Deciphering the seasonal dynamics of multifaceted aerosol-ozone interplay: Implications for air quality management in Eastern China.

We employed an enhanced WRF-Chem to investigate the discrete mechanisms of aerosol-radiation-feedback (ARF), extinction-photochemistry (AEP), and heterogeneous-reactions (AHR) across different seasons in eastern China, aiming to assess the synergistic effects arising from the simultaneous operation of multiple processes on O3 and PM2.5. Our findings demonstrated that ARF fostered the accumulation of pollutants and moisture, initiating two distinct feedback mechanisms concerning O3. The elevation in the NO/NO2 ratio amplified O3 consumption. Increased near-surface moisture diminished upper-level cloud formation, thereby enhancing photolysis rates and O3 photochemical production. The pronounced impact of heightened NO/NO2 on O3 led to a decrease of 0.1-2.7 ppb. When decoupled from ARF, AEP led to a more significant reduction in photolysis rates, resulting in declines in both O3 and PM2.5, except for an anomalous increase observed in summer, with O3 increasing by 1.6 ppb and PM2.5 by 2.5 µg m-3. The heterogeneous absorption of hydroxides in spring, autumn, and winter predominantly governed the AHR-induced variation of O3, leading to a decrease in O3 by 0.7-1 ppb. Conversely, O3 variations in summer were primarily dictated by O3-sensitive chemistry, with heterogeneous absorption of NOy catalyzing a decrease of 2.4 ppb in O3. Furthermore, AHR accentuated PM2.5 by facilitating the formation of fine sulfates and ammonium while impeding nitrate formation. In summer, the collective impact of ARF, AEP, and AHR (ALL) led to a substantial reduction of 6.2 ppb in O3, alleviating the secondary oxidation of PM2.5 and leading to a decrease of 0.3 µg m-3 in PM2.5. Conversely, albeit aerosol substantially depleted O3 by 0.4-4 ppb through their interactions except for summer, aerosol feedback on PM2.5 was more pronounced, resulting in a significant increase of 1.7-6.1 µg m-3 in PM2.5. Our study underscored the seasonal disparities in the ramifications of multifaceted aerosol-ozone interplay on air quality.

Influence of dissolved organic matter on the anaerobic biotransformation of roxarsone accompanying microbial community response.

Roxarsone (ROX), commonly employed as a livestock feed additive, largely remains unmetabolized and is subsequently excreted via feces. ROX could cause serious environmental risks due to its rapid transformation and high mobility in the anaerobic subsurface environment. Dissolved organic matter (DOM) is an important constituent of fecal organics in livestock waste and could affect the ROX biotransformation. Nonetheless, the underlying mechanisms governing the interaction between DOM and ROX biotransformation have not yet been elucidated in the anaerobic environment. In this study, the changes of ROX, metabolites, and microbial biomass in the solutions with varying DOM concentrations (0, 50, 100, 200, and 400 mg/L) under anaerobic environments were investigated during the ROX (200 mg/L) degradation. EEM-PARAFAC and metagenomic sequencing were combined to identify the dynamic shifts of DOM components and the functional microbial populations responsible for ROX degradation. Results indicated that DOM facilitated the anaerobic biotransformation of ROX and 200 mg/L ROX could be degraded completely in 28 h. The tryptophan-like within DOM functioned as a carbon source to promote the growth of microorganisms, thus accelerating the degradation of ROX. The mixed microflora involved in ROX anaerobic degrading contained genes associated with arsenic metabolism (arsR, arsC, acr3, arsA, nfnB, and arsB), and arsR, arsC, acr3 exhibited high microbial diversity. Variations in DOM concentrations significantly impacted the population dynamics of microorganisms involved in arsenic metabolism (Proteiniclasticum, Exiguobacterium, Clostridium, Proteiniphilum, Alkaliphilus, and Corynebacterium spp.), which in turn affected the transformation of ROX and its derivatives. This study reveals the mechanism of ROX degradation influenced by the varying concentrations of DOM under anaerobic environments, which is important for the prevention of arsenic contamination with elevated levels of organic matter.

Anaerobic oxidation of methane driven by different electron acceptors: A review.

Methane, the most significant reduced form of carbon on Earth, acts as a crucial fuel and greenhouse gas. Globally, microbial methane sinks encompass both aerobic oxidation of methane (AeOM), conducted by oxygen-utilizing methanotrophs, and anaerobic oxidation of methane (AOM), performed by anaerobic methanotrophs employing various alternative electron acceptors. These electron acceptors involved in AOM include sulfate, nitrate/nitrite, humic substances, and diverse metal oxides. The known anaerobic methanotrophic pathways comprise the internal aerobic oxidation pathway found in NC10 bacteria and the reverse methanogenesis pathway utilized by anaerobic methanotrophic archaea (ANME). Diverse anaerobic methanotrophs can perform AOM independently or in cooperation with symbiotic partners through several extracellular electron transfer (EET) pathways. AOM has been documented in various environments, including seafloor methane seepages, coastal wetlands, freshwater lakes, soils, and even extreme environments like hydrothermal vents. The environmental activities of AOM processes, driven by different electron acceptors, primarily depend on the energy yields, availability of electron acceptors, and environmental adaptability of methanotrophs. It has been suggested that different electron acceptors driving AOM may occur across a wider range of habitats than previously recognized. Additionally, it is proposed that methanotrophs have evolved flexible metabolic strategies to adapt to complex environmental conditions. This review primarily focuses on AOM, driven by different electron acceptors, discussing the associated reaction mechanisms and the habitats where these processes are active. Furthermore, it emphasizes the pivotal role of AOM in mitigating methane emissions.

Evolution of groundwater hydrochemical characteristics and formation mechanism during groundwater recharge: A case study in the Hutuo River alluvial-pluvial fan, North China Plain.

A pilot project for groundwater recharge from rivers is currently being carried out in North China Plain. To investigate the influence of river recharge on groundwater hydrochemical characteristics, dynamic monitoring and analysis of groundwater samples were conducted at a typical recharge site in the Hutuo River alluvial-pluvial fan in the North China Plain from 2019 to 2021. Hydrochemical, isotopic, and multivariate statistical analyses were used to systematically reveal the spatiotemporal variation of groundwater chemistry and its driving factors during groundwater recharge process. The results showed that the groundwater hydrochemical types and characteristics in different recharge areas and recharge periods exhibited obvious spatiotemporal differences. The groundwater type varied from HCO3·SO4-Na·Mg to HCO3·SO4-Ca·Mg in an upstream ecological area, while the groundwater type changed from SO4·HCO3-Mg·Ca to HCO3·SO4-Ca·Mg in the downstream impacted by reclaimed water. Changes in the contents of Ca2+, Mg2+ and HCO3- were mostly controlled by the water-rock interactions and mixing-dilution of recharge water, while the increases in Na+, NO3-, Cl-, SO42- and NO3- contents were mainly due to the infiltration of reclaimed water. Nitrogen and oxygen isotope (δ15N and δ18O) tests and the Bayesian isotope mixing model results further demonstrated that nitrate pollution mainly originated from anthropogenic sources, and the major contribution came from manure and sewage, with an average proportion of 64.6 %. Principal component analysis indicated that water-rock interactions, river-groundwater mixing and redox environment alternation were dominant factors controlling groundwater chemical evolution in groundwater recharge process.

Multiple stable isotopic approaches for tracing nitrate contamination sources: Implications for nitrogen management in complex watersheds.

Nitrate (NO3-) contamination of surface water is a global environmental problem that has serious consequences for watershed ecosystems and endangers human health. It is crucial to identify influences of different sources of NO3-, especially the incoming water from upper reaches. A combination of hydrochemistry and multi-isotope tracers (δ11B, δ15N-NO3-, and δ18O-NO3-) were used to determine NO3- sources and their transformation the North Jiulong River (NJLR), Southeast China. The findings revealed that NO3-, which accounted for an average of 87.1% of dissolved inorganic nitrogen (DIN), was the main chemical form of nitrogen species. The integration of dual stable isotopes of NO3-, δ11B, and hydrochemistry showed that NO3- was primarily contributed by sewage, soil nitrogen (SN), and ammonium (NH4+) via precipitation or fertilizers. The contributions from the sewage and soil nitrate source were almost equivalent and much higher than those from other sources in the NJLR watershed. The contributions from diverse sources varied seasonally and spatially. Manure and sewage (M&S) were the leading sources in the summer and autumn, accounting for 60.9 ± 8.5% and 47.3 ± 7.9%, respectively. However, NO3- fertilizers were the predominant source in the spring and winter. The NO3- inflow from upper reaches was proposed as an additional end-member to identify its contribution in the midstream and downstream in this study. The contributions of NO3- from the upper reaches were significant sources in the midstream and downstream, accounting for 27.2 ± 17.8% and 42.9 ± 21.9%, respectively. The obvious decline in local NO3-contribution shares from midstream to downstream implied structural changes in pollutant sources and regional environmental responsibility. Therefore, tracing nitrate sources and quantifying their contributions is critical for clarifying environmental responsibilities for precise local nitrogen management in watersheds.

Spatio-temporal analysis of the sources and transformations of anthropogenic nitrogen in a highly degraded coastal basin in Southeast China.

Nitrogen transport from terrestrial to aquatic environments could cause water quality deterioration and eutrophication. By sampling in the high- and low-flow periods in a highly disturbed coastal basin of Southeast China, hydrochemical characteristics, nitrate stable isotope composition, estimation of potential nitrogen source input fluxes, and the Bayesian mixing model were combined to determine the sources and transformation of nitrogen. Nitrate was the main form of nitrogen. Nitrification, nitrate assimilation, and NH4+ volatilization were the main nitrogen transformation processes, whereas denitrification was limited due to the high flow rate and unsuitable physicochemical properties. For both sampling periods, non-point source pollution from the upper to the middle reaches was the main source of nitrogen, especially in the high-flow period. In addition to synthetic fertilizer, atmospheric deposition and sewage and manure input were also major nitrate sources in the low-flow period. Hydrological condition was the main factor determining nitrate transformation in this coastal basin, despite the high degree of urbanization and the high volume of sewage discharge in the middle to the lower reaches. The findings of this study highlight that the control of agricultural non-point contamination sources is essential to pollution and eutrophication alleviation, especially for watersheds that receive high amounts of annual precipitation.

Assessment of HCHO in Beijing during 2009 to 2020 using satellite observation and numerical model: Spatial characteristic and impact factor.

Formaldehyde (HCHO) is an air pollutant that has a detrimental effect on human health and atmospheric environment. Until now, satellite observation has been increasingly a valuable source for monitoring the unconventional atmospheric pollutants due to the limited availability of ground-based HCHO data. Here, we used Ozone Monitoring Instrument (OMI) and the weather research and forecasting with chemistry (WRF-Chem) model to synergistically analyze the spatiotemporal variations of tropospheric HCHO in Beijing during 2009-2020, and the response of O3 to HCHO and NO2 in hotspots. We also discuss the multiple factors influencing the variation of HCHO and identify potential source area. The results indicated that HCHO column concentration is higher in eastern Beijing, and peaking in 2018 (16.68 × 1015 mol/cm2). O3 shows a good response to HCHO, with higher HCHO and NO2 photolysis leading to O3 increase in summer. In winter, decreasing HCHO and increasing NO2 inhibits the formation of O3. Transportation emissions contributed the most to HCHO, followed by the industrial sector, while residential sources have long-term effects. Isoprene produced by plants is one of the main sources of HCHO, whereas meteorological conditions can affect production efficiency. Biomass burning contributes less. Moreover, HCHO in Beijing is affected by the combined effects of local emission and external transport, and Hebei is the potential source area. This study reveals HCHO has a great accumulation potential in cities and highlights the dominant role of anthropogenic emissions, but also need to consider the influence of natural factors and regional transport.

Predicting the speciation of ionizable antibiotic ciprofloxacin by biochars with varying carbonization degrees.

Sorption mechanisms of ionizable organic pollutants by biochars and approaches for the prediction of sorption are still unclear. In this study, batch experiments were conducted to explore the sorption mechanisms of woodchip-derived biochars prepared at 200-700 °C (referred as WC200-WC700) for cationic, zwitterionic and anionic species of ciprofloxacin (referred as CIP+, CIP± and CIP-, respectively). The results revealed that the sorption affinity of WC200 for different CIP species was in the order of CIP± > CIP+ > CIP-, while that of WC300-WC700 remained the order of CIP+ > CIP± > CIP-. WC200 exhibited a strong sorption ability, which could be attributed to hydrogen bonding and electrostatic attraction with CIP+, electrostatic attraction with CIP±, and charge-assisted hydrogen bonding with CIP-. Pore filling and π-π interactions contributed to the sorption of WC300-WC700 for CIP+, CIP± and CIP-. Rising temperature facilitated CIP sorption to WC400 as verified by site energy distribution analysis. Proposed models including the proportion of the three CIP species and sorbent aromaticity index (H/C) can quantitatively predict CIP sorption to biochars with varying carbonization degrees. These findings are vital to elucidating the sorption behaviors of ionizable antibiotics to biochars and exploring potential sorbents for environmental remediation.

Management of Rheumatoid Arthritis With a Digital Health Application: A Multicenter, Pragmatic Randomized Clinical Trial.

IMPORTANCE: Digital health applications have been shown to be effective in the management of chronic diseases with simple treatment targets. The potential clinical value of digital health applications in rheumatoid arthritis (RA) has not been well studied. OBJECTIVE: To investigate whether assessing patient-reported outcomes using digital health applications could result in disease control for patients with RA. DESIGN, SETTING, AND PARTICIPANTS: This is a multicenter, open-label randomized clinical trial in 22 tertiary hospitals across China. Eligible participants were adult patients with RA. Participants were enrolled from November 1, 2018, to May 28, 2019, with a 12-month follow-up. The statisticians and rheumatologists who assessed disease activity were blinded. Investigators and participants were not blind to group assignment. Analysis was conducted from October 2020 to May 2022. INTERVENTIONS: Participants were randomly assigned at a 1:1 ratio (block size of 4) to a smart system of disease management group (SSDM) or a conventional care control group. Upon the completion of the 6-month parallel comparison, patients in the conventional care control group were instructed to use the SSDM application for an extension of 6 months. MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of patients with disease activity score in 28 joints using the C-reactive protein (DAS28-CRP) of 3.2 or less at month 6. RESULTS: Of 3374 participants screened, 2204 were randomized, and 2197 patients with RA (mean [SD] age, 50.5 [12.4] years; 1812 [82.5%] female) were enrolled. The study included 1099 participants in the SSDM group and 1098 participants in the control group. At month 6, the rate of patients with DAS28-CRP of 3.2 or less was 71.0% (780 of 1099 patients) in the SSDM group vs 64.5% (708 of 1098 patients) in the control group (difference between groups, 6.6%; 95% CI, 2.7% to 10.4%; P = .001). At month 12, the rate of patients with DAS28-CRP of 3.2 or less in the control group increased to a level (77.7%) that was comparable with that (78,2%) in the SSDM group (difference between groups, -0.2%; 95% CI, -3.9% to 3.4%; P = .90). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of RA, the use of a digital health application with patient-reported outcomes was associated with an increase in disease control rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03715595.

The underlying mechanisms of PM2.5 and O3 synergistic pollution in East China: Photochemical and heterogeneous interactions.

The rapid development of Chinese cities is accompanied by air pollution. Although the implementation of air pollution control strategies in recent years has alleviated PM2.5 pollution, O3 pollution and the synergistic pollution of PM2.5 and O3 have become more serious. To understand the underlying chemical interaction mechanisms between PM2.5 and O3, we applied the modified Weather Research and Forecasting model with Chemistry (WRF-Chem) to study the effects of aerosol-photolysis feedback and heterogeneous reactions on the two pollutants and revealed the contribution of different mechanisms in different seasons and regions in Yangtze River Delta (YRD) in eastern China. We found that, through the aerosol-photolysis feedback, PM2.5 decreased the surface photolysis rates JNO2 and JO1D, resulting in a decrease in O3 concentration in the VOC-sensitive area and a slight increase in the NOx-sensitive area. The heterogeneous reactions reduced O3 concentration in the YRD in spring, autumn and winter by consuming HxOy. While in summer, the heterogeneous absorption of NOx decreased O3 in the NOx-sensitive areas and increased O3 in the VOC-sensitive areas. Heterogeneous reactions also promoted the secondary formation of fine sulfate and nitrate aerosols, especially in winter. Through the combined effect of two chemical processes, PM2.5 can lead to a decrease in O3 concentration of -3.3 ppb (-7.6 %), -2.2 ppb (-4.0 %), -2.9 ppb (-6.3 %), and - 5.9 ppb (-18.7 %), in spring, summer, autumn and winter in YRD. Therefore, if the PM2.5 concentration decreases, the weakening effect of PM2.5 on the ozone concentration will be reduced, resulting in the aggravation of ozone pollution. This study is important for understanding the synergistic pollution mechanism and provides a scientific basis for the coordinated control of urban air pollution.

Pharmaceuticals in multi-media environment from the Jin River to adjacent marine embayment in Southeast China.

Multi-media environmental distribution of 21 pharmaceuticals in river water, coastal water, groundwater and sediments from the Jin River to adjacent marine embayment, Southeast China, was reported for the first time. All the detected 10 pharmaceuticals were antibiotics. Oxytetracycline (OTC), ciprofloxacin (CFC) and enrofloxacin (EFC) were the most ubiquitous antibiotics and could be detected in all water samples. EFC also showed the highest detection frequency (100%) in both riverine and coastal sediments. The detected antibiotics were more widely distributed in coastal environment of Asia, especially China, rather than Europe, USA and Australia. Sulfamethoxazole (SMX) showed stronger sorption onto sediments compared with other antibiotics due to its higher pseudo-partitioning coefficients (846-10,786 L kg-1). The discharged wastewater and aquaculture were the main sources of antibiotics in the multi-media environment. Risk assessment indicated that CFC and SMX posed high risks to Microcystis aeruginosa and Synechococcus leopolensis in river water, coastal water and groundwater.

Effects of dissolved organic matter derived from chicken manure on the biotransformation of roxarsone in soil.

Roxarsone (3-nitro-4-hydroxyphenylarsonic acid, ROX), widely used as a livestock feed additive, is excreted untransformed in large concentrations. Accumulation of this manure in the open environment increases dissolved organic matter (DOM) and ROX in soil within the aeration zone. And microbial action plays a dominant role in the transformation of ROX. However, the specific effect of DOM on the biotransformation of ROX is not known. In this paper, we investigated the transformation rate, metabolite content, and microbial community response of ROX in soils with different DOM concentrations (71.61, 100, 200, 500, and 800 mg L-1). The transformation of ROX was consistent with first-order transformation kinetics. DOM promoted the transformation of ROX, and with high DOM (DOM ≥200 mg L-1), ROX was transformed almost completely within two days. In this case, DOM provided nutrients to microorganisms and promoted their growth, accelerating the transformation of ROX. Also, the solubility of ROX was enhanced by DOM to increase its bioavailability. The microbial diversity was negatively correlated with DOM concentration and ROX transformation time; during the transformation of ROX, Bacillus, Arthrobacter, Enterococcus, Acinetobacter, and Pseudomonas became dominant in the soil with anomalously high levels of DOM. This study demonstrates the transformation process of ROX under actual environmental conditions where organic matter coexists with ROX, and this understanding is important for the prevention and control of arsenic pollution in soil within the aeration zone with anomalously high levels of DOM.

Variational Attention-Based Interpretable Transformer Network for Rotary Machine Fault Diagnosis.

Deep learning technology provides a promising approach for rotary machine fault diagnosis (RMFD), where vibration signals are commonly utilized as input of a deep network model to reveal the internal state of machinery. However, most existing methods fail to mine association relationships within signals. Unlike deep neural networks, transformer networks are capable of capturing association relationships through the global self-attention mechanism to enhance feature representations from vibration signals. Despite this, transformer networks cannot explicitly establish the causal association between signal patterns and fault types, resulting in poor interpretability. To tackle these problems, an interpretable deep learning model named the variational attention-based transformer network (VATN) is proposed for RMFD. VATN is improved from transformer encoder to mine the association relationships within signals. To embed the prior knowledge of the fault type, which can be recognized based on several key features of vibration signals, a sparse constraint is designed for attention weights. Variational inference is employed to force attention weights to samples from Dirichlet distributions, and Laplace approximation is applied to realize reparameterization. Finally, two experimental studies conducted on bevel gear and bearing datasets demonstrate the effectiveness of VATN to other comparison methods, and the heat map of attention weights illustrates the causal association between fault types and signal patterns.

Genetically predicted physical activity is associated with lower serum urate concentrations.

BACKGROUND: Physical activity (PA) is considered to play an important role in the reduced gout risk. However, the epidemiology results are inconsistent and causality remains unclear. OBJECTIVE: To investigate the causal relationship of PA with serum urate concentrations and gout risk by a bidirectional Mendelian randomization (MR) approach. METHOD: Two genome-wide association studies (GWASs) from UK Biobank were used to identify instrumental variables for self-reported moderate-to-vigorous PA (including 377,234 European individuals), accelerometer-measured 'average acceleration' PA (including 91,084 European individuals) and accelerometer-measured overall PA (including 91,105 European individuals). The summary data for serum urate (including 110,347 European individuals) and gout (including 2,115 cases and 67,259 controls) were derived from GWAS of Global Urate Genetics Consortium. Moreover, reverse direction Mendelian randomization study was conducted. The inverse-variance weighted, weighted median, Mendelian randomization Egger regression, simple mode and weighted mode and Mendelian Randomization Pleiotropy RESidual Sum and Outlier were methods we performed. RESULT: Genetic predisposition to accelerometer-measured 'average acceleration' PA [beta = -0.038; 95% confidence interval (CI) = -0.060,-0.015; P = 0.001] and accelerometer-measured overall PA (beta = -0.339; 95% CI = -0.522,-0.156; P = 2.8E-4) were significantly associated with decreased serum urate concentrations. Besides, there was no evidence supporting the causal association between PA and gout risk. In the reverse direction analysis, genetic predisposition to both urate and gout were not associated with PA being investigated. CONCLUSIONS: In MR study, we found that PA may reduce serum urate concentrations but not the risk of gout. Moreover, serum urate concentrations and gout were not associated with PA.

Mechanism evolution and prediction of carbamazepine sorption by mangrove plant residue-derived biochars.

A mechanism for carbamazepine (CBZ) sorption by mangrove plant residue-derived biochars pyrolyzed at 200-700 °C (referred as MPR200-MPR700) was elucidated in this study. The experimental results demonstrated that the dominant sorption mechanism of biochars for CBZ was evolved from partition to adsorption with increasing pyrolysis temperature. The CBZ concentration-dependent contributions of partition and adsorption were controlled by the relative noncarbonized and carbonized fractions of biochars. The partition medium changed from a polymeric aliphatic fraction (mangrove plant residue [MPR]200-MPR400) to a more condensed aromatic phase (MPR500-MPR600), which made the partition less favorable. Meanwhile, the adsorption was selectively regulated by polarity (MPR200-MPR300) and porosity (MPR400-MPR700) for different biochars. A pragmatic model including the sorbent aromaticity index (H/C) was put forward to predict CBZ sorption to MPR200-MPR700 and other carbonaceous materials reported in the literature. The findings can be helpful in understanding CBZ-biochar interactions and developing effective sorbents (such as biochars) for pollutant sequestration.

Occurrence and Risk Assessment of Perfluorooctanoate (PFOA) and Perfluorooctane Sulfonate (PFOS) in Surface Water, Groundwater and Sediments of the Jin River Basin, Southeastern China.

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) levels were determined in surface water, groundwater and sediments of the Jin River Basin, southeastern China. PFOA was detected in most of the samples, and its concentrations ranged from 0.53 to 8.77 ng/L, 0.26 to 15.1 ng/L and not detected (ND) to 23.9 ng/g in surface water, groundwater and sediments, respectively. Unlike PFOA, the detection frequency of PFOS was lower than 32%, and its concentrations ranged from ND to 2.56 ng/L, ND to 7.01 ng/L, ND to 11.1 ng/g in surface water, groundwater and sediments, respectively. The environmental risk assessment showed that PFOA could pose a high risk to surface water and groundwater, and both PFOA and PFOS posed a high risk to sediments. Moreover, the adults living in the Jin River Basin were at insignificant health risk to exposure to PFOA and PFOS through water consumption.

No Causal Association Between Adiponectin and the Risk of Rheumatoid Arthritis: A Mendelian Randomization Study.

Background: Accumulating evidence from observational studies suggested that circulating adiponectin levels are associated with the risk of rheumatoid arthritis (RA), but the causality remains unknown. We aimed to assess the causal relationship of adiponectin with RA risk. Methods: Based on summary statistics from large-scale genome-wide association studies (GWAS), we quantified the genetic correlation between adiponectin and RA. Then bidirectional Mendelian randomization (MR) analysis was performed to assess the causal relationship. Twenty single-nucleotide polymorphisms (SNPs) associated with adiponectin were selected as instrumental variables from a recent GWAS (n = 67,739). We applied theses SNPs to a large-scale GWAS for RA (14,361 cases and 43,923 controls) with replication using RA data from the FinnGen consortium (6,236 cases and 147,221 controls) and the UK Biobank (5,201 cases and 457,732 controls). The inverse-variance weighted (IVW) and multiple pleiotropy-robust methods were used for two-sample MR analyses. Results: Our analyses showed no significant genetic correlation between circulating adiponectin levels and RA [rG = 0.127, 95% confidence interval (CI): -0.012 to 0.266, P = 0.074]. In MR analyses, genetically predicted adiponectin levels were not significantly associated with the RA risk (odds ratio: 0.98, 95% CI: 0.88-1.09, P = 0.669). In the reverse direction analysis, there is little evidence supporting an association of genetic susceptibility to RA with adiponectin (ß: 0.007, 95% CI: -0.003 to 0.018, P = 0.177). Replication analyses and sensitivity analyses using different models yielded consistent results. Conclusions: Our findings provided no evidence to support the causal effect of adiponectin levels on RA risk and of RA on circulating adiponectin levels.

Genetically Predicted Longer Telomere Length May Reduce Risk of Hip Osteoarthritis.

Objective: This two-sample Mendelian randomization (MR) study aimed to examine the potential causal association of telomere length (TL) with the risk of osteoarthritis (OA). Method: The summary-level data for OA was derived from the United Kingdom Biobank cohort, including 50,508 individuals of European descent. Eighteen single nucleotide polymorphisms associated with TL were identified as instrumental variables from the most up-to-date TL genome-wide association study (GWAS) involving over 78,592 individuals of European descent. Based on the GWASs data, MR was performed using established statistical analysis methods including the inverse variance weighted, weighted median, MR-Egger, and MR pleiotropy residual sum and outlier. Results: Genetically determined TL was not associated with the risk of total OA (IVW odds ratio [OR] = 1.00, 95% confidence interval [CI] = 0.83, 1.21). In subgroup analyses stratified by OA site, no evidence in favor of association between genetically determined TL and knee OA was found (IVW OR = 1.18, 95% CI = 0.89, 1.58). However, using WM method, we observed a limited protective effect of longer TL on the risk of hip OA (OR = 0.60, 95% CI = 0.36-0.99), whereas the results of the IVW (p = 0.931) and MR-PRESSO (p = 0.932) showed that TL had no effect on hip OA. Conclusions: This study does not support a causal association between TL and total OA. A potential protective association between longer TL and hip OA, though possible, remains less certain.

Causal association of monounsaturated fatty acids with rheumatoid arthritis but not osteoarthritis: A two-sample Mendelian randomization study.

OBJECTIVES: Previous studies have indicated that dietary monounsaturated fatty acids (MUFAs) are associated with decreased risk of osteoarthritis (OA) and rheumatoid arthritis (RA). However, the causality of the observed associations is largely undetermined. We sought to ascertain the potential causal roles of two of the most common MUFAs, oleic acid and palmitoleic acid, in RA and OA risk using a two-sample Mendelian randomization approach. METHODS: For the outcomes, we used summary-level data for RA (14 361 people with RA and 43 923 controls) and OA (10 083 people with OA and 40 425 controls) from two genome-wide association studies in European ancestry. For the exposures, five single-nucleotide polymorphisms associated with palmitoleic acid and one associated with oleic acid with genome-wide significance (P < 5 × 10-8) were selected as instrumental variables. The causal effects were estimated using the inverse-variance weighted method with several sensitivity analyses. RESULTS: For genetically predicted levels, an increase of one SD in palmitoleic acid (odds ratio, 0.24; 95% confidence interval, 0.10-0.59; P = 0.002) and oleic acid (odds ratio, 0.78; 95% confidence interval, 0.67-0.90; P < 0.001) was significantly associated with lower risk of RA. However, genetic predisposition to either of the two individual MUFAs was not associated with OA risk. Sensitivity analyses yielded similar results. CONCLUSIONS: Our Mendelian randomization analyses suggest a causal relationship between higher genetically predicted MUFA levels and lower risks of RA. However, the causality between MUFAs and OA cannot be inferred from this study. Further research is required to unravel the role of MUFA supplementation in arthritis prevention.

Detachable string magnetically controlled capsule endoscopy for detecting high-risk varices in compensated advanced chronic liver disease (CHESS1801): A prospective multicenter study.

BACKGROUND: Gastroesophageal varices is a serious complication of compensated advanced chronic liver disease (cACLD). Primary prophylaxis to reduce the risk of variceal hemorrhage is recommended if high-risk varices (HRV) are detected. We performed this study to compare the accuracy, patients' satisfaction and safety of detection of HRV by detachable string magnetically controlled capsule endoscopy (DS-MCCE) with esophagogastroduodenoscopy (EGD) as the reference. METHODS: We prospectively recruited participants with cACLD from 12 university hospitals (11 in China and one in the United Kingdom) between November 2018 and December 2019 (ClinicalTrials.gov, NCT03749954). All participants underwent DS-MCCE, followed by EGD within a week in a blinded fashion. Following endoscopy, and on the same day, participants were asked to fill in a satisfaction questionnaire regarding their experience. FINDINGS: A total of 105 eligible participants were enrolled. With EGD as the reference standard, the concordance index, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of DS-MCCE in diagnosis of HRV were 0•90 (95% confidence interval [CI]: 0•83-0•95), 92% (95% CI: 78-98%), 88% (95% CI: 78-95%), 80% (95% CI: 70-92%), 95% (95% CI: 90-100%), 7•91 (95% CI: 4•10-15•30), and 0•09 (95% CI: 0•03-0•30), respectively. The kappa score of 0•78 (95% CI: 0•65-0•90) suggested substantial agreement between DS-MCCE and EGD. Moreover, in participants undergoing EGD without sedation, the satisfaction of DS-MCCE was significantly better than that of EGD (p < 0•0001, d = 1•15 [95%CI: 0•88-1•42]). All participants confirmed the excretion of the capsule, and no adverse events occurred. INTERPRETATION: DS-MCCE is an accurate alternative to EGD for detecting HRV in cACLD, which is safe and associated with better satisfaction. FUNDING: A full list of funding can be found in the Funding Support section.