Effect of Sodium-Glucose Co-transporter 2 Inhibitors on Bone Metabolism and Fracture Risk

The effect of anti-diabetic medications on bone metabolism has received increasing attention, considering that type 2 diabetes mellitus is a common metabolic disorder with adverse effects on bone metabolism. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel anti-diabetic medications that prevent glucose resorption at the proximal convoluted tubules in the kidney, increasing urinary glucose excretion, and decreasing the blood glucose level. The superiority of SGLT2 inhibitors shows in reducing the glucose level independent of insulin secretion, lowering the risk of hypoglycemia, and improving cardiovascular outcomes. SGLT2 inhibitors have been associated with genital mycotic infections, increased risk of acute kidney injury, dehydration, orthostatic hypotension, and ketoacidosis. Moreover, the effect of SGLT2 inhibitors on bone metabolism and fracture risk has been widely taken into consideration. Our review summarizes the results of current studies investigating the effects of SGLT2 inhibitors on bone metabolism (possibly including increased bone turnover, disrupted bone microarchitecture, and reduced bone mineral density). Several mechanisms are probably involved, such as bone mineral losses due to the disturbed calcium and phosphate homeostasis, as confirmed by an increase in fibroblast growth factor 23 and parathyroid hormone levels and a decrease in 1,25-dihydroxyvitamin D levels. SGLT2 inhibitors might indirectly increase bone turnover by weight loss. Lowering the blood glucose level might ameliorate bone metabolism impairment in diabetes. The effect of SGLT2 inhibitors on bone fractures remains unclear. Evidence indicating the direct effect of SGLT2 inhibitors on fracture risk is lacking and increased falls probably contribute to fractures

Parameter design of coal pillar in highwall mining under action of dynamic-static load

In view of the application of end slope shearer mining technology to recover a large amount of residual coal, the determination of reasonable width of supporting coal pillar is a key factor whether it can be safely and efficiently popularization and application, especially considering the influence of blasting vibration on the stability of supporting coal pillar. Based on the southern end slope at the open-pit coal mine of Pingshuo, field vibration test, theoretical analysis and numerical calculation were used to study the web pillar stability in open-pit highwall mining and its parameter design under the action of triangular load and blasting vibration on the side slope. Based on the theory of limit balance and the mutation theory, the stress distribution at the coal pillar was analyzed, combined with Mohr-Coulomb failure criterion. Besides, the ultimate strength function expression of coal pillar under the influence of mining height, mining width, load stress of overlying strata, cohesion and internal friction angle of coal pillar is established. The calculation formula of the maximum allowable plastic zone width and rational width of web pillar under different safety reserve factor conditions are established. The three-dimensional simple harmonic vibration response model of the supported coal pillar was established, and the blasting parameters such as the amount of single shot, elevation difference and horizontal distance of the blast center were studied on the response of the maximum instantaneous dynamic stress of the coal pillar, which revealed the influence mechanism of the blasting dynamic load effect on the width and stability of the plastic zone of the supported coal pillar and proposed the design method of the parameters of the supported coal pillar under the blasting dynamic load. The results show that the blasting vibration has a greater influence on the stability of coal pillar, and the instantaneous maximum dynamic stress response of coal pillar under the blasting dynamic load is positively correlated with the amount of single shot, and negatively correlated with the elevation difference and horizontal distance. With the increase of the maximum instantaneous dynamic stress response of coal pillar, the width of plastic zone of coal pillar increases proportionally, and the safety factor of coal pillar decays in an approximately linear pattern. The width of coal pillar under dynamic-static load is determined to be 5 m, and its reasonableness is verified by engineering practice

Association Between Bone Mineral Density, Bone Turnover Markers, and Serum Cholesterol Levels in Type 2 Diabetes

Purpose: The association between bone mineral density (BMD), bone turnover markers, and serum cholesterol in healthy population has already been proved. However, in patients with type 2 diabetes mellitus (T2D), it has not been adequately analyzed. In this study, we investigated the correlation between BMD, bone turnover markers, and serum cholesterol levels in people with T2D.Methods: We enrolled 1,040 men and 735 women with T2D from Zhongshan Hospital between October 2009 and January 2013. Their general condition, history of diseases and medication, serum markers, and BMD data were collected. We used logistic regression analysis to identify the association between serum cholesterol levels and BMD as well as bone turnover markers.Results: In multivariate regression analysis, we observed that in men with T2D, high high-density lipoprotein-cholesterol and total cholesterol levels were significantly associated with low total lumbar, femur neck, and total hip BMD, while low-density lipoprotein-cholesterol level was only inversely associated with total lumbar and femur neck BMD. Total cholesterol and low-density lipoprotein-cholesterol levels were also negatively associated with osteocalcin, procollagen type I N-terminal propeptide, and β-crosslaps. In women with T2D, high-density lipoprotein-cholesterol level was observed to be negatively correlated with total lumbar, femur neck, and total hip BMD, while total cholesterol and low-density lipoprotein-cholesterol levels were only associated with BMD at the total lumbar. Furthermore, total cholesterol was also negatively associated with osteocalcin, procollagen type I N-terminal propeptide, and β-crosslaps; high-density lipoprotein-cholesterol was only related to osteocalcin and parathyroid hormone, while low-density lipoprotein-cholesterol was only related to β-crosslaps in women.Conclusion: Our study suggests a significantly negative correlation between serum cholesterol levels and BMD in both men and women with T2D. The associations between serum cholesterol levels and bone turnover markers were also observed in T2D patients

Association between renal function and bone mineral density in patients with type 2 diabetes mellitus

Background: This study evaluated the association between renal function, assessed by serum creatinine and estimated glomerular filtration rate (eGFR) according to the Cockcroft–Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations, and bone mineral density (BMD) in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: 1322 patients with T2DM were included, and their basic clinical information, serum biochemical tests, and BMD at the total hip and femur neck were collected. Multivariate adjusted linear regression, smooth curve fitting and a piecewise linear regression model were used to analyze linear and nonlinear associations. Age, BMI, drinking, smoking, systolic blood pressure and diastolic blood pressure, FBG, HbA1C, course of diabetes, hsCRP, TC, TG, HDL-C, LDL-C, Ca, P, PTH, ALP, OC, P1NP, β-CTX and 25(OH)D were adjusted. Results: After adjusting the variables, no correlation between eGFR CG and eGFR MDRD and femur neck BMD was observed in women, men, or the total population. The eGFR CG and eGFR MDRD had a significant positive association with total hip BMD in men and the total population with T2DM. With a 10-unit decrease in eGFR CG, total hip BMD reduced by 0.012 g/cm2 in men and 0.010 g/cm2 the total population. Total hip BMD reduced by 0.014 g/cm2 in men and 0.022 g/cm2 in the total population with a 10-unit decrease in eGFR MDRD. There was no correlation between eGFR CG or eGFR MDRD and total hip BMD in female participants. Conclusion: Impaired renal function was associated with decreased total hip BMD in men and the total population with T2DM. No associated between renal function with femur neck BMD was observed

Study on web pillar failure mechanism during auger mining and its associated risk assessment

Abstract To safely and efficiently recover trapped coal under final endwalls in open cut mines, theoretical analysis and numerical calculation were used to study the stability of web pillar during auger mining. The partial ordered set (poset) evaluation model was used to develop a risk assessment methodology, and auger mining at Pingshuo Antaibao open cut coal mine was used as a field example for validation. Based on the catastrophe theory, the failure criterion of web pillar was established. From the limit equilibrium theory, the maximum allowable plastic yield zone width and minimum web pillar width were proposed under various Factor of Safety (FoS) thresholds. This in turn provides a new method for web pillar design. Based on the poset theory and combining with the risk evaluation and proposed hazard levels, input data were standardized and weighted. Subsequently, the comparison matrix, HASSE matrix and HASSE diagram were established. The study shows that: when the width of the plastic zone of web pillar exceeds 88% of the total width, web pillar may be unstable. Based on the calculation formula for the required width of web pillar, the required pillar width was 4.93 m and it was deemed as “mostly stable”. This was consistent with the field condition on site. Such that this method was validated

Metastasis-associated fibroblasts: an emerging target for metastatic cancer

Abstract Metastasis suggests a poor prognosis for cancer patients, and treatment strategies for metastatic cancer are still very limited. Numerous studies have shown that cancer-associated fibroblasts (CAFs), a large component of the tumor microenvironment, contribute to tumor metastasis. Stromal fibroblasts at metastatic sites are different from CAFs within primary tumors and can be termed metastasis-associated fibroblasts (MAFs), and they also make great contributions to the establishment of metastatic lesions and the therapeutic resistance of metastatic tumors. MAFs are capable of remodeling the extracellular matrix of metastatic tumors, modulating immune cells in the tumor microenvironment, promoting angiogenesis and enhancing malignant tumor phenotypes. Thus, MAFs can help establish premetastatic niches and mediate resistance to therapeutic strategies, including immunotherapy and antiangiogenic therapy. The results of preclinical studies suggest that targeting MAFs can alleviate the progression of metastatic cancer and mitigate therapeutic resistance, indicating that MAFs are a promising target for metastatic cancer. Here, we comprehensively summarize the existing evidence on MAFs and discuss their origins, generation, functions and related therapeutic strategies in an effort to provide a better understanding of MAFs and offer treatment perspectives for metastatic cancer

Exploring the Drivers for Changes in Lake Area in a Typical Arid Region during Past Decades

Lakes are important surface water bodies, and ongoing climate change is a growing threat to the hydrological cycle and water resource availability of lakes in arid regions. Accurately estimating different drivers’ contributions to lake water volume can enhance our understanding of lake variations in arid regions. In this study, we combined the land surface model and hydrological model, as well as statistical methods, to analyze the spatiotemporal heterogeneity of lake area changes and the factors affecting these changes during the past decades in Bosten Lake, Ulungur Lake, Ebinur Lake, and Sayram Lake, which are located in a typical dry region in China. The study revealed that the average amounts of river inflow, TWVF, lake ice sublimation, lake surface precipitation, and river outflow in the four lakes were 17.41 × 108 m3 yr−1, 6.60 × 108 m3 yr−1, 0.41 × 108 m3 yr−1, 0.98 × 108 m3 yr−1, and 9.12 × 108 m3 yr−1, respectively. We found that river inflow is the dominant factor affecting changes in open lake areas, while lake surface precipitation is the main factor affecting changes in closed lake areas. Our findings suggest that the main factors dominating the variability of lake water volume differ in different phases and lake types

Bioinformatic identification of candidate biomarkers and related transcription factors in nasopharyngeal carcinoma

Abstract Background The incidence of nasopharyngeal carcinoma (NPC) is rare, but a certain amount of mortality remains in NPC patients. Our study aimed to identify candidate genes as biomarkers for NPC screening, diagnosis, and therapy. Methods We investigated two microarray profile datasets GSE64634 and GSE12452 to screen the potential differentially expressed genes (DEGs) in NPC. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs were also performed. A protein-protein interaction (PPI) network of DEGs was constructed by STRING and visualized by Cytoscape software. The associated transcriptional factor regulatory network of the DEGs was also constructed. Results A total of 152 DEGs were identified from the GSE64634 and GSE12452 datasets, including 10 upregulated and 142 downregulated genes. Gene functional enrichment analysis indicated that these DEGs were enriched in the cilium movement, antimicrobial humoral response, O-glycan processing, mucosal immune response, carbohydrate transmembrane transporter activity, hormone biosynthetic process, neurotransmitter biosynthetic process, and drug metabolism-cytochrome P450 pathway. Five hub genes (DNALI1, RSPH4A, RSPH9, DNAI2, and ALDH3A1) and one significant module (score = 5.6) were obtained from the PPI network. Key transcriptional factors, such as SPI1, SIN3B, and GATA2, were identified with close interactions with these five hub DEGs from the gene-transcriptional factor network. Conclusions With the integrated bioinformatic analysis, numerous DEGs related to NPC were screened, and the hub DEGs we identified may be potential biomarkers for NPC

miR-24-3p/FGFR3 Signaling as a Novel Axis Is Involved in Epithelial-Mesenchymal Transition and Regulates Lung Adenocarcinoma Progression

Our previous studies showed that Fibroblast growth factor receptor 3 (FGFR3) contributed to cell growth in lung cancer. However, the correlation between FGFR3 and tumor progression, coupled with the underlying mechanisms, are not fully understood. The clinical significance of FGFR3 was determined in two cohorts of clinical samples (n=22, n=78). A panel of biochemical assays and functional experiments was utilized to elucidate the underlying mechanisms and effects of FGFR3 and miR-24-3p on lung adenocarcinoma progression. Upregulated FGFR3 expression indicated an adverse prognosis for lung adenocarcinoma individuals and promoted metastatic potential of lung adenocarcinoma cells. Owing to the direct regulation towards FGFR3, miR-24-3p could interfere with the potential of proliferation, migration, and invasion in lung adenocarcinoma, following variations of EMT-related protein expression. As a significant marker of EMT, E-cadherin was negatively correlated with FGFR3, of which ectopic overexpression could neutralize the antitumour effects of miR-24-3p and reverse its regulatory effects on EMT markers. Taken together, these findings define a novel insight into the miR-24-3p/FGFR3 signaling axis in regulating lung adenocarcinoma progression and suggest that targeting the miR-24-3p/FGFR3 axis could be an effective and efficient way to prevent tumor progression

Temperature-dependent magnetization in (Mn, N)-codoped ZnO-based diluted magnetic semiconductors

The influences of Mn doping on the structural quality of the ZnxMn1-xO:N alloy films have been investigated by XRD. Chemical compositions of the samples (Zn and Mn content) and their valence states were determined by X-ray photoelectron spectrometry (XPS). Hall effect measurements versus temperature for ZnxMn1-xO:N samples have been designed and studied in detail. The ferromagnetic transitions happened at different TC should explain that the magnetic transition in field-cooled magnetization of Zn1-xMnxO:N films at low temperature is caused by the strong pd exchange interactions besides magnetic transition at 46 K resulting from Mn oxide, and that the room temperature ferromagnetic signatures are attributed to the uncompensated spins at the surface of anti-ferromagnetic nano-crystal of Mn-related Zn(Mn)O