FGF signaling promotes spreading of fat body precursors necessary for adult adipogenesis in Drosophila.

Knowledge of adipogenetic mechanisms is essential to understand and treat conditions affecting organismal metabolism and adipose tissue health. In Drosophila, mature adipose tissue (fat body) exists in larvae and adults. In contrast to the well-known development of the larval fat body from the embryonic mesoderm, adult adipogenesis has remained mysterious. Furthermore, conclusive proof of its physiological significance is lacking. Here, we show that the adult fat body originates from a pool of undifferentiated mesodermal precursors that migrate from the thorax into the abdomen during metamorphosis. Through in vivo imaging, we found that these precursors spread from the ventral midline and cover the inner surface of the abdomen in a process strikingly reminiscent of embryonic mesoderm migration, requiring fibroblast growth factor (FGF) signaling as well. FGF signaling guides migration dorsally and regulates adhesion to the substrate. After spreading is complete, precursor differentiation involves fat accumulation and cell fusion that produces mature binucleate and tetranucleate adipocytes. Finally, we show that flies where adult adipogenesis is impaired by knock down of FGF receptor Heartless or transcription factor Serpent display ectopic fat accumulation in oenocytes and decreased resistance to starvation. Our results reveal that adult adipogenesis occurs de novo during metamorphosis and demonstrate its crucial physiological role.

Comprehensive analysis and identification of subtypes and hub genes of high immune response in lung adenocarcinoma.

BACKGROUND: The advent of immunotherapy targeting immune checkpoints has conferred significant clinical advantages to patients with lung adenocarcinoma (LUAD); However, only a limited subset of patients exhibit responsiveness to this treatment. Consequently, there is an imperative need to stratify LUAD patients based on their response to immunotherapy and enhance the therapeutic efficacy of these treatments. METHODS: The differentially co-expressed genes associated with CD8 + T cells were identified through weighted gene co-expression network analysis (WGCNA) and the Search Tool for the Retrieval of Interacting Genes (STRING) database. These gene signatures facilitated consensus clustering for TCGA-LUAD and GEO cohorts, categorizing them into distinct immune subtypes (C1, C2, C3, and C4). The Tumor Immune Dysfunction and Exclusion (TIDE) model and Immunophenoscore (IPS) analysis were employed to assess the immunotherapy response of these subtypes. Additionally, the impact of inhibitors targeting five hub genes on the interaction between CD8 + T cells and LUAD cells was evaluated using CCK8 and EDU assays. To ascertain the effects of these inhibitors on immune checkpoint genes and the cytotoxicity mediated by CD8 + T cells, flow cytometry, qPCR, and ELISA methods were utilized. RESULTS: Among the identified immune subtypes, subtypes C1 and C3 were characterized by an abundance of immune components and enhanced immunogenicity. Notably, both C1 and C3 exhibited higher T cell dysfunction scores and elevated expression of immune checkpoint genes. Multi-cohort analysis of Lung Adenocarcinoma (LUAD) suggested that these subtypes might elicit superior responses to immunotherapy and chemotherapy. In vitro experiments involved co-culturing LUAD cells with CD8 + T cells and implementing the inhibition of five pivotal genes to assess their function. The inhibition of these genes mitigated the immunosuppression on CD8 + T cells, reduced the levels of PD1 and PD-L1, and promoted the secretion of IFN-γ and IL-2. CONCLUSIONS: Collectively, this study delineated LUAD into four distinct subtypes and identified five hub genes correlated with CD8 + T cell activity. It lays the groundwork for refining personalized therapy and immunotherapy strategies for patients with LUAD.

Study on Photochemical Properties of a Sr-SnS2/CaIn2S4 Heterostructure to Improve Cr(VI) Removal.

Compound semiconductor photocatalysis technology is considered to be a promising treatment for solving water problems efficiently. The point of designing high-efficiency catalysts is to optimize the band gap structure and facilitate the separation of charge carriers by establishing new electron migration pathways. Recently, 3D porous CaIn2S4 was found to have good photocatalytic ability. However, the quick recombination and agglomeration of carriers still limit its application. Herein, we prepared a heterostructure by introducing 2D Sr-doped SnS2 to 3D CaIn2S4 by a hydrothermal synthesis method. The optimal dosage of Sr-SnS2 is 3%, and the photocatalytic Cr(VI) removal efficiency of 3% Sr-SnS2/CaIn2S4 (SSCS-3) is 5.82 and 10.83 times those of pure CaIn2S4 and SnS2, respectively. According to the results of characterization tests and calculation verification, we inferred that the enhanced photocatalytic removal of Cr(VI) is due to the introduction of Sr-SnS2 that can promote the rapid transfer of photogenerated electrons to the surface of CaIn2S4, and the heterostructure formed between 2D Sr-SnS2 and 3D CaIn2S4 can also provide abundant reaction sites. The promotion of carrier separation is mainly due to the formation of a built-in electric field of the Sr-SnS2/CaIn2S4 heterostructure. This work provides new ideas and technologies for the treatment of Cr(VI) in wastewater.

Comparing the efficacy and safety of different analgesic strategies after open hemorrhoidectomy: a systematic review and network meta-analysis.

PURPOSE: To evaluate the clinical efficacy and safety of different analgesic interventions in the treatment of pain after open hemorrhoidectomy by systematic review and network meta-analysis. METHODS: Randomized controlled trials that met the inclusion criteria in PubMed, Cochrane Library, Embase, Web of Science, Scopus, CNKI, WANFANG DATA, and VIP were searched from the date of database construction to June 28, 2022. RESULTS: Among the 13 randomized controlled trials (RCTs), 731 patients were included in the network meta-analysis. Most interventions are more effective than placebo in relieving postoperative pain. 24 h postoperative Visual Analogue Scale (VAS): glyceryl trinitrate (GTN) (mean difference (MD) - 4.20, 95% CI - 5.35, - 3.05), diltiazem (MD - 1.97, 95% CI - 2.44, - 1.51), botulinum toxin (BT) (MD - 1.50, 95% CI - 2.25, - 0.75), sucralfate (MD - 1.01, 95% CI - 1.53, - 0.49), and electroacupuncture (EA) (MD - 0.45, 95% CI - 0.87, - 0.04). 48 h postoperative VAS: diltiazem (MD - 2.45, 95% CI - 2.74, - 2.15), BT (MD - 2.18, 95% CI - 2.52, - 1.84), and sucralfate (MD - 1.41, 95% CI - 1.85, - 0.97). 7 d postoperative VAS: diltiazem (MD - 2.49, 95% CI - 3.20, - 1.78) and sucralfate (MD - 1.42, 95% CI - 2.00, - 0.85). The first postoperative defecation VAS: EA (MD - 0.70, 95% CI - 0.95, - 0.46). There are few data on intervention safety, and additional high-quality RCTs are expected to study this topic in the future. CONCLUSION: Diltiazem ointment may be the most effective medication for pain relief following open hemorrhoidectomy, and it can dramatically reduce pain within one week of surgery. The second and third recommended medications are BT and sucralfate ointment. GTN has a significant advantage in alleviating pain 24 h after open hemorrhoidectomy, but whether it causes headache is debatable; thus, it should be used with caution. EA's analgesic efficacy is still unknown. There was limited evidence on the safety of the intervention in this study, and it was simply presented statistically.

Dihydroartemisinin improves hypercholesterolemia in ovariectomized mice via enhancing vectorial transport of cholesterol and bile acids from blood to bile.

The increase of concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the serum of postmenopausal women is the important risk factor of the high morbidity of cardiovascular diseases of old women worldwide. To test the anti-hypercholesterolemia function of dihydroartemisinin (DHA) in postmenopausal women, ovariectomized (OVX) mice were generated, and DHA were administrated to OVX mice for 4 weeks. The blood and liver tissues were collected for biochemical and histological tests respectively. The mRNA and protein expression levels of genes related to metabolism and transport of cholesterol, bile acid and fatty acid in the liver or ileum were checked through qPCR and western blot. DHA could significantly reduce the high concentrations of TC and LDL-C in the serum and the lipid accumulation in the liver of ovariectomized mice. The expression of ABCG5/8 was reduced in liver of OVX mice, and DHA could up-regulate the expression of them. Genes of transport proteins for bile salt transport from blood to bile, including Slc10a1, Slco1b2 and Abcb11, were also significantly up-regulated by DHA. DHA also down-regulated the expression of Slc10a2 in the ileum of OVX mice to reduce the absorption of bile salts. Genes required for fatty acid synthesis and uptake, such as Fasn and CD36, were reduced in the liver of OVX mice, and DHA administration could significantly up-regulate the expression of them. These results demonstrated that DHA could improve hypercholesterolemia in OVX mice through enhancing the vectorial transport of cholesterol and bile acid from blood to bile.

Clinical Study on Anesthesia with Remifentanil and Propofol in Patients with High Hemodynamics.

Objective: To study the effect of remifentanil and propofol as an anesthesia regimen in patients with high hemodynamics. Methods: From January 2019 to October 2020, 200 patients with high hemodynamics undergoing surgery at the First Affiliated Hospital of Nanchang University in China were selected as study participants, including 100 patients anesthetized with remifentanil and propofol (research group), and 100 patients anesthetized with fentanyl and propofol (control group). Vital signs, hemodynamic changes and recovery time after anesthesia were compared in the 2 groups and any adverse events while under anesthesia were recorded. Results: Both groups had significant fluctuations in vital signs and hemodynamics during anesthesia (P > .05), but the research group showed smaller changes with more stable vital signs and hemodynamics (P < .05). In addition, postoperative recovery time from anesthesia was shorter and the incidence of adverse events was lower in the research group than in the control group (P < .05). Conclusion: Remifentanil-propofol anesthesia is simple, convenient, safe and reliable in patients with high hemodynamics, and can integrate narcotic drugs with blood pressure control.

One-Step Synthesis of Aminobenzoic Acid Functionalized Graphene Oxide by Electrochemical Exfoliation of Graphite for Oxygen Reduction to Hydrogen Peroxide and Supercapacitors.

Graphene-based materials have attracted considerable attention as promising electrocatalysts for the oxygen reduction reaction (ORR) and as electrode materials for supercapacitors. In this work, electrochemical exfoliation of graphite in the presence of 4-aminebenzoic acid (4-ABA) is used as a one-step method to prepare graphene oxide materials (EGO) functionalized with aminobenzoic acid (EGO-ABA). The EGO and EGO-ABAs materials were characterized by FT-IR spectroscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, X-ray diffraction and scanning electron microscopy. It was found that the EGO-ABA materials have smaller flake size and higher density of oxygenated functional groups compared to bare EGO. The electrochemical studies showed that the EGO-ABA catalysts have higher activity for the ORR to H2O2 in alkaline medium compared to EGO due to their higher density of oxygenated functional groups. However, bare EGO has a higher selectivity for the 2-electron process (81%) compared to the EGO-ABA (between 64 and 72%) which was related to a lower content of carbonyl groups. The specific capacitance of the EGO-ABA materials was higher than that of EGO, with an increase by a factor of 3 for the materials prepared from exfoliation in 5 mM 4-ABA/0.1 M H2SO4. This electrode material also showed a remarkable cycling capability with a loss of only 19.4% after 5000 cycles at 50 mVs-1.

Encapsulation of Zanthoxylum bungeanum essential oil to enhance flavor stability and inhibit lipid oxidation of Chinese-style sausage.

BACKGROUND: Zanthoxylum bungeanum essential oil (ZBEO) is a popular seasoning, commonly used in the food industry. It contains many easily degraded and highly volatile bioactive substances. Control of the stability of the bioactive substances in ZBEO is therefore very important in the food industry. RESULTS: In this study, microencapsulation was applied to improve ZBEO stability. The key parameters for microcapsule preparation were optimized by the Box-Behnken design method, and the optimum conditions were as follows: ratio of core to wall, 1:8; ratio of hydroxypropyl-α-cyclodextrin (HPCD) to soy protein isolate (SPI), 4; total solids content, 12%; and homogenization speed, 12 000 rpm. Antioxidant experiments have indicated that tea polyphenols (TPPs) effectively inhibited hydroxy-α-sanshool degradation in ZBEO microcapsules. Application of ZBEO microcapsules in Chinese-style sausage effectively inhibited lipid oxidation in sausages and protected hydroxy-α-sanshool and typical volatiles from volatilization and degradation during sausage storage. CONCLUSION: The results suggested that ZBEO microencapsulation is an effective strategy for improving the stability of its bioactive components and flavor ingredients during food processing. © 2022 Society of Chemical Industry.

IκB kinase promotes Nrf2 ubiquitination and degradation by phosphorylating cylindromatosis, aggravating oxidative stress injury in obesity-related nephropathy.

BACKGROUND: Obesity-related nephropathy (ORN) has become one of the leading causes of end-stage renal disease and has tripled over the past decade. Previous studies have demonstrated that decreased reactive oxygen species production may contribute to improving ORN by ameliorating oxidative stress injury. Here, IκB kinase (IKK) was hypothesized to inactivate the deubiquitination activity of cylindromatosis (CYLD) by activating the phosphorylation of CYLD, thus promoting the ubiquitination of NF-E2-related factor 2 (Nrf2) and further aggravating oxidative stress injury of the kidney in ORN. This study was aimed to confirm this hypothesis. METHODS: Haematoxylin and eosin (HE), periodic acid-Schiff (PAS) and Oil Red O staining were performed to assess histopathology. Dihydroethidium (DHE) staining and MDA, SOD, CAT, and GSH-PX assessments were performed to measure reactive oxygen species (ROS) production. Immunohistochemical (IHC) staining, qRT-PCR and/or western blotting were performed to assess the expression of related genes. JC-1 assays were used to measure the mitochondrial membrane potential (ΔΨm) of treated HK-2 cells. Co-immunoprecipitation experiments (Co-IP) were used to analyse the interaction between CYLD and Nrf2 in ORN. RESULTS: ORN in vivo and in vitro models were successfully constructed, and oxidative stress injury was detected in the model tissues and cells. Compared with the control groups, the phosphorylation level of CYLD increased while Nrf2 levels decreased in ORN model cells. An IKK inhibitor reduced lipid deposition, ROS production, CYLD phosphorylation levels and ΔΨm in vitro, which were reversed by knockdown of CYLD. Nrf2 directly bound to CYLD and was ubiquitinated in ORN cells. The proteasome inhibitor MG132 activated the Nrf2/ARE signalling pathway, thereby reversing the promoting effect of CYLD knockdown on oxidative stress. CONCLUSION: IKK inactivates the deubiquitination activity of CYLD by activating the phosphorylation of CYLD, thus promoting the ubiquitination of Nrf2 and further aggravating oxidative stress injury of the kidney in ORN. This observation provided a feasible basis for the treatment of kidney damage caused by ORN.

Risk factors for mortality in critically ill patients with COVID-19 in Huanggang, China: A single-center multivariate pattern analysis.

To date, the coronavirus disease 2019 (COVID-19) has a worldwide distribution. Risk factors for mortality in critically ill patients, especially detailed self-evaluation indicators and laboratory-examination indicators, have not been well described. In this paper, a total of 192 critically ill patients (142 were discharged and 50 died in the hospital) with COVID-19 were included. Self-evaluation indicators including demographics, baseline characteristics, and symptoms and detailed lab-examination indicators were extracted. Data were first compared between survivors and nonsurvivors. Multivariate pattern analysis (MVPA) was performed to identify possible risk factors for mortality of COVID-19 patients. MVPA achieved a relatively high classification accuracy of 93% when using both self-evaluation indicators and laboratory-examination indicators. Several self-evaluation factors related to COVID-19 were highly associated with mortality, including age, duration (time from illness onset to admission), and the Barthel index (BI) score. When the duration, age increased by 1 day, 1 year, BI decreased by 1 point, the mortality increased by 3.6%, 2.4%, and 0.9% respectively. Laboratory-examination indicators including C-reactive protein, white blood cell count, platelet count, fibrin degradation products, oxygenation index, lymphocyte count, and d-dimer were also risk factors. Among them, duration was the strongest predictor of all-cause mortality. Several self-evaluation indicators that can simply be obtained by questionnaires and without clinical examination were the risk factors of all-cause mortality in critically ill COVID-19 patients. The prediction model can be used by individuals to improve health awareness, and by clinicians to identify high-risk individuals.