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Preparation of calibration curves is a critical step for large-scale quantification. However, this procedure is time-consuming, labor intensive. Herein, a novel isotopologue multipoint calibration (IMC) strategy, was proposed and demonstrated for the simultaneous quantitation of 120 pesticides and 83 veterinary drugs in surface water samples using Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS). In this strategy, the natural isotopic distribution was used to generate external calibration curves, eliminating the need of analyst's adjustment and many sets of chemical standard solutions required in external calibration curves. Additionally, this strategy was comprehensively validated, and the results indicated this strategy had better performance in both accuracy and precision, fully meeting the requirements for the quantitative analysis. Interestingly, for the samples with high concentration beyond the upper limit of quantitation, the IMC strategy could avoid samples dilution by monitoring the less abundant isotopic channels. Furthermore, the IMC method was successfully applied in the surface water samples collected from Anhui province, China. Among which, sulfamethoxazole and imidacoprid were the main contributors. In conclusion, we present a promising LC-HRMS strategy for the accurate quantitation of small molecules, which has a potential application in food and environmental analysis. [Display omitted] • Isotopologue multipoint as a novel calibration strategy using LC-HRMS is presented. • The strategy was used to quantitate 120 pesticides and 83 veterinary drugs in water. • The strategy simplifies the preparation of calibration curves and sample dilution. [ABSTRACT FROM AUTHOR]

• An approach to detect five antiviral drugs in honey was first developed. • A two-step fraction capture strategy was used to adsorb antiviral drugs in honey. • Five drugs with drastic polarity differences were simultaneously extracted. • The total positive rate of five antiviral drugs was 2.84% among 563 honey samples. • Stability studies showed moroxydine can be used as a potential drug to cure SBD. An effective sample pretreatment method followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) was first developed for simultaneous determination of five antiviral drug residues including ribavirin, moroxydine, amantadine, rimantadine and memantine in honey. To adsorb analytes with different binding properties and overcome the interference of sugars and uridine as endogenous ribavirin structural analogs in honey, the target drugs were extracted with 1% formic acid and then purified by a phenylboronic acid (PBA) solid phase extraction cartridge using two-step fraction capture prior to LC-MS/MS analysis. This method was validated by analyzing honey samples from nine floral origins including miscellaneous flowers, citrus, vitex, rape, acacia, sunflower, linden, buckwheat and jujube spiking at multiple levels, and the recoveries ranged from 82.46% to 116.34%, with relative standard deviations (RSDs) less than 14.58%. The limits of detection (LODs) and limits of quantitation (LOQs) of moroxydine, ribavirin, amantadine, rimantadine, and memantine were 0.1–2 µg/kg and 0.2–5 µg/kg, respectively. Depletion experiments of five antiviral drugs in honey at different storage and process temperatures demonstrated that moroxydine can potentially be used as a drug to cure sacbrood disease in honeybees. [ABSTRACT FROM AUTHOR]

• The toxicokinetics of α-ZEL and α-ZEL-14G were firstly compared and characterized in rats. • The metabolic pathways of α-ZEL and α-ZEL-14G were comprehensively investigated. • α-ZEL-14 G could be deglycosylated into α-ZEL, and glucuronidation was the predominant route for both α-ZEL and α-ZEL-14G. • α-ZEL and α-ZEL-14G was mediated by CYP 3A4, 2C8, and 1A2, while the deglycosylation of α-ZEL-14G by CES-I and CES-II. Alpha-zearalenol (α-ZEL) and its masked form α-zearalenol-14 glucoside (α-ZEL-14G) have much higher oestrogenic activity than zearalenone. Owing to very limited toxicokinetic and metabolic data, no reference points could be established for risk assessment. To circumvent it, the toxicokinetic, metabolic profiles, and phenotyping of α-ZEL and α-ZEL-14G were comprehensively investigated in this study. As a result, the plasma concentrations of α-ZEL and α-ZEL-14G were all below LOQ after oral administration, while after iv injection, both could be significantly bio-transformed into various metabolites. A complete hydrolysis of α-ZEL-14G contributed to α-ZEL overall toxicity. Additionally, 31 phase I and 10 phase II metabolites of α-ZEL, and 9 phase I and 5 phase II metabolites were identified for α-ZEL-14G. For α-ZEL, hydroxylation, dehydrogenation, and glucuronidation were the major metabolic pathways, while for α-ZEL-14G, it was deglycosylation, reduction, hydroxylation, and glucuronidation. Significant metabolic differences were observed for α-ZEL and α-ZEL-14G in the liver microsomes of rats, chickens, swine, goats, cows and humans. Phenotyping studies indicated that α-ZEL and α-ZEL-14G were mediated by CYP 3A4, 2C8, and 1A2. Moreover, the deglycosylation of α-ZEL-14G was critically mediated by CES-I and CES-II. The acquired data would provide fundamental perspectives for risk evaluation of mycotoxins and their modified forms. [ABSTRACT FROM AUTHOR]

• 14-(R) -hydroxy-gelsenicine, a novel plant toxin separated from poisonous honey, was firstly reported and identified. • The prevalence, toxicity, toxicokinetics and metabolic profile of 14-(R) -hydroxy-gelsenicine were investigated. • Flumazenil could effectively relieve symptoms of poisoning caused by 14-(R) -hydroxy-gelsenicine. The fascinating collection and evaluation of natural products with enormous structural and chemical diversity can contribute to ensure human health and inspire potential drug discovery. We reported the identification of 14-(R)-hydroxy-gelsenicine (HGE), a new component from poisonous honey, which has recently caused multiple serious intoxications and deaths up on consumption. The prevalence, toxicity, toxicokinetics and metabolic profile of HGE were evaluated through in vitro and in vivo analyses. HGE is a very toxic substance and shows significant gender difference with LD 50 of 0.125 mg kg−1 and 0.295 mg kg−1 for the female and male mice, respectively. Toxicokinetics test indicates that HGE has good bioavailability in rats, and is metabolized extensively, in which hydroxylation, reduction, N -demethyl ether and glucuronication are the major metabolic pathways. Additionally, HGE shows specific neurotoxicity by enhancing the binding of γ -aminobutyric acid (GABA) to its receptors. We found that flumazenil, a selective antagonist of GABA receptor, could effectively increase the survival of the tested animals, which provides a potential therapy for future clinical applications. [ABSTRACT FROM AUTHOR]

The shape of nanochannels plays a crucial role in the ion selectivity and overall performance of reverse electrodialysis (RED) systems. However, current research on two-dimensional nanochannel shapes is largely limited to a few fixed asymmetric forms. This study explores the impact of randomly shaped nanochannels using dimensionless methods, controlling their randomness by varying their length and shape amplitude. The research systematically compares how alterations in the nanochannel length and shape amplitude influence various system performance parameters. Our findings indicate that increasing the nanochannel length can significantly enhance the system performance. While drastic changes in the nanochannel shape amplitude positively affect the system performance, the most significant improvements arise from the interplay between the nanochannel length and shape amplitude. This compounding effect creates a local optimum, resulting in peak system performance. Within the range of dimensionless lengths from 0 to 30, the system reaches its optimal performance at a dimensionless length of approximately 25. Additionally, we explored two other influencing factors: the nanochannel surface charge density and the concentration gradient of the solution across the nanochannel. Optimal performance is observed when the nanochannel has a high surface charge density and a low concentration gradient, particularly with random shapes. This study advances the theoretical understanding of RED systems in two-dimensional nanochannels, guiding research towards practical operational conditions.

Cathode-electrolyte interphase (CEI) is crucial for the reversibility of rechargeable batteries, yet receives less attention compared to solid-electrolyte interphase (SEI). The prevalent weakly-solvating electrolyte is usually proposed from the standing point of obtaining robust SEI, however, the resultant weak ion-solvent interaction gives rise to excessive free solvents and forms thick CEI with high kinetic barriers, which is disadvantageous for interfacial stability at the high working voltage. Herein, a highly-solvating electrolyte is reported to immobilize free solvents by generating stable ternary complexes and facilitate the growth of homogeneous and ultrathin CEI to boost the electrochemical performances of potassium-ion batteries (PIBs). Through time-of-flight secondary ion mass spectrometry and cryogenic transmission electron microscopy, It is revealed that the deliberately coordinated complexes are the key to forming mechanically stable and inorganic-rich CEI with superior diffusion kinetics for high-performing PIBs. Coupling with a K 0.5 MnO 2 cathode and a soft carbon (SC) anode, a high energy density (202.3 Wh kg -1 ) is achieved with an exceptional cycle lifespan (92.5% capacity retention after 500 cycles) in a SC||K 0.5 MnO 2 full cell, setting new performance benchmarks for PIBs., (© 2024 Wiley‐VCH GmbH.)

Excessive anthropogenic phosphorus (P) emissions put constant pressure on aquatic ecosystems. This pressure can be quantified as the freshwater eutrophication potential (FEP) by linking P emissions, P fate in environmental compartments, and the potentially disappeared fraction of species due to increase of P concentrations in freshwater. However, previous fate modeling on global and regional scales is mainly based on the eight-direction algorithm without distinguishing pollution sources. The algorithm fails to characterize the fate paths of point-source emissions via subsurface pipelines and wastewater treatment infrastructure, and exhibits suboptimal performance in accounting for multidirectional paths caused by river bifurcations, especially in flat terrains. Here we aim to improve the fate modeling by incorporating various fate paths and addressing multidirectional scenarios. We also update the P estimates by complementing potential untreated point-source emissions (PSu). The improved method is examined in a rapidly urbanizing area in Taihu Lake Basin, China in 2017 at a spatial resolution of 100 m × 100 m. Results show that the contribution of PSu on FEP (62.6%) is greater than that on P emissions (58.5%). The FEP is more spatially widely distributed with the improved fate modeling, facilitating targeted regulatory strategies tailored to local conditions.

Background and Aims: Emerging evidence has raised an obesity paradox in observational studies of body mass index (BMI) and health among the oldest-old (aged ≥80 years), as an inverse relationship of BMI with mortality was reported. This study was to investigate the causal associations of BMI, waist circumference (WC), or both with mortality in the oldest-old people in China., Methods: A total of 5306 community-based oldest-old (mean age 90.6 years) were enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) between 1998 and 2018. Genetic risk scores were constructed from 58 single-nucleotide polymorphisms (SNPs) associated with BMI and 49 SNPs associated with WC to subsequently derive causal estimates for Mendelian randomization (MR) models. One-sample linear MR along with non-linear MR analyses were performed to explore the associations of genetically predicted BMI, WC, and their joint effect with all-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality., Results: During 24 337 person-years of follow-up, 3766 deaths were documented. In observational analyses, higher BMI and WC were both associated with decreased mortality risk [hazard ratio (HR) 0.963, 95% confidence interval (CI) 0.955-0.971 for a 1-kg/m2 increment of BMI and HR 0.971 (95% CI 0.950-0.993) for each 5 cm increase of WC]. Linear MR models indicated that each 1 kg/m2 increase in genetically predicted BMI was monotonically associated with a 4.5% decrease in all-cause mortality risk [HR 0.955 (95% CI 0.928-0.983)]. Non-linear curves showed the lowest mortality risk at the BMI of around 28.0 kg/m2, suggesting that optimal BMI for the oldest-old may be around overweight or mild obesity. Positive monotonic causal associations were observed between WC and all-cause mortality [HR 1.108 (95% CI 1.036-1.185) per 5 cm increase], CVD mortality [HR 1.193 (95% CI 1.064-1.337)], and non-CVD mortality [HR 1.110 (95% CI 1.016-1.212)]. The joint effect analyses indicated that the lowest risk was observed among those with higher BMI and lower WC., Conclusions: Among the oldest-old, opposite causal associations of BMI and WC with mortality were observed, and a body figure with higher BMI and lower WC could substantially decrease the mortality risk. Guidelines for the weight management should be cautiously designed and implemented among the oldest-old people, considering distinct roles of BMI and WC., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

What Is Already Known About This Topic?: Antimony (Sb) has been identified as a new neurotoxicant that impacts neurological functions in animal studies. However, its effects on the human population remain unknown., What Is Added by This Report?: The study reveals that there is an association between exposure to Sb and a higher incidence of cognitive impairment in older adults. The dose-response curve demonstrates that the risk of cognitive impairment consistently increased with higher levels of Sb exposure without a discernible threshold., What Are the Implications for Public Health Practice?: Reducing exposure to Sb may have a beneficial effect in delaying or preventing the onset of cognitive impairment. This intervention has the potential to significantly decrease the disease burden associated with cognitive impairment, ultimately contributing to social development., Competing Interests: Xiaoming Shi is a editorial board member of the journal China CDC Weekly. He was not involved in the peer-review or handling of the manuscript. The authors have no other competing interests to disclose., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2024.)

Background: Hepatocellular carcinoma (HCC) heterogeneity impacts prognosis, and imaging is a potential indicator., Purpose: To characterize HCC image subtypes in MRI and correlate subtypes with recurrence., Study Type: Retrospective., Population: A total of 440 patients (training cohort = 213, internal test cohort = 140, external test cohort = 87) from three centers., Field Strength/sequence: 1.5-T/3.0-T, fast/turbo spin-echo T 2 -weighted, spin-echo echo-planar diffusion-weighted, contrast-enhanced three-dimensional gradient-recalled-echo T 1 -weighted with extracellular agents (Gd-DTPA, Gd-DTPA-BMA, and Gd-BOPTA)., Assessment: Three-dimensional volume-of-interest of HCC was contoured on portal venous phase, then coregistered with precontrast and late arterial phases. Subtypes were identified using non-negative matrix factorization by analyzing radiomics features from volume-of-interests, and correlated with recurrence. Clinical (demographic and laboratory data), pathological, and radiologic features were compared across subtypes. Among clinical, radiologic features and subtypes, variables with variance inflation factor above 10 were excluded. Variables (P < 0.10) in univariate Cox regression were included in stepwise multivariate analysis. Three recurrence estimation models were built: clinical-radiologic model, subtype model, hybrid model integrating clinical-radiologic characteristics, and subtypes., Statistical Tests: Mann-Whitney U test, Kruskal-Wallis H test, chi-square test, Fisher's exact test, Kaplan-Meier curves, log-rank test, concordance index (C-index). Significance level: P < 0.05., Results: Two subtypes were identified across three cohorts (subtype 1:subtype 2 of 86:127, 60:80, and 36:51, respectively). Subtype 1 showed higher microvascular invasion (MVI)-positive rates (53%-57% vs. 26%-31%), and worse recurrence-free survival. Hazard ratio (HR) for the subtype is 6.10 in subtype model. Clinical-radiologic model included alpha-fetoprotein (HR: 3.01), macrovascular invasion (HR: 2.32), nonsmooth tumor margin (HR: 1.81), rim enhancement (HR: 3.13), and intratumoral artery (HR: 2.21). Hybrid model included alpha-fetoprotein (HR: 2.70), nonsmooth tumor margin (HR: 1.51), rim enhancement (HR: 3.25), and subtypes (HR: 5.34). Subtype model was comparable to clinical-radiologic model (C-index: 0.71-0.73 vs. 0.71-0.73), but hybrid model outperformed both (C-index: 0.77-0.79)., Conclusion: MRI radiomics-based clustering identified two HCC subtypes with distinct MVI status and recurrence-free survival. Hybrid model showed superior capability to estimate recurrence., Level of Evidence: 3 TECHNICAL EFFICACY STAGE: 2., (© 2024 International Society for Magnetic Resonance in Medicine.)

The growing and increasingly intensified agricultural sector exerts major pressures on the environment. Specifically, nitrogen (N) and phosphorus (P) runoff can induce eutrophication in freshwater ecosystems. To formulate environmental strategies for controlling eutrophication, decision-makers commonly consider the importance of pollutant contributors before developing sector-specific environmental policies. These types of science-based decisions benefit from nutrient models that quantify nutrient transport and fate. However, due to a lack of fertilizer application data, distributed models are generally not suitable for most rural regions with extensive agriculture, while lumped models cannot properly characterize the spatial variation of nutrient fate in these regions. To assess the nutrient contributions from different emission sources to freshwater, we developed a localized semi-distributed model to simulate total nitrogen (TN) and total phosphorus (TP) in 52 inflow rivers of Fuxian Lake Basin in China. The results show that diffuse sources contributed 82 % TN and 92 % TP loading to the inflow rivers. The highest eutrophication potentials (i.e., loading per area) is from the built environment, which is more than 10 times that of forests, but the contribution of the built environment to total diffuse loading is only the second-highest as it occupies 8.7 % of the surface area. Farmland is the main contributor, generating 49 % of diffuse TN and 57 % TP, respectively. Our results show that promoting a 10 % increase in nutrient use efficiency would reduce 5 % of N and 30 % of P diffuse loadings to the rivers. Through examining the impact of nutrient use efficiency, we emphasize the potential trade-offs between food productivity and environmental effects. This analysis workflow can be applied to other agricultural regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Vitamin D deficiency and disability are both prevalent among older adults. However, the association between them has rarely been investigated in the oldest-old subjects (aged ≥80 y), and the causality remains unclear., Objective: This study aimed to elucidate the causal effect of vitamin D on the incident risk of disability in activities of daily living (ADL) among Chinese oldest-old based on the 2012-2018 Chinese Healthy Ageing and Biomarkers Cohort Study., Methods: Serum 25-hydroxyvitamin D [25(OH)D] concentrations and ADL status at baseline and follow-up interviews were documented. Cox regression models were applied among 1427 oldest-old (mean age, 91.2 y) with normal baseline ADL status. One sample Mendelian randomization (MR) analyses were performed on a subset of 941 participants with qualified genetic data, using a 25(OH)D-associated genetic risk score as the genetic instrument., Results: During a median follow-up of 3.4 y, 231 participants developed disability in ADL. Serum 25(OH)D concentration was inversely associated with the risk of disability in ADL [per 10 nmol/L increase hazard ratio (HR) 0.85; 95% CI: 0.75, 0.96]. Consistent results from MR analyses showed that a 10 nmol/L increment in genetically predicted 25(OH)D concentration corresponded to a 20% reduced risk of ADL disability (HR 0.80; 95% CI: 0.68, 0.94). Nonlinear MR demonstrated a monotonic declining curve, with the HRs exhibiting a more pronounced reduction among individuals with 25(OH)D concentrations below 50 nmol/L. Subgroup analyses showed that the associations were more distinct among females and those with poorer health conditions., Conclusions: Our study supports an inverse causal relationship between serum 25(OH)D concentration and the risk of disability in ADL among Chinese oldest-old. This protective effect was more distinct, especially for participants with vitamin D deficiency. Appropriate measures for improving vitamin D might help reduce the incidence of physical disability in this specific age group., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Inefficient global nutrient (i.e., phosphorus (P) and nitrogen (N)) management leads to an increase in nutrient delivery to freshwater and coastal ecosystems and induces eutrophication in these aquatic environments. This process threatens the various species inhabiting these ecosystems. In this study, we developed regionalized characterization factors (CFs) for freshwater eutrophication at 0.5 × 0.5-degree resolution, considering different fates for direct emissions to freshwater, diffuse emissions, and increased erosion due to agricultural land use. The CFs were provided for global and regional species loss of freshwater fish. CFs for global species loss were quantified by integrating global extinction probabilities. Results showed that the CFs for P and N impacts on freshwater fish are higher in densely populated regions that encompass either large lakes or the headwaters of large rivers. Focusing on nutrient-limited areas increases country-level CFs in 51.9 % of the countries for P and 49.5 % of the countries for N compared to not considering nutrient limitation. This study highlights the relevance of considering freshwater eutrophication impacts via both P and N emissions and identifying the limiting nutrient when performing life cycle impact assessments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The associations between plasma vitamin B 12 level and anemia under different dietary patterns in elderly Chinese people are poorly understood. We aimed to examine the associations between plasma vitamin B 12 levels and anemia under different dietary patterns in adults aged 65 years and older in nine longevity areas in China., Methods: A total of 2405 older adults completed a food frequency questionnaire at the same time as a face-to-face interview. The dietary diversity score (DDS) was assessed based on the food frequency questionnaire, with the low DDS group referring to participants with a DDS score ≤ 4 points. Vitamin B 12 levels were divided into two groups of high (>295 pg/mL) and low (≤ 295 pg/mL) with the median used as the cut-off point. Sub-analyses were also performed on older adults divided into tertiles of vitamin B 12 levels: low (< 277 pg/mL), medium (277-375 pg/mL) and high (> 375 pg/mL) to study the association of these levels with anemia., Results: Six hundred ninety-five (28.89%) of these people were diagnosed with anemia and had a mean age of 89.3 years. Higher vitamin B 12 levels were associated with a decreased risk of anemia (multi-adjusted OR, 0.59, [95% CI, 0.45 ~ 0.77] P < 0.001) in older adults with a low DDS, whereas no significant association between vitamin B 12 levels and anemia was found in older adults with a high DDS in a full-model after adjustment for various confounding factors (multi-adjusted OR, 0.88, [95% CI, 0.65 ~ 1.19], P = 0.41)., Conclusion: The relationship between vitamin B 12 levels and the prevalence of anemia was significant only when the level of dietary diversity in the older adults was relatively low. The dietary structure of the population should be taken into consideration in combination in order to effectively improve anemia status by supplementing vitamin B 12 ., (© 2024. The Author(s).)

Objective: To explore the abnormal expression of HORMA domain containing protein 1 (HORMAD1) in chronic rhinosinusitis (CRS) patients and its correlation with the expression of inflammatory factors., Study Design: Observational study. Place and Duration of the Study: Department of Otolaryngology Head and Neck Surgery, the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, China, from August 2021 to October 2022., Methodology: Eighty CRS patients and 80 healthy volunteers participated in this study according to the inclusion and exclusion criteria. The plasma samples of the patients were collected and the level of HORMAD1 was determined by RT-qPCR methods. Commercially available ELISA kits were used for the detection of the levels of cytokines, and the correlation between HORMAD1 expression and the level of cytokines was analysed., Results: HORMAD1 expression was significantly increased in CRS patients as compared to the healthy subjects. Moreover, the results of ROC curve suggested AUC for HORMAD1 was 0.9442, 95% confidence interval, 0.9057 to 0.9827. IL-1β, TNF-α, IL-6 as well as IFN-γ were all markedly elevated in the CRS group. Positive correlations were found between HORMAD1 expression and the cytokines., Conclusion: HORMAD1 may trigger an inflammatory response in CRS patients. The results of the current study could be beneficial for improving the therapeutic efficacy of CRS patients., Key Words: HORMAD1, Chronic rhinosinusitis, Expression, Inflammatory factors, DNA damage, Cytokines.

Background and Objectives: Physical function deterioration is always accompanied by a cognitive decline in older adults. However, evidence is lacking for the long-term simultaneous changing patterns of cognition and physical frailty and their associations with mortality among older adults., Research Design and Methods: This study included 8,231 adults aged ≥65 with a baseline and at least one follow-up assessment of both cognition and physical frailty from the 2007-2018 Chinese Longitudinal Healthy Longevity Survey. Physical frailty (FRAIL phenotype) and cognition (Mini-Mental State Examination) were applied. Group-based joint trajectory modeling was used to fit the joint trajectories of cognition and physical frailty. Cox proportional hazards model was used to evaluate the trajectory-mortality associations., Results: Three distinct joint trajectories were identified: no joint progression (34.4%), moderate joint progression (47.0%), and rapid joint progression (18.6%). During a median follow-up of 8.3 years, the rapid joint progression group, compared to the no joint progression , had the highest risk for all-cause mortality (hazard ratio (HR), 3.37 [95% CI: 2.99-3.81]), cardiovascular (CVD) mortality (3.21 [2.08-4.96]) and non-CVD mortality (2.99 [2.28-3.92]), respectively. Joint trajectory was found to be more predictive of mortality as compared to baseline measures of cognition and/or frailty ( C -statistic ranged from 0.774 to 0.798). Higher changing rates of cognition and frailty were observed among all-cause decedents compared to CVD and non-CVD decedents over a 45-year span (aged 65-110) before death., Discussion and Implications: Our study suggested that subjects with the worst cognitive decline and severest physical frailty progression were at the highest risk for all-cause and cause-specific mortality. Our findings expand the limited prior knowledge on the dynamic course of cognition and frailty., Competing Interests: None reported., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objective: This study aimed to examine the impact of greenness and fine particulate matter <2.5 μm (PM 2.5 ) on overweight/obesity among older adults in China., Methods: A total of 21,355 participants aged ≥65 years were included from the Chinese Longitudinal Healthy Longevity Survey between 2000 and 2018. Normalized difference vegetation index (NDVI) with a radius of 250 m and PM 2.5 in a 1 × 1-km grid resolution were calculated around each participant's residence. Cox proportional hazards models were used to estimate the effects of NDVI and PM 2.5 on overweight/obesity. Interaction and mediation analyses were conducted to explore combined effects., Results: The study observed 1895 incident cases of overweight/obesity over 109,566 person-years. For every 0.1-unit increase in NDVI the hazard ratio of overweight/obesity was 0.91 (95% CI: 0.88-0.95), and for every 10-μg/m 3 increase in PM 2.5 the hazard ratio was 1.11 (95% CI: 1.07-1.14). The effect of NDVI on overweight/obesity was partially mediated by PM 2.5 , with a relative mediation proportion of 20.10% (95% CI: 1.63%-38.57%)., Conclusions: Greenness exposure appears to lower the risk of overweight/obesity in older adults in China, whereas PM 2.5 , acting as a mediator, partly mediated this protective effect., (© 2023 The Obesity Society.)

Background: Lifestyle and longevity genes have different and important roles in the human lifespan; however, the association between a healthy lifestyle in late-life and life expectancy mediated by genetic risk is yet to be elucidated. We aimed to investigate the associations of healthy lifestyle in late-life and genetic risk with life expectancy among older adults., Methods: A weighted healthy lifestyle score was constructed from the following variables: current non-smoking, non-harmful alcohol consumption, regular physical activity, and a healthy diet. Participants were recruited from the Chinese Longitudinal Healthy Longevity Survey, a prospective community-based cohort study that took place between 1998 and 2018. Eligible participants were aged 65 years and older with available information on lifestyle factors at baseline, and then were categorised into unhealthy (bottom tertile of the weighted healthy lifestyle score), intermediate (middle tertile), and healthy (top tertile) lifestyle groups. A genetic risk score was constructed based on 11 lifespan loci among 9633 participants, divided by the median and classified into low and high genetic risk groups. Stratified Cox proportional hazard regression was used to estimate the interaction between genetic and lifestyle factors on all-cause mortality risk., Findings: Between Jan 13, 1998, and Dec 31, 2018, 36 164 adults aged 65 years and older were recruited, among whom a total of 27 462 deaths were documented during a median follow-up of 3·12 years (IQR 1·62-5·94) and included in the lifestyle association analysis. Compared with the unhealthy lifestyle category, participants in the healthy lifestyle group had a lower all-cause mortality risk (hazard ratio [HR] 0·56 [95% CI 0·54-0·57]; p<0·0001). The highest mortality risk was observed in individuals in the high genetic risk and unhealthy lifestyle group (HR 1·80 [95% CI 1·63-1·98]; p<0·0001). The absolute risk reduction was greater for participants in the high genetic risk group. A healthy lifestyle was associated with a gain of 3·84 years (95% CI 3·05-4·64) at the age of 65 years in the low genetic risk group, and 4·35 years (3·70-5·06) in the high genetic risk group., Interpretation: A healthy lifestyle, even in late-life, was associated with lower mortality risk and longer life expectancy among Chinese older adults, highlighting the importance of a healthy lifestyle in extending the lifespan, especially for individuals with high genetic risk., Funding: National Natural Science Foundation of China., Translation: For the Mandarin translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Advancing electrocatalysts for alkaline hydrogen oxidation/evolution reaction (HOR/HER) is essential for anion exchange membrane-based devices. The state-of-the-art Pt-based electrocatalysts for alkaline HOR suffer from low intrinsic activities and severe CO poisoning due to the challenge of simultaneously optimizing surface adsorption toward different adsorbates. Herein, this challenge is overcome by tuning an atomic MoO x layer with high oxophilicity onto PtMo nanoparticles (NPs) with optimized H ad , OH ad , and CO ad adsorption for boosting anti-CO-poisoning hydrogen-cycle electrocatalysis in alkaline media. For alkaline HOR, this catalyst exhibits high kinetics and an exchange current density of 3.19 mA µg Pt -1 at 50 mV versus reversible hydrogen electrode and 0.83 mA cm Pt -2 , 10.3- and 3.8-fold higher than those of commercial Pt/C, respectively. For alkaline HER, it achieves an unprecedented overpotential of 37 mV at 10 mA cm -2 . Experimental and theoretical studies show that the orchestrated electronic and oxophilic regulation of the PtMo/MoO x interface NPs simultaneously optimizes H ad and OH ad adsorption for boosting alkaline hydrogen electrocatalysis, whereas reactive oxygen from the amorphous MoO x atomic layer lowers the CO oxidation reaction barrier, leading to superior anti-poisoning ability even at 100 ppm CO., (© 2023 Wiley-VCH GmbH.)

Kawasaki disease (KD), an acute febrile systemic vasculitis in children, has become the leading cause of acquired heart disease in developed countries. Recently, the altered gut microbiota was found in KD patients during the acute phase. However, little is known about its characteristics and role in the pathogenesis of KD. In our study, an altered gut microbiota composition featured by the reduction in SCFAs-producing bacteria was demonstrated in the KD mouse model. Next, probiotic Clostridium butyricum ( C. butyricum ) and antibiotic cocktails were respectively employed to modulate gut microbiota. The use of C. butyricum significantly increased the abundance of SCFAs-producing bacteria and attenuated the coronary lesions with reduced inflammatory markers IL-1β and IL-6, but antibiotics depleting gut bacteria oppositely deteriorated the inflammation response. The gut leakage induced by dysbiosis to deteriorate the host's inflammation was confirmed by the decreased intestinal barrier proteins Claudin-1, Jam-1, Occludin, and ZO-1, and increased plasma D-lactate level in KD mice. Mechanistically, SCFAs, the major beneficial metabolites of gut microbes to maintain the intestinal barrier integrity and inhibit inflammation, was also found decreased, especially butyrate, acetate and propionate, in KD mice by gas chromatography-mass spectrometry (GC-MS). Moreover, the reduced expression of SCFAs transporters, monocarboxylate transporter 1 (MCT-1) and sodium-dependent monocarboxylate transporter 1 (SMCT-1), was also shown in KD mice by western blot and RT-qPCR analyses. As expected, the decrease of fecal SCFAs production and barrier dysfunction were improved by oral C. butyricum treatment but was deteriorated by antibiotics. In vitro , butyrate, not acetate or propionate, increased the expression of phosphatase MKP-1 to dephosphorylate activated JNK, ERK1/2 and p38 MAPK against excessive inflammation in RAW264.7 macrophages. It suggests a new insight into probiotics and their metabolites supplements to treat KD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Qian, Zhang, Zhao, Cen, Zhang, Zhou, Luo, Jia, Rong and Chu.)

The increasing application of synthetic fertilizer has tripled nitrogen (N) inputs over the 20th century. N enrichment decreases water quality and threatens aquatic species such as fish through eutrophication and toxicity. However, the impacts of N on freshwater ecosystems are typically neglected in life cycle assessment (LCA). Due to the variety of environmental conditions and species compositions, the response of species to N emissions differs among ecoregions, requiring a regionalized effect assessment. Our study tackled this issue by establishing regionalized species sensitivity distributions (SSDs) of freshwater fish against N concentrations for 367 ecoregions and 48 combinations of realms and major habitat types globally. Subsequently, effect factors (EFs) were derived for LCA to assess the effects of N on fish species richness at a 0.5 degree × 0.5 degree resolution. Results show good SSD fits for all of the ecoregions that contain sufficient data and similar patterns for average and marginal EFs. The SSDs highlight strong effects on species richness due to high N concentrations in the tropical zone and the vulnerability of cold regions. Our study revealed the regional differences in sensitivities of freshwater ecosystems against N content in great spatial detail and can be used to assess more precisely and comprehensively nutrient-induced impacts in LCA.

Ruthenium chalcogenide is a highly promising catalytic system as a Pt alternative for hydrogen evolution reaction (HER). However, well-studied ruthenium selenide (RuSe 2 ) still exhibits sluggish HER kinetics in alkaline media due to the inappropriate adsorption strength of H and H 2 O. Herein, xx report a new design of Cu-doped Ru/RuSe 2 heterogeneous nanosheets (NSs) with optimized H and H 2 O adsorption strength for highly efficient HER catalysis in alkaline media. Theoretical calculations reveal that the superior HER performance is attributed to a synergistic effect of the unique heterointerfaced structure and Cu doping, which not only optimizes the electronic structure with a suitable d-band center to suppress proton overbinding but also alleviates the energy barrier with enhanced H 2 O adsorption. As a result, Cu-doped heterogeneous Ru/RuSe 2 NSs exhibit a small overpotential of 23 mV at 10 mA cm -2 , a low Tafel slope of 58.5 mV dec -1 and a high turnover frequency (TOF) value of 0.88 s -1 at 100 mV for HER in alkaline media, which is among the best catalysts in noble metal-based electrocatalysts toward HER. The present Cu-doped Ru/RuSe 2 NSs interface catalyst is very stable for HER by showing no activity decay after 5000-cycle potential sweeps. This work heralds that heterogeneous interface modulation opens up a new strategy for the designing of more efficient electrocatalysts., (© 2023 Wiley-VCH GmbH.)

What Is Already Known About This Topic?: Limited evidence on healthy longevity was provided in the world, and no studies investigated the fractions of healthy longevity attributed to modifiable factors., What Is Added by This Report?: Incidences of longevity and healthy longevity in China are provided. It reveals that the total weighted population attributable fractions for lifestyles and all modifiable factors were 32.8% and 83.7% for longevity, respectively, and 30.4% and 73.4% for healthy longevity, respectively., What Are the Implications for Public Health Practice?: China has a high potential for longevity and healthy longevity. Strategies may be targeted at education and residence in early life as well as healthy lifestyles, disease prevention, and functional optimization in late life., Competing Interests: No conflicts of interest., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2023.)

Introduction: About half of adults aged ≥80 years suffer from frailty. Exercise is considered effective in preventing frailty but may be inapplicable to adults aged ≥80 years due to physical limitations. As an alternative, we aimed to explore the association of leisure activities with frailty and identify potential interaction with established polygenic risk score (PRS) among adults aged ≥80 years., Methods: Analyses were performed in a prospective cohort study of 7,471 community-living older adults aged ≥80 years who were recruited between 2002 and 2014 from 23 provinces in China. Leisure activity was assessed using a seven-question leisure activity index and frailty was defined as a frailty index ≥0.25 using a validated 39-item health-related scale. The PRS was constructed using 59 single-nucleotide polymorphisms associated with frailty in a subsample of 2,541 older adults. Cox proportional hazards models were used to explore the associations of leisure activities, PRS with frailty., Results: The mean age of participants was 89.4 ± 6.6 years (range: 80-116). In total, 2,930 cases of frailty were identified during 42,216 person-years of follow-up. Each 1 unit increase in the leisure activity index was associated with 12% lower risk of frailty (hazard ratio: 0.88 [95% confidence interval, 0.85-0.91]). Participants with high genetic risk (PRS &gt;2.47 × 10-4) suffered from 26% higher risk of frailty. Interaction between leisure activity and genetic risk was not observed., Conclusion: Evidence is presented for the independent association of leisure activities and genetic risk with frailty. Engagement in leisure activities is suggested to be associated with lower risk of frailty across all levels of genetic risk among adults aged ≥80 years., (© 2023 S. Karger AG, Basel.)

Background: The heavy metals cadmium (Cd) and mercury (Hg) are known to be widespread environmental contaminants and high occupational exposure adversely affects the risk of chronic kidney disease (CKD). However, evidence from epidemiological studies linking low Cd and Hg exposure (or non-industrial) to the risk of progression to CKD are conflicting. This study aimed to explore the association of low Cd and Hg exposure with the risk of CKD in Chinese adults aged ≥80 years., Methods: The participants were recruited for the Healthy Aging and Biomarkers Cohort Study in 2017, an ongoing perspective survey conducted in longevity areas in China initially involving 3016 older adults. We used logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals of CKD setting Cd and Hg as categorical variables. Logistic regression with restricted cubic spline was used to characterize a dose-response relationships between Cd or Hg concentrations and the risk of CKD in the study population., Results: The ORs for the risk of CKD comparing the fourth to the first quartile of blood Cd, blood Hg, urine Cd, and urine Hg were 1.77, 1.57, 2.03, and 1.50, respectively. Restricted cubic spline models showed that blood Cd and urine Hg were significantly linearly correlated with the risk of CKD, while blood Hg and urine Cd were non-linearly correlated with the risk of CKD with a steeper slope at concentrations <2.30 μg/L and 3.30 μg/g creatinine., Conclusions: Our findings suggest that even low Cd and Hg exposure (or non-industrial) were associated with increased risk of CKD in Chinese oldest old, although we did not find a significant multiplicative and additive interaction between Cd and Hg levels in relation to the risk of CKD., (Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

The necessary step of directly adding hydrogen peroxide (H 2 O 2 ) into the detection system in traditional immunoassays hampers their applications as a portable device for point-of-care analysis due to the unstable liquid form of H 2 O 2 . Herein, a strategy of self-supplying H 2 O 2 and signal amplification triggering by copper peroxide nanodots encapsulated (CPNs) in metal-organic frameworks (ZIF-8) was proposed in an immunoassay for dual-signal detection of bisphenol A (a typical emerging organic pollutant), which was further fabricated as a lab-in-a-tube device integrated with a smartphone sensing platform. Herein, CPNs@ZIF-8 was modified on the antibody against bisphenol A; after the competitive binding of analytes, coating antigens, and antibodies, the released H 2 O 2 and Cu 2+ from encapsulated CPNs under the acidic condition will trigger a Fenton-like reaction to generate ·OH for oxidization of TMB; meanwhile, Cu 2+ could quench the fluorescence of GSH-Au NCs, resulting in dual-mode signals for measurements. Most importantly, self-supplying H 2 O 2 with high stability was undertaken by CPNs, and the remarkably increased signal molecule (CPN) loading was ascribed to the excellent capacity of metal-organic frameworks (ZIF-8). In addition, good recoveries were obtained from a colorimetric/fluorescent dual-mode strategy. The constructed device demonstrated great potential as a universal platform for rapid detection of various environmental contaminants using corresponding antibodies relying on its performance of satisfactory stability, sensitivity, and accuracy.

Background: To investigate the association between coping styles, gender, their interactions and non-suicidal self-injurious (NSSI) behaviors among middle school students in rural western China under COVID-19., Methods: A multicentre cross-sectional study method was used to conduct an online survey of 8,361 students from 23 middle schools in the northern Sichuan region by clustering sampling, using the General Information Questionnaire, the Ottawa Self-Injury Inventory, and the Coping Style Scale for Middle School Students., Results: The past year prevalence of NSSI among middle school students in rural west China was 5.7%. The differences in scores between those with and without NSSI on all dimensions of coping styles were statistically significant ( p < 0.001). Multivariate logistic regression analysis revealed that vocational high school ( OR = 1.67), girls ( OR = 2.5), single parent with divorced parents ( OR = 1.89), remarriage with divorced parents ( OR = 1.81), and tolerance ( OR = 1.17), venting emotions ( OR = 1.15) and fantasy/denial ( OR = 1.07) in coping styles may increase the risk of NSSI among middle school students, while problem solving ( OR = 0.9) and seeking social support ( OR = 0.9) among coping styles may reduce the risk of NSSI among middle school students. The interaction results show that gender has a moderating role in the process of endurance, avoidance, venting of emotions, and fantasy/denial influencing non-suicidal self-injury in middle school students., Conclusion: There is an association between coping styles and self-injury among middle school students in rural areas in western China, with gender playing a moderating role. Active attention should be paid to students' coping styles and encouraging them to adopt positive coping styles as well as avoid negative coping styles, especially in the case of girls, which can help prevent self-injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Zhang, Huang, Zhao, Xiao, Zhang, Li, Zhao, Ma, Ou, Wang, Ou and Luo.)

Moderate adsorption of oxygenated intermediates takes a significant role in rational design of high-efficiency oxygen reduction reaction (ORR) electrocatalysts. Long-serving as a reliable strategy to tune geometric structure of nanomaterials, defect engineering enjoys the great ability of adjusting the coordination environment of catalytic active sites, which enables dominant regulation of adsorption energy and kinetics of ORR catalysis. However, limited to controllable nanocrystals fabrication, inducing uniformly dispersed high-coordinated defects into ultrathin 2D nanosheets remains challenging. Herein, atomic-scale cavities (ASCs) are proposed as a new kind of high-coordinated active site and successfully introduced into suprathin Pd (111)-exposed metallene. Due to its atomic concave architecture, leading to elevated CN and moderately downshifted d-band center, the as-made Pd metallene with ASCs (c-Pd M) exhibits excellent ORR performance with mass activity of 2.76 A mg Pd -1 at 0.9 V versus reversible hydrogen electrode (RHE) and half-wave potential as high as 0.947 V, which is 18.9 (2.7) times higher and 104 (46) mV larger than that of commercial Pt/C (Pd metallene without ASCs). Besides, the durability of c-Pd M exceeds its commercial counterpart with ≈30% loss after 5000 cycles. This work highlights a new-style mentality of designing fancy active sites toward efficient ORR electrocatalysis., (© 2022 Wiley-VCH GmbH.)

Endothelial-to-mesenchymal transition (EndMT) is implicated in myofibroblast-like cell-mediated damage to coronary artery wall of Kawasaki disease (KD) patients, which subsequently increases the risk of coronary artery aneurysm. Many circular RNAs (circRNAs) have been reported to be associated with cardiovascular diseases. However, the roles and underlying molecular mechanism of circRNAs in KD-associated EndMT remains indefinite. In this research, we screened out circRNA-3302 from human umbilical vein endothelial cells (HUVECs) treated by sera from healthy controls (HCs) or KD patients via circRNA sequencing (circRNA-seq). In addition, circRNA-3302 upregulation was verified in endothelial cells stimulated by KD serum and pathological KD mice modeled with Candida albicans cell wall extracts (CAWS). Moreover, in vitro experiments demonstrated that overexpression of circRNA-3302 could markedly induce EndMT, and silencing of circRNA-3302 significantly alleviated KD serum-mediated EndMT. To further explore the molecular mechanisms of circRNA-3302 inducing EndMT, RNA sequencing (RNA-seq), a dual-luciferase reporter system, nuclear and extra-nuclear RNA isolation, RT-qPCR and Western blot analyses and so on, were utilized. Our data demonstrated that circRNA-3302 contributed to the KD-associated EndMT via sponging miR-135b-5p to enhance KIT expression. Collectively, our results imply that circRNA-3302 plays an important role in KD-associated EndMT, providing new insights into minimizing the risks of developing coronary artery aneurysms., (© 2022. The Author(s).)

National and international recommendations of healthy body mass index (BMI) are primarily based on evidence in young and middle-aged populations, with an insufficient representation of the oldest old (aged ≥80 years). Here, we report associations between BMI and mortality risk in 27,026 community-dwelling oldest old (mean age, 92.7 ± 7.5 years) in China from 1998 to 2018. Nonlinear curves showed reverse J-shaped associations of BMI with cardiovascular disease (CVD), non-CVD and all-cause mortality, with a monotonic decreased risk up to BMIs in the overweight and mild obesity range and flat hazard ratios thereafter. Compared to normal weight, overweight and obesity were significantly associated with decreased non-CVD and all-cause mortality, but not with CVD mortality. Similar associations were found for waist circumference. Our results lend support to the notion that optimal BMI in the oldest old may be around the overweight or mild obesity range and challenge the application of international and national guidelines on optimal BMI in this age group., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Targeted therapy is an important therapeutic strategy currently, however, the development of targeted therapy for nasopharyngeal carcinoma (NPC) is relatively lagging. Cullin 4A (CUL4A) was reported to be overexpressed in NPC; nevertheless, the specific role of CUL4A remains unrevealed. NPC cells and tumor-bearing mice were cultivated to explore the role and mechanism of CUL4A in NPC. After evaluating CUL4A levels in NPC cells, functional experiments were carried out to investigate the effects of CUL4A knockdown and overexpression on cell proliferative, invasive and migratory aptitude as well as NF-κB signaling. Following the GeneMANIA database predicted that protein arginine methyltransferase 5 (PRMT5) was downstream of CUL4A, the mediated role of PRMT5 in the regulation of CUL4A on cells was then determined. Moreover, the tumor volumes and weights of tumor-bearing mice were recorded, and the levels of proliferation-, migration-, and NF-κB signaling-related proteins in the tumor were determined. Herein, CUL4A was enhanced in NPC cells, and its knockdown and overexpression separately suppressed and promoted cell proliferative, invasive, and migratory aptitude as well as NF-κB signal activation. Novelty, PRMT5 knockdown reversed the influences of CUL4A overexpression on these aspects. In addition, its knockdown likewise reversed the facilitating impact of CUL4A expression on tumor growth and declined the expression levels of proliferation-, migration-, and NF-κB signaling-related protein in the tumor. Together, this paper indicated that CUL4A promoted the proliferative, invasive, and migratory aptitude of NPC cells as well as tumor growth by promoting PRMT5 to activate NF-κB signaling.

Flaxseed supplementation in diet of dairy cow can effectively enhance the production of ω-3 polyunsaturated fatty acids (n-3 PUFA) in raw milk, which further give rise to the changes of volatile organic compounds (VOCs). In this study, we used headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) to investigate the VOCs in milk from cows fed three different diets (CK: supplemented with 0 g/d flaxseed; WF: 1,500 g/d whole flaxseed and GF: 1,500 g/d ground flaxseed). A total of 40 VOCs including three acids, six esters, 11 aldehydes, seven alcohols, 13 ketones were identified in all the raw milk samples. Compared with GF supplementation, suppling with WF could influence more compounds in raw milk (GF: five compounds; WF: 22 compounds). Supplementation with WF could increase the concentration of nonanal, heptanal, hexanal, which could cause the occurrence of off-flavors, and reduce the concentration of hexanoic acid (monomer; M), 2-hexanol, ethanol (M), 2-heptanone (dimer; D), 2-pentanone (M), 2-pentanone (D), acetoin (M) in raw milk. GF supplementation in diet could reduce the 2-pentanone (M), 2-pentanone (D). In addition, principal component analysis (PCA) based on the signal intensity of identified VOCs indicated that it is possible to distinguish between the CK and WF milk. However, GF milk could not be distinguished from CK milk. The results demonstrate that compared with GF milk, WF supplementation in diet of dairy cows could increase fishy (heptanal) cardboard-like (pentanal) flavor in milk and decrease sweet (hexanoic acid, 2-heptanone), fruity (ethyl butanoate, ethyl hexanoate, 2-heptanone) flavor which may lead the milk less acceptable. In conclusion, compared with WF, GF supplementation in diet of dairy cow showed higher increase in n-3 PUFA in raw milk, and less influence in VOCs of raw milk and this study might provide theoretical supports for the production of milk rich in n-3 PUFA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Li, Liu, Yang, Zhao, Zheng, Zhou, Zhang and Wang.)

Nasopharyngeal carcinoma (NPC) is a malignant tumor caused by an infection of the epithelial cells of the nasopharynx, which is highly metastatic and aggressive. Due to the deep anatomical site and atypical early symptoms, the majority of NPC patients are diagnosed at terminal stages. There is growing evidence that microRNAs offer options for early detection, accurate diagnosis, and prediction of malignancy treatment response. Therefore, the purpose of this article was to identify microRNAs that predict the prognosis of patients with NPC by integrating biological information analysis. In this study, we utilized the GSE36682 dataset rooted in the Gene Expression Omnibus (GEO) data bank, including 62 cases of NPC tissues and six cases of non-cancerous tissues. The miRNAs were subjected to weighted gene co-expression network analysis, and hub miRNAs were screened for differentially upregulated miRNAs from modules highly correlated with tumor progression. We took a lot of time to calculate the risk scores of miRNA markers for 62 NPC patients, and incidentally combined the clinical survival information of patients to finally identify the three key miRNAs, and then divided the patients into low- and high-risk groups. Kaplan-Meier curve analysis revealed that the overall survival of patients in the high-risk group was obviously shorter than that of the low-risk group. Subsequently, the target genes of the three miRNAs were predicted and analyzed for functional enrichment. In summary, a prognostic predictive risk model based on three miRNA profiles may increase prognostic predictive value and provide reference information for the precise treatment of nasopharyngeal carcinoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Zhang, Zhang, Wang and Xu.)

The sluggish oxygen reaction kinetics concomitant with the high overpotentials and parasitic reactions from cathodes and solvents is the major challenge in aprotic lithium-oxygen (Li-O 2 ) batteries. Herein, PtIr multipods with a low Lewis acidity of the Pt atoms are reported as an advanced cathode for improving overpotentials and stabilities. DFT calculations disclose that electrons have a strong disposition to transfer from Ir to Pt, since Pt has a higher electronegativity than Ir, resulting in a lower Lewis acidity of the Pt atoms than that on the pure Pt surface. The low Lewis acidity of Pt atoms on the PtIr surface entails a high electron density and a down-shifting of the d-band center, thereby weakening the binding energy towards intermediates (LiO 2 ), which is the key in achieving low oxygen-reduction-reaction (ORR) and oxygen-evolution-reaction (OER) overpotentials. The Li-O 2 cell based on PtIr electrodes exhibits a very low overall discharge/charge overpotential (0.44 V) and an excellent cycle life (180 cycles), outperforming the bulk of reported noble-metal-based cathodes., (© 2021 Wiley-VCH GmbH.)

Background: It remains unsolved that whether blood uric acid (UA) is a neuroprotective or neurotoxic agent. This study aimed to evaluate the longitudinal association of blood UA with mild cognitive impairment (MCI) among older adults in China. Methods: A total of 3,103 older adults (aged 65+ years) free of MCI at baseline were included from the Healthy Aging and Biomarkers Cohort Study (HABCS). Blood UA level was determined by the uricase colorimetry assay and analyzed as both continuous and categorical (by quartile) variables. Global cognition was assessed using the Mini-Mental State Examination four times between 2008 and 2017, with a score below 24 being considered as MCI. Cox proportional hazards models were used to examine the associations. Results: During a 9-year follow-up, 486 (15.7%) participants developed MCI. After adjustment for all covariates, higher UA had a dose-response association with a lower risk of MCI (all P for  trend < 0.05). Participants in the highest UA quartile group had a reduced risk [hazard ratio (HR), 0.73; 95% (CI): 0.55-0.96] of MCI, compared with those in the lowest quartile group. The associations were still robust even when considering death as a competing risk. Subgroup analyses revealed that these associations were statistically significant in younger older adults (65-79 years) and those without hyperuricemia. Similar significant associations were observed when treating UA as a continuous variable. Conclusions: High blood UA level is associated with reduced risks of MCI among Chinese older adults, highlighting the potential of managing UA in daily life for maintaining late-life cognition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Li, Lv, Yin, Zhao, Liu, Li, Ji, Zhou, Wei, Cao, Wang, Gu, Lu, Liu and Shi.)

Atomically dispersed metal catalysts with well-defined structures have been the research hotspot in heterogeneous catalysis because of their high atomic utilization efficiency, outstanding activity, and selectivity. Dual-atomic-site catalysts (DASCs), as an extension of single-atom catalysts (SACs), have recently drawn surging attention. The DASCs possess higher metal loading, more sophisticated and flexible active sites, offering more chance for achieving better catalytic performance, compared with SACs. In this review, recent advances on how to design new DASCs for enhancing energy catalysis will be highlighted. It will start with the classification of marriage of two kinds of single-atom active sites, homonuclear DASCs and heteronuclear DASCs according to the configuration of active sites. Then, the state-of-the-art characterization techniques for DASCs will be discussed. Different synthetic methods and catalytic applications of the DASCs in various reactions, including oxygen reduction reaction, carbon dioxide reduction reaction, carbon monoxide oxidation reaction, and others will be followed. Finally, the major challenges and perspectives of DASCs will be provided., (© 2021 Wiley-VCH GmbH.)

Background: Ginsenosides accumulation responses to temperature are critical to quality formation in cold-dependent American ginseng. However, the studies on cold requirement mechanism relevant to ginsenosides have been limited in this species., Methods: Two experiments were carried out: one was a multivariate linear regression analysis between the ginsenosides accumulation and the environmental conditions of American ginseng from different sites of China and the other was a synchronous determination of ginsenosides accumulation, overall DNA methylation, and relative gene expression in different tissues during different developmental stages of American ginseng after experiencing different cold exposure duration treatments., Results: Results showed that the variation of the contents as well as the yields of total and individual ginsenosides Rg1, Re, and Rb1 in the roots were closely associated with environmental temperature conditions which implied that the cold environment plays a decisive role in the ginsenoside accumulation of American ginseng. Further results showed that there is a cyclically reversible dynamism between methylation and demethylation of DNA in the perennial American ginseng in response to temperature seasonality. And sufficient cold exposure duration in winter caused sufficient DNA demethylation in tender leaves in early spring and then accompanied the high expression of flowering gene PqFT in flowering stages and ginsenosides biosynthesis gene PqDDS in green berry stages successively, and finally, maximum ginsenosides accumulation occurred in the roots of American ginseng., Conclusion: We, therefore, hypothesized that cold-induced DNA methylation changes might regulate relative gene expression involving both plant development and plant secondary metabolites in such cold-dependent perennial plant species., (© 2019 The Korean Society of Ginseng, Published by Elsevier Korea LLC.)

Background: Research on the relationship between long-term exposure to particulate matter with aerodynamic diameter ≤ 2.5 μ m ( PM 2.5 ) and poor cognitive function is lacking in developing countries, especially in highly polluted areas., Objectives: We evaluated associations of long-term exposure to PM 2.5 with poor cognitive function in a diverse, national sample of older adults in China., Methods: This analysis included data on 13,324 older adults (5,879 who were 65-79 years of age, 3,052 who were 80-89 years of age, 2,634 who were 90-99 years of age, and 1,759 who were ≥ 100  years of age) with normal cognitive function at baseline from March 2002 to September 2014, with 64,648 person-years of follow-up. We used a geographic information system analysis to estimate the annual average satellite-derived PM 2.5 concentration for the geocoded location of the participants' baseline residences. Poor cognitive function was defined as a score of less than 18 on the Chinese version of the Mini-Mental State Examination (MMSE). Competing risk models were performed to explore the association of PM 2.5 with poor cognitive function., Results: Each 10 - μ g / m 3 increase in PM 2.5 was associated with a 5.1% increased risk of poor cognitive function [adjusted hazard ratio (HR): 1.051; 95% confidence interval (CI): 1.023, 1.079]. Compared to the lowest quartile of PM 2.5 ( < 41.4   μ g / m 3 ), adjusted HR values were 1.20 (95% CI: 1.09, 1.33), 1.27 (95% CI: 1.15, 1.41), and 1.21 (95% CI: 1.09, 1.34) for the second ( ≥ 41.4 - 50.3  ug / m 3 ), third ( ≥ 50.3 - 60.7 μ g / m 3 ), and fourth ( ≥ 60.7   μ g / m 3 ) quartiles of PM 2.5 , respectively ( p for trend < 0.001 ). Subgroup analyses suggested stronger associations between PM 2.5 and poor cognitive impairment in men than women. The association was positive in the 65- to 79- and ≥ 100 - y age group but not significant and positive in the other two age groups with similar results., Conclusion: PM 2.5 was identified as a risk factor for poor cognitive function in Chinese older adults. Improving air quality may reduce the future population burden of poor cognitive function, especially in areas with high air pollution. https://doi.org/10.1289/EHP5304.

Currently the Chinese government has adopted World Health Organization interim target-1 values as the national ambient air quality standards values. However, the population-based evidence was insufficient, especially for the oldest old (aged 80+). We evaluated the association of fine particulate matters (PM 2.5 ) exposure and incidence of disability in activities of daily living (ADL) in 15 453 oldest old in 886 counties/cities in China from 2002 to 2014 using Cox model with penalized splines and competing risk models to evaluate the linear or non-linear association. After adjusting for potential confounders, a J-shaped association existed between PM 2.5 exposure with a threshold concentration of 33 μg/m 3 , and incident disability in ADL. Above this threshold, the risk magnitude significantly increased with increase of PM 2.5 concentrations; compared to 33 μg/m 3 , the hazard ratio ranged from 1.03 (1.00-1.06) at 40 μg/m 3 to 2.25 (1.54-3.29) at 110 μg/m 3 . The risk magnitude was not significantly changed below this threshold. Each 10 μg/m 3 increase in PM 2.5 exposure corresponded to a 7.7% increase in the risk of disability in ADL (hazard ratio 1.077, 95% CI 1.051-1.104). Men, smokers, and participants with cognitive impairment might be more vulnerable to PM 2.5 exposure. The study provided limited population-based evidence for the oldest old and detected a threshold of 33 μg/m 3 , and supported that reduction to current World Health Organization interim target-1value (35 μg/m 3 ) and Chinese national ambient air quality standards (35 μg/m 3 ) or lower may be associated with lower risk of disability in ADL., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Air pollution and its adverse effects on public health remain a considerable problem in China, where policies have been implemented to improve the situation. We aimed to estimate the disease burden associated with particulate matter (PM) 2·5 across China for 2020 and 2030 to identify the populations and regions most at risk, quantify the health benefits of air quality improvement targets, and determine the effect of population growth and ageing on this disease burden., Methods: In this modelling study, we investigated premature deaths associated with PM 2·5 across China on the basis of air quality scenarios proposed by the expert group involved in the formulation of the 13th Five-Year Plan for Eco-Environmental Protection and population scenarios based on the Shared Socioeconomic Pathways of the Intergovernmental Panel on Climate Change. We used the integrated exposure-response model used for the Global Burden of Disease Study to estimate the number of PM 2·5 -related premature deaths under each scenario., Findings: The projected health benefits of the air-quality-improving targets are substantial, and could reduce the number of PM 2.5 -related premature deaths in China by approximately 129 278 by 2020 and 217 988 by 2030, compared with 2010. However, since China's population is increasing and ageing, the number of PM 2.5 -related premature deaths was estimated to increase by 84 102 by 2020 and by 244 191 by 2030, indicating that the health benefits induced by air quality improvements could be offset by the effect of the population increasing in size and ageing., Interpretation: To reduce the future disease burden in China, targets that are stricter than the interim target and stringent policies to improve air quality and protect public health are needed, especially for at-risk population groups, such as older individuals (aged >55 years) and patients with cardiovascular diseases, particularly in regions with a high disease burden., Funding: National Key Research and Development Program of China, National Natural Science Foundation of China, Beijing Natural Science Foundation, National High-level Talents Special Support Plan of China for Young Talents, and Special Foundation of Basic Science and Technology Resources Survey of Ministry of Science and Technology of China., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

With its inherent zig-zag layered structure and open framework, Na 2 Ti 3 O 7 (NTO) is a promising anode material for potassium-ion batteries (KIBs). However, its poor electronic conductivity caused by large band gap (∼3.7 eV) usually leads to low-performance KIBs. In this work, we synthesize the fluff-like hydrogenated Na 2 Ti 3 O 7 (HNTO) nanowires grown on N-doped carbon sponge (CS) as a binder-free and current-collector-free flexible anode for KIBs (denoted as HNTO/CS). High-resolution X-ray photoelectron spectroscopy (XPS) and electron spin-resonance spectroscopy (ESR) confirm the existence of Ti-OHs and O vacancies in HNTO. The first-principles calculation discloses that both Ti-OHs and O vacancies are equivalent to n-type doping because they can shift the Fermi level up to the conduction band, thus leading to a higher electronic conductivity and better performance for KIBs. In addition, the N-doped CS can further reinforce the conductivity and avoid the aggregation of HNTO nanowires during cycling. As a result, the as-made HNTO/CS can deliver a capacity of 107.8 mAh g -1 at 100 mA g -1 after 20 cycles, and keep the capacity of 90.9% and 82.5% after 200 and 1555 cycles, respectively, much better than the samples without hydrogenation treatment or N-doped CS and reported KTi x O y -based materials. Our work highlights the importance of hydrogenation treatment and N-doped CS in enhancing the electrochemical property for KIBs.

Potassium-ion batteries (KIBs) are receiving increasing interest in grid-scale energy storage owing to the earth abundant and low cost of potassium resources. However, their development still stays at the infancy stage due to the lack of suitable electrode materials with reversible depotassiation/potassiation behavior, resulting in poor rate performance, low capacity, and cycling stability. Herein, the first example of synthesizing single-crystalline metallic graphene-like VSe 2 nanosheets for greatly boosting the performance of KIBs in term of capacity, rate capability, and cycling stability is reported. Benefiting from the unique 2D nanostructure, high electron/K + -ion conductivity, and outstanding pseudocapacitance effects, ultrathin VSe 2 nanosheets show a very high reversible capacity of 366 mAh g -1 at 100 mA g -1 , a high rate capability of 169 mAh g -1 at 2000 mA g -1 , and a very low decay of 0.025% per cycle over 500 cycles, which are the best in all the reported anode materials in KIBs. The first-principles calculations reveal that VSe 2 nanosheets have large adsorption energy and low diffusion barriers for the intercalation of K + -ion. Ex situ X-ray diffraction analysis indicates that VSe 2 nanosheets undertake a reversible phase evolution by initially proceeding with the K + -ion insertion within VSe 2 layers, followed by the conversion reaction mechanism., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Potassium-ion batteries (KIBs) have recently attracted intensive attention because of the abundant potassium resources and their low cost and high safety. However, the major challenge faced by KIBs lies in the lack of stable and high-capacity materials for the intercalation/deintercalation of large-size potassium ions. A unique pistachio-shuck-like MoSe 2 /C core/shell nanostructure (PMC) is synthesized herein as an advanced anode for boosting the performance of KIBs. This PMC is featured with a few layers of molybdenum selenide as the core with an expanded interlayer spacing of ≈0.85 nm, facilitating the intercalation/deintercalation of K ions, and a thin amorphous carbon as the shell, which can confine the active molybdenum selenide nanosheets during cycling for maintaining the high structural stability. Most importantly, as a whole, the PMC has the advantages of reducing the surplus hollow interior space for improving its packing density and buffering the volume expansion during the K-ion intercalation for further enhancing the stability. As a consequence, the PMC shows a very high capacity of 322 mAh g -1 at 0.2 A g -1 over 100 cycles, and can still remain 226 mAh g -1 at 1.0 A g -1 for a long period of 1000 cycles, which is among the best-reported KIBs anodes., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To provide the theory basis for clinical diagnosis, treatment and prognosis of sudden deafness patients, we detected the relative factors of degree of tinnitus of the patients with sudden deafness., Method: Prospective analysis was used to compare degree of tinnitus with sex, ears, age, degree of hearing lose, hearing curve type and curative effect of tinnitus and sudden deafness., Result: Tinnitus was detected in 87.2% in the 70 patients who with sudden deafness, and the most and least degree of tinnitus patients was the degree 3 (32.9%) and the degree 5 and 6 (0). The total effective rate of sudden deafness and tinnitus was 66.2% and 74.3%, respectively. The statistical analysis shown the degree of tinnitus was not related to sex, ears, age, degree of hearing lose, auditory curve type and curative effect of tinnitus and sudden deafness (P > 0.05)., Conclusion: There was a high rate of tinnitus occurrence in sudden deafness patients, and the moderate degree predominated. The curative effect of tinnitus was better than sudden deafness. There was no relationship between the degree of tinnitus and sex, ears, age, degree of hearing lose, auditory curve type and curative effect of tinnitus and sudden deafness.

In this study, a fast, selective and sensitive ultra-performance liquid chromatographic method (UPLC) with photodiode array detection (DAD) was developed to determine 12 active compounds, such as flavonoids, ferulic acid, caffeic acid phenethyl ester, etc. in propolis. The propolis sample was diluted with methanol and extracted by sonication. The gradient separation was achieved within 9.5 min by using an Acquity BEH C18 column (100 mm x 2.1 mm, 1.7 microm) with 0.4% phosphoric acid aqueous solution and methanol as the mobile phase. The experimental parameters were optimized and adapted to analyse propolis samples from different production areas in China. The spiked recoveries were 90.1% - 104.3% with relative standard deviations of 2.12% -4.90%. This method can be used as a novel method for quality control of propolis. The results are validated through testing 106 propolis samples from various production areas.

A rapid and sensitive gas chromatography (GC) method was developed to detect chloramphenicol in chicken tissues. The extracted samples were cleaned up using the immunoaffinity column prepared by coupling antichloramphenicol monoclonal antibody with cyanogen bromide-activated Sepharose 4B. The dynamic column capacity of chloramphenicol was 3265 ng/mL gel. The eluate was evaporated to dryness, and residues were derivatized and determined by GC with a microcell electron capture detector. Average recoveries were 86.6 to 96.9% for chicken muscle and 74.3 to 96.1% for chicken liver. The limit of quantitation of the method was 0.05 ng/g for chicken muscle and 0.1 ng/g for chicken liver.