The combination of high uric acid and high C-reactive protein increased the risk of cardiovascular disease: A 15-year prospective cohort study.

BACKGROUND AND AIMS: Uric acid (UA) and C-reactive protein (CRP) may interact synergistically to accelerate the initiation and progression of cardiovascular disease (CVD). This study investigated the effects of a combination of high UA and high CRP on the risks of CVD. METHODS AND RESULTS: A total of 90,270 participants recruited from the Kailuan study were included, who were divided into four groups according to the presence/absence of hyperuricemia and inflammation. Cox regression was applied to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CVD. C-statistics, net classification index (NRI), and integrated discrimination improvement (IDI) were used to compare the incremental predictive of UA, CRP, and their combined effects on CVD. Mediation analysis was to explore the impact of CRP on the association between UA and CVD. Over a median follow-up of 14.95 years, we identified 11398 incident CVD cases. Compared to the low UA/low CRP group, the high UA/low CRP, low UA/high CRP and high UA/high CRP groups showed progressively higher risks of CVD, HR (95% CI): 1.18(1.10-1.27), 1.27(1.21-1.33) and 1.50 (1.33-1.69), respectively. The incorporation of UA and CRP into the traditional China-PAR model led to improvement in the C-statistic, NRI, and IDI, and was better than incorporation of either UA or CRP alone. Mediation analysis showed that CRP mediated the association between UA and CVD, accounting for 11.57% of the total effects. CONCLUSIONS: High UA/high CRP is associated with increased risks of CVD. Incorporation of both UA and CRP provided additional value for risk stratification.

Discovery of lupus nephritis targeted inhibitors based on De novo molecular design: comprehensive application of vinardo scoring, ADMET analysis, and molecular dynamics simulation.

Lupus Nephritis (LN) is an autoimmune disease affecting the kidneys, and conventional drug studies have limitations due to its imprecise and complex pathogenesis. Therefore, the aim of this study was to design a novel Lupus Nephritis-targeted drug with good clinical due potential, high potency and selectivity by computer-assisted approach.NIK belongs to the serine/threonine protein kinase, which is gaining attention as a drug target for Lupus Nephritis. we used bioinformatics, homology modelling and sequence comparison analysis, small molecule ab initio design, ADMET analysis, molecular docking, molecular dynamics simulation, and MM/PBSA analysis to design and explore the selectivity and efficiency of a novel Lupus Nephritis-targeting drug, ClImYnib, and a classical NIK inhibitor, NIK SMI1. We used bioinformatics techniques to determine the correlation between lupus nephritis and the NF-κB signaling pathway. De novo drugs design was used to create a NIK-targeted inhibitor, ClImYnib, with lower toxicity, after which we used molecular dynamics to simulate NIK SMI1 against ClImYnib, and the simulation results showed that ClImYnib had better selectivity and efficiency. Our research delves into the molecular mechanism of protein ligands, and we have designed and validated an excellent NIK inhibitor using multiple computational simulation methods. More importantly, it provides an idea of target designing small molecules.Communicated by Ramaswamy H. Sarma.

Trends by age and sex and projections of disease prevalence from studying hypertensive heart disease in China over the past three decades.

BACKGROUND: Hypertensive heart disease (HHD) is a common cause of cardiovascular disease and mortality worldwide, and its burden is increasing with aging populations. OBJECTIVES: This study aimed to estimate the prevalence and mortality rates of HHD in mainland China and Taiwan Province using data from the Global Burden of Disease Study 2019 (GBD 2019), and forecast the development trend of HHD from 2020 to 2024. METHODS: We obtained data on number of cases, deaths, crude prevalence rate, crude death rate, age-standardized prevalence rate (ASPR), and age-standardized death rate (ASDR) for mainland China and Taiwan Province from 1990 to 2019 from the GBD 2019. Joinpoint software was used to estimate average annual percentage change (AAPC) with 95% confidence intervals, and the number of HHD cases in China from 2022 to 2024 was predicted by the exponential smoothing method. RESULTS: Between 1990 and 2019, HHD cases and deaths increased in mainland China, but the ASPR and ASDR decreased by 5.96% and 48.72%, respectively. In Taiwan Province, ASPR and ASDR decreased by 7.66% and 52.14%, respectively. The number of HHD cases and death rates varied by region, age, and sex, with a higher number of cases in mainland China than in Taiwan Province. By 2024, the number of HHD cases in mainland China was projected to be over 9.6 million cases, and in Taiwan Province, it was projected to surpass 120,000 cases. CONCLUSION: The differences in HHD cases between mainland China and Taiwan Province in terms of age and sex indicated the need for effective prevention and control measures, especially targeting the elderly population. These findings can inform policymakers and health professionals in the development of targeted prevention and treatment strategies and resource allocation for HHD in China.

Amide and Multihydroxyl Complementary Tailored Metal-Organic Framework with Enhanced Glycan Affinity for Efficient Glycoproteomic Analysis.

Protein glycosylation is ubiquitous and crucial for regulating biological processes in organisms. Given the heterogeneity and low abundance of glycoproteins, efficient and specific enrichment procedures are required for the mass spectrometry analysis of glycopeptides. Hydrophilic interaction liquid chromatography (HILIC) has emerged as an effective strategy for glycopeptide enrichment. However, the relatively weak hydrophilic affinity restricts the achievement of a satisfactory enrichment performance. Here, we presented a rational design of an amide and multihydroxyl complementary tailored metal-organic framework, denoted as U6N/Pv@Glc, which exhibited ultrahydrophilicity and enhanced glycan affinity. Our results demonstrated a significant increase in glycopeptide coverage after enrichment, accompanied by extremely low detection limits (0.05 fmol µL-1) and high selectivity (IgG/BSA, 1:4000) as evaluated using trypsin-digested standard glycoproteins. A total of 379 glycopeptides and 247 intact glycopeptides (containing a total of 1577 site-specific N-glycans) were identified and characterized within human serum samples from individuals with type 2 diabetes in-depth. Additionally, we extended the application of this material to capture undigested glycoproteins, demonstrating potential compatibility with top-down MS analysis. These results highlight the promising potential of this novel material for comprehensive glycoproteomic analysis of every potential aspect.

The associated evolution of raptorial foreleg and mantispid diversification during 200 million years.

Mantispidae have developed multidimensional specializations of predation that are leveraged by trade-offs involving attack properties, which is revealed by interdisciplinary analyses of phylogeny, morphometrics, and mechanical modeling. The lineage diversification was stimulated by its raptorial foreleg evolution, and was influenced by the ecosystem of corresponding periods, involving biotic and physical factors.

High levels of high-sensitivity C reactive protein to albumin ratio can increase the risk of cardiovascular disease.

BACKGROUND: The high levels of C reactive protein (CRP) to albumin ratio (CAR) is thought to increase the risk of poor outcomes for cancer and cardiovascular disease (CVD). However, the association between CAR and CVD in the Chinese community population has not been investigated. OBJECTIVE: The aim of this study was to investigate the association between CAR and CVD in the Chinese community population. METHODS: A total of 62 067 participants without a history of CVD or cancer were included in this study. Kaplan-Meier survival curves were used to calculate the cumulative incidence of endpoint events in CAR quartile groups, and the results were tested by log-rank test. Fine-Gray model was used to analyse the competing risk of death. C-index, Net Reclassification Index (NRI) and Integrated Discrimination Improvement Index (IDI) of different indicators were calculated to distinguish the predictive performance of different indicators. RESULTS: During an average follow-up period of 10.3±2.1 years, 4025 participants developed CVD. In multivariable Cox regression analysis, compared with Q1 group, model 3 showed that the hazard ratio (HR) (95% confidence interval (95%CI)) of CVD in Q4 group was 1.26 (1.15 to 1.38) (p<0.01), and the HR (95% CI) per 1 SD increase was 1.06 (1.03 to 1.08) (p<0.01). The C-index, continuous NRI and IDI for predicting 10-year CVD were 73.48%, 0.1366 (0.1049 to 0.1684) (p<0.01) and 0.0002 (0.0001 to 0.0004) (p<0.01), respectively, which were higher than those of hs-CRP (C-index:0.7344, NRI:0.0711, IDI: 0.0001) and albumin (C-index:0.7339, NRI: -0.0090, IDI: 0.0000). CONCLUSION: High levels of CAR can increase the risk of CVD and the predictive performance of CAR for CVD is better than that of hs-CRP or albumin alone.

Deciphering the Atlas of Post-Translational Modification in Sugarcane.

In plants, lysine acetylation (Kac), 2-hydroxyisobutyrylation (Khib), and lysine lactylation (Kla), the three new types of post-translational modification (PTM), play very important roles in growth, development, and resistance to adverse environmental stresses. Herein, we report the first global acetylome, 2-hydroxyisobutyrylome, and lactylome in sugarcane. A total of 8573 Kac, 4637 Khib, and 215 Kla sites across 3903, 1507, and 139 modified proteins were identified. Besides, homology analyses revealed the Kac, Khib, and Kla sites on histones were conserved between sugarcane and rice or poplar. Functional annotations demonstrated that the Kac, Khib, and Kla proteins were mainly involved in energy metabolism. In addition, a number of modified transcription factors and stress-related proteins, which were constitutively expressed in different tissues of sugarcane and induced by drought, cold or Sporisorium scitamineum stress, were identified. Finally, a proposed working mode on how PTM functions in sugarcane was depicted. We thus concluded that PTM should play a role in sugarcane growth, development, and response to biotic and abiotic stresses, but the mechanisms require further investigation. The present study provided the all-new comprehensive profile of proteins Kac, Khib, and Kla and a new perspective to understand the molecular mechanisms of protein PTMs in sugarcane.

Perovskite Ink with an Ultrawide Processing Window for Efficient and Scalable Perovskite Solar Cells in Ambient Air.

Perovskite solar cells (PSCs) have attracted tremendous attention because of their rapidly growing efficiency and low cost. However, the efficiency of scalably deposited PSCs, especially spray-coated devices, is still lagging far behind that of spin-coated devices because of the complicated crystallization of coated precursor ink. Here, we show a precursor ink with an ultrawide processing window (more than 40 min) for spray-coating by adjusting the precursor component, which benefits the scalable deposition of perovskite films. Coupled with antisolvent extraction and addition of methylamine chloride to perovskite ink, high-quality perovskite films were achieved with large-scale uniformity. A power conversion efficiency (PCE) of 18.5% for rigid sprayed PSCs and 16.15% for flexible sprayed PSCs were achieved. At the square-centimeter level, sprayed PSCs on rigid and flexible substrates were achieved with PCEs of 15.07 and 13.21%, respectively. The one-step single-pass spraying method for versatility substrates at a deposition rate of 540 m h-1 brings great prospects for commercialization of PSCs.

Efficient Perovskite Solar Cells Prepared by Hot Air Blowing to Ultrasonic Spraying in Ambient Air.

Substrate heating is the most common method for controlling crystallization during spray coating. However, due to poor controllability during substrate heating, the sprayed films have variable thicknesses and rich pores, which limit the efficiency of the device. Here, hot air blowing was applied to spray coating to promote the crystallization of perovskite films under ambient conditions. Upon employing a hot air blowing method that stimulated uniformly distributed nuclei growth, the pinhole-free and thickness-controllable perovskite film was prepared. This enabled more reproducible high-quality perovskite films to achieve a power conversion efficiency of 13.5% and obtain a stabilized power output of >12% in ambient conditions.

The sinemydid turtle Ordosemys from the Lower Cretaceous Mengyin Formation of Shandong, China and its implication for the age of the Luohandong Formation of the Ordos Basin.

Chronostratigraphic correlation of terrestrial Early Cretaceous biotas in China is highly problematic due to the lack of marine deposits, few absolute dates, and limited number of index fossils. This often leaves vertebrate faunas as one of the few potential tools for a preliminary biostratigraphy. Taxonomic identity of fragmentary fossils is, however, often uncertain and many faunas are insufficiently sampled. Turtles are one of the most common elements of Early Cretaceous biotas of Asia and their skeleton is frequently preserved more completely than that of other vertebrates- they yet receive little attention from vertebrate paleontologists. We here record the presence of the sinemydid turtle Ordosemys leios from the Lower Cretaceous Mengyin Formation of Shandong Province, China, best known for the first dinosaurs and Mesozoic turtles described from the country. Ordosemys is the third turtle reported from the Mengyin Formation along with Sinemys lens and Sinochelys applanata and the only other formation where Ordosemys is known to co-occur with Sinemys is the Luohandong Formation of the Ordos Basin (Inner Mongolia), the type and so far only horizon of Ordosemys leios. The presence of the crocodyliform Shantungosuchus may further define a fauna that is so far only known from these two formations. The stratigraphic position of the Luohandong Formation is poorly controlled and it has been placed anywhere between the Valanginian and Aptian. Published absolute dates from the Mengyin Formation and the numerous shared vertebrate and invertebrate taxa (now also including turtles) implies a Valanginian-early Hauterivian age for the Luohandong Formation-in contrast to late Hauterivian-Albian as previously proposed using the temporal distribution of Psittacosaurus. The new specimen of Ordosemys leios preserves the only known manus of this species and ecomorphological analysis of limb proportions implies that it was a less capable swimmer compared to Ordosemys liaoxiensis coming from the younger Jehol Biota.

Morphological Structure, Rheological Behavior, Mechanical Properties and Sound Insulation Performance of Thermoplastic Rubber Composites Reinforced by Different Inorganic Fillers.

The application area of a sound insulation material is highly dependent on the technology adopted for its processing. In this study, thermoplastic rubber (TPR, polypropylene/ethylene propylene diene monomer) composites were simply prepared via an extrusion method. Two microscale particles, CaCO3 and hollow glass microspheres (HGW) were chosen to not only enhance the sound insulation but also reinforced the mechanical properties. Meanwhile, the processing capability of composites was confirmed. SEM images showed that the CaCO3 was uniformly dispersed in TPR matrix with ~3 µm scale aggregates, while the HGM was slightly aggregated to ~13 µm scale. The heterogeneous dispersion of micro-scale fillers strongly affected the sound transmission loss (STL) value of composites. The STL values of TPR composites with 40 wt % CaCO3 and 20 wt % HGM composites were about 12 dB and 7 dB higher than that of pure TPR sample, respectively. The improved sound insulation performances of the composites have been attributed to the enhanced reflection and dissipate sound energy in the heterogeneous composite. Moreover, the mechanical properties were also enhanced. The discontinued sound impedance and reinforced stiffness were considered as crucial for the sound insulation.