The potential molecular mechanism underlying gypenoside amelioration of atherosclerosis in ApoE-/- mice: A multi-omics investigation.

Gypenosides (Gyp) are bioactive components of Gynostemma pentaphyllum that have a variety of pharmacological properties. Extracts of G. pentaphyllum have been found to be effective in the reduction of blood sugar and lipids and prevention of atherosclerosis. Here, the functions of Gyp and the mechanisms underlying their effects on atherosclerosis were investigated. Mice were allocated to three groups, namely, the control (C57BL/6), atherosclerosis model (ApoE-/- mice with high-fat diet), and Gyp-treated groups. Differentially expressed mRNAs, miRNAs, circRNA, and differential metabolites among the groups were analyzed. The results showed that "Fatty acid metabolism", "Fatty acid elongation", "Cytokine-cytokine receptor interaction", and "PI3K-Akt signaling pathway", amongst others, were involved in treatment process. Differentially expressed genes, including Fabp1, Apoe, FADS1, ADH1, SYNPO2, and Lmod1were also identified. Mmu-miR-30a and mmu-miR-30e showed reduced expression in atherosclerosis models but were increased following Gyp treatment, suggesting involvement in the effects of Gyp. In addition, chr5:150604177-150608440 were found to interact with mmu-miR-30a and mmu-miR-30e to regulate their abundance. In terms of metabolomics, Gyp may regulate biological processes involving PGD2 and PGJ2, potentially alleviating atherosclerosis. In conclusion, Gyp appeared to have complex effects on atherosclerosis, most of which were positive. These results support the use of Gyp in the treatment of atherosclerosis.

The cost-effectiveness of syphilis screening in pregnant women: a systematic literature review.

Introduction: The cost-effectiveness study of syphilis screening in pregnant women has not been synthesized. This study aimed to synthesize the economic evidence on the cost-effectiveness of syphilis screening in pregnant women that might contribute to making recommendations on the future direction of syphilis screening approaches. Methods: We systematically searched MEDLINE, PubMed, and Web of Science databases for relevant studies published before 19 January 2023 and identified the cost-effectiveness analyses for syphilis screening in pregnant women. The methodological design quality was appraised by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklist. Results: In total, 17 literature met the eligibility criteria for a full review. Of the 17 studies, four evaluated interventions using different screening methods, seven assessed a combination of syphilis testing and treatment interventions, three focused on repeat screening intervention, and four evaluated the interventions that integrated syphilis and HIV testing. The most cost-effective strategy appeared to be rapid syphilis testing with high treatment rates in pregnant women who were positive. Discussion: The cost-effectiveness of syphilis screening for pregnancy has been widely demonstrated. It is very essential to improve the compliance with maternal screening and the treatment rates for positive pregnant women while implementing screening.

Atrial Cardiomyopathy Predicts the Functional Outcome and Mortality in Stroke Patients.

AIM: Atrial cardiomyopathy (ACM) is characterized by atrial dysfunction. This study aims to assess the prognostic significance of ACM in patients with noncardioembolic stroke (NCS). METHODS: Patients with NCS within seven days of onset were prospectively enrolled between January 2019 and December 2020. ACM was defined as either an N-terminal pro-brain natriuretic peptide (NT-pro BNP) ＞250 pg/ml or a P-terminal force in precordial lead V1 (PTFV1) ≥ 5000µV·ms. A poor functional outcome was determined as a score of 3-6 on the modified Rankin Scale (mRS) within a 2-year follow-up period. Logistic regression and Cox regression analyses were employed to examine the relationship between ACM and the long-term prognosis of patients with NCS. RESULTS: A total of 1,346 patients were enrolled, of whom 299 (22.2%) patients were diagnosed with ACM. A total of 207(15.4%) patients experienced a poor functional outcome, and 58 (4.3%) patients died. A multivariate logistic regression analysis indicated that ACM was significantly associated with a poor functional outcome in NCS patients [adjusted odds ratio (aOR): 2.01; 95% confidence interval (CI): 1.42-2.87; p＜0.001]. Additionally, a multivariate Cox regression analysis showed that an NT-pro BNP ＞250 pg/ml was significantly associated with an increased risk of all-cause mortality [adjusted hazard ratio (aHR), 2.51; 95% CI: 1.42-4.43; p=0.001]. CONCLUSIONS: ACM may serve as a novel predictor of a poor long-term functional outcome in patients with NCS. Elevated NT-pro BNP levels (＞250 pg/ml) were found to be associated with a higher risk of all-cause mortality. These findings warrant further validation in multicenter studies.

Postpartum uterine involution promoted by penetrating-moxibustion therapy: a randomized controlled trial. / é€ç¸æ³•ä¿ƒè¿›äº§åŽå­å®«å¤æ—§ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the effect of penetrating-moxibustion therapy on postpartum uterine involution. METHODS: Eighty puerpera were randomized into an observation group and a control group, 40 cases in each one. In the control group, oxytocin injection was administered by intravenous drip, 20 U each time, once daily. In the observation group, on the base of the treatment as the control group, the penetrating-moxibustion therapy was used at Shenque (GV 8), Qihai (CV 6) and Guanyuan (CV 4), 30 min to 40 min each time, twice a day. The intervention of each group started from the first day after childbirth and lasted 3 days. The uterine volume before and after treatment, and in 42 days of postpartum, the height decrease of the fundus of the uterus, the score of visual analogue scale (VAS) for uterine contraction, the volume of lochia rubra in 1 to 3 days of treatment, and lochia duration were compared between the two groups; and the clinical effect was evaluated. RESULTS: The uterine volume in the observation group was smaller than that of the control group after treatment (P<0.01). In 1 to 3 days of treatment, the height decrease of the fundus of the uterus in the observation group was larger (P<0.01), VAS scores of uterine contraction were lower (P<0.05, P<0.01), the lochia rubra volume was less (P<0.01) than those in the control group. The duration of lochia rubra and lochia was shorter (P<0.01) in the observation group when compared with that of the control group. The favorable rate of uterine involution in the observation group was 95.0% (38/40), higher than that of the control group (75.0%, 30/40, P<0.05). CONCLUSIONS: Penetrating-moxibustion therapy accelerates the recovery of the uterine volume, relieves uterine contraction, shortens the duration of lochia, reduces the lochia volume and promotes the postpartum uterine involution.

TSPAN8+ myofibroblastic cancer-associated fibroblasts promote chemoresistance in patients with breast cancer.

Cancer-associated fibroblasts (CAFs) are abundant stromal cells in the tumor microenvironment that promote cancer progression and relapse. However, the heterogeneity and regulatory roles of CAFs underlying chemoresistance remain largely unclear. Here, we performed a single-cell analysis using high-dimensional flow cytometry analysis and identified a distinct senescence-like tetraspanin-8 (TSPAN8)+ myofibroblastic CAF (myCAF) subset, which is correlated with therapeutic resistance and poor survival in multiple cohorts of patients with breast cancer (BC). TSPAN8+ myCAFs potentiate the stemness of the surrounding BC cells through secretion of senescence-associated secretory phenotype (SASP)-related factors IL-6 and IL-8 to counteract chemotherapy. NAD-dependent protein deacetylase sirtuin 6 (SIRT6) reduction was responsible for the senescence-like phenotype and tumor-promoting role of TSPAN8+ myCAFs. Mechanistically, TSPAN8 promoted the phosphorylation of ubiquitin E3 ligase retinoblastoma binding protein 6 (RBBP6) at Ser772 by recruiting MAPK11, thereby inducing SIRT6 protein destruction. In turn, SIRT6 down-regulation up-regulated GLS1 and PYCR1, which caused TSPAN8+ myCAFs to secrete aspartate and proline, and therefore proved a nutritional niche to support BC outgrowth. By demonstrating that TSPAN8+SIRT6low myCAFs were tightly associated with unfavorable disease outcomes, we proposed that the combined regimen of anti-TSPAN8 antibody and SIRT6 activator MDL-800 is a promising approach to overcome chemoresistance. These findings highlight that senescence contributes to CAF heterogeneity and chemoresistance and suggest that targeting TSPAN8+ myCAFs is a promising approach to circumvent chemoresistance.

Fractional exhaled nitric oxide in idiopathic pulmonary arterial hypertension and mixed connective tissue disease complicating pulmonary hypertension.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) has been extensively studied in various causes of pulmonary hypertension (PH), but its utility as a noninvasive marker remains highly debated. The objective of our study was to assess FeNO levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and mixed connective tissue disease complicating pulmonary hypertension (MCTD-PH), and to correlate them with respiratory functional data, disease severity, and cardiopulmonary function. METHODS: We collected data from 54 patients diagnosed with IPAH and 78 patients diagnosed with MCTD-PH at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Our data collection included measurements of brain natriuretic peptide (pro-BNP), cardiopulmonary exercise test (CPET), pulmonary function test (PFT), impulse oscillometry (IOS), and FeNO levels. Additionally, we assessed World Health Organization functional class (WHO-FC) of each patient. RESULTS: (1) The fractional exhaled concentration of nitric oxide was notably higher in patients with IPAH compared to those with MCTD-PH. Furthermore, within the IPAH group, FeNO levels were found to be lower in cases of severe IPAH compared to mild IPAH (P = 0.024); (2) In severe pulmonary hypertension as per the WHO-FC classification, FeNO levels in IPAH exhibited negative correlations with FEV1/FVC (Forced Expiratory Velocity at one second /Forced Vital Capacity), MEF50% (Maximum Expiratory Flow at 50%), MEF25%, and MMEF75/25% (Maximum Mid-expiratory Flow between 75% and 25%), while in severe MCTD-PH, FeNO levels were negatively correlated with R20% (Resistance at 20 Hz); (3) ROC (Receiving operator characteristic curve) analysis indicated that the optimal cutoff value of FeNO for diagnosing severe IPAH was 23ppb; (4) While FeNO levels tend to be negatively correlated with peakPETO2(peak end-tidal partial pressure for oxygen) in severe IPAH, in mild IPAH they had a positive correlation to peakO2/Heart rate (HR). An interesting find was observed in cases of severe MCTD-PH, where FeNO levels were negatively correlated with HR and respiratory exchange ratio (RER), while positively correlated with O2/HR throughout the cardiopulmonary exercise test. CONCLUSION: FeNO levels serve as a non-invasive measure of IPAH severity. Although FeNO levels may not assess the severity of MCTD-PH, their significant makes them a valuable tool when assessing severe MCTD-PH.

Improving mental health literacy using web- or app-based interventions: A scoping review.

Background: Given the rapid advancement in technology, the Internet has grown to play a significant role in the field of healthcare. Individuals can now access a profusion of easily available materials for self-management of their health. The purpose of this review is to describe Web/App-based interventions that are primarily or secondarily designed to improve mental health literacy (MHL) and to investigate the effectiveness of online interventions for improving mental health. Materials and Method: A scoping review was conducted by searching five databases: PsycINFO, EMBASE, PubMed, CINAHL, and Web of Science. The search was limited to peer-reviewed journals published in English between 2000 and 2022. Studies focusing on enhancements of MHL or its constituent components were included. Results: Twenty-four studies met the inclusion criteria. The interventions primarily targeted patients or individuals exhibiting symptoms of mental disorders, with a higher representation of female participants. All the interventions yielded positive outcomes. The included studies were categorized according to three themes: knowledge, attitude, and self-care skills. Although numerous studies have focused on knowledge improvement, research on interventions targeting self-care skills is scarce. Furthermore, existing literature on knowledge enhancement is limited in terms of the coverage of risk factors. Conclusion: This review indicates gaps in web/app interventions including limited evidence on risk factors, inconsistent help-seeking awareness, and inadequate self-care skills training. Further research is critically needed to address these deficiencies and promote comprehensive MHL.

Clinical significance of small extracellular vesicles in cholangiocarcinoma.

Cholangiocarcinoma is an aggressive and heterogeneous malignancy originating from the bile duct epithelium. It is associated with poor prognosis and high mortality. The global incidence of cholangiocarcinoma is rising, and there is an urgent need for effective early diagnosis and treatment strategies to reduce the burden of this devastating tumor. Small extracellular vesicles, including exosomes and microparticles, are nanoscale vesicles formed by membranes that are released both normally and pathologically from cells, mediating the intercellular transfer of substances and information. Recent studies have demonstrated the involvement of small extracellular vesicles in numerous biological processes, as well as the proliferation, invasion, and metastasis of tumor cells. The present review summarizes the tumorigenic roles of small extracellular vesicles in the cholangiocarcinoma microenvironment. Owing to their unique composition, accessibility, and stability in biological fluids, small extracellular vesicles have emerged as ideal biomarkers for use in liquid biopsies for diagnosing and outcome prediction of cholangiocarcinoma. Specific tissue tropism, theoretical biocompatibility, low clearance, and strong biological barrier penetration of small extracellular vesicles make them suitable drug carriers for cancer therapy. Furthermore, the potential value of small extracellular vesicle-based therapies for cholangiocarcinoma is also reviewed.

Gastrointestinal Dysmotility Predisposes to Colitis through Regulation of Gut Microbial Composition and Linoleic Acid Metabolism.

Disrupted gastrointestinal (GI) motility is highly prevalent in patients with inflammatory bowel disease (IBD), but its potential causative role remains unknown. Herein, the role and the mechanism of impaired GI motility in colitis pathogenesis are investigated. Increased colonic mucosal inflammation is found in patients with chronic constipation (CC). Mice with GI dysmotility induced by genetic mutation or chemical insult exhibit increased susceptibility to colitis, dependent on the gut microbiota. GI dysmotility markedly decreases the abundance of Lactobacillus animlalis and increases the abundance of Akkermansia muciniphila. The reduction in L. animlalis, leads to the accumulation of linoleic acid due to compromised conversion to conjugated linoleic acid. The accumulation of linoleic acid inhibits Treg cell differentiation and increases colitis susceptibility via inducing macrophage infiltration and proinflammatory cytokine expression in macrophage. Lactobacillus and A. muciniphila abnormalities are also observed in CC and IBD patients, and mice receiving fecal microbiota from CC patients displayed an increased susceptibility to colitis. These findings suggest that GI dysmotility predisposes host to colitis development by modulating the composition of microbiota and facilitating linoleic acid accumulation. Targeted modulation of microbiota and linoleic acid metabolism may be promising to protect patients with motility disorder from intestinal inflammation.

Synthesis of Diaryl Tellurides with Sodium Aryltellurites under Mild Conditions.

A highly efficient new protocol has been developed for the formation of C-Te bonds, leading to both symmetrical and unsymmetrical diaryl tellurides. This protocol utilizes sodium aryltellurites (4), which can be easily prepared from low-cost aryltelluride trichlorides and NaOH. The synthesis involves the use of 4 and arylazo sulfones as starting materials in the presence of (MeO)2P(O)H. A variety of diaryl tellurides are obtained in moderate to good yields using this method. Importantly, this innovative protocol eliminates the need for traditional, highly toxic aryltellurolating reagents such as diaryl ditellurides and elemental tellurium. This study will bring new vitality to the synthesis of tellurides.

miR-200a-3p inhibits the PDGF-BB-induced proliferation of VSMCs by affecting their phenotype-associated proteins.

Accumulating evidence shows that the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) can significantly affect the long-term prognosis of coronary artery bypass grafting. This study aimed to explore the factors affecting the proliferation, migration, and phenotypic transformation of VSMCs. First, we stimulated VSMCs with different platelet-derived growth factor-BB (PDGF-BB) concentrations, analyzed the expression of phenotype-associated proteins by Western blotting, and examined cell proliferation by scratch wound healing and the 5-ethynyl-2-deoxyuridine (EdU) assay. VSMC proliferation was induced most by PDGF-BB treatment at 20 ng/mL. miR-200a-3p decreased significantly in A7r5 cells stimulated with PDGF-BB. The overexpression of miR-200a-3p reversed the downregulation of α-SMA (p < 0.001) and the upregulation of vimentin (p < 0.001) caused by PDGF-BB. CCK8 and EdU analyses showed that miR-200a-3p overexpression could inhibit PDGF-BB-induced cell proliferation (p < 0.001). However, flow cytometric analysis showed that it did not significantly increase cell apoptosis. Collectively, the overexpression of miR-200a-3p inhibited the proliferation and migration of VSMCs induced by PDGF-BB, partly by affecting phenotypic transformation-related proteins, providing a new strategy for relieving the restenosis of vein grafts.

Prediction of cervical lymph node metastasis in differentiated thyroid cancer based on radiomics models.

OBJECTIVE: The accurate clinical diagnosis of cervical lymph node metastasis plays an important role in the treatment of differentiated thyroid cancer (DTC). This study aimed to explore and summarize a more objective approach to detect cervical malignant lymph node metastasis of DTC via radiomics models. METHODS: PubMed, Web of Science, MEDLINE, EMBASE, and Cochrane databases were searched for all eligible studies. Articles using radiomics models based on ultrasound, computed tomography, or magnetic resonance imaging to assess cervical lymph node metastasis preoperatively were included. Characteristics and diagnostic accuracy measures were extracted. Bias and applicability judgments were evaluated by the revised QUADAS-2 tool. The estimates were pooled using a random-effects model. Additionally, the leave-one-out method was conducted to assess the heterogeneity. RESULTS: Twenty-nine radiomics studies with 6160 validation set patients were included in the qualitative analysis, and 11 studies with 3863 validation set patients were included in the meta-analysis. Four of them had an external independent validation set. The studies were heterogeneous, and a significant risk of bias was found in 29 studies. Meta-analysis showed that the pooled sensitivity and specificity for preoperative prediction of lymph node metastasis via US-based radiomics were 0.81 (95% CI, 0.73-0.86) and 0.87 (95% CI, 0.83-0.91), respectively. CONCLUSIONS: Although radiomics-based models for cervical lymphatic metastasis in DTC have been demonstrated to have moderate diagnostic capabilities, broader data, standardized radiomics features, robust feature selection, and model exploitation are still needed in the future. ADVANCES IN KNOWLEDGE: The radiomics models showed great potential in detecting malignant lymph nodes in thyroid cancer.

Indirubin alleviates retinal neurodegeneration through the regulation of PI3K/AKT signaling.

Retinal neurodegenerative disease is a leading cause of blindness among the elderly in developed countries, including glaucoma, diabetic retinopathy, traumatic optic neuropathy and optic neuritis, etc. The current clinical treatment is not very effective. We investigated indirubin, one of the main bioactive components of the traditional Chinese medicine Danggui Longhui Pill, in the present study for its role in retinal neurodegeneration. Indirubin exhibited no detectable tissue toxicity in vivo or cytotoxicity in vitro. Moreover, indirubin improved visual function and ameliorated retinal neurodegeneration in mice after optic nerve crush injury in vivo. Furthermore, indirubin reduced the apoptosis of retinal ganglion cells induced by oxidative stress in vitro. In addition, indirubin significantly suppressed the increased production of intracellular reactive oxygen species and the decreased activity of superoxide dismutase induced by oxidative stress. Mechanically, indirubin played a neuroprotective role by regulating the PI3K/AKT/BAD/BCL-2 signaling. In conclusion, indirubin protected retinal ganglion cells from oxidative damage and alleviated retinal neurodegeneration induced by optic nerve crush injury. The present study provides a potential therapeutic medicine for retinal neurodegenerative diseases.

Interpretable machine learning for predicting risk of invasive fungal infection in critically ill patients in the intensive care unit: A retrospective cohort study based on MIMIC-IV database.

IMPORTANCE: Invasive fungal infections are characterized by high incidence and high mortality rates characteristics. In this study, we developed a clinical prediction model for invasive fungal infections in critically ill patients based on machine learning algorithms. The results show that the machine learning model based on 20 clinical features has good predictive value.

Association between perceived stress and motoric cognitive risk syndrome in an elderly population: Rugao longevity and ageing study.

Introduction Previous studies have indicated a correlation between perceived stress and cognitive decline. However, it remains unknown whether high levels of perceived stress can result in motoric cognitive risk (MCR) syndrome. This study investigated the relationship between perceived stress and MCR in a community-based population. Methods The study cohort comprised 852 elderly individuals from the Rugao Longitudinal Aging Cohort. Perceived stress was assessed using the 10-item Perceived Stress Scale (PSS-10), while MCR was defined as the coexistence of subjective memory complaints (SMCs) and slow gait speed. Results The average age of the study participants is 79.84 ± 4.34 years. The mean score of PSS-10 among participants is 10.32 (range = 0-33; [SD] = 5.71), with a median score of 10.00 (6.00, 14.00). The prevalence of MCR is 9.3%. In the logistic regression analysis, for each 1-SD (5.71) increase in the global PSS-10 score, the risk of MCR increased by 40% (95% CI 1.09-1.80). Additionally, in the aspect of two components of MCR, with a 1-SD increase (5.71) in the global PSS-10 score, there was a 50% (95% CI 1.29-1.75) increase in the risk of SMCs and a 27% (95% CI 1.04-1.55) increase in the risk of slow gait speed. In terms of specific walking speed, there was a reverse correlation between the global PSS-10 score and walking speed (r = -0.14, p < 0.001). Conclusions This study provided preliminary evidence that high levels of perceived stress were associated with the risk of MCR in a community-dwelling population.

"Two-Stage Rocket-Propelled" Strategy Boosting Theranostic Efficacy with Mitochondria-Specific Type I-II Photosensitizers.

Imaging-guided photodynamic therapy (PDT) holds great potential for tumor therapy. However, achieving the synergistic enhancement of the reactive oxygen species (ROS) generation efficiency and fluorescence emission of photosensitizers (PSs) remains a challenge, resulting in suboptimal image guidance and theranostic efficacy. The hypoxic tumor microenvironment also hinders the efficacy of PDT. Herein, we propose a "two-stage rocket-propelled" photosensitive system for tumor cell ablation. This system utilizes MitoS, a mitochondria-targeted PS, to ablate tumor cells. Importantly, MitoS can react with HClO to generate a more efficient PS, MitoSO, with a significantly improved fluorescence quantum yield. Both MitoS and MitoSO exhibit less O2-dependent type I ROS generation capability, inducing apoptosis and ferroptosis. In vivo PDT results confirm that this mitochondrial-specific type I-II cascade phototherapeutic strategy is a potent intervention for tumor downstaging. This study not only sheds light on the correlation between the PS structure and the ROS generation pathway but also proposes a novel and effective strategy for tumor downstaging intervention.

Hydrological impacts of vegetation cover change in China through terrestrial moisture recycling.

Terrestrial moisture recycling (TMR), characterized by a continuous process comprising green water flow (i.e., terrestrial evaporation), atmospheric transport, and terrestrial precipitation, functions as a nexus connecting hydrosphere, atmosphere, biosphere, and anthroposphere. During this process, land cover changes that impact green water flow can modify regional and remote precipitation patterns, potentially yielding far-reaching effects on water resources and human livelihoods. However, the comprehensive patterns of moisture recycling and transfer across eco-geographical regions in China, and their connection with various land cover types and vegetation transitions, remain insufficiently evaluated. This study employed an atmospheric moisture tracking model to quantify China's TMR pattern and evaluate the hydrological impacts of vegetation cover changes in China's ecosystems through TMR. The results demonstrate a significant moisture recycling ratio (52.4 %) and a considerable recycled volume (1.9 trillion m3/a) over China, characterized by pronounced moisture transfer from south to north and southwest to northeast. Among various land cover types, grasslands, croplands, and forests play pivotal supportive roles in China's TMR, contributing 738.8, 470.0, and 450.0 billion m3/a of precipitation in China, respectively. Moreover, the potential transition of vegetation between forest and cropland exerts the most significant and extensive impact on China's hydrological cycle. The conversion from forest to cropland leads to a total decrease of 44.7 billion m3/a in precipitation, whereas reforestation from cropland corresponds to a precipitation increase of 74.9 billion m3/a. This study provides a quantitative approach to comprehending the TMR pattern and its relationship with ecosystems, substantiating the significance of a comprehensive water management framework that considers the contribution of atmospheric moisture recycling and the impact of vegetation cover change.

RvD1 improves resident alveolar macrophage self-renewal via the ALX/MAPK14/S100A8/A9 pathway in acute respiratory distress syndrome.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a pulmonary inflammatory process primarily caused by sepsis. The resolution of inflammation is an active process involving the endogenous biosynthesis of specialized pro-resolving mediators, including resolvin D1 (RvD1). Resident alveolar macrophages (RAMs) maintain pulmonary homeostasis and play a key role in the resolution phase. However, the role of RAMs in promoting the resolution of inflammation by RvD1 is unclear. OBJECTIVES: Here, we investigated the mechanisms of RvD1 on regulating RAMs to promote the resolution of ARDS. METHODS: Mice were administered lipopolysaccharide and/or Escherichia coli via aerosol inhalation to establish a self-limited ARDS model. Then, RvD1 was administered at the peak inflammatory response. RAMs self-renewal was measured by flow cytometry, RAM phagocytosis was measured by two-photon fluorescence imaging. In addition, plasma was collected from intensive care unit patients on days 0-2, 3-5, and 6-9 to measure RvD1 and S100A8/A9 levels using triple quadrupole/linear ion trap mass spectrometry. RESULTS: RAMs were found to play a pivotal role in resolving inflammation during ARDS, and RvD1 enhanced RAM proliferation and phagocytosis, which was abrogated by a lipoxin A4 receptor (ALX, RvD1 receptor) inhibitor. Both primary RAMs transfected with rS100A8/A9 and/or S100A8/A9 siRNA and S100A9-/- mice (also deficient in S100A8 function) showed higher turnover and phagocytic function, indicating that RvD1 exerted its effects on RAMs by inhibiting S100A8/A9 production in the resolution phase. RvD1 reduced S100A8/A9 and its upstream MAPK14 levels in vivo and in vitro. Finally, in the patients, RvD1 levels were lower, but S100A8/A9 levels were higher. CONCLUSIONS: We propose that RvD1 improved RAM self-renewal and phagocytosis via the ALX/MAPK14/S100A8/A9 signaling pathway. Plasma RvD1 and S100A8/A9 levels were negatively correlated, and associated with the outcome of sepsis-induced ARDS.