Associations of fine particulate matter and its metal constituents with blood pressure: A panel study during the seventh World Military Games.

Evidence is needed to elucidate the association of blood pressure (BP) changes with metal constituents in fine particulate matter (PM2.5). Therefore, we designed a longitudinal panel study enrolling 70 healthy students from Wuhan University in the context of the seventh World Military Games (the 7th WMG) from September 2019 to January 2020. A total of eight visits were conducted before, during, and after the 7th WMG. During every visit, each participant was asked to carry a personal PM2.5 monitor to measure hourly PM2.5 levels for three consecutive days. Questionnaire investigation and physical examination were completed on the fourth day. We analyzed ten metal constituents of ambient PM2.5 collected from the fixed station, and blood pressure was recorded during each visit. The linear mixed-effects models were performed to evaluate associations of metal constituents and blood pressure measurements. We observed a dramatic variation of PM2.5 concentration ranging from 7.38 to 132.04 µg/m3. A 10 µg/m3 increment of PM2.5 was associated with an increase of 0.64 mmHg (95% CI: 0.44, 0.84) in systolic BP (SBP), 0.40 mmHg (0.26, 0.54) in diastolic BP (DBP), 0.31 mmHg (0.15, 0.47) in pulse pressure (PP) and 0.44 mmHg (0.26, 0.62) in mean artery pressure (MAP), respectively. For metal constituents in PM2.5, robust positive associations were observed between BP and selenium, manganese, arsenic, cadmium, and thallium. For example, for an IQR (0.93 ng/m3) increment of selenium, SBP and MAP elevated by 0.98 mmHg (0.09, 1.87) and 0.71 mmHg (0.03, 1.39), respectively. Aluminum was found to be robustly associated with decreased SBP, DBP, and MAP. The study indicated that exposure to PM2.5 total mass and metal constituents including selenium, manganese, arsenic, cadmium, and thallium were associated with the elevated BP.

How long-term air pollution and its metal constituents affect type 2 diabetes mellitus prevalence? Results from Wuhan Chronic Disease Cohort.

BACKGROUND: Epidemiological evidence linking type 2 diabetes mellitus (T2DM) with air pollution is discrepant and most are restricted to the influences of air-pollutant mass concentration. This study aims to explore the effects of long-term exposure to air pollution and its metal constituents on T2DM prevalence in China. METHODS: We used data on 10,253 adult residents from the baseline survey of Wuhan Chronic Disease Cohort in 2019. Ambient PM2.5, PM10 and NO2 exposure were estimated at residences based on Chinese Air Quality Reanalysis Dataset. Concentrations of 10 metal constituents were measured by 976 PM2.5 filter samples collected from four monitoring stations. Logistic regression models were employed to examine associations of T2DM prevalence with 3-year mean concentrations of each air pollutant and PM2.5 metal constituents prior to the baseline investigation. RESULTS: A total of 673 T2DM cases (6.6%) were identified. The 3-year mean exposures to PM2.5, PM10 and NO2 were 50.89 µg/m3, 82.86 µg/m3, and 39.79 µg/m3, respectively. And interquartile range (IQR) of 10 metals in PM2.5 varied from 0.03 ng/m3 to 78.30 ng/m3. For 1 µg/m3 increment in PM2.5, PM10 and NO2, the odds of T2DM increased by 7.2% (95%CI: 1.026, 1.136), 3.1% (95%CI: 1.013, 1.050), and 2.1% (95%CI: 1.005, 1.038) after adjusting for potential confounders. Cd and Sb in PM2.5 were significant risk factors to T2DM with odds ratios of 1.350 (95%CI: 1.089, 1.673) and 1.389 (95%CI: 1.164, 1.658) for per IQR increase, respectively. Stratification analyses indicated that males and those aged ≥45 years were more susceptive to long-term air pollution. CONCLUSIONS: Long-term exposure to PM2.5, PM10 and NO2 increased T2DM prevalence in a Wuhan population, especially for men and middle-aged and elderly people. Moreover, T2DM was significantly associated with Cd and Sb in PM2.5. Further research to validate these results and to clarify the underlying mechanisms is warranted.

Short-term exposure to fine particulate matter and its constituents may affect renal function via oxidative stress: A longitudinal panel study.

Exposure to fine particulate matter (PM2.5) has been reported to increase the risks of chronic kidney disease. However, limited research has assessed the effect of PM2.5 and its constituents on renal function, and the underlying mechanism has not been well characterized. We aimed to evaluate the association of PM2.5 and its constituents with kidney indicators and to explore the roles of systematic oxidative stress and inflammation in the association. We conducted a longitudinal panel study among 35 healthy adults before-, intra- and after-the 2019 Wuhan Military World Games. We repeatedly measured 6 renal function parameters and 5 circulating biomarkers of oxidative stress and inflammation at 6 rounds of follow-ups. We monitored hourly personal PM2.5 concentrations with 3 consecutive days and measured 10 metals (metalloids) and 16 polycyclic aromatic hydrocarbons (PAHs) components. The linear mixed-effect models were applied to examine the association between PM2.5 and renal function parameters, and the mediation analysis was performed to explore potential bio-pathways. PM2.5 concentrations across Wuhan showed a slight decrease during the Military Games. We observed significant associations between elevated blood urea nitrogen (BUN) levels and PM2.5 and its several metals and PAHs components. For an interquartile range (IQR) increase of PM2.5, BUN increased 0.42 mmol/L (95% CI: 0.14 to 0.69). On average, an IQR higher of lead (Pb), cadmium (Cd), arsenic (As), selenium (Se), thallium (Tl) and Indeno (1,2,3-cd) pyrene (IPY) were associated with 0.90, 0.65, 0.29, 0.27, 0.26 and 0.90 mmol/L increment of BUN, respectively. Moreover, superoxide dismutase was positively associated with PM2.5 and mediated 18.24% association. Our research indicated that exposure to PM2.5 might affect renal function by activating oxidative stress pathways, in which the constituents of Pb, Cd, As, Se, Tl and IPY might contribute to the associations.

Associations of long-term exposure to ambient air pollutants with metabolic syndrome: The Wuhan Chronic Disease Cohort Study (WCDCS).

BACKGROUND: Evidence on the associations between long-term exposure to ambient air pollutants (including particle with aerodynamic diameter ≤10 µm (PM10), particle with aerodynamic diameter ≤2.5 µm (PM2.5), ozone (O3), nitrogen dioxide (NO2), and sulfur dioxide (SO2)) and prevalence of metabolic syndrome (MetS) remains inconclusive. This study aimed to determine the associations based on a case-control study nested in the Wuhan Chronic Disease Cohort study (WCDCS), a population-based study with baseline survey in 2019. METHODS: A total of 10,253 residents living in Wuhan were recruited. The 3-year average concentrations of main pollutants (PM10, PM2.5, O3, NO2, and SO2) at residences prior to the survey date were estimated to evaluate the long-term exposures. The generalized linear mixed models were used to investigate the changes in MetS prevalence by an IQR increases in each air pollutant exposure concentrations. Interaction effects between air pollutants and demographic, lifestyle, and dietary factors on MetS were evaluated by including an interactive item in the main model. RESULTS: The prevalence of MetS in Wuhan was 9.8%, and the 3-year exposure concentrations of PM10, PM2.5, O3, NO2, and SO2 were 84.1 µg/m3, 50.5 µg/m3, 55.7 µg/m3, 46.0 µg/m3, and 9.4 µg/m3, respectively. Higher PM10, PM2.5 and O3 exposure concentrations were associated with an elevated MetS prevalence (e.g. an IQR increase in PM2.5, OR = 1.193, 95% confidence intervals (95%CIs): 1.028, 1.385; for O3, OR = 1.074, 95%CIs: 1.025, 1.124), whereas NO2, and SO2 were negatively or insignificant correlated with odds of Mets (e.g. an IQR increase in NO2, OR = 0.865, 95%CIs: 0.795, 0.941). Males, smokers, alcohol drinkers and individuals who intake fruits occasionally exposure to PM10 and PM2.5 were found had a higher risk of developing MetS. CONCLUSIONS: Long-term exposure to higher concentrations of ambient air pollutants may elevate the prevalence of MetS in populations in Central China. Susceptible individuals especially those with unhealthy lifestyles had a higher risk for MetS.

"Watson-Crick G[triple bond, length as m-dash]C"-inspired supramolecular nanodrug of methotrexate and 5-fluorouracil for tumor microenvironment-activatable self-recognizing synergistic chemotherapy.

Carrier-free nanodrugs, generated via the straightforward small-molecule self-assembly of anticancer drugs, provide a promising route for cancer chemotherapy. However, their low structural stability, lack of targeting specificity, and poor stimulus responsiveness are still limiting their therapeutic effect. Inspired by Watson-Crick G[triple bond, length as m-dash]C base pairing, the FDA-approved chemo-drug methotrexate (MTX, which can bind with folate receptors) and 5-fluorouracil (5-FU, a DNA/RNA synthetase inhibitor) were adopted for direct assembly into self-recognizing MTX-5-FU nanoparticles via "Watson-Crick-like base pairing"-driven precise supramolecular assembly. Sequentially, our synthesized weak acidity-responsive polyethylene glycol (PEG) was inserted onto the nanoparticle surface to temporarily shield the self-targeting function of MTX and prolong the blood circulation time. Once PEG-MTX-5-FU nanoparticles reached the weakly acidic tumor microenvironment, the PEG corona could be cleaved from their surface and then MTX could be re-exposed to recover its self-recognition ability and significantly elevate tumor cell uptake; furthermore, the de-PEGylated MTX-5-FU nanoparticles could respond to the stronger acidity of lysosome, triggering core disassembly and thus the burst release of both MTX and 5-FU. Further in vitro and in vivo studies consistently confirmed that the nanodrugs exhibited preferable accumulation at the tumor sites with highly synergistic chemotherapeutic effects. The supramolecular recognition-inspired, cascade-triggered self-targeting and controlled release of nanodrugs could be a promising strategy to improve synergistic chemotherapy.

Synthesis and Characterization of Photothermal Osmium Carbolong Complexes.

Metallacycles with chelating polydentate conjugated-carbon chain ligands are called carbolong complexes, which are expected to have interesting properties. In this work, the preparation of 12-carbon carbolong complexes in which all of the coordinated atoms in the equatorial plane are carbon atoms was studied. With the help of the well-established mechanism, a new approach to prepare coplanar carbolong complexes bearing different organic functional groups was developed by adding different terminal alkynes in sequence. In the presence of HBF4 , these coplanar carbolong complexes were converted to η3 -allyl osmapentalene derivatives, which can be produced directly from the reaction of cyclopropaosmapentalene 1 with terminal alkynes in the presence of AgBF4 under anhydrous conditions. This study offers a new route for the preparation of functional osmium carbolong complexes with excellent photothermal properties, which can be used to prepare photothermal materials.

A modified laparoscopic splenectomy for massive splenomegaly in children with hematological disorder: a single institute retrospective clinical research.

PURPOSE: With the optimal acceptance of its clinical advantages, laparoscopic splenectomy (LS) emerged as a gold standard procedure as compared with open splenectomy (OS). However, it is still controversial and even counted as contraindication for massive splenomegaly. Here, we aim to summarize the experiences, characteristics and trends of modified LS for massive splenomegaly in children with hematological disorders. METHODS: Retrospective series of 57 pediatric patients with massive splenomegaly who underwent splenectomy from March 2007 to December 2011 were designated for this clinical analysis. The main outcome measures were dealt by statistics. For 30 cases of LS, we strictly adhered to the principle of using only three trocars to operate and initial ligation of the splenic artery, followed by retrieving the piecemeal of spleen through an accessory incision of 2-3 cm at 12 mm trocar port site. RESULTS: Of the 57 pediatric patients, 27 underwent OS and 30 underwent LS, respectively. Despite the operative time being shorter for OS than for LS (P < 0.001), the blood loss was lower in LS than in OS (P < 0.001); the time required for oral intake as well as duration of hospital stay was lower in LS than in OS (P < 0.001). Post-operatively, 7 (25.9 %) complications occurred in OS and 3 (10 %) in LS. The conversion rate of LS to OS was 13.33 % in four cases till 2009. CONCLUSIONS: Despite the conflicting reports regarding the safety of LS for massive splenomegaly, we demonstrated that our modified laparoscopic splenectomy in the treatment of children with massive splenomegaly in hematological diseases seemed to achieve the fundamental goal of less invasion; it was safe and feasible.

The difluoromethylene group as a replacement for the labile oxygen in steroid sulfates: a new approach to steroid sulfatase inhibitors.

Several estrone sulfate and estradiol sulfate analogues, in which the sulfate group was replaced with an alpha,alpha-difluoromethylenesulfonate group or an alpha,alpha-difluoromethylenetetrazole group, were examined as inhibitors of steroid sulfatase (STS). These compounds were 4.5-10.5 times more potent than their non-fluorinated analogues. Moreover, the presence of the fluorines changed the mode of inhibition from mixed to competitive. The inhibitor bearing the alpha,alpha-difluoromethylenetetrazole group exhibited an affinity for STS approaching that of the natural STS substrate, estrone sulfate. Possible reasons for the enhanced affinity of the fluorinated compounds compared to their non-fluorinated counterparts are discussed.