Parvalbumin Regulates GAD Expression through Calcium Ion Concentration to Affect the Balance of Glu-GABA and Improve KA-Induced Status Epilepticus in PV-Cre Transgenic Mice.

Aims: the study aimed to (i) use adeno-associated virus technology to modulate parvalbumin (PV) gene expression, both through overexpression and silencing, within the hippocampus of male mice and (ii) assess the impact of PV on the metabolic pathway of glutamate and γ-aminobutyric acid (GABA). Methods: a status epilepticus (SE) mouse model was established by injecting kainic acid into the hippocampus of transgenic mice. When the seizures of mice reached SE, the mice were killed at that time point and 30 min after the onset of SE. Hippocampal tissues were extracted and the mRNA and protein levels of PV and the 65 kDa (GAD65) and 67 kDa (GAD67) isoforms of glutamate decarboxylase were assessed using real-time quantitative polymerase chain reaction and Western blot, respectively. The concentrations of glutamate and GABA were detected with high-performance liquid chromatography (HPLC), and the intracellular calcium concentration was detected using flow cytometry. Results: we demonstrate that the expression of PV is associated with GAD65 and GAD67 and that PV regulates the levels of GAD65 and GAD67. PV was correlated with calcium concentration and GAD expression. Interestingly, PV overexpression resulted in a reduction in calcium ion concentration, upregulation of GAD65 and GAD67, elevation of GABA concentration, reduction in glutamate concentration, and an extension of seizure latency. Conversely, PV silencing induced the opposite effects. Conclusion: parvalbumin may affect the expression of GAD65 and GAD67 by regulating calcium ion concentration, thereby affecting the metabolic pathways associated with glutamate and GABA. In turn, this contributes to the regulation of seizure activity.

A Porphyrin-Based 3D Metal-Organic Framework Featuring [Cu8Cl6]10+ Cluster Secondary Building Units: Synthesis, Structure Elucidation, Anion Exchange, and Peroxidase-Like Activity.

Herein, we report a rare example of cationic three-dimensional (3D) metal-organic framework (MOF) of [Cu5Cl3(TMPP)]Cl5 ⋅ xSol (denoted as Cu-TMPP; H2TMPP=meso-tetrakis (6-methylpyridin-3-yl) porphyrin; xSol=encapsulated solvates) supported by [Cu8Cl6]10+ cluster secondary building units (SBUs) wherein the eight faces of the Cl--based octahedron are capped by eight Cu2+. Surface-area analysis indicated that Cu-TMPP features a mesoporous structure and its solvate-like Cl- counterions can be exchanged by BF4 -, PF6 -, and NO3 -. The polyvinylpyrrolidone (PVP) coated Cu-TMPP (denoted as Cu-TMPP-PVP) demonstrated good ROS generating ability, producing ⋅OH in the absence of light (peroxidase-like activity) and 1O2 on light irradiation (650 nm; 25 mW cm-2). This work highlights the potential of Cu-TMPP as a functional carrier of anionic guests such as drugs, for the combination therapy of cancer and other diseases.

Role of metabolic risk factors in the relationship between ambient fine particulate matter and depressive symptoms: Evidence from a longitudinal population study.

BACKGROUND: There is growing evidence indicating a connection between fine particulate matter (PM2.5) and depressive symptoms. Metabolic risk factors are critical determinants of depressive symptoms. However, the mediating role of these factors on the association between PM2.5 and depressive symptoms remains elusive. We aimed to investigate whether and to what extent metabolic risk factors mediated the link between long-term PM2.5 exposure and depressive symptoms. METHODS: This study comprised 7794 individuals aged between 30 and 79 years who participated in two waves of the on-site surveys in the China Multi-Ethnic Cohort. Ambient PM2.5 concentrations were assessed utilizing a random forest method based on satellite data. We employed the Patient Health Questionnaire-9 to assess depressive symptoms at wave 2, and the overall as well as three sub-domain symptom scores (emotional, neurovegetative, and neurocognitive symptoms) were calculated. Three metabolic risk factors, including hypertension, diabetes, and dyslipidemia, were considered. Mediation analyses were conducted to assess the indirect effects of PM2.5 on depressive symptoms through metabolic risk factors. RESULTS: We found a positive association between chronic exposure to ambient PM2.5 and overall depressive symptoms as well as the three sub-domains. In mediation analyses, metabolic risk factors partially mediated the associations of PM2.5 on depressive symptoms. The natural indirect effects (RR, 95% CI) of PM2.5 on overall, emotional, neurovegetative, and neurocognitive symptoms mediated through metabolic risk factors were 1.004(1.001, 1.007), 1.004 (1.001, 1.008), 1.004 (1.001, 1.007), and 1.003(0.999, 1.007), respectively. Larger indirect effects were found in elderly participants (mediated proportion, 29.3%), females (13.3%), and people who did not consume alcohol (19.6%). CONCLUSIONS: Metabolic risk factors may act as mediators in the relationship between chronic PM2.5 exposure and depression. Treatment of metabolic risk factors may be an opportunity to reduce the burden of depression caused by long-term exposure to PM2.5.

Benzopyrone-mediated quinolones as potential multitargeting antibacterial agents.

A new type of benzopyrone-mediated quinolones (BMQs) was rationally designed and efficiently synthesized as novel potential antibacterial molecules to overcome the global increasingly serious drug resistance. Some synthesized BMQs effectively suppressed the growth of the tested strains, outperforming clinical drugs. Notably, ethylidene-derived BMQ 17a exhibited superior antibacterial potential with low MICs of 0.5-2 µg/mL to clinical drugs norfloxacin, it not only displayed rapid bactericidal performance and inhibited bacterial biofilm formation, but also showed low toxicity toward human red blood cells and normal MDA-kb2 cells. Mechanistic investigation demonstrated that BMQ 17a could effectually induce bacterial metabolic disorders and promote the enhancement of reactive oxygen species to disrupt the bacterial antioxidant defense system. It was found that the active molecule BMQ 17a could not only form supramolecular complex with lactate dehydrogenase, which disturbed the biological functions, but also effectively embed into calf thymus DNA, thus affecting the normal function of DNA and achieving cell death. This work would provide an insight into developing new molecules to reduce drug resistance and expand antibacterial spectrum.

The effects of rate pressure product at admission on cardiopulmonary function during hospitalization in patients with acute myocardial infarction.

OBJECTIVE: This study aimed to analyze the correlation between the rate pressure product (RPP) and cardiopulmonary function during hospitalization in patients with acute myocardial infarction (AMI). METHODS: A total of 362 patients with AMI were selected for the study, and the median admission RPP was used as the cutoff point to divide the patients into a low-RPP group (n = 181) and a high-RPP group (n = 181). The relationship between the RPP at admission and the cardiopulmonary function during hospitalization was analyzed. RESULTS: The patients in the high-RPP group had a higher body mass index (BMI) (p = 0.014), a higher prevalence of combined hypertension and diabetes mellitus (p < 0.001), a lower incidence of smoking (p = 0.044), and a higher incidence of oscillatory ventilation (6.1% vs. 1.7%, p = 0.029). The differences in RPP at rest, during warm-up, and within 1 and 4 minutes of recovery were statistically significant between the two groups (p < 0.01 on each occasion), while the differences in anaerobic threshold (AT) and watt max (Max) were not statistically significant (p > 0.05 for both). The patients in the low-RPP group had higher oxygen uptake (VO2 [AT]: 14.9 ± 3.4 vs. 14.2 ± 3.6, p = 0.048) and (VO2peak [Max]:18.2 ± 3.8 vs. 17.3 ± 3.8, p = 0.020). The RPP at admission was negatively correlated with VO2 (AT) and VO2peak (p < 0.05) using the regression Equation VO2peak = 33.682 + (-0.012 * RPP at admission/100) + (-0.105 * Age) + (-0.350 * BMI), while there was no correlation between the RPP at admission and VO2 (AT) (p = 0.149). CONCLUSION: The RPP at admission was negatively correlated with cardiopulmonary function during hospitalization in patients with AMI. Patients with a high RPP were more likely to have a combination of obesity, hypertension, diabetes mellitus, and reduced oxygen uptake during exercise, while a high RPP at admission appeared to affect their cardiovascular response indicators during exercise.

Anemia is associated with long-term exposure to PM2.5 and its components: a large population-based study in Southwest China.

Background: Anemia is linked to PM2.5 (particulate matter with aerodynamic diameters of ⩽2.5 µm) exposure, which can increase the risk of various negative health outcomes. It remains unclear which PM2.5 components are associated with anemia and the respective contribution of each component to this association. Objective: This study aimed at investigating the association between PM2.5 and anemia in the general population and to identify the most critical PM2.5 toxic components in this association. Design: Cross-sectional study. Methods: Our study involved a large cohort of 73,511 individuals aged 30-79 from China's multi-ethnic population. We employed satellite observations and the chemical transport model (GEOS-Chem)to estimate the long-term exposure to PM2.5 and its components. Anemia was defined, according to WHO guidelines, as Hb levels below 130 g/L for men and below 120 g/L for women. Through logistic regression, we investigated the association between PM2.5 components and anemia. By utilizing weighted quantile sum (WQS) analysis, we identified key components and gained insights into their combined impact on anemia. Overall, our study sheds light on the relationship between PM2.5 exposure, its constituents, and the risk of anemia in a large cohort. Results: PM2.5 and three components, nitrate (NIT), organic matter (OM), and soil particles (SOIL), were associated with anemia. Per-standard deviation increase in the 3-year average concentrations of PM2.5 [odds ratio (OR): 1.14, 95% confidence interval (CI): 1.01, 1.28], NIT (1.20, 1.06, 1.35), OM (1.17, 1.04, 1.32), and SOIL (1.22, 1.11, 1.33) were associated with higher odds of anemia. In WQS regression analysis, the WQS index was associated with anemia (OR: 1.29, 95% CI: 1.13, 1.47). SOIL has the highest weight among all PM2.5 components. Conclusions: Long-term exposure to PM2.5 and its constituents is associated with anemia. Moreover, SOIL might be the most critical component of the relationship between PM2.5 and anemia. Our research increases the evidence of the association between PM2.5 and anemia in the general population, and targeted emission control measures should be taken into consideration to mitigate the adverse effects of PM2.5-related anemia.

Ambient PM2.5 and its components associated with 10-year atherosclerotic cardiovascular disease risk in Chinese adults.

BACKGROUND: Exposure to particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5) may increase the risk of 10-year atherosclerotic cardiovascular disease (ASCVD) risk. While PM2.5 is comprised of various components, the evidence on the correlation of its components with 10-year ASCVD risk and which component contributes most remains limited. METHODS: Data were derived from the baseline assessments of China Multi-Ethnic Cohort (CMEC). In total, 69,722 individuals aged 35-74 years were included into this study. The annual average concentration of PM2.5 and its components (black carbon, ammonium, nitrate, sulfate, organic matter, soil particles, and sea salt) were estimated by satellite remote sensing and chemical transport models. The ASCVD risk of individuals was calculated by the equations from the China-PAR Project (prediction for ASCVD risk in China). The relationship between single exposure to PM2.5 and its components and predicted 10-year ASCVD risk was assessed using the logistic regression model. The effect of joint exposure was estimated, and the most significant contributor was identified using the weighted quantile sum approach. RESULTS: Totally 69,722 participants were included, of which 95.8 % and 4.2 % had low and high 10-year ASCVD risk, respectively. Per standard deviation increases in the 3-year average concentration of PM2.5 mass (odds ratio [OR] 1.23, 95 % confidence interval [CI]: 1.12-1.35), black carbon (1.21, 1.11-1.33), ammonium (1.21, 1.10-1.32), nitrate (1.25, 1.14-1.38), organic matter (1.29, 1.18-1.42), sulfate (1.17, 1.07-1.28), and soil particles (1.15, 1.04-1.26) were related to high 10-year ASCVD risk. The overall effect (1.19, 1.11-1.28) of the PM2.5 components was positively associated with 10-year ASCVD risk, and organic matter had the most contribution to this relationship. Female participants were more significantly impacted by PM2.5, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles compared to others. CONCLUSION: Long-term exposure to PM2.5 mass, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles were positively associated with high 10-year ASCVD risk, while sea salt exhibited a protective effect. Moreover, the organic matter might take primary responsibility for the relationship between PM2.5 and 10-year ASCVD risk. Females were more susceptible to the adverse effect.

Facile Synthesis Hyper-Crosslinked PdFe Bimetallic Polymer as Highly Active Catalyst for Ullmann Coupling Reaction of Chlorobenzene.

The synthesis of efficient and sustainable heterogeneous Pd-based catalysts has been an active field of research due to their crucial role in carbon-carbon coupling reactions. In this study, we developed a facile and eco-friendly in situ assembly technique to produce a PdFe bimetallic hyper-crosslinked polymer (HCP@Pd/Fe) to use as a highly active and durable catalyst in the Ullmann reaction. The HCP@Pd/Fe catalyst exhibits a hierarchical pore structure, high specific surface area, and uniform distribution of active sites, which promote catalytic activity and stability. Under mild conditions, the HCP@Pd/Fe catalyst is capable of efficiently catalyzing the Ullmann reaction of aryl chlorides in aqueous media. The exceptional catalytic performance of HCP@Pd/Fe is attributed to its robust absorption capability, high dispersion, and strong interaction between Fe and Pd, as confirmed by various material characterizations and control experiments. Furthermore, the coated structure of a hyper-crosslinked polymer enables easy recycling and reuse of the catalyst for at least 10 cycles without any significant loss of activity.

Synthesis and Biological Evaluation of Piperazine Hybridized Coumarin Indolylcyanoenones with Antibacterial Potential.

A class of piperazine hybridized coumarin indolylcyanoenones was exploited as new structural antibacterial frameworks to combat intractable bacterial resistance. Bioactive assessment discovered that 4-chlorobenzyl derivative 11f showed a prominent inhibition on Pseudomonas aeruginosa ATCC 27853 with a low MIC of 1 µg/mL, which was four-fold more effective than norfloxacin. Importantly, the highly active 11f with inconspicuous hemolysis towards human red blood cells displayed quite low proneness to trigger bacterial resistance. Preliminary explorations on its antibacterial behavior disclosed that 11f possessed the ability to destroy bacterial cell membrane, leading to increased permeability of inner and outer membranes, the depolarization and fracture of membrane, and the effusion of intracellular components. Furthermore, bacterial oxidative stress and metabolic turbulence aroused by 11f also accelerated bacterial apoptosis. In particular, 11f could not only effectively inset into DNA, but also bind with DNA gyrase through forming supramolecular complex, thereby affecting the biological function of DNA. The above findings of new piperazine hybridized coumarin indolylcyanoenones provided an inspired possibility for the treatment of resistant bacterial infections.

Parvalbumin in the metabolic pathway of glutamate and γ-aminobutyric acid: Influence on expression of GAD65 and GAD67.

Parvalbumin-expressing neurons are a type of inhibitory intermediate neuron that play an important role in terminating seizures. The aim of the present study was to use lentiviral construction and packaging technology to overexpress and silence the parvalbumin gene in pheochromocytoma (PC12) cells, and to evaluate how parvalbumin influences the metabolic pathway involving glutamate and γ-aminobutyric acid (GABA). In this work, Immunofluorescence staining was used to verify the differentiation of PC12 cells into neurons after adding nerve growth factor (NGF). Western blotting and real-time quantitative polymerase chain reaction (qRT-PCR) were used to confirm lentivirus-mediated knockdown or overexpression of parvalbumin. Expression of parvalbumin, the 65-kDa GAD isoform (GAD65), and the 67-kDa GAD isoform (GAD67) in neuronal cells was examined at the mRNA and protein levels using qRT-PCR, western blotting and immunofluorescence staining, while intracellular glutamate and GABA levels were determined by high performance liquid chromatography (HPLC). We demonstrate that the expression of parvalbumin is associated with GAD65 and GAD67. Interestingly, overexpression of parvalbumin up-regulated GAD65 and GAD67, increased GABA concentration, and decreased glutamate concentration. Silencing of parvalbumin led to the opposite effects. Altogether, parvalbumin affected the expression of GAD65 and GAD67, thereby influencing the metabolic pathway involving glutamate and GABA.

The relationship between homocysteine and cardiopulmonary exercise testing in patients with acute coronary syndrome after percutaneous coronary intervention.

OBJECTIVE: The purpose of this study was to investigate the relationship between homocysteine (Hcy) levels and cardiopulmonary exercise testing (CPET) in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). We also explored the relationship between Hcy levels and cardiac ultrasonography. METHODS: This study comprised 261 patients with ACS who underwent coronary angiography and PCI at Yulin First Hospital from January 2020 to June 2021. All subjects completed basic data collection, laboratory examination, CPET and cardiac ultrasonography. The CPET includes the peak oxygen uptake (peak VO2), anaerobic threshold (AT), metabolic equivalents (METs), exercise load (load), oxygen pulse (O2 pulse), end-tidal CO2 partial pressure (PETCO2), ventilatory equivalents for carbon dioxide (VE/VCO2) and Oxygen uptake efficiency (OUES). Cardiac ultrasonography was used to evaluate the left ventricular end diastolic diameter (LVEDD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT) and left ventricular ejection fraction (LVEF). A serum Hcy level ≥ 15 µmol/L was defined as hyperhomocysteinemia (HHcy). The patients were divided into the Hcy < 15 µmol/L group (n = 189) and the Hcy ≥ 15 µmol/L group (n = 72). RESULTS: The average age of the participating patients was 58.9 ± 10.1 years. The majority of participants were male (86.6%). The CPET indices of METs, load, VO2/kg, and PETCO2 were significantly decreased in the Hcy ≥ 15 µmol/L group compared with the Hcy < 15 µmol/L group. Additionally, the CPET index of the VE/VCO2 slope and the cardiac ultrasonography indices of IVST and LVPWT were significantly increased in the Hcy ≥ 15 µmol/L group compared with the Hcy < 15 µmol/L group. These differences were statistically significant (P < 0.05). Correlation analysis showed that Hcy levels were negatively correlated with METs, VO2/kg and PETCO2 and positively correlated with the VE/VCO2 slope (P < 0.05). Partial correlation analysis showed that Hcy levels were negatively correlated with METs and VO2/kg in the AT state. The correlation coefficients were - 0.172 and - 0.172, respectively (P < 0.05). Hcy levels were negatively correlated with METs, VO2/kg and PETCO2 in the peak state. The correlation coefficients were - 0.177, -0.153 and - 0.129, respectively (P < 0.05). After further adjustment for confounders, multiple linear regression analysis showed that Hcy levels were negatively correlated with METs and VO2/kg in the AT state and peak state. The standardized regression coefficients were - 0.035, -0.122, -0.048 and - 0.128, respectively (P < 0.05). Correlation analysis showed that Hcy levels were positively correlated with the IVST and LVPWT (P < 0.05), but after adjusting for confounding factors, partial correlation analysis showed that there was no correlation between them. CONCLUSION: A high Hcy level is associated with lower METs and VO2/kg and worse cardiopulmonary function in patients with ACS after PCI.

Novel coumarin aminophosphonates as potential multitargeting antibacterial agents against Staphylococcus aureus.

Unique coumarin aminophosphonates as new antibacterial agents were designed and synthesized to combat severely bacterial resistance. Bioactivity assessment identified that 3-hydroxylphenyl aminophosphonate 6f with low hemolytic activity not only exhibited excellent inhibition potency against Staphylococcus aureus at low concentration (0.5 µg/mL) in vitro but also showed considerable antibacterial potency in vivo. Meanwhile, the active compound 6f was capable of eradicating the S. aureus biofilm, thus alleviating the development of S. aureus resistance. Furthermore, the drug combination of compound 6f with norfloxacin could enhance the antibacterial efficacy. Mechanistic explorations manifested that molecule 6f was able to destroy the integrity of cell membrane, which resulted in the leakage of protein and metabolism inhibition. The cellular redox homeostasis was interfered through inducing the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), leading to the reduction of glutathione (GSH) activity and lipid peroxidation. Furthermore, compound 6f could intercalate into DNA base pair to hinder normal biological function. The above results provided powerful information for the further development of coumarin aminophosphonates as antibacterial agents.

Reduction in risk of contrast-induced nephropathy in patients with chronic kidney disease and diabetes mellitus by enhanced external counterpulsation.

Objective: To evaluate the efficacy of enhanced external counterpulsation (EECP) in the prevention of contrast-induced nephropathy (CIN) in patients with combined chronic kidney disease (CKD) and diabetes mellitus (DM) by comparing the changes in renal function-related indicators in patients before and after coronary angiography (CAG) or percutaneous coronary intervention (PCI). Methods: There were 230 subjects consecutively included in the study. Of these, 30 cases with DM underwent rehydration therapy, and 200 cases underwent EECP therapy in addition to rehydration therapy, comprising 53 patients with DM and 147 patients without. All the patients were tested to measure the renal function indicators before and after CAG/PCI. Results: The postoperative results of blood urea nitrogen (BUN), serum creatinine (Scr), estimated glomerular filtration rate (eGFR), B2 microglobulin, and high-sensitivity C-reactive protein in the three groups showed a statistically significant difference (P < 0.05). After EECP therapy, patients with DM showed a significant decrease in BUN (9.1 ± 4.2 vs. 7.2 ± 3.0, t = 3.899, P < 0.001) and a significant increase in eGFR (41.5 ± 12.7 vs. 44.0 ± 15.6, t = -2.031, P = 0.047), while the patients without DM showed a more significant difference (P < 0.001). Patients with DM showed a lower percentage of elevated Scr (66.7% vs. 43.4%, P = 0.042), a higher percentage of elevated eGFR (30.0% vs. 52.8%, P = 0.044), and a lower incidence of CIN (16.7% vs. 3.8%, P = 0.042) after EECP therapy. Conclusion: Treatment with EECP can reduce Scr in patients with combined CKD and DM post CAG/PCI, increase eGFR, and decrease the incidence of CIN.

White matter abnormalities and multivariate pattern analysis in anti-NMDA receptor encephalitis.

Objective: This study aimed to investigate white matter (WM) microstructural alterations and their relationship correlation with disease severity in anti-NMDA receptor (NMDAR) encephalitis. Multivariate pattern analysis (MVPA) was applied to discriminate between patients and healthy controls and explore potential imaging biomarkers. Methods: Thirty-two patients with anti-NMDAR encephalitis and 26 matched healthy controls underwent diffusion tensor imaging. Tract-based spatial statistics and atlas-based analysis were used to determine WM microstructural alterations between the two groups. MVPA, based on a machine-learning algorithm, was applied to classify patients and healthy controls. Results: Patients exhibited significantly reduced fractional anisotropy in the corpus callosum, fornix, cingulum, anterior limb of the internal capsule, and corona radiata. Moreover, mean diffusivity was increased in the anterior corona radiata and body of the corpus callosum. On the other hand, radial diffusivity was increased in the anterior limb of the internal capsule, cingulum, corpus callosum, corona radiata, and fornix. WM changes in the cingulum, fornix, and retrolenticular part of the internal capsule were correlated with disease severity. The accuracy, sensitivity, and specificity of fractional anisotropy-based classification were each 78.33%, while they were 67.71, 65.83, and 70% for radial diffusivity. Conclusion: Widespread WM lesions were detected in anti-NMDAR encephalitis. The correlation between WM abnormalities and disease severity suggests that these alterations may serve a key role in the pathophysiological mechanisms of anti-NMDAR encephalitis. The combination of tract-based spatial statistics and MVPA may provide more specific and complementary information at the group and individual levels.

Clinical outcome of bioceramic sealer iRoot SP extrusion in root canal treatment: a retrospective analysis.

BACKGROUND: During the obturation procedure, sealer extrusion occurs in some cases. iRoot SP is a kind of bioceramic sealer with superior physicochemical and biological properties. This article reports the outcome of iRoot SP extrusion in root canal treatment and the potential factors associated with the outcome. METHODS: Ninety-nine patients and one hundred and eighty-five teeth treated between 2014 and 2020 were included in this retrospective study. All of the cases were filled with a single-cone technique and the iRoot SP sealer. The minimum follow-up visit period was 1 year. The outcome was evaluated by clinical examination and radiographic examination at recall and was classified as healed, healing (success), or not healed (failure). RESULTS: The overall success rate of all teeth was 96.8%. The success rate of adequately filled teeth was 97.3%, while that of iRoot SP extrusion was 95.8%; the difference was not statistically significant. Factors such as gender, age, tooth position, follow-up visit period, size of periapical lesion, treatment type and extruding sealer amount had no influence on the outcome of iRoot SP extruded teeth. CONCLUSIONS: The results suggested that iRoot SP extrusion has no adverse effect on the outcome of root canal treatment, which may contribute to the endodontic treatment.

Role of Liver Enzymes in the Relationship Between Particulate Matter Exposure and Diabetes Risk: A Longitudinal Cohort Study.

CONTEXT: Particulate matter (PM) is an important risk factor for diabetes. However, its underlying mechanisms remain poorly understood. Although liver-derived biological intermediates may play irreplaceable roles in the pathophysiology of diabetes, few studies have explored this in the association between PM and diabetes. OBJECTIVE: We investigated the role of liver enzymes in mediating the relationship between PM exposure and diabetes. METHODS: We included a total of 7963 participants from the China Multi-Ethnic Cohort. Residential exposure to PM was assessed using a validated spatial-temporal assessment method. Diabetes was diagnosed according to the criteria from American Diabetes Association. Associations between PM, liver enzyme [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase (GGT)], and diabetes were estimated using multivariable regression models. The function of liver enzymes in the relationship between PM and diabetes was assessed using mediation analysis. RESULTS: PM exposure was positively associated with the odds of diabetes, with odds ratios of 1.32 (95% CI 0.83, 2.09), 1.33 (95% CI 1.07, 1.65), and 1.18 (95% CI 1.02, 1.36) for every 10-µg/m3 increment in ≤1 µm (PM1), ≤2.5 µm (PM2.5), and ≤10 µm (PM10) PM, respectively. ALT (4.47%) and GGT (4.78%) exhibited statistically significant mediation effects on the association between PM2.5 and diabetes, and the ALT (4.30%) also had a mediating role on PM10. However, none of the liver enzymes had a significant mediating effect on PM1. CONCLUSION: The relationship between PM and diabetes is partially mediated by liver enzymes, suggesting that lipid accumulation, oxidative stress, and chronic inflammation in the liver may be involved in its pathogenesis.

The role of lipid profile in the relationship between particulate matters and hyperuricemia: A prospective population study.

CONTEXT: Recent studies in specific population subgroups (e.g., pregnant women) have suggested PM exposure increases the risk of hyperuricemia. However, no studies have examined this in the general population. Furthermore, the underlying mechanism through which PM impacts hyperuricemia risk is poorly understood. OBJECTIVE: To assess the association between long-term exposure to PM and risk of hyperuricemia and whether this association is mediated by lipid profile. METHODS: We included 5939 participants in Southwest China from the China Multi-Ethnic Cohort (baseline 2018-2019, follow-up 2020-2021). Long-term PM pollutants (PM1, PM2.5, PM10) exposure for each individual was represented by the three-year average PM levels before the baseline survey. Hyperuricemia at follow-up was defined as the serum uric acid above 7.0 mg/dL in men and 6.0 mg/dL in women. Serum lipids were measured at baseline including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). The association of PM with hyperuricemia was accessed through logistic regression. The potential mediation effects of serum lipids were evaluated through causal mediation analyses. RESULTS: A total of 837 participants were newly diagnosed with hyperuricemia. The odds ratios of hyperuricemia associated with an interquartile range (IQR) increase in PM1, PM2.5, and PM10 (IQR: 21.10, 25.78, 30.43 µg m-3) were 1.72 (95% CI: 1.23, 2.39), 2.68 (95% CI: 1.59, 4.49), and 1.81 (95% CI: 1.20, 2.72), respectively. The association between PM2.5, PM1, and PM10 on hyperuricemia was mediated by HDL-C (10%) and LDL-C (3%). CONCLUSION: Higher particulate matter exposure was associated with higher hyperuricemia incidence. The decline in HDL-C and rise in LDL-C partially mediated this association. These findings were conducive to scientific research about the underlying mechanism of PM on hyperuricemia.

Associations between long-term exposure to ambient air pollution and renal function in Southwest China: The China Multi-Ethnic Cohort (CMEC) study.

BACKGROUND: Limited studies have examined associations between air pollutants exposure and renal function, especially in China, with the most extensive chronic kidney disease (CKD) disease burden worldwide. OBJECTIVES: This study examines associations between long-term exposure to ambient PM2.5, NO2, CO, O3, SO2 and renal function. METHODS: We included 80,225 participants aged 30-79 years from the baseline data of the China Multi-Ethnic Cohort (CMEC) study. Three-year average concentrations of PM2.5, NO2, CO, O3, and SO2 were estimated using satellite-based spatiotemporal models. Renal function is determined by the estimated glomerular filtration rate (eGFR) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. After adjusting for covariates, generalized propensity scores (GPS) weighting regression was used to estimate associations between ambient air pollutants and renal function. RESULTS: An increase of 0.1 mg/m3 CO (OR [odds ratio] =1.20 95% CI [confidence interval], 1.05-1.37) was positively associated with CKD. An increase of 1 µg/m3 in SO2 (1.07, 1.00-1.14) concentration was positively associated with CKD. An increase of 10 µg/m3 in PM2.5 (1.17, 0.99-1.38), NO2 (1.12, 0.83-1.51) and O3 (1.10, 0.81-1.50) concentration was not associated with CKD. These effects are stronger in those younger than 65, smoking and with low BMI. CONCLUSIONS: In this study, we found that long-term exposure to ambient CO and SO2 were positively associated with CKD. Gaseous pollutants should also arouse the concern of relevant departments.

Joint exposure to air pollution, ambient temperature and residential greenness and their association with metabolic syndrome (MetS): A large population-based study among Chinese adults.

Previous studies assessing adverse health have traditionally focused on a single environmental exposure, failing to reflect the reality of various exposures present simultaneously. Air pollution, ambient temperature and greenness have been proposed as critical environmental factors associated with metabolic syndrome (MetS). However, evidence exploring their joint relationships with MetS is needed for identifying interactive factors and developing more targeted public health interventions. The baseline data was obtained from China Multi-Ethnic Cohort (CMEC). Environmental data of air pollutants (PM2.5, O3) and NDVI for greenness was calculated from satellites data. Ambient temperature data were obtained from European Center for Medium-Range Weather Forecasts (ECMWF). MetS was classified based on National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) using anthropometric measures and biomarkers. Logistic regression models were utilized to examine the combined relationship of MetS with three-year exposure to air pollutants, temperature and NDVI. Relative excess risk due to interaction (RERI) was calculated to evaluate interaction on an additive scale. We found associations between prevalent MetS and interquartile range (IQR) increases in PM2.5 (OR: 1.38; 95% confidence interval [95% CI]: 1.23, 1.55) and O3 (OR: 1.15; 95% CI: 1.09, 1.22). Additive and multiplicative interactions were observed between air pollutants and temperature exposure. Compared to low-temperature level, the relationship between PM2.5 and MetS attenuated (RERI: 0.22, 95% CI: 0.44, -0.04) at high-temperature level, while the relationship between O3 and MetS enhanced (RERI: 0.05, 95% CI: 0.02, 0.11). At low NDVI 250 m, the association between PM2.5 and MetS was stronger (RERI: 0.13, 95% CI: 0.05, 0.19) with high NDVI 250 m as the reference group. Our findings showed that ambient temperature and residential greenness could affect the relationship between air pollutants and MetS.

Living near greenness is associated with higher bone strength: A large cross-sectional epidemiological study in China.

BACKGROUND: Living near green spaces may benefit various health outcomes. However, no studies have investigated the greenness-bone linkage in the general population. Moreover, to which extent ambient air pollution (AAP), physical activity (PA), and body mass index (BMI) mediate this relationship remains unclear. We aimed to explore the association between greenness and bone strength and the potential mediating roles of AAP, PA, and BMI in Chinese adults. METHODS: This cross-sectional analysis enrolled 66,053 adults from the China Multi-Ethnic Cohort in 2018-2019. The normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) were employed to define residential greenness. The calcaneus quantitative ultrasound index (QUI) was used to indicate bone strength. Multiple linear regression models and mediation analyses were used to estimate the residential greenness-bone strength association and potential pathways operating through AAP (represented by PM2.5 [particulate matter <2.5 µm in diameter]), PA, and BMI. Stratification analyses were performed to identify susceptible populations. RESULTS: Higher residential exposure to greenness was significantly associated with an increase in QUI, with changes (95% confidence interval) of 3.28 (3.05, 3.50), 3.57 (3.34, 3.80), 2.68 (2.46, 2.90), and 2.93 (2.71, 3.15) for every interquartile range increase in NDVI500m, NDVI1000m, EVI500m, and EVI1000m, respectively. Sex, urbanicity, annual family income, smoking, and drinking significantly modified the association of greenness-bone strength, with more remarkable associations in males, urban residents, subjects from wealthier families, smokers, and drinkers. For the NDVI500m/EVI500m-QUI relationship, the positive mediating roles of PM2.5 and PA were 6.70%/8.50 and 2.43%/2.69%, respectively, whereas those negative for BMI and PA-BMI were 0.88%/1.06% and 0.05%/0.05%, respectively. CONCLUSION: Living in a greener area may predict higher bone strength, particularly among males, urban residents, wealthier people, smokers, and drinkers. AAP, PA, BMI, and other factors may partially mediate the positive association. Our findings underscore the importance of optimizing greenness planning and management policies.