Causal effects of childhood obesity on neuroticism and subjective well-being: A two-sample Mendelian randomization study.

BACKGROUND: Childhood obesity is linked to both neuroticism and subjective wellbeing (SWB); however, the causal relations between them remain unclear. METHODS: Two-sample Mendelian randomization (MR) analysis was applied to determine the causal effects of childhood BMI (n = 39,620) on neuroticism (n = 366,301) and SWB (n = 298,420) using summary statistics from large scale genome-wide association studies (GWASs). Inverse-variance weighting (IVW), weighted mode, weighted median, and MR-Egger approaches were used to estimate the causal effects. Sensitivity analyses including the Cochran's Q statistics, MR-Egger intercept test, MR-PRESSO global test, and the leave-one-out (LOO) analysis were used to assess potential heterogeneity and horizontal pleiotropy. Two-step MR mediation analysis was employed to explore the potential mediation effects of neuroticism on the causal relationship between childhood BMI and SWB. RESULTS: Our study revealed that genetically predicted higher childhood BMI was causally associated with increased neuroticism (beta = 0.045, 95%CI = 0.013,0.077, p = 6.066e-03) and reduced SWB (beta = -0.059, 95%CI = -0.093,-0.024, p = 9.585e-04). Sensitivity analyses didn't detect any significant heterogeneity and horizontal pleiotropy (all p > 0.05). Additionally, the two-step MR mediation analysis indicated that the causal relationship between childhood BMI and SWB was partially mediated by neuroticism (proportion of mediation effects in total effects: 21.3 %, 95%CI: 5.4 % to 37.2, p = 0.0088). CONCLUSION: Genetically proxy for higher childhood BMI was associated with increased neuroticism and reduced SWB. Further studies were warranted to investigate the underlying molecular mechanisms and potential use of weight management for improving personality and SWB.

Cost-Effective and Scalable Solar Interface Evaporators Derived from Industry Waste for Efficient Solar Steam Generation.

Interfacial solar steam generation for sustainable and eco-friendly desalination and wastewater treatment has attracted much attention. However, costly raw materials and complex preparation processes pose constant challenges to its wide promotion. Herein, a novel, cost-effective, and scalable strategy is presented for preparing solar interface evaporators using industrial waste as a raw material. Modified polyethylene foam evaporators (M-EPEs) are simply prepared by drilling and then hydrophilic modification of industrial waste (EPE-1). M-EPEs not only retain the strong mechanical properties and thermal insulating properties (0.047 W·m-1·K-1) of EPE-1 but also exhibit superhydrophilicity and strong light absorption (over 90%). M-EPEs achieve a high evaporation rate of 1.497 kg·m-2·h-1 and photothermal efficiency of up to 93.8% under 1 kW·m-2 solar illumination. Moreover, it has excellent stability and salt tolerance. Our work addresses the environmental issues of recycling polyethylene waste and provides a facile and efficient strategy for designing low-cost, large-scale solar interface evaporators for desalination.

Prediction models for children/adolescents with obesity/overweight: A systematic review and meta-analysis.

The incidence of obesity and overweight in children and adolescents is increasing worldwide and becomes a global health concern. This study aims to evaluate the accuracy of available prediction models in early identification of obesity and overweight in general children or adolescents and identify predictive factors for the models, thus provide a reference for subsequent development of risk prediction tools for obesity and overweight in children or adolescents. Related publications were obtained from several databases such as PubMed, Embase, Cochrane Library, and Web of Science from their inception to September 18th, 2022. The novel Prediction Model Risk of Bias Assessment Tool (PROBAST) was employed to assess the bias risk of the included studies. R4.2.0 and Stata15.1 softwares were used to conduct meta-analysis. This study involved 45 cross-sectional and/or prospective studies with 126 models. Meta-analyses showed that the overall pooled index of concordance (c-index) of prediction models for children/adolescents with obesity and overweight in the training set was 0.769 (95% CI 0.754-0.785) and 0.835(95% CI 0.792-0.879), respectively. Additionally, a large number of predictors were found to be related to children's lifestyles, such as sleep duration, sleep quality, and eating speed. In conclusions, prediction models can be employed to predict obesity/overweight in children and adolescents. Most predictors are controllable factors and are associated with lifestyle. Therefore, the prediction model serves as an excellent tool to formulate effective strategies for combating obesity/overweight in pediatric patients.

Efficacy and safety of liraglutide for weight management in children and adolescents: a systematic review and meta-analysis of randomized controlled trials.

Obesity represents a risk factor for multiple coexisting conditions and complications. Liraglutide is mainly reserved for populations who fail to achieve weight loss goals with lifestyle changes alone. This study aims to systematically evaluate the safety and effectiveness of liraglutide in weight management in children and youth. A systematic search was performed of PubMed, Embase, Cochrane Library, and Web of Science from inception to February 23rd, 2023. Randomized controlled trials (RCTs) evaluating the effects of liraglutide in children and youth were included. All data analyses were performed using Review Manager 5.3 version. Seven eligible articles were finally included, covering a population of 547 participants. Liraglutide use was associated with reduced body weight (WMD: -2.13 kg; 95%CI: -4.23, -0.03), BMI (WMD: -1.56 kg/m2; 95% CI: -2.41, -0.7), and BMI SDS (WMD: -0.17; 95% CI: -0.26, -0.08). Similar associations were found in HbA1c (WMD: -0.29%; 95% CI: -0.52, -0.06) and fasting plasma glucose (SMD: -0.39; 95% CI: -0.64, -0.14). Subgroup analysis shows an improvement in HbA1c control only among children with type 2 diabetes (WMD: -1.06%; 95% CI: -1.44, -0.67). No differences were found in fasting serum insulin, SBP, DBP, HDL, LDL, and TG between liraglutide and placebo. In addition, no difference was found in the frequencies of adverse events, serious adverse events, and adverse events resulting in discontinuation of therapy between liraglutide and placebo treatment groups. CONCLUSION: Liraglutide is safe and effective in weight-reducing and glycemic control in children and adolescents. WHAT IS KNOWN: • A few first-line treatment of these children and adolescents with overweight and obesity is a multi-component lifestyle intervention. • Lifestyle modifications are not suitable for all individuals, therefore, new treatment strategies urgent need to be established. WHAT IS NEW: • This is the first meta-analysis conducted to assess the efficacy and safety of liraglutide for weight management in children and adolescents. • Liraglutide is safe and effective in weight-reducing and glycemic control in children and adolescents.

Efficacy of vitamin D supplementation on child and adolescent overweight/obesity: a systematic review and meta-analysis of randomized controlled trials.

The global prevalence of overweight and obesity in children and adolescents has been increasing. Child and adolescent overweight/obesity has been demonstrated to be partially associated with vitamin D deficiency. This systematic review and meta-analysis aims to assess the efficacy of vitamin D supplementation on child and adolescent overweight/obesity. PubMed, Embase, Cochrane Library, and Web of science were searched from inception to June 20th, 2022. Randomized controlled trials (RCTs) assessing the efficacy of vitamin D on child and adolescent overweight/obesity were included. The Cochrane bias risk assessment tool was used to assess the bias risk of included studies, and subgroup analysis was conducted based on different administration dosages. All data-analyses were performed using R 4.2.1. There were 1502 articles retrieved, and 10 eligible studies were finally included, with a total of 595 participants. Meta-analysis showed no differences in LDL, TC, TG, BMI, ALP, Ca, and PTH between vitamin-D (Vit-D) group and placebo, while Vit-D group resulted in improved HOMA-IR[WMD = - 0.348, 95%CI (- 0.477, - 0.219), p = 0.26]. Subgroup-analysis showed no significant difference in the increase of 25-(OH)-D between subgroups (p = 0.39), whereas the serum 25-(OH)-D level was increased under different Vit-D doses [WMD = 6.973, 95%CI (3.072, 10.873)]. High daily dose (≥ 4000 IU/d) of Vit-D might decrease CRP and increase HDL levels.   Conclusion: High dose of Vit-D supplementation (over 4000 IU/d) would reduce several cardiometabolic risk indicators and improve insulin resistance. More high-quality and large-scale RCTs are needed to provide more robust evidence. What is Known: • Vit-D deficiency is common in overweight/obesity (OW/OB) children and adolescents. • Previous randomized studies on the benefit of Vit-D supplementation to OW/OB children and adolescents are inconsistent. What is New: • This is the first meta-analysis conducted to assess the efficacy of Vit-D supplementation on child and adolescent OW/OB. • High dose of Vit-D supplementation is beneficial to cardiovascular metabolism, and improve insulin resistance on child and adolescent OW/OB.

Human umbilical cord mesenchymal stem cells combined with pirfenidone upregulates the expression of RGS2 in the pulmonary fibrosis in mice.

OBJECTIVE: The therapeutic effect of umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in combination with pirfenidone (PFD) on pulmonary fibrosis in mice and its possible mechanism were investigated. METHODS: C57BL/6 mice were randomly divided into six groups: control group, model group, P10 group, P30 group, P100 group, and P300 group. Modeled by tracheal intubation with 3 mg/kg bleomycin drip, each dose of PFD was administered daily by gavage from day 7 onwards. The mice were observed continuously for 21 days and survival was recorded. Lung tissues were collected on day 21, and hematoxylin-eosin (HE) and Masson staining were performed to assess morphological changes and collagen deposition in the lungs. Collagen content was measured by the Sircol method, and fibrosis marker levels were detected by PCR and Western blot. Another batch of C57BL/6 mice was then randomly divided into five groups: hUC-MSC control group, model group, P100 group, hUC-MSC treatment group, and hUC-MSCs + P30 group. On day 7, 5 × 105 hUC-MSCs were injected into the tail vein, the mice were administered PFD gavage daily from day 7 onwards, and their survival was recorded. Lung tissues were collected on day 21 to detect pathological changes, the collagen content, and the expression of regulator of G protein signaling 2 (RGS2). Pulmonary myofibroblasts (MFBs) were divided into an MFB group and an MFB + hUC-MSCs group; different doses of PFD were administered to each group, and the levels of RGS2, intracellular Ca2+, and fibrosis markers were recorded for each group. RESULTS: Compared with other PFD group doses, the P100 group had significantly improved mouse survival and lung pathology and significantly reduced collagen and fibrosis marker levels (p < 0.05). The hUC-MSCs + P30 group had significantly improved mouse survival and lung pathology, significantly reduced collagen content and fibrosis marker levels (p < 0.05), and the efficacy was better than that of the P100 and hUC-MSCs groups (p < 0.05). RGS2 expression was significantly higher in the MSCs + P30 group compared with the P100 and hUC-MSCs groups (p < 0.05). PFD increased RGS2 expression in MFBs (p < 0.05) in a dose-dependent manner. Compared with PFD and hUC-MSCs treatment alone, combination of hUC-MSCs and PFD increased RGS2 protein levels, significantly decreased intracellular Ca2+ concentration, and significantly reduced fibrosis markers. CONCLUSION: The findings suggest that hUC-MSCs combined with low-dose PFD have a therapeutic effect better than that of the two treatments used separately. Its effect on attenuating bleomycin-induced pulmonary fibrosis in mice is related to the increase of RGS2.

Castleman disease of the pancreas mimicking pancreatic malignancy on 68Ga-DOTATATE and 18F-fluorodeoxyglucose positron emission tomography/computed tomography: A case report.

BACKGROUND: Castleman disease is an uncommon nonclonal lymphoproliferative disorder, which frequently mimics both benign and malignant abnormalities in several regions. Depending on the number of lymph nodes or regions involved, Castleman disease (CD) varies in diagnosis, treatment and prognosis. It rarely occurs in the pancreas alone without any distinct clinical feature and tends to be confused with pancreatic paraganglioma (PGL), neuroendocrine tumors (NETs), and primary tumors, thus impeding proper diagnosis and treatment. CASE SUMMARY: A 28-year-old woman presented with a lesion on the neck of the pancreas, detected by ultrasound during a health examination. Physical examination and laboratory findings were normal. The mass showed hypervascularity on enhanced computed tomography (CT), significantly increased 18F-fluorodeoxyglucose uptake on positron emission tomography (PET)/CT, and slightly increased somatostatin receptor (SSTR) expression on 68Ga-DOTATATE PET/CT, suggesting no distant metastases and subdiagnoses such as pancreatic PGL, NET, or primary tumor. Intraoperative pathology suggested lymphatic hyperplasia, and only simple tumor resection was performed. The patient was diagnosed with the hyaline vascular variant of CD, which was confirmed by postoperative immunohistochemistry. The patient was discharged successfully, and no recurrence was observed on regular review. CONCLUSION: High glucose uptake and slightly elevated SSTR expression are potentially new diagnostic features of CD of the pancreas.

A label-free and modification-free ratiometric electrochemical strategy for enhanced natural enzyme detection using a bare electrode and nanozymes system.

Ratiometric electrochemical assays have been demonstrated to be more sensitive and selective in various sensing events, mainly due to their affordable built-in correction and good self-reference capability. But it is known that complicated modification and labeling operations usually are necessary for the construction of ratiometric electrochemical assays, therefore is a hot and important issue needing consideration carefully. We herein report a new yet simple bare electrode-based ratiometric electrochemical bioassay to achieve sensitive and selective analysis of alkaline phosphatase (ALP), using a liquid phase system that contains CoOOH nanozymes and commercially available indicator substrate. This proposed bioassay works based on the ratiometric change of dual electrochemical signals, arising from an exclusive target ALP-triggered hydrolysis of electrochemical substrate p-nitrophenyl phosphate (PNPP). In this design, the two hydrolyzed products of electrochemically active p-nitrophenol (PNP) and electrochemically inactive phosphate anion (PO43-) are responsible together for the ratiometric electrochemical analysis of ALP. PNP exhibits a straightforward current response toward ALP content; however, PO43- cannot show a direct electrochemical signal thus is rationally designed to offer an alternative response by linking it with the specific CoOOH nanozyme-catalyzed reaction of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2, in which the nanozyme-catalyzed product oxTMB shows a direct reduction current at the GCE, and significantly decreases with increasing PO43- species due to the good inhibition of PO43- toward CoOOH nanozyme activity. As a result, a ratiometric electrochemical strategy for ALP analysis with a low limit of detection of 0.366 U/L (S/N = 3) was successfully achieved by integrating the above direct and indirect dual electrochemical responses. This developed bioassay can allow the quantitative diagnosis of ALP activity especially with a label-free and modification-free merit, therefore paving the way for simple, convenient, and portable electroanalytical tools in biosensing design and application.

Design of dual targeting immunomicelles loaded with bufalin and study of their anti-tumor effect on liver cancer.

OBJECTIVE: Bufalin is an effective drug for the treatment of liver cancer. But its high toxicity, poor water-solubility, fast metabolism and short elimination half-life limit its use in tumor treatment. How to make the drug accumulate in the tumor and reduce side effects while maintaining its efficacy are urgent problems to be solved. The goal of this study is to solve these problems. METHODS: A copolymer with tunable poly-N-isopropylacrylamide and polylactic acid was designed and synthesized. The corresponding dual targeting immunomicelles (DTIs) loaded with bufalin (DTIs-BF) were synthesized by copolymer self-assembly in an aqueous solution. The size and structure of DTIs-BF were determined by ZetaSizer Nano-ZS and transmission electron microscopy. Then, its temperature sensitivity, serum stability, critical micelle concentration (CMC), entrapment efficiency (EE), drug release and non-cytotoxicity of blank block copolymer micelles (BCMs) were evaluated. Next, the effects of DTIs-BF on cellular uptake, cytotoxicity, and tumor cell inhibition were evaluated. Finally, the accumulation of DTIs-fluorescein isothiocyanate (FITC) and the in vivo anti-tumor effect were observed using an interactive video information system. RESULTS: DTIs-BF had a small size, spherical shape, good temperature sensitivity, high serum stability, low CMC, high EE, and slow drug release. The blank BCMs had very low cytotoxicity. Compared with free bufalin, the in vitro cellular internalization and cytotoxicity of DTIs-BF against SMMC-7721 cells were significantly enhanced, and the effects were obviously better at 40 °C than 37 °C. In addition, the therapeutic effect on SMMC-7721 cells was further enhanced by the programmed cell death specifically caused by bufalin. When DTIs-FITC were injected intravenously in BALB/c nude mice bearing liver cancer, the accumulation of FITC was significantly increased in tumors. CONCLUSION: DTIs-BF is a potentially effective nano-formulation and has broad prospects in the clinical treatment of liver cancer.

Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice.

Alveolar epithelial cells (AECs) injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis (PF). Nevertheless, the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear. SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is essential for kidney and heart fibrosis. We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II (ATII) cells. Moreover, we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/(tetO) 7 -Cre/SMARCA4 f/f mice (SOSM4 Δ/Δ ) model, as well as a new SMARCA4-deleted alveolar type II (ATII)-like mle-12 cell line. We found that the bleomycin-induced PF was more aggressive in SOSM4 Δ/Δ mice. Also, the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro. In addition, we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections. These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells, which might affect the progression of PF.