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Upon perception of pathogens, plants can rapidly close their stomata to restrict pathogen entry into internal tissue, leading to stomatal immunity as one aspect of innate immune responses. The actin cytoskeleton is required for plant defense against microbial invaders. However, the precise functions of host actin during plant immunity remain largely unknown. Here, we report that Arabidopsis villin3 (VLN3) is critical for plant resistance to bacteria by regulating stomatal immunity. Our in vitro and in vivo phosphorylation assays show that VLN3 is a physiological substrate of two pathogen-responsive mitogen-activated protein kinases, MPK3/6. Quantitative analyses of actin dynamics and genetic studies reveal that VLN3 phosphorylation by MPK3/6 modulates actin remodeling to activate stomatal defense in Arabidopsis . Plants can rapidly close stomata to restrict pathogen entry into leaves. Here the authors show that phosphorylation of villin3 by mitogen-activated protein kinases modulates actin remodeling to activate stomatal defense in Arabidopsis.

The rock mass is one of the key parameters in engineering design. Accurate rock mass classification is also essential to ensure operational safety. Over the past decades, various models have been proposed to evaluate and predict rock mass. Among these models, artificial intelligence (AI) based models are becoming more popular due to their outstanding prediction results and generalization ability for multiinfluential factors. In order to develop an easy-to-use rock mass classification model, support vector machine (SVM) techniques are adopted as the basic prediction tools, and three types of optimization algorithms, i.e., particle swarm optimization (PSO), genetic algorithm (GA) and grey wolf optimization (GWO), are implemented to improve the prediction classification and optimize the hyper-parameters. A database was assembled, consisting of 80 sets of real engineering data, involving four influencing factors. The three combined models are compared in accuracy, precision, recall, F 1 value and computational time. The results reveal that among three models, the GWO-SVC-based model shows the best classification performance by training. The accuracy of training and testing sets of GWO-SVC are 90.6250% (58/64) and 93.7500% (15/16), respectively. For Grades I, II, III, IV and V, the precision value is 1, 0.93, 0.90, 0.92, 0.83, the recall value is 1, 1, 0.93, 0.73, 0.83, and the F 1 value is 1, 0.96, 0.92, 0.81, 0.83, respectively. Sensitivity analysis is performed to understand the influence of input parameters on rock mass classification. It shows that the sensitive factor in rock mass quality is the RQD. Finally, the GWO-SVC is employed to assess the quality of rocks from the southeastern ore body of the Chambishi copper mine. Overall, the current study demonstrates the potential of using artificial intelligence methods in rock mass assessment, rendering far better results than the previous reports.

Despite the growing surge in the literature about employee creativity, the mainstream literature largely views it from an organizational perspective, and ignores the underlying mechanism that motivates employees to be engaged in different creative tasks. Against this backdrop, the current work was carried out to explore the relationship of corporate social responsibility (CSR) and employee creativity with the mediating effect of autonomy to explain the motivational pull for employee creativity. The data were collected from the employees of the hotel sector of Pakistan through a self-administered questionnaire (n = 511) and were analyzed by employing the structural equation modeling (SEM) technique. The results revealed that CSR, through the mediating effect of job autonomy, influences employees’ creativity significantly. The findings of the current analysis will help both academia and professionals from the hotel sector to understand the importance of CSR as a booster for employee creativity. Furthermore, the potential role of job autonomy as a mediator in explaining this relationship will also help policymakers to understand the importance of freedom at the workplace to engage the workforce in different extra-roles, including creativity.

MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate posttranscriptional expression of target genes. Accumulating evidences have demonstrated that the miR-30 family, as a member of microRNAs, played a crucial regulating role in the development of tissues and organs and the pathogenesis of clinical diseases, which indicated that it may be a promising regulator in development and disease. This review aims to clarify the current progress on the regulating role of miR-30 family in tissues and organs development and related disease and highlight their research prospective in the future.

Protein -palmitoylation, a universal posttranslational modification catalyzed by a specific group of palmitoyltransferases, plays crucial roles in diverse biological processes across organisms by modulating protein functions. However, its roles in the virulence of plant pathogenic fungi remain underexplored. In a recent study, Y. Duan, P. Li, D. Zhang, L. Wang, et al. (mBio 15:e02704-24, 2024, https://doi.org/10.1128/mbio.02704-24) reported that the palmitoyltransferases UvPfa3 and UvPfa4 regulate the virulence of the rice false smut pathogen . Through comprehensive characterization of -palmitoylation sites, they revealed that -palmitoylated proteins in are enriched in mitogen-activated protein (MAP) kinase and autophagy pathways, with MAP kinase UvSlt2 being a key target of UvPfa4-mediated -palmitoylation. Further investigation demonstrated that -palmitoylation of UvSlt2 is critical for its kinase activity, substrate interaction ability, and virulence function in . These findings reveal UvPfa4-mediated -palmitoylation as a vital regulatory mechanism in virulence, highlighting the importance of protein -palmitoylation in the pathogenicity of plant pathogenic fungi.

Macrophages, with diverse functions and variable phenotypes, are considered as an important executor of inflammatory diseases. And it has been proved that autophagy is deeply connected with the development of inflammation, while the exact regulatory mechanism still remains unclear, and the application of autophagy regulators in anti-inflammation needs to be further confirmed. Here, we firstly verified that neochromine S5 (hereinafter referred to as S5) significantly inhibited M1-like macrophage polarization with decrease of the proinflammatory cytokines and downregulation of NF-κB and STAT1 signals. Then, in vivo experiments demonstrated S5 improved cecal ligation and puncture (CLP)-induced sepsis specially based on the regulation of M1-like macrophages. Mechanistic studies indicated that S5 treatment dramatically upregulated cellular autophagy in M1-like macrophage. Furthermore, by multiple methods, S5 was revealed to directly bind with ubiquitin-specific proteases 14 (USP14) at Ser404, Phe405, and Cys414 by hydrogen bond to inhibit its deubiquitinating activity, and block USP14–TRAF6 (TNF receptor associated factor 6) interaction, subsequently promoting ubiquitination of Beclin1, interrupting Beclin1–Bcl2 interaction, and accumulating the autophagosome in macrophages, which finally resulted in the blockade of M1-like macrophage polarization. Animal experiments also confirmed the protection of S5 in CLP mice was dependent on activation of macrophage autophagy. What’s more, as a novel USP14 inhibitor, S5 exhibited higher efficiency and safety than IU1, the known USP14 inhibitor. Therefore, this study has demonstrated that typically inhibiting USP14 promotes autophagy in M1-like macrophages and alleviates CLP-induced sepsis. Moreover, we provide a new candidate compound, S5, for sensitizing autophagy to interfere with the macrophage inflammation.

Lung cancer is a commonly diagnosed cancer and the leading cause of cancer-related deaths, posing a serious health risk. Despite new advances in immune checkpoint and targeted therapies in recent years, the prognosis for lung cancer patients, especially those in advanced stages, remains poor. MicroRNAs (miRNAs) have been shown to modulate tumor development at multiple levels, and as such, miRNA mimics and molecules aimed at regulating miRNAs have shown promise in preclinical development. More importantly, miRNA-based therapies can also complement conventional chemoradiotherapy, immunotherapy, and targeted therapies to reverse drug resistance and increase the sensitivity of lung cancer cells. Furthermore, small interfering RNA (siRNA) and miRNA-based therapies have entered clinical trials and have shown favorable development prospects. Therefore, in this paper, we review recent advances in miRNA-based therapies in lung cancer treatment as well as adjuvant therapy and present the current state of clinical lung cancer treatment. We also discuss the challenges facing miRNA-based therapies in the clinical application of lung cancer treatment to provide new ideas for the development of novel lung cancer therapies.

Background In colorectal cancer (CRC), the normal tissue adjacent to tumor (NAT) communicates actively with the tumor. Adult stem cells from the colon play a crucial role in the development of the colonic epithelium. In the tumor microenvironment, however, it is unclear what changes have occurred in colonic stem cells derived from NAT. Methods Using an intestinal stem cell culture system, we cultured colonic cells from NAT and paired CRC tissue, as well as cells from healthy tissue (HLT). Clonogenicity and differentiation ability were used to compare the function of clones from NAT, HLT and CRC tissues. RNA high-throughput sequencing of these clones was used to identify the molecular characteristics of NAT-derived clones. Coculture of clones from HLT and CRC was used to assess molecular changes. Results We found that the morphological characteristics, clonogenic ability, and differentiation ability of NAT-derived clones were consistent with those of HLT-derived clones. However, NAT-derived clones changed at the molecular level. A number of genes were specifically activated in NAT. NAT-derived clones enriched pathways related to inflammation and fibrosis, including epithelial mesenchymal transition (EMT) pathway and TGF-beta signaling pathway. Our results also confirmed that NAT-derived clones could recruit fibroblasts in mice. In addition, HLT-derived clones showed high expression of FOSB when cocultured with tumor cells. Conclusions Our results demonstrate that colonic stem cells from NAT in the tumor microenvironment undergo changes at the molecular level, and these molecular characteristics can be maintained in vitro, which can induce fibrosis and an inflammatory response. AdcUiJqvdgZYHMRXwfb-XH Video Abstract

The purpose of this study was to evaluate the predictive value of monocyte-to-lymphocyte ratio (MLR) on the short-term (28 days) and long-term (365 days) mortality risk in patients with acute pancreatitis (AP) using multiple statistical and machine learning (ML) models. Studies selected 1,044 eligible AP patients from the MIMIC-IV database and divided them into four groups based on their MLR values (MLR<0.32; 0.32 ≤ MLR<0.57; 0.57 ≤ MLR<1; MLR ≥ 1). Findings revealed that MLR demonstrated a U-shaped relationship with patient mortality risk, with the minimal mortality risk occurring at an MLR of approximately 0.57. Cox regression model analysis showed that after adjusting for multiple parameters, MLR was still significantly associated with the risk of death. Moreover, ML model analysis identified that MLR has potential value in predicting AP patient outcomes. This study suggests that MLR can be used as a potential indicator to assess prognostic risk in critically ill patients with AP to support clinical decision-making.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level and play critical roles in regulating physiological function, and are becoming worldwide research hot spot in brain development and diseases. However, the exact value of miRNAs in brain physiological and pathological processes remain to be fully elucidated, which is vital for the application of miRNAs as diagnostic, prognostic, and therapeutic biomarkers for brain diseases. MicroRNA-7 (miR-7), as a highly expressed miRNA molecule in the mammalian brain, is well documented to play a critical role in development of various diseases. Importantly, accumulating evidence has shown that miR-7 is involved in a range of developmental and pathological processes of brain. Expressively, miR-7, encoded by three genes located different chromosomes, is dominantly expressed in neurons with sensory or neurosecretory. Moreover, the expression of miR-7 is regulated at three levels including gene transcription, process of primary and precursor sequence and formation of mature sequence. Physiologically, miR-7 principally governs the physiological development of Pituitary gland, Optic nervous system and Cerebral cortex. Pathologically, miR-7 can regulate multiple genes thereby manipulating the process of various brain diseases including neurodegenerative diseases, neuroinflammation, and mental disorders and so on. These emerging studies have shown that miR-7, a representative member of miRNA family, might be a novel intrinsic regulatory molecule involved in the physiological and pathological process of brain. Therefore, in-depth studies on the role of miR-7 in brain physiology and pathology undoubtedly not only provide a light on the roles of miRNAs in brain development and diseases, but also are much helpful for ultimate development of therapeutic strategies against brain diseases. In this review, we provide an overview of current scientific knowledge regarding the expression and function of miR-7 in development and disease of brain and raise many issues involved in the relationship between miR-7 and brain physiological and pathological processes.