The association between the neutrophil-to-lymphocyte ratio and type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease often accompanied by low-grade inflammation. Recently, the neutrophil-to-lymphocyte ratio (NLR) has garnered researchers' interest as an emerging inflammation biomarker. This study aimed to comprehensively explore the relationship between NLR and T2DM using the National Health and Nutrition Examination Survey (NHANES) database. METHOD: We employed a cross-sectional study design to analyze data from five NHANES cycles from 2007 to 2016, excluding individuals with incomplete data. This study utilized a weighted logistic regression model, subgroup analyses, and restricted cubic spline (RCS) analysis to assess the potential relationship between NLR and T2DM. RESULTS: A total of 9903 participants were eligible for the analysis, of which 1280 were diagnosed with T2DM. The T2DM group exhibited significantly higher NLR levels than the non-T2DM group. After adjusting for potential confounders, elevated NLR levels were associated with an increased risk of developing T2DM, indicated by an odds ratio (OR) of 1.14, 95% CI: (1.05,1.24), P = 0.003. The results of the subgroup analyses revealed a significant interaction effect between NLR and T2DM concerning race and hypertension (P for interaction < 0.05). In contrast, no significant interactions were found for age, sex, education level, body mass index (BMI), smoking status, recreational activities, and alcohol drinker (P for interaction > 0.05). RCS analysis showed a significant non-linear relationship between NLR and T2DM, with an inflection point at 2.27 (all P for non-linearity < 0.05). CONCLUSION: Our study indicates that an elevated neutrophil-to-lymphocyte ratio is associated with a higher risk of T2DM.

Effects of tanshinone IIA on endothelial cell dysfunction in uremic condition.

An arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis in uremic patients, yet its dysfunction poses a significant clinical challenge. Venous stenosis, primarily caused by venous neointimal hyperplasia, is a key factor in the failure of vascular access. During vascular access dysfunction, endothelial cells (ECs) transform mechanical stimuli into intracellular signals and interact with vascular smooth muscle cells. Tanshinone IIA, an important compound derived from Salvia miltiorrhiza, has been widely used to treat cardiovascular diseases. However, its role in modulating ECs under uremic conditions remains incompletely understood. In this research, ECs were exposed to sodium tanshinone IIA sulfonate (STS) and subjected to shear stress and uremic conditions. The results indicate that STS can reduce the suppressive effects on the expression of NF-κB p65, JNK and Collagen I in uremia-induced ECs. Moreover, the downregulation of NF-κB p65, JNK and Collagen I can be enhanced through the inhibition of ERK1/2 and the upregulation of Caveolin-1. These findings suggest that tanshinone IIA may improve EC function under uremic conditions by targeting the Caveolin-1/ERK1/2 pathway, presenting tanshinone IIA as a potential therapeutic agent against AVF immaturity caused by EC dysfunction.

Integrative Omics Uncovers Low Tumorous Magnesium Content as A Driver Factor of Colorectal Cancer.

Magnesium (Mg) deficiency is associated with increased risk and malignancy in colorectal cancer (CRC), yet the underlying mechanisms remain elusive. Here, we used genomic, proteomic, and phosphoproteomic data to elucidate the impact of Mg deficiency on CRC. Genomic analysis identified 160 genes with higher mutation frequencies in Low-Mg tumors, including key driver genes such as KMT2C and ERBB3. Unexpectedly, initiation driver genes of CRC, such as TP53 and APC, displayed higher mutation frequencies in High-Mg tumors. Additionally, proteomic and phosphoproteomic data indicated that low Mg content in tumors may activate epithelial-mesenchymal transition (EMT) by modulating inflammation or remodeling the phosphoproteome of cancer cells. Notably, we observed a negative correlation between the phosphorylation of DBN1 at S142 (DBN1S142p) and Mg content. A mutation in S142 to D (DBN1S142D) mimicking DBN1S142p upregulated MMP2 and enhanced cell migration, while treatment with MgCl2 reduced DBN1S142p, thereby reversing this phenotype. Mechanistically, Mg2+ attenuated the DBN1-ACTN4 interaction by decreasing DBN1S142p, which in turn enhanced the binding of ACTN4 to F-actin and promoted F-actin polymerization, ultimately reducing MMP2 expression. These findings shed new light on the crucial role of Mg deficiency in CRC progression and suggest that Mg supplementation may be a promising preventive and therapeutic strategy for CRC.

Excited-Ground-State Transition of the RNA Strand Slippage Mechanism Captured by the Base-Specific Force Field.

Excited-ground-state transition and strand slippage of RNA play key roles in transcription and translation of central dogma. Due to limitation of current experimental techniques, the dynamic structure ensembles of RNA remain inadequately understood. Molecular dynamics simulations offer a promising complementary approach, whose accuracy depends on the force field. Here, we develop the new version of RNA base-specific force field (BSFF2) to address underestimation of base pairing stability and artificial backbone conformations. Extensive evaluations on typical RNA systems have comprehensively confirmed the accuracy of BSFF2. Furthermore, BSFF2 demonstrates exceptional efficiency in de novo folding of tetraloops and reproducing base pair reshuffling transition between RNA excited and ground states. Then, we explored the RNA strand slippage mechanism with BSFF2. We conducted a comprehensive three-dimensional structural investigation into the strand slippage of the most complex r(G4C2)9 repeat element and presented the molecular details in the dynamic transition along with the underlying mechanism. Our results of capturing the strand slippage, excited-ground transition, de novo folding, and simulations for various typical RNA motifs indicate that BSFF2 should be one of valuable tools for dynamic conformation research and structure prediction of RNA, and a future contribution to RNA-targeted drug design as well as RNA therapy development.

Effects of secondary cross-linking on the physicochemical properties of sodium alginate-hydrogel and in vitro release of anthocyanins.

To enhance the physicochemical properties and extend the release duration of sodium alginate (SA) hydrogels, this study explored the impact of acidifier type and the number of cross-linking on the physicochemical characteristics and in vitro anthocyanin release from SA hydrogels, utilizing calcium carbonate as the cross-linking agent. The findings revealed that the utilization of gluconolactone (GDL) as an acidifying agent in the preparation of SA hydrogels, as opposed to hydrochloric acid, resulted in a deceleration of the hydrolysis process of calcium carbonate. This deceleration led to the strengthening of hydrogen-bonding interactions and the development of a more compact network structure within the SA hydrogels. Consequently, there was a noticeable enhancement in the hardness, relaxation time, and anthocyanin encapsulation efficiency of the gels. Additionally, the release of anthocyanins in simulated intestinal fluid was delayed. Secondary cross-linking was found to facilitate ionic interactions between SA and Ca2+, further intensifying the denseness of the network structure and enhancing the physicochemical characteristics of the SA hydrogels. Overall, SA hydrogels processed with GDL as the acidifier and subjected to secondary cross-linking exhibited improved physicochemical properties, delayed release effects, and proved to be an efficient system for the delayed release of anthocyanins.

AQDS-functionalized biochar enhances the bioreduction of Cr(VI) by Shewanella putrefaciens CN32.

The bioreduction of toxic chromium(VI) to sparingly soluble chromium(III) represents an environmentally friendly and cost-effective method for remediating Cr contamination. Usually, this bioreduction process is slow and requires the addition of quinone compounds as electron shuttles to enhance the reaction rate. However, the dissolved quinone compounds are susceptible to loss with water flow, thereby limiting their effectiveness. To address this challenge, this study loaded anthraquinone-2,6-disulfonate (AQDS), a typical quinone compound, onto biochar (BC) to create a novel solid-phase electron mediator (BC-AQDS) that can sustainably promote Cr(VI) bioreduction. The experimental results demonstrated that BC-AQDS significantly promoted the bioreduction of Cr(VI), where the reaction rate constant increased by 4.81 times, and the reduction extent increased by 38.31%. X-ray photoelectron spectroscopy and Fourier-Transform Infrared Spectroscopy analysis revealed that AQDS replaced the -OH functional groups on the BC surface to form BC-AQDS. Upon receiving electrons from Shewanella putrefaciens CN32, BC-AQDS was reduced to BC-AH2DS, which subsequently facilitated the reduction of Cr(VI) to Cr(III). This redox cycle between BC-AQDS and BC-AH2DS effectively enhanced the bioreduction rate of Cr(VI). Our study also found that a lower carbonization temperature of BC resulted in a higher surface -OH functional group content, enabling a greater load of AQDS and a more pronounced enhancement effect on the bioreduction of Cr(VI). Additionally, a smaller particle size of BC and a higher dosage of BC-AQDS further contributed to the enhancement of Cr(VI) bioreduction. The preparation of BC-AQDS in this study effectively improve the utilization of quinone compounds and offer a promising approach for enhancing the bioreduction of Cr(VI). It provides a more comprehensive reference for understanding and solving the problem of Cr pollution in groundwater.

Characterization and Genomic Analysis of Affinirhizobium gouqiense sp. nov. Isolated from Seawater of Gouqi Island Located in the East China Sea and Reclassification of Rhizobium lemnae to the Genus Affinirhizobium as Affinirhizobium lemnae comb. nov.

A novel bacterium designated as SSA5.23T was isolated from seawater. Cells of SSA5.23T are Gram-stain-negative, short, rod-shaped, and exhibit motility via numerous peritrichous flagella. The strain could grow at temperatures ranging from 15 to 35 °C (optimum at 25 °C), in a salinity range of 0-5.0% (w/v) NaCl, and within a pH range of 6.0-9.0 (optimum at pH 7.0). The predominant cellular fatty acid of SSA5.23T was C18:1 ω7c/C18:1 ω6c, and the major respiratory quinones were Q-9 and Q-10. Diphosphatidylglycerol, phosphatidylethanolamine, and phosphatidylglycerol were identified as the primary polar lipids. The complete genome (5.47 Mb) of SSA5.23T comprises of a circular chromosome of 3.64 Mb and three plasmids, specifically sized at 59.73 kb, 227.82 kb, and 1.54 Mb, respectively. Certain genes located on the plasmids play roles in denitrification, oxidative stress resistance, and osmotic tolerance, which likely contribute to the adaptability of this strain in marine conditions. Core-proteome average amino acid identity analysis effectively identified the strain's affiliation with the genus Affinirhizobium, showing the highest value (89.9%) with Affinirhizobium pseudoryzae DSM 19479T. This classification was further supported by the phylogenetic analysis of concatenated alignment of 170 single-copy orthologous proteins. When compared to related reference strains, SSA5.23T displayed an average nucleotide identity ranging from 74.9 to 80.3% and digital DNA-DNA hybridization values ranging from 19.9 to 23.9%. Our findings confirmed that strain SSA5.23T represents a novel species of the genus Affinirhizobium, for which the name Affinirhizobium gouqiense sp. nov. (type strain SSA5.23T = LMG 32560T = MCCC 1K07165T) was suggested.

Norwegian scabies presenting as erythroderma: A case report.

BACKGROUND: Norwegian scabies (NS) is a serious parasitic skin condition. Although NS is one of the causes of erythroderma, it is frequently overlooked. Therefore, it is essential to raise awareness regarding NS presenting as erythroderma. CASE SUMMARY: We present a case of NS that persisted for more than 3 years. After following nonstandard treatment, the patient's rash worsened and gradually progressed into erythroderma. Finally, NS was diagnosed by skin microscopy and pathology. CONCLUSION: When patients with pruritic dermatosis have high-risk factors such as prolonged bed rest and immunodeficiency, clinicians need to enhance their awareness of NS and ensure prompt diagnosis and treatment.

Preoperative Contrast-Enhanced CT-Based Deep Learning Radiomics Model for Distinguishing Retroperitoneal Lipomas and Well­Differentiated Liposarcomas.

RATIONALE AND OBJECTIVES: To assess the efficacy of a preoperative contrast-enhanced CT (CECT)-based deep learning radiomics nomogram (DLRN) for predicting murine double minute 2 (MDM2) gene amplification as a means of distinguishing between retroperitoneal well-differentiated liposarcomas (WDLPS) and lipomas. METHODS: This retrospective multi-center study included 167 patients (training/external test cohort, 104/63) with MDM2-positive WDLPS or MDM2-negative lipomas. Clinical data and CECT features were independently measured and analyzed by two radiologists. A clinico-radiological model, radiomics signature (RS), deep learning and radiomics signature (DLRS), and a DLRN incorporating radiomics and deep learning features were developed to differentiate between WDLPS and lipoma. The model utility was evaluated based on the area under the receiver operating characteristic curve (AUC), accuracy, calibration curve, and decision curve analysis (DCA). RESULTS: The DLRN showed good performance for distinguishing retroperitoneal lipomas and WDLPS in the training (AUC, 0.981; accuracy, 0.933) and external validation group (AUC, 0.861; accuracy, 0.810). The DeLong test revealed the DLRN was noticeably better than clinico-radiological and RS models (training: 0.981 vs. 0.890 vs. 0.751; validation: 0.861 vs. 0.724 vs. 0.700; both P < 0.05); however, no discernible difference in performance was seen between the DLRN and DLRS (training: 0.981 vs. 0.969; validation: 0.861 vs. 0.837; both P > 0.05). The calibration curve analysis and DCA demonstrated that the nomogram exhibited good calibration and offered substantial clinical advantages. CONCLUSION: The DLRN exhibited strong predictive capability in predicting WDLPS and retroperitoneal lipomas preoperatively, making it a promising imaging biomarker that can facilitate personalized management and precision medicine.

Metabolomic and transcriptomic analyses of peach leaves and fruits in response to pruning.

BACKGROUND: Pruning is an important cultivation management option that has important effects on peach yield and quality. However, the effects of pruning on the overall genetic and metabolic changes in peach leaves and fruits are poorly understood. RESULTS: The transcriptomic and metabolomic profiles of leaves and fruits from trees subjected to pruning and unpruning treatments were measured. A total of 20,633 genes and 622 metabolites were detected. Compared with those in the control, 1,127 differentially expressed genes (DEGs) and 77 differentially expressed metabolites (DEMs) were identified in leaves from pruned and unpruned trees (pdLvsupdL), whereas 423 DEGs and 29 DEMs were identified in fruits from the pairwise comparison pdFvsupdF. The content of three auxin analogues was upregulated in the leaves of pruned trees, the content of all flavonoids detected in the leaves decreased, and the expression of almost all genes involved in the flavonoid biosynthesis pathway decreased. The phenolic acid and amino acid metabolites detected in fruits from pruned trees were downregulated, and all terpenoids were upregulated. The correlation analysis revealed that DEGs and DEMs in leaves were enriched in tryptophan metabolism, auxin signal transduction, and flavonoid biosynthesis. DEGs and DEMs in fruits were enriched in flavonoid and phenylpropanoid biosynthesis, as well as L-glutamic acid biosynthesis. CONCLUSIONS: Pruning has different effects on the leaves and fruits of peach trees, affecting mainly the secondary metabolism and hormone signalling pathways in leaves and amino acid biosynthesis in fruits.

Point mutation P174L of the penA gene endowing ceftazidime resistance to Burkholderia pseudomallei in China.

In a clinical isolate of Burkholderia pseudomallei from Hainan, the association between the emergence of ceftazidime resistance and a novel PenA P174L allele was identified for the first time, providing an understanding of one mechanism by which ceftazidime resistance arises in B. pseudomallei.

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OBJECTIVES: To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma. METHODS: In a prospective randomized controlled study, 98 children with dust mite-induced allergic asthma were randomly divided into a control group (n=49) and an SCIT group (n=49). The control group received inhaled corticosteroid treatment, while the SCIT group additionally received a standardized three-year SCIT regimen. The two groups were compared based on peripheral blood eosinophil percentage, visual analogue score (VAS), total medication score, Asthma Control Test/Childhood Asthma Control Test scores, fractional exhaled nitric oxide (FeNO), and lung function before treatment, and at 6 months, 1 year, 2 years, and 3 years after treatment. Adverse reactions were recorded post-injection to evaluate the safety of SCIT. RESULTS: Compared with pre-treatment levels, the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils, VAS, total medication score, and FeNO, while lung function significantly improved, and asthma control levels were better 3 years after treatment (P<0.05). Compared with the control group, the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment (P<0.05). A total of 2 744 injections were administered, resulting in 157 cases (5.72%) of local adverse reactions and 4 cases (0.15%) of systemic adverse reactions, with no severe systemic adverse events. CONCLUSIONS: SCIT is an effective and safe treatment for allergic asthma in children.

Properties regulation and mechanism on ferritin/chitooligosaccharide dual-compartmental emulsions and its application for co-encapsulation of curcumin and quercetin bioactive compounds.

Dual-compartmental emulsions, containing multiple chambers, possess great advantages in co-encapsulation of different cargoes. Herein, we reported a stable dual-compartmental emulsion by regulating the ratio of Marsupenaeus japonicus ferritin (MF) and chitooligosaccharide (COS), enabling efficient co-encapsulation of different compounds. The adsorption behavior of MF/COS complex over droplet interface varied at different ratios, thereby exerting an influence on the emulsion properties. Remarkably, emulsions stabilized by MF/COS complex at a ratio of 2:1 exhibited superior stability, as evidenced by no significant creaming or demulsification during storage or heat treatment. The mechanism is that MF/COS2:1 complex can enhance the formation of thicker interfacial layer and dense continuous phase network structure. Additionally, curcumin and quercetin can be co-encapsulated into the emulsions and their retention rates were significantly improved than those in oils, implying the potential of the resulting dual-compartmental emulsions in co-encapsulation and delivery of bioactive compounds.

Meta-analysis of the clinical efficacy and safety of single versus dual plate in the treatment of comminuted distal femur fractures.

Objective: Through meta-analysis, this study aims to comprehensively evaluate the efficacy of single-plating and double-plating in the treatment of comminuted fractures of the distal femur. Methods: Computer searches of PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP, and Wanfang digital journals were performed, and the timeframe for the searches was from the establishment of each database to July 2023 for each of the databases. Meta-analysis was performed using RevMan 5.4 software provided by the Cochrane Library, and the review process was registered in the PROSPERO database. Results: A total of ten studies were included for statistical analysis. One randomised controlled study and nine retrospective cohort studies with a total of 563 patients were included. The double-plate group was superior to the single-plate group in terms of knee mobility at 6 months postoperatively, overall postoperative complications, and the rate of healing of knee deformity. However, it increased the operation time and intraoperative bleeding, and the difference between the two groups was statistically significant (P < 0.05). There was no significant difference between the two groups in terms of excellent knee function rate, fracture healing time, plate fracture, postoperative infection, delayed fracture healing, and non-union (P ≥ 0.05). Conclusion: Double plate fixation for comminuted fractures of the distal femur can improve knee mobility at 6 months postoperatively, reduce overall postoperative complications, and decrease the incidence of malunion healing. However, it increases operative time and bleeding. Randomised studies are needed to provide strong evidence in the future.

Burkholderia pseudomallei BipD modulates host mitophagy to evade killing.

Mitophagy is critical for mitochondrial quality control and function to clear damaged mitochondria. Here, we found that Burkholderia pseudomallei maneuvered host mitophagy for its intracellular survival through the type III secretion system needle tip protein BipD. We identified BipD, interacting with BTB-containing proteins KLHL9 and KLHL13 by binding to the Back and Kelch domains, recruited NEDD8 family RING E3 ligase CUL3 in response to B. pseudomallei infection. Although evidently not involved in regulation of infectious diseases, KLHL9/KLHL13/CUL3 E3 ligase complex was essential for BipD-dependent ubiquitination of mitochondria in mouse macrophages. Mechanistically, we discovered the inner mitochondrial membrane IMMT via host ubiquitome profiling as a substrate of KLHL9/KLHL13/CUL3 complex. Notably, K63-linked ubiquitination of IMMT K211 was required for initiating host mitophagy, thereby reducing mitochondrial ROS production. Here, we show a unique mechanism used by bacterial pathogens that hijacks host mitophagy for their survival.

Jianpi-Tiaoqi decoction inhibits tumour proliferation and lung metastasis in tumour-bearing mice with triple-negative breast cancer.

Traditional Chinese medicine, specifically the Jianpi Tiaoqi (JPTQ) decoction, has been explored for its role in treating breast cancer, particularly in inhibiting lung metastasis in affected mice. Our study evaluated the effects of JPTQ on several factors, including tumour growth, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT) and immune microenvironment regulation. We used bioluminescence imaging to observe in situ tumour growth and potential lung metastasis. Transcriptomic analysis provided insights into gene expression, whereas flow cytometry was used to examine changes in specific immune cells, such as CD4+ T cells and myeloid-derived suppressor cells. Several essential proteins and genes, including vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9) and B-cell lymphoma 2 (Bcl-2), were assessed through quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. Our findings showed that JPTQ treatment inhibited tumour proliferation in cancer-bearing mice. Bioluminescence imaging and pathological analysis indicated a reduction in lung metastasis. Transcriptome analysis of lung and tumour tissues indicated that the genes associated with EMT, angiogenesis, proliferation and apoptosis were regulated in the JPTQ-treated group. Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment of immune-related pathways. Flow cytometry indicated that JPTQ treatment reduced the proportion of monocyte-myeloid-derived suppressor cells in the lung and increased the number of CD4+ T cells in the peripheral blood and the number of T helper 1 (Th1) cells in the spleen (P < 0.05). E-cadherin and cleaved caspase 3 were upregulated, whereas Snail, Bcl-2, Ki67 and VEGF were downregulated in the lung and tumour tissues; moreover, the expression of MMP-9 was downregulated in the lung tissue (P < 0.05). In essence, JPTQ not only inhibits tumour growth in affected mice, but also promotes positive immune responses, reduces angiogenesis, boosts tumour cell apoptosis, reverses EMT and decreases breast cancer lung metastasis.

Reproductive chemical database: a curated database of chemicals that modulate protein targets regulating important reproductive biological processes.

Recent studies have shifted the spotlight from adult disease to gametogenesis and embryo developmental events, and these are greatly affected by various environmental chemicals, such as drugs, metabolites, pollutants, and others. Growing research has highlighted the critical importance of identifying and understanding the roles of chemicals in reproductive biology. However, the functions and mechanisms of chemicals in reproductive processes remain incomplete. We developed a comprehensive database called the Reproductive Chemical Database (RCDB) ( https://yu.life.sjtu.edu.cn/ChenLab/RCDB ) to facilitate research on chemicals in reproductive biology. This resource is founded on rigorous manual literature extraction and precise protein target prediction methodologies. This database focuses on the delineation of chemicals associated with phenotypes, diseases, or endpoints intricately associated with four important reproductive processes: female and male gamete generation, fertilization, and embryo development in human and mouse. The RCDB encompasses 93 sub-GO processes, and it revealed 1447 intricate chemical-biological process interactions. To date, the RCDB has meticulously cataloged and annotated 830 distinct chemicals, while also predicting 614 target proteins from a selection of 3800 potential candidates. Additionally, the RCDB offers an online predictive tool that empowers researchers to ascertain whether specific chemicals play discernible functional roles in these reproductive processes. The RCDB is an exhaustive, cross-platform, manually curated database, which provides a user-friendly interface to search, browse, and use reproductive processes modulators and their comprehensive related information. The RCDB will help researchers to understand the whole reproductive process and related diseases and it has the potential to promote reproduction research in the pharmacological and pathophysiological areas.

Aberration of social behavior and gut microbiota induced by cross-fostering implicating the gut-brain axis.

The gut microbiota and neurological development of neonatal mice are susceptible to environmental factors that may lead to altered behavior into adulthood. However, the role that changed gut microbiota and neurodevelopment early in life play in this needs to be clarified. In this study, by modeling early-life environmental changes by cross-fostering BALB/c mice, we revealed the effects of the environment during the critical period of postnatal development on adult social behavior and their relationship with the gut microbiota and the nervous system. The neural projections exist between the ascending colon and oxytocin neurons in the paraventricular nuclei (PVN), peripheral oxytocin levels and PVN neuron numbers decreased after cross-fostering, and sex-specific alteration in gut microbiota and its metabolites may be involved in social impairments and immune imbalances brought by cross-fostering via the gut-brain axis. Our findings also suggest that social cognitive impairment may result from a combination of PVN oxytocinergic neurons, gut microbiota, and metabolites.

Cholinergic macrophages promote the resolution of peritoneal inflammation.

The non-neural cholinergic system plays a critical role in regulating immune equilibrium and tissue homeostasis. While the expression of choline acetyltransferase (ChAT), the enzyme catalyzing acetylcholine biosynthesis, has been well documented in lymphocytes, its role in the myeloid compartment is less understood. Here, we identify a significant population of macrophages (Mϕs) expressing ChAT and synthesizing acetylcholine in the resolution phase of acute peritonitis. Using Chat-GFP reporter mice, we observed marked upregulation of ChAT in monocyte-derived small peritoneal Mϕs (SmPMs) in response to Toll-like receptor agonists and bacterial infections. These SmPMs, phenotypically and transcriptionally distinct from tissue-resident large peritoneal macrophages, up-regulated ChAT expression through a MyD88-dependent pathway involving MAPK signaling. Notably, this process was attenuated by the TRIF-dependent TLR signaling pathway, and our tests with a range of neurotransmitters and cytokines failed to induce a similar response. Functionally, Chat deficiency in Mϕs led to significantly decreased peritoneal acetylcholine levels, reduced efferocytosis of apoptotic neutrophils, and a delayed resolution of peritonitis, which were reversible with exogenous ACh supplementation. Intriguingly, despite B lymphocytes being a notable ChAT-expressing population within the peritoneal cavity, Chat deletion in B cells did not significantly alter the resolution process. Collectively, these findings underscore the crucial role of Mϕ-derived acetylcholine in the resolution of inflammation and highlight the importance of the non-neuronal cholinergic system in immune regulation.