Lung injuries induced by ozone exposure in female mice: Potential roles of the gut and lung microbes.

Ozone (O3) is one of the most harmful pollutants affecting health. However, the potential effects of O3 exposure on microbes in the gut-lung axis related to lung injuries remain elusive. In this study, female mice were exposed to 0-, 0.5- and 1-ppm O3 for 28 days, followed by routine blood tests, lung function tests and histopathological examination of the colon, nasal cavity and lung. Mouse faeces and lungs were collected for 16s rRNA sequencing to assess the overall microbiological profile and screen for key differential enriched microbes (DEMs). The key DEMs in faecal samples were Butyricimonas, Rikenellaceae RC9 and Escherichia-Shigella, whereas those in lung samples were DNF00809, Fluviicola, Bryobacter, Family XII AD3011 group, Sharpea, MND1 and unclassified Phycisphaeraceae. After a search in microbe-disease databases, these key DEMs were found to be associated with lung diseases such as lung neoplasms, cystic fibrosis, pneumonia, chronic obstructive pulmonary disease, respiratory distress syndrome and bronchiectasis. Subsequently, we used transcriptomic data from Gene Expression Omnibus (GEO) with exposure conditions similar to those in this study to cross-reference with Comparative Toxicogenomic Database (CTD). Il-6 and Ccl2 were identified as the key causative genes and were validated. The findings of this study suggest that exposure to O3 leads to significant changes in the microbial composition of the gut and lungs. These changes are associated with increased levels of inflammatory factors in the lungs and impaired lung function, resulting in an increased risk of lung disease. Altogether, this study provides novel insights into the role of microbes present in the gut-lung axis in O3 exposure-induced lung injury.

Invisible Hand behind Female Reproductive Disorders: Bisphenols, Recent Evidence and Future Perspectives.

Reproductive disorders are considered a global health problem influenced by physiological, genetic, environmental, and lifestyle factors. The increased exposure to bisphenols, a chemical used in large quantities for the production of polycarbonate plastics, has raised concerns regarding health risks in humans, particularly their endocrine-disrupting effects on female reproductive health. To provide a basis for future research on environmental interference and reproductive health, we reviewed relevant studies on the exposure patterns and levels of bisphenols in environmental matrices and humans (including susceptible populations such as pregnant women and children). In addition, we focused on in vivo, in vitro, and epidemiological studies evaluating the effects of bisphenols on the female reproductive system (the uterus, ovaries, fallopian tubes, and vagina). The results indicate that bisphenols cause structural and functional damage to the female reproductive system by interfering with hormones; activating receptors; inducing oxidative stress, DNA damage, and carcinogenesis; and triggering epigenetic changes, with the damaging effects being intergenerational. Epidemiological studies support the association between bisphenols and diseases such as cancer of the female reproductive system, reproductive dysfunction, and miscarriage, which may negatively affect the establishment and maintenance of pregnancy. Altogether, this review provides a reference for assessing the adverse effects of bisphenols on female reproductive health.

A single-center analysis of genotype-phenotype characteristics of Chinese patients with autosomal dominant polycystic kidney disease by targeted exome sequencing.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by PKD1 and PKD2 mutations. However, only a few studies have investigated the genotype and phenotype characteristics of Asian patients with ADPKD. This study aimed to investigate the relationship between the natural course of ADPKD genotype and phenotype. Methods: Genetic studies of PKD1/2 genes of Chinese patients with ADPKD in a single center were performed using targeted exome sequencing and next-generation sequencing on peripheral blood DNA. Results: Among the 140 patients analyzed, 80.00% (n = 112) harbored PKD1 mutations, 11.43% (n = 16) harbored PKD2 mutations, and 8.57% (n = 12) harbored neither PKD1 nor PKD2 mutations. The average age at dialysis was 52.60 ± 11.36, 60.67 ± 5.64, and 52.11 ± 14.63 years, respectively. The renal survival rate of ADPKD patients with PKD1 mutations (77/112) was significantly lower than that of those with PKD2 mutations (9/16), leading to an earlier onset of end-stage renal disease (ESRD). Renal prognosis was poor for those with nonsense mutations, and they required earlier renal replacement therapy. Conclusions: The genotype and phenotype characteristics of ADPKD patients potentially vary across ethnic groups. Our findings supplement the genetic profiles of Chinese ADPKD patients, could serve as a guide for therapy monitoring and prognosis assessment of ADPKD, and may improve the clinical diagnosis.

Delegate contract signing mechanism based on smart contract.

In this paper, a delegate contract signing solution is proposed to eliminate the potential risk of contract fraud caused by information and interest asymmetry. By utilizing the functional properties of the Ethereum blockchain and smart contracts, a delegate contract signing mechanism is established. By running the mechanism, the delegate contract signing information is received and processed, and the information is broadcast to the blockchain network nodes. By designing the algorithms of "requesting contract signing", "successful contract signing" and "contract fraud dispute resolution", the delegate contract signing is realized. By proposing algorithms and their calling processes, the smart contracts are completed. Finally, the smart contracts based on the solution are tested and verified. The source code of the smart contracts has been published on GitHub.

Genome-wide profiling of BK polyomavirus integration in bladder cancer of kidney transplant recipients reveals mechanisms of the integration at the nucleotide level.

Chronic BK polyomavirus (BKPyV) infection is recognized as a potential oncogenic factor of urothelial carcinoma (UC) in renal transplant recipients. Recent studies have reported a positive correlation among BKPyV integration, persistent overexpression of viral large T antigen (TAg), and malignancy, yet little is known about the specific integration mechanisms and the impacts of viral integration. Here, we performed whole-genome sequencing (WGS) and viral capture-based sequencing on high-grade immunohistochemically TAg-positive UCs in two renal transplant recipients. A total of 181 integration sites, including the three found by WGS, were identified by viral capture-based sequencing, indicating its enhanced sensitivity and ability in identifying low-read integration sites in subpopulations of the tumor cells. The microhomologies between human and BKPyV genomes were significantly enriched in the flanking regions of 84.5% the integration sites, with a median length of 7 bp. Notably, 75 human genes formed fusion sequences due to viral insertional integration. Among them, the expression of 15 genes were statistically associated with UC based on GEO2R expression analysis. Our results indicated a multisite and multifragment linear integration pattern and a potential microhomology or nonhomologous end joining integration mechanism at the single-nucleotide level. We put forward a potential selection mechanism driven by immunity and centered on viral integration in the carcinogenesis of BKPyV.

[Application of immunosuppressants in patients with autosomal dominant polycystic kidney disease after kidney transplantation].

OBJECTIVE: To investigate the optimal dose range of immunosuppressants in patients with autosomal dominant polycystic kidney disease (ADPKD) after renal transplantation. METHODS: A cohort of 68 patients with ADPKD who received their first renal transplantation between March, 2000 and January, 2018 in our institute were retrospectively analyzed, with 68 non-ADPKD renal transplant recipients matched for gender, age and date of transplant as the control group. We analyzed the differences in patient and renal survival rates, postoperative complications and concentrations of immunosuppressive agents between the two groups at different time points within 1 year after kidney transplantation. The concentrations of the immunosuppressants were also compared between the ADPKD patients with urinary tract infections (UTI) and those without UTI after the transplantation. RESULTS: The recipients with ADPKD and the control recipients showed no significantly difference in the overall 1-, 5-, and 10- year patient survival rates (96.6% vs 96.0%, 94.1% vs 93.9%, and 90.6% vs 93.9%, respectively; P > 0.05), 1-, 5-, and 10-year graft survival rates (95.2% vs 96.0%, 90.8% vs 87.2%, and 79.0% vs 82.3%, respectively; P > 0.05), or the incidences of other post- transplant complications including acute rejection, gastrointestinal symptoms, cardiovascular events, pneumonia, and neoplasms (P > 0.05). The plasma concentrations of both tacrolimus and mycophenolate mofetil (MPA) in ADPKD group were significantly lower than those in the control group at 9 months after operation (P < 0.05). The incidence of UTI was significantly higher in ADPKD patients than in the control group (P < 0.05). In patients with ADPKD, those with UTI after transplantation had a significantly higher MPA plasma concentration (P < 0.05). CONCLUSIONS: In patients with ADPKD after renal transplant, a higher dose of MPA is associated with a increased risk of UTI, and their plasma concentrations of immunosuppressants for long-term maintenance of immunosuppression regimen can be lower than those in other kidney transplantation recipients.

Hot Deformation Behavior Considering Strain Effects and Recrystallization Mechanism of an Al-Zn-Mg-Cu Alloy.

The hot deformation behavior of an Al-Zn-Mg-Cu alloy was investigated by hot compression test at deformation temperatures varying from 320 to 440 °C with strain rates ranging from 0.01 to 10 s-1. The results show that the Mg(Zn, Cu)2 particles as a result of the sufficient static precipitation prior to hot compression have an influence on flow softening. A constitutive model compensated with strain was developed from the experimental results, and it proved to be accurate for predicting the hot deformation behavior. Processing maps at various strains were established. The microstructural evolution demonstrates that the dominant dynamic softening mechanism stems from dynamic recovery (DRV) and partial dynamic recrystallization (DRX). The recrystallization mechanism is continuous dynamic recrystallization (CDRX). The microstructure observations are in good agreement with the results of processing maps. On account of the processing map and microstructural observation, the optimal hot processing parameters at a strain of 0.6 are at deformation temperature range of 390-440 °C and strain rate range of 0.010-0.316 s-1 with a peak efficiency of 0.390.

P-Texture Effect on the Fatigue Crack Propagation Resistance in an Al-Cu-Mg Alloy Bearing a Small Amount of Silver.

P-texture effect on the fatigue crack propagation (FCP) resistance in an Al-Cu-Mg alloy containing a small amount of Ag, is investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and electron back scattering diffraction (EBSD). Results shows that the high intensity P-texture sheet has lower σ 0.2 / σ b , lower FCP rate and higher damage tolerance than random texture sheet. Fracture analysis indicates that the striations spacing of high intensity P-texture sheet is much smaller than that of random texture sheet and it has a rougher fatigue fracture surface, which causes a significant roughness induced crack closure (RICC) effect. The calculation results manifest that high intensity P-texture sheet possesses a higher crack closure level reaching 0.73 as compared to random texture sheet (only 0.25). The statistical analysis results reveal the P-grains have large twist angle of 105⁻170° and tilt angle of 5⁻60° with neighboring grains, which is similar to Goss-grains. This is the fundamental reason that P-texture sheet has the same FCP resistance and induces fatigue crack deflection as Goss-texture sheet. Additionally, the most {111} slipping planes of P-grains are distributed in the range of 30⁻50° deviating from transverse direction of the sheet. This results in more {111} slipping planes to participate in cyclic plastic deformation, which is beneficial to reduce fatigue damage accumulation and improve the damage tolerance of Al-Cu-Mg-Ag alloy.

Seroprevalence of hepatitis B virus in Taiwan 30 years after the commencement of the national vaccination program.

BACKGROUND: In this study, the long-term efficacy of hepatitis B virus (HBV) vaccination was assessed using seroprevalence and an age-period-cohort (APC) model of HBV seromarkers among university entrants 30 years after the introduction of the national neonatal HBV vaccination program in Taiwan. METHODS: In total, data of 17,611 university entrants who underwent university entrance health examinations between 2005 and 2016 were included. The seroprevalence of the HBV surface antigen (HBsAg) and the levels of the antibody against the HBV surface antigen (anti-HBs) in each year group and sex were calculated. The levels of the antibody against the HBV core antigen were examined only for 2012 and 2016. The APC model was used to analyze the HBV carrier rates. RESULTS: The chronic HBV infection (HBsAg positivity) rate decreased from 9.7% in university students born before June 1974 to <1.0% in students born after 1992. The prevalence of anti-HBs positivity declined, particularly between the 1984-1988 cohort (78.2%-53.2%) and the 1990-1994 cohort (60.6%-44.4%). Our APC model revealed that the chronic HBV carrier rate among the student population was affected significantly by age, period, and cohort (P < 0.001). CONCLUSIONS: HBV vaccination is one of the most effective strategies for preventing HBV infection. However, for complete eradication of HBV infection, the development of strategies that detect vaccination failure more effectively than current strategies do and early implementation of appropriate treatments are both necessary.