirable over-hydrogenation. Here the authors report an efficient additive-free WO3-based single-atom Pd catalytic system with a vertical size effect of hydrogen spillover to mediate the trade-off between activity and selectivity.

Brown planthopper (BPH) is one of the most destructive insects affecting rice (Oryza sativa L.) production. Phenylalanine ammonialyase (PAL) is a key enzyme involved in plant defense against pathogens, but the role of PAL in insect resistance is still poorly understood. Here we show that expression of the majority of PALs in rice is significantly induced by BPH feeding. Knockdown of OsPALs significantly reduces BPH resistance, whereas overexpression of OsPAL8 in a susceptible rice cultivar significantly enhances its BPH resistance. We found that OsPALs mediate resistance to BPH by regulating the biosynthesis and accumulation of salicylic acid and lignin. Furthermore, we show that expression of OsPAL6 and OsPAL8 in response to BPH attack is directly up-regulated by OsMYB30, an R2R3 MYB transcription factor. Taken together, our results demonstrate that the phenylpropanoid pathway plays an important role in BPH resistance response, and provide valuable targets for genetic improvement of BPH resistance in rice.

Inflammatory bowel disease (IBD) represents chronic recurrent intestinal inflammation resulting from various factors. Crohn’s disease (CD) and ulcerative colitis (UC) have been identified as the two major types of IBD. Currently, most of the drugs for IBD used commonly in the clinic have adverse reactions, and only a few drugs present long-lasting treatment effects. Moreover, issues of drug resistance and disease recurrence are frequent and difficult to resolve. Together, these issues cause difficulties in treating patients with IBD. Therefore, the development of novel therapeutic agents for the prevention and treatment of IBD is of significance. In this context, research on natural compounds exhibiting anti-inflammatory activity could be a novel approach to developing effective therapeutic strategies for IBD. Phytochemicals such as astragalus polysaccharide (APS), quercetin, limonin, ginsenoside Rd, luteolin, kaempferol, and icariin are reported to be effective in IBD treatment. In brief, natural compounds with anti-inflammatory activities are considered important candidate drugs for IBD treatment. The present review discusses the potential of certain natural compounds and their synthetic derivatives in the prevention and treatment of IBD.

This study is the first to investigate the association between the Atherogenic Index of Plasma (AIP) and depression in women, stratified by menopausal status. A total of 9,060 subjects were enrolled from the National Health and Nutrition Examination Survey (NHANES) conducted from 2005 to 2020. AIP was computed by Log10 (triglycerides/high-density lipoprotein cholesterol). Depression was assessed using the Patient Health Questionnaire (PHQ-9), with a score of ≥10 indicating a diagnosis of depression. Multivariate logistic regression, restricted cubic splines (RCS), and subgroup analysis were employed to explore the associations between AIP and depression. In comparison to quartile 1, Multivariate logistic regression revealed that AIP in quartiles 2-4 yielded odd ratios (ORs) (95% confidence interval, 95% CI) of premenopausal women of 1.14 (0.87, 1.50), 1.06 (0.79, 1.42), and 1.49 (1.11, 2.00), and postmenopausal women of 0.88 (0.64, 1.22), 1.03 (0.76, 1.41) and 1.40 (1.04, 1.89), respectively. RCS showed a linear correlation between AIP and depression in premenopausal women and a nonlinear correlation between AIP and depression in postmenopausal women. When AIP > 0.60, premenopausal women had an increased risk of depression, while postmenopausal women had a decreased risk of depression. This study demonstrates that elevated AIP levels are significantly associated with an increased risk of depression in both premenopausal and postmenopausal women. However, the strength and direction of these associations varied between the two groups, suggesting that menopausal status may play a critical role in modulating the impact of lipid metabolism on mental health outcomes.

Photothermal therapy (PTT) is a promising approach for cancer targeting therapy. However, the temperature-dependent killing of tumor cells in PTT remains unclear. In this study, we report necroptosis plays a role in the anti-tumor effects observed in gold nanorod (GNR)-mediated PTT in melanoma. We first synthesized gold nanorods with a targeting adaptor FA (GNRs-FA), which achieved high efficacy of targeted delivery to melanoma cells. We further demonstrated PTT, precipitated by GNRs-FA under the induction of near-infrared laser, was temperature-dependent. Furthermore, the photothermal killing of melanoma cells showed different patterns of cell death depending on varying temperature in PTT. In a lower temperature at 43 °C, the percentages of apoptosis, necroptosis and necrosis of tumor cells were 10.2%, 18.3%, and 17.6%, respectively, suggesting the cell killing is ineffective at lower temperatures. When the temperature increased to 49 °C, the cell death pattern switched to necrosis dominant (52.8%). Interestingly, when the PTT achieved a moderate temperature of 46 °C, necroptosis was significantly increased (35.1%). Additionally, GNRs-FA/PPT-mediated necroptosis was regulated by RIPK1 pathway. Taken together, this study is the first to demonstrate that temperature-dependent necroptosis is an important mechanism of inducing melanoma cell death in GNR-mediated PTT in addition to apoptosis and necrosis.

Segmental bone defects, arising from factors such as trauma, tumor resection, and congenital malformations, present significant clinical challenges that often necessitate complex reconstruction strategies. Hydrogels loaded with multiple osteogenesis-promoting components have emerged as promising tools for bone defect repair. While the osteogenic potential of the Piezo1 agonist Yoda1 has been demonstrated previously, its hydrophobic nature poses challenges for effective loading onto hydrogel matrices.In this study, we address this challenge by employing Yoda1-pretreated bone marrow-derived mesenchymal stem cell (BMSCs) exosomes (Exo-Yoda1) alongside exosomes derived from BMSCs (Exo-MSC). Comparatively, Exo-Yoda1-treated BMSCs exhibited enhanced osteogenic capabilities compared to both control groups and Exo-MSC-treated counterparts. Notably, Exo-Yoda1-treated cells demonstrated similar functionality to Yoda1 itself. Transcriptome analysis revealed activation of osteogenesis-associated signaling pathways, indicating the potential transduction of Yoda1-mediated signals such as ErK, a finding validated in this study. Furthermore, we successfully integrated Exo-Yoda1 into gelatin methacryloyl (GelMA)/methacrylated sodium alginate (SAMA)/β-tricalcium phosphate (β-TCP) hydrogels. These Exo-Yoda1-loaded hydrogels demonstrated augmented osteogenesis in subcutaneous ectopic osteogenesis nude mice models and in rat skull bone defect model. In conclusion, our study introduces Exo-Yoda1-loaded GELMA/SAMA/β-TCP hydrogels as a promising approach to promoting osteogenesis. This innovative strategy holds significant promise for future widespread clinical applications in the realm of bone defect reconstruction. Graphical Abstract Highlights • Exosomes derived from Yoda1 pretreated BMSCs promoted osteogenesis by transducing biological signals activated by Yoda1. • GELMA/SAMA/β-TCP hydrogels loading with Exo-Yoda1 was highly bio-compatibility and suitable for massive commercial application.

A change in precipitation can profoundly change the structure of soil microbial communities, especially in arid and semi-arid areas which are limited by moisture conditions. Therefore, it is crucial to explore how soil bacterial community composition and diversity will respond to variation in precipitation. Here we conducted a precipitation control experiment to simulate precipitation change by reducing and increasing rainfall by 25%, 50%, and 75% in the alpine grasslands of northern Tibet. The composition, diversity, and species interaction network of soil microbial community were studied by high-throughput sequencing, and the relationship between microbial community species and soil environmental factors was analyzed. Our results showed that Proteobacteria (45%–52%) and Actinobacteria (37%–45%) were the dominant bacteria in the soil. The alpha diversity index based on Shannon, Chao1, and Simpson indices revealed that precipitation change had no significant effect on richness and evenness of soil microbial communities. Non-metric multidimensional scaling (NMDS) and analysis of similarities (ANOSIM) showed that a clear separation of soil microbial communities between D2(-50%),D3(-75%) and W2(+50%), W3(+75%) treatments. The microbial interaction network indicated that the water-increasing treatment group had closer connections, and Proteobacteria and Actinomycetes were the core species. Furthermore, there was a stronger positive correlation between species in the water-reducing treatment group, the contribution of Proteobacteria decreased significantly, the role of connecting hub decreased, and Actinomycetes became the most important core microbial species. In addition, soil water content (SWC) and available phosphorus (AP) were closely related to the variations in soil microbial compositions. The findings of this study provide a theoretical basis for the driving mechanism of global climate change on soil microbial community and grassland ecosystem in alpine grassland.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Here, using whole-genome, exome and transcriptome sequencing of 2,754 childhood patients with ALL, we find that, despite a generally low mutation burden, ALL cases harbor a median of four putative somatic driver alterations per sample, with 376 putative driver genes identified varying in prevalence across ALL subtypes. Most samples harbor at least one rare gene alteration, including 70 putative cancer driver genes associated with ubiquitination, SUMOylation, noncoding transcripts and other functions. In hyperdiploid B-ALL, chromosomal gains are acquired early and synchronously before ultraviolet-induced mutation. By contrast, ultraviolet-induced mutations precede chromosomal gains in B-ALL cases with intrachromosomal amplification of chromosome 21. We also demonstrate the prognostic significance of genetic alterations within subtypes. Intriguingly, DUX4 - and KMT2A -rearranged subtypes separate into CEBPA/FLT3 - or NFATC4 -expressing subgroups with potential clinical implications. Together, these results deepen understanding of the ALL genomic landscape and associated outcomes. A genomic and transcriptomic analysis of 2,754 childhood acute lymphoblastic leukemias identifies 376 putative driver genes, and associations between disease subtypes and prognosis.

Background Rumination has been thought to relate to deficits in core executive functions (EFs), but the empirical findings for this idea are mixed. The aim of the present study is to synthesize existing literature to clarify these relations. Methods A comprehensive literature search revealed 34 published as well as unpublished studies on the associations between rumination and core EF. These studies report on 3,066 participants. The effect size in the meta‐analyses was obtained by the z transformation of correlation coefficients. Results Analysis revealed significant negative associations between rumination and both inhibition (r = ‒.23) and set‐shifting (r = ‒.19). There was no significant association between rumination and working memory. These associations were not moderated by age, sex, type of sample (depressed or healthy), type of outcome measure (accuracy vs. reaction time), or affective content of the task, although statistical power for these tests was limited. Conclusions We found significant negative associations between rumination and inhibition or set‐shifting. There was no significant association between rumination and working memory. Future research should adopt multiple measures of EF to provide clear evidence on the associations between EF and rumination. A better understanding of this relationship may have important implications for intervention of rumination, such as training programs to improve EF or teach compensatory strategies to mitigate the effects of EF impairments.