[Association between polymorphism of CASP and NOX3 with risk of noise-induced hearing loss].

Objective: To explore the effect of gene polymorphism on workers suffering from noise induced hearing loss (NIHL) . Methods: In May 2019, a case-control study was conducted to select noise exposed workers in five factories in Zhejiang Province from 2017 to 2018. The average hearing threshold of binaural high frequency (3, 4, 6 kHz) was >25 dB (A) as the NIHL group, and the hearing threshold of any language frequency (0.5, 1, 2 kHz) was ≤25 dB (A) as the non NIHL group, with 307 people in each group. The general demographic data, occupational history, pure tone audiometry results and oral swab mucosal samples of noise exposed workers were collected, and the DNA of oral mucosal cells was extracted. The relationship between genetic risk score (GRS) and NIHL was analyzed, single nucleotide polymorphisms (SNP) were genotyped, the relationship between genotype and NIHL was analyzed by logistic regression, and the relationship between haplotype and NIHL was analyzed by R language. Results: After adjusting for gender, age, education and working years, the risk of NIHL among workers carrying cysteine-aspartic acid protease 3 gene (CASP3) rs1049216 recessive model GG genotype, rs6948 recessive model TT genotype, NADPH oxidase 3 gene (NOX3) rs12195525 additive model GT genotype and dominant model TT+GT genotype decreased (P<0.05) , the risk of disease was higher in workers with AA genotype carrying cysteine-aspartic acid protease 7 gene (CASP7) rs12415607 additive model (P<0.05) . There was a strong linkage disequilibrium (LD) relationship between rs1049216 and rs6948 (D'>0.8) . Haplotype AT and GG composed of rs1049216-rs6948 increased the risk of NIHL (P<0.05) . The risk of NIHL increased with the increase of GRS (OR=2.69, P<0.05) . Conclusion: Genotype polymorphisms at rs1049216 and rs6948 (CASP3) , rs12195525 (NOX3) , rs12415607 (CASP7) may be associated with susceptibility to NIHL.

[Survey on present status of noise exposure of workers in metal processing industry].

Objective: To investigate the distribution of noise exposure between non-steady state noise and steady-state noise for metal processing workers, which will provide scientific basis for the prevention and treatment of noise hazards in metal processing industry. Methods: The cross-section method was used to investigate the noise exposure of 737 workers from three metal processing industries in Zhejiang Province from October to December 2017. The general demographic information and occupational history were collected by questionnaire. The noise was recorded by individual noise meters, and the noise exposure intensity (equivalent continuous A-weighted noise exposure level normalized to an 8 h-working-day, L(Aeq, 8 h)) and kurtosis were calculated. Results: Workers exposed to noise in the metal processing industry were mainly 18-40 years old (527 workers, 71.51%) , men (570 workers, 77.34%) , and junior high school education background (416 workers, 56.45%) . There were 572 workers (77.61%) with noise exposure intensity (L(Aeq, 8 h)) greater than 85 dB (A) , 558 workers (75.71%) exposed to non-steady state noise (kurtosis ≥4) , and 634 workers (86.02%) with exposure duration less than 8 years. Among the 30 work types investigated, the work types with noise intensity reaching 100% were the stamping, welding and others from a children's car manufacturing factory in Ningbo, operating, chamfering, tapping, and thread rolling from an automobile parts manufacturing factory in Ningbo; The work types with a rate of 100% exposed to non-steady state noise were the grinding from a children's car manufacturing factory in Ningbo, assembling, assembly operating and others from an automobile brake manufacturing factory in Wenzhou, and polishing from an automobile parts manufacturing factory in Ningbo. Conclusion: Metal processing workers have a high rate of over-standard exposed to high noise intensity and a high proportion exposed to non-steady state noise. It is necessary to take sound insulation and noise reduction engineering control, and strengthen personal protection and occupational health management measures to prevent and control the noise hazards.

Spatial Distribution of Culex tritaeniorhynchus Giles, 1901 (Diptera: Culicidae) in Relation to Pigsties and Other Geo-environmental Features in Dao County, Hunan Province, China.

In this study, we investigated the spatial distribution of Culex tritaeniorhynchus Giles, 1901 (Diptera: Culicidae) (the vector of Japanese B Encephalitis) and geo-environmental features (rice fields, forests, watercourses, and highways) correlated with their abundance in pigsties of Dao County, Hunan Province, China. First, light trapping in pigsties was carried out to determine vector density. Second, based on Advanced Land Observing Satellite remote-sensing datasets, spatial datasets of mosquito density and various geo-environmental features were constructed using Geography Information System. Finally, spatial statistical analysis and general linear regression were used to analyze the spatial distribution of vectors in relation to the geo-environmental features correlating with the abundance of mosquitoes in pigsties. As the results show, the distribution of mosquitoes in pigsties was not spatially autocorrelated, and several geo-environmental features that were either positively or negatively correlated with mosquito abundance in pigsties were identified. The application of these results to improve the control of vectors of Japanese B Encephalitis is also discussed.

Synergistic antinociception between ZC88, an N-type voltage-dependent calcium channel blocker, and ibuprofen in mouse models of visceral and somatic inflammatory pain.

BACKGROUND: A combination of analgesic agents with different mechanisms can induce additive or synergistic analgesia. The N-type voltage-dependent calcium channel (N-VDCC) is a novel therapeutic target for pain control. In addition to providing effective pain relief when used alone, N-VDCC blockers produce synergistic analgesia when used in combination with opiates. However, the interaction between N-VDCC blockers and nonsteroidal anti-inflammatory drugs (NSAIDs) remains unclear. METHODS: Using isobolographic analysis and composite additive curve analysis, the antinociceptive interaction between ZC88, a selective N-VDCC blocker and ibuprofen, a classical NSAID, was investigated in two mouse models of visceral and somatic inflammatory pain. RESULTS: In the acetic acid writhing test, both ZC88 (10.5-42 mg/kg, intraperitoneally) and ibuprofen (50-200 mg/kg, orally) produced dose-dependent antinociception, with ED50 values of 27.2 and 100.5 mg/kg, respectively. ZC88 in combination with ibuprofen (ZC88 + ibuprofen) also induced significant antinociception, and isobolographic analysis revealed a synergistic interaction at 50% effect level. The experimental ED50 (ED50 mix ) of this combination (34.5 mg/kg) was significantly lower than the theoretical ED50 (ED50 add ; 63.8 mg/kg). Additionally, composite additive curve analysis displayed synergistic interaction at other effect levels. In the formalin test, ZC88 or ibuprofen alone significantly reduced late-phase rather than early-phase pain, with ED50 values of 31.3 and 123.9 mg/kg, respectively. Similarly, both isobolographic analysis and composite additive curve analysis revealed synergistic antinociception of ZC88 + ibuprofen (40.6 mg/kg of ED50 mix vs. 77.6 mg/kg of ED50 add ). CONCLUSION: ZC88 in combination with ibuprofen produces synergistic antinociception in mouse models of somatic and visceral inflammatory pain. SIGNIFICANCE: Because ZC88 + ibuprofen achieves the same antinociceptive effect at lower doses, the use of this combination could result in fewer dose-related untoward effects. The potentiation of ZC88 on ibuprofen-induced antinociception indicates that N-VDCC blocker has potential benefit to treat severe inflammatory pain.

Direct observation of the topological spin configurations mediated by the substitution of rare-earth element Y in MnNiGa alloy.

The evolution of topological magnetic domains microscopically correlates the dynamic behavior of memory units in spintronic application. Nanometric bubbles with variation of spin configurations have been directly observed in a centrosymmetric hexagonal magnet (Mn0.5Ni0.5)65(Ga1-yYy)35 (y = 0.01) using Lorentz transmission electron microscopy. Magnetic bubbles instead of biskyrmions are generated due to the enhancement of quality factor Q caused by the substitution of rare-earth element Y. Furthermore, the bubble density and diversified spin configurations are systematically manipulated via combining the electric current with perpendicular magnetic fields. The magnetic bubble lattice at zero field is achieved after the optimized manipulation.

Efficacy of Omega-3 Polyunsaturated Fatty Acids Supplementation in Managing Overweight and Obesity: A Meta-Analysis of Randomized Clinical Trials.

OBJECTIVE: Studies in rodents and humans have indicated that omega-3 polyunsaturated fatty acids (n-3 PUFA) may reduce weight. The aim of this meta-analysis was to evaluate evidence for the efficacy of n-3 PUFA in managing overweight and obesity. METHODS: We performed a systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials until May 2015. Two reviewers independently determined the eligibility of studies and assessed the reporting quality of included randomized controlled trials (RCTs). RESULTS: A total of 11 RCTs involving 617 participants were included in this meta-analysis. Based on the meta-analysis of nine studies, a statistically nonsignificant difference was revealed in weight loss between n-3 PUFA and placebo (p=0.99; weighted mean difference [WMD]: 0.00; 95% confidence interval [CI] -0.42 to 0.43), whereas n-3 PUFA was superior to placebo in reducing serum triglyceride levels (p=0.0007; standard median difference [Std MD]: -0.59; 95% CI -0.93 to -0.25). Based on meta-analysis of seven studies, the analysis of aggregated data showed a significant reduction in waist circumference (p=0.005; WMD: -0.53; 95% CI -0.90 to -0.16). There were no significant differences in body mass index, total serum levels of cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and fasting glucose levels. CONCLUSIONS: The evidence from RCTs showed that n-3 PUFA might effectively reduce waist circumference and triglyceride levels in overweight and obese adults, but n-3 PUFA may not effectively reduce body weight. Given the small number and poor quality of RCTs included in the meta-analysis, these results are inconclusive. A large-scale, well-designed RCT is needed to further address this issue.

Acetal-linked branched poly(dimethyl-aminoethyl methacrylate) as an acid cleavable gene vector with reduced cytotoxicity.

An acid labile branched PDMAEMA/acetal copolymer with amino group was synthesized by the DE-ATRP and followed by Michael addition. The degradation of the polymer was strongly pH-dependent. High nucleic acid transfection efficiency with low cytotoxicity was observed compared to its non-degradable copolymer counterpart.

Effects of acarbose on polycystic ovary syndrome: a meta-analysis.

OBJECTIVE: Whether or not acarbose benefits patients with polycystic ovary syndrome (PCOS) remains controversial. Therefore, we performed a meta-analysis to synthesize the literature regarding the therapeutic effects of acarbose on PCOS. METHODS: A comprehensive literature search was performed using terms, such as polycystic ovary syndrome, ovary polycystic disease, PCOS, hyperandrogenemia, acarbose, alpha-glucosidase inhibitors, and randomized controlled trials (RCTs), in the following bibliographic databases: Medline; Embase; and Cochrane Controlled Trials Register. The identified reference lists were checked manually. RESULTS: 6 RCTs met the inclusion criteria. Based on the meta-analysis of 3 studies, acarbose was superior to placebo or no treatment in reducing serum levels of testosterone (Std MD = - 3.38, 95% CI:-5.97~-0.78, P = 0.01) and acarbose caused a significantly higher incidence of side effects, such as abdominal distention and diarrhea (OR = 23.78, 95% CI: 5.67~99.75, P < 0.0001). The changes in Ferriman-Gallwey score or body mass index (BMI) were not significant. Based on the meta-analysis of 2 studies, acarbose were superior to placebo or no treatment in reducing triglycerides (TG; WMD = -18.18, 95% CI:-36.30~-0.06, P = 0.05) and very low-density lipoprotein (VLDL) cholesterol (WMD = - 6.49, 95% CI:-9.14~-3.84, P < 0.00001), and increasing high-density lipoprotein (HDL) cholesterol (WMD = 5.14, 95% CI:1.73~8.55, P = 0.003). There were no significant differences between acarbose and metformin with respect to improvements in ovulation rate, menstrual patterns, or changes in serum levels of testosterone, adverse events, or BMI. Heterogeneities were detected during the meta-analysis. CONCLUSIONS: This is the first meta-analysis to evaluate the role that acarbose plays in the treatment of PCOS. The currently available data showed that acarbose can reduce testosterone, TG, and VLDL, and increase HDL. Acarbose caused a significantly higher incidence of gastrointestinal disturbance. Given the small RCTs and poor quality of RCTs included, these results are not conclusive. A large-scale, randomized controlled study is needed to ascertain this uncertainty.

A preliminary investigation of the mechanisms underlying the effect of berberine in preventing high-fat diet-induced insulin resistance in rats.

Berberine exerts insulin resistance-improving effects, the underlying mechanism of which is not well understood. We herein aimed to examine the effects of berberine on mediators of insulin signaling in pancreatic ß- and α- islet cells and hepatocytes using a rat obesity model. Rats were fed the following diets for 22 weeks: normal control (NC); normal+berberine (NC+BBR 200 mg/kg/day); high-fat (HF); HF+BBR(1) (BBR 100 mg/kg/day); HF+BBR(2) (BBR 200 mg/kg/day). Metabolic parameters were assessed and mediators of insulin signaling were quantified by immunohistochemistry. The HF diet significantly increased body weight (BW), visceral fat (VF), the visceral fat to BW ratio (VF/BW), and insulin resistance index in the HF group compared with the NC group. Both doses of BBR significantly reduced HF diet-induced increases in BW, VF, and VF/BW. IR and IRS-1 expression in ß-cells was significantly lower in the HF group, but not the HF+BBR groups, compared with the NC and NC+BBR groups. Glucagon expression in α-cells was significantly higher in the HF group compared with all other groups. IR expression in α-cells was significantly lower in the HF group compared with the NC, NC+BBR, and HF+BBR(2) groups. IR expression in hepatocytes was significantly lower in the HF group compared with all groups. Our preliminary findings suggest that berberine may ameliorate the development of insulin resistance by differentially preventing alterations in expression of IR, IRS-1, and glucagon in ß-cells, α-cells, and hepatocytes.

Detection and widespread distribution of sodium channel alleles characteristic of insecticide resistance in Culex pipiens complex mosquitoes in China.

Culex pipiens complex mosquitoes are widely distributed throughout China and are known to be important disease vectors. Two pyrethroid resistance associated mutations have been identified in Cx. pipiens complex (Diptera: Culicidae), but there is little information on the diversity and distribution of kdr alleles in pyrethroid resistance in Cx. pipiens complex mosquitoes in China. In the present study, we report on a modified three tube allele-specific (AS)-PCR method for detecting the 1014F and 1014S alleles. The new technique was applied to identify the distribution of the two alleles in natural Cx. pipiens complex populations in China. The results confirmed that the new method is both sensitive and specific. The 1014F allele was found in all 14 of the field populations tested (frequency ranged from 6.8 to 76.2%) and the 1014S allele was found in almost two-thirds (frequency from 2.4 to 28.6%), indicating that the genotypes known to be associated with pyrethroid resistance are widespread in China. The resistance-associated alleles were more common in southern Chinese sampling sites than in northern sites. The coexistence of the two resistant mutations in individual mosquitoes was also observed in five of the field populations. Two alternative mutations within the L1014 codon were identified in Culex pipiens molestus Forskal, 1775, including a non-synonymous mutation resulting in a 1014C substitution.

The protective effect of berberine on ß-cell lipoapoptosis.

AIMS: To evaluate the protective effect of berberine on ß-cell lipoapoptosis induced by palmitate and to explore the possible underlying mechanisms. MATERIALS AND METHODS: HIT-T15 pancreatic ß-cells were divided into the following treatment groups: untreated controls; 100 µM berberine; 0.5 mM palmitate; 0.5 mM palmitate + 0.1 µM berberine; 0.5 mM palmitate + 1 µM berberine; 0.5 mM palmitate + 10 µM berberine; and 0.5 mM palmitate + 100 µM berberine. After 48 h, cell apoptosis was assessed by flow cytometry and the Hoechst 33258 fluorescent assay. Basal and glucose-stimulated insulin levels in culture medium were measured by radioimmunoassay. Peroxisome proliferator- activated receptor-γ (PPAR-γ) mRNA and protein levels were determined by real-time PCR and immunocytochemistry, respectively. RESULTS: Apoptosis was significantly increased upon treatment with palmitate as compared to the untreated controls (p<0.0001). In addition, glucose-stimulated insulin secretion (GSIS), PPAR-γ mRNA and protein expression were significantly reduced in response to palmitate (p<0.0001); however, palmitate-induced apoptosis and reduction in PPAR-γ expression were reversed in response to berberine in a dose-dependent manner (p<0.05). Furthermore, there was a non-significant increase in GSIS with increasing berberine dose. CONCLUSION: Palmitate exerted lipotoxic effects on HIT-T15 cells, inducing apoptosis and reducing GSIS. Berberine reduced palmitate-induced lipoapoptosis and tended to increase GSIS in HIT-T15 cells, possibly through increased PPAR-γ expression.

Expression and hormonal regulation of IL-11Ralpha in canine uterus during early pregnancy.

Embryo implantation is critical for the successful establishment of pregnancy. Interleukin-11 (IL-11) is essential for adequate decidualization in the mouse and human via binding to the specific IL-11 receptor alpha (IL-11Ralpha). But the expression and regulation of IL-11 and IL-11Ralpha in the canine endometrium remain unknown. The aim of this study was to investigate the differential expression of IL-11Ralpha in canine uterus during early pregnancy and its regulation under different conditions by in situ hybridization. Interleukin-11Ralpha mRNA was mainly localized in glandular epithelium in canine uterus. There was a low level of IL-11Ralpha expression in the glandular epithelium on days 6, 12 and 17 of pregnancy. On day 20 of pregnancy when embryo implanted, IL-11Ralpha mRNA was highly expressed in the glandular epithelium surrounding the embryo, but not in the luminal epithelium and stroma. On day 23 of pregnancy, the expression of IL-11Ralpha mRNA maintained a constant level compared with the expression of day 20 and increased on day 28 of pregnancy. During the oestrous cycle, a high level of IL-11Ralpha mRNA expression was seen in the oestrous uterus. Progesterone slightly induced the expression of IL-11Ralpha mRNA in the ovariectomized canine uterus. These results suggest that IL-11Ralpha expression is closely related to canine implantation and up-regulated by progesterone.