Spatiotemporal transcriptomics and metabolic profiling provide insights into gene regulatory networks during lentil seed development.

Lentil (Lens culinaris Medik.) is a nutritious legume with seeds rich in protein, minerals and an array of diverse specialized metabolites. The formation of a seed requires regulation and tight coordination of developmental programs to form the embryo, endosperm and seed coat compartments, which determines the structure and composition of mature seed and thus its end-use quality. Understanding the molecular and cellular events and metabolic processes of seed development is essential for improving lentil yield and seed nutritional value. However, such information remains largely unknown, especially at the seed compartment level. In this study, we generated high-resolution spatiotemporal gene expression profiles in lentil embryo, seed coat and whole seeds from fertilization through maturation. Apart from anatomic differences between the embryo and seed coat, comparative transcriptomics and weighted gene co-expression network analysis revealed embryo- and seed coat-specific genes and gene modules predominant in specific tissues and stages, which highlights distinct genetic programming. Furthermore, we investigated the dynamic profiles of flavonoid, isoflavone, phytic acid and saponin in seed compartments across seed development. Coupled with transcriptome data, we identified sets of candidate genes involved in the biosynthesis of these metabolites. The global view of the transcriptional and metabolic changes of lentil seed tissues throughout development provides a valuable resource for dissecting the genetic control of secondary metabolism and development of molecular tools for improving seed nutritional quality.

Unlocking Dynamic Solvation Chemistry and Hydrogen Evolution Mechanism in Aqueous Zinc Batteries.

Understanding the interfacial hydrogen evolution reaction (HER) is crucial to regulate the electrochemical behavior in aqueous zinc batteries. However, the mechanism of HER related to solvation chemistry remains elusive, especially the time-dependent dynamic evolution of the hydrogen bond (H-bond) under an electric field. Herein, we combine in situ spectroscopy with molecular dynamics simulation to unravel the dynamic evolution of the interfacial solvation structure. We find two critical change processes involving Zn-electroplating/stripping, including the initial electric double layer establishment to form an H2O-rich interface (abrupt change) and the subsequent dynamic evolution of an H-bond (gradual change). Moreover, the number of H-bonds increases, and their strength weakens in comparison with the bulk electrolyte under bias potential during Zn2+ desolvation, forming a diluted interface, resulting in massive hydrogen production. On the contrary, a concentrated interface (H-bond number decreases and strength enhances) is formed and produces a small amount of hydrogen during Zn2+ solvation. The insights on the above results contribute to deciphering the H-bond evolution with competition/corrosion HER during Zn-electroplating/stripping and clarifying the essence of electrochemical window widened and HER suppression by high concentration. This work presents a new strategy for aqueous electrolyte regulation by benchmarking the abrupt change of the interfacial state under an electric field as a zinc performance-enhancement criterion.

Sestrin2 remedies neuroinflammatory response by inhibiting A1 astrocyte conversion via autophagy.

Most central nervous diseases are accompanied by astrocyte activation. Autophagy, an important pathway for cells to protect themselves and maintain homeostasis, is widely involved in regulation of astrocyte activation. Reactive astrocytes may play a protective or harmful role in different diseases due to different phenotypes of astrocytes. It is an urgent task to clarify the formation mechanisms of inflammatory astrocyte phenotype, A1 astrocytes. Sestrin2 is a highly conserved protein that can be induced under a variety of stress conditions as a potential protective role in oxidative damage process. However, whether Sestrin2 can affect autophagy and involve in A1 astrocyte conversion is still uncovered. In this study, we reported that Sestrin2 and autophagy were significantly induced in mouse hippocampus after multiple intraperitoneal injections of lipopolysaccharide, with the elevation of A1 astrocyte conversion and inflammatory mediators. Knockdown Sestrin2 in C8-D1A astrocytes promoted the levels of A1 astrocyte marker C3 mRNA and inflammatory factors, which was rescued by autophagy inducer rapamycin. Overexpression of Sestrin2 in C8-D1A astrocytes attenuated A1 astrocyte conversion and reduced inflammatory factor levels via abundant autophagy. Moreover, Sestrin2 overexpression improved mitochondrial structure and morphology. These results suggest that Sestrin2 can suppress neuroinflammation by inhibiting A1 astrocyte conversion via autophagy, which is a potential drug target for treating neuroinflammation.

Hemicyanine-Based Highly Water-Soluble Probe for Extracellular Nitroreductase.

Nitroreductase (NTR) has long been a target of interest for its important role involved in the nitro compounds metabolism. Various probes have been reported for NTR analysis, but rarely able to distinguish the extracellular NTR from intracellular ones. Herein we reported a new NTR sensor, HCyS-NO2, which was a hemicyanine molecule with one nitro and two sulfo groups attached. The nitro group acted as the reporting group to respond NTR reduction. Direct linkage of nitro group into the hemicyanine π conjugate system facilitated the intramolecular electron transfer (IET) process and thus quenched the fluorescence of hemicyanine core. Upon reduction with NTR, the nitro group was rapidly converted into the hydroxylamino and then the amino group, eliminating IET process and thus restoring the fluorescence. The sulfo groups installed significantly increased the hydrophilicity of the molecule, and introduced negative charges at physiological pH, preventing the diffusion into bacteria. Both gram-negative and gram-positive bacteria were able to turn on the fluorescence of HCyS-NO2, without detectable diffusion into cells, providing a useful tool to probe the extracellular reduction process.

M6A methylation-regulated autophagy may be a new therapeutic target for intervertebral disc degeneration.

Degeneration of intervertebral discs is considered one of the most important causes of low back pain and disability. The intervertebral disc (IVD) is characterized by its susceptibility to various stressors that accelerate the senescence and apoptosis of nucleus pulposus cells, resulting in the loss of these cells and dysfunction of the intervertebral disc. Therefore, how to reduce the loss of nucleus pulposus cells under stress environment is the main problem in treating intervertebral disc degeneration. Autophagy is a kind of programmed cell death, which can provide energy by recycling substances in cells. It is considered to be an effective method to reduce the senescence and apoptosis of nucleus pulposus cells under stress. However, further research is needed on the mechanisms by which autophagy of nucleus pulposus cells is regulated under stress environments. M6A methylation, as the most extensive RNA modification in eukaryotic cells, participates in various cellular biological functions and is believed to be related to the regulation of autophagy under stress environments, may play a significant role in nucleus pulposus responding to stress. This article first summarizes the effects of various stressors on the death and autophagy of nucleus pulposus cells. Then, it summarizes the regulatory mechanism of m6A methylation on autophagy-related genes under stress and the role of these autophagy genes in nucleus pulposus cells. Finally, it proposes that the methylation modification of autophagy-related genes regulated by m6A may become a new treatment approach for intervertebral disc degeneration, providing new insights and ideas for the clinical treatment of intervertebral disc degeneration.

Sphingosylphosphorylcholine alleviates pressure overload-induced myocardial remodeling in mice via inhibiting CaM-JNK/p38 signaling pathway.

Apoptosis plays a critical role in the development of heart failure, and sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid naturally occurring in blood plasma. Some studies have shown that SPC inhibits hypoxia-induced apoptosis in myofibroblasts, the crucial non-muscle cells in the heart. Calmodulin (CaM) is a known SPC receptor. In this study we investigated the role of CaM in cardiomyocyte apoptosis in heart failure and the associated signaling pathways. Pressure overload was induced in mice by trans-aortic constriction (TAC) surgery. TAC mice were administered SPC (10 µM·kg-1·d-1) for 4 weeks post-surgery. We showed that SPC administration significantly improved survival rate and cardiac hypertrophy, and inhibited cardiac fibrosis in TAC mice. In neonatal mouse cardiomyocytes, treatment with SPC (10 µM) significantly inhibited Ang II-induced cardiomyocyte hypertrophy, fibroblast-to-myofibroblast transition and cell apoptosis accompanied by reduced Bax and phosphorylation levels of CaM, JNK and p38, as well as upregulated Bcl-2, a cardiomyocyte-protective protein. Thapsigargin (TG) could enhance CaM functions by increasing Ca2+ levels in cytoplasm. TG (3 µM) annulled the protective effect of SPC against Ang II-induced cardiomyocyte apoptosis. Furthermore, we demonstrated that SPC-mediated inhibition of cardiomyocyte apoptosis involved the regulation of p38 and JNK phosphorylation, which was downstream of CaM. These results offer new evidence for SPC regulation of cardiomyocyte apoptosis, potentially providing a new therapeutic target for cardiac remodeling following stress overload.

Impact of PRR11 Expression on Prognosis in Pancreatic Cancer Patients with Diabetes.

Objective: This study aimed to analyze the impact of PRR11 protein expression levels on the prognosis of patients with diabetes mellitus and pancreatic cancer. Methods: Immunohistochemical staining was performed to detect the expression levels of PRR11 protein in cancerous tissues of 70 pancreatic cancer patients, including 45 patients with diabetes mellitus (Group A) and 25 patients without diabetes mellitus (Group B). Patients' blood glucose, lipid profiles, and glycemic control status were compared between the groups. Survival curves were plotted to explore the impact of PRR11 protein expression levels on the prognosis of patients with diabetes mellitus and pancreatic cancer. Results: The positive rate of PRR11 protein expression in Group A patients (86.67%) was significantly higher than in Group B patients (52.00%), P < .05. Group A patients exhibited significantly higher levels of fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), and glycated hemoglobin (HbAlc) compared to Group B patients (P < .05). Interestingly, the expression levels of PRR11 in cancerous tissues were positively correlated with FBG, TC, TG, and HbAlc levels (P < .05). The positive rate of PRR11 protein expression in patients with poor glycemic control (93.75%) was significantly higher than in patients with good glycemic control (53.85%), P < .05. Notably, the survival rate of PRR11 protein-positive patients was significantly lower than that of negative patients (P < .05). Conclusion: The finding highlights that the positive expression of PRR11 protein in patients with diabetes mellitus and pancreatic cancer is associated with a poor prognosis. It suggests that PRR11 may play a role in the occurrence and development of pancreatic cancer and could serve as a potential predictive marker and therapeutic target. However, further research is warranted to explore the functional mechanisms and pathways of PRR11 to better understand its role in pancreatic cancer, and develop personalized therapies.

A Vascular Feature Detection and Matching Method Based on Dual-Branch Fusion and Structure Enhancement.

How to obtain internal cavity features and perform image matching is a great challenge for laparoscopic 3D reconstruction. This paper proposes a method for detecting and associating vascular features based on dual-branch weighted fusion vascular structure enhancement. Our proposed method is divided into three stages, including analyzing various types of minimally invasive surgery (MIS) images and designing a universal preprocessing framework to make our method generalized. We propose a Gaussian weighted fusion vascular structure enhancement algorithm using the dual-branch Frangi measure and MFAT (multiscale fractional anisotropic tensor) to address the structural measurement differences and uneven responses between venous vessels and microvessels, providing effective structural information for vascular feature extraction. We extract vascular features through dual-circle detection based on branch point characteristics, and introduce NMS (non-maximum suppression) to reduce feature point redundancy. We also calculate the ZSSD (zero sum of squared differences) and perform feature matching on the neighboring blocks of feature points extracted from the front and back frames. The experimental results show that the proposed method has an average accuracy and repeatability score of 0.7149 and 0.5612 in the Vivo data set, respectively. By evaluating the quantity, repeatability, and accuracy of feature detection, our method has more advantages and robustness than the existing methods.

Visualizing and Regulating Dynamic Evolution of Interfacial Electrolyte Configuration during De-solvation Process on Lithium-Metal Anode.

Acting as a passive protective layer, solid-electrolyte interphase (SEI) plays a crucial role in maintaining the stability of the Li-metal anode. Derived from the reductive decomposition of electrolytes (e.g., anion and solvent), the SEI construction presents as an interfacial process accompanied by the dynamic de-solvation process during Li-metal plating. However, typical electrolyte engineering and related SEI modification strategies always ignore the dynamic evolution of electrolyte configuration at the Li/electrolyte interface, which essentially determines the SEI architecture. Herein, by employing advanced electrochemical in situ FT-IR and MRI technologies, we directly visualize the dynamic variations of solvation environments involving Li+-solvent/anion. Remarkably, a weakened Li+-solvent interaction and anion-lean interfacial electrolyte configuration have been synchronously revealed, which is difficult for the fabrication of anion-derived SEI layer. Moreover, as a simple electrochemical regulation strategy, pulse protocol was introduced to effectively restore the interfacial anion concentration, resulting in an enhanced LiF-rich SEI layer and improved Li-metal plating/stripping reversibility.

Genofunc: genome annotation and identification of genome features for automated pipelining analysis of virus whole genome sequences.

BACKGROUND: Viral genomics and epidemiology have been increasingly important tools for analysing the spread of key pathogens affecting daily lives of individuals worldwide. With the rapidly expanding scale of pathogen genome sequencing efforts for epidemics and outbreaks efficient workflows in extracting genomic information are becoming increasingly important for answering key research questions. RESULTS: Here we present Genofunc, a toolkit offering a range of command line orientated functions for processing of raw virus genome sequences into aligned and annotated data ready for analysis. The tool contains functions such as genome annotation, feature extraction etc. for processing of large genomic datasets both manual or as part of pipeline such as Snakemake or Nextflow ready for down-stream phylogenetic analysis. Originally designed for a large-scale HIV sequencing project, Genofunc has been benchmarked against annotated sequence gene coordinates from the Los Alamos HIV database as validation with downstream phylogenetic analysis result comparable to past literature as case study. CONCLUSION: Genofunc is implemented fully in Python and licensed under the MIT license. Source code and documentation is available at: https://github.com/xiaoyu518/genofunc .

METTL13 promotes nasopharyngeal carcinoma progression through regulating the ZEB1/TPT1 axis.

BACKGROUND: Globally, nasopharyngeal carcinoma (NPC) is a prevalent and deadly malignancy. Despite the role of methyltransferase like 13 (METTL13) having been highlighted in a majority of human cancers, its function and mechanism in NPC is indistinct. METHODS: The expression level of METTL13 in NPC cell lines and normal cells was detected using a quantitative real-time polymerase chain reaction. Gain- and loss-of function experiments were conducted. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound-healing, Transwell and tube formation assays, respectively, appraised the proliferative, migratory, invasive and angiogenic cellular responses. Corresponding protein expression was measured by western blotting. A chromatin immunoprecipitation assay was applied to verify the association between ZEB1 and the TPT1 promoter. Eventually, to substantiate the critical role of METTL13 in NPC, the establishment of an in vivo tumorigenesis model was accomplished. RESULTS: METTL13 possessed fortified expression in NPC cells. METTL13 silencing markedly suppressed NPC cellular phenotypes in vitro, including proliferative, migratory, invasive and angiogenic events, as well as hindered tumorigenesis in vivo. Additionally, METTL13 positively regulated ZEB1, whereas ZEB1 could bind to TPT1 promoter and transcriptionally regulate TPT1. TPT1 was also found to be upregulated in NPC cells. TPT1 silencing suppressed NPC cellular phenotypes in vitro. TPT1 overexpression partly weakened the anti-tumor effect of METTL13 in NPC. CONCLUSIONS: In summary, METTL13 up-regulated ZEB1, which facilitated the transcriptional activation of TPT1, ultimately promoting NPC growth and metastasis, providing a potential therapeutic strategy for NPC treatment.

From Li to Na: Exploratory Analysis of Fe-Based Phosphates Polyanion-Type Cathode Materials by Mn Substitution.

Both LiFePO4 (LFP) and NaFePO4 (NFP) are phosphate polyanion-type cathode materials, which have received much attention due to their low cost and high theoretical capacity. Substitution of manganese (Mn) elements for LFP/NFP materials can improve the electrochemical properties, but the connection between local structural changes and electrochemical behaviors after Mn substitution is still not clear. This study not only achieves improvements in energy density of LFP and cyclic stability of NFP through Mn substitution, but also provides an in-depth analysis of the structural evolutions induced by the substitution. Among them, the substitution of Mn enables LiFe0.5 Mn0.5 PO4 to achieve a high energy density of 535.3 Wh kg-1 , while NaFe0.7 Mn0.3 PO4 exhibits outstanding cyclability with 89.6% capacity retention after 250 cycles. Specifically, Mn substitution broadens the ion-transport channels, improving the ion diffusion coefficient. Moreover, LiFe0.5 Mn0.5 PO4 maintains a more stable single-phase transition during the charge/discharge process. The transition of NaFe0.7 Mn0.3 PO4 to the amorphous phase is avoided, which can maintain structural stability and achieve better electrochemical performance. With systematic analysis, this research provides valuable guidance for the subsequent design of high-performance polyanion-type cathodes.

ELK3 Targeting AEG1 Promotes Migration and Invasion of Ovarian Cancer Cells under Hypoxia.

Ovarian cancer (OC) is one of the most common tumors in female reproductive organs with a five-year survival rate of less than 45%. Metastasis is a crucial contributor to OC development. ETS transcription factor (ELK3), as a transcriptional factor, have been involved in multiple tumor development. However, its role in OC remains elusive. In this study, we observed high expression of ELK3 and AEG1 in human OC tissues. OVCAR-3 and SKOV3 cells were treated with hypoxia to mimic tumor microenvironment in vivo. We found that the expression of ELK3 was significantly increased in cells under hypoxia compared with normoxia. ELK3 knockdown inhibited cell migration and invasion abilities under hypoxia. Moreover, ELK3 knockdown decreased ß-catenin expression and inhibited the activation of Wnt/ß-catenin pathway in SKOV3 cells under hypoxia. Astrocyte-elevated gene-1 (AEG1) has been reported to promote OC progression. Our results showed that the mRNA level of AEG1 was decreased when ELK3 knockdown under hypoxia. Dural luciferase assay confirmed that ELK3 bound to gene AEG1 promoter (-2005-+15) and enhanced its transcriptional activity under hypoxia. Overexpression of AEG1 increased the migration and invasion abilities of SKOV3 cell with ELK3 knockdown. In the absence of ELK3, the activation of ß-catenin was recovered by AEG1 overexpression. To sum up, we conclude that ELK3 promotes AEG1 expression by binding to its promoter. ELK3 could promote migration and invasion of OC cells by targeting AEG1, which provides a potential basis for therapeutic approaches to OC.

A Novel Evaluation Method for SLAM-Based 3D Reconstruction of Lumen Panoramas.

Laparoscopy is employed in conventional minimally invasive surgery to inspect internal cavities by viewing two-dimensional images on a monitor. This method has a limited field of view and provides insufficient information for surgeons, increasing surgical complexity. Utilizing simultaneous localization and mapping (SLAM) technology to reconstruct laparoscopic scenes can offer more comprehensive and intuitive visual feedback. Moreover, the precision of the reconstructed models is a crucial factor for further applications of surgical assistance systems. However, challenges such as data scarcity and scale uncertainty hinder effective assessment of the accuracy of endoscopic monocular SLAM reconstructions. Therefore, this paper proposes a technique that incorporates existing knowledge from calibration objects to supplement metric information and resolve scale ambiguity issues, and it quantifies the endoscopic reconstruction accuracy based on local alignment metrics. The experimental results demonstrate that the reconstructed models restore realistic scales and enable error analysis for laparoscopic SLAM reconstruction systems. This suggests that for the evaluation of monocular SLAM three-dimensional (3D) reconstruction accuracy in minimally invasive surgery scenarios, our proposed scheme for recovering scale factors is viable, and our evaluation outcomes can serve as criteria for measuring reconstruction precision.

Long-Life Aqueous Zn-I2 Battery Enabled by a Low-Cost Multifunctional Zeolite Membrane Separator.

Aqueous zinc iodide (Zn-I2) batteries are promising large-scale energy-storage devices. However, the uncontrollable diffuse away/shuttle of soluble I3- leads to energy loss (low Coulombic efficiency, CE), and poor reversibility (self-discharge). Herein, we employ an ordered framework window within a zeolite molecular sieve to restrain I3- crossover and prepare zeolite molecular sieve particles into compact, large-scale, and flexible membranes at the engineering level. The as-prepared membrane can confine I3- within the catholyte region and restrain its irreversible escape, which is proved via space-resolution and electrochemical in situ time-resolution Raman technologies. As a result, overcharge/self-discharge and Zn corrosion are effectively controlled by zeolite separator. After replacing the typically used glass fiber separator to a zeolite membrane, the CE of Zn-I2 battery improves from 78.9 to 98.6% at 0.2 A/g. Besides, after aging at the fully charged state for 5.0 h, self-discharge is restrained and CE is enhanced from 44.0 to 85.65%. Moreover, the Zn-I2 cell maintains 91.0% capacity over 30,000 cycles at 4.0 A/g.

Compilation and evaluation of gastrointestinal endoscopy satisfaction scale. / æ¶ˆåŒ–å† é•œè¯Šç–—æ»¡æ„åº¦é‡è¡¨çš„ç¼–åˆ¶åŠè¯„ä»·.

OBJECTIVES: Gastrointestinal endoscopy plays an important role in the diagnosis and treatment of gastrointestinal diseases. The satisfaction degree of gastrointestinal endoscopy can directly affect the patient's compliance and further impact the treating effect. At present, there is no scale to evaluate the satisfaction degree of gastrointestinal endoscopy in China. This study aims to develop a satisfaction scale of gastrointestinal endoscopy suitable for national conditions and to evaluate its reliability and validity, which provides a tool for clinic to evaluate patients' satisfaction with gastrointestinal endoscopy. METHODS: The original gastrointestinal endoscopy satisfaction scale was compiled by literature review, consulting senior endoscopists and experts. Through the first round of survey about 120 patients, the original scale was analyzed and modified according to the results to get the gastrointestinal endoscopy satisfaction scale (formal scale). The formal scale was used to conduct the second round of survey about 200 patients. The reliability and validity of the scale were analyzed and evaluated according to the survey results. RESULTS: The reliability of the original scale was good but the validity was poor. The formal scale had 2 dimensions and 10 items, the Cronbach's alpha and split-half reliability were 0.889 and 0.823. The structure validity index χ2/df was 2.513, root mean square error of approximation (RMSEA) was 0.094, goodness of fit index (GFI) was 0.914, adjusted goodness of fit index (AGFI) was 0.861, comparative fit index (CFI) was 0.946, normed fit index (NFI) was 0.915. The aggregate validity was general, the discriminative validity was good, and the direct score of patients was strongly correlated with the total score of the scale. CONCLUSIONS: The gastrointestinal endoscopy satisfaction scale has good reliability and validity, which can be used as a tool to evaluate patients' satisfaction with gastrointestinal endoscopy in China.

Development and evaluation of acceptance scale for artificial intelligence in digestive endoscopy by subjects. / å—æ£€è€ å¯¹æ¶ˆåŒ–å† é•œäººå·¥æ™ºèƒ½æŽ¥å—åº¦é‡è¡¨çš„ç¼–åˆ¶åŠè¯„ä»·.

OBJECTIVES: Digestive endoscopy is an important diagnostic and therapeutic tool for digestive system diseases. The artificial intelligence (AI)-assisted system in endoscopy (hereinafter referred to as AI in digestive endoscopy) has broad application prospects in the field of digestive endoscopy. The trust and acceptance of endoscopic subjects are the cornerstone of the research, application, and promotion of AI in digestive endoscopy. Currently, the tools for measuring the acceptance of AI in digestive endoscopy by subjects are limited at home and abroad. This study aims to develop a scale for measuring the acceptance of AI in digestive endoscopy by subjects, then to evaluate its reliability and validity. METHODS: By conducting literature research, an item pool and dimensions were constructed, and a preliminary scale was constructed using Delphi method. Through the first stage of the survey on the subjects, the reliability and validity of the scale were tested, and the revised scale was used for the second stage of survey on the subjects to further verify the structural validity of the scale. RESULTS: The acceptance scale for AI in digestive endoscopy included 11 items in 3 dimensions: accuracy, ethics, benefit and willingness. In the first stage of the survey, 351 valid questionnaires were collected, and the Cronbach's α was 0.864. The correlation coefficient between the total score of the scale and the score of the test item was 0.636, and the Kaiser-Meyer-Olkin (KMO) value in exploratory factor analysis was 0.788. In the second stage of the survey, 335 valid questionnaires were collected, and in confirmatory factor analysis, the χ2/df was 3.774, while the root mean squared error of approximation (RMSEA) was 0.091. CONCLUSIONS: Acceptance scale for AI in digestive endoscopy by subjects developed in this study has good reliability and validity.

The Regulatory Network Involving PcoR, RsaL, and MvaT Coordinates the Quorum-Sensing System in Pseudomonas fluorescens 2P24.

Pseudomonas fluorescens 2P24 is a beneficial plant root-associated microorganism capable of suppressing several soilborne plant diseases. The capacity of P. fluorescens to aggressively colonize the rhizosphere is an important requirement for its biocontrol trait. We previously found that the PcoI/PcoR quorum-sensing system (QS) is involved in regulating the rhizosphere colonization of P. fluorescens. Here, we revealed a sophisticated regulatory network that connects PcoR, RsaL, and MvaT proteins to fine-tune the PcoI/PcoR QS system. Our data showed that PcoR could directly bind to the promoter region of pcoI thereby inducing the PcoI/PcoR QS system, whereas RsaL binds simultaneously with PcoR to the promoter region of pcoI and represses the PcoR-dependent activation of pcoI gene. In addition, RsaL indirectly downregulates the expression of pcoR. Furthermore, we showed that disruption of mvaT enhanced the expression of pcoI, pcoR, and rsaL, whereas MvaT controls the PcoI/PcoR QS in a RsaL-independent manner. Overall, this study elucidates that PcoR, RsaL, and MvaT regulate the PcoI/PcoR QS through a multi-tiered regulatory mechanism and that PcoR is necessary in the RsaL- and MvaT-mediated repression on the expression of pcoI. IMPORTANCE The PcoI/PcoR quorum-sensing system of Pseudomonas fluorescens 2P24 is important for its effective colonization in the plant rhizosphere. Many regulatory elements appear to directly or indirectly influence the QS system. Here, we found a complex regulatory network employing transcriptional factors PcoR, RsaL, and MvaT to influence the expression of the PcoI/PcoR QS in P. fluorescens 2P24. Our results indicate that PcoR and RsaL directly bind to the promoter region of pcoI and then positively and negatively regulate the expression of pcoI, respectively. Furthermore, the H-NS family protein MvaT negatively controls the PcoI/PcoR QS in a RsaL-independent manner. Taken together, our data provide new insights into the interplays between different regulatory elements that fine-tune the QS system of P. fluorescens.

Can visceral adipose tissue and skeletal muscle predict recurrence of newly diagnosed Crohn's disease in different treatments.

BACKGROUND AND AIMS: It is crucial to manage the recurrence of Crohn's disease (CD). This study is aimed to explore whether visceral adipose tissue (VAT) and skeletal muscle (SM) are associated with the recurrence of CD upon different treatments. METHODS: All patients with a definite diagnosis of CD were retrospectively divided into three groups according to distinct treatment regimens: 5-amino salicylic acid group (Group A), steroids + azathioprine (Group B) and biologics (Group C). The pretreatment computerized tomography (CT) images and clinical data were collected. The VAT area, mesenteric fat index (MFI), the ratio of VAT area to fat mass (VAT area/FM) were assessed. The primary end point was the recurrence of CD within 1 year of follow-up. RESULTS: A total of 171 CD patients were enrolled, including 57 (33.33%) patients in Group A, 70 (40.94%) patients in Group B and 44 (25.73%) patients in Group C. Patients with 1-year recurrence had higher MFI (P = 0.011) and VAT area/FM (P = 0.000). ROC curve demonstrated that patients with the ratio of VAT area/FM and MFI higher than 0.578 and 1.394 tended to have recurrence with the AUC of 0.707 and 0.709. Similar results could be observed in Group A & B but not in Group C. CONCLUSIONS: High VAT area/FM and MFI are related to recurrence within 1 year for newly diagnosed CD patients treated by 5-amino salicylic or azathioprine + steroids rather than biologics. We could not observe any radiological data associated with the recurrence of CD patients under biological treatment.

Necroptosis in inflammatory bowel disease: A potential effective target. / ç‚Žç—‡æ€§è‚ ç— ä¸­çš„åæ­»æ€§å‡‹äº¡ï¼šä¸€ä¸ªæ½œåœ¨çš„æ²»ç–—é¶ç‚¹ï¼ˆè‹±æ–‡ï¼‰.

The morbidity of inflammatory bowel diseases (IBD) is rising rapidly but no curative therapies to prevent its recurrence. Cell death is crucial to maintaining homeostasis. Necroptosis is a newly identified programmed cell death and its roles played in IBD need to be explored. Necroptosis is mediated by receptor interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL), which resulted in cell swelling, plasma membrane rupture, intracellular content leaking, and eventually cell death as well as the promotion of inflammation. Studies have found that inhibiting necroptosis alleviated IBD in animal models and IBD patients with an increased level of necroptosis in inflammatory tissues, indicating that necroptosis is related to the pathogenesis of IBD. However, due to the complexity in regulation of necroptosis and the involvement of multiple functions of relevant signaling molecules, the specific mechanism remains elusive. Necroptosis may play a vital regulatory role in the pathogenesis of IBD, which provides a new idea and method for further exploring the therapeutic target of IBD.