Aqueous VOCs in complex water environment of oil exploitation sites: Spatial distribution, migration flux, and risk assessment.

Pollution of the aqueous environment by volatile organic compounds (VOCs) has caused increasing concerns. However, the occurrence and risks of aqueous VOCs in oil exploitation areas remain unclear. Herein, spatial distribution, migration flux, and environmental risks of VOCs in complex surface waters (including River, Estuary, Offshore and Aquaculture areas) were investigated at a typical coastal oil exploitation site. Among these surface waters, River was the most polluted area, and 1,2-Dichloropropane-which emerges from oil extraction activities-was the most prevalent VOC. Positive matrix factorization showed that VOCs pollution sources changed from oil exploitation to offshore disinfection activities along River, Estuary, Offshore and Aquaculture areas. Annual volatilization of VOCs to the atmosphere was predicted to be ∼34.42 tons, and rivers discharge ∼23.70 tons VOCs into the Bohai Sea annually. Ecological risk assessment indicated that Ethylbenzene and Bromochloromethane posed potential ecological risks to the aquatic environment, while olfactory assessment indicated that VOCs in surface waters did not pose an odor exposure risk. This study provides the first assessment of the pollution characteristics of aqueous VOCs in complex aqueous environments of oil exploitation sites, highlighting that oil exploitation activities can have nonnegligible impacts on VOCs pollution profiles.

Correlations of SDF-1ɑ and XRCC1 gene polymorphisms with the risk of renal cancer development and bioinformatics studies of SDF-1α and XRCC1 and the prognosis of renal cancer.

To study the relationships between stromal cell-derived factor-1 (SDF-1ɑ) and renal cell carcinoma (RCC) susceptibility and the presence of single nucleotide polymorphisms in the human X-ray cross-complementary repair gene (XRCC1). Compare SDF-1 based on RCC related data in the TCGA database α, The expression difference of XRCC1 between RCC tissue and normal tissue; Collect 166 newly diagnosed RCC cases and 166 healthy individuals who underwent physical examinations during the same period, and detect genotype using iMLDR method. The results The rs1801157 locus (C:T) of the SDF-1α gene was not significantly associated with the pathohistological type, the rs1799782 locus (G:A) of the XRCC1 gene was associated with the pathohistological type of RCC, and there were interactions between rs1799782 and smoking, alcohol consumption, pesticide exposure, hair dye, and urine holding. The rs1799782 locus of the XRCC1 gene may be a key factor in the pathogenesis and pathological development of RCC. High SDF-1ɑ expression is a protective factor for the overall survival of patients with RCC, and SDF-1ɑ and XRCC1 may be important for the treatment of RCC.

Occurrence of BTX and PAHs in underground drinking water of coking contaminated sites: Linkage with altitude and health risk assessment by boiling-modified models.

The safety of underground drinking water has received widespread attention. However, few studies have focused on the occurrence and health risks of pollutants in underground drinking water of coking contaminated sites. In this study, the distribution characteristics, sources, and human health risks of benzene, toluene, xylene (BTX) and polycyclic aromatic hydrocarbons (PAHs) in underground drinking water from a typical coking contaminated site in Shanxi of China were investigated. The average concentrations of BTX and PAHs in coking plant (CP) were 5.1 and 4.8 times higher than those in residential area (RA), respectively. Toluene and Benzene were the main BTX, while Acenaphthene, Fluorene, and Pyrene were the main PAHs. Concentrations of BTX/PAHs were negatively correlated with altitude, revealing altitude might be an important geological factor influencing spatial distribution of BTX/PAHs. PMF model demonstrated that the BTX/PAHs pollution in RA mainly originated from coking industrial activities. Health risk assessments were conducted by a modified US EPA-based model, in which environmental concentrations were replaced by residual concentrations after boiling. Residual ratios of different BTX/PAHs were determined by boiling experiments to be 9.4-93.8 %. The average total carcinogenic risks after boiling were decreased from 2.6 × 10-6 to 1.4 × 10-6 for adults, and from 4.3 × 10-6 to 2.1 × 10-6 for children, suggesting boiling was an effective strategy to reduce the carcinogenic risks from BTX/PAHs, especially for ingestion pathway. Monte Carlo simulation results matched well with the calculated results, suggesting the uncertainty was acceptable and the risk assessment results were reliable. This study provided useful information for revealing the spatial distribution of BTX/PAHs in underground drinking water of coking contaminated sites, understanding their linkage with altitude, and also helped to more accurately evaluate the health risks by using the newly established boiling-modified models.

Analysis of the heavy metal contents' effect on steroidal saponins and the anti-breast cancer activity of Paris polyphylla var. yunnanensis.

Background: P. polyphylla var. yunnanensis, as a near-threatened and ethnic medicine in China, used to be a key ingredient in traditional Chinese medicine in treatment of traumatic injuries, sore throat, snakebites, and convulsions for thousands of years. However, there were no reports on the inverse relationship between the contents of heavy metals and saponins and its anti-breast cancer pharmacological activity in P. polyphylla var. yunnanensis. Methods: The present study aimed to reveal the characteristics of heavy metal contents and saponins and its anti-breast cancer pharmacological activity and their interrelationships in P. polyphylla var. yunnanensis from different production areas. The contents of heavy metal and steroidal saponins in P. polyphylla var. yunnanensis were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) and the high-performance liquid chromatography technique, respectively. The Pearson correlation was used to study the correlation between saponins and heavy metals. 4T1 mouse mammary tumor cells were selected and cultivated for antitumor studies in vitro. Cell Counting Kit-8 (CCK-8) assay, Hoechst staining, and flow cytometry analysis were used for the examination of the proliferation and apoptosis of 4T1 tumor cells. Mouse breast cancer 4T1 cells were subcutaneously injected into BALB/c mice to construct a tumor model to explore the in vivo inhibitory effect on breast cancer. TUNEL assay and immunohistochemistry were used for the examination of the effect of P. polyphylla var. yunnanensis from different origins on cancer cell proliferation and apoptosis induction in 4T1 tumor mice. Results: Heavy metal contents were highly correlated with the content of steroidal saponins. The overall content of 10 metals in the three producing origins was of the order C3 >C2 >C1. The total content of eight steroidal saponins in the extracts of P. polyphylla var. yunnanensis from three different origins was C1 >C2 >C3. The Pearson correlation study showed that in all of the heavy metals, the contents of Cd and Ba were positively correlated with the main steroidal saponins in P. polyphylla var. yunnanensis, while Al, Cr, Cu, Fe, Zn, As, Hg, and Pb showed a negative correlation. In vitro experiments showed that the extracts of P. polyphylla var. yunnanensis from three origins could inhibit the proliferation and induce cell apoptosis of 4T1 cells in a concentration- and time-dependent manner, especially in the C1 origin. In vivo experiments showed that the extract of P. polyphylla var. yunnanensis from the three origins could inhibit the growth of tumors and induce the apoptosis of tumor cells. In the three origins, C1 origin had the lowest total heavy metal level but the highest total steroidal saponin level. Therefore, it showed a better effect in reducing the expression of the human epidermal growth factor receptor 2 (HER2) and Kiel 67 (Ki67) and increasing the expression of p53 in tumor tissues compared to the other origins. In conclusion, in the three origins, C1 origin exhibits antitumor pharmacological effects in vivo and in vitro which are better than those in the other origins. Conclusion: In this study, we found that with the increase of the heavy metal content, the content of steroid saponins and anti-breast cancer activity decreased. The results showed that the high content of the total heavy metals may not be conducive to the accumulation of steroidal saponins in P. polyphylla var. yunnanensis and lead to the low anti-breast cancer activity. The results of this study suggest that the content of heavy metals should be controlled in the artificial cultivation process of P. polyphylla var. yunnanensis.

Coking-Produced Aromatic Compounds in Urine of Exposed and Nonexposed Populations: Exposure Levels, Source Identification, and Model-Based Health Implications.

Coking contamination in China is complex and poses potential health risks to humans. In this study, we collected urine samples from coking plant workers, nearby residents, and control individuals to analyze 25 coking-produced aromatic compounds (ACs), including metabolites of polycyclic aromatic hydrocarbons (PAHs) and their derivatives, chlorophenols, and nitrophenols. The median concentration of total ACs in urine of workers was 102 µg·g-1 creatinine, significantly higher than that in the other two groups. Hydroxy-PAHs and hydroxy hetero-PAHs were the dominant ACs. Workers directly exposed from coking industrial processes, i.e., coking, coal preparation, and chemical production processes, showed higher concentrations of hydroxy-PAHs and hydroxy hetero-PAHs (excluding 5-hydroxyisoquinoline), while those from indirect exposure workshops had higher levels of other ACs, indicating different sources in the coking plant. The AC mixture in workers demonstrated positive effects on DNA damage and lipid peroxidation with 5-hydroxyisoquinoline and 3-hydroxycarbazole playing a significant role using a quantile g-computation model. Monte Carlo simulation revealed that coking contamination elevated the carcinogenic risk for exposed workers by 5-fold compared to controls with pyrene, pentachlorophenol, and carbazole contributing the most, and workers from coking process are at the highest risk. This study enhances understanding of coking-produced AC levels and provides valuable insights into coking contamination control.

Nontarget Screening of Novel Urinary Biomarkers for Occupational Exposure to Toxic Chemicals from Coking Industry Using HPLC-QTOF-MS.

High-resolution mass spectrometry is an advanced technique for comprehensive screening of toxic chemicals. In this study, urine samples were collected from both an occupationally exposed population at a coking site and normal inhabitants to identify novel urinary biomarkers for occupational exposure to coking contaminants. A coking-site-appropriate analytical method was developed for unknown chemical screening. Through nontarget screening, 515 differential features were identified, and finally, 32 differential compounds were confirmed as candidates for the current study, including 13 polycyclic aromatic hydrocarbon (PAH) metabolites. Besides monohydroxy-PAHs (such as 1-&2-naphthol, 2-&9-hydroxyfluorene, 2-&4-phenanthrol, and 1-&2-hydroxypyrene), many other PAH metabolites including dihydroxy metabolites, PAH oxide, and sulfate conjugate were detected, suggesting that the quantification based solely on monohydroxy-PAHs significantly underestimated the human exposure to PAHs. Furthermore, several novel compounds were recognized that could be considered as biomarkers for the exposure to coking contaminants, including quinolin-2-ol (1.10 ± 0.44 ng/mL), naphthylmethanols (11.4 ± 5.47 ng/mL), N-hydroxy-1-aminonaphthalene (0.78 ± 0.43 ng/mL), hydroxydibenzofurans (17.4 ± 7.85 ng/mL), hydroxyanthraquinone (0.13 ± 0.053 ng/mL), and hydroxybiphenyl (2.70 ± 1.03 ng/mL). Despite their lower levels compared with hydroxy-PAHs (95.1 ± 30.8 ng/mL), their severe toxicities should not be overlooked. The study provides a nontarget screening approach to identify chemicals in human urine, which is crucial for accurately assessing the health risks of toxic chemicals in the coking industry.

Heme and Cu2+-induced vasoactive intestinal peptide (VIP) tyrosine nitration: A possible molecular mechanism for the attenuated anti-inflammatory effect of VIP in inflammatory diseases.

Vasoactive intestinal peptide (VIP) is a neuropeptide that play an important role in immunoregulation and anti-inflammation. Numerous inflammatory/autoimmune disorders are associated with decreased VIP binding ability to receptors and diminished VIP activation of cAMP generation in immune cells. However, the mechanisms linking oxidative/nitrative stress to VIP immune dysfunction remain unknown. It has been reported that the elevated heme or Cu2+ in inflammatory diseases can cause oxidative and nitrative damage to nearby biological targets under high oxidative stress conditions, which affects the structure and activity of linked peptides or proteins. Thus, the VIP down-regulated immune response may be interfered by redox metal catalyzed VIP tyrosine nitration. To explore this, we systematically investigated the possibility of heme or Cu2+ to catalyze VIP tyrosine nitration. The results showed that Tyr10 and Tyr22 of VIP can both be nitrated in heme/H2O2/NO2- system as well as in Cu2+/H2O2/NO2- system. Then, we used synthetic mutant VIPs with tyrosine residues substituted by 3-nitrotyrosine to study the impact of tyrosine nitration on VIP activity in SHSY-5Y cells. Our findings demonstrated that VIP nitration dramatically decreased the content of its α-helix and random coil, suggesting that VIP nitration might reduce its affinity to the receptor. This was further confirmed in the cAMP assay. The results showed that 10 nM of these tyrosine nitrated VIPs could significantly (p < 0.01) decrease cAMP secretion compared to the wild type VIP. Our data reveal that the attenuation of the neuroprotective effect of VIP in inflammation-related diseases might be attributed to metal-catalyzed VIP tyrosine nitration.

The Relationship between VEGF and AGT Gene Single Nucleotide Polymorphisms and Susceptibility to Renal and Bladder Cancers.

BACKGROUND: We aimed to examine the relationships between the angiotensinogen (AGT) and vascular endothelial growth factor (VEGF) gene single nucleotide polymorphisms and susceptibility to bladder and kidney cancers. METHODS: A 1:1 paired case-control study was conducted, which included 143 newly diagnosed kidney cancer cases, 182 newly diagnosed bladder cancer cases, and healthy subjects in the same period collected from two hospitals. Medical records and a questionnaire were used to obtain relevant information. Genotypes were determined by improved multiple ligase detection reaction (iMLDR) and VEGF serum expression levels were detected by enzyme-linked immunosorbent assays (ELISAs). RESULTS: The VEGF gene/genotype frequencies of rs833061 and rs1570360 were statistically different among various pathological grades of kidney cancer, while the AGT rs699 gene/genotype frequencies were statistically different among various pathological types of bladder cancer. In kidney cancer, rs699 was associated with smoking, drinking, and hair coloring, while in bladder cancer, rs699, rs1570360, rs3025039, and rs833061 were associated with smoking, drinking, hair coloring, exercise, and urine holding. CONCLUSIONS: This work will help identify biomarkers that can predict the early metastasis and recurrence of kidney or bladder cancer, as well as help improve patient survival rates by predicting their susceptibility. SIGNIFICANCE: This work will provide reference for the prevention and treatment of kidney and bladder cancers.

Knockdown of lncRNA Meg3 delays the onset of puberty in female rats.

This study investigated how lncRNA Meg3 affects the onset of puberty in female rats. We determined Meg3 expression in the hypothalamus-pituitary-ovary axis of female rats at the infancy, prepubertal, pubertal, and adult life stages, using quantitative reverse transcription polymerase chain reaction (qRT-PCR). We also assessed the effects of Meg3 knockdown on the expression levels of puberty-related genes and Wnt/ß-catenin proteins in the hypothalamus, time of puberty onset, levels of reproductive genes and hormones, and ovarian morphology in female rats. Meg3 expression in the ovary varied significantly between prepuberty and puberty (P < 0.01). Meg3 knockdown decreased the expression of Gnrh, and Kiss1 mRNA (P < 0.05) and increased the expression of Wnt (P < 0.01) and ß-catenin proteins (P < 0.05) in the hypothalamic cells. Onset of puberty in Meg3 knockdown rats was delayed compared to the control group (P < 0.05). Meg3 knockdown decreased Gnrh mRNA levels (P < 0.05) and increased Rfrp-3 mRNA levels (P < 0.05) in the hypothalamus. The serum concentrations of progesterone (P4) and estradiol (E2) of Meg3 knockdown rats were lower than those in the control animals (P < 0.05). Higher longitudinal diameter and ovary weight were found in Meg3 knockdown rats (P < 0.05). These findings suggest that Meg3 regulates the expression of Gnrh, Kiss-1 mRNA and Wnt/ß-catenin proteins in the hypothalamic cells, and Gnrh, Rfrp-3 mRNA of the hypothalamus and the serum concentration of P4 and E2, and its knockdown delays the onset of puberty in female rats.

Internal exposure risk based on urinary metabolites of PAHs of occupation and non-occupation populations around a non-ferrous metal smelting plant.

The emission of various metals from non-ferrous metal smelting activities is well known. However, relative investigations on potential occupational exposure of organic pollutants are still limited. Herein, total of 619 human urine samples were collected from workers engaged in smelting activities and residents living near and/or far from the smelting sites, and ten mono-hydroxylated metabolites of polycyclic aromatic hydrocarbons (OH-PAHs) in human urine were determined. The median levels of Σ10OH-PAHs in smelting workers (25.6 ng/mL) were significantly higher (p < 0.01) than that of surrounding residents (9.00 ng/mL) and rural residents as the control (8.17 ng/mL), indicating an increase in occupational PAH exposure in non-ferrous metal smelting activities. The composition profiles of OH-PAH congeners were similar in three groups, in which naphthalene metabolites accounted for 76-82% of the total. The effects of smoking, drinking, gender, BMI, and occupational categories on urinary OH-PAHs were considered. The partial correlation analysis showed an insignificant effect of non-ferrous metal smelting activities on PAH exposure for surrounding residents. In the health risk assessments, almost all smelting workers had cancer risks exceeded the acceptable level of 10-6. This study provides a reference to occupational PAH exposure and reinforce the necessary of health monitoring among smelting workers.

Characterization and Immunogenicity of Recombinant A. flavus Uox Modified by Co/EDTA Carbon Dots.

BACKGROUND: Uricase (Uox) is a major drug in gout and a supplementary drug in cancer treatment. Because allergic reactions caused by Uox limit its clinical application,10% Co/EDTA was used to chemically modify Uox from A. flavus to reduce its immunogenicity. METHODS: The immunogenicity of Uox and 10% Co/EDTA-Uox was examined by determining the antibody titer and concentration of IL-2, IL-6, IL-10, and TNF-ß in quail and rat serum. Moreover, we examined the pharmacokinetics of 10% Co/EDTA-Uox in rats and acute toxicity in mice. RESULTS: The concentration of UA decreased from 771.85 ±180.99 to 299.47 ±20.37 µmoL/L（p<0.01） in the hyperuricemia model of quails injected by 10% Co/EDTA-Uox. Two-way immuno-diffusion electrophoresis revealed that 10% Co/EDTA-Uox did not produce antibody, whereas the antibody titer against Uox was 1:16. The concentrations of four cytokines in the 10% Co/EDTA-Uox group were significantly lower than in Uox group (p < 0.01)； The titer of IgG and IgM against 10% Co/EDTA-Uox was significantly lower than that against Uox at different serum dilutions (p < 0.0001). The pharmacokinetic data indicated that the half-life time of 10% Co/EDTA- Uox( 69.315h) was significantly longer than that of Uox(13.4 h)（p<0.01）. The tissue section of the liver, heart, kidney, and spleen revealed no toxicity in Uox and 10% Co/EDTA- Uox groups. CONCLUSION: 10% Co/EDTA-Uox possesses little immunogenicity, a long half-life time, and a highly efficient degradation of UA.

Pan-cancer analysis reveals IGFL2 as a potential target for cancer prognosis and immunotherapy.

Insulin-like growth factor like family member 2 (IGFL2) is a gene in the IGFL family, located on chromosome 19, whose role in cancer is unclear, and the aim of this study was to investigate the relevance of IGFL2 expression, prognosis, immunity, and mutation in pan-cancer. Obtaining information from The Cancer Genome Atlas and The Genotype-Tissue Expression Project (GTEx) databases for expression analysis and combining with The Gene Expression Profile Interaction Analysis database for prognostic aspects. Analysis of immune cell infiltration by TIMER and CIBERSORT algorithms. Calculation of correlation of immune-related genes with IGFL2 expression and tumor mutational burden and microsatellite instability. Mutations and DNA methylation were analyzed using the cBioPortal database and the UALCAN database, and functional enrichment was performed using Gene set enrichment analysis (GSEA). IGFL2 expression is significantly elevated in tumor tissue and high expression has a worse prognosis in most cancers. In immune correlation analysis, it was associated with most immune cells and immune-related genes. In most cancers, IGFL2 methylation is lower and the group with mutations in IGFL2 has a worse prognosis than the normal group. The GSEA analysis showed that IGFL2 was significantly enriched in signaling and metabolism. IGFL2 may be involved in the development of many types of cancer, influencing the course of cancer with different biological functions. It may also be a biomarker for tumor immunotherapy.

Myosin light-chain 4 gene-transfer attenuates atrial fibrosis while correcting autophagic flux dysregulation.

OBJECTIVES: To determine the role of MYL4 regulation of lysosomal function and its disturbance in fibrotic atrial cardiomyopathy. BACKGROUND: We have previously demonstrated that the atrial-specific essential light chain protein MYL4 is required for atrial contractile, electrical, and structural integrity. MYL4 mutation/dysfunction leads to atrial fibrosis, standstill, and dysrhythmia. However, the underlying pathogenic mechanisms remain unclear. METHODS AND RESULTS: Rats subjected to knock-in of a pathogenic MYL4 mutant (p.E11K) developed fibrotic atrial cardiomyopathy. Proteome analysis and single-cell RNA sequencing indicate enrichment of autophagy pathways in mutant-MYL4 atrial dysfunction. Immunofluorescence and electron microscopy revealed undegraded autophagic vesicles accumulated in MYL4p.E11K rat atrium. Next, we identified that dysfunctional MYL4 protein impairs autophagy flux in vitro and in vivo. Cardiac lysosome positioning and mobility were regulated by MYL4 in cardiomyocytes, which affected lysosomal acidification and maturation of lysosomal cathepsins. We then examined the effects of MYL4 overexpression via adenoviral gene-transfer on atrial cardiomyopathy induced by MYL4 mutation: MYL4 protein overexpression attenuated atrial structural remodeling and autophagy dysfunction. CONCLUSIONS: MYL4 regulates autophagic flux in atrial cardiomyocytes via lysosomal mobility. MYL4 overexpression attenuates MYL4 p.E11K induced fibrotic atrial cardiomyopathy, while correcting autophagy and lysosomal function. These results provide a molecular basis for MYL4-mutant induced fibrotic atrial cardiomyopathy and identify a potential biological-therapy approach for the treatment of atrial fibrosis.

How does carbon emissions trading scheme affect steel enterprises' pollution control performance? A quasi natural experiment from China.

Taking advantage of a 2005-2018 sample of 86 Chinese steel enterprises (CSEs) and the difference-in-differences method, this paper utilizes the carbon emissions trading scheme (ETS) - as a quasi-natural experiment to investigate the impact of the carbon ETS on the total factor pollution control efficiency (TFPCE) of CSEs to test the green development effect of the carbon ETS. Then, the green development effect of the carbon ETS is empirically tested by a variety of robustness tests, such as DDD and PSM-DID. The results show that the carbon ETS policy significantly improves the TFPCE of CSEs located in the pilot area, generating the green development effect, and that this the annual effect lags by one year. Additionally, the channel analysis from the perspective of enterprise internal management and the external environment shows that strategic innovation, substantive innovation and institutional quality play a positive role in enhancing pollution control performance respectively. The heterogeneity test shows that the green development effect is better for state-owned CSEs and CSEs located in the eastern and central China. The conclusion has significant implications for green and low-carbon development in heavy pollution industries and has implications for further promoting the implementation of market-oriented environmental regulations.

Spatial distribution, source identification, and human health risk assessment of PAHs and their derivatives in soils nearby the coke plants.

The coking industry can generate large amounts of polycyclic aromatic hydrocarbons (PAHs) and their derivatives, which may negatively impact the environment and human health. In this study, soils nearby a typical coking plant were sampled to assess the impact of coke production on the surrounding residential areas and human health. The mean concentration of PAHs and their derivatives in residential area soils nearby the coke plant was 4270 ng/g dw, which was 1 order of magnitude higher than that observed in areas far from the coke plant and approximately 4 times lower than that revealed the coke plant. In addition, the results showed that coking processing area was the most contaminant area of the coke plant (mean: 74.4 µg/g dw), where was also the main source of pollutants in residential areas. In terms of vertical soils in coking plant, the maximum levels of chemicals (mean: 205 µg/g dw) were presented at the leakage of underground pipelines, where were much higher than those in surface soils, and decreased with the increase of depth. The analysis of variance (ANOVA) results showed obvious differences in the concentrations of 6-nitrochrysene between the plant, residential areas and control areas. Meanwhile, 6-nitrochrysene had potential cancer risk (CR) for human in the coking site. Thus, 6-nitrochrysene was the most noteworthy PAH derivatives. Furthermore, the CR (mean: 5.94 × 10-5) and toxic equivalent quantities (TEQs) (mean: 14.8 µg·TEQ/g) of PAHs and their derivatives was assessed in this study. This finding suggested that PAHs and their derivatives especially those extremely toxic chemicals (Nitro-PAHs (NPAHs) and Br/Cl-PAHs (XPAHs)) might pose a potential health risk to residents nearby the coke plant. The current study provides further insights into the pollution characteristics of PAHs and their derivatives in coke plants and potential risks to the workers and surrounding residents.

Structure-activity relationship of a housefly neuroprotective dodecapeptide that activates the nuclear factor erythroid 2-related factor 2 pathway.

Neuroprotective antioxidants, especially peptide-based antioxidants, are effective against oxidative stress in neurodegenerative disorders. In this study, we measured the neuroprotective effects of the antioxidant peptide DFTPVCTTELGR (DR12) from housefly Musca domestica L. pupae. Treatment of PC12 and HT22 cells with DR12 significantly reduced glutamate-induced cytotoxicity. Peptide DR12 appeared to exert its neuroprotective effects by attenuating production of reactive oxygen species and malonaldehyde, upregulating the endogenous antioxidants superoxide dismutase and glutathione, and reversing the loss of mitochondrial membrane potential. In addition, DR12 treatment activated the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway. Structure-activity analysis indicated that the superior neuroprotective function of DR12 was related to its cysteine residue. In summary, DR12 may be an attractive therapeutic peptide or precursor to treat neurodegenerative diseases.

Premature mortality from four chronic diseases in Wuhai, China and impact on life expectancy, 2015 to 2020.

To analyze the change trend of life expectancy, the change trend of premature death due to 4 major chronic diseases, and its impact on the life expectancy of Wuhai residents from 2015 to 2020, and to provide evidence for the prevention and control of chronic diseases in this area. The data on population death comes from the Wuhai City Residents' Causes of Death Network Reporting System and the total population is calculated using statistics from Wuhai City's permanent population management, from 2015 to 2020. Premature mortality from the 4 main chronic illnesses was calculated using the abridged life table approach. The impact of premature death from chronic diseases on life expectancy was analyzed using the Arriaga method. The increasing trend of life expectancy of Wuhai citizens was not statistically significant from 2015 to 2020 (t = 2.570, P = .062). Each year, men had a lower life expectancy than women (P < .05). From 2015 to 2020, the downward trend of premature deaths caused by the 4 major non-communicable diseases in Wuhai City was statistically significant (EAPC = -7.74%, P = .041). Premature death from cancer and chronic respiratory disorders decreased, both of which were statistically significant (EAPC < 0, P < .05). The decline in premature mortality from cancer, cardiovascular and cerebrovascular disorders, and chronic respiratory system diseases has contributed to increased life expectancy. Diabetes's rise in premature mortality made a possible "negative contribution" to life expectancy (-0.036 years, -1.79%). From 2015 to 2020, the decreasing trend of the overall premature mortality caused by the 4 major non-communicable diseases in Wuhai was statistically significant, and the life expectancy of females was higher than that of males. We should concentrate on the prevention and control of major chronic illnesses in males, as well as the influence of changes in diabetes-related early mortality on life expectancy.

The expression of IGFBP-5 in the reproductive axis and effect on the onset of puberty in female rats.

Insulin-like growth factor-binding protein-5 (IGFBP-5) has recently been shown to alter the reproductive capacity by regulating insulin-like growth factor (IGF) bioavailability or IGF-independent effects. The present study aimed to investigate the effect and mechanism of IGFBP-5 on the onset of puberty in female rats. Immunofluorescence and real-time quantitative PCR were used to determine the expression and location of IGFBP-5 mRNA and protein distribution in the infant's hypothalamus-pituitary-ovary (HPO) axis prepuberty, peripuberty, puberty and adult female rats. Prepubertal rats with IGFBP-5 intracerebroventricular (ICV) were injected to determine the puberty-related genes expression and the concentrations of reproductive hormones. Primary hypothalamic cells were treated with IGFBP-5 to determine the expression of puberty-related genes and the Akt and mTOR proteins. Results showed that Igfbp-5 mRNA and protein were present on the HPO axis. The addition of IGFBP-5 to primary hypothalamic cells inhibited the expression of Gnrh and Igf-1 mRNAs (P < 0.05) and increased the expression of AKT and mTOR protein (P < 0.01). IGFBP-5 ICV-injection delayed the onset of puberty, reduced Gnrh, Igf-1, and Fshß mRNAs, and decreased the concentrations of E2, P4, FSH,serum LH levels and the ovaries weight (P < 0.05). More corpus luteum and fewer primary follicles were found after IGFBP-5 injection (P < 0.05).

Quantitative proteomics analysis to assess protein expression levels in the ovaries of pubescent goats.

BACKGROUND: Changes in the abundance of ovarian proteins play a key role in the regulation of reproduction. However, to date, no studies have investigated such changes in pubescent goats. Herein we applied isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography-tandem mass spectrometry to analyze the expression levels of ovarian proteins in pre-pubertal (n = 3) and pubertal (n = 3) goats. RESULTS: Overall, 7,550 proteins were recognized; 301 (176 up- and 125 downregulated) were identified as differentially abundant proteins (DAPs). Five DAPs were randomly selected for expression level validation by Western blotting; the results of Western blotting and iTRAQ analysis were consistent. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that DAPs were enriched in olfactory transduction, glutathione metabolism, and calcium signaling pathways. Besides, gene ontology functional enrichment analysis revealed that several DAPs enriched in biological processes were associated with cellular process, biological regulation, metabolic process, and response to stimulus. Protein-protein interaction network showed that proteins interacting with CDK1, HSPA1A, and UCK2 were the most abundant. CONCLUSIONS: We identified 301 DAPs, which were enriched in olfactory transduction, glutathione metabolism, and calcium signaling pathways, suggesting the involvement of these processes in the onset of puberty. Further studies are warranted to more comprehensively explore the function of the identified DAPs and aforementioned signaling pathways to gain novel, deeper insights into the mechanisms underlying the onset of puberty.

Short-term association of PM 2.5 /PM 10 on lung cancer mortality in Wuhai city, China (2015-2019): a time series analysis.

OBJECTIVE: The objective of this study was to evaluate the relationship between short-term fine particulate matter (PM 2.5 )/inhalable particulate matter (PM 10 ) exposure and lung cancer mortality. METHOD: From 2015 to 2019, data concerning air pollution, meteorology, and deaths were obtained in Wuhai, China. The association between PM 2.5 /PM 10 and lung cancer mortality was investigated using time series analysis. RESULT: According to the single-pollutant model, a 10 µg/m 3 increase in PM 2.5 /PM 10 was associated with an excess risk of 7.95% (95% CI, 2.22-13.95%), and 2.44% (95% CI, 0.32-4.62%), respectively ( P < 0.05). PM 2.5 /PM 10 had a stronger impact on men and the elderly (>65 years old). Particulate matter had a larger influence on lung cancer mortality during the warm season than the cold season. Furthermore, except for PM 2.5 and PM 10 , the two-pollution model indicated that the other models were statistically significant. The study's single and dual pollutant models were both relatively robust. CONCLUSION: Short-term exposure to PM 2.5 /PM 10 was correlated with a higher risk of lung cancer death in Wuhai, particularly among men and the elderly (>65 years old). Exposure to PM 2.5 /PM 10 really does have a bigger effect on the population during the warm season. Moreover, it is essential that health administration departments should strengthen their regulatory mechanisms for particulate emissions and take the responsibility for safeguarding the vulnerable populations.