Mechanistic insights into cardiovascular effects of ultrafine particle exposure: A longitudinal panel study.

BACKGROUND: Ultrafine particle (UFP) has been linked with higher risks of cardiovascular diseases; however, the biological mechanisms remain to be fully elucidated. OBJECTIVES: This study aims to investigate the cardiovascular responses to short-term UFP exposure and the biological pathways involved. METHODS: A longitudinal panel study was conducted among 32 healthy, non-smoking young adults in Shanghai, China, who were engaged in five rounds of follow-ups between December 2020 and November 2021. Individual exposures were calculated based on the indoor and outdoor real-time measurements. Blood pressure, arterial stiffness, targeted biomarkers, and untargeted proteomics and metabolomics were examined during each follow-up. Linear mixed-effect models were applied to analyze the exposure and health data. The differential proteins and metabolites were used for pathway enrichment analyses. RESULTS: Short-term UFP exposure was associated with significant increases in blood pressure and arterial stiffness. For example, systolic blood pressure increased by 2.10 % (95 % confidence interval: 0.63 %, 3.59 %) corresponding to each interquartile increase in UFP concentrations at lag 0-3 h, while pulse wave velocity increased by 2.26 % (95 % confidence interval: 0.52 %, 4.04 %) at lag 7-12 h. In addition, dozens of molecular biomarkers altered significantly. These effects were generally present within 24 h after UFP exposure, and were robust to the adjustment of co-pollutants. Molecular changes detected in proteomics and metabolomics analyses were mainly involved in systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and disturbance in lipid transport and metabolism. DISCUSSION: This study provides novel and compelling evidence on the detrimental subclinical cardiovascular effects in response to short-term UFP exposure. The multi-omics profiling further offers holistic insights into the underlying biological pathways.

Particulate matter pollution, polygenic risk score and mosaic loss of chromosome Y in middle-aged and older men from the Dongfeng-Tongji cohort study.

Mosaic loss of chromosome Y (mLOY) is the most common somatic alteration as men aging and may reflect genome instability. PM exposure is a major health concern worldwide, but its effects with genetic factors on mLOY has never been investigated. Here we explored the associations of PM2.5 and PM10 exposure with mLOY of 10,158 males measured via signal intensity of 2186 probes in male-specific chromosome-Y region from Illumina array data. The interactive and joint effects of PM2.5 and PM10 with genetic factors and smoking on mLOY were further evaluated. Compared with the lowest tertiles of PM2.5 levels in each exposure window, the highest tertiles in the same day, 7-, 14-, 21-, and 28-day showed a 0.005, 0.006, 0.007, 0.007, and 0.006 decrease in mLRR-Y, respectively (all P < 0.05), with adjustment for age, BMI, smoking pack-years, alcohol drinking status, physical activity, education levels, season of blood draw, and experimental batch. Such adverse effects were also observed in PM10-mLOY associations. Moreover, the unweighted and weighted PRS presented significant negative associations with mLRR-Y (both P < 0.001). Participants with high PRS and high PM2.5 or PM10 exposure in the 28-day separately showed a 0.018 or 0.019 lower mLRR-Y level [ß (95 %CI) = -0.018 (-0.023, -0.012) and - 0.019 (-0.025, -0.014), respectively, both P < 0.001], when compared to those with low PRS and low PM2.5 or PM10 exposure. We also observed joint effects of PM with smoking on exacerbated mLOY. This large study is the first to elucidate the impacts of PM2.5 exposure on mLOY, and provides key evidence regarding the interactive and joint effects of PM with genetic factors on mLOY, which may promote understanding of mLOY development, further modifying and increasing healthy aging in males.

Mechanism insights into hydrothermal-activated tannic acid (TA) for simultaneously sewage sludge deep dewatering and antibiotics removal.

Tannic acid (TA) aided hydrothermal treatment (HT) can decrease effective HT temperatures for sludge deep dewatering by chelator protein, but faces notable and economic challenges including the failure to remove antibiotics and the limited protein binding capacity. Herein, hydrothermally activated TA (in situ TA + HT) was conducted to simultaneously improve sludge dewaterability and antibiotic (tetracycline (TC), oxytetracycline (OTC), norfloxacin (NOR), ofloxacin (OFL)) removal. Compared to traditional HT and HT + TA treatment, the in-situ TA + HT process could further strengthen the TA-aided HT efficacy in enhancing sludge and reducing the protein content in the filtrate simultaneously; in which the optimal HT temperature for the dewatering of the sludge was reduced from 180 °C to 140 °C. Furthermore, the total removal efficiency of target antibiotics was achieved at more than 71.0-94.7% for TC and OTC, and 72.0-84.8% for NOR and OFL. The highly reactive species (·OH) generation and the electron transfer efficiency from the hydrothermal-activated TA process were responsible for the elimination of antibiotics and promoted the hydrolyzation and mineralization of HMW protein in sludge during the HT process. Meanwhile, the degradation of HMW proteins and the destruction of the secondary structure of these proteins resulted in improved hydrophobicity and dewaterability of sludge. Hydrothermally activated TA induces covalent binding with the protein. As a result, hydrothermal-activated TA could promote the removal of antibiotics and proteinaceous compounds from the sludge samples, improving the hydrophobicity of sludge and releasing bound water from the sludge flocs during HT. Finally, the cost of hydrothermal-activated TA was 66.51% lower than that of thermal drying treatment. This study not only proposed an effective method to improve traditional HT for sludge thermal dry-free treatment, but also provided new information on the catalysis roles of polyphenols in the hydrothermal conversion of sludge.

Association between exposure to a mixture of organochlorine pesticides and hyperuricemia in U.S. adults: A comparison of four statistical models.

The association between the exposure of organochlorine pesticides (OCPs) and serum uric acid (UA) levels remained uncertain. In this study, to investigate the combined effects of OCP mixtures on hyperuricemia, we analyzed serum OCPs and UA levels in adults from the National Health and Nutrition Examination Survey (2005-2016). Four statistical models including weighted logistic regression, weighted quantile sum (WQS), quantile g-computation (QGC), and bayesian kernel machine regression (BKMR) were used to assess the relationship between mixed chemical exposures and hyperuricemia. Subgroup analyses were conducted to explore potential modifiers. Among 6,529 participants, the prevalence of hyperuricemia was 21.15%. Logistic regression revealed a significant association between both hexachlorobenzene (HCB) and trans-nonachlor and hyperuricemia in the fifth quintile (OR: 1.54, 95% CI: 1.08-2.19; OR: 1.58, 95% CI: 1.05-2.39, respectively), utilizing the first quintile as a reference. WQS and QGC analyses showed significant overall effects of OCPs on hyperuricemia, with an OR of 1.25 (95% CI: 1.09-1.44) and 1.20 (95% CI: 1.06-1.37), respectively. BKMR indicated a positive trend between mixed OCPs and hyperuricemia, with HCB having the largest weight in all three mixture analyses. Subgroup analyses revealed that females, individuals aged 50 years and above, and those with a low income were more vulnerable to mixed OCP exposure. These results highlight the urgent need to protect vulnerable populations from OCPs and to properly evaluate the health effects of multiple exposures on hyperuricemia using mutual validation approaches.

Construction of Selective Ion Transport Polymer at Anode-Electrolyte Interface for Stable Aqueous Zinc-Ion Batteries.

Rampant dendrite formation and serious adverse parasitic reactions induced by migration of dissolved V/Mn cathode ions on Zn anode have hampered the high performance of aqueous zinc-ion batteries (AZIBs). Inspired by the coordination chemistry between functional groups of polymer and electrolyte ions, a freestanding layer consisting of dopamine-functionalized polypyrrole (DA-PPy) nanowires served as a selective ion transport layer at the anode-electrolyte interface to address these two issues, which could simultaneously avoid polarization caused by the introduction of an additional interface. On the one hand, the DA-PPy layer displays excellent zinc ion and charge transfer ability, as well as provides chemical homochanneling for zinc ions at the interface, which endow the DA-PPy layer with properties as a chemical guider and physical barrier for dendrite inhibition. On the other hand, the DA-PPy layer can trap excess transition metal ions fleeing from the cathodes, thus serving as a chemical barrier, preventing the formation of Vx+/Mnx+-passivation on the surface of the zinc anode. Consequently, the AZIBs based on V2O5 and MnO2 cathodes involving the DA-PPy functional layer show a great improvement in the capacity retention.

Bipolar Polymeric Protective Layer for Dendrite-Free and Corrosion-Resistant Lithium Metal Anode in Ethylene Carbonate Electrolyte.

The unstable interface between Li metal and ethylene carbonate (EC)-based electrolytes triggers continuous side reactions and uncontrolled dendrite growth, significantly impacting the lifespan of Li metal batteries (LMBs). Herein, a bipolar polymeric protective layer (BPPL) is developed using cyanoethyl (-CH2CH2C≡N) and hydroxyl (-OH) polar groups, aiming to prevent EC-induced corrosion and facilitating rapid, uniform Li+ ion transport. Hydrogen-bonding interactions between -OH and EC facilitates the Li+ desolvation process and effectively traps free EC molecules, thereby eliminating parasitic reactions. Meanwhile, the -CH2CH2C≡N group anchors TFSI- anions through ion-dipole interactions, enhancing Li+ transport and eliminating concentration polarization, ultimately suppressing the growth of Li dendrite. This BPPL enabling Li|Li cell stable cycling over 750 cycles at 10 mA cm-2 for 2 mAh cm-2. The Li|LiNi0.8Mn0.1Co0.1O2 and Li|LiFePO4 full cells display superior electrochemical performance. The BPPL provides a practical strategy to enhanced stability and performance in LMBs application.

Osteotomy Correction Angle Cut-off Points Can Guide the Operation to Prevent a Significant Decrease in Patella Height.

OBJECTIVE: Patients who undergo a biplanar ascending medial open-wedge high tibial osteotomy with an excessive correction angle might experience patella infera and even knee pain after surgery. The purpose of this study was to identify the cut-off points for the degree of knee varus correction of open-wedge high tibial osteotomy, which is related to the symptomatic patellar position change. METHODS: This retrospective study included 124 patients (mean age 61.69 ± 6.28 years; 78 women, 46 men) with varying degrees of varus knee osteoarthritis. All patients had undergone standard biplanar medial open-wedge high tibial osteotomy. They were divided into nine groups according to the change in hip-knee-ankle angle. Plain radiographs and three-dimensional CT images were obtained preoperatively and 18 months postoperatively. Patellar height was assessed using the Caton-Deschamps index, the Insall-Salvati index, and the Blackburne-Peel index. The patellofemoral index and patellar tilt were used to evaluate the degree of horizontal displacement of the patella. The varus correction, medial-proximal tibial angles, joint line convergence angles, and hip-knee-ankle angles were also measured. The subjective score was evaluated using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). RESULTS: There were significant changes in patella indexes in each group after surgery, among which there was no significant difference in patellar height changes for Groups A to F (p > 0.05), which were significantly lower than those in Group G, H, and I (p < 0.001). The patellar tilt and patellofemoral index also followed the same trend. The improvement in WOMAC scores for Groups G, H, and I was also significantly less for Groups A to F (p < 0.001). CONCLUSION: The patellar height, patellar tilt, and patellofemoral index all changed significantly in parallel with increasing degrees of osteotomy correction. The cut-off points for correction angle are 12.5° to 13.4°. When the correction angle is larger than this range, the patellar position can be significantly affected. Postoperative patellofemoral joint pain may be related to the changes in patella position.

Defective oxygen inert phase stabilized high-voltage nickel-rich cathode for high-energy lithium-ion batteries.

Pushing layered cathode to higher operating voltage can facilitate the realization of high-energy lithium-ion batteries. However, the released oxygen species initiate materials surface upon highly delithiated states will react severely with electrolyte, accelerating the structure deterioration and triggering the thermal degradation. Here we propose an inert phase of La2Mo2O9 with abundant oxygen vacancies (about 41%) by regulating the annealing temperature to engineer the cathode interface beyond conventional modifications. By employing LiNi0.8Co0.1Mn0.1O2 as a model system and extending to higher voltage-operated LiCoO2 and Li-rich cathode, we demonstrate that the introduced lanthanum and molybdenum ions will transfer electrons to enhance the surface oxygen electronegativities, thus served as "oxygen anchor" to alleviate oxygen evolution. Furthermore, the possible released oxygen can be operando captured and reserved by ß-phase La2Mo2O9 depositor for the intrinsic high oxygen vacancy formation energy. The reaction involving oxygen species with electrolyte is fundamentally diminished, thus effectively mitigate the structure deterioration and elevate the electrochemical performances, enabling a 1.5-Ah pouch-type full cell to exhibit negligible 6.0% capacity loss after 400 cycles.

Sirolimus in combination with low-dose extended-release tacrolimus in kidney transplant recipients.

Introduction: Many challenges remain for long-term survival of renal allografts. Once-daily sirolimus (SRL) combined with low-dose extended-release tacrolimus (LER-TAC) may improve medication adherence and reduce the potential nephrotoxicity of calcineurin inhibitors (CNI) compared with standard immunosuppression regimens, thus potentially improving long-term graft survival. Methods: This retrospective, observational, single-center, propensity score matching (PSM) study compared conversion to SRL combined with low-dose ER-TAC and mycophenolic acid (MPA) combined with standard-dose TAC in kidney transplant recipients. After PSM, there were 56 patients in each group. Efficacy, safety, and medication adherence were evaluated over 12 months. Results: There was no significant difference between the two groups in terms of graft and recipient survival and incidence of biopsy-proven acute rejection (p = 1.000), and none of the recipients developed dnDSA after conversion. The mean eGFR improved in SRL + LER-TAC group after conversion compared to before conversion (51.12 ± 20.1 ml/min/1.73 m2 vs. 56.97 ± 19.23 ml/min/1.73 m2, p < 0.05). The medication adherence at 12 months after conversion was superior to before conversion (p = 0.002). Discussion: Our findings suggest that an immunosuppressive regimen of SRL combined with low-dose ER-TAC is no less effective and safe than standard immunosuppressive regimens for renal transplant recipients and may improve graft renal function and medication adherence.

Molecular recognition effect enabled by novel crown ether as macrocyclic host towards highly reversible Zn anode.

Aqueous Zn2+ ion batteries present notable advantages, including high abundance, low toxicity, and intrinsic nonflammability. However, they exhibit severe irreversibility due to uncontrolled dendrite growth and corrosion reactions, which limit their practical applications. Inspired by their distinct molecular recognition characteristics, supramolecular crown ethers featuring interior cavity sizes identical to the diameter of Zn2+ ions were screened as macrocyclic hosts to optimize the Zn2+ coordination environment, facilitating the suppression of the reactivity of H2O molecules and inducing the in-situ formation of organic-inorganic hybrid dual-protective interphase. The in-situ assembled interphase confers the system with an "ion-sieving" effect to repel H2O molecules and facilitate rapid Zn2+ transport, enabling the suppression of side reactions and uniform deposition of Zn2+ ions. Consequently, we were able to achieve dendrite-free Zn2+ plating/stripping at 98.4% Coulombic efficiency for approximately 300 cycles in Zn||Cu cell, steady charge-discharge for 1360 h in Zn||Zn symmetric cell, and improved cyclability of 70% retention for 200 cycles in Zn||LMO full cell, outlining a promising strategy to challenge lithium-ion batteries in low-cost, and large-scale applications.

Association of Fine Particulate Matter and Its Components with Macrosomia: A Nationwide Birth Cohort Study of 336 Chinese Cities.

To examine the associations between macrosomia risk and exposure to fine particulate matter (PM2.5) and its chemical components during pregnancy, we collected birth records between 2010 and 2015 in mainland China from the National Free Preconception Health Examination Project and used satellite-based models to estimate concentrations of PM2.5 mass and five main components, namely, black carbon (BC), organic carbon (OC), nitrate (NO3-), sulfate (SO42-), and ammonium (NH4+). Associations between macrosomia risk and prenatal exposure to PM2.5 were examined by logistic regression analysis, and the sensitive subgroups were explored by stratified analyses. Of the 3,248,263 singleton newborns from 336 cities, 165,119 (5.1%) had macrosomia. Each interquartile range increase in concentration of PM2.5 during the entire pregnancy was associated with increased risk of macrosomia (odds ratio (OR) = 1.18; 95% confidence interval (CI), 1.17-1.20). Among specific components, the largest effect estimates were found on NO3- (OR = 1.36; 95% CI, 1.35-1.38) followed by OC (OR = 1.23; 95% CI, 1.22-1.24), NH4+ (OR = 1.22; 95% CI, 1.21-1.23), and BC (OR = 1.21; 95% CI, 1.20-1.22). We also that found boys, women with a normal or lower prepregnancy body mass index, and women with irregular or no folic acid supplementation experienced higher risk of macrosomia associated with PM2.5 exposure.

Respiratory Effects of Traffic-Related Air Pollution: A Randomized, Crossover Analysis of Lung Function, Airway Metabolome, and Biomarkers of Airway Injury.

BACKGROUND: Exposure to traffic-related air pollution (TRAP) has been associated with increased risks of respiratory diseases, but the biological mechanisms are not yet fully elucidated. OBJECTIVES: Our aim was to evaluate the respiratory responses and explore potential biological mechanisms of TRAP exposure in a randomized crossover trial. METHODS: We conducted a randomized crossover trial in 56 healthy adults. Each participant was exposed to high- and low-TRAP exposure sessions by walking in a park and down a road with high traffic volume for 4 h in random order. Respiratory symptoms and lung function, including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), the ratio of FEV1 to FVC, and maximal mid-expiratory flow (MMEF), were measured before and after each exposure session. Markers of 8-isoprostane, tumor necrosis factor-α (TNF-α), and ezrin in exhaled breath condensate (EBC), and surfactant proteins D (SP-D) in serum were also measured. We used linear mixed-effects models to estimate the associations, adjusted for age, sex, body mass index, meteorological condition, and batch (only for biomarkers). Liquid chromatography-mass spectrometry was used to profile the EBC metabolome. Untargeted metabolome-wide association study (MWAS) analysis and pathway enrichment analysis using mummichog were performed to identify critical metabolomic features and pathways associated with TRAP exposure. RESULTS: Participants had two to three times higher exposure to traffic-related air pollutants except for fine particulate matter while walking along the road compared with in the park. Compared with the low-TRAP exposure at the park, high-TRAP exposure at the road was associated with a higher score of respiratory symptoms [2.615 (95% CI: 0.605, 4.626), p=1.2×10-2] and relatively lower lung function indicators [-0.075L (95% CI: -0.138, -0.012), p=2.1×10-2] for FEV1 and -0.190L/s (95% CI: -0.351, -0.029; p=2.4×10-2) for MMEF]. Exposure to TRAP was significantly associated with changes in some, but not all, biomarkers, particularly with a 0.494-ng/mL (95% CI: 0.297, 0.691; p=9.5×10-6) increase for serum SP-D and a 0.123-ng/mL (95% CI: -0.208, -0.037; p=7.2×10-3) decrease for EBC ezrin. Untargeted MWAS analysis revealed that elevated TRAP exposure was significantly associated with perturbations in 23 and 32 metabolic pathways under positive- and negative-ion modes, respectively. These pathways were most related to inflammatory response, oxidative stress, and energy use metabolism. CONCLUSIONS: This study suggests that TRAP exposure might lead to lung function impairment and respiratory symptoms. Possible underlying mechanisms include lung epithelial injury, inflammation, oxidative stress, and energy metabolism disorders. https://doi.org/10.1289/EHP11139.

PM2.5 exposure and its interaction of oxidative balance score on ovarian cancer survival: A prospective cohort study.

Recent evidence advises particles with a diameter of 2.5 µm or less (PM2.5) might be a prognostic factor for ovarian cancer (OC) survival. The oxidative balance score (OBS) incorporates diet-lifestyle factors to estimate individuals' anti-oxidant exposure status which may be relevant to cancer prognosis. We aimed to investigate the roles of PM2.5, and OBS and their interaction in OC prognosis. 663 patients with OC were enrolled in the current study. Satellite-derived annual average exposures to PM2.5 based on patients' residential locations. The OBS was calculated based on 16 different diet-lifestyle components derived using an acknowledged self-reported questionnaire. The Cox regression model was performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS). We also assessed the effect of modification between PM2.5 and OS by OBS via interaction terms. During a median follow-up of 37.57 (interquartile:35.27-40.17) months, 123 patients died. Compared to low-concentration PM2.5 exposure, high PM2.5 during 1 year before diagnosis was associated with worse OC survival (HR= 1.19, 95% CI = 1.01-1.42). We observed an improved OS with the highest compared with the lowest OBS (HR = 0.46, 95% CI = 0.27-0.79, P for trend < 0.05). Notably, we also found an additive interaction between low OBS and high exposure to PM2.5, with the corresponding associations of PM2.5 being more pronounced among participants with lower OBS (HR = 1.42, 95% CI = 1.09-1.86). PM2.5 may blunt OC survival, but high OBS represented an antioxidative performance that could alleviate the adverse association of PM2.5 and OS.

Association of long-term particulate matter exposure with all-cause mortality among patients with ovarian cancer: A prospective cohort.

BACKGROUND: Evidence of the association between particles with a diameter of 2.5 µm or less (PM2.5) in long term and ovarian cancer (OC) mortality is limited. METHODS: This prospective cohort study analyzed data collected between 2015 and 2020 from 610 newly diagnosed OC patients, aged 18-79 years. The residential average PM2.5 concentrations 10 years before the date of OC diagnosis were assessed by random forest models at a 1 km × 1 km resolution. Cox proportional hazard models fully adjusted for the covariates (including age at diagnosis, education, physical activity, kitchen ventilation, FIGO stage, and comorbidities) and distributed lag non-linear models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of PM2.5 and all-cause mortality of OC. RESULTS: During a median follow-up of 37.6 months (interquartile: 24.8-50.5 months), 118 (19.34 %) deaths were confirmed among 610 OC patients. One-year PM2.5 exposure levels before OC diagnosis was significantly associated with an increase in all-cause mortality among OC patients (single-pollutant model: HR = 1.22, 95 % CI: 1.02-1.46; multi-pollutant models: HR = 1.38, 95 % CI: 1.10-1.72). Furthermore, during 1 to 10 years prior to diagnosis, the lag-specific effect of long-term PM2.5 exposure on the all-cause mortality of OC had a risk increase for lag 1-6 years, and the exposure-response relationship was linear. Of note, significant interactions between several immunological indicators as well as solid fuel use for cooking and ambient PM2.5 concentrations were observed. CONCLUSION: Higher ambient PM2.5 concentrations were associated with an increased risk of all-cause mortality among OC patients, and there was a lag effect in long-term PM2.5 exposure.

Cyclic pentapeptides with anti-inflammatory, cytotoxic or α-glucosidase inhibitory activities from Basidiobolus meristosporus.

Basidiobolus meristosporus is an opportunistic pathogen of mammals with unique habitats, but its metabolites have not been extensively studied. Through semi-preparative HPLC, nine undescribed cyclic pentapeptides were isolated from mycelia of B. meristosporus RCEF4516. The structure of the compounds 1-9 were identified with MS/MS and NMR data and designated as basidiosin D-L respectively. The absolute configurations were determined according to the advanced Marfey's method after compound hydrolysis. Bioactivity testing showed that compounds 1, 2, 3, 4 and 8 decreased NO production in LPS-activated RAW264.7 cells in a concentration-dependent manner. The nine compounds showed cytotoxicity against RAW264.7, 293 T and HepG2 cells. All the compounds except compound 7 showed stronger inhibitory effects on α-glucosidase than acarbose.

[Application of cartilage in tympanoplasty].

Cartilage has undergone rapid development in ear surgery since Heermann used the grid cartilage technique to repair large perforations of the tympanic membrane. Cartilage has been widely used in tympanoplasty, ossicular chain reconstruction, reconstruction of the lateral wall of the upper tympanic cavity and the posterior wall of the external auditory canal due to its advantages of convenient sampling, high stability, good elasticity, low metabolic rate, easy survival and strong plasticity. This paper reviews the use of cartilage in tympanoplasty and discusses the possibility of placing cartilage on the stapes head for reconstruction of the auditory chain in type Ⅱ tympanoplasty.

Lithium Salt Dissociation Promoted by 18-Crown-6 Ether Additive toward Dilute Electrolytes for High Performance Lithium Oxygen Batteries.

Lithium-oxygen batteries (LOBs) are well known for their high energy density. However, their reversibility and rate performance are challenged due to the sluggish oxygen reduction/evolution reactions (ORR/OER) kinetics, serious side reactions and uncontrollable Li dendrite growth. The electrolyte plays a key role in transport of Li+ and reactive oxygen species in LOBs. Here, we tailored a dilute electrolyte by screening suitable crown ether additives to promote lithium salt dissociation and Li+ solvation through electrostatic interaction. The electrolyte containing 100 mM 18-crown-6 ether (100-18C6) exhibits enhanced electrochemical stability and triggers a solution-mediated Li2 O2 growth pathway in LOBs, showing high discharge capacity of 10 828.8 mAh gcarbon -1 . Moreover, optimized electrode/electrolyte interfaces promote ORR/OER kinetics on cathode and achieve dendrite-free Li anode, which enhances the cycle life. This work casts new lights on the design of low-cost dilute electrolytes for high performance LOBs.

Residential greenness exposure and decreased prevalence of diabetic retinopathy: A nationwide analysis in China.

OBJECTIVE: Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness among diabetics. We aimed to explore whether long-term exposure to residential greenness was beneficial to DR. RESEARCH DESIGN AND METHODS: We used data from a large-scale, cross-sectional screening survey conducted in 129 cities of 27 provincial regions of China from 2018 to 2021 among patients with diabetes. We measured residential greenness exposure as the 3-year average of annual maximum Normalized Difference Vegetation Index (NDVI) at a spatial resolution of 250 m. DR was assessed by ophthalmologists based on fundus photographs. The primary outcome was DR, and secondary outcome included DR severity status (i.e., nonproliferative and proliferative), hallmarks of retinal lesions and macular oedema. RESULTS: A total of 484,380 adult participants with diabetes were included in the current analysis, and 15.7% of them were diagnosed with DR. NDVI was inversely and linearly associated with DR prevalence, and an increment of 0.1 NDVI was associated with a 10% (9%-10%) decrease in DR prevalence. Significant and inverse associations were further found for nonproliferative and proliferative DR, hallmarks of lesions and macular oedema. The association between greenness and DR was stronger among participants who were older, obese, lived in the south, had longer duration of diabetes or did not take antidiabetic medications. CONCLUSIONS: This large-scale nationwide study provides the first-hand epidemiological evidence on the associations of residential greenness with DR. Our findings highlight the importance of residential greenness in alleviating DR risk especially in an era of aging and urbanization.

Fine particulate matter and cardiorespiratory health in China: A systematic review and meta-analysis of epidemiological studies.

This review aimed to systematically summarize the epidemiological literature on the cardiorespiratory effects of PM2.5 published during the 13th Five-Year Plan period (2016-2020) in China. Original articles published between January 1, 2016 and June 30, 2021 were searched in PubMed, Web of Science, the China National Knowledge Internet Database and Wanfang Database. Random- or fixed-effects models were used to pool effect estimates where appropriate. Of 8558 records identified, 145 met the full eligibility criteria. A 10 µg/m³ increase in short-term PM2.5 exposure was significantly associated with increases of 0.70%, 0.86%, 0.38% and 0.96% in cardiovascular mortality, respiratory mortality, cardiovascular morbidity, and respiratory morbidity, respectively. The specific diseases with significant associations included stroke, ischemic heart disease, heart failure, arrhythmia, chronic obstructive pulmonary disease, pneumonia and allergic rhinitis. The pooled estimates per 10 µg/m³ increase in long-term PM2.5 exposure were 15.1%, 11.9% and 21.0% increases in cardiovascular, stroke and lung cancer mortality, and 17.4%, 11.0% and 4.88% increases in cardiovascular, hypertension and lung cancer incidence respectively. Adverse changes in blood pressure, heart rate variability, systemic inflammation, blood lipids, lung function and airway inflammation were observed for either short-term or long-term PM2.5 exposure, or both. Collectively, we summarized representative exposure-response relationships between short- and long-term PM2.5 exposure and a wide range of cardiorespiratory outcomes applicable to China. The magnitudes of estimates were generally smaller in short-term associations and comparable in long-term associations compared with those in developed countries. Our findings are helpful for future standard revisions and policy formulation. There are still some notable gaps that merit further investigation in China.

Discovery of Potent Inhibitors of Cyclin-Dependent Kinases 7 and 9: Design, Synthesis, Structure-Activity Relationship Analysis and Biological Evaluation.

Cyclin-dependent kinases (CDKs) 7 and 9 are deregulated in various types of human cancer and are thus viewed as therapeutic targets. Accordingly, small-molecule inhibitors of both CDKs are highly sought-after. Capitalising on our previous discovery of CDKI-73, a potent CDK9 inhibitor, medicinal chemistry optimisation was pursued. A number of N-pyridinylpyrimidin-2-amines were rationally designed, chemically synthesised and biologically assessed. Among them, N-(6-(4-cyclopentylpiperazin-1-yl)pyridin-3-yl)-4-(imidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-amine was found to be one of the most potent inhibitors of CDKs 7 and 9 as well as the most effective anti-proliferative agent towards multiple human cancer cell lines. The cellular mode of action of this compound was investigated in MV4-11 acute myeloid leukaemia cells, revealing that the compound dampened the kinase activity of cellular CDKs 7 and 9, arrested the cell cycle at sub-G1 phase and induced apoptosis.