Prevalence of nonalcoholic fatty liver disease and liver cirrhosis in Chinese adults with type 2 diabetes mellitus.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and liver cirrhosis are significant clinical concerns, especially among individuals with type 2 diabetes mellitus (T2DM). However, in China, there is a paucity of reliable evidence detailing the characteristics of NAFLD and liver cirrhosis in T2DM. Furthermore, the relationship between blood glucose levels and NAFLD prevalence remains unclear. METHODS: Data from the Shanghai Suburban Adult Cohort and Biobank were analyzed, including 6621 participants with T2DM. NAFLD was diagnosed by ultrasonography and liver cirrhosis was performed according to the health information systems. Logistic regression and restricted cubic spline analysis were used to explore the potential risk factors for NAFLD and liver cirrhosis. RESULTS: The prevalence of NAFLD was 59.36%, and liver cirrhosis was 1.43% among T2DM patients. In these patients, factors like age, being female, marital status, and obesity significantly increased the risk of NAFLD. Specifically, obesity had a strong positive association with NAFLD (odds ratio [OR] = 4.70, 95% confidence interval [CI]: 4.13-5.34). The higher glycated hemoglobin (HbA1c) quartile was associated with a heightened NAFLD risk compared to the lowest quartile (all p < .001). The HbA1c-NAFLD relationship displayed a linear that mimicked an inverted L-shaped pattern. A significant positive association existed between HbA1c levels and NAFLD for HbA1c <8.00% (OR = 1.59, 95% CI: 1.44-1.75), but this was not observed for HbA1c >8.00% (OR = 1.03, 95% CI: 0.92-1.15). CONCLUSION: Systematic screening for NAFLD is essential in T2DM patients, especially with poor glucose control and obesity in female.

Comparative analysis of tropomyosin allergenicity in three different species of molluscs: insights into the role of amino acid composition in IgE epitopes.

Limited research has been conducted on the differences in allergenicity among Alectryonella plicatula tropomyosin (ATM), Haliotis discus hannai tropomyosin (HTM), and Mimachlamys nobilis tropomyosin (MTM) in molluscs. Our study aimed to comprehensively analyze and compare their immunoreactivity, sensitization, and allergenicity while simultaneously elucidating the underlying molecular mechanisms involved. We assessed the immune binding activity of TM utilizing 86 sera from allergic patients and evaluated sensitization and allergenicity through two different types of mouse models. The dot-blot and basophil activation test assays revealed strong immunoreactivity for HTM, ATM, and MTM, with HTM exhibiting significantly lower levels compared to ATM. In the BALB/c mouse sensitization model, all TM groups stimulated the production of specific antibodies, elicited IgE-mediated immediate hypersensitivity responses, and caused an imbalance in the IL-4/IFN-γ ratio. Similarly, in the BALB/c mouse model of food allergy, all TM variants induced IgE-mediated type I hypersensitivity responses, leading to the development of food allergies characterized by clinical symptoms and an imbalance in the IL-4/IFN-γ ratio. The stimulation ability of sensitization and the severity of food allergies consistently ranked as ATM > MTM > HTM. Through an in-depth analysis of non-polar amino acid frequency and polar hydrogen bonds, HTM exhibited higher frequencies of non-polar amino acids in its amino acid sequence and IgE epitopes, in comparison with ATM and MTM. Furthermore, HTM demonstrated a lower number of polar hydrogen bonds in IgE epitopes. Overall, HTM exhibited the lowest allergenic potential in both allergic patients and mouse models, likely due to its lower polarity in the amino acid sequence and IgE epitopes.

Machine learning-based plasma metabolomic profiles for predicting long-term complications of cirrhosis.

BACKGROUND AND AIMS: The liver cirrhosis complications occur after long asymptomatic stages of progressive fibrosis and are generally diagnosed late. We aimed to develop a plasma metabolomic-based score tool to predict these events. APPROACH AND RESULTS: We enrolled 64,005 UK biobank participants with metabolomic profile. Participants were randomly divided into the training (n=43,734) and validation cohorts (n=20,271). Liver cirrhosis complications were defined as hospitalization for liver cirrhosis or presentation with hepatocellular carcinoma. Interpretable machine learning framework was applied to learn the metabolomic states extracted from 168 circulating metabolites in the training cohort. An integrated nomogram was developed and compared to conventional and genetic risk scores. We created three groups: low-risk, middle-risk, and high-risk through selected cut-offs of the nomogram. The predictive performance was validated through area under time-dependent receiver operating characteristic curve (time-dependent AUC), calibration curves, and decision curve analysis. The metabolomic state model could accurately predict 10-year risk of liver cirrhosis complications in the training cohort (time-dependent AUC 0.84 [95% CI 0.82-0.86]), and outperform the fibrosis-4 index (time-dependent AUC difference 0.06 [0.03-0.10]) and polygenic risk score (0.25 [0.21-0.29]). The nomogram, integrating metabolomic state, aspartate aminotransferase, platelet count, waist/hip ratio, and smoking status, showed a time-dependent AUC of 0.930 at 3 years, 0.889 at 5 years, and 0.861 at 10 years in the validation cohort, respectively. The hazard ratio in the high-risk group was 43.58 (95% CI 27.08-70.12) compared with the low-risk group. CONCLUSIONS: We developed a metabolomic state-integrated nomogram, which enables risk stratification and personalized administration of liver-related events.

Spinocerebellar Ataxia Type 3 Pathophysiology-Implications for Translational Research and Clinical Studies.

The spinocerebellar ataxias (SCA) comprise a group of inherited neurodegenerative diseases. Machado-Joseph Disease (MJD) or spinocerebellar ataxia 3 (SCA3) is the most common autosomal dominant form, caused by the expansion of CAG repeats within the ataxin-3 (ATXN3) gene. This mutation results in the expression of an abnormal protein containing long polyglutamine (polyQ) stretches that confers a toxic gain of function and leads to misfolding and aggregation of ATXN3 in neurons. As a result of the neurodegenerative process, SCA3 patients are severely disabled and die prematurely. Several screening approaches, e.g., druggable genome-wide and drug library screenings have been performed, focussing on the reduction in stably overexpressed ATXN3(polyQ) protein and improvement in the resultant toxicity. Transgenic overexpression models of toxic ATXN3, however, missed potential modulators of endogenous ATXN3 regulation. In another approach to identify modifiers of endogenous ATXN3 expression using a CRISPR/Cas9-modified SK-N-SH wild-type cell line with a GFP-T2A-luciferase (LUC) cassette under the control of the endogenous ATXN3 promotor, four statins were identified as potential activators of expression. We here provide an overview of the high throughput screening approaches yet performed to find compounds or genomic modifiers of ATXN3(polyQ) toxicity in different SCA3 model organisms and cell lines to ameliorate and halt SCA3 progression in patients. Furthermore, the putative role of cholesterol in neurodegenerative diseases (NDDs) in general and SCA3 in particular is discussed.

Long-term exposure to fine particulate matter constituents in relation to chronic kidney disease: evidence from a large population-based study in China.

The effects of long-term exposure to fine particulate matter (PM2.5) constituents on chronic kidney disease (CKD) are not fully known. This study sought to examine the association between long-term exposure to major PM2.5 constituents and CKD and look for potential constituents contributing substantially to CKD. This study included 81,137 adults from the 2018 to 2019 baseline survey of China Multi-Ethnic Cohort. CKD was defined by the estimated glomerular filtration rate. Exposure concentration data of 7 major PM2.5 constituents were assessed by satellite remote sensing. Logistic regression models were used to estimate the effect of each PM2.5 constituent exposure on CKD. The weighted quantile sum regression was used to estimate the effect of mixed exposure to all constituents. PM2.5 constituents had positive correlations with CKD (per standard deviation increase), with ORs (95% CIs) of 1.20 (1.02-1.41) for black carbon, 1.27 (1.07-1.51) for ammonium, 1.29 (1.08-1.55) for nitrate, 1.20 (1.01-1.43) for organic matter, 1.25 (1.06-1.46) for sulfate, 1.30 (1.11-1.54) for soil particles, and 1.63 (1.39-1.91) for sea salt. Mixed exposure to all constituents was positively associated with CKD (1.68, 1.32-2.11). Sea salt was the constituent with the largest weight (0.36), which suggested its importance in the PM2.5-CKD association, followed by nitrate (0.32), organic matter (0.18), soil particles (0.10), ammonium (0.03), BC (0.01). Sulfate had the least weight (< 0.01). Long-term exposure to PM2.5 sea salt and nitrate may contribute more than other constituents in increasing CKD risk, providing new evidence and insights for PM2.5-CKD mechanism research and air pollution control strategy.

Establishment of a mild cognitive impairment risk model in middle-aged and older adults: a longitudinal study.

BACKGROUND: Early identification individuals at high risk of mild cognitive impairment (MCI) is essential for prevention and intervention strategies of dementia, such as Alzheimer's disease. MCI prediction considering the interdependence of predictors in longitudinal data needs to be further explored. We aimed to employ machine learning (ML) to develop and verify a prediction model of MCI. METHODS: In a longitudinal population-based cohort of China Health and Retirement Longitudinal Study (CHARLS), 8390 non-MCI participants were enrolled. The diagnosis of MCI was based on the aging-associated cognitive decline (AACD), and 13 factors (gender, education, marital status, residence, diabetes, hypertension, depression, hearing impairment, social isolation, physical activity, drinking status, body mass index and expenditure) were finally selected as predictors. We implemented a long short-term memory (LSTM) to predict the MCI risks in middle-aged and older adults within 7 years. The Receiver Operating Characteristic curve (ROC) and calibration curve were used to evaluate the performance of the model. RESULTS: Through 7 years of follow-up, 1925 participants developed MCI. The model for all incident MCI achieved an AUC of 0.774, and its deployment to the participants followed 2, 4, and 7 years achieved results of 0.739, 0.747, and 0.750, respectively. The model was well-calibrated with predicted probabilities plotted against the observed proportions of cognitive impairment. Education level, gender, marital status, and depression contributed most to the prediction of MCI. CONCLUSIONS: This model could be widely applied to medical institutions, even in the community, to identify middle-aged and older adults at high risk of MCI.

Low energy consumption layout of exhibition buildings in Yangtze River Delta region.

The issue of high energy consumption in exhibition buildings has long been a focal point in the field of architectural design. However, current energy consumption assessments for exhibition buildings mainly focus on post-construction evaluations, lacking corresponding guidance during the initial design phase. To address this issue, this study selected 48 well-known exhibition buildings both domestically and internationally as research subjects. Utilizing scatter plot curve fitting, it was discovered that there exists a nonlinear quadratic relationship between the building area of the first floor and the courtyard area. Based on this relationship, four typical layouts were established to match the climatic characteristics of Hangzhou, a representative region in the Yangtze River Delta of China. Taking into account regional architectural features, the study specifically examined the impact of different orientations and window-to-wall ratios on energy consumption levels. The influence of these factors on energy consumption was analyzed using the DesignBuilder software. The results revealed that there exists an optimal window-to-wall ratio for exhibition buildings, with parallel, L-shaped enclosed south-facing courtyards, and U-shaped enclosed east-facing courtyards showing greater energy efficiency. This research provides guidance for designing exhibition buildings that are energy-efficient and foster a harmonious indoor-outdoor relationship.

Intervention Efficacy of Slightly Processed Allergen/Meat in Oral Immunotherapy for Seafood Allergy: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis in Mouse Models and Clinical Patients.

Background: Seafood allergy is a significant global health concern that greatly impacts a patient's quality of life. The intervention efficacy of oral immunotherapy (OIT), an emerging intervention strategy, for seafood allergy remains controversial. This study aimed to perform a systematic review and meta-analysis to evaluate the efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. Methods: A comprehensive literature search was performed in four mainstream databases and the EBSCOhost database to identify all relevant case-control and cohort studies. The aim was to elucidate the intervention efficacy, encompassing various processing methods and assessing the efficacy of multiple major allergens in OIT. Results: The meta-analysis included five case-control studies on crustacean allergens in mouse models and 11 cohort studies on meat from fish and crustacea in clinical patients for final quantitative assessments. In mouse models, crustacean allergen substantially decreased the anaphylactic score after OIT treatment (mean difference (MD) = -1.30, p < 0.01). Subgroup analyses with low-level heterogeneities provided more reliable results for crab species (MD = -0.63, p < 0.01, I2 = 0), arginine kinase allergen (MD = -0.83, p < 0.01, I2 = 0), and Maillard reaction processing method (MD = -0.65, p < 0.01, I2 = 29%), respectively. In clinical patients, the main meta-analysis showed that the slightly processed meat significantly increased the incidence rate of oral tolerance (OT, incidence rate ratio (IRR) = 2.90, p < 0.01). Subgroup analyses for fish meat (IRR = 2.79, p < 0.01) and a simple cooking treatment (IRR = 2.36, p = 0.01) also demonstrated a substantial increase in the incidence rate of OT. Sensitivity and meta-regression analyses successfully identified specific studies contributing to heterogeneity in mouse models and clinical patients, although these studies did not impact the overall significant pooled effects. Conclusions: This meta-analysis provides preliminary evidence for the high intervention efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. The Maillard reaction and cooking processing methods may emerge as potentially effective approaches to treating allergen/meat in OIT for clinical patients, offering a promising and specific treatment strategy for seafood allergy. However, these findings should be interpreted cautiously, and further supporting evidence is necessary.

A systematic two-sample and bidirectional MR process highlights a unidirectional genetic causal effect of allergic diseases on COVID-19 infection/severity.

BACKGROUND: Allergic diseases (ADs) such as asthma are presumed risk factors for COVID-19 infection. However, recent observational studies suggest that the assumed correlation contradicts each other. We therefore systematically investigated the genetic causal correlations between various ADs and COVID-19 infection/severity. METHODS: We performed a two-sample, bidirectional Mendelian randomization (MR) study for five types of ADs and the latest round of COVID-19 GWAS meta-analysis datasets (critically ill, hospitalized, and infection cases). We also further validated the significant causal correlations and elucidated the potential underlying molecular mechanisms. RESULTS: With the most suitable MR method, asthma consistently demonstrated causal protective effects on critically ill and hospitalized COVID-19 cases (OR < 0.93, p < 2.01 × 10-2), which were further confirmed by another validated GWAS dataset (OR < 0.92, p < 4.22 × 10-3). In addition, our MR analyses also observed significant causal correlations of food allergies such as shrimp allergy with the risk of COVID-19 infection/severity. However, we did not find any significant causal effect of COVID-19 phenotypes on the risk of ADs. Regarding the underlying molecular mechanisms, not only multiple immune-related cells such as CD4+ T, CD8+ T and the ratio of CD4+/CD8+ T cells showed significant causal effects on COVID-19 phenotypes and various ADs, the hematology traits including monocytes were also significantly correlated with them. Conversely, various ADs such as asthma and shrimp allergy may be causally correlated with COVID-19 infection/severity by affecting multiple hematological traits and immune-related cells. CONCLUSIONS: Our systematic and bidirectional MR analyses suggest a unidirectional causal effect of various ADs, particularly of asthma on COVID-19 infection/severity, but the reverse is not true. The potential underlying molecular mechanisms of the causal effects call for more attention to clinical monitoring of hematological cells/traits and may be beneficial in developing effective therapeutic strategies for allergic patients following infection with COVID-19.

Learning Quadrupedal High-Speed Running on Uneven Terrain.

Reinforcement learning (RL)-based controllers have been applied to the high-speed movement of quadruped robots on uneven terrains. The external disturbances increase as the robot moves faster on such terrains, affecting the stability of the robot. Many existing RL-based methods adopt higher control frequencies to respond quickly to the disturbance, which requires a significant computational cost. We propose a control framework that consists of an RL-based control policy updating at a low frequency and a model-based joint controller updating at a high frequency. Unlike previous methods, our policy outputs the control law for each joint, executed by the corresponding high-frequency joint controller to reduce the impact of external disturbances on the robot. We evaluated our method on various simulated terrains with height differences of up to 6 cm. We achieved a running motion of 1.8 m/s in the simulation using the Unitree A1 quadruped. The RL-based control policy updates at 50 Hz with a latency of 20 ms, while the model-based joint controller runs at 1000 Hz. The experimental results show that the proposed framework can overcome the latency caused by low-frequency updates, making it applicable for real-robot deployment.

Particulate polycyclic aromatic hydrocarbons in rural households burning solid fuels in Xuanwei County, Southwest China: occurrence, size distribution, and health risks.

The study is about the size distribution and health risks of polycyclic aromatic hydrocarbons (PAHs) in indoor environment of Xuanwei, Southwest China particle samples were collected by Anderson 8-stage impactor which was used to gather particle samples to nine size ranges. Size-segregated samples were collected in indoor from a rural village in Xuanwei during the non-heating and heating seasons. The results showed that the total concentrations of the indoor particulate matter (PM) were 757 ± 60 and 990 ± 78 µg/m3 in non-heating and heating seasons, respectively. The total concentration of indoor PAHs reached to 8.42 ± 0.53 µg/m3 in the heating season, which was considerably greater than the concentration in the non-heating season (2.85 ± 1.72 µg/m3). The size distribution of PAHs showed that PAHs were mainly enriched in PMs with the diameter <1.1 µm. The diagnostic ratios (DR) and principal component analysis (PCA) showed that coal and wood for residential heating and cooking were the main sources of indoor PAHs. The results of the health risk showed that the total deposition concentration (DC) in the alveolar region (AR) was 0.25 and 0.68 µg/m3 in the non-heating and heating seasons respectively. Throughout the entire sampling periods, the lifetime cancer risk (R) based on DC of children and adults varied between 3.53 ×10-5 to 1.79 ×10-4. During the heating season, the potential cancer risk of PAHs in adults was significant, exceeding 10-4, with a rate of 96%.

Serological characteristics and clinical implications of IgG subclasses in visceral leishmaniasis.

OBJECTIVES: Visceral leishmaniasis (VL) represents the most severe form of Leishmaniasis infection, often resulting in fatality without timely treatment. Previous studies have found that immunosuppression increases the risk of VL disease progression and mortality, and the total immunoglobulin G (IgG) levels in peripheral blood vary before and after treatment. However, the distinct levels and roles of IgG subclasses in VL have not been documented yet. This study aims to elucidate the characteristics and clinical significance of IgG subclasses in VL. METHODS: A total of 43 cases newly-diagnosed with VL were enrolled in the cohort. We measured the levels of IgG subclasses before and after standard treatment and conducted assessments of bone marrow features. In addition, we analysed other haematological indices and examined the variations in IgG subclasses, as well as their correlation with clinical and laboratory factors. RESULTS: The levels of total IgG, IgG1, and the ratios of both IgG1/IgG and IgG1/IgG2 decreased significantly after treatment, whereas the ratios of IgG2/ IgG showed an obvious increase. The VL patients without hyperglobulinemia displayed significant lower IgG1/IgG2 ratios, but higher IgG2/IgG ratios compared with those with hyperglobulinemia. In addition, VL patients with positive bone marrow amastigotes had significant higher IgG1/IgG and IgG1/IgG2 ratios, but lower IgG2/IgG ratios. IgG subclasses were correlated with abnormal blood test results, particularly immunological elements including IgM and Complement 4 (C4). CONCLUSIONS: IgG1 and IgG2 exhibited contrasting changes after treatment in VL patients. The features of bone marrow and laboratory tests indicated that IgG1 and IgG2 serve different roles in the progression of VL. The ratios of IgG subclasses may be more precise indicators to evaluate immune reaction in VL than traditional total IgG.

Global epidemiology of early-onset liver cancer attributable to specific aetiologies and risk factors from 2010 to 2019.

Background: Considering its emergence as a public health concern worldwide, with potential spatial-temporal heterogeneities, we aimed to determine the global burden of early-onset liver cancer attributable to aetiologies and concomitant risk factors. Methods: We used data from the Global Burden of Diseases Study 2019 to determine age-standardised disability-adjusted life-year (DALY) rates for early-onset liver cancer by aetiologies and the population DALYs attributable to concomitant risk factors between 2010 and 2019. We also calculated estimated annual percentage changes (EAPCs) to measure temporal trends. Results: There were 2.9 million DALYs related to early-onset liver cancer globally in 2019. East Asia contributed over half of DALYs, which increased annually by 1.23% (95% confidence interval (CI) = 0.71, 1.76) between 2010 and 2019. Non-alcoholic steatohepatitis was the only growing aetiology. The proportion of DALYs attributed to metabolic risks increased by 22.50% (95% CI = 14.33, 38.13), while behavioral risks remained stable. Obesity surpassed smoking as the most prevalent nondeterministic aetiological risk factor from 2010 to 2019, while the population DALY attributable to hepatitis B combined with obesity increased by 29.93% (95% CI = 8.49, 60.77) in the same period, making it the principal joint contributor. Conclusions: Early-onset liver cancer poses considerable disability and continues to increase in many regions, especially in East Asia. Metabolic risk factors, particularly when hepatitis B and obesity coexist, are the fastest-growing contributors to this type of cancer. More targeted interventions are imperative to curb the growing burden of early-onset liver cancer due to metabolic risks.

Long-term exposure to ambient PM2.5 and its constituents is associated with MAFLD.

Background & Aims: Existing evidence suggests that long-term exposure to ambient fine particulate pollution (PM2.5) may increase metabolic dysfunction-associated fatty liver disease (MAFLD) risk. However, there is still limited evidence on the association of PM2.5 constituents with MAFLD. Therefore, this study explores the associations between the five main chemical constituents of PM2.5 and MAFLD to provide more explicit information on the liver exposome. Methods: A total of 76,727 participants derived from the China Multi-Ethnic Cohort, a large-scale epidemic survey in southwest China, were included in this study. Multiple linear regression models were used to estimate the pollutant-specific association with MAFLD. Weighted quantile sum regression was used to evaluate the joint effect of the pollutant-mixture on MAFLD and identify which constituents contribute most to it. Results: Three-year exposure to PM2.5 constituents was associated with a higher MAFLD risk and more severe liver fibrosis. Odds ratios for MAFLD were 1.480, 1.426, 1.294, 1.561, 1.618, and 1.368 per standard deviation increase in PM2.5, black carbon, organic matter, ammonium, sulfate, and nitrate, respectively. Joint exposure to the five major chemical constituents was also positively associated with MAFLD (odds ratio 1.490, 95% CI 1.360-1.632). Nitrate contributed most to the joint effect of the pollutant-mixture. Further stratified analyses indicate that males, current smokers, and individuals with a high-fat diet might be more susceptible to ambient PM2.5 exposure than others. Conclusions: Long-term exposure to PM2.5 and its five major chemical constituents may increase the risk of MAFLD. Nitrate might contribute most to MAFLD, which may provide new clues for liver health. Males, current smokers, and participants with high-fat diets were more susceptible to these associations. Impact and implications: This large-scale epidemiologic study explored the associations between constituents of fine particulate pollution (PM2.5) and metabolic dysfunction-associated fatty liver disease (MAFLD), and further revealed which constituents play a more important role in increasing the risk of MAFLD. In contrast to previous studies that examined the effects of PM2.5 as a whole substance, this study carefully explored the health effects of the individual constituents of PM2.5. These findings could (1) help researchers to identify the specific particles responsible for hepatotoxicity, and (2) indicate possible directions for policymakers to efficiently control ambient air pollution, such as targeting the sources of nitrate pollution.

Increased diversity of Malassezia species on the skin of Parkinson's disease patients.

Background: Parkinson's disease (PD) is characterized by motor disorders and the composition of Lewy bodies (LBs) in the substantia nigra. Due to the lack of a definitive biomarker, the current treatments do not modify the progression of PD. Recently, researchers revealed lipid dysregulation and some potential volatile biomarkers of PD related to a unique odor from PD patients by metabolomics of sebum, which is supposed to cause a potential change for skin microflora. In this study, we identified the 4 Malassezia species in PD patients and compared them with healthy controls. Methods: We collected 95 sebum samples (47 PDs and 48 Controls) by cotton swabs and extracted the DNA. The identification of Malassezia species was performed by Nested PCR. Specific primers for each species were used to amplify corresponding yeasts in each sample. Results: M. restricta and M. globosa are the most common species for both groups. The prevalence of M. slooffiae and M. sympodialis were significantly higher in the PD group compared with controls (63.8% vs. 29.1 and 74.5% vs. 54.2% respectively), the binary logistic regression model further indicated that M. slooffiae (OR = 9.358, p < 0.001) was associated with PD. Moreover, the diversity of Malassezia species was significantly greater (3.5 vs. 2.9 species per individual, p = 0.002) in the PD group. Conclusion: Based on our results, we preliminarily observed a change in Malassezia species incidence and diversity on the skin of PD patients, which could be associated with lipid dysregulation; meanwhile, it might also be a noninvasive biomarker for PD.

Visible-light-induced [3+2] cycloadditions of donor/donor diazo intermediates with alkenes to achieve (spiro)-pyrazolines and pyrazoles.

To date, [3 + 2] cycloadditions of diazo esters with alkynes or alkenes have been a robust tool to generate pyrazoles and pyrazolines. However, methods capable of generating donor/donor diazo species from readily available N-tosylhydrazones to furnish [3 + 2] cycloadditions, remain elusive. Herein, we describe the first visible-light-induced [3 + 2] cycloadditions of donor/donor diazo precursors with alkenes to afford pyrazoles and novel (spiro)pyrazolines bearing a quaternary center. This protocol shows a tolerable substrate scope covering versatile carbonyl compounds and alkenes. Late-stage functionalization of bioactive molecules, one-pot approach, and gram-scale synthesis have also been introduced successfully to prove the practicability. At last, mechanistic experiments and DFT studies suggested the formation of non-covalent interactions enabling the activation of N-tosylhydrazones and the formation of the donor/donor diazo intermediates.

Associations of healthy lifestyle and three latent socioeconomic status patterns with physical multimorbidity among middle-aged and older adults in China.

BACKGROUND: Multimorbidity is an emerging global public health concern. However, complex associations of healthy lifestyle and socioeconomic status (SES) with multimorbidity have not been identified. METHODS: This population-based prospective cohort study used data from four waves of the China Health and Retirement Longitudinal Study (CHARLS) to explore these relationships. Physical multimorbidity was measured using 12 non-communicable diseases. Latent class analysis (LCA) was conducted to determine the optimal SES patterns based on annual per-capita household expenditure, occupation, education level, and health insurance. The healthy lifestyle score (0-5) was constructed comprising information on smoking, drinking, physical activity, sleep, and body shape. RESULTS: Of 17,708 participants in the CHARLS, 7776 were eligible for inclusion in our analysis (13.3% with high SES, 26.1% with medium SES, and 60.6% with low SES). Compared with high SES participants, those with low SES had higher risks of incident physical multimorbidity (OR 1.22, 95% CI 1.05, 1.42), which was competitively mediated by lifestyle (mediation proportion, -10.17%, 95% CI -19.12%, -1.23%). Significant interactions were observed between lifestyle factors and SES in patients with incident diabetes. Participants with low SES and no or one healthy lifestyle factor had a higher risk of incident physical multimorbidity than those with high SES and four to five healthy lifestyle factors (OR 2.19, 95% CI 1.57, 3.04). CONCLUSION: Healthy lifestyles competitively mediate a fractional proportion of socioeconomic inequity in incident physical multimorbidity. Furthermore, healthy lifestyles were associated with lower multimorbidity risk in the SES subgroups, supporting the important role of lifestyle in reducing physical multimorbidity burden.

Active Control and Sensing Application of Ultra-Narrowband Circular Dichroism in Multilayer Chiral Nanorod Arrays.

Narrowband circular dichroism (CD) has attracted wide attention for its high sensitivity in detecting chiral molecules and catalysis. However, designing a chiral metasurface with excellent sensing performance that can be dynamically tuned still poses challenges. This paper introduces lithium niobate, an electrically tunable material, and a distributed Bragg reflector into chiral nanorod structures to form multilayer chiral nanorod arrays (MCNAs). Simulation results show that MCNAs can generate four strong ultra-narrowband (UNB) CD signals in the visible light spectrum. The UNB CD signal intensity was up to 0.86, and the minimum full width at half-maximum (FWHM) was up to 0.21 nm. The surface electric field and current distribution of MCNAs indicate that the four UNB CD signals mainly originate from the x and y direction Tamm resonances in the chiral nanorod layer. The refractive index of lithium niobate can be tuned by changing the electric field, allowing the active tuning of UNB CD signals. In addition, the sensing performance of MCNAs in the SARS-CoV-2 solution was analyzed, and the figure of merit (FOM) can reach an astonishing 2092. These findings not only assist with the design of UNB chiral devices but also offer new possibilities for the environmental monitoring and ultrasensitive detection of chiral molecules.