FASN regulates STING palmitoylation via malonyl-CoA in macrophages to alleviate sepsis-induced liver injury.

STING (stimulator of interferon genes) is a critical immunoregulatory protein in sepsis and is regulated by various mechanisms, especially palmitoylation. FASN (fatty acid synthase) is the rate-limiting enzyme to generate cellular palmitic acid (PA) via acetyl-CoA and malonyl-CoA and participates in protein palmitoylation. However, the mechanisms underlying the interaction between STING and FASN have not been completely understood. In this study, STING-knockout mice were used to confirm the pivotal role of STING in sepsis-induced liver injury. Metabolomics confirmed the dyslipidemia in septic mice and patients. The compounds library was screened, revealing that FASN inhibitors exerted a significant inhibitory effect on the STING pathway. Mechanically, the regulatory effect of FASN on the STING pathway was dependent on palmitoylation. Further experiments indicated that the upstream of FASN, malonyl-CoA inhibited STING pathway possibly due to C91 (palmitoylated residue) of STING. Overall, this study reveals a novel paradigm of STING regulation and provides a new perspective on immunity and metabolism.

Recent Advances in Functional Hydrogel for Repair of Abdominal Wall Defects: A Review.

The abdominal wall plays a crucial role in safeguarding the internal organs of the body, serving as an essential protective barrier. Defects in the abdominal wall are common due to surgery, infection, or trauma. Complex defects have limited self-healing capacity and require external intervention. Traditional treatments have drawbacks, and biomaterials have not fully achieved the desired outcomes. Hydrogel has emerged as a promising strategy that is extensively studied and applied in promoting tissue regeneration by filling or repairing damaged tissue due to its unique properties. This review summarizes the five prominent properties and advances in using hydrogels to enhance the healing and repair of abdominal wall defects: (a) good biocompatibility with host tissues that reduces adverse reactions and immune responses while supporting cell adhesion migration proliferation; (b) tunable mechanical properties matching those of the abdominal wall that adapt to normal movement deformations while reducing tissue stress, thereby influencing regulating cell behavior tissue regeneration; (c) drug carriers continuously delivering drugs and bioactive molecules to sites optimizing healing processes enhancing tissue regeneration; (d) promotion of cell interactions by simulating hydrated extracellular matrix environments, providing physical support, space, and cues for cell migration, adhesion, and proliferation; (e) easy manipulation and application in surgical procedures, allowing precise placement and close adhesion to the defective abdominal wall, providing mechanical support. Additionally, the advances of hydrogels for repairing defects in the abdominal wall are also mentioned. Finally, an overview is provided on the current obstacles and constraints faced by hydrogels, along with potential prospects in the repair of abdominal wall defects.

Clinical and Molecular Characteristics of Patients with Bloodstream Infections Caused by KPC and NDM Co-Producing Carbapenem-Resistant Klebsiella pneumoniae.

Purpose: Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-ß-lactamase (NDM) co-producing carbapenem-resistant Klebsiella pneumoniae (KPC-NDM-CRKP) isolates have been increasingly reported worldwide but have not yet been systematically studied. Thus, we have conducted a study to compare the risk factors, molecular characteristics, and mortality involved in clinical bloodstream infections (BSIs) caused by KPC-NDM-CRKP and KPC-CRKP strains. Methods: A retrospective study was conducted on 231 patients with BSIs caused by CRKP at Jinling Hospital in China from January 2020 to December 2022. Antimicrobial susceptibility testing, carbapenemase genes detection and whole-genome sequencing were performed subsequently. Results: Overall, 231 patients were included in this study: 25 patients with KPC-NDM-CRKP BSIs and 206 patients with KPC-CRKP BSIs. Multivariate analysis implicated ICU-acquired BSI, surgery within 30 days, and longer stay of hospitalization prior to CRKP isolation as independent risk factors for KPC-NDM-CRKP BSIs. The 30-day mortality rate of the KPC-NDM-CRKP BSIs group was 56% (14/25) compared with 32.5% (67/206) in the KPC-CRKP BSIs control group (P = 0.02). The ICU-acquired BSIs, APACHE II score at BSI onset, and BSIs caused by KPC-NDM-CRKP were independent predictors for 30-day mortality in patients with CRKP bacteremia. The most prevalent ST in KPC-NDM-CRKP isolates was ST11 (23/25, 92%), followed by ST15 (2/25, 8%). Conclusion: In patients with CRKP BSIs, KPC-NDM-CRKP was associated with an excess of mortality. The likelihood that KPC-NDM-CRKP will become the next "superbug" highlights the significance of epidemiologic surveillance and clinical awareness of this pathogen.

Polyaspartic acid increases potassium content and reduces the ratio of total sugar to nicotine in tobacco leaves.

Tobacco is an important cash crop in China, but the low potassium (K) content and high ratio of total sugar to nicotine in tobacco leaves have seriously affected the quality of tobacco leaves. As a fertilizer synergist, polyaspartic acid (PASP) can improve the K content in tobacco leaves, but it is unknown how it affects the K content in different parts of tobacco leaves, and how PASP affects the ratio of total sugar to nicotine in tobacco leaves has not been reported. Therefore, "Zhongyan 100" was selected for pot experiments with 5 different PASP addition levels: CK (0.0 %), P1 (0.1 %), P2 (0.2 %), P3 (0.4 %) and P4 (0.6 %), to reveal the effects of PASP on tobacco growth, K content, sugar content, nicotine content and the ratio of total sugar to nicotine in different tobacco parts, and determine the optimal PASP dosage for regulating the K content and the ratio of total sugar to nicotine in tobacco. The results showed that P1 (0.1 %) and P2 (0.2 %) only had slighter effects on tobacco growth and quality, while P3 (0.4 %) and P4 (0.6 %)treatments significantly promoted dry matter accumulation, increased K and nicotine content in leaves, decreased reducing sugar and total soluble sugar content in leaves, thereby reducing the ratio of total sugar to nicotine in tobacco leaves, especially in upper leaves. Considering the economic cost savings, 0.4% PASP was determined as the best application level to improve the growth and quality of tobacco. Thus, proper application of PASP is beneficial to improve tobacco leaf quality and reduce chemical K fertilizer application, thereby decreasing agricultural environmental risks of chemical fertilizer and alleviating the rapid depletion of potash in the world.

Amino acid application inhibits root-to-shoot cadmium translocation in Chinese cabbage by modulating pectin methyl-esterification.

The exogenous application of amino acids (AAs) generally alleviates cadmium (Cd) toxicity in plants by altering their subcellular distribution. However, the physiological mechanisms underlying AA-mediated cell wall (CW) sequestration of Cd in Chinese cabbage remain unclear. Using two genotypes of Chinses cabbage, Jingcui 60 (Cd-tolerant) and 16-7 (Cd-sensitive), we characterized the root structure, subcellular distribution of Cd, CW component, and related gene expression under the Cd stress. Cysteine (Cys) supplementation led to a reduction in the Cd concentration in the shoots of Jingcui 60 and 16-7 by 65.09 % and 64.03 %, respectively. Addition of Cys alleviated leaf chlorosis in both cultivars by increasing Cd chelation in the root CW and reducing its distribution in the cytoplasm and organelles. We further demonstrated that Cys supplementation mediated the downregulation of PMEI1 expression and improving the activity of pectin methyl-esterase (PME) by 17.98 % and 25.52 % in both cultivars, respectively, compared to the Cd treatment, resulting in an approximate 12.00 %-14.70 % increase in Cd retention in pectin. In contrast, threonine (Thr) application did not significantly alter Cd distribution in the shoots of either cultivar. Taken together, our results suggest that Cys application reduces Cd root-to-shoot translocation by increasing Cd sequestration in the root CW through the downregulation of pectin methyl-esterification.

Prediction models of surgical site infection after gastrointestinal surgery: a nationwide prospective cohort study.

OBJECTIVE: This study aimed to construct and validate a clinical prediction model for surgical site infection (SSI) risk 30 days after gastrointestinal surgery. MATERIALS AND METHODS: This multicentre study involving 57 units conducted a 30-day postoperative follow-up of 17 353 patients who underwent gastrointestinal surgery at the unit from 1 March 2021 to 28 February 2022. The authors collected a series of hospitalisation data, including demographic data, preoperative preparation, intraoperative procedures and postoperative care. The main outcome variable was SSI, defined according to the Centres for Disease Control and Prevention guidelines. This study used the least absolute shrinkage and selection operator (LASSO) algorithm to screen predictive variables and construct a prediction model. The receiver operating characteristic curve, calibration and clinical decision curves were used to evaluate the prediction performance of the prediction model. RESULTS: Overall, 17 353 patients were included in this study, and the incidence of SSI was 1.6%. The univariate analysis combined with LASSO analysis showed that 20 variables, namely, chronic liver disease, chronic kidney disease, steroid use, smoking history, C-reactive protein, blood urea nitrogen, creatinine, albumin, blood glucose, bowel preparation, surgical antibiotic prophylaxis, appendix surgery, colon surgery, approach, incision type, colostomy/ileostomy at the start of the surgery, colostomy/ileostomy at the end of the surgery, length of incision, surgical duration and blood loss were identified as predictors of SSI occurrence ( P <0.05). The area under the curve values of the model in the train and test groups were 0.7778 and 0.7868, respectively. The calibration curve and Hosmer-Lemeshow test results demonstrated that the model-predicted and actual risks were in good agreement, and the model forecast accuracy was high. CONCLUSIONS: The risk assessment system constructed in this study has good differentiation, calibration and clinical benefits and can be used as a reference tool for predicting SSI risk in patients.

Establishment and evaluation of an improved rat model of open abdomen.

INTRODUCTION: This study aimed to establish an animal model of open abdomen (OA) through temporary abdominal closure via different techniques. METHODS: Adult male Sprague-Dawley rats were randomly divided into three groups: group A (OA with polypropylene mesh alone); group B (OA with polypropylene mesh combined with a patch); and group C (OA with polypropylene mesh and a sutured patch). Vital signs, pathophysiological changes, and survival rates were closely monitored in the rats for 7 days after surgery. Abdominal X-rays and histopathological examinations were performed to assess abdominal organ changes and wound healing. RESULTS: The results showed no significant difference in mortality rates among the three groups (p > 0.05). However, rats in group B exhibited superior overall condition, cleaner wounds, and a higher rate of wound healing compared to the other groups (p < 0.05). Abdominal X-rays indicated that varying degrees of distal intestinal obstruction in all groups. Histopathological examinations revealed fibrous hyperplasia, inflammatory cell infiltration, neovascularization, and collagen deposition in all groups. Group B demonstrated enhanced granulation tissue generation, neovascularization, and collagen deposition compared to the other groups (p < 0.05). CONCLUSIONS: Polypropylene mesh combined with patches is the most suitable method for establishing an animal model of OA. This model successfully replicated the pathological and physiological changes in postoperative patients with OA, specifically the progress of abdominal skin wound healing. It provides a practical and reliable animal model for OA research.

Phenethylferulate as a natural inhibitor of inflammation in LPS-stimulated RAW 264.7 macrophages: focus on NF-κB, Akt and MAPK signaling pathways.

BACKGROUND: Notopterygii Rhizoma et Radix (NRR) is commonly used for the treatment of inflammation-linked diseases. Phenethylferulate (PF) is high content in NRR crude, but its anti-inflammatory effect remains unclear. Therefore, we aimed to investigate the anti-inflammatory properties of PF and its underlying molecular mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. METHODS: The effect of PF on cell viability was measured by MTT assay. The anti-inflammatory properties of PF were studied by detecting the levels of inflammatory mediators and cytokines using enzyme-linked immunosorbent assay (ELISA). Furthermore, the anti-inflammatory mechanisms of PF were determined by Western blot analysis. RESULTS: PF was not cytotoxic to RAW 264.7 macrophages at the concentrations of below 48 µM. ELISA showed that PF conspicuously inhibited overproduction of prostaglandin E2 (PGE2), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6). Western blot analysis showed that PF remarkably suppressed overproduction of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), the phosphorylation of inhibitor of NF-κB kinase α (IκB-α), protein kinase B (Akt), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK) and p38, as well as the degradation and subsequent nuclear translocation of p65. CONCLUSIONS: PF is a potent inhibitor of inflammation acting on nuclear factor kappa-B (NF-κB), Akt and mitogen-activated protein kinase (MAPK) signaling pathways in LPS-stimulated RAW 264.7 macrophages. This work provides evidence for the suitability of PF as a therapeutic candidate for the management of inflammatory-mediated immune disorders.

A click chemistry-mediated all-peptide cell printing hydrogel platform for diabetic wound healing.

High glucose-induced vascular endothelial injury is a major pathological factor involved in non-healing diabetic wounds. To interrupt this pathological process, we design an all-peptide printable hydrogel platform based on highly efficient and precise one-step click chemistry of thiolated γ-polyglutamic acid, glycidyl methacrylate-conjugated γ-polyglutamic acid, and thiolated arginine-glycine-aspartate sequences. Vascular endothelial growth factor 165-overexpressed human umbilical vein endothelial cells are printed using this platform, hence fabricating a living material with high cell viability and precise cell spatial distribution control. This cell-laden hydrogel platform accelerates the diabetic wound healing of rats based on the unabated vascular endothelial growth factor 165 release, which promotes angiogenesis and alleviates damages on vascular endothelial mitochondria, thereby reducing tissue hypoxia, downregulating inflammation, and facilitating extracellular matrix remodeling. Together, this study offers a promising strategy for fabricating tissue-friendly, high-efficient, and accurate 3D printed all-peptide hydrogel platform for cell delivery and self-renewable growth factor therapy.

Precise Orchestration of Gasdermins' Pore-Forming Function by Posttranslational Modifications in Health and Disease.

Gasdermins (GSDMs) serve as pivotal executors of pyroptosis and play crucial roles in host defence, cytokine secretion, innate immunity, and cancer. However, excessive or inappropriate GSDMs activation is invariably accompanied by exaggerated inflammation and results in tissue damage. In contrast, deficient or impaired activation of GSDMs often fails to promptly eliminate pathogens, leading to the increasing severity of infections. The activity of GSDMs requires meticulous regulation. The dynamic modulation of GSDMs involves many aspects, including autoinhibitory structures, proteolytic cleavage, lipid binding and membrane translocation (oligomerization and pre-pore formation), oligomerization (pore formation) and pore removal for membrane repair. As the most comprehensive and efficient regulatory pathway, posttranslational modifications (PTMs) are widely implicated in the regulation of these aspects. In this comprehensive review, we delve into the complex mechanisms through which a variety of proteases cleave GSDMs to enhance or hinder their function. Moreover, we summarize the intricate regulatory mechanisms of PTMs that govern GSDMs-induced pyroptosis.

Smart implants: 4D-printed shape-morphing scaffolds for medical implantation.

Biomedical implants have recently shown excellent application potential in tissue repair and replacement. Applying three-dimensional (3D) printing to implant scaffold fabrication can help to address individual needs more precisely. Fourdimensional (4D) printing emerges rapidly based on the development of shape-responsive materials and design methods, which makes the production of dynamic functional implants possible. Smart implants can be pre-designed to respond to endogenous or exogenous stimuli and perform seamless integration with regular/ irregular tissue defects, defect-luminal organs, or curved structures via programmed shape morphing. At the same time, they offer great advantages in minimally invasive surgery due to the small-to-large volume transition. In addition, 4D-printed cellular scaffolds can generate extracellular matrix (ECM)-mimetic structures that interact with the contacting cells, expanding the possible sources of tissue/organ grafts and substitutes. This review summarizes the typical technologies and materials of 4D-printed scaffolds, and the programming designs and applications of these scaffolds are further highlighted. Finally, we propose the prospects and outlook of 4D-printed shape-morphing implants.

Identification of Risk Factors and Phenotypes of Surgical Site Infection in Patients After Abdominal Surgery.

OBJECTIVES: We aimed to determine the current incidence rate and risk factors for surgical site infection (SSI) after abdominal surgery in China and to further demonstrate the clinical features of patients with SSI. BACKGROUND: Contemporary epidemiology and clinical features of SSI after abdominal surgery remain poorly characterized. METHODS: A prospective multicenter cohort study was conducted from March 2021 to February 2022; the study included patients who underwent abdominal surgery at 42 hospitals in China. Multivariable logistic regression analysis was performed to identify risk factors for SSI. Latent class analysis (LCA) was used to explore the population characteristics of SSI. RESULTS: In total, 23,982 patients were included in the study, of whom 1.8% developed SSI. There was a higher SSI incidence in open surgery (5.0%) than in laparoscopic or robotic surgeries (0.9%). Multivariable logistic regression indicated that the independent risk factors for SSI after abdominal surgery were older age, chronic liver disease, mechanical bowel preparation, oral antibiotic bowel preparation, colon or pancreas surgery, contaminated or dirty wounds, open surgery, and colostomy/ileostomy. LCA revealed 4 subphenotypes in patients undergoing abdominal surgery. Types α and ß were mild subclasses with a lower SSI incidence; whereas types γ and δ were the critical subgroups with a higher SSI incidence, but their clinical features were different. CONCLUSIONS: LCA identified 4 subphenotypes in patients who underwent abdominal surgery. Types γ and δ were critical subgroups with a higher SSI incidence. This phenotype classification can be used to predict SSI after abdominal surgery.

Melt electrowriting-printed peritoneal scaffold prevents peritoneal adhesion and facilitates peritoneal repair.

Peritoneal adhesion is a critical issue after abdominal surgery. Cell-based methods for preventing peritoneal adhesion have not yet been fully investigated. Here, we constructed a highly biomimetic peritoneal scaffold by seeding mesothelial cells, the natural physiological barrier of the peritoneum, onto a melt electrowriting-printed scaffold. The scaffolds with the microfibers crossed at different angles (30°, 60°, and 90°) were screened based on mesothelial cell proliferation and orientation. Thirty degrees were more suitable for improving proliferation of mesothelial cells and cell growth in a single direction; therefore, the 30° peritoneal scaffold could better mimic the physiological structure of native peritoneum. Mechanistically, such a peritoneal scaffold was able to act as a barrier to prevent peritoneal resident macrophages from migrating to the site of the peritoneal lesion. In vivo mesothelial cell tracking using lentivirus technology confirmed that the peritoneal scaffold, compared to the scaffold without mesothelial cells, could prevent peritoneal adhesion and was directly involved in the repair of injured peritoneum. This study suggests that the peritoneal scaffolds can potentially prevent peritoneal adhesion, offering a new approach for clinical treatment.

Optimizing The Timing of Stereotactic Minimally Invasive Drainage for Hypertensive Intracerebral Hemorrhage.

INTRODUCTION: Intracerebral hemorrhage is a high-risk pathological event that is associated with formidable morality rates. Here, our objective was to perform a retrospective study to determine the best timing for drainage using physiological data on patients who received drainage at different timings. METHODS: In this retrospective study, we reviewed 198 patients with hypertensive cerebral hemorrhage who underwent stereotactic drainage at the conventional timing (surgery within 12 h of admission; control group) and 216 patients who underwent stereotactic drainage at a customized surgical timing (elective group). Follow-ups were performed at 3 and 6 months after surgery. RESULTS: The clinical indicators, including prognosis, hematoma clearance, recurrent hemorrhage, intracerebral infection, pulmonary infection, deep venous thrombosis, gastrointestinal hemorrhage, National Institutes of Health Stroke Scale scores, and matrix metallopeptidase 2 and 9 levels, were compared between the control and elective groups. Our data indicated that the elective group had significantly better prognosis compared to the control group (p = 0.021), with a higher rate of hematoma clearance (p = 0.004) and a lower rate of recurrent hemorrhage (p = 0.018). The total occurrence rate of post-surgery complications was also lower for the elective group (p = 0.026). NIHSS scores and serum MMP2/9 levels of the elective group were lower than those of the control group. CONCLUSIONS: Customized timing of stereotactic drainage may be superior to conventional fixed timing (within 12 h post-hemorrhage) in reducing post-surgery complications and promoting recovery, which supports the potential use of customized timing of stereotactic minimally invasive drainage as a new convention in clinics.

4-octyl itaconate as a metabolite derivative inhibits inflammation via alkylation of STING.

The Krebs cycle-derived metabolite itaconate, whose production is catalyzed by immune response gene 1 (IRG1), has potential to link immunity and metabolism in activated macrophages through alkylation or competitive inhibition of target proteins. In support of this, our previous study demonstrated that the stimulator of interferon genes (STING) signaling platform functions as a hub in macrophage immunity and has a profound impact on the prognosis of sepsis. Interestingly, we find that itaconate, an endogenous immunomodulator, can significantly inhibit the activation of STING signaling. Moreover, 4-octyl itaconate (4-OI), which is a permeable itaconate derivative, can alkylate cysteine sites 65, 71, 88, and 147 of STING, thereby inhibiting its phosphorylation. Furthermore, itaconate and 4-OI inhibit the production of inflammatory factors in sepsis models. Our results broaden the knowledge on the role of the IRG1-itaconate axis in immunomodulation and highlight itaconate and its derivatives as potential therapeutic agents in sepsis.

Extracellular matrix bioink boosts stemness and facilitates transplantation of intestinal organoids as a biosafe Matrigel alternative.

Organoids hold inestimable therapeutic potential in regenerative medicine and are increasingly serving as an in vitro research platform. Still, their expanding applications are critically restricted by the canonical culture matrix and system. Synthesis of a suitable bioink of bioactivity, biosecurity, tunable stiffness, and printability to replace conventional matrices and fabricate customized culture systems remains challenging. Here, we envisaged a novel bioink formulation based on decellularized extracellular matrix (dECM) from porcine small intestinal submucosa for organoids bioprinting, which provides intestinal stem cells (ISCs) with niche-specific ECM content and biomimetic microstructure. Intestinal organoids cultured in the fabricated bioink exhibited robust generation as well as a distinct differentiation pattern and transcriptomic signature. This bioink established a new co-culture system able to study interaction between epithelial homeostasis and submucosal cells and promote organoids maturation after transplantation into the mesentery of immune-deficient NODSCID-gamma (NSG) mice. In summary, the development of such photo-responsive bioink has the potential to replace tumor-derived Matrigel and facilitate the application of organoids in translational medicine and disease modeling.

Removal of nitrides and fluorides from secondary aluminum dross by catalytic hydrolysis and its mechanism.

Secondary aluminum dross (SAD) refers to hazardous waste from secondary aluminum refinement. It contains a large amount of aluminum nitride and fluorides that cause serious environmental pollution for direct discharge and hinder the resource utilization of SAD. However, it is difficult to remove nitride and fluoride simultaneously for their complicated phases. In this paper, the catalytic hydrolysis of SAD using NaOH as a catalyst to remove nitrides and fluorides synchronously was investigated systemically through single factor and response surface experiments. In addition, the chemical speciation and transformation of nitrides and fluorides were analyzed systematically. The catalytic hydrolysis removal mechanism was summarized. The optimal conditions for catalytic hydrolysis were established as follows: reaction temperature 96.60 °C; reaction time 2.85 h; liquid-solid ratio 9.28 mL/g and catalyst addition 12.62 wt %; and removal efficiency of nitrides and fluorides reached 99.03% and 81.93%, respectively. The mechanism of nitrides removal was that aluminum nitride was hydrolyzed to Al(OH)3 and NH3. NaOH reacting with Al(OH)3 covering on the surface of AlN and the rapid escape of NH3 promoted the hydrolysis of AlN under the catalysis of NaOH. The mechanism of fluorides removal was that the encapsulated fluoride particles were opened by catalytic hydrolysis to be dissolved in the solution. In this research, nitrides and fluorides were removed efficiently and synchronously. The hydrolysis residues can be used to prepare polyaluminum chloride (PAC) and ceramic materials. The hydrolysate can be prepared NH3·H2O by evaporative in alkaline solution. Then the solution without NH4 + was prepared Al(OH)3 by precipitation of adjusting pH value using HCl. And the remained liquid after removing NaAlO2 was used to prepare refining agent by evaporative crystallization. The work in this paper was beneficial for the utilization of SAD.

The IRG1-Itaconate axis: A regulatory hub for immunity and metabolism in macrophages.

Metabolism could be served as a guiding force for immunity, and macrophages undergo drastic metabolic reprogramming during inflammatory processes, including enhancing glycolysis and reshaping the tricarboxylic acid cycle (TCA) cycle. The disrupted TCA cycle facilitates itaconate accumulation, consistent with the significant up-regulation of immune response gene 1 (IRG1) in activated macrophages. IRG1 catalyzes the decarboxylation of cis-aconitate to synthesize itaconate, and notably, the IRG1-Itaconate axis has excellent potential to link macrophages' immunity and metabolism. Here, we review vital molecules that affect the activation of the IRG1-Itaconate axis, including interferon regulatory factor 1/9 (IRF1/9), transcription 1 and 3 (STAT1/3), CCAAT enhancer-binding protein ß (C/EBPß), and the protein kinase C (PKC). We then focus on how the IRG1-Itaconate axis regulates the inflammatory pathway in macrophages, proposed to involve kelch-like ECH-associated protein 1 (Keap1), NOD-, LRR- and pyrin domain-containing 3 (NLRP3), gasdermin D (GSDMD), activating transcription factor 3 (ATF3), receptor-interacting protein kinase-3 (RIPK3), et al. In addition, we provide an overview of the way the axis participates in the metabolism of macrophages. Eventually, we summarize current connections between the IRG1-Itaconate axis and inflammatory diseases, bringing light to new therapeutic opportunities in inflammatory diseases.

Macrophages-microenvironment crosstalk in fibrostenotic inflammatory bowel disease: from basic mechanisms to clinical applications.

INTRODUCTION: Intestinal fibrosis is a common complication of Inflammatory Bowel Disease (IBD) with no available drugs. The current therapeutic principle is surgical intervention as the core. Intestinal macrophages contribute to both the progression of inflammation and fibrosis. Understanding the role of macrophages in the intestinal microenvironment could bring new hope for fibrosis prevention or even reversal. AREAS COVERED: This article reviewed the most relevant reports on macrophage in the field of intestinal fibrosis. The authors discussed current opinions about how intestinal macrophages function and interact with surrounding mediators during inflammation resolution and fibrostenotic IBD. Based on biological mechanisms findings, authors summarized related clinical trial outcomes. EXPERT OPINION: The plasticity of intestinal macrophages allows them to undergo dramatic alterations in their phenotypes or functions when exposed to gastrointestinal environmental stimuli. They exhibit distinct metabolic characteristics, secrete various cytokines, express unique surface markers, and transmit different signals. Nevertheless, the specific mechanism through which the intestinal macrophages contribute to intestinal fibrosis remains unclear. It should further elucidate a novel therapeutic approach by targeting macrophages, especially distinct mechanisms in specific subgroups of macrophages involved in the progression of fibrogenesis in IBD.

Hormone Regulation of CCCH Zinc Finger Proteins in Plants.

CCCH zinc finger proteins contain one to six tandem CCCH motifs composed of three cysteine and one histidine residues and have been widely found in eukaryotes. Plant CCCH proteins control a wide range of developmental and adaptive processes through DNA-protein, RNA-protein and/or protein-protein interactions. The complex networks underlying these processes regulated by plant CCCH proteins are often involved in phytohormones as signal molecules. In this review, we described the evolution of CCCH proteins from green algae to vascular plants and summarized the functions of plant CCCH proteins that are influenced by six major hormones, including abscisic acid, gibberellic acid, brassinosteroid, jasmonate, ethylene and auxin. We further compared the regulatory mechanisms of plant and animal CCCH proteins via hormone signaling. Among them, Arabidopsis AtC3H14, 15 and human hTTP, three typical CCCH proteins, are able to integrate multiple hormones to participate in various biological processes.