Macrophages are critical for regulation of inflammatory response during endotoxemia and septic shock. However, the mediators underlying their regulatory function remain obscure. Growth differentiation factor 3 (GDF3), a member of transforming growth factor beta (TGF-β) superfamily, has been implicated in inflammatory response. Nonetheless, the role of GDF3 in macrophage-regulated endotoxemia/sepsis is unknown. Here, we show that serum GDF3 levels in septic patients are elevated and strongly correlate with severity of sepsis and 28-day mortality. Interestingly, macrophages treated with recombinant GDF3 protein (rGDF3) exhibit greatly reduced production of pro-inflammatory cytokines, comparing to controls upon endotoxin challenge. Moreover, acute administration of rGDF3 to endotoxin-treated mice suppresses macrophage infiltration to the heart, attenuates systemic and cardiac inflammation with less pro-inflammatory macrophages (M1) and more anti-inflammatory macrophages (M2), as well as prolongs mouse survival. Mechanistically, GDF3 is able to activate Smad2/Smad3 phosphorylation, and consequently inhibits the expression of nod-like receptor protein-3 (NLRP3) in macrophages. Accordingly, blockade of Smad2/Smad3 phosphorylation with SB431542 significantly offsets rGDF3-mediated anti-inflammatory effects. Taken together, this study uncovers that GDF3, as a novel sepsis-associated factor, may have a dual role in the pathophysiology of sepsis. Acute administration of rGDF3 into endotoxic shock mice could increase survival outcome and improve cardiac function through anti-inflammatory response by suppression of M1 macrophage phenotype. However, constitutive high levels of GDF3 in human sepsis patients are associated with lethality, suggesting that GDF3 may promote macrophage polarization toward M2 phenotype which could lead to immunosuppression.

Background: Children and adolescents in the USA consume large amounts of daily calories from ultraprocessed foods (UPFs). Recent evidence links UPF consumption to increased body fat in youth. We aimed to estimate the potential impact of reducing UPF consumption on childhood obesity rate in the USA. Methods: We developed a microsimulation model to project the effect of reducing UPF consumption in children’s diet on reducing the prevalence of overweight or obesity among US youth. The model incorporated nationally representative data on body mass index (BMI) percentile and dietary intake of 5804 children and adolescents aged 7–18 years from the National Health and Nutrition Examination Survey 2011–2016, and the effect of reducing UPF consumption on calorie intake from a recent randomised controlled trial. Uncertainties of model inputs were incorporated using probabilistic sensitivity analysis with 1000 simulations. Results: Reducing UPFs in children’s diet was estimated to result in a median of −2.09 kg/m ² (95% uncertainty interval −3.21 to –0.80) reduction in BMI among children and adolescents aged 7–18 years. The median prevalence of overweight (BMI percentile ≥85th) and obesity (BMI percentile ≥95th percentile) was reduced from 37.0% (35.9%, 38.1%) to 20.9% (15.1%, 29.9%) and from 20.1% (19.2%, 21.0%) to 11.0% (7.86%, 15.8%), respectively. Larger BMI and weight reductions were seen among boys than girls, adolescents than children, non-Hispanic black and Hispanic youth than non-Hispanic white youth, and those with lower levels of parental education and family income. Conclusions: Reducing UPF consumption in children’s diet has the potential to substantially reduce childhood obesity rate among children and adolescents in the USA.

Background: Macrophages play an important role in the pathogenesis of ulcerative colitis (UC). We will explore the effects of sodium butyrate (SB) on macrophage function. Methods: The targets of butyric acid were identified using SwissTargetPrediction database and surface plasmon resonance (SPR). Limited proteolysis mass spectrometry (Lip-MS) was used to further investigate the binding sites of butyric acid with its targets and molecular docking was employed to simulate their binding modes. Macrophage polarization model was established with lipopolysaccharide (LPS) in vitro. Takeda G protein-coupled receptor 5 (TGR5) and β-arrestin2 expression and macrophage polarization markers were detected with or without SB. Results: TGR5 was identified as the target of butyric acid. Moreover, the amino acid regions 275–286 and 321–330 of TGR5 (GPBAR1 [275–286] and GPBAR1 [321–330]) were the potential binding regions for butyric acid. Based on molecular docking analysis, butyric acid formed effective hydrogen-bonding interactions with ASP-284 and TYR-287 of TGR5. In cell experiments, LPS inhibited the expression of TGR5, β-arrestin2, IL-10, ARG1, and CD206 and increased the expression of IL-1β, iNOS, and CD86, while SB reversed the effect of LPS. SBI-115, a TGR5 antagonist, and knockdown of β-arrestin2 inhibited the effect of sodium butyrate. INT-777, a TGR5 agonist, reversed the inhibitory effect of knockdown of β-arrestin2. Conclusion: SB inhibited M1-like polarization and promoted M2-like polarization induced by LPS via TGR5/β-arrestin2 in RAW264.7 cells and TGR5 was the target of SB.

As the Chinese population ages, unhealthfully high body mass index (BMI) levels in older adults are becoming a public health concern as an unhealthfully high BMI is an ill-being condition and can contribute to the risk of disease. Education and lifestyle choices affect BMI; however, the evidence on the relationships and interactions among these factors remains unclear. This study aimed to investigate the mediating effect of lifestyle choices on educational attainment and BMI among older adults in China. Using the Chinese Family Panel Studies (CFPS) 2018 panel data, this study integrated personal- and family-level economic data libraries, including 7,359 adults aged ≥60 years. Lifestyle parameters included smoking amount and screen time. Height and weight values were used to calculate BMI. The chi-square test, binary logistic regression analysis, stepwise regression analysis, and bootstrapping mediating effect tests were used for data analysis. Single-factor chi-square test revealed differences in BMI levels among groups defined by sex, age, residence, marital status, per capita annual household income, education years, and lifestyle choices. Binary logistic regression showed that age, residence, education years, smoking amount, and screen time influenced BMI. Stepwise regression results showed that education years, smoking amount, and screen time were associated with BMI (t = 3.907, −4.902, 7.491, P < 0.001). The lifestyle variables had partial mediating effects on BMI. The mediating effect of lifestyle on BMI was 0.009, while smoking amount was 0.003, and screen time was 0.006. Unhealthfully high BMI levels are increasing among older adults in China and are affected by many factors. Lifestyle factors and educational attainment can interact, affecting BMI. Interventions should consider lifestyle factors and education attainment to help maintain healthy BMI and reduce unhealthfully high BMI incidence.

Myasthenia gravis (MG) is a disease involving neuromuscular transmission that causes fatigue of skeletal muscles and fluctuating weakness. It has been shown that impairment of myogenic differentiation and myofiber maturation may be the underlying cause of MG. In this study, we detected the abnormal expression of circular RNA (circRNA) using next‐generation sequencing in patients with MG. We then investigated the regulatory mechanism and the relationship among circRNA, microRNA, and messenger RNA using quantitative reverse‐transcription polymerase chain reaction, bioinformatics analysis, and luciferase report analysis. The expression of inflammatory cytokines and regulatory T lymphocytes was shown to be increased. Circ‐FBL was significantly increased in MG patients. Bioinformatics and luciferase report analyses confirmed that miR‐133 and PAX7 were the downstream targets of circ‐FBL. Overexpression of circ‐FBL promoted myoblast proliferation by regulation of miR‐133/PAX7. Taken together, our study showed that upregulation of circ‐FBL promoted myogenic proliferation in patients with MG by regulating miR‐133/PAX7.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease caused by a bunyaviridae virus. Its main clinical manifestation is fever with thrombocytopenia, which may be accompanied by other clinical symptoms. Here, we report a patient diagnosed with SFTS using metagenomic next‑generation sequencing (mNGS). Case Presentation: A 56-year-old female patient was hospitalized with intermittent diarrhea and fever. She visited a local clinic for treatment, but instead of improving, the symptoms progressed to unconsciousness. Diagnosis: Using mNGS, we isolated the bunyaviridae virus and several other pathogens from the patient’s blood samples to confirm the diagnosis. Interventions: The patient was treated with symptomatic and supportive therapy, including intravenous human γ-globulin (20 g/d), platelet transfusion, platelet elevation (subcutaneous injection of recombinant human thrombopoietin, 15,000 IU), white blood cell elevation (subcutaneous injection of recombinant human granulocyte colony-stimulating factor, 200 ug, qd); and antibiotic (cefoperazone sodium and tazobactam sodium, 2 g, q8h), antiviral (ganciclovir, 250 mg, q12h), and antifungal therapy (voriconazole for injection, 0.2 g, q12h). After ten days of treatment, the patient’s condition gradually improved. Conclusion: Compared to traditional detection methods, mNGS has many advantages. It can quickly identify the pathogen when the patient’s clinical manifestations are complex and difficult to diagnose, resulting in the formulation of an effective treatment.