Recent-year variations in O3 pollution with high-temperature suppression over central China.

By analyzing environmental and meteorological monitoring data over recent years of 2015-2022, the Twain-Hu Basin (THB) in central China was identified as a regional O3 pollution center over China with the highest increasing trend at 1.10 %⸱yr-1 in interannual variations of O3 concentrations with deteriorating O3 pollution over recent years. We explored the spatiotemporal variations in O3 pollution in the THB with ozone suppression (OS) under high air temperature over metropolitan, small urban, and mountainous areas. The bipolarized interannual trends in interannual O3 variations in urban and mountainous areas over central China were characterized with the increasing and decreasing 90th percentiles of the daily maximum 8-h (MDA8-90) O3 concentrations respectively in polluted urban areas and clean mountainous areas over recent eight years. The changes of the near-surface O3 concentrations with air temperature exhibited the inflection points of OS from increasing to decreasing O3 at air temperature of 30.5 °C in mountainous areas, 32.5 °C in small urban areas, and 34.5 °C in metropolitan areas, and the intensity of OS was estimated in the ranking with mountainous areas (-2.30 µg⸱m-3⸱°C-1) > small urban areas (-1.96 µg⸱m-3⸱°C-1) > metropolitan areas (-1.54 µg⸱m-3⸱°C-1), indicating that the OS was more significant over the lower-O3 mountainous areas. This study has implications for understanding O3 pollution variations with the meteorological drivers.

Mechanistic Insights into the Inhibition of a Common CTLA-4 Gene Mutation in the Cytoplasmic Domain.

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a pivotal immune checkpoint receptor, playing a crucial role in modulating T-cell activation. In this study, we delved into the underlying mechanism by which a common mutation, G199R, in the cytoplasmic domain of CTLA-4 impacts its inhibitory function. Utilizing nuclear magnetic resonance (NMR) spectroscopy and biochemical techniques, we mapped the conformational changes induced by this mutation and investigated its role in CTLA-4 activity. Our findings reveal that this mutation leads to a distinct conformational alteration, enhancing protein-membrane interactions. Moreover, functional assays demonstrated an improved capacity of the G199R mutant to downregulate T-cell activation, underscoring its potential role in immune-related disorders. These results not only enhance our understanding of CTLA-4 regulatory mechanisms but also provide insights for targeted therapeutic strategies addressing immune dysregulation linked to CTLA-4 mutations.

Designed Synthesis of Fe/Zr Bimetallic Organic Framework to Enhance the Selective Conversion of H2S to Sulfur.

The development of stable and effective catalysts to convert toxic H2S into high value-added sulfur is essential for production safety and environmental protection. However, the inherent defects of traditional iron- and zirconium-based catalysts, such as poor activity, high oxygen consumption, and low sulfur selectivity, limit their further developments and applications. Herein, the Fe-Zr bimetallic organic framework FeUIO-66(x) with different cubic morphologies was synthesized via a facile solvothermal method. The results indicate that the introduction of Fe not only increases the specific surface area and weak L-sites of the catalyst without changing its crystal structure, which provides enough reaction space and more active sites for the adsorption and activation of H2S, but also reduces the activation energy of the reaction, significantly promoting the selective oxidation of H2S. As a result, the as-obtained FeUIO-66(1) catalyst exhibits the highest desulfurization activity and superior durability and water resistance stability, and its H2S conversion and sulfur selectivity within 50 h are 100 and 88%, respectively. More importantly, the structure of the catalyst after the desulfurization reaction is consistent with that of the fresh counterpart. The study offers new insights into the development of effective and stable bimetallic catalysts to eliminate H2S and recycle sulfur.

Eliminating bias: enhancing children's book recommendation using a hybrid model of graph convolutional networks and neural matrix factorization.

Managing user bias in large-scale user review data is a significant challenge in optimizing children's book recommendation systems. To tackle this issue, this study introduces a novel hybrid model that combines graph convolutional networks (GCN) based on bipartite graphs and neural matrix factorization (NMF). This model aims to enhance the precision and efficiency of children's book recommendations by accurately capturing user biases. In this model, the complex interactions between users and books are modeled as a bipartite graph, with the users' book ratings serving as the weights of the edges. Through GCN and NMF, we can delve into the structure of the graph and the behavioral patterns of users, more accurately identify and address user biases, and predict their future behaviors. Compared to traditional recommendation systems, our hybrid model excels in handling large-scale user review data. Experimental results confirm that our model has significantly improved in terms of recommendation accuracy and scalability, positively contributing to the advancement of children's book recommendation systems.

Deciphering Cholesterol's Role in PD-L2 Stability: A Distinct Regulatory Mechanism From PD-L1.

Programmed cell death 1 ligand 2 (PD-L2), a member of the B7 immune checkpoint protein family, emerges as a crucial player in immune modulation. Despite its functional overlap with programmed cell death 1 ligand 1 (PD-L1) in binding to the programmed cell death protein 1 (PD-1) on T cells, PD-L2 exhibits a divergent expression pattern and a higher affinity for PD-1. However, the regulatory mechanisms of PD-L2 remain under-explored. Here, our investigations illustrate the pivotal role of cholesterol in modulating PD-L2 stability. Using advanced nuclear magnetic resonance (NMR) and biochemical analyses, we demonstrate a direct and specific binding between cholesterol and PD-L2, mediated by an F-xxx-V-xx-LR motif in its transmembrane domain, distinct from that in PD-L1. This interaction stabilizes PD-L2 and prevents its downstream degradation. Disruption of this binding motif compromises PD-L2's cellular stability, underscoring its potential significance in cancer biology. These findings not only deepen our understanding of PD-L2 regulation in the context of tumors, but also open avenues for potential therapeutic interventions.

Impacts of the aerosol mixing state and new particle formation on CCN in summer at the summit of Mount Tai (1534m) in Central East China.

In this study, the aerosol size distributions, cloud condensation nuclei (CCN) number concentration (NCCN), single-particle chemical composition and meteorological data were collected from May 12 to June 8, 2017, at the summit of Mt. Tai. The effects of new particle formation (NPF) events and aerosol chemical components on CCN at Mt. Tai were analyzed in detail. The results showed that, NPF events significantly enhanced the CCN population, and the enhancement effect increased with increasing supersaturation (SS) value at Mt.Tai. NCCN at SS ranging from 0.1 to 0.9 % on NPF days was 10.9 %, 36.5 %, 44.6 %, 53.5 % and 51.5 % higher than that on non-NPF days from 10:00-13:00 as NPF events progressed. The effect of chemical components on CCN activation under the influence of NPF events was greater than that in the absence of NPF events. The correlation coefficients of EC-Nitrate particles (EC-Sulfate particles) and CCN at all SS levels on NPF days were 1.31-1.59 times (1.17-1.35 times) higher than those on non-NPF days. Nitrate particles promoted CCN activation but sulfate particles inhibited activation at Mt. Tai. There are differences or even opposite effects of the same group of particles on CCN activation under the influence of NPF events in different air masses. EC-Sulfate particles inhibited CCN activation at all SS levels for type I but weakly promoted activation at lower SS ranging from 0.1 to 0.3 % and weakly inhibited it at higher 0.9 % SS for type II. OCEC particles significantly inhibited CCN activation for type II, and this effect decreased with increasing SS. OCEC particles only weakly inhibited activation at SS ranging from 0.5 to 0.7 % for type I. OCEC particles only weakly inhibited this process at 0.1 % SS, while they very weakly promoted activation for SS > 0.1 %. This reveals that the CCN activity is not only related to the chemical composition of the particles, but the mixing state also has an important effect on the CCN activity.

Directional Charge Pumping from Photoactive P-doped CdS to Catalytic Active Ni2 P via Funneled Bandgap and Bridged Interface for Greatly Enhanced Photocatalytic H2 Evolution.

Loading cocatalysts onto semiconductors is one of the most popular strategies to inhibit charge recombination, but the efficiency is generally hindered by the localized built-in electric field and the weakly connected interface. Here, this work designs and synthesizes a 1D P-doped CdS nanowire/Ni2 P heterojunction with gradient doped P to address the challenges. In the composite, the gradient P doping not only creates a funneled bandgap structure with a built-in electric field oriented from the bulk of P-CdS to the surface, but also facilitates the formation of a tightly connected interface using the co-shared P element. Consequently, the photogenerated charge carriers are enabled to be pumped from inside to surface of the P-CdS and then smoothly across the interface to the Ni2 P. The as-obtained P-CdS/Ni2 P displays high visible-light-driven H2 evolution rate of ≈8265 µmol g-1 h-1 , which is 336 times and 120 times as that of CdS and P-CdS, respectively. This work is anticipated to inspire more research attention for designing new gradient-doped semiconductor/cocatalyst heterojunction photocatalysts with bridged interface for efficient solar energy conversion.

Meteorological influence on persistent O3 pollution events in Wuxi in the Yangtze River Delta, China.

The number of O3 pollution days indicates an overall increasing trend over 2014-2021 in Wuxi in the Yangtze River Delta, with the pollution concentrations of MDA8-O3 between 186 and 200 µg·m-3. Specifically, a total of 62 POPEs (persistent O3 pollution events), defined as episodes with 3 or more continuous O3 pollution days, were observed for the 8 years. Using a multi-linear regression model, we find that the meteorology can explain approximately 56.5 % of the O3 variations for the 8 years in Wuxi, with temperature being the most crucial meteorological factor, followed by relative humidity (RH) and wind speeds. High temperature, low RH, low wind speeds and downward airflows significantly correlate with POPE-O3 changes. Three types of synoptic circulations are further identified during the POPEs from 2014 to 2021 by the T-mode (T-PCA) classification method. The primary circulation patterns governing the interannual changes of POPEs are characterized by the largest positive anomalies of temperature and planetary boundary layer (PBL) height; moreover, a distinct vertical mixing process is observed with uplifting airflows in the convective PBL during the afternoon and sinking airflows in the stable PBL at night, which is incredibly conducive to the downward transport of O3 after its upward delivery during daytime and substantially contributes to midnight O3 at the surface. The other two circulation types are associated with uniform descending flows in the PBL; as a result, surface O3 accumulates only near the ground and decreases significantly at night due to the titration effect. This study systematically highlights the influence of critical meteorological factors regulated by different synoptic circulations on the POPE in Wuxi, which provides a scientific basis for pollution control and prediction.

Twin boundary defect engineering in Au cocatalyst to promote alcohol splitting for coproduction of H2 and fine chemicals.

The microstructure of Au metal cocatalyst has been shown to significantly influence its optical and electronic properties. However, the impact of Au defect engineering on photocatalytic activity remains underexplored. In this study, we synthesize different Au-TiO2 composites by in-situ hybridizing face-centered cubic (F-Au) and twin boundary defect Au (T-Au) nanoparticles (NPs) onto the surface of TiO2. We find that T-Au NPs with twin defects serve as highly efficient cocatalysts for converting alcohols into their corresponding aldehydes while also generating H2. The optimized T-Au/TiO2 composite yields an H2 evolution rate of 6850 µmol h-1 g-1 and a BAD formation rate of 6830 µmol h-1 g-1, about 38 times higher than that of blank TiO2. Compared to F-Au/TiO2, the T-Au/TiO2 composite enhances charge separation, extends the lifetime of electrons, and provides more active sites for H2 reduction. The twin defect also improves alcohol reactant adsorption, boosting overall photocatalytic performance. This research paves the way for more studies on defect engineering in metal cocatalysts for enhanced catalytic activities in organic synthesis and H2 evolution.

Nrf2/PHB2 alleviates mitochondrial damage and protects against Staphylococcus aureus-induced acute lung injury.

Staphylococcus aureus (SA) is a major cause of sepsis, leading to acute lung injury (ALI) characterized by inflammation and oxidative stress. However, the role of the Nrf2/PHB2 pathway in SA-induced ALI (SA-ALI) remains unclear. In this study, serum samples were collected from SA-sepsis patients, and a SA-ALI mouse model was established by grouping WT and Nrf2-/- mice after 6 h of intraperitoneal injection. A cell model simulating SA-ALI was developed using lipoteichoic acid (LTA) treatment. The results showed reduced serum Nrf2 levels in SA-sepsis patients, negatively correlated with the severity of ALI. In SA-ALI mice, downregulation of Nrf2 impaired mitochondrial function and exacerbated inflammation-induced ALI. Moreover, PHB2 translocation from mitochondria to the cytoplasm was observed in SA-ALI. The p-Nrf2/total-Nrf2 ratio increased in A549 cells with LTA concentration and treatment duration. Nrf2 overexpression in LTA-treated A549 cells elevated PHB2 content on the inner mitochondrial membrane, preserving genomic integrity, reducing oxidative stress, and inhibiting excessive mitochondrial division. Bioinformatic analysis and dual-luciferase reporter assay confirmed direct binding of Nrf2 to the PHB2 promoter, resulting in increased PHB2 expression. In conclusion, Nrf2 plays a role in alleviating SA-ALI by directly regulating PHB2 transcription and maintaining mitochondrial function in lung cells.

Carbon-doped boron nitride nanosheets as an efficient metal-free catalyst for the selective oxidation of H2S.

We report the first use of carbon-doped boron nitride (BCN) for H2S-selective catalytic oxidation. The obtained carbon-doped BN with an ultrathin layer structure exhibits outstanding H2S elimination and high S yield. In particular, BN doped carbon nanosheets display better catalytic performance than traditional catalysts, such as iron- and carbon-based catalysts. The findings of the present work shed a new light on metal-free catalysts for efficient catalytic removal of toxic H2S.

A SARS-CoV-2 nanoparticle vaccine based on chemical conjugation of loxoribine and SpyCatcher/SpyTag.

SARS-CoV-2 is a particularly transmissible virus that renders the worldwide COVID-19 pandemic and global severe respiratory distress syndrome. Protein-based vaccines hold great advantages to build the herd immunity for their specificity, effectiveness, and safety. Receptor-binding domain (RBD) of SARS-CoV-2 is an appealing antigen for vaccine development. However, adjuvants and delivery system are necessitated to enhance the immunogenicity of RBD. In the present study, RBD was chemically conjugated with loxoribine and SpyCatcher/SpyTag, followed by assembly to form a nanoparticle vaccine. Loxoribine (a TLR7/8 agonist) acted as an adjuvant, and nanoparticles functioned as delivery system for the antigen and the adjuvant. The nanoparticle vaccine elicited high RBD-specific antibody titers, high neutralizing antibody titer, and strong ACE2-blocking activity. It stimulated high splenic levels of Th1-type cytokines (IFN-γ and IL-2) and Th2-type cytokines (IL-4 and IL-5) in BALB/c mice. It promoted the splenocyte proliferation, enhanced the CD4+ and CD8+ T cell percentage and stimulated the maturation of dendritic cells. The vaccine did not render apparent toxicity to the organs of mice. Thus, the nanoparticle vaccine was of potential to act as a preliminarily safe and effective candidate against SARS-CoV-2.

Predicting and overcoming resistance to CDK9 inhibitors for cancer therapy.

Abnormally activated CDK9 participates in the super-enhancer mediated transcription of short-lived proteins required for cancer cell survival. Targeting CDK9 has shown potent anti-tumor activity in clinical trials among different cancers. However, the study and knowledge on drug resistance to CDK9 inhibitors are very limited. In this study, we established an AML cell line with acquired resistance to a highly selective CDK9 inhibitor BAY1251152. Through genomic sequencing, we identified in the kinase domain of CDK9 a mutation L156F, which is also a coding SNP in the CDK9 gene. By knocking in L156F into cancer cells using CRISPR/Cas9, we found that single CDK9 L156F could drive the resistance to CDK9 inhibitors, not only ATP competitive inhibitor but also PROTAC degrader. Mechanistically, CDK9 L156F disrupts the binding with inhibitors due to steric hindrance, further, the mutation affects the thermal stability and catalytic activity of CDK9 protein. To overcome the drug resistance mediated by the CDK9-L156F mutation, we discovered a compound, IHMT-CDK9-36 which showed potent inhibition activity both for CDK9 WT and L156F mutant. Together, we report a novel resistance mechanism for CDK9 inhibitors and provide a novel chemical scaffold for the future development of CDK9 inhibitors.

[Pollution Characteristics of Carbonaceous Components in PM10 and PM2.5 of Road Dust Fall and Soil Dust in Xi'an].

To investigate the pollution characteristics of carbonaceous components in PM10 and PM2.5 of road dust fall and soil dust in Xi'an and enrich their source profiles, samples from five sites of road dust fall and 16 sites of soil dust were collected in Xi'an from April to May 2015. The ZDA-CY01 particulate matter resuspension sampler was used to obtain PM10 and PM2.5 samples, and the Model5L-NDIR OC and EC analyzer were used to determine the concentrations of organic carbon (OC) and elemental carbon (EC) in PM10 and PM2.5. The pollution and sources of carbonaceous aerosol in PM10 and PM2.5 were investigated by analyzing OC and EC characteristics, ratio, and the principal component analysis statistical model. The results showed that the proportions of OC in PM10 and PM2.5 at the various dust fall sites differed, ranging from 6.0% to 19.4% and 7.6% to 29.8%, respectively. The ratios of EC in PM10 and PM2.5at the different dust fall sites were relatively small, accounting for 0.6%-2.2% and 0.2%-3.6% in urban sites, respectively; however, EC was almost undetectable in most peripheral soil dust. The proportions of carbonaceous components in PM10 and PM2.5 followed the order of urban road dust fall>external control dust>river beach soil dust>soil dust and urban road dust fall>soil dust>external control dust>river beach soil dust, respectively. OC dominated the carbonaceous aerosols at the different sites, which was relatively low in urban road dust fall. The OC to total carbon (TC) ratios in PM10 and PM2.5 at urban road dust fall were 85.2%-95.3% and 87.9%-98.9%, respectively. The OC to TC ratios in PM10 and PM2.5 of soil dust were relatively high, exceeding 99%. Carbonaceous components were primarily concentrated in fine particles. The pollution distribution of carbonaceous components in the urban road dust fall sites was consistent, whereas that in the different soil dust sites were quite different. The carbonaceous components in urban road dust fall and soil dust were primarily affected by pollutant source emissions such as biomass burning, coal burning, gasoline, and diesel vehicle exhaust. There were differences in the source contribution rates of carbonaceous aerosols in PM10 and PM2.5.

High-efficiency visible-light-driven oxidation of primary C-H bonds in toluene over a CsPbBr3 perovskite supported by hierarchical TiO2 nanoflakes.

Photocatalytic oxidation of toluene to valuable fine chemicals is of great significance, yet faces challenges in the development of advanced catalysts with both high activity and selectivity for the activation of inert C(sp3)-H bonds. Halide perovskites with remarkable optoelectronic properties have shown to be prospective photoactive materials, but the bulky structure with a small surface area and severe recombination of photogenerated electron-hole pairs are obstacles to application. Here, we fabricate a hierarchical nanoflower-shaped CsPbBr3/TiO2 heterojunction by assembling CsPbBr3 nanoparticles on 2D TiO2 nanoflake subunits. The design significantly downsizes the size of CsPbBr3 from micrometers to nanometers, and forms a type II heterojunction with intimate interfacial contact between CsPbBr3 and TiO2 nanoflakes, thereby accelerating the separation and transfer of photogenerated charges. Moreover, the formed hierarchical heterojunction increaseslight absorption by refraction and scattering, offers a large surface area and enhances the adsorption of toluene molecules. Consequently, the optimized CsPbBr3/TiO2 exhibits a high performance (10 200 µmol g-1 h-1) for photocatalytic toluene oxidation with high selectivity (85%) for benzaldehyde generation under visible light. The photoactivity is about 20 times higher than that of blank CsPbBr3, and is among the best photocatalytic performances reported for selective oxidation of toluene under visible light irradiation.

Comparative Efficacy of Different Drugs for the Treatment of Dilated Cardiomyopathy: A Systematic Review and Network Meta-analysis.

BACKGROUND AND OBJECTIVE: At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical efficacy of a combination of various conventional and adjuvant drugs in treating dilated cardiomyopathy via network meta-analysis. METHODS: The study was reported according to the PRISMA 2020 statement. From inception through 27 June 2022, the PubMed, Embase, Cochrane library, and Web of Science databases were searched for randomized controlled trials on medicines for treating dilated cardiomyopathy. The quality of the included studies was evaluated according to the Cochrane risk of bias assessment. R4.1.3 and Revman5.3 software were used for analysis. RESULTS: There were 52 randomized controlled trials in this study, with a total of 25 medications and a sample size of 3048 cases. The network meta-analysis found that carvedilol, verapamil, and trimetazidine were the top three medicines for improving left ventricular ejection fraction (LVEF). Ivabradine, bucindolol, and verapamil were the top 3 drugs for improving left ventricular end-diastolic dimension (LVEDD). Ivabradine, L-thyroxine, and atorvastatin were the top 3 drugs for improving left ventricular end-systolic dimension (LVESD). Trimetazidine, pentoxifylline, and bucindolol were the top 3 drugs for improving the New York Heart Association classification (NYHA) cardiac function score. Ivabradine, carvedilol, and bucindolol were the top 3 drugs for reducing heart rate (HR). CONCLUSION: A combination of different medications and conventional therapy may increase the clinical effectiveness of treating dilated cardiomyopathy. Beta-blockers, especially carvedilol, can improve ventricular remodeling, cardiac function, and clinical efficacy in patients with dilated cardiomyopathy (DCM). Hence, they can be used if patients tolerate them. If LVEF and HR do not meet the standard, ivabradine can also be used in combination with other treatments. However, since the quality and number of studies in our research were limited, large sample size, multi-center, and high-quality randomized controlled trials are required to corroborate our findings.

An online diagnosis method for cancer lesions based on intelligent imaging analysis.

With the popularization and application of artificial intelligence and medical image big data in the field of medical image, the universality of modes and the rapid development of deep learning have endowed multi-mode fusion technology with great development potential. Technologies of 5G and artificial intelligence have rapidly promoted the innovation of online hospitals. To assist doctors in the remote diagnosis of cancer lesions, this article proposes a cancer localization and recognition model based on magnetic resonance images. We combine a convolution neural network with Transformer to achieve local features and global context information, which can suppress the interference of noise and background regions in magnetic resonance imaging. We design a module combining convolutional neural networks and Transformer architecture, which interactively fuses the extracted features to increase the cancer localization accuracy of magnetic resonance imaging (MRI) images. We extract tumor regions and perform feature fusion to further improve the interactive ability of features and achieve cancer recognition. Our model can achieve an accuracy of 88.65%, which means our model can locate cancer regions in MRI images and effectively identify them. Furthermore, our model can be embedded into the online hospital system by 5G technology to provide technical support for the construction of network hospitals.

Burden of non-communicable diseases among adolescents and young adults aged 10-24 years in the South-East Asia and Western Pacific regions, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Although non-communicable diseases (NCDs) remain the leading causes of mortality and disability worldwide, little comprehensive or recent evidence of the burden of NCDs among adolescents and young adults in the South-East Asia and Western Pacific regions is available. We aimed to report population shifts in people aged 10-24 years and their NCD burden from 1990 to 2019 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS: We retrieved data from GBD 2019 for people aged 10-24 years in the South-East Asia and Western Pacific regions from 1990 to 2019. We presented population shifts and analysed deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for NCDs. We also quantified the associations of deaths and DALYs with the Socio-demographic Index (SDI) and Universal Health Coverage (UHC) effective coverage index using Spearman correlation and linear regression analyses. Percentages are reported to 1 decimal place and rates are reported to 2 decimal places. FINDINGS: In 2019, there were 559·2 million young people aged 10-24 years in the South-East Asia region and 335·0 million in the Western Pacific region; India and China remained the countries with greatest number of this age group. In 1990-2019, India had an absolute increase of 139·4 million adolescents, while China had a decrease of 134·3 million. In 2019, NCDs accounted for 27·3% (95% uncertainty interval 25·1 to 29·2) and 34·6% (33·5 to 36·1) of total deaths, and 49·8% (45·3 to 54·4) and 65·1% (60·6 to 69·3) of total DALYs in the South-East Asia and the Western Pacific regions, respectively. Neoplasms, cardiovascular diseases, and mental disorders were the leading causes of NCD burden in 42 countries. Kiribati had the highest rates of deaths (62·82 [50·77 to 76·11] per 100 000 population), YLLs (4364·73 [3545·04 to 5275·63] per 100 000 population), and DALYs (9368·73 [7713·65 to 11340·99] per 100 000 population) for NCDs, whereas Australia (6976·51 [5044·46 to 9190·01] per 100 000 population) and New Zealand (6716·81 [4827·25 to 8827·69] per 100 000 population) had the largest rates of YLDs due to NCDs. From 1990 to 2019 across both regions, the rate of death due to NCDs declined by over a third (-32·8% [-41·1 to -22·9] in the South-East Asia region and -40·0% [-48·6 to -30·4] in the Western Pacific region), and DALYs decreased by about 12% (-12·0% [-16·8 to -7·7] in the South-East Asia region and -12·8% [-17·7 to -8·7] in the Western Pacific region), whereas the proportion of NCD burden relative to all-cause burden increased (45·7% [32·9 to 61·7] for deaths and 41·2% [35·2 to 48·8] for DALYs in the South-East Asia region; 11·8% [7·1 to 21·5] for deaths and 18·2% [14·6 to 22·0] for DALYs in the Western Pacific region). The rate of deaths and DALYs due to NCDs decreased monotonically alongside increases in SDI (rs=-0·57 [95% CI -0·81 to -0·32] for deaths and rs=-0·30 [-0·61 to 0·03] for DALYs). The rate of deaths (rs=-0·89 [95% CI -0·97 to -0·80]) and DALYs (rs=-0·67 [-0·93 to -0·41]) due to NCDs also decreased alongside increases in the UHC effective coverage index. INTERPRETATION: Specific preventive and health service measures are needed for adolescents and young adults in countries with different levels of socioeconomic development to reduce the burden from NCDs. FUNDING: National Natural Science Foundation of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Mucosal SARS-CoV-2 Nanoparticle Vaccine Based on Mucosal Adjuvants and Its Immune Effectiveness by Intranasal Administration.

SARS-CoV-2 is a respiratory virus that causes significant threats to human health. Mucosal immunity provides a first-line defense to prevent the infection of SARS-CoV-2 in the respiratory tract. Because most SARS-CoV-2 vaccines could not stimulate mucosal immunity in the respiratory tract, appropriate mucosal adjuvants or delivery systems are needed for mucosal vaccine development. Mannan, polyarginine, and 2',3'-cGAMP are three mucosal adjuvants that could stimulate mucosal immunity. In the present study, the three adjuvants were assembled with a receptor-binding domain (RBD) by electrostatic interaction to generate a nanoparticle vaccine (RBD-MP-cG). RBD-MP-cG elicited mucosal IgA and IgG response in bronchoalveolar lavage and nasal lavage by intranasal administration. It induced a robust RBD-specific antibody response, high levels of protective neutralizing antibody, and ACE2-blocking activity in the mouse sera. It stimulated the splenic secretion of high levels of Th1-, Th2-, and Th17-type cytokines. Thus, RBD-MP-cG elicited strong mucosal immunity and systematic immunity by intranasal administration. RBD-MP-cG was expected to act as a safe, effective, and easily produced mucosal nanoparticle vaccine to combat the infection of SARS-CoV-2.

Higher vegetable consumption is related to a lower risk of cardiometabolic risk cluster among children and adolescents: A national cross-sectional study in China.

BACKGROUND AND AIMS: Evidence about the association between vegetable consumption and cardiometabolic risk factors (CMRFs) cluster among children and adolescents was inconsistent. We aimed to investigate the prevalence of CMRFs and CMRFs cluster, and to evaluate their associations with vegetable consumption. METHODS AND RESULTS: A total of 14,061 participants aged 6-19 years were recruited from 7 provinces of China. A standard physical examination, including height, weight and blood pressure, was conducted. Information regarding CMRFs was obtained through anthropometric measurements and blood sample testing, while weekly frequency and daily servings of vegetable consumption data collected by questionnaires. Logistic regression models were used to analyze the odds ratios (OR) for associations between CMRFs, CMRFs cluster and vegetable consumption. The prevalence of no CMRFs cluster among children and adolescents was 26.4%. Participants whose daily vegetable consumption was 0.75-1.5 and ≥1.5 servings showed a lower risk of high blood pressure (HBP), high total cholesterol (TC), high triglyceride (TG), and high low-density lipoprotein cholesterol (LDL-C) compared to those with daily vegetable consumption of <0.75 servings. Besides, higher average daily vegetable consumption was strongly associated with lower risks of CMRFs cluster. Stratified analyses showed that the protective effects of more vegetable intake on CMRFs cluster were profounder in boys and young adolescents. CONCLUSION: More vegetable intake was associated with lower risks of CMRFs cluster in Chinese children and adolescents aged 6-19 years, which further highlighted the significance of vegetable consumption to improve the cardiometabolic risk status.