Major changes in prevalence and genotypes of rotavirus diarrhea in Beijing, China after RV5 rotavirus vaccine introduction.

To analyze the epidemiological characteristics of group A rotavirus (RVA) diarrhea in Beijing between 2019 and 2022 and evaluate the effectiveness of the RV5 vaccine. Stool specimens were collected from patients with acute diarrhea, and RVA was detected and genotyped. The whole genome of RVA was sequenced by fragment amplification and Sanger sequencing. Phylogenetic trees were constructed using Bayesian and maximum likelihood methods. Descriptive epidemiological methods were used to analyze the characteristics of RVA diarrhea. Test-negative design was used to evaluate the vaccine effectiveness (VE) of the RV5. Compared with 2011-2018, RVA-positive rates in patients with acute diarrhea under 5 years of age and adults decreased significantly between 2019 and 2022, to 9.45% (249/634) and 3.66% (220/6016), respectively. The predominant genotype of RVA had changed from G9-VIP[8]-III between 2019 and 2021 to G8-VP[8]-III in 2022, and P[8] sequences from G8-VP[8]-III strains formed a new branch called P[8]-IIIb. The complete genotype of G8-VP[8]-III was G8-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. The VE of 3 doses of RV5 was 90.4% (95% CI: 28.8%-98.7%) against RVA diarrhea. The prevalence of RVA decreased in Beijing between 2019 and 2022, and the predominant genotype changed to G8P[8], which may be related to RV5 vaccination. Continuous surveillance is necessary to evaluate vaccine effectiveness and improve vaccine design.

Cost-effectiveness of latent tuberculosis infection testing and treatment with 6-week regimen among key population in rural communities in China: a decision analysis study.

PURPOSE: Several model studies suggested the implementation of latent tuberculosis infection (LTBI) testing and treatment could greatly reduce the incidence of tuberculosis (TB) and achieve the 2035 target of the "End TB" Strategy in China. The present study aimed to evaluate the cost-effectiveness of LTBI testing and TB preventive treatment among key population (≥ 50 years old) susceptible to TB at community level in China. METHODS: A Markov model was developed to investigate the cost-effectiveness of LTBI testing using interferon gamma release assay (IGRA) and subsequent treatment with 6-month daily isoniazid regimen (6H) (as a standard regimen for comparison) or 6-week twice-weekly rifapentine and isoniazid regimen (6-week H2P2) in a cohort of 10,000 adults with an average initial age of 50 years. RESULTS: In the base-case analysis, LTBI testing and treatment with 6H was dominated (i.e., more expensive with a lower quality-adjusted life year (QALY)) by LTBI testing and treatment with 6-week H2P2. LTBI testing and treatment with 6-week H2P2 was more effective than no intervention at a cost of $20,943.81 per QALY gained, which was below the willingness-to-pay (WTP) threshold of $24,211.84 per QALY gained in China. The one-way sensitivity analysis showed the change of LTBI prevalence was the parameter that most influenced the results of the incremental cost-effectiveness ratios (ICERs). CONCLUSION: As estimated by a Markov model, LTBI testing and treatment with 6-week H2P2 was cost-saving compared with LTBI testing and treatment with 6H, and it was considered to be a cost-effective option for TB control in rural China.

Excess acute diarrhoea cases attributed to norovirus variants in Beijing, China between 2011 and 2018.

New norovirus (NoV) variants emerge often leading to increased acute gastroenteritis outbreaks and outpatient visits. However, these increases are rarely quantified. Between September 2011 and August 2018, we included a total of 133 131 acute diarrhoea cases in 11 enteric disease outpatient clinics which were open all year round in Beijing. Over the same period, the etiology surveillance for acute diarrhoea was conducted, a total of 13 139 specimens were collected and tested, and 16.84% (2213/13 139) of all specimens were NoV-positive. The partial VP1 genes were successfully sequenced in 965 NoV strains. GII.4 Sydney, GII.17, and GII.2 predominated in 2012-2013, 2014-2015, and 2016-2017, respectively. We estimated the excess NoV-associated acute diarrhoea cases using the adjusted Serfling regression model, and three excess periods were found, corresponding to the predominance periods of GII.4 Sydney, GII.17 and GII.2, respectively, represented increases of 180.5% (95% confidence interval [CI]: 115.0%-246.0%), 114.7% (95% CI: 66.4%-163.1%) and 152.6% (95% CI: 100.2%-205.0%), compared with the baseline level. New NoV variants often caused an excess in their first year of predominance, and the excess periods of NoV-associated acute diarrhoea cases coincided with the predominance periods of NoV variants.

Transmissibility quantification of norovirus outbreaks in 2016-2021 in Beijing, China.

The transmissibility is a crucial feature for norovirus, yet its quantitative estimation has been limited. Our objective was to estimate the basic reproduction number (R0 ) of norovirus and investigate its variation characteristics. Norovirus outbreaks reported from September 2016 to August 2021 in Beijing were analyzed. The susceptible-infected-removed compartment model was established to estimate R0 . Linear regression models and logistic regression models were used to explore the factors affecting the transmissibility of norovirus. The overall median R0 of norovirus was estimated as 2.1 (interquartile range [IQR] 1.8-2.5), with 650 norovirus outbreaks. The transmissibility of norovirus varied by year, outbreak setting and genotype. The R0 of norovirus during September 2019 to August 2020 (median 2.1, IQR 1.8-2.4) and September 2020 to August 2021 (median 2.0, IQR 1.7-2.3) was lower than that of September 2016 to August 2017 (median 2.3, IQR 1.8-2.7) (ß = 0.94, p = 0.05; ß = 0.93, p = 0.008). The R0 of norovirus for all other settings was lower than that for kindergarten (median 2.4, IQR 2.0-2.9) (primary school: median 2.0, IQR 1.7-2.4, ß = 0.94, p = 0.001; secondary school: median 1.7, IQR 1.5-2.0, ß = 0.87, p < 0.001; college: median 1.7, IQR 1.5-1.8, ß = 0.89, p = 0.03; other closed settings: median 1.8, IQR 1.5-2.0, ß = 0.90, p = 0.004). GⅡ.2[P16] outbreaks had a median R0 of 2.2 (IQR 1.8-2.7), which was higher than that for GⅡ.6[P7] outbreaks (median 1.8, IQR: 1.8-2.0, odds ratio = 0.19, p = 0.03; GⅡ.2[P16] as reference) and mixed-genotype outbreaks (median 1.7, IQR: 1.5-1.8, ß = 0.92, p = 0.02; mixed-genotype as reference). In kindergartens and primary schools, norovirus shows increased transmissibility, emphasizing the vulnerable population and high-risk settings. Furthermore, the transmissibility of norovirus may change over time and with virus evolution, necessitating additional research to uncover the underlying mechanisms.

Spatio-temporal distribution and influencing factors of norovirus outbreaks in Beijing, China from 2016 to 2020.

BACKGROUND: Noroviruses are a leading cause of acute gastroenteritis (AGE) worldwide. The geographical characteristics of norovirus outbreaks in Beijing and their influencing factors remain unknown. This study aimed to explore the spatial distributions, geographical characteristics, and influencing factors of norovirus outbreaks in Beijing, China. METHODS: Epidemiological data and specimens were collected through the AGE outbreak surveillance system in all 16 districts of Beijing. Data on spatial distribution, geographical characteristics, and influencing factors of norovirus outbreaks were analyzed using descriptive statistics methods. We measured spatial, geographical clustering of high- or low-value deviance from random distribution using Z-scores and P-values as statistical significance measures with Global Moran's I statistics and Getis-Ord Gi in ArcGIS. Linear regression and correlation methods were used to explore influencing factors. RESULTS: Between September 2016 and August 2020, 1,193 norovirus outbreaks were laboratory-confirmed. The number of outbreaks varied seasonally, typically peaking in spring (March to May) or winter (October to December). Outbreaks primarily occurred around central districts at the town level, and spatial autocorrelation was evident in both the entire study period and in individual years. Hotspots of norovirus outbreaks in Beijing were primarily found in contiguous areas between three central districts (Chaoyang, Haidian, Fengtai) and four suburban districts (Changping, Daxing, Fangshan, Tongzhou). The average population numbers, mean number of all schools, and mean number of kindergartens and primary schools for towns in central districts and hotspot areas were higher than those in suburban districts and non-hotspot areas respectively. Additionally, population numbers and densities of kindergartens and primary schools were influencing factors at the town level. CONCLUSIONS: Hotspots of norovirus outbreaks in Beijing were in contiguous areas between central and suburban districts with high populations, and high kindergarten and primary school densities were the likely driving forces. Outbreak surveillance needs to focus on contiguous areas between central and suburban districts with increased monitoring, medical resources, and health education.

Association between serum homocysteine and sarcopenia among hospitalized older Chinese adults: a cross-sectional study.

OBJECTIVE: Hyperhomocysteinemia (HHcy) is considered to increase the risk of sarcopenia (S) and remains controversial. In this study, we aimed to investigate the prevalence of S among older Chinese adults and explore whether homocysteine (Hcy) was independently associated with S. METHODS: This cross-sectional study was performed among older adults hospitalized in the Geriatric Hospital of Nanjing Medical University between June 2017 and December 2021. We measured all participants' serum Hcy levels, hand grip strength, gait speed and appendicular skeletal muscle index(ASMI) using bioelectrical impedance analysis (BIA). S was defined based on the criteria of the Asian Working Group for Sarcopenia 2 (AWGS2), which included muscle mass (ASMI< 7.0 kg/m2 for men and ASMI< 5.7 kg/m2 for women by BIA) and low muscle strength (handgrip strength < 28 kg for men and < 18 kg for women), and/or gait speed < 1.0 m/s. HHcy defined as Hcy ≥10 µmol/L. The strength of the association between Hcy and the risk of S was analyzed by multivariate logistic regression using three models that adjusted for possible confounding variables to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among the 441 subjects, 161 (36.5%) were diagnosed with S, and 343 (77.8%) were diagnosed with HHcy. A significant association was detected between S and serum Hcy per 1-µmol/L increase after adjustment for age, gender, education, smoking, body mass index (BMI), Mini Nutritional Assessment Short Form (MNA-SF), alanine aminotransferase (ALT), C-reactive protein (CRP), hemoglobin (Hb), albumin (ALB), diabetes, kidney disease, and statin use (OR = 1.07, 95% CI = 1.03-1.12, P = 0.002). The OR for S in the HHcy group (≥10 µmol/L) was nearly 5-fold that in the normal Hcy group (OR 4.96, 95% CI 2.67-9.24, P < 0.001). In a gender-based subgroup analysis that adjusted for age, education, smoking, BMI, MNA-SF, ALT, CRP, Hb, and ALB, female subjects with HHcy had an increased risk of S (OR 10.35, 95% CI 2.84-37.68, P < 0.001). CONCLUSIONS: Our results demonstrated that elevated Hcy levels have an independent association with S in older adults. This suggests that the downward adjustment of HHcy (cutoff value < 10 µmol/l) might decrease the risk of S.

Seroepidemiology of enterovirus D68 in a healthy population in Beijing, China, between 2012 and 2017: A retrospective study.

To investigate the seroepidemiological features of enterovirus D68 (EV-D68) in the healthy population from 2012 to 2017 in Beijing, China. A retrospective cross-sectional investigation was conducted using serum specimens collected from healthy individuals in Beijing from 2012 to 2017. These samples were tested for neutralization antibodies (NtAbs) against EV-D68. The sera from six EV-D68 infected patients in the acute or convalescent phase were used to determine the protection level of NtAbs against EV-D68. The geometric means of the titers (GMT) of EV-D68 NtAbs in 2012 and 2017 were 92.82 and 242.91, respectively; the seroprevalences of EV-D68 were 89.43% and 98.43%, respectively. The GMT reached its peak in the 11 to 15 age group in 2012, while in 16 to 20 age group in 2017. We also observed that EV-D68 NtAbs titers of six sera from the acute phase were all less than equal to 1:64 and that of three sera from the convalescent phase were all more than 1:64. Anti-EV-D68 NtAbs in the population remained low from 2012 to 2016 but increased significantly in 2017. Although most of the EV-D68 infections remain undetected in Beijing, the risk of a large outbreak of EV-D68 exists and should be taken seriously.

Association of Helicobacter pylori infection with colorectal adenoma in the Chinese urban population: A cross-sectional study.

OBJECTION: Helicobacter pylori (H. pylori) infection is considered to increase the risk of colorectal adenoma (CRA) and remains controversial. In this study, we aimed to evaluate the association between H. pylori infection and CAR in the Chinese urban population. METHODS: A cross-sectional study of 301 urban adults, who underwent both screening colonoscopy and 13C urea breath test (13C UBT) from June 2018 to December 2019 at Geriatric Hospital of Nanjing Medical University, was carried out to assess the relationship between H. pylori infection and CRA. All baseline characteristics and laboratory examination of subjects were collected and analyzed by specific personnel. The strength of association between H. pylori infection and the risk of CRA was described by multivariate logistic regression analyses to calculate the odds ratios (ORs) and 95% confidence interval (CIs). RESULTS: Among the 301 subjects, 82 (27.24%) patients with H. pylori positive and 141 (46.84%) were confirmed to have CRA. Multivariate analysis adjusted for age, gender, uric acid and fatty liver revealed that H. pylori infection increased the risk of CRA significantly (adjusted OR 2.007, 95%CI 1.153-3.492, p = 0.014). In addition, the correlation between H. pylori infection and CRA persisted after further adjusting for metabolic variables (adjusted OR 2.029, 95%CI 1.161-3.544, p = 0.013) or other potential confounding factors related to CRA including smoking status, alcohol intake, cholecystitis and gallstone (adjusted OR 1.996, 95%CI 1.141-3.492, p = 0.015). In a gender-based subgroup analysis, H. pylori infection had an increased risk of CRA in male group (adjusted OR 1.997, 95%CI 1.010-3.945, p = 0.047). CONCLUSIONS: H. pylori infection had a significant association with the risk of CRA in Chinese urban populations, which will provide new insights into selecting high-risk subjects with CRA.

Comparison of four commercial RT-PCR diagnostic kits for COVID-19 in China.

We compared the sensitivity and specificity of four commercial coronavirus disease (COVID-19) diagnostic kits using real-time reverse transcription-polymerase chain reaction (RT-PCR). Kits I-IV approved by the State Drug Administration of China were selected, and the detection targets were ORF1ab gene and N gene. Specificity was evaluated by detecting other respiratory viruses. The sensitivity and batch effect of each kit were evaluated by testing 10-fold dilutions of RNA. Clinical application was verified by testing nasopharyngeal swab and sputum specimens from COVID-19 patients. Among the 78 cases infected by other respiratory viruses, no amplification curve was observed using these four COVID-19 RT-PCR kits. The minimum detection limits of kits I-IV were 10-6 , 10-5 , 10-5 , and 10-6 dilutions, respectively, and concentrations were 10 copies/mL (10-5 dilution) and 1 copies/mL (10-6 dilution). The sensitivities of kits I-IV detected using 142 nasopharyngeal swab specimens from COVID-19 patients were 91.55%, 81.69%, 80.28%, and 90.85%, respectively, while they were 92.68%, 85.37%, 82.93%, and 93.90%, respectively, for the 82 sputum samples. The specificity of each kit was 100.00% (77/77). The total expected detection rate using sputum samples was 88.59% (691/780) higher than 86.15% (672/780) of nasopharyngeal swabs. Comparison of nasopharyngeal swab and sputum samples from the same COVID-19 patient led to the detection of ORF1ab and N genes in 16 (100%) sputum samples; only ORF1ab and N genes were detected in 12 (75%) and 14 (87.5%) nasopharyngeal swab specimens, respectively. In conclusion, comparison of commercial COVID-19 RT-PCR kits should be performed before using a new batch of such kits in routine diagnostics.

Evaluations of modes of pooling specimens for COVID-19 screened by quantitative PCR and droplet digital PCR.

Though pooling samples for SARS-CoV-2 detection has effectively met the need for rapid diagnostic and screening tests, many factors can influence the sensitivity of a pooled test. In this study, we conducted a simulation experiment to evaluate modes of pooling specimens and aimed at formulating an optimal pooling strategy. We focussed on the type of swab, their solvent adsorption ability, pool size, pooling volume, and different factors affecting the quality of preserving RNA by different virus solutions. Both quantitative PCR and digital PCR were used to evaluate the sampling performance. In addition, we determined the detection limit by sampling which is simulated from the virus of different titers and evaluated the effect of sample-storage conditions by determining the viral load after storage. We found that flocked swabs were better than fibre swabs. The RNA-preserving ability of the non-inactivating virus solution was slightly better than that of the inactivating virus solution. The optimal pooling strategy was a pool size of 10 samples in a total volume of 9 mL. Storing the collected samples at 4 °C or 25 °C for up to 48 h had little effect on the detection sensitivity. Further, we observed that our optimal pooling strategy performed equally well as the single-tube test did. In clinical applications, we recommend adopting this pooling strategy for low-risk populations to improve screening efficiency and shape future strategies for detecting and managing other respiratory pathogens, thus contributing to preparedness for future public health challenges.

Metadherin orchestrates PKA and PKM2 to activate ß-catenin signaling in podocytes during proteinuric chronic kidney disease.

Podocyte damage is the major cause of glomerular injury and proteinuria in multiple chronic kidney diseases. Metadherin (MTDH) is involved in podocyte apoptosis and promotes renal tubular injury in mouse models of diabetic nephropathy and renal fibrosis; however, its role in podocyte injury and proteinuria needs further exploration. Here, we show that MTDH was induced in the glomerular podocytes of patients with proteinuric chronic kidney disease and correlated with proteinuria. Podocyte-specific knockout of MTDH in mice reversed proteinuria, attenuated podocyte injury, and prevented glomerulosclerosis after advanced oxidation protein products challenge or adriamycin injury. Furthermore, specific knockout of MTDH in podocytes repressed ß-catenin phosphorylation at the Ser675 site and inhibited its downstream target gene transcription. Mechanistically, on the one hand, MTDH increased cAMP and then activated protein kinase A (PKA) to induce ß-catenin phosphorylation at the Ser675 site, facilitating the nuclear translocation of MTDH and ß-catenin; on the other hand, MTDH induced the deaggregation of pyruvate kinase M2 (PKM2) tetramers and promoted PKM2 monomers to enter the nucleus. This cascade of events leads to the formation of the MTDH/PKM2/ß-catenin/CBP/TCF4 transcription complex, thus triggering TCF4-dependent gene transcription. Inhibition of PKA activity by H-89 or blockade of PKM2 deaggregation by TEPP-46 abolished this cascade of events and disrupted transcription complex formation. These results suggest that MTDH induces podocyte injury and proteinuria by assembling the ß-catenin-mediated transcription complex by regulating PKA and PKM2 function.

Spatiotemporal dynamics of bacterioplankton communities in the estuaries of two differently contaminated coastal areas: Composition, driving factors and ecological process.

Seasonal variations of environmental parameters usually lead to considerable changes in microbial communities. Nevertheless, the specific response patterns of these communities in coastal areas subjected to different levels of contamination remain unclear. Our results revealed notable fluctuations in the bacterioplankton community both seasonally and spatially, with seasonal variations being particularly significant. The diversity and composition of bacterioplankton communities in the estuaries varied significantly across seasons and between seas. Some bacterial phyla that were highly abundant in the dry season (e.g., Patescibacteria and Epsilonbacteraeota) were almost absent in the wet season. Furthermore, the network analysis revealed that the bacterioplankton networks were more complex during the wet season than in the dry season. In the wet season, the estuarine bacterioplankton network in the Yellow Sea region was more complex and stable, while the opposite was true in the dry season. According to the neutral community model, stochastic processes played a more significant role in the formation of bacterioplankton communities during the wet season than during the dry season. Estuarine bacterioplankton communities in the Yellow Sea region were more affected by stochastic processes compared to those in the Bohai Sea. In summary, in the estuaries of two differently contaminated coastal areas, the seasonal increase in nutrient levels enhanced the deterministic processes and network complexity of the bacterioplankton communities.

Why did the world's largest green tides occur exclusively in the southern Yellow Sea?

The world's largest green tide, caused by the nuisance green algae Ulva prolifera, has occurred in the southern Yellow Sea for 16 consecutive years. It is puzzling why the extensive floating green tide occurs exclusively in the southern Yellow Sea, rather than other waters. We speculate that the transition of U. prolifera from a sessile state to a surface-floating one is the underlying cause of the floating green tide. Here we founded that the floating of U. prolifera was attributed to detachment from substrata and appropriate desiccation. The convergence of unreasonable green algae disposal, geographical features and farming patterns of Porphyra (economic red algae) in Subei Shoal contributed to mass production of floating U. prolifera, resulting in the exclusive occurrence of the floating green tides. Inducing the natural inactivation of green algae to prevent the floating of U. prolifera may effectively mitigate the extensive Ulva bloom at zero cost.

Association of Fine Particulate Matter and Residential Greenness With Risk of Pulmonary Tuberculosis Retreatment: Population-Based Retrospective Study.

Background: The evidence on the association of fine particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) with pulmonary tuberculosis (PTB) retreatment is limited. There are no data on whether greenness exposure protects air pollution-related PTB retreatment in patients with prior PTB. Objective: In a population-based retrospective study, we aimed to investigate the influence of PM2.5 and residential greenness on the risk of PTB retreatment. Methods: A total of 26,482 patients with incident PTB, registered in a mandatory web-based reporting system between 2012 and 2019 in Zhengzhou, China, were included in the analysis. The exposure to PM2.5 was assessed based on the China High Air Pollutants dataset, and the level of greenness was estimated using the Normalized Difference Vegetation Index (NDVI) values. The associations of PTB retreatment with exposure to PM2.5 and greenness were evaluated, respectively, considering the local socioeconomic level indicated by the nighttime light index. Results: Among the 26,482 patients (mean age 46.86, SD 19.52 years) with a median follow-up time of 1523 days per patient, 1542 (5.82%) PTB retreatments were observed between 2012 and 2019. Exposure to PM2.5 was observed to be significantly associated with the increased risk of PTB retreatment in fully adjusted models with a hazard ratio of 1.97 (95% CI 1.34-2.83) per 10 µg/m3 increase in PM2.5. Patients living in the regions with relatively high quartiles of NDVI values had a 45% lower risk of PTB retreatment than those living in the regions with the lowest quartile for the 500 m buffers (hazard ratio 0.55, 95% CI 0.40-0.77). Such a protective effect of residential greenness was more pronounced among patients living in lower nighttime light areas. The strength of the association between PM2.5 exposure and the risk of PTB retreatment was attenuated by greenness. No significant association was observed between NDVI and the incidence of drug resistance. Conclusions: Long-term exposure to PM2.5 might be a risk factor for PTB retreatment, while an increased level of residential greenness was found to be associated with reduced risks of PTB retreatment. Our results suggest strengthening the control of ambient air pollution and improving residential greenness may contribute to the reduction of PTB retreatment.

CD8+ T cell response in QuantiFERON-TB Gold Plus testing was associated with tuberculosis recurrence: a 2-year prospective study.

BACKGROUND: Recurrence posed an important challenge to pulmonary tuberculosis (PTB) control in China. The prospective study aimed to identify potential risk factors and to explore the value of QuantiFERON-TB Gold Plus (QFT-Plus) in identifying at-risk individuals with treated prior PTB history. METHODS: All eligible individuals aged ≥18 years who had been diagnosed with PTB before 2016 in Zhongmu County, where with an average level of TB prevalence in China, were included and received baseline survey including chest radiography, QuantiFERON-TB Gold In-Tube (QFT-GIT) and QFT-Plus, then PTB recurrence was tracked through a 2-year follow-up. RESULTS: Half of 1068 (52.34%, 559/1068) included eligible participants were QFT-Plus positive at baseline and 21 of them recurred active TB in 2-year follow-up. Individuals aged ≥ 60 years, who had a recent history of TB and smokers were associated with increased risk of TB recurrence with an adjusted odds ratio (aOR) of 3.97 (95% confidence interval (CI): 1.29-12.24), 7.71 (95% CI: 1.74-34.25) and 4.56 (95% CI: 1.62-12.83), respectively. Compared to QFT-Plus negatives, those who were TB2+/TB1- (aOR = 15.34) exhibited stronger association with the risk of TB recurrence than those who were TB1+/TB2+ (aOR = 6.06). A dose response relationship was also found between the risk of TB recurrence with the baseline level of TB2-TB1 (p for trend < 0.001). CONCLUSIONS: High burden of TB infection and high risk of PTB recurrence were observed in the study population. Those with recent onset of prior TB, elderly smokers and QFT-Plus positives especially with TB2 single positive deserved further attention in active TB surveillance.

BRG1 accelerates mesothelial cell senescence and peritoneal fibrosis by inhibiting mitophagy through repression of OXR1.

Peritoneal mesothelial cell senescence promotes the development of peritoneal dialysis (PD)-related peritoneal fibrosis. We previously revealed that Brahma-related gene 1 (BRG1) is increased in peritoneal fibrosis yet its role in modulating peritoneal mesothelial cell senescence is still unknown. This study evaluated the mechanism of BRG1 in peritoneal mesothelial cell senescence and peritoneal fibrosis using BRG1 knockdown mice, primary peritoneal mesothelial cells and human peritoneal samples from PD patients. The augmentation of BRG1 expression accelerated peritoneal mesothelial cell senescence, which attributed to mitochondrial dysfunction and mitophagy inhibition. Mitophagy activator salidroside rescued fibrotic responses and cellular senescence induced by BRG1. Mechanistically, BRG1 was recruited to oxidation resistance 1 (OXR1) promoter, where it suppressed transcription of OXR1 through interacting with forkhead box protein p2. Inhibition of OXR1 abrogated the improvement of BRG1 deficiency in mitophagy, fibrotic responses and cellular senescence. In a mouse PD model, BRG1 knockdown restored mitophagy, alleviated senescence and ameliorated peritoneal fibrosis. More importantly, the elevation level of BRG1 in human PD was associated with PD duration and D/P creatinine values. In conclusion, BRG1 accelerates mesothelial cell senescence and peritoneal fibrosis by inhibiting mitophagy through repression of OXR1. This indicates that modulating BRG1-OXR1-mitophagy signaling may represent an effective treatment for PD-related peritoneal fibrosis.

Impact of fine particulate matter on latent tuberculosis infection and active tuberculosis in older adults: a population-based multicentre cohort study.

Evidence showed that air pollution was associated with an increased risk of tuberculosis (TB). This study aimed to study the impact of long-term exposure to ambient particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) on the acquisition of LTBI and on the risk of subsequent active disease development among rural older adults from a multicentre cohort, which have not yet been investigated to date. A total of 4790 older adults were included in a population-based, multicentre, prospective cohort study (LATENTTB-NSTM) from 2013 to 2018. The level of long-term exposure to PM2.5 for each participant was assessed by aggregating satellite-based estimates. Logistic regression and time-varying Cox proportional hazards models with province-level random intercepts were employed to assess associations of long-term exposures to PM2.5 with the risk of LTBI and subsequent development of active TB, respectively. Out of 4790 participants, 3284 were LTBI-free at baseline, among whom 2806 completed the one-year follow-up and 127 developed newly identified LTBI. No significant associations were identified between PM2.5 and the risk of LTBI. And among 1506 participants with LTBI at baseline, 30 active TB cases were recorded during the 5-year follow-up. Particularly, an increment of 5 µg/m3 in 2-year moving averaged PM2.5 was associated with a 50.6% increased risk of active TB (HR = 1.506, 95% CI: 1.161-1.955). Long-term air pollution might be a neglected risk factor for active TB development from LTBI, especially for those living in developing or less-developed areas where the air quality is poor.

Virome survey of the bat, Rhinolophus affinis, in Hainan Province, China.

Bats are important mammal reservoirs of zoonotic pathogens. However, due to research limitations involving species, locations, pathogens, or sample types, the full diversity of viruses in bats remains to be discovered. We used next-generation sequencing technology to characterize the mammalian virome and analyze the phylogenetic evolution and diversity of mammalian viruses carried by bats from Haikou City and Tunchang County in Hainan Province, China. We collected 200 pharyngeal swab and anal swab samples from Rhinolophus affinis, combining them into nine pools based on the sample type and collection location. We subjected the samples to next-generation sequencing and conducted bioinformatics analysis. All samples were screened via specific PCR and phylogenetic analysis. The diverse viral reads, closely related to mammals, were assigned into 17 viral families. We discovered many novel bat viruses and identified some closely related to known human/animal pathogens. In the current study, 6 complete genomes and 2 partial genomic sequences of 6 viral families and 8 viral genera have been amplified, among which 5 strains are suggested to be new virus species. These included coronavirus, pestivirus, bastrovirus, bocavirus, papillomavirus, parvovirus, and paramyxovirus. The primary finding is that a SADS-related CoV and a HoBi-like pestivirus identified in R. affinis in Hainan Province could be pathogenic to livestock. This study expands our understanding of bats as a virus reservoir, providing a basis for further research on the transmission of viruses from bats to humans.

Facile preparation of coprecipitates between iron oxides and dissolved organic matter for efficient Fenton-like degradation of norfloxacin.

As two important components of dissolved organic matter (DOM), dissolved black carbon (DBC) and humic acid (HA) possess different chemical and structural properties, which might influence their activities like metal complexation and mediating electron transfer. In this study, a series of coprecipitates of iron oxides (FeOx) and DOM (HA or DBC) having different C/Fe molar ratios (0.2-3.0) was prepared under ambient conditions, which exhibited excellent catalytic efficiencies upon Fenton-like degradation of norfloxacin (NOR). Pseudo-first-order rate constant of NOR oxidation catalyzed by DBC-FeOx (C/Fe=3.0, 1.13 h-1) was 30.5, 4.3-14.2, and 1.3-15.7 folds higher than those mediated by FeOx alone, HA-FeOx and DBC-FeOx coprecipitates having C/Fe molar ratios of 0.2 and 1.6, respectively. Due to the higher concentrations of surface-bound Fe(III)/Fe(II) in the DBC-FeOx mediated systems, improved Fe(III)/Fe(II) cycling rates, •OH accumulation and NOR degradation were observed as compared with those of counterpart systems mediated by HA-FeOx. Besides functioning in Fe-C complexation to accelerate FeOOH cleavage, carbonyl/carboxyl groups of the coprecipitates also serve as electron shuttles, both of which improved Fe(III)/Fe(II) cycling and •OH production. Our findings emphasized the influence of DOM source and compositions on Fe(III)/Fe(II) cycling and provided a facile approach of preparing Fe-C catalyst for contaminants elimination.

The effect of acupuncture on oestrogen receptors in rats with benign prostatic hyperplasia.

The effects of acupuncture on the protein and gene expression of oestrogen receptors (ERs) alpha (α) and beta (ß) in testosterone-induced benign prostatic hyperplasia (BPH) in rats remains unclear. In this study, rats were randomly divided into four groups (n = 10 per group). The rats in the blank group did not receive any treatment, while the rats in the model group were injected intraperitoneally with testosterone propionate for 28 days to establish the BPH model and then randomly sub-divided into a control group, an acupuncture group and a finasteride group (positive control group). Dissections were performed after rats were anesthetized with isoflurane, and then the weight and volume of the prostate were then measured. The expression of ERs was detected via immunohistochemistry, western blot and real-time polymerase chain reaction. The results showed that ERα was discontinuously distributed in epithelial cells and expressed in large quantities in stromal cells, and ERß was aggregated and expressed in hyperplastic nodules. Acupuncture and finasteride could significantly improve the distribution of ERα and ERß which suggested that acupuncture and finasteride could improve BPH. There was no significant difference in ERα messenger ribonucleic acid (mRNA) expression among the groups, but the ERß mRNA expression in the finasteride group showed a significant difference compared with the control and acupuncture groups. The mechanism of the acupuncture treatment of BPH may be related to the increased transcription level of ERß mRNA in prostate tissues, the improved distribution of ERα expression in epithelial cells and the aggregation expression of ERs in hyperplastic nodules.