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Diabetic kidney disease (DKD) is one of the major causes of end-stage renal disease and one of the significant complications of diabetes. This study aims to identify the main differentially expressed genes in DKD from transcriptome sequencing results and analyze their diagnostic value. The present study sequenced db/m mouse and db/db mouse to determine the ALOX12 genetic changes related to DKD. After preliminary validation, ALOX12 levels were significantly elevated in the blood of DKD patients, but not during disease progression. Moreover, urine ALOX12 was increased only in macroalbuminuria patients. Therefore, to visualize the diagnostic efficacy of ALOX12 on the onset and progression of renal injury in DKD, we collected kidney tissue from patients for immunohistochemical staining. ALOX12 was increased in the kidneys of patients with DKD and was more elevated in macroalbuminuria patients. Clinical chemical and pathological data analysis indicated a correlation between ALOX12 protein expression and renal tubule injury. Further immunofluorescence double staining showed that ALOX12 was expressed in both proximal tubules and distal tubules. Finally, the diagnostic value of the identified gene in the progression of DKD was assessed using receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) value for ALOX12 in the diagnosis of DKD entering the macroalbuminuria stage was 0.736, suggesting that ALOX12 has good diagnostic efficacy. During the development of DKD, the expression levels of ALOX12 in renal tubules were significantly increased and can be used as one of the predictors of the progression to macroalbuminuria in patients with DKD. [ABSTRACT FROM AUTHOR]

The geological conditions evaluation of coalbed methane (CBM) is of great significance to CBM exploration and development. The CBM resources in the Southern Sichuan Coalfield (SSC) of China are very abundant; however, the CBM investigation works in this area are only just beginning, and the basic geological research of CBM is seriously inadequate, restricting CBM exploration and development. Therefore, in this study, a representative CBM block (Dacun) in the SSC was selected, and the CBM geological conditions were evaluated based on field injection/fall-off well testing, gas content and composition measurements, and a series of laboratory experiments. The results show that the CH4 concentrations of coal seams in the Dacun Block, overall, take on an increasing trend as the depth increases, and the CH4 weathering zone depth is 310 m. Due to the coupled control of temperature and formation pressure, the gas content shows a "increase→decrease" trend as the depth increases, and the critical depth is around 700 m. The CBM is enriched in the hinge zone of the Dacun syncline. The moisture content shows a negative correlation with CBM gas content. The porosities of coal seams vary from 4.20% to 5.41% and increase with the Ro,max. The permeabilities of coal seams show a strong heterogeneity with values ranging from 0.001mD to 2.85 mD and present a decreasing trend with the increase in depth. Moreover, a negative relationship exists between coal permeability and minimum horizontal stress magnitude. The reservoir pressure coefficients are between 0.51 and 1.26 and show a fluctuation change trend (increase→decrease→increase) as the depth increases, reflecting that three sets of independent superposed gas-bearing systems possibly exist vertically in the Longtan Formation of the study area. The Langmuir volumes (VL) of coals range from 22.67 to 36.84 m3/t, indicating the coals have strong adsorptivity. The VL presents a parabolic change of first increasing and then decreasing with the increase in depth, and the turning depth is around 700 m, consistent with the critical depth of gas content. The gas saturations of coal seams are, overall, low, with values varying from 29.10% to 116.48% (avg. 68.45%). Both gas content and reservoir pressure show a positive correlation with gas saturation. The CBM development in the Dacun Block needs a large depressurization of reservoir pressure due to the low ratio (avg. 0.37) of critical desorption pressure to reservoir pressure. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are special non-coding RNA (ncRNA) molecules that play a significant role in many diseases. However, the biogenesis and regulation of circRNAs in diabetic nephropathy (DN) are largely unknown. Here, we investigated the expression profile of circRNAs in kidney of DN mice through circular RNA sequencing (circRNA-seq). The renal biopsy samples of patients with DN had low circ -0,000,953 expression, which was significantly associated with renal function. Furthermore, loss-of-function and gain-of-function experiments were carried out to prove the role of circ -0,000,953 in DN. Podocyte conditional knockin (cKI) or systemic overexpression of circ -0,000,953 alleviated albuminuria and restored macroautophagy/autophagy in kidney of diabetic mice. However, circ -0,000,953 knockdown exacerbated albuminuria and podocyte injury. Mechanistically, we found circ -0,000,953 directly binds to Mir665-3p-Atg4b to perform its function. Silencing of Mir665-3p or overexpression of Atg4b recovered podocyte autophagy both in vitro and in vivo. To examine the cause of circ -0,000,953 downregulation in DN, bioinformatics prediction found that circ -0,000,953 sequence has a high possibility of containing an m6A methylation site. Additionally, METTL3 was proved to regulate the expression and methylation level of circ -0,000,953 through YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). In conclusion, this study revealed that circ -0,000,953 regulates podocyte autophagy by targeting Mir665-3p-Atg4b in DN. Therefore, circ -0,000,953 is a potential biomarker for prevention and cure of DN. Abbreviation: CCL2/MCP-1: C-C motif chemokine ligand 2; ceRNA: competing endogenous RNA; circRNA: circular RNA; cKI: conditional knockin; cKO: conditional knockout; CRE: creatinine; DM: diabetes mellitus; DN: diabetic nephropathy; ESRD: end-stage renal disease; HG: high glucose; IF: immunofluorescence; MAP1LC3/LC3B: microtubule-associated protein 1 light chain 3 beta; MPC5: mouse podocyte clone 5; MTECs: mouse tubular epithelial cells; MTOR: mechanistic target of rapamycin kinase; NC: normal control; ncRNA: non-coding RNA; NPHS1: nephrosis 1, nephrin; NPHS2: nephrosis 2, podocin; PAS: periodic acid-Schiff; RELA/p65: v-rel reticuloendotheliosis viral oncogene homolog A (avian); SDs: slit diaphragm proteins; Seq: sequencing; STZ: streptozotocin; SV40: SV40-MES13-cells, mouse mesangial cell line; T1D: type 1 diabetes mellitus; T2D: type 2 diabetes mellitus; TEM: transmission electron microscopy; TNF/TNF-α: tumor necrosis factor; VECs: vascular endothelial cells; WT1: WT1 transcription factor; YTHDF2: YTH N6-methyladenosine RNA binding protein 2. [ABSTRACT FROM AUTHOR]