Brown adipocyte mineralocorticoid receptor deficiency impairs metabolic regulation in diet-induced obese mice.

Activation of brown adipose tissue (BAT) contributes to energy dissipation and metabolic health. Although mineralocorticoid receptor (MR) antagonists have been demonstrated to improve metabolism under obesity, the underlying mechanisms remain incompletely understood. We aimed to evaluate the role of BAT MR in metabolic regulation. After 8 weeks of high-fat diet (HFD) feeding, BAT MR KO (BMRKO) mice manifested significantly increased bodyweight, fat mass, serum fasting glucose, and impaired glucose homeostasis compared with littermate control (LC) mice, although insulin resistance and fasting serum insulin were not significantly changed. Metabolic cage experiments showed no change in O2 consumption, CO2 production, or energy expenditure in obese BMRKO mice. RNA sequencing analysis revealed downregulation of genes related to fatty acid metabolism in BAT of BMRKO-HFD mice compared with LC-HFD mice. Moreover, H&E and immunohistochemical staining demonstrated that BMRKO exacerbated HFD-induced macrophage infiltration and proinflammatory genes in epididymal white adipose tissue (eWAT). BMRKO-HFD mice also manifested significantly increased liver weights and hepatic lipid accumulation, an increasing trend of genes related to lipogenesis and lipid uptake, and significantly decreased genes related to lipolytic and fatty acid oxidation in the liver. Finally, the level of insulin-induced AKT phosphorylation was substantially blunted in eWAT but not liver or skeletal muscle of BMRKO-HFD mice compared with LC-HFD mice. These data suggest that BAT MR is required to maintain metabolic homeostasis, likely through its regulation of fatty acid metabolism in BAT and impacts on eWAT and liver.

Synthesis of α-Aryl Primary Amides from α-Silyl Nitriles and Aryl Sulfoxides through [3,3]-Sigmatropic Rearrangement.

A simple and efficient protocol was developed for the preparation of challenging α-aryl primary amides. This metal-free coupling process was triggered by TfOH-promoted electrophilic activation of α-silyl nitrile to generate keteniminium ion species, followed by reaction with aryl sulfoxide through [3,3]-sigmatrophic rearrangement to provide the target product. To the best of our knowledge, α-silyl nitrile has been rarely used as a pro-electrophilic reagent. Computational investigations confirmed the transient existence of a highly electrophilic keteniminium intermediate.

Damage to the Blood-Aqueous Barrier in Ocular Blunt Trauma and Its Association with Intraocular Pressure Elevation.

BACKGROUND: The aim of this study is to provide a quantitative evaluation of the blood-aqueous barrier (BAB) in patients with ocular blunt trauma and evaluate its association with intraocular pressure (IOP) elevation. METHODS: This is a prospective case-control study, and the following 3 groups were included: elevated IOP (45 patients with an elevated IOP secondary to ocular blunt trauma), normal IOP (27 patients with a normal IOP after ocular blunt trauma), and healthy controls. The main outcome measures were IOP and BAB function evaluated using a laser flare-cell meter (LFCM). RESULTS: Patients had significantly higher flare intensities and cell counts than the normal controls (both p < 0.001), and the elevated-IOP group displayed even higher LFCM readings than the normal-IOP group. Aqueous flare and cell readings were positively correlated with IOP (r = 0.529 and 0.590, respectively, p < 0.001). LFCM readings in the elevated-IOP group were still significantly high even on postraumatic day 120 following anti-inflammatory treatment. CONCLUSION: BAB dysfunction occurred following ocular blunt trauma. Eyes with an elevated IOP displayed a more seriously disturbed BAB and a longer recovery course. Examination with a LFCM provides insight into the pathophysiology of IOP elevation and assists in making decisions concerning anti-inflammatory treatment during follow-up.

[Epidemiological characteristics and risk factors of hospital patients with clonorchiasis].

OBJECTIVE: To investigate the epidemiological characteristics and risk factors of clonorchiasis of hospital patients in Heilongjiang Province, so as to provide the evidence for formulating the control and prevention strategies. METHODS: A total of 2,359 suspected patients from human parasitic disease research institute of Harbin medical university were investigated. Totally 6,718 stool samples and 2 359 serum samples were tested by Kato-Katz technique and the enzyme linked immune method re- spectively. Meanwhile, the information of the patients was collected by questionnaires. RESULTS: Totally 513 suspected patients were infected with Clonorchis sinensis. The infection rate of the suspected patients was higher in the ≥29 group (P < 0.05), and the infection rate and positive rate of blood tests of the rural suspected patients were both higher than those of the urban suspected patients (both P < 0.05). The habit of eating raw fish and shrimp was the risk factor of clonorchiasis. CONCLUSION: Clonorchiasis is one of the main food-borne parasitic diseases in Heilongjiang Province. The habit of eating raw fish and shrimp is the risk factor of clonorchiasis.

Effects of tacrolimus on infection of Friend murine leukemia virus to Fv-4 gene heterozygous mice.

AIM: To investigate the effect of tacrolimus (FK506) on the infection of Friend murine leukemia virus (Friend MuLV) in vivo. METHODS: Three kinds of mice were used including Friend MuLV-sensitive BALB/c mice, Friend MuLV-resistant Fv-4 gene-homozygous mice (Fv-4 mice), and Friend MuLV-resistant Fv-4 gene-heterozygous mice (F1 mice). Tacrolimus was administrated i.p. to those mice in every 2 d. Those treated mice were inoculated i.p. with Friend MuLV once on d 3. The symptoms and viral proliferations in those mice were observed to recognize the Friend MuLV infection. The expression and genotype of Fv-4 gene that resistant against the infection of Friend MuLV were analyzed to confirm the genomic background and related mechanism of the resistance. RESULTS: BALB/c mice and F1 mice, but not Fv-4 mice, appeared obvious early death, spleenomegaly, and viral proliferation after both treatments of viral inoculation and tacrolimus administration, whereas the expression and genotype of Fv-4 gene was not changed in F1 mice and Fv-4 mice with treatment of tacrolimus. Compared to the virus-inoculated control, the Friend MuLV-sensitivity of tacrolimus-treated BALB/c mice and the Friend MuLV-resistance of tacrolimus-treated Fv-4 mice were the same as the controls, but only F1 mice became the symptoms and viral proliferation after both treatments. It suggested the Friend MuLV-resistant F1 mice could be converted to be Friend MuLV-sensitive by treatment of tacrolimus, and this conversion was not depended on the expression and genotype of Fv-4 gene. CONCLUSION: Tacrolimus could not inhibit the infection of Friend MuLV in all mice, furthermore, it could enhance the infection of Friend MuLV in F1 mice. The enhancement may be related to the immunosuppressive effect of tacrolimus.

Ultrastructure of cultured cells from Schistosoma japonicum.

Ultrastructures and their dynamic changes of the cultured cells from Schistosoma japonicum were observed in the present experiments. Several types-including polygonal, round granular, deltaic fan-shaped and flagellated cells-were found in the cultures. The polygonal cells took a major ratio in the cultures from adult S. japonicum, while the majority from schistosomula was round granular cells. The ultrastuctures on the cell surface were different between the cells from adults and schistosomula. Some papilla-like tubercula, microvilli and pinocytotic vesicles were observed on the surface of adult cells, but none were found on schistosomula cells. However, more or less mitochondria, endoplasmic reticula, ribosomes and glycogen were observed in the cytoplasm of the cultured cells from both adults and schistosomula. Golgi complexes were rarely found. The nucleus was round, with round nucleolus inside and clear pores on the unit membrane. There was much lumpish heterochromatin located near to the nuclear membrane. Cells from different worm tissues had their own organelles. The germ cells, vitelline cells, flame cells, multinucleate subtegumental cells and nerve cells could be observed in the cultures from adults. The vitelline cells were the greatest in number and nerve cells were the least in number among them. Similarly, there were germ cells, sustentacular cells, flame cells, nerve cells, mast cells, muscle cells, multinucleate subtegumental cells, interstitial cells and penetration gland cells in the cultures from the schistomomula. In addition, a few division cells were also found. It indicated that the schistosomula cells had greater potential ability to proliferate than the adult cells in in vitro culture. Along with the prolongation of the culture time, degeneration of schistosomal cell occurred more and more. Generally, the electron density of cultures gradually got lower, the cristae of mitochondria blurred and disappeared and the mitochondria themselves swelled and finally vacuoled completely. Vitelline cells were most sensitive to the changes of the in vitro condition in all cultures. Their degeneration showed the following characteristics: (1) vitelline globules fused each other, the space between vitelline globules and the membrane surrounding them broadened gradually and vitelline globules were released and uncovered; (2) rough-surfaced endoplasmic reticula enlarged, vacuolated and the ribosomes dropped; and (3) the number and volume of lipid increased. The ultrastructural changes of most of the cultures from schistosomula had the following trends: (1) heterochromatin increased and euchromatin decreased gradually; and (2) endoplasmic reticula changed into short tubes and vacuoles and disappeared finally. The degenerative process of the cultures from S. japonicum consisted of necrosis according to the ultrastructural changes of the mitochondria, vitelline globules, chromatin and endoplasmic reticula within the cells. The changes of the above structures could be used to estimate whether the culture conditions were appropriate.