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Abstract Background The arcuate nucleus of the hypothalamus regulates food intake. Ankyrin repeat and SOCS box containing protein 4 (Asb-4) is expressed in neuropeptide Y and proopiomelanocortin (POMC) neurons in the arcuate nucleus, target neurons in the regulation of food intake and metabolism by insulin and leptin. However, the target protein(s) of Asb-4 in these neurons remains unknown. Insulin receptor substrate 4 (IRS4) is an adaptor molecule involved in the signal transduction by both insulin and leptin. In the present study we examined the colocalization and interaction of Asb-4 with IRS4 and the involvement of Asb-4 in insulin signaling. Results In situ hybridization showed that the expression pattern of Asb-4 was consistent with that of IRS4 in the rat brain. Double in situ hybridization showed that IRS4 colocalized with Asb-4, and both Asb-4 and IRS4 mRNA were expressed in proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons within the arcuate nucleus of the hypothalamus. In HEK293 cells co-transfected with Myc-tagged Asb-4 and Flag-tagged IRS4, Asb-4 co-immunoprecipitated with IRS4; In these cells endogenous IRS4 also co-immunoprecipitated with transfected Myc-Asb-4; Furthermore, Asb-4 co-immunoprecipitated with IRS4 in rat hypothalamic extracts. In HEK293 cells over expression of Asb-4 decreased IRS4 protein levels and deletion of the SOCS box abolished this effect. Asb-4 increased the ubiquitination of IRS4; Deletion of SOCS box abolished this effect. Expression of Asb-4 decreased both basal and insulin-stimulated phosphorylation of AKT at Thr308. Conclusions These data demonstrated that Asb-4 co-localizes and interacts with IRS4 in hypothalamic neurons. The interaction of Asb-4 with IRS4 in cell lines mediates the degradation of IRS4 and decreases insulin signaling.

Peritoneal adhesion occurs frequently after gastrointestinal/gynecological surgery. Tissue repair and regeneration are very important during this process. IL‐22 is an important cytokine that is secreted from immune cells but functions on mesenchymal cells, such as mesothelial cells. The objective of this study was to investigate the roles of IL‐22 and its regulators during adhesion formation. Postsurgical peritoneal drainage fluid from patients and rodent models was examined by enzyme‐linked immunosorbent assay and fluorescence‐activated cell sorting. It was observed that IL‐22 expression in the abdominal cavity was rapidly induced 12 hours after surgery and then slowly decreased to a lower, steady level for up to 7 days after surgery. However, neutralizing IL‐22 at the time point at which the highest level of expression was observed failed to reduce adhesion, but neutralizing IL‐22 at a later time point, i.e., 3 days after surgery, prevented adhesion significantly. The IL‐22 receptor was induced on the mesothelial membrane, and IL‐22BP, an inhibitor of IL‐22, was reduced 3 days after surgery. Furthermore, IFN‐γ was identified to have the ability to induce IL‐22R, and IL‐18, which was induced by the infiltrating macrophages, was found to inhibit IL‐22BP expression both in vivo and in vitro. Together, these data suggest that IL‐22 may promote adhesion formation and that the regulation of IL‐22, IL‐22R, and IL‐22BP may have therapeutic potential to prevent adhesion formation after surgery without disturbing the normal immune process. [ABSTRACT FROM AUTHOR]

Background: Obesity is a global disease with at least 2.8 million people dying each year as a result of being overweight or obese according to the world health organization figures. This paper aims to explore the links between obesity and mortality in COVID-19., Methods: Electronic search was made for the papers studying obesity as a risk factor for mortality following COVID-19 infection. Three authors independently selected the papers and agreed for final inclusion. The outcomes were the age, gender, body mass index, severe comorbidities, respiratory support and the critical illness related mortality in COVID-19. 572 publications were identified and 42 studies were selected including one unpublished study data. Only 14 studies were selected for quantitative analysis., Results: All the primary points but the gender are significantly associated with COVID-19 mortality. The age >70, [odd ratio (OR): 0.17, CI; 95%, P-value: <0.00001], gender [OR: 0.89; CI: 95%, P-value: 0.32], BMI > 25 kg/m 2 [OR: 3.68, CI: 95%, P-value: <0.003], severe comorbidities [OR: 1.84, CI:95%, P-value: <0.00001], advanced respiratory support [OR: 6.98, CI: 95%, P-value: <0.00001], and critical illness [OR: 2.03, CI: 95%, P-value: <0.00001]., Conclusions: Patients with obesity are at high risk of mortality from COVID-19 infection., (Copyright © 2020 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

The HKUST-1@SBA-15 composites with hierarchical pore structure were constructed by in situ self-assembly of metal-organic framework (MOF) with mesoporous silica. The structure directing role of SBA-15 had an obvious impact on the growth of MOF crystals, which in turn affected the morphologies and structural properties of the composites. The pristine HKUST-1 and the composites with different content of SBA-15 were characterized by XRD, N 2 adsorption-desorption, SEM, TEM, FT-IR, TG, XPS, and CO 2 -TPD techniques. It was found that the composites were assembled by oriented growth of MOF nanocrystals on the surfaces of SBA-15 matrix. The interactions between surface silanol groups and metal centers induced structural changes and resulted in the increases in surface areas as well as micropore volumes of hybrid materials. Besides, the additional constraints from SBA-15 also restrained the expansion of HKUST-1, contributing to their smaller crystal sizes in the composites. The adsorption isotherms of CO 2 on the materials were measured and applied to calculate the isosteric heats of adsorption. The HS-1 composite exhibited an increase of 15.9% in CO 2 uptake capacity compared with that of HKUST-1. Moreover, its higher isosteric heats of CO 2 adsorption indicated the stronger interactions between the surfaces and CO 2 molecules. The adsorption rate of the composite was also improved due to the introduction of mesopores. Ten cycles of CO 2 adsorption-desorption experiments implied that the HS-1 had excellent reversibility of CO 2 adsorption. This study was intended to provide the possibility of assembling new composites with tailored properties based on MOF and mesoporous silica to satisfy the requirements of various applications.

The aim of this study was to review the clinicopathological characteristics and survival outcomes of patients with concurrent gastrointestinal stromal tumor (GIST) and digestive tract carcinoma. Among 585 patients diagnosed with GIST from January 2005 to July 2014, 32 (5.5%) had synchronous digestive tract carcinoma, including 19 (59.4%) men and 13 (40.6%) women. The median age was 64 years (range, 43-84). GIST was located in the stomach (n=24), small intestine (n=6), duodenum (n=1) and retroperitoneum (n=1). GISTs were intra- or postoperatively discovered (n=28) or preoperatively identified (n=4). The tumor size was less than 10 mm (microGIST) in 23 (71.9%) GIST patients. The preoperatively identified GIST subgroup showed a significantly larger tumor size, more mitotic figures and a higher risk grade than the intra- or postoperatively identified GIST subgroup. Concurrent digestive tract carcinomas were most frequently located in the stomach (24 cases, 75%). The other involved sites were the esophagus (n=5), duodenum (n=2) and colon (n=1). With a median follow-up of 32 months (range, 9-80), 24 patients were alive without evidence of disease, 6 patients had died of carcinoma progression, 1 patient had died from an accident, and 1 patient experienced GIST metastasis to the liver. In summary, we discovered that 5.5% of GIST patients also developed a concurrent digestive tract carcinoma in a series of 585 GIST cases. The majority of GISTs are incidentally identified microGISTs. The concurrent carcinoma seems to have a greater unfavorable effect on prognosis than the GIST. However, for a GIST that is identified preoperatively with a high risk of progression, adjuvant therapy is warranted.

The nano-magnetic ferrofluid was prepared by chemical coprecipitation and its acute toxicology was investigated. The effective diameter (Eff. Diam. ) of the magnetic particles was about 19.9 nm, and the concentration of the ferrofluid was 17. 54 mg/ml. The acute toxic reaction and the main viscera pathological morphology of mice were evaluated after oral, intravenous and intraperitoneal administration of the nano-magnetic ferrofluid of different doses respectively. Half lethal dose (LD50) > 2104. 8 mg/kg,maximum non-effect dose (ED0) = 320. 10mg/kg with oral; LDs,> 438. 50 mg/kg, EDo = 160. 05 mg/kg with intravenous route; and LDso >1578. 6 mg/kg, ED0 = 320. 10 mg/kg with intraperitoneal administration. Degeneration and necrosis of viscera were not found. So the nano-magnetic ferrofluid, of which toxicity is very low, may be used as a drug carrier.