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Diabetic cognitive impairment (DCI) is a common diabetic complication with hallmarks of loss of learning ability and disorders of memory and behavior. Glucocorticoid receptor (GR) dysfunction is a main reason for neuronal impairment in brain of diabetic patients. Here, we determined that ipriflavone (IP) a clinical anti-osteoporosis drug functioned as a non-steroidal GR antagonist and efficiently ameliorated learning and memory dysfunction in both type 1 and 2 diabetic mice. The underlying mechanism has been intensively investigated by assay against the diabetic mice with GR-specific knockdown in the brain by injection of adeno-associated virus (AAV)-ePHP-si-GR. IP suppressed tau hyperphosphorylation through GR/PI3K/AKT/GSK3β pathway, alleviated neuronal inflammation through GR/NF-κB/NLRP3/ASC/Caspase-1 pathway, and protected against synaptic impairment through GR/CREB/BDNF pathway. To our knowledge, our work might be the first to expound the detailed mechanism underlying the amelioration of non-steroidal GR antagonist on DCI-like pathology in mice and report the potential of IP in treatment of DCI.

Background Liver enzyme abnormality is common in patients with coronavirus disease 2019 (COVID-19). Whether or not SARS-CoV-2 infection can lead to liver damage per se remains unknown. Here we reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with liver enzyme abnormality. Methods We received 156 patients diagnosed of COVID-19 from two designated centers in China, and compared clinical features between patients with elevated aminotransferase or not. Postmortem liver biopsies were obtained from two cases who had elevated aminotransferase. We investigated the patterns of liver impairment by electron microscopy, immunohistochemistry, TUNEL assay, and pathological studies. Results 64 of 156 (41.0%) COVID-19 patients had elevated aminotransferase. The median levels of ALT were 50 U/L vs. 19 U/L, respectively, AST were 45.5 U/L vs. 24 U/L, respectively in abnormal and normal aminotransferase groups. The liver enzyme abnormality was associated with disease severity, as well as a series of laboratory tests including higher A-aDO2, higher GGT, lower albumin, decreased CD4+ T cells and B lymphocytes. Ultrastructural examination identified typical coronavirus particles characterized by spike structure in cytoplasm of hepatocytes in two COVID-19 cases. SARS-CoV-2 infected hepatocytes displayed conspicuous mitochondrial swelling, endoplasmic reticulum dilatation, and glycogen granule decrease. Histologically, massive hepatic apoptosis and a certain binuclear hepatocytes were observed. Taken together, both ultrastructural and histological evidence indicated a typical lesion of viral infection. Immunohistochemical results showed scanty CD4+ and CD8+ lymphocytes. No obvious eosinophil infiltration, cholestasis, fibrin deposition, granuloma, massive central necrosis, or interface hepatitis were observed. Conclusions SARS-CoV-2 infection in liver is a crucial cause of hepatic impairment in COVID-19 patients. Hence, a surveillance of viral clearance in liver and long outcome of COVID-19 is required., Graphical abstract, Highlights ● Liver enzyme abnormality in COVID-19 patients is associated with disease severity. ● COVID-19 patients with liver enzyme abnormality have higher A-aDO2, higher GGT, lower albumin and decreased circulating CD4+ T cells and B lymphocytes. ● SARS-CoV-2 is able to infect liver and cause conspicuous hepatic cytopathy. ● Massive apoptosis and binuclear hepatocytes were the predominant histological features of SARS-CoV-2 infected liver., Lay summary Liver enzyme abnormality is common in patients with coronavirus disease 2019 (COVID-19). We reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with elevated liver enzymes. Our findings suggested SARS-CoV-2 infection in liver is a crucial cause of hepatic impairment in COVID-19 patients

A novel and efficient method for the synthesis of N S substituted sulfoximines has been established with h-BN-supported copper(II) nanomaterial as the catalyst. Catalyzed by this heterogeneous catalyst, the desired products were obtained with wide scope of substrates, good to excellent yields, free ligand and low-toxicity solvent. Moreover, after being reused ten times, there is almost no significant loss of its catalytic activity.

A copper-γ-cyclodextrin complex immobilized on hexagonal boron nitride (h-BN@γ-CD@Cu(OAc)2) has been prepared for the first time. This recoverable and reusable heterogeneous catalyst can be used in the click synthesis of 1,2,3-triazoles via a one-pot three-component reaction of boracic acid, terminal alkynes, and sodium azide at room temperature in water. FT-IR, XRD, SEM, XPS, TG, and ICP-AES techniques were used to characterize the catalyst. In general, this reaction, with the aid of this new catalyst, afforded the corresponding products with good yields and excellent tolerance of the functional groups.

A novel and temperature-controlled oxidation of α-hydroxy amides in the presence of IBX is described. The divergent one-pot synthesis of isatins and α-formyl amides was achieved in good to excellent yields under metal-free conditions. And these two mild methods can tolerate a variety of functional groups, and are operationally simple.

Objective. Previously, we have shown that Danshen-Honghua (DSHH) for cognitive deficits after ischemia induced impairments of the hippocampus. Here, we investigate the effects of DSHH on stress-induced depression in menopausal rats. Methods. A rat model with menopausal depression was established with bilateral ovariectomies in female SD rats followed by chronic mild stress treatment for 21 days. 40 rats were randomly divided into the sham surgery group (sham surgery and no stress treatment), surgery group (surgery with no stress treatment), surgery/stress group (surgery and stress treatment), fluoxetine group (2.4 mg·kg−1, with surgery and stress treatment), and DSHH group (35 g·kg−1, with surgery and stress treatment). The rats in the last two groups were treated with stresses together with intragastric drug administration for three weeks after the surgery. Then open-field locomotor scores and sucrose intake were tested for behavior changes. Also, the levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and cortisone were determined by high-performance liquid chromatography (HPLC). Serum estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined by radioimmunoassay. Results. The results of open-field locomotor scores, sucrose intake in both the fluoxetine group and DSHH group, were significantly higher than those of the surgery/stress group (P<0.01). Serum LH, FSH, and cortisone levels in both the DSHH group and fluoxetine group were significantly lower than those in the surgery/stress group (P<0.01). Serum E2 levels in these groups were slightly increased in these medicine groups (P<0.01). The monoamine levels in the DSHH group were much higher than those in the surgery/stress group (P<0.01). Conclusion. DSHH can ameliorate stress-induced depressed syndromes in the surgery/stressed rats via regulating LH and FSH levels as well as monoamine levels.