https://bura.brunel.ac.uk/bitstream/2438/21160/1/FullText.pdf

Association between short-term exposure to air pollution and COVID-19 infection: Evidence from China.

The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by inhibiting let-7 biogenesis. We have uncovered unexpected roles for the Lin28/let-7 pathway in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promote an insulin-sensitized state that resists high-fat-diet induced diabetes. Conversely, muscle-specific loss of Lin28a or overexpression of let-7 results in insulin resistance and impaired glucose tolerance. These phenomena occur, in part, through the let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. In addition, the mTOR inhibitor, rapamycin, abrogates Lin28a-mediated insulin sensitivity and enhanced glucose uptake. Moreover, let-7 targets are enriched for genes containing SNPs associated with type 2 diabetes and control of fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism.

The Lin28/let-7 Axis Regulates Glucose Metabolism

Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ∼150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10−6), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (−0.17 s.d., P = 4.6 × 10−4). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.

Loss-of-function mutations in SLC30A8 protect against type 2 diabetes

The present capabilities of speech recognition algorithms will be surveyed. The application of IC technology to the implementation of these algorithms will be explored and potential future directions will be determined.

Speech recognition

Previous research has identified that air pollution is associated with various respiratory diseases, but few studies have investigated the function served by particulate matter 2.5 (PM2.5) in these diseases. PM2.5 is known to cause epigenetic and microenvironmental alterations in lung cancer, including tumor-associated signaling pathway activation mediated by microRNA dysregulation, DNA methylation, and increased levels of cytokines and inflammatory cells. Autophagy and apoptosis of tumor cells may also be detected in lung cancer associated with PM2.5 exposure. A number of mechanisms are involved in triggering and aggravating asthma and COPD, including PM2.5-induced cytokine release and oxidative stress. The present review is an overview of the underlying molecular mechanisms of PM2.5-induced pathogenesis in lung cancer and chronic airway inflammatory diseases.

/pdf/function-of-pm2-5-in-the-pathogenesis-of-lung-cancer-and-43x36wzvle.pdf

Function of PM2.5 in the pathogenesis of lung cancer and chronic airway inflammatory diseases (Review)

Background
Heavy fine particulate matter (PM2.5) air pollution occurs frequently in China. However, epidemiological research on the association between short-term exposure to PM2.5 pollution and respiratory disease morbidity is still limited. This study aimed to explore the association between PM2.5 pollution and hospital emergency room visits (ERV) for total and cause-specific respiratory diseases in urban areas in Beijing.

/pdf/fine-particulate-air-pollution-and-hospital-emergency-room-g9c9qwxcxl.pdf

Fine Particulate Air Pollution and Hospital Emergency Room Visits for Respiratory Disease in Urban Areas in Beijing, China, in 2013

Background Ferroptosis is a recently identified iron-dependent form of cell death as a result of increased reactive oxygen species (ROS) and lipid peroxidation. In this study, we investigated whether ferroptosis aggravated diabetic nephropathy (DN) and damaged renal tubules through hypoxia-inducible factor (HIF)-1α/heme oxygenase (HO)-1 pathway in db/db mice. Methods Db/db mice were administered with or without ferroptosis inhibitor Ferrostatin-1 treatment, and were compared with db/m mice. Results Db/db mice showed higher urinary albumin-to-creatinine ratio (UACR) than db/m mice, and Ferrostatin-1 reduced UACR in db/db mice. Db/db mice presented higher kidney injury molecular-1 and neutrophil gelatinase-associated lipocalin in kidneys and urine compared to db/m mice, with renal tubular basement membranes folding and faulting. However, these changes were ameliorated in db/db mice after Ferrostatin-1 treatment. Fibrosis area and collagen I were promoted in db/db mouse kidneys as compared to db/m mouse kidneys, which was alleviated by Ferrostatin-1 in db/db mouse kidneys. HIF-1α and HO-1 were increased in db/db mouse kidneys compared with db/m mouse kidneys, and Ferrostatin-1 decreased HIF-1α and HO-1 in db/db mouse kidneys. Iron content was elevated in db/db mouse renal tubules compared with db/m mouse renal tubules, and was relieved in renal tubules of db/db mice after Ferrostatin-1 treatment. Ferritin was increased in db/db mouse kidneys compared with db/m mouse kidneys, but Ferrostatin-1 reduced ferritin in kidneys of db/db mice. Diabetes accelerated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived ROS formation in mouse kidneys, but Ferrostatin-1 prevented ROS formation derived by NADPH oxidases in db/db mouse kidneys. The increased malondialdehyde (MDA) and the decreased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (GSH-Px) were detected in db/db mouse kidneys compared to db/m mouse kidneys, whereas Ferrostatin-1 suppressed MDA and elevated SOD, CAT, and GSH-Px in db/db mouse kidneys. Glutathione peroxidase 4 was lower in db/db mouse kidneys than db/m mouse kidneys, and was exacerbated by Ferrostatin-1 in kidneys of db/db mice. Conclusions Our study indicated that ferroptosis might enhance DN and damage renal tubules in diabetic models through HIF-1α/HO-1 pathway.

/pdf/ferroptosis-enhanced-diabetic-renal-tubular-injury-via-hif-ke83u1y3an.pdf

Ferroptosis Enhanced Diabetic Renal Tubular Injury via HIF-1α/HO-1 Pathway in db/db Mice.

https://ro.ecu.edu.au/cgi/viewcontent.cgi?article=3723&context=ecuworkspost2013

Acute exposure to fine particulate matter and cardiovascular hospital emergency room visits in Beijing, China

Conclusions: In prelingually deaf children with cochlear implants, tone perception and production performance are highly correlated. This result is consistent with the hypothesis that tone percepti...

Tone perception and production in pediatric cochlear implants users

Background: Chronic stress plays an important role in the development of type 2 diabetes mellitus (T2DM) and insulin resistance (IR). MicroRNAs (miRNAs) play key roles in mediating stress responses by regulating the expression of target genes. This study systematically screened and identified the neuroendocrine stress response related circulating miRNAs which associated with T2DM and IR. Methods: Based on the differential plasma expression profiles between individuals with and without T2DM, stress related miRNAs were selected from those differently expressed miRNAs whose targets are involved in known neuroendocrine pathway of stress response. Candidate miRNAs were further validated by qRT-PCR in a large sample including 112 T2DM patients, 72 individuals with impaired fasting glucose (IFG) and 94 healthy controls. The association between miRNA expression and potential risk of T2DM and IFG was assessed by multivariate logistic regression models. The miRNA predictors of IR were identified by stepwise multiple regression analysis. The diagnostic performance for T2DM was evaluate by area under the receiver operating characteristic curve (AUC). Results: Let-7b, let-7i, miR-142, miR-144, miR-155 and miR-29a were selected as candidate miRNAs for validation. Increased expression of let-7b, miR-144 and miR-29a and decreased expression of miR-142 were significant independent predictors of T2DM, IFG and IR (P<0.0125). These miRNAs significantly correlated with stress hormone levels (P<0.0125). A three-miRNA panel including let-7b, miR-142 and miR-144 had a high accuracy for diagnosing T2DM (AUC=0.871, 95% CI: 0.722–0.919). Conclusion: Let-7b, miR-142, miR-144, and miR-29a in plasma may be important markers of neuroendocrine stress response and may play a role in the pathogenesis of T2DM and IR.

/pdf/identification-of-neuroendocrine-stress-response-related-2l6m4n37u4.pdf

Shuo Wang

Papers

Fine Particulate Air Pollution and Hospital Emergency Room Visits for Respiratory Disease in Urban Areas in Beijing, China, in 2013

Ferroptosis Enhanced Diabetic Renal Tubular Injury via HIF-1α/HO-1 Pathway in db/db Mice.

Acute exposure to fine particulate matter and cardiovascular hospital emergency room visits in Beijing, China

Tone perception and production in pediatric cochlear implants users

Identification of Neuroendocrine Stress Response-Related Circulating MicroRNAs as Biomarkers for Type 2 Diabetes Mellitus and Insulin Resistance