Autophagy and its therapeutic potential in diabetic nephropathy.

Diabetic nephropathy (DN), the leading cause of end-stage renal disease, is the most significant microvascular complication of diabetes and poses a severe public health concern due to a lack of effective clinical treatments. Autophagy is a lysosomal process that degrades damaged proteins and organelles to preserve cellular homeostasis. Emerging studies have shown that disorder in autophagy results in the accumulation of damaged proteins and organelles in diabetic renal cells and promotes the development of DN. Autophagy is regulated by nutrient-sensing pathways including AMPK, mTOR, and Sirt1, and several intracellular stress signaling pathways such as oxidative stress and endoplasmic reticulum stress. An abnormal nutritional status and excess cellular stresses caused by diabetes-related metabolic disorders disturb the autophagic flux, leading to cellular dysfunction and DN. Here, we summarized the role of autophagy in DN focusing on signaling pathways to modulate autophagy and therapeutic interferences of autophagy in DN.

The protection of luteolin against diabetic cardiomyopathy in rats is related to reversing JNK-suppressed autophagy.

Increasing evidence has shown that impaired autophagy dramatically causes myocardial hypertrophy and fibrosis in the diabetic heart, ultimately leading to diabetic cardiomyopathy (DCM). Luteolin has been reported to effectively attenuate diabetic cardiovascular injury by inhibiting oxidative stress and alleviate sepsis-induced myocardial injury by enhancing autophagy. However, whether luteolin can reduce DCM through activating autophagy and the underlying mechanism remain unclear. Here, reversing the c-Jun N-terminal kinase (JNK)-suppressed autophagy pathway by which luteolin attenuates DCM was explored. Male Sprague-Dawley rats were injected with streptozotocin to induce diabetes. After 6 weeks of diabetes, rats were treated with luteolin (50, 100 and 200 mg kg-1, i.g.) for 4 weeks. Histological and functional alterations in the diabetic heart were determined using HE staining, Masson staining and echocardiography. The expressions of myocardial miR-221, JNK, and c-Jun and autophagic vesicles in diabetes were evaluated by quantitative PCR, Western blotting and electron microscopy. Luteolin significantly improved cardiac function and attenuated myocardial disorganization and fibrosis in the diabetic rat accompanying the dose-dependent down-regulation of JNK, c-Jun, miR-221 and p62, increase of LC3-II/I and autophagic vesicles, and decrease of mitochondrial swelling in the diabetic heart. These data suggest that the protection of luteolin against DCM, at least, is related to suppressing JNK/c-Jun-regulated miR-221 and the subsequent blockage of autophagy.

Profile of crosstalk between glucose and lipid metabolic disturbance and diabetic cardiomyopathy: Inflammation and oxidative stress.

In recent years, the risk, such as hypertension, obesity and diabetes mellitus, of cardiovascular diseases has been increasing explosively with the development of living conditions and the expansion of social psychological pressure. The disturbance of glucose and lipid metabolism contributes to both collapse of myocardial structure and cardiac dysfunction, which ultimately leads to diabetic cardiomyopathy. The pathogenesis of diabetic cardiomyopathy is multifactorial, including inflammatory cascade activation, oxidative/nitrative stress, and the following impaired Ca2+ handling induced by insulin resistance/hyperinsulinemia, hyperglycemia, hyperlipidemia in diabetes. Some key alterations of cellular signaling network, such as translocation of CD36 to sarcolemma, activation of NLRP3 inflammasome, up-regulation of AGE/RAGE system, and disequilibrium of micro-RNA, mediate diabetic oxidative stress/inflammation related myocardial remodeling and ventricular dysfunction in the context of glucose and lipid metabolic disturbance. Here, we summarized the detailed oxidative stress/inflammation network by which the abnormality of glucose and lipid metabolism facilitates diabetic cardiomyopathy.

Metal-Organic Framework with Structural Flexibility Responding Specifically to Acetylene and Its Adsorption Behavior.

Flexible metal-organic frameworks (MOFs) are one kind of stimuli-responsive materials that exhibit reversible structural transformations in response to external stimuli. Exploring and understanding the stimuli response behavior of flexible MOFs is challenging, as it involves weak host-guest interaction. We report here the unique flexibility of MOF Zn(int)(Ad) (TIF-A1, Hint = isonicotinic acid, Had = adenine) induced by acetylene adsorption. TIF-A1 is rigid toward most gas molecules, while only C2H2 can induce the flexibility of TIF-A1. C2H2-loaded TIF-A1 is characterized by single-crystal X-ray diffraction and molecular modeling. It is revealed that the flexibility of TIF-A1 originates from the strong interaction between acetylene and the framework, which pushes the rotation of the int ligand and the expansion of the framework simultaneously. This work is helpful in deeply understanding the flexibility of MOFs and guides exploring new flexible MOFs in the future.

A taxonomic study of the genus Macromotettixoides (Tetrigidae, Metrodorinae) with descriptions of two new species and two newly discovered males.

Fifteen species of Macromotettixoides are systematically researched in this paper. Two new species (M. tuberculata Mao, Li Han, sp. n. and M. truncata Mao, Li Han, sp. n.) and two newly discovered males (M. curvimarginus (Zheng Xu) and M. longling Deng) are introduced with descriptions and illustrations. An updated identification key to all known species of the genus is given.

Characterization of the complete mitochondrial genome of the Yunnan endemic grasshopper Longchuanacris curvifurculus (Insecta: Orthoptera: Catantopidae).

Longchuanacris curvifurculus (L. curvifurculus) was once a dominating grasshopper in the Yunnan province (People's Republic of China) that occupy important ecological niche. However, its population has severely declined because of the deterioration of ecological environment. Identifying the species and source of L. curvifurculus is important for biodiversity conservation and ecological/environmental preservation. In the study, the complete mitochondrial genome of L. curvifurculus was assembled from high-coverage (36.8×) Illumina MiSeq sequencing data. The circular genome is 15,450 bp in length, harboring 37 typical mitochondrial genes and one control region. The nucleotide composition is asymmetric (43.0% A, 14.3% C, 10.5% G, and 32.2% T), with an overall A + T content of 75.2%. All the protein-coding genes (PCGs) are initiated with typical ATN start codons and terminated by the typical TAA codons or the incomplete T(aa) codon. The control region has a remarkably high A + T content (84.9%) and is located between genes rrnS and trnV.