Roles of high/low nucleic acid bacteria in flocs and probing their dynamic migrations with respirogram.

Bacterial migration is crucial for the stability of activated sludge but rarely reported. The static distribution was explored by changes in bacteria concentration with extracellular polymeric substances (EPS) extractions. Next, denitrification and aeration were conducted as normal running conditions for examining the bacterial migration between floc-attached and dispersed growth. Above observations were further explored by conducting copper ion (Cu2+) shock as an extreme running condition. After extracting EPS, low nucleic acid (LNA) bacteria migrated from the sludge to the supernatant primarily, and high nucleic acid (HNA) bacteria remained in the residual sludge, suggesting that HNA bacteria mainly distributed inside the sludge while LNA bacteria outside the sludge. During the denitrification process, LNA bacteria migrated out of flocs, which increased by 6.94 × 106 events/mL in the supernatant. During the feast phase of aeration, LNA bacteria grew attached to flocs, causing the increased flocs diameter from 45.60 to 47.40 µm. During the following aerobic famine phase, LNA bacteria grew dispersedly, but HNA bacteria remained unchanged. However, a further severe famine phase drove HNA bacteria to be dispersed, breaking flocs with the decreased diameter from 48.10 to 46.50 µm. When the Cu2+ shock was employed, LNA and HNA bacteria increased but the LNA/HNA ratio decreased in the supernatant, indicating more HNA bacteria migrating to the dispersed phase. From a structural perspective, HNA bacteria distributed inside the sludge and functioned as the backbone of flocs, undertaking the maintenance of flocs stability primarily; while LNA bacteria distributed outside the sludge and functioned as filling materials, having a secondary influence on flocs stability. These processes were also probed by respirogram exactly, correlating the system-scale measurement and microscale migrations and providing an early warning signal under abnormal circumstances. The processed HNA-backbone theory is promising for regulating the stability of activated sludge based on bacterial migrations.

Hierarchical stringent response behaviors of activated sludge system to stressed conditions.

The stringent response of activated sludge systems to either stressed or harmful environments is important for the stable operation of activated sludge, which is examined by taking copper ion (Cu2+) as a stress model in this study. When weak stress was employed (Cu2+ ≤ 2.5 mg/L), the N-acyl-homoserine lactones (AHLs) of C6-, C8-, and C10-HSL increased by 30 %, 13 %, and 127 %, respectively, while the redox sensor green (RSG) intensity decreased by 28 %. Encountering the increased stress (2.5 mg/L < Cu2+ ≤ 5 mg/L), bacteria concentration in the supernatant increased by 87 %. However, the respiration rates of autotrophic and heterotrophic bacteria (SOURa and SOURh) and adenosine triphosphate decreased by 52 %, 18 %, and 27 %, respectively, and the flocs disintegrated with a diameter decreasing from 57 to 51 µm. When the stress became more serious (Cu2+ > 5 mg/L), the respiration rates continued to decline, but the quasi-endogenous respiration ratio (Rq/t) increased from 31 % to 47 %. Negligible changes occurred in the endogenous respiration rate (SOURe), adenosine diphosphate, and adenosine monophosphate. Based on these results, a hierarchical stringent response model of the activated sludge system to stressed conditions was proposed, and these responses were evaluated by respirogram. The initial response to weak stress was related to the most sensitive signals of quorum sensing and RSG intensity, well described by the quasi-endogenous respiration rate. The adaptive response to increased stress was the proactive migrations of low- and high-nucleic-acid bacteria to the supernatant, causing the looseness and even disintegration of sludge flocs, well described by SOURa, SOURh, and Rq/t. The lethal response to lethal stress was related to endogenous metabolic processes, well described by SOURe. This work provides new insights into understanding the stringent response of activated sludge systems to some stressed conditions. It helps to regulate the stability of activated sludge systems with respirogram technology.

Encapsulation of bacteria in different stratified extracellular polymeric substances and its implications for performance enhancement and resource recovery.

Simultaneous recovery of biopolymers and enhanced bio-reactor performance are promising options for sustainable wastewater treatment, and the bioactivity of sludge after biopolymer extraction is thus critical for the performance of the system. To this end, stratified extracellular polymeric substances (EPS), including slime, loosely bound EPS (LB-EPS), and tightly bound EPS (TB-EPS), were extracted, and the bioactivities of the consequent extraction residues were assessed using aerobic respirogram, kinetic, and flow cytometry (FCM). After the initial weak extraction of slime, the particle size distribution of the sludge significantly decreased, and subsequent extractions of LB-EPS and TB-EPS produced an equivalent size distribution. In contrast, the fractal dimension decreased after each extraction, suggesting that LB-EPS and TB-EPS affected the compactness of flocs rather than the size. The aerobic bacteria distribution estimated using respirogram shows that slime mainly encapsulated heterotrophs while LB-EPS mainly encapsulated nitrifiers. In addition, the ammonia-nitrogen affinity coefficient decreased from 1.79 to 0.28 mg/L when slime was removed, thereby encouraging the activities of autotrophic nitrifiers. Further removal of LB-EPS induced high energy dispersion as the maintenance coefficient m and the metabolic dispersion index µ/m increased from 0.11 to 0.22 and 0.44 to 0.63, respectively. Meanwhile, the yield rate decreased from 0.77 to 0.66. Although pellets that resulted from TB-EPS extraction were not aerobically active as described by respirogram and growth curves, they were still metabolically active as measured by live/dead cell counting and redox sensor green signal. These pellets used more energy for maintenance as indicated by the high maintenance coefficient than those residual after either slime or LB-EPS extraction. In addition, the variation in bacteria community distribution across flocs was related to the variation in temperatures, suggesting that the inner part of a floc might be hotter than the outer side. Therefore, compared to bacteria in the raw sludge, the viable bacteria bounded in LB-EPS and TB-EPS convert more energy to heat rather than growth. These results indicate that energy was dispersed as metabolic heat for the LB-EPS extracted sludge, and removal of LB-EPS favored thermogenesis and sludge reduction. Based on the above findings, a simultaneously EPS-recovery and performance enhancement configuration is thus proposed, which holds great promise for the integration of next-generation wastewater treatment plants.

Genomic analyses of 10,376 individuals in the Westlake BioBank for Chinese (WBBC) pilot project.

We initiate the Westlake BioBank for Chinese (WBBC) pilot project with 4,535 whole-genome sequencing (WGS) individuals and 5,841 high-density genotyping individuals, and identify 81.5 million SNPs and INDELs, of which 38.5% are absent in dbSNP Build 151. We provide a population-specific reference panel and an online imputation server ( https://wbbc.westlake.edu.cn/ ) which could yield substantial improvement of imputation performance in Chinese population, especially for low-frequency and rare variants. By analyzing the singleton density of the WGS data, we find selection signatures in SNX29, DNAH1 and WDR1 genes, and the derived alleles of the alcohol metabolism genes (ADH1A and ADH1B) emerge around 7,000 years ago and tend to be more common from 4,000 years ago in East Asia. Genetic evidence supports the corresponding geographical boundaries of the Qinling-Huaihe Line and Nanling Mountains, which separate the Han Chinese into subgroups, and we reveal that North Han was more homogeneous than South Han.

Cohort profile: the Westlake BioBank for Chinese (WBBC) pilot project.

PURPOSE: The Westlake BioBank for Chinese (WBBC) pilot cohort is a population-based prospective study with its major purpose to better understand the effect of genetic and environmental factors on growth and development from adolescents to adults. PARTICIPANTS: A total of 14 726 participants (4751 males and 9975 females) aged 14-25 years were recruited and the baseline survey was carried out from 2017 to 2019. The pilot cohort contains rich range of information regarding of demographics and anthropometric measurements, lifestyle and sleep patterns, clinical and health outcomes. Visit the WBBC website for more information (https://wbbc.westlake.edu.cn/index.html). FINDINGS TO DATE: The mean age of the study samples were 18.6 years for males and 18.5 years for females, respectively. The mean height and weight were 172.9 cm and 65.81 kg for males, and 160.1 cm and 52.85 kg for females. Results indicated that the prevalence of underweight in female was much higher than male, but the prevalence of overweight and obesity in female was lower than male. The mean serum 25(OH)D level in the 14 726 young participants was 22.4±5.3 ng/mL, and male had a higher level of serum 25(OH)D than female, overall, 33.5% of the participants had vitamin D deficiency and even more participants suffered from vitamin D insufficiency (58.2%). The proportion of deficiency in females was much higher than that in males (41.8 vs 16.4%). The issue of underweight and vitamin D deficiency in young people should be paid attention, especially in females. These results reflected the fact that thinness and paler skin are preferred in modern aesthetics of Chinese culture. FUTURE PLANS: WBBC pilot is designed as a prospective cohort study and provides a unique and rich data set analysing health trajectories from adolescents to young adults. WBBC will continue to collect samples with old age.

Systemic evaluation of the relationship between psoriasis, psoriatic arthritis and osteoporosis: observational and Mendelian randomisation study.

OBJECTIVES AND METHODS: With 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them. RESULTS: Lower eBMD were observed in patients with PsA than in controls in both model0 (ß-coefficient=-0.014, p=0.0006) and model1 (ß-coefficient=-0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (ß-coefficient=-0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture. CONCLUSIONS: The effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.

Relationship between alcohol use, blood pressure and hypertension: an association study and a Mendelian randomisation study.

BACKGROUND: Past studies have found a strong relationship between alcohol drinking and human health. METHODS: In this study, we first tested the association of rs671 with alcohol use in 2349 participants in southeast China. We then evaluated the causal impact between alcohol use and cardiovascular traits through a Mendelian randomisation (MR) analysis. RESULTS: We found strong evidence for the association of rs671 in the ALDH2 gene with alcohol drinking (p=6.08×10-47; ORadj G=4.50, 95% CI 3.67 to 5.52). We found that female G carriers of rs671 had a higher proportion of non-drinkers than male G carriers (88.01% vs 38.70%). In non-drinkers, the female G allele frequency was higher than the male G allele frequency (71.1% vs 55.2%). MR analysis suggested that alcohol use had a causal effect on blood pressure (increasing 9.46 mm Hg for systolic blood pressure (p=9.67×10-4) and 7.50 mm Hg for diastolic blood pressure (p=9.62×10-5)), and on hypertension in men (p=0.011; OR =1.19, 95% CI 1.04 to 1.36) and in pooled samples (p=0.013; OR =1.20, 95% CI 1.04 to 1.39), but not in women. We did not observe a causal effect of alcohol use on body mass index and lipid levels; further studies are needed to clarify the non-causal relationship. CONCLUSIONS: Compared to never-drinkers, current and previous alcohol use had a causal effect on blood pressure and hypertension in pooled samples and in men. These results reflect Chinese culture which does not encourage women to drink.

Effect of CD14 polymorphisms on the risk of cardiovascular disease: evidence from a meta-analysis.

BACKGROUND: CD14 polymorphisms are associated with an increased risk of cardiovascular events. So far, many studies have been conducted, whereas the results were not always consistent. MATERIALS AND METHODS: Twenty-six articles involving thirty-seven datasets were recruited to evaluate the association between rs2569190 (9413 patients and 7337 controls), C-159T (4813 patients and 2852 controls) polymorphisms and cardiovascular diseases in a meta-analysis. The random or fixed effect models were used to evaluate the pooled odds ratios (ORs) and their corresponding 95% confidence intervals. RESULTS: The strongest association was observed between rs2569190 and CVD in overall population (T vs. C, OR = 1.169, 95% CI: 1.087-1.257, p = 2.44 × 10- 5). Analysis after stratification by ethnicity indicated that rs2569190 was related to CVD in East Asian population (T vs. C, OR = 1.370, 95% CI; 1.226-1.531, p = 2.86 × 10- 8) and a potential relationship in European (T vs. C, OR = 1.100, 95% CI: 1.019-1.189, p = 0.015). In the stratification of endpoints, the associations were found in CHD subgroup (T vs. C, OR = 1.357, 95% CI: 1.157-1.592, p = 2.47 × 10- 7) and in AMI subgroup (T vs. C, OR = 1.152, 95% CI: 1.036-1.281, p = 0.009). However, we did not find any association between C-159T polymorphism with cardiovascular disease under any model. CONCLUSIONS: The SNP rs2569190 significantly contribute to susceptibility and development of cardiovascular disease, particularly in the East Asian population and in the subtype CHD group, in addition, a potential association was observed in the AMI group, T allele acts as a risk factor for cardiovascular disease.

Comprehensive assessment of the association between genes on JAK-STAT pathway (IFIH1, TYK2, IL-10) and systemic lupus erythematosus: a meta-analysis.

Previous studies have reported that genes relating to JAK-STAT pathway (IFIH1, TYK2 and IL-10) conferred the susceptibility to SLE. In this study, we performed a meta-analysis (including 43 studies) to evaluate the association between IFIH1 (9288 patients and 24,040 controls), TYK2 (4928 patients and 11,536 controls), IL-10 (3623 patients and 4907 controls) polymorphisms and systemic lupus erythematosus (SLE) in a comprehensive way. We found that IFIH1 rs1990760_T allele was associated with risk of SLE in overall population under three models (allelic: P = 2.56 × 10-11, OR 1.135, 95% CI 1.094-1.179, dominant: P = 1.8 × 10-8, OR 1.203, 95% CI 1.128-1.284, recessive: P = 2.6 × 10-7, OR 1.163, 95% CI 1.098-1.231). A strong association had been observed between TYK2 polymorphism rs2304256_C allele and SLE in Europeans (P = 5.82 × 10-5, OR 1.434, 95% CI 1.203-1.710). When coming to overall population, TYK2 rs2304256_C showed a significant association with SLE under recessive model (P = 8.05 × 10-3, OR 1.314, 95% CI 1.074-1.608). However, the other two SNPs (rs12720270, rs280519) of TYK2 were not significant. The results also indicated an association between IL-10 rs1800896_G allele and SLE in Asians under recessive model (P = 4.65 × 10-3, OR 2.623, 95% CI 1.346-5.115), while, IL-10 rs1800896_G had a trend of association with SLE in European population in dominant model (P = 1.21 × 10-2, OR 1.375, 95% CI 1.072-1.764). In addition, we found IL-10 rs1800896 GG homozygote might be associated with increased susceptibility to SLE (GG vs AA, P = 4.65 × 10-3, OR 1.539, 95% CI 1.142-2.072). We concluded that IFIH1 rs1990760_T and TYK2 rs2304256_C alleles were significantly associated with SLE, and IL-10 rs1800896 GG homozygote might have an enhancement effect on SLE risk.

Associations between PTPN22 and TLR9 polymorphisms and systemic lupus erythematosus: a comprehensive meta-analysis.

Previous studies have explored the relationship of PTPN22 and TLR9 polymorphisms with systemic lupus erythematosus (SLE). In consideration of the population stratification, conflicting results and updating data, we conducted a comprehensive meta-analysis, which consists of a total of 17 research articles (9120 cases and 11,724 controls) for PTPN22 and 20 articles (including up to 2808 cases and 3386 controls) for TLR9. Significant association was verified between PTPN22 rs2476601 and SLE in the overall population (OR = 1.511 per T allele, 95% CI 1.338-1.706, P = 2.931 × 10-11) and under dominant model of T allele (TT+CT vs. CC: OR = 1.531, 95% CI 1.346-1.742, P = 9.17 × 10-11). Analysis after stratification by ethnicity indicated that PTPN22 rs2476601 was related to SLE in Americans (OR = 2.566, 95% CI 1.796-3.665, P = 2.219 × 10-7), Europeans (OR = 1.399, 95% CI 1.261-1.552, P = 2.153 × 10-10), and Africans (OR = 4.14, 95% CI 1.753-9.775, P = 1.0 × 10-3). We did not observe any association between TLR9 polymorphisms (rs187084, rs352140, rs5743836 and rs352139) and SLE under any model, after excluding the data that were inconsistent with Hardy-Weinberg equilibrium (HWE). In summary, PTPN22 rs2476601 was significantly interrelated with SLE and contributed to susceptibility and development of SLE in Americans, Europeans and Africans in this analysis, while their relationship needs to be validated in Africans by future research.

Comprehensive Assessment of the Association between FCGRs polymorphisms and the risk of systemic lupus erythematosus: Evidence from a Meta-Analysis.

We performed a meta analysis to assess the relationship of FCGRs polymorphisms with the risk of SLE. Thirty-five articles (including up to 5741 cases and 6530 controls) were recruited for meta-analysis. The strongest association was observed between FCGR2B rs1050501 and SLE under the recessive genotypic model of C allele in the overall population (CC vs CT/TT, OR = 1.754, 95%CI: 1.422-2.165, P = 1.61 × 10(-7)) and in Asian population (CC vs CT/TT, OR = 1.784, 95%CI; 1.408-2.261, P = 1.67 × 10(-6)). We also found that FCGR3A rs396991 were significant association with the susceptibility to SLE in overall population in recessive model of T allele (TT vs TG/GG, OR = 1.263, 95%CI: 1.123-1.421, P = 9.62 × 10(-5)). The results also showed that significant association between FCGR2A rs1801274 and SLE under the allelic model in the overall population (OR = 0.879 per A allele, 95%CI: 0.819-0.943, P = 3.31 × 10(-4)). The meta-analysis indicated that FCGR3B copy number polymorphism NA1·NA2 was modestly associated with SLE in overall population (OR = 0.851 per NA1, 95%CI: 0.772-0.938, P = 1.2 × 10(-3)). We concluded that FCGR2B rs1050501 C allele and FCGR3A rs396991 T allele might contribute to susceptibility and development of SLE, and were under recessive association model. While, FCGR2A rs1801274 A allele and FCGR3B NA1 were associated with SLE and reduced the risk of SLE.