Effects of Ambient O₃ on Respiratory Mortality, Especially the Combined Effects of PM_2.5 and O₃

Background: In China, the increasing concentration of ozone (O3) has emerged as a significant air pollution issue, leading to adverse effects on public health, particularly the respiratory system. Despite the progress made in managing air pollution in China, it is crucial to address the problem of environmental O3 pollution at present. Methods: The connection between O3 exposure and respiratory mortality in Shenyang, China, from 2014 to 2018 was analyzed by a time-series generalized additive regression model (GAM) with quasi-Poisson regression. Additionally, the potential combined effects of fine particulate matter (PM2.5) and O3 were investigated using the synergy index (SI). Results: Our findings indicate that each 10 μg/m3 increase in O3 at lag 2 days was associated with a maximum relative risk (RR) of 1.0150 (95% CI: 1.0098–1.0202) for respiratory mortality in the total population. For individuals aged ≥55 years, unmarried individuals, those engaged in indoor occupations, and those with low educational attainment, each 10 μg/m3 increase in O3 at lag 07 days was linked to RR values of 1.0301 (95% CI: 1.0187–1.0417), 1.0437 (95% CI: 1.0266–1.0610), 1.0317 (95% CI: 1.0186–1.0450), and 1.0346 (95% CI: 1.0222–1.0471), respectively. Importantly, we discovered a synergistic effect of PM2.5 and O3, resulting in an SI of 2.372 on the occurrence of respiratory mortality. Conclusions: This study confirmed a positive association between O3 exposure and respiratory mortality. Furthermore, it highlighted the interaction between O3 and PM2.5 in exacerbating respiratory deaths

High-Discrimination Circular Polarization Detection Based on Dielectric-Metal-Hybrid Chiral Metamirror Integrated Quantum Well Infrared Photodetectors

Circular polarization detection enables a wide range of applications. With the miniaturization of optoelectronic systems, integrated circular polarization detectors with native sensitivity to the spin state of light have become highly sought after. The key issues with this type of device are its low circular polarization extinction ratios (CPERs) and reduced responsivities. Metallic two-dimensional chiral metamaterials have been integrated with detection materials for filterless circular polarization detection. However, the CPERs of such devices are typically below five, and the light absorption in the detection materials is hardly enhanced and is even sometimes reduced. Here, we propose to sandwich multiple quantum wells between a dielectric two-dimensional chiral metamaterial and a metal grating to obtain both a high CPER and a photoresponse enhancement. The dielectric-metal-hybrid chiral metamirror integrated quantum well infrared photodetector (QWIP) exhibits a CPER as high as 100 in the long wave infrared range, exceeding all reported CPERs for integrated circular polarization detectors. The absorption efficiency of this device reaches 54%, which is 17 times higher than that of a standard 45° edge facet coupled device. The circular polarization discrimination is attributed to the interference between the principle-polarization radiation and the cross-polarization radiation of the chiral structure during multiple reflections and the structure-material double polarization selection. The enhanced absorption efficiency is due to the excitation of a surface plasmon polariton wave. The dielectric-metal-hybrid chiral mirror structure is compatible with QWIP focal plane arrays

Synthesis, Biological Evaluation, and Autophagy Mechanism of 12<i>N</i>‑Substituted Sophoridinamines as Novel Anticancer Agents

A series of 12<i>N</i>-substituted sophoridinamine derivatives were synthesized and evaluated for their cytotoxic activities in human HepG2 hepatoma cells. Structure–activity relationship revealed that introduction of a suitable arylidene or arylethyl at the <i>N</i>′-end could greatly enhance antiproliferation potency. Among them, compound <b>6b</b> possessing a <i>N</i>′-trimethoxyphenyl methylene exhibited potent antiproliferation effect against three human tumor cell lines including HepG2, leukemia (K562), and breast cancer (HMLE), with IC₅₀ between 0.55 and 1.7 μM. The underlying mechanism of <b>6b</b> against tumor cells is to block autophagic flux, mainly through neutralizing lysosomal acidity. Our results indicated that compound <b>6b</b> is a potent lysosomal deacidification agent and is accordingly able to block autophagic flux and inhibit tumor cell growth

Discovery and Development of 8‑Substituted Cycloberberine Derivatives as Novel Antibacterial Agents against MRSA

8-Acetoxycycloberberine (<b>2</b>) with a unique skeleton was first identified to display a potent activity profile against Gram-positive bacteria, especially methicillin-resistant <i>S. aureus</i> (MRSA) with minimum inhibitory concentration (MIC) values of 1–8 μg/mL, suggesting a possible novel mechanism of action against bacteria. Taking <b>2</b> as the lead, 23 new 8-substituted cycloberberine (CBBR) derivatives including ether, amine, and amide were synthesized and evaluated for their antibacterial effect. The structure–activity relationship revealed that the introduction of a suitable substituent at the 8-position could greatly enhance the potency against MRSA. Among them, compounds <b>5d</b> and <b>9e</b> demonstrated equally effective anti-MRSA potency as lead <b>2</b>, with an advantage of having a more stable pharmacokinetics feature. A preliminary mechanism study indicated that compound <b>9e</b> acted upon bacteria partly through catalyzing the cleavage of bacterial DNA. Therefore, we consider that 8-substituted CBBR derivatives constitute a promising class of antibacterial agents in the treatment of MRSA infections

Table_1_Association of NAD+ levels with metabolic disease in a community-based study.docx

BackgroundNicotinamide adenine dinucleotide (NAD+) is a coenzyme and plays a crucial role in several metabolic processes. This study explored the association of nicotinamide adenine dinucleotide (NAD+) levels with metabolic disease (MD) in adults.MethodsIn this cross-sectional study, all data were collected from the Jidong community. MD was defined as the presence of one or more of the following disease components: hypertension, dyslipidemia, diabetes, hyperuricemia, obesity, and non-alcoholic fatty liver disease (NAFLD). The MD components were categorized into three groups: those with one component, those with two components, and those with three to six components. The whole blood NAD+ level was measured using a cycling assay and LC-MS/MS analysis. The participants were divided into four groups based on their NAD+ level quartiles. Multivariable logistic regression was used to evaluate the association of the whole blood NAD+ levels with MD.ResultsOf the 1,394 eligible participants, the average age was 43.2 years, and 74.3% had MD. In the top quartile of NAD+, the prevalence of MD and each of its components (hypertension, hyperlipidemia, diabetes, hyperuricemia, obesity, and NAFLD) were 87.9% 35.2%, 62.3%, 8.7%, 36.9%, 21.0%, and 60.5%, respectively. As compared with the lowest NAD+ quartile (≤29.4 μmol/L), the adjusted odds ratios and 95% confidence interval of the highest quartile were 3.01 (1.87-4.87) for MD, 2.48 (1.44-4.29) for 1 MD component, 2.74 (1.45-5.17) for 2 MD components, and 4.30 (2.32-7.98) for 3-6 MD components. The risk of MD began to increase at NAD+ levels of 31.0 μmol/L, as revealed by the gradient associations of NAD+ levels with MD. There was no significant interaction between age, sex, drinking, smoking, and NAD+ for MD (p for interaction ≥0.10).ConclusionsIncreased NAD+ was significantly associated with MD, as well as its individual components. Our findings provide new evidence for the relationship between blood NAD+ levels and MD.</p

Are medical record front page data suitable for risk adjustment in hospital performance measurement? Development and validation of a risk model of in-hospital mortality after acute myocardial infarction

Objectives To develop a model of in-hospital mortality using medical record front page (MRFP) data and assess its validity in case-mix standardisation by comparison with a model developed using the complete medical record data.Design A nationally representative retrospective study.Setting Representative hospitals in China, covering 161 hospitals in modelling cohort and 156 hospitals in validation cohort.Participants Representative patients admitted for acute myocardial infarction. 8370 patients in modelling cohort and 9704 patients in validation cohort.Primary outcome measures In-hospital mortality, which was defined explicitly as death that occurred during hospitalisation, and the hospital-level risk standardised mortality rate (RSMR).Results A total of 14 variables were included in the model predicting in-hospital mortality based on MRFP data, with the area under receiver operating characteristic curve of 0.78 among modelling cohort and 0.79 among validation cohort. The median of absolute difference between the hospital RSMR predicted by hierarchical generalised linear models established based on MRFP data and complete medical record data, which was built as ‘reference model’, was 0.08% (10th and 90th percentiles: −1.8% and 1.6%). In the regression model comparing the RSMR between two models, the slope and intercept of the regression equation is 0.90 and 0.007 in modelling cohort, while 0.85 and 0.010 in validation cohort, which indicated that the evaluation capability from two models were very similar.Conclusions The models based on MRFP data showed good discrimination and calibration capability, as well as similar risk prediction effect in comparison with the model based on complete medical record data, which proved that MRFP data could be suitable for risk adjustment in hospital performance measurement