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Water pollution has emerged as a significant worldwide issue, with organic pollutants being a key contributor. Titanium dioxide (TiO2) has demonstrated promising photocatalytic performance in removing organic pollutants under ultraviolet (UV) irradiation. However, the wide band gap (3.2 eV) of TiO2 results in low absorption capacity of visible light, hindering its overall efficiency in degrading organic pollutants. To address the limitation, this research aimed to synthesize visible light-driven TiO2 photocatalyst with different polymorphs (anatase and rutile) and investigate the effect of various doping combination (Nb, B and Nb,B) and concentrations (0.25, 0.50, 0.75 and 1.00 mol%) on the photodegradation efficiency towards methylene blue (MB) dye solution. Anatase phase was obtained when TiO2-based nanopowders were calcined at 400 °C, while the rutile phase was formed at 900 °C based on XRD analyses. Additionally, the morphology analyses revealed that the particle size of anatase is much smaller than that of rutile. The presence of dopants further reduced the particle size of both anatase and rutile phases. Based on UV-Vis absorbance spectra analyses, the anatase Nb,B-TiO2 with 0.50 mol% of dopant concentration exhibited the best photocatalytic performance towards MB. Moreover, the anatse phase of 0.50 mol% Nb,B-TiO2 showed the narrowest band gap of 2.74 eV compared to the TiO2 (3.4 eV), representing a reduction of 19.41 %, according to UV-Vis analyses. These outcomes suggest the potential application of anatase phase of 0.50 mol% Nb,B-TiO2 in treating organic pollutants in wastewater under visible light conditions in future. Copyright © 2024 by Authors, Published by BCREC Publishing Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).

Abstract Data sources The Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2019. Background To describe burden, and to explore cross-country inequalities according to socio-demographic index (SDI) for stroke and subtypes attributable to diet. Methods Death and years lived with disability (YLDs) data and corresponding estimated annual percentage changes (EAPCs) were estimated by year, age, gender, location and SDI. Pearson correlation analysis was performed to evaluate the connections between age-standardized rates (ASRs) of death, YLDs, their EAPCs and SDI. We used ARIMA model to predict the trend. Slope index of inequality (SII) and relative concentration index (RCI) were utilized to quantify the distributive inequalities in the burden of stroke. Results A total of 1.74 million deaths (56.17% male) and 5.52 million YLDs (55.27% female) attributable to diet were included in the analysis in 2019.Between 1990 and 2019, the number of global stroke deaths and YLDs related to poor diet increased by 25.96% and 74.76% while ASRs for death and YLDs decreased by 42.29% and 11.34% respectively. The disease burden generally increased with age. The trends varied among stroke subtypes, with ischemic stroke (IS) being the primary cause of YLDs and intracerebral hemorrhage (ICH) being the leading cause of death. Mortality is inversely proportional to SDI (R = -0.45, p

Abstract CSF1R is a receptor tyrosine kinase responsible for the growth/survival/polarization of macrophages and overexpressed in some AML patients. We hypothesized that a novel multi-kinase inhibitor (TKi), narazaciclib (HX301/ON123300), with high potency against CSF1R (IC50 ~ 0.285 nM), would have anti-AML effects. We tested this by confirming HX301’s high potency against CSF1R (IC50 ~ 0.285 nM), as well as other kinases, e.g. FLT3 (IC50 of ~ 19.77 nM) and CDK6 (0.53 nM). An in vitro proliferation assay showed that narazaciclib has a high growth inhibitory effect in cell cultures where CSF1R or mutant FLT3-ITD variants that may be proliferation drivers, including primary macrophages (IC50 of 72.5 nM) and a subset of AML lines (IC50

Abstract Many organismal traits are genetically determined and covary in evolving populations. The resulting trait correlations can either help or hinder evolvability – the ability to bring forth new and adaptive phenotypes. The evolution of evolvability requires that trait correlations themselves must be able to evolve, but we know little about this ability. To learn more about it, we here study two evolvable systems, a yellow fluorescent protein and the antibiotic resistance protein VIM-2 metallo beta-lactamase. We consider two traits in the fluorescent protein, namely the ability to emit yellow and green light, and three traits in our enzyme, namely the resistance against ampicillin, cefotaxime, and meropenem. We show that correlations between these traits can evolve rapidly through both mutation and selection on short evolutionary time scales. In addition, we show that these correlations are driven by a protein’s ability to fold, because single mutations that alter foldability can dramatically change trait correlations. Since foldability is important for most proteins and their traits, mutations affecting protein folding may alter trait correlations mediated by many other proteins. Thus, mutations that affect protein foldability may also help shape the correlations of complex traits that are affected by hundreds of proteins.

To develop a unique flavor of rice wine, coffee flowers (by-products of the coffee industry) were added because of their biologically active compounds that are conducive to health, and the fermentation parameters were optimized. In addition, the dynamic changes of microbial communities and volatile flavor compounds (VFCs) during the different fermentation stages were investigated. After the optimization of the fermentation parameters, a novel product, i.e., the coffee flower rice wine (CFRW), was obtained with a bright yellow transparent, fragrant, and harmonious aroma and mellow and refreshing taste by sensory evaluation, when 4.62% of the coffee flowers and 1.93% koji were added and fermented at 24.10°C for 3.88 days. The results showed that Lactococcus was the dominant bacteria, accounting for 87.0–95.7%, while Rhizopus and Cladosporium were the main fungi, accounting for 68.2% and 11.3% on average, respectively, in the fermentation process of the CFRW. Meanwhile, twenty-three VFCs were detected in the CFRW, which included three alcohols, six terpenes, ten esters, three aromatics, and one furan. The correlation analysis revealed that there were 16 significant positive correlations and 23 significant negative correlations between the bacterium and VFCs (|ρ| > 0.6, p 0.6, p 0.6, p 0.6, p

Background: Coronary heart disease (CHD) is the most common cardiovascular disease facing human beings. Cardiac remodelling is an important pathological factor for the progression of heart failure (HF) after CHD. At present, Chinese medicine is widely used in the treatment of HF, but there are still some drugs lack of evidence-based and mechanism evidence. Multi-omics techniques can deep explore candidate pathogenic factors and construct gene regulatory networks.This trial is intended to evaluate the effect on Huoxin pill (HXP) in the treatment of HF after programmable communication interface (PCI). Meantime, multi-omics analysis technique will be used to target the fundamental pathological links of cardiac remodelling, so as to study the mechanism of HXP in the treatment of HF after PCI. Methods: This study is a randomized, double-blind, placebo-controlled trial. Sixty patients with HF undergoing PCI are recruited from the First Affiliated Hospital of Henan University of CM. All selected patients will be randomly attributed to receive conventional treatment + HXP or placebo. The packaging, dosage and smell of placebo and heart activating pill were identical. The primary outcome is NYHA cardiac function grade, while the secondary outcomes included Lee's HF score, exercise tolerance test, and quality of life evaluation. Additional indicators include cardiac ultrasound, electrocardiogram, 24-h dynamic electrocardiogram, myocardial injury indicators, and energy metabolism indicators. Discussion: This study may provide a new treatment option for patients with HF after PCI and provide evidence for the treatment of CHD and HF with HXP. Trial registration: 2023-10-08 registered in China Clinical Trial Registry, registration number ChiCTR2300076402.

BackgroundInteractions between the immune and metabolic systems may play a crucial role in the pathogenesis of metabolic syndrome-associated rheumatoid arthritis (MetS-RA). The purpose of this study was to discover candidate biomarkers for the diagnosis of RA patients who also had MetS.MethodsThree RA datasets and one MetS dataset were obtained from the Gene Expression Omnibus (GEO) database. Differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning algorithms including Least Absolute Shrinkage and Selection Operator (LASSO) regression and Random Forest (RF) were employed to identify hub genes in MetS-RA. Enrichment analysis was used to explore underlying common pathways between MetS and RA. Receiver operating characteristic curves were applied to assess the diagnostic performance of nomogram constructed based on hub genes. Protein−protein interaction, Connectivity Map (CMap) analyses, and molecular docking were utilized to predict the potential small molecule compounds for MetS-RA treatment. qRT-PCR was used to verify the expression of hub genes in fibroblast-like synoviocytes (FLS) of MetS-RA. The effects of small molecule compounds on the function of RA-FLS were evaluated by wound-healing assays and angiogenesis experiments. The CIBERSORT algorithm was used to explore immune cell infiltration in MetS and RA.ResultsMetS-RA key genes were mainly enriched in immune cell-related signaling pathways and immune-related processes. Two hub genes (TYK2 and TRAF2) were selected as candidate biomarkers for developing nomogram with ideal diagnostic performance through machine learning and proved to have a high diagnostic value (area under the curve, TYK2, 0.92; TRAF2, 0.90). qRT-PCR results showed that the expression of TYK2 and TRAF2 in MetS-RA-FLS was significantly higher than that in non-MetS-RA-FLS (nMetS-RA-FLS). The combination of CMap analysis and molecular docking predicted camptothecin (CPT) as a potential drug for MetS-RA treatment. In vitro validation, CPT was observed to suppress the cell migration capacity and angiogenesis capacity of MetS-RA-FLS. Immune cell infiltration results revealed immune dysregulation in MetS and RA.ConclusionTwo hub genes were identified in MetS-RA, a nomogram for the diagnosis of RA and MetS was established based on them, and a potential therapeutic small molecule compound for MetS-RA was predicted, which offered a novel research perspective for future serum−based diagnosis and therapeutic intervention of MetS-RA.

Key Clinical Message In previous reports, hypothyroidism, hypopituitrism, and hypogonadism were common endocrine causes of SCFE, but this is the first time that congenital adrenal hyperplasia has been observed. As such, patients who have undergone long‐term endocrine treatment for congenital adrenal hyperplasia could potentially be subjected to a higher risk for SCFE.

Summary: Maternal obesity has long-term effects on offspring metabolic health. Among the potential mechanisms, prior research has indicated potential disruptions in circadian rhythms and gut microbiota in the offspring. To challenge this hypothesis, we implemented a maternal high fat diet regimen before and during pregnancy, followed by a standard diet after birth. Our findings confirm that maternal obesity impacts offspring birth weight and glucose and lipid metabolisms. However, we found minimal impact on circadian rhythms and microbiota that are predominantly driven by the feeding/fasting cycle. Notably, maternal obesity altered rhythmic liver gene expression, affecting mitochondrial function and inflammatory response without disrupting the hepatic circadian clock. These changes could be explained by a masculinization of liver gene expression similar to the changes observed in polycystic ovarian syndrome. Intriguingly, such alterations seem to provide the first-generation offspring with a degree of protection against obesity when exposed to a high fat diet.

Abstract Since the origin of life, temperatures on earth have fluctuated both on short and long time scales. How such changes affect the rate at which Darwinian evolution can bring forth new phenotypes remains unclear. On the one hand, high temperature may accelerate phenotypic evolution because it accelerates most biological processes. On the other hand, it may slow phenotypic evolution, because proteins are usually less stable at high temperatures and therefore less evolvable. Here, to test these hypotheses experimentally, we evolved a green fluorescent protein in E. coli towards the new phenotype of yellow fluorescence at different temperatures. Yellow fluorescence evolved most slowly at high temperature and most rapidly at low temperature, in contradiction to the first hypothesis. Using high-throughput population sequencing, protein engineering, and biochemical assays, we determined that this is due to the protein-destabilizing effect of neofunctionalizing mutations. Destabilization is highly detrimental at high temperature, where neofunctionalizing mutations cannot be tolerated. Their detrimental effects can be mitigated through excess stability at low temperature, leading to accelerated adaptive evolution. By modifying protein folding stability, temperature alters the accessibility of mutational paths towards high-fitness genotypes. Our observations have broad implications for our understanding of how temperature changes affect evolutionary adaptations and innovations.

Abstract Butyric acid is a volatile saturated monocarboxylic acid, which is widely used in the chemical, food, pharmaceutical, energy, and animal feed industries. This study focuses on producing butyric acid from pre-treated rape straw using simultaneous enzymatic hydrolysis semi-solid fermentation (SEHSF). Clostridium beijerinckii BRM001 screened from pit mud of Chinese nongxiangxing baijiu was used. The genome of C. beijerinckii BRM001 was sequenced and annotated. Using rape straw as the sole carbon source, fermentation optimization was carried out based on the genomic analysis of BRM001. The optimized butyric acid yield was as high as 13.86 ± 0.77 g/L, which was 2.1 times higher than that of the initial screening. Furthermore, under optimal conditions, non-sterile SEHSF was carried out, and the yield of butyric acid was 13.42 ± 0.83 g/L in a 2.5-L fermentor. This study provides a new approach for butyric acid production which eliminates the need for detoxification of straw hydrolysate and makes full use of the value of fermentation waste residue without secondary pollution, making the whole process greener and more economical, which has a certain industrial potential. Graphical Abstract

Timely and accurate monitoring of large-scale crop harvest progress (CHP) is crucial for optimizing agricultural management. Remote sensing shows great potential, but most studies focus on small-scale analysis with limited features and single data sources, lacking large-area mapping. To address this, we developed a regional-scale CHP monitoring framework combining optical and radar data. We analyzed the response of features to corn harvest at Youyi Farm. We developed new indices and algorithms, achieving large-scale CHP mapping. Our findings: First, all 15 features respond to harvest, with shortwave infrared reflectance and the vegetation tillage index (VTI) being the most sensitive. Second, the current binary classification algorithm for mature corn (MC) and crushed straw (CS) is unsuitable for regions with plowed soil (PS). It often misclassifies PS as MC due to similar optical characteristics, causing inaccurate corn harvest monitoring. The new VTI and simple VTI solve this by better distinguishing MC, CS, and PS. Third, corn harvest progress monitoring shows high accuracy, with an overall accuracy of 0.99 for optical data and 0.95 for radar data. Fourth, combining Sentinel-1 and Sentinel-2 data increased the monitoring frequency from 6–8 days to an average of 2–3 days. Fifth, a time-series misclassification correction strategy was developed and applied, correcting an average area of 3.3% of the study area. Sixth, an earlier harvest start time in 2021, aligned with drought occurrences, confirms the feasibility of the CHP mapping framework. This research provides an effective tool for monitoring CHP, which can support agricultural management.

Soil surface roughness (SSR) is an important factor affecting soil erosion and soil nutrient transport. Human tillage leads to increased instability in SSR, and the characteristics of SSR caused by different tillage practices await further study. This research utilizes terrestrial laser scanning (TLS) to measure the SSR of six farmland plots (25 m × 25 m) and analyzes the characteristics of SSR under different tillage practices (plowing, harrowing, ridging, crusting, etc.). The study results show: 1) Different agricultural tillage practices lead to significant differences in SSR. The plowed and harrowed plot corresponds to the maximum (2.49 cm) and minimum (1.5 cm) root mean square height (RMSH), respectively. Correlation length (CL) is more affected by different tillage practices than RMSH. The difference in CL between the ridged and harrowed plot is 2.6 times. 2) Ridging and crusting caused significant directional variation in SSR. The SSR anisotropy of the harrowed plot can be disregarded. 3) Under the condition of measuring soil profile in 12 directions and randomly sampling 70 times in each direction, the profile length must be at least 3 m to ensure that the measurement error of SSR is better than 5% compared to the “true” value. TLS can measure two-dimensional SSR. Therefore, it is only necessary to ensure that the measurement range is at least 3 m × 3 m. The study results provide a reference for the high-precision measurement of SSR (RMSH and CL) under different agricultural tillage practices.

Synthetic aperture radar (SAR) target classification methods based on convolutional neural networks (CNNs) are susceptible to overfitting due to limited samples. In addition, the position and deformation variations of SAR targets can also affect the feature extraction capabilities of CNN. To address these issues, this article proposes a novel few-shot learning (FSL) method, called position-aware graph neural network (PA-GNN). The PA-GNN introduces a PAM to enhance the feature representation of the target. Specifically, deformable convolution is incorporated into the embedding network to accommodate the various shapes of SAR targets. Then, the self-attention network is brought in to capture the spatial dependence of any two positions in the feature maps, and the cross-attention network calculates the cross-attention between support and query feature maps to handle the problem of unseen categories. These two attention networks can be exploited to highlight the target regions. Besides, to integrate the features extracted by these two attention networks, an adaptive feature fusion module is designed to obtain discriminative features of the target position. The PA-GNN conducts measurement by constructing multiple layers of GNN and utilizes residual learning to alleviate oversmoothing. Furthermore, we introduce a fused loss to enhance the separability between different categories and the similarity within the same category. Experiments on OpenSARShip and MSTAR datasets demonstrate that the proposed PA-GNN can achieve comparable classification results compared with other FSL algorithms.

Osteoarthritis (OA) is a progressive degenerative disease resulting in joint deterioration. It is a whole organ disease characterized by cartilage degeneration and varying degrees of synovitis, involving pathological changes in all joint tissues, such as cartilage, subchondral bone, ligaments, meniscus, synovium, and infrapatellar fat pad (IPFP). IPFP is the largest adipose tissue structure in the knee joint and is composed of fat cells, immune cells and blood vessels. Moreover, IPFP is located close to the cartilage and bone surface so that it may reduce the impact of loading and absorb forces generated through the knee joint, and may have a protective role in joint health. IPFP has been shown to release various cytokines and adipokines that play pro-inflammatory and pro-catabolic roles in cartilage, promoting OA progression. Intra-articular injections of IPFP-derived mesenchymal stem cells and exosomes have been shown to reduce pain and prevent OA progression in patients with knee OA. Previous studies have shown that IPFP has a biphasic effect on OA progression. This article reviews the latest research progress of IPFP, discusses the role and mechanism of IPFP in OA, provide new intervention strategies for the treatment of OA. This article will also discuss the handling of IPFP during the procedure of total knee arthroplasty.

Abstract Parents confront multiple aspects of offspring demands and need to coordinate different parental care tasks. Biparental care is considered to evolve under circumstances where one parent is not competent for all tasks and cannot efficiently raise offspring. However, this hypothesis is difficult to test, as uniparental and biparental care rarely coexist. Chinese penduline tits (Remiz consobrinus) provide such a system where both parental care types occur. Here, we experimentally investigated whether parents in biparental nests are less capable of caring than parents in uniparental nests. We monitored parenting efforts at (1) naturally uniparental and biparental nests and (2) biparental nests before and during the temporary removal of a parent. Given the relatively small sample sizes, we have employed various statistical analyses confirming the robustness of our results. We found that total feeding frequency and brooding duration were similar for natural uniparental and biparental nests. Feeding frequency, but not brooding duration, contributed significantly to nestling mass. In line with this, a temporary parental removal revealed that the remaining parents at biparental nests fully compensated for the partner's feeding absence but not for brooding duration. This reflects that the manipulated parents are confronted with a trade‐off between feeding and brooding and were selected to invest in the more influential one. However, such a trade‐off may not occur in parents of natural uniparental care nests. The different capabilities of a parent independently coordinating feeding and brooding tasks suggest that parents from biparental and uniparental nests were exposed to different resource conditions, thereby foraging efficiency may differ between care types.

The igfbp family proteins are key regulators of the biological activities of igfs, which play a pivotal role in controlling growth. Growth is highly variable between different fish species and even between growth stages and sexes within the same fish species. For determining the igfbps significantly associated to growth, we identified igfbp genes from the whole-wide genomes of mandarin fish Siniperca chuatsi and big-eye mandarin fish Siniperca kneri, and detected their expression profiles under different growth conditions. The results revealed that: 1) both mandarin fish and big-eye mandarin fish have 10 igfbp family members (igfbp-1a/b, igfbp-2a/b, igfbp-3, igfbp−4, igfbp-5a/b, and igfbp-6a/b), which are highly conserved among igfbp family members; 2) in early development, the expression of igf1 mRNA showed an increasing trend, igfbp-1a/b expression increased significantly with development and the expression trend was strongly similar to that of igf1; 3) variation of body sizes in adult revealed a strong correlation between the serum Gh content and igf1 mRNA expression level in the liver, and the expression levels of hepatic igfbp-2a/b, -4 showed a positive correlation; 4) serum Gh levels and the relative expression of hepatic igf1 mRNA were significantly higher in females than in males, the fold change in igfbp-1a in muscle, -2a, -5a in liver mRNA expression was strongly similar to that of igf1; 5) variation of the interspecific growth showed that the expression of serum Gh and hepatic igf1 mRNA in mandarin fish was significantly higher than that in big-eye mandarin fish. The expression of igfbps mRNA in mandarin fish was significantly higher than that in big-eye mandarin fish, except for igfbp-2a/2b in muscle and igfbp-6a in liver. Taken together, our results suggest that the different effects on growth of mandarin fish are regulated by the actions of different igfbps, where igfbp-1a/b, -2a/b, -4 and -5a may be a candidate for growth rate difference studies. The inherently low expression of Gh, igf1, and igfbps might have contributed to the slow growth of big-eye mandarin fish.

Abstract Background The death burden attributable to modifiable risk factors is key to colorectal cancer (CRC) prevention. This study aimed to assess the prevalence and regional distribution of attributable CRC death burden worldwide from 1990 to 2019. Methods We extracted data from the Global Burden of Disease Study in 2019 and assessed the mortality, age‐standardized death rate (ASDR), population attributable fractions, and time trend in CRC attributable to risk factors by geography, socio‐demographic index (SDI) quintile, age, and sex. Results Over the past 30 years, from high to low SDI region, the number of deaths increased by 46.56%, 103.55%, 249.64%, 231.89%, 163.11%, and the average annual percentage change (AAPC) for ASDR were −1.06%, −0.01%, 1.32%, 1.19%, and 0.65%, respectively. ASDR in males was 1.88 times than in females in 2019; ASDR in males showed an increasing trend (AAPC 0.07%), whereas ASDR in females showed a decreasing trend (AAPC −0.69%) compared to figures in 1990. In 2019, from high to low SDI region, the 15–49 age group accounted for 3%, 6%, 10%, 11%, and 15% of the total population; dietary and metabolic factors contributed 43.4% and 20.8% to CRC‐attributable death worldwide. From high to low SDI region, ASDRs caused by dietary and metabolic factors increased by −23.4%, −5.5%, 25.8%, 29.1%, 13.5%, and 1.4%, 33.3%, 100.8%, 128.4%, 77.7% respectively, compared to 1990. Conclusions The attributable CRC death burden gradually shifted from higher SDI to lower SDI regions. The limitation in males was more significant, and the gap is expected to be further expanded. In lower SDI regions, the death burden tended to affect younger people. The leading cause of CRC‐attributable deaths was the inadequate control of dietary and metabolic risk factors.

Abstract The signal in the receiver is mainly a combination of different modulation types due to the complex electromagnetic environment, which makes the modulation recognition of the mixed signal a hot topic in recent years. In response to the poor adaptability of existing mixed signals recognition methods, this paper proposes a new recognition method for mixed signals based on cyclic spectrum projection and deep neural network. Firstly, through theoretical derivation, we prove the feasibility of using cyclic spectrum for mixed communication signal identification. Then, we adopt grayscale projections on the two-dimensional cyclic spectrum as identifying representation. And a new nonlinear piecewise mapping and directed pseudo-clustering method are used to enhance the above-mentioned grayscale images, which reduces the impact of energy ratios and symbol rates on signal identification. Finally, we use deep neural networks to extract deep abstract modulation information to achieve effective recognition of mixed signals. Simulation results show that the proposed method is robust against noise. When signal-to-noise ratio is not less than 0 dB, the average recognition rate is greater than 95%. Furthermore, this method exhibits good robustness towards the changes in signal symbol rates and energy ratios between mixed signals.

Abstract Background The triglyceride-glucose (TyG) index is a predictor of cardiovascular diseases; however, to what extent the TyG index is associated with cardiovascular diseases through renal function is unclear. This study aimed to evaluate the complex association of the TyG index and renal function with cardiovascular diseases using a cohort design. Methods This study included participants from the China Health and Retirement Longitudinal Study (CHARLS) free of cardiovascular diseases at baseline. We performed adjusted regression analyses and mediation analyses using Cox models. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Renal function was defined by the estimated glomerular filtration rate (eGFR). Results A total of 6 496 participants were included in this study. The mean age of the participants was 59.6 ± 9.5 years, and 2996 (46.1%) were females. During a maximum follow-up of 7.0 years, 1 996 (30.7%) people developed cardiovascular diseases, including 1 541 (23.7%) cases of heart diseases and 651 (10.0%) cases of stroke. Both the TyG index and eGFR level were significantly associated with cardiovascular diseases. Compared with people with a lower TyG index (median level) and eGFR ≥ 60 ml/minute/1.73 m2, those with a higher TyG index and decreased eGFR had the highest risk of cardiovascular diseases (HR, 1.870; 95% CI 1.131–3.069). Decreased eGFR significantly mediated 29.6% of the associations between the TyG index and cardiovascular diseases. Conclusions The combination of a higher TyG index and lower eGFR level was associated with the highest risk of cardiovascular diseases. Renal function could mediate the association between the TyG index and cardiovascular risk.

In this study, an in-depth analysis of the microstructure and hardness of 6082 aluminum alloy under a novel solution-forging integrated process was conducted by performing a series of isothermal uniaxial compression tests at various strain rates and aging durations. The results indicated that the highest hardness was 125.0 ± 1.2 HV at peak aging with a forming strain rate of 10 s−1; a 16.1% improvement compared to the conventional T6 forming process. The deformation reduced the subsequent peak aging time from 8 h in the conventional process to 6 h. In addition, the composite phases, including short-range disordered B'/U2 phase and composite phase with multiple structures, were also observed under a strain rate of 10 s−1 with 6 h of aging. As the strain rate increased, the grain size increased, accompanied by an increase in dislocation density. For the integrated process, the deformation microstructure would inherit to the aging state and affect the precipitation kinetics during aging, including grain morphology, dislocation density, and the aging precipitated phase, especially for the formation of composite phase; these were the main reasons for the higher hardness after ageing when compared to the hardness of the alloy under traditional T6 state.

Solanum nigrum is a cadmium (Cd) and zinc (Zn) accumulator with potential for phytoextraction of soil contaminated with heavy metals. However, how Zn affects Cd accumulation in S. nigrum remains unclear. In this study, S. nigrum seedlings were treated with 100 μmol·L−1 Zn (Zn100), 100 μmol·L−1 Cd (Cd100), and the Zn and Cd combination (Zn100+Cd100) for 10 days under hydroponic culture. Compared with Cd100, the Cd content in stems, leaves, and xylem saps was 1.8, 1.6, and 1.3 times more than that in Zn100+Cd100, respectively. In addition, the production of reactive oxygen species in leaves was significantly upregulated in Cd100 compared with the control, and it was downregulated in Zn100. Comparative analyses of transcriptomes and proteomes were conducted with S. nigrum leaves. Differentially expressed genes (DEGs) were involved in Cd uptake, transport, and sequestration, and the upregulation of some transporter genes of Zn transporters (ZIPs), a natural resistance associated macrophage protein (Nramp1), a metal–nicotianamine transporter (YSL2), ATP-binding cassette transporters (ABCs), oligopeptide transporters (OPTs), and metallothionein (MTs) and glutathione S-transferase (GSTs) genes was higher in Zn100+Cd100 than in Cd100. In addition, differentially expressed proteins (DEPs) involved in electron transport chain, ATP, and chlorophyll biosynthesis, such as malate dehydrogenases (MDHs), ATPases, and chlorophyll a/b binding proteins, were mostly upregulated in Zn100. The results indicate that Zn supplement increases Cd accumulation and tolerance in S. nigrum by upregulating ATP-dependent Cd transport and sequestration pathways.

The consistent speckle noise in SAR images easily interferes with the semantic information of the target. Additionally, the limited quantity of supervisory information available in one-shot learning leads to poor performance. To address the aforementioned issues, we creatively propose an SAR target recognition model based on one-shot learning. This model incorporates a background noise removal technique to eliminate the interference caused by consistent speckle noise in the image. Then, a global and local complementary strategy is employed to utilize the data’s inherent a priori information as a supplement to the supervisory information. The experimental results show that our approach achieves a recognition performance of 70.867% under the three-way one-shot condition, which attains a minimum improvement of 7.467% compared to five state-of-the-art one-shot learning methods. The ablation studies demonstrate the efficacy of each design introduced in our model.

BackgroundPrevious studies have confirmed the separate effect of arterial stiffness and obesity on type 2 diabetes; however, the joint effect of arterial stiffness and obesity on diabetes onset remains unclear. ObjectiveThis study aimed to propose the concept of arterial stiffness obesity phenotype and explore the risk stratification capacity for diabetes. MethodsThis longitudinal cohort study used baseline data of 12,298 participants from Beijing Xiaotangshan Examination Center between 2008 and 2013 and then annually followed them until incident diabetes or 2019. BMI (waist circumference) and brachial-ankle pulse wave velocity were measured to define arterial stiffness abdominal obesity phenotype. The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% CI. ResultsOf the 12,298 participants, the mean baseline age was 51.2 (SD 13.6) years, and 8448 (68.7%) were male. After a median follow-up of 5.0 (IQR 2.0-8.0) years, 1240 (10.1%) participants developed diabetes. Compared with the ideal vascular function and nonobese group, the highest risk of diabetes was observed in the elevated arterial stiffness and obese group (HR 1.94, 95% CI 1.60-2.35). Those with exclusive arterial stiffness or obesity exhibited a similar risk of diabetes, and the adjusted HRs were 1.63 (95% CI 1.37-1.94) and 1.64 (95% CI 1.32-2.04), respectively. Consistent results were observed in multiple sensitivity analyses, among subgroups of age and fasting glucose level, and alternatively using arterial stiffness abdominal obesity phenotype. ConclusionsThis study proposed the concept of arterial stiffness abdominal obesity phenotype, which could improve the risk stratification and management of diabetes. The clinical significance of arterial stiffness abdominal obesity phenotype needs further validation for other cardiometabolic disorders.

Background: Energy-dissipating brown adipocytes have significant potential for improving systemic metabolism. Vanin-1, a membrane-bound pantetheinase, is involved in various biological processes in mice. However, its role in BAT mitochondrial function is still unclear. In this study, we aimed to elucidate the impact of Vanin-1 on BAT function and contribution during overnutrition-induced obesity. Methods: Vanin-1 expression was analyzed in different adipose depots in mice. The cellular localization of Vanin-1 was analyzed by confocal microscopy and western blots. Mice lacking Vanin-1 (Vanin-1−/−) were continuously fed either a chow diet or a high-fat diet (HFD) to establish an obesity model. RNA-seq analysis was performed to identify the molecular changes associated with Vanin-1 deficiency during obesity. BAT-specific Vanin-1 overexpression mice were established to determine the effects of Vanin-1 in vivo. Cysteamine treatment was used to examine the effect of enzymatic reaction products of Vanin-1 on BAT mitochondria function in Vanin-1−/− mice. Results: The results indicate that the expression of Vanin-1 is reduced in BAT from both diet-induced and leptin-deficient obese mice. Study on the subcellular location of Vanin-1 shows that it has a mitochondrial localization. Vanin-1 deficiency results in increased adiposity, BAT dysfunction, aberrant mitochondrial structure, and promotes HFD induced-BAT whitening. This is attributed to the impairment of the electron transport chain (ETC) in mitochondria due to Vanin-1 deficiency, resulting in reduced mitochondrial respiration. Overexpression of Vanin-1 significantly enhances energy expenditure and thermogenesis in BAT, renders mice resistant to diet-induced obesity. Furthermore, treatment with cysteamine rescue the mitochondrial dysfunction in Vanin-1−/− mice. Conclusions: Collectively, these findings suggest that Vanin-1 plays a crucial role in promoting mitochondrial respiration to counteract diet-induced obesity, making it a potential therapeutic target for obesity.

The cultivation of innovative talents in psychology requires experimental teaching as a key link. Based on the curriculum structure of psychology experimental teaching, this paper extracts the influencing factors of innovative talent cultivation and selects faculty supporting, teaching methods, teaching system, and innovation guarantee system as the antecedent variables of the fsQCA method. The analysis process of fsQCA for experimental teaching of psychology was oriented to achieve the reliability test based on Cronbach’s alpha coefficient, combined with principal component analysis to construct a direct data calibration method, and used the consistency score to test the relationship between independent and dependent variables. The factor loadings of each question item were above 0.62, the mean extracted variance of all variables was above 0.55, and the combined reliability values were all greater than 0.78, indicating that the convergent validity passed the test.

Abstract Background To develop and validate a multivariable risk prediction model for ketosis‐prone type 2 diabetes mellitus (T2DM) based on clinical characteristics. Methods A total of 964 participants newly diagnosed with T2DM were enrolled in the modeling and validation cohort. Baseline clinical data were collected and analyzed. Multivariable logistic regression analysis was performed to select independent risk factors, develop the prediction model, and construct the nomogram. The model's reliability and validity were checked using the receiver operating characteristic curve and the calibration curve. Results A high morbidity of ketosis‐prone T2DM was observed (20.2%), who presented as lower age and fasting C‐peptide, and higher free fatty acids, glycated hemoglobin A1c and urinary protein. Based on these five independent influence factors, we developed a risk prediction model for ketosis‐prone T2DM and constructed the nomogram. Areas under the curve of the modeling and validation cohorts were 0.806 (95% confidence interval [CI]: 0.760–0.851) and 0.856 (95% CI: 0.803–0.908). The calibration curves that were both internally and externally checked indicated that the projected results were reasonably close to the actual values. Conclusions Our study provided an effective clinical risk prediction model for ketosis‐prone T2DM, which could help for precise classification and management.

(AlCrTiZrMox)N coatings with varying Mo content were successfully prepared using a multi-target co-deposition magnetron sputtering system. The results reveal that the Mo content significantly affects the microstructure, hardness, fracture toughness, and tribological behavior of the coatings. As the Mo content in the coatings increases gradually, the preferred orientation changes from (200) to (111). The coatings consistently exhibit a distinct columnar structure. Additionally, the hardness of the coatings increases from 24.39 to 30.24 GPa, along with an increase in fracture toughness. The friction coefficient is reduced from 0.72 to 0.26, and the wear rate is reduced by 10 times. During the friction process, the inter-column regions of the coatings are initially damaged, causing the wear track to exhibit a wavy pattern. Greater frictional heat is generated at the crest of the wave, resulting in the formation of a MoO2 lubricating layer. The friction reaction helps to reduce the shear force during friction, demonstrating the lower friction coefficient of the (AlCrTiZrMox)N coatings. Both the hardness and fracture toughness work together to reduce the wear rate, and the (AlCrTiZrMox)N coatings show excellent wear resistance. Most notably, although the columnar structure plays a negative role in the hardness, it contributes greatly to the wear resistance.

Abstract Background Visceral obesity is associated with high cardiovascular events risk in type 2 diabetes mellitus (T2DM). Whether normal-weight visceral obesity will pose a higher atherosclerotic cardiovascular disease (ASCVD) risk than body mass index (BMI)-defined overweight or obese counterparts with or without visceral obesity remains unclear. We aimed to explore the relationship between general obesity and visceral obesity and 10-year ASCVD risk in patients with T2DM. Methods Patients with T2DM (6997) who satisfied the requirements for inclusion were enrolled. Patients were considered to have normal weight when 18.5 kg/m2 ≤ BMI

Due to Butylparaben (BuP) widespread application in cosmetics, food, pharmaceuticals, and its presence as an environmental residue, human and animal exposure to BuP is common, potentially posing hazards to both human and animal health. Congenital heart disease is already a serious problem. However, the effects of BuP on the developing heart and its underlying mechanisms remain unclear. Here, zebrafish embryos were exposed to environmentally and human-relevant concentrations of BuP (0.6 mg/L, 1.2 mg/L, and 1.8 mg/L, calculated but not measured) at 6 h post-fertilization (hpf) and were treated until 72 hpf. Exposure to BuP led to cardiac morphological defects and cardiac dysfunction in zebrafish embryos, manifesting symptoms similar to systolic heart failure. The etiology of BuP-induced systolic heart failure in zebrafish embryos is multifactorial, including cardiomyocyte apoptosis, endocardial and atrioventricular valve damage, insufficient myocardial energy, impaired Ca2+ homeostasis, depletion of cardiac-resident macrophages, cardiac immune non-responsiveness, and cardiac oxidative stress. However, excessive accumulation of reactive oxygen species (ROS) in the cardiac region and cardiac immunosuppression (depletion of cardiac-resident macrophages and cardiac immune non-responsiveness) may be the predominant factors. In conclusion, this study indicates that BuP is a potential hazardous substance that can cause adverse effects on the developing heart and provides evidence and insights into the pathological mechanisms by which BuP leads to cardiac dysfunction. It may help to prevent the BuP-based congenital heart disease heart failure in human through ameliorating strategies and BuP discharge policies, while raising awareness to prevent the misuse of preservatives.

Baijiu, deeply entrenched in the Chinese food industry, is revered as the nation's quintessential liquor. Among the various attributes of Baijiu, sweetness serves a pivotal role in defining the overall flavor of this beverage. The perception of sweetness can be partially attributed to the amalgamation of volatile and non-volatile compounds, with the brewing process playing a fundamental role in the establishment of this flavor characteristic. Sweetness perception also involves intricate conduction mechanisms within the gustatory system, necessitating a more profound understanding of sweetness from this neurophysiological perspective. Therefore, this review consolidates knowledge about sweetness-related compounds, sensory perception mechanisms and their effects on consumer preference and demand for Baijiu. Moreover, the application of extraction methodologies and detection techniques utilized for the verification and assessment of volatile and non-volatile compounds in Baijiu will be addressed. Future focus is expected to shift towards unraveling dynamic mechanisms of sweetness alteration and metabolic regulation during the brewing of Baijiu, thereby equipping future research on Baijiu flavor with a robust reference framework.

Background and aimsDyslipidemia is known to contribute to arterial stiffness, while the inverse association remains unknown. This study aimed to explore the association of baseline arterial stiffness and its changes, as determined by brachial-ankle pulse wave velocity (baPWV), with dyslipidemia onset in the general population.MethodsThis study enrolled participants from Beijing Health Management Cohort using measurements of the first visit from 2012 to 2013 as baseline, and followed until the dyslipidemia onset or the end of 2019. Unadjusted and adjusted Cox proportional regression models were used to evaluate the associations of baseline baPWV and baPWV transition (persistent low, onset, remitted and persistent high) with incident dyslipidemia.ResultsOf 4362 individuals (mean age: 55.5 years), 1490 (34.2%) developed dyslipidemia during a median follow-up of 5.9 years. After adjusting for potential confounders, participants with elevated arterial stiffness at baseline had an increased risk of dyslipidemia (HR, 1.194; 95% CI, 1.050-1.358). Compared with persistent low baPWV, new-onset and persistent high baPWV were associated with a 51.2% and 37.1% excess risk of dyslipidemia.ConclusionThe findings indicated that arterial stiffness is an early risk factor of dyslipidemia, suggesting a bidirectional association between arterial stiffness and lipid metabolism.

PurposeThyroid hormones sensitivity is a newly proposed clinical entity closely related with metabolic health. Prior studies have reported the cross-sectional relationship between thyroid hormones sensitivity and diabetes; however, the longitudinal association is unclear to date. We aimed to explore the relationship between impaired thyroid hormone sensitivity at baseline and diabetes onset using a cohort design.MethodsThis study enrolled 7283 euthyroid participants at the first visit between 2008 and 2009, and then annually followed until diabetes onset or 2019. Thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) were measured to calculate thyroid hormone sensitivity by thyroid feedback quantile-based index (TFQI), Chinese-referenced parametric thyroid feedback quantile-based index (PTFQI), thyrotropin index (TSHI), thyrotroph thyroxine resistance index (TT4RI) and FT3/FT4 ratio. Cox proportional hazard model and cross-lagged panel analysis were used.ResultsThe mean baseline age was 44.2 ± 11.9 years, including 4170 (57.3%) male. During a median follow-up of 5.2 years, 359 cases developed diabetes. There was no significant association between thyroid hormones sensitivity indices and diabetes onset, and adjusted hazard ratios per unit (95% CIs) were 0.89 (0.65-1.23) for TFQI, 0.91 (0.57-1.45) for PTFQI, 0.95 (0.70-1.29) for TSHI, 0.98 (0.70-1.01) for TT4RI and 2.12 (0.17-5.78) for FT3/FT4 ratio. Cross-lagged analysis supported the temporal association from fasting glucose to impaired thyroid hormones sensitivity indices.ConclusionsOur findings could not demonstrate that thyroid hormones sensitivity status is a predictor of diabetes onset in the euthyroid population. Elevated fasting glucose (above 7.0 mmol/L) appeared to precede impaired sensitivity indices of thyroid hormones.

Phasic small interfering RNAs are plant secondary small interference RNAs that typically generated by the convergence of miRNAs and polyadenylated mRNAs. A growing number of studies have shown that miRNA-initiated phasiRNA plays crucial roles in regulating plant growth and stress responses. Experimental verification of miRNA-initiated phasiRNA loci may take considerable time, energy and labor. Therefore, computational methods capable of processing high throughput data have been proposed one by one. In this work, we proposed a predictor (DIGITAL) for identifying miRNA-initiated phasiRNAs in plant, which combined a multi-scale residual network with a bi-directional long-short term memory network. The negative dataset was constructed based on positive data, through replacing 60% of nucleotides randomly in each positive sample. Our predictor achieved the accuracy of 98.48% and 94.02% respectively on two independent test datasets with different sequence length. These independent testing results indicate the effectiveness of our model. Furthermore, DIGITAL is of robustness and generalization ability, and thus can be easily extended and applied for miRNA target recognition of other species. We provide the source code of DIGITAL, which is freely available at https://github.com/yuanyuanbu/DIGITAL.

Porosity is one of the important characteristics reflecting the microstructure of loess and directly affects the physical and mechanical properties of loess, such as water sensitivity, permeability and strength. To study the micropore structure characteristics of loess under hydraulic coupling, micro CT technology was used to scan the initial structure of natural undisturbed, undisturbed saturated and remolded loess and the soil structure after unconsolidated-undrained shear tests. The evolution characteristics of the pore structure before and after shear tests are analyzed through the three-dimensional structure model of loess. The results show that the pore structures of the natural undisturbed loess, the saturated undisturbed loess and the remolded loess are significantly different, and the pore structures of the samples have a significant impact on the shear failure process. The process of saturation and remodeling can reduce the macropores of undisturbed soil.Shear stress can cause shear failure of natural undisturbed and remolded loess, compression failure of undisturbed saturated loess, and the increases of local porosity. The natural undisturbed and undisturbed saturated loess show a large number of micropores and small pores before and after shear, and the pore dip angle is mainly distributed between 50°-90°, which explains the main reason for the formation of the metastable structure of loess. The remodeled loess has a uniform pore size distribution due to the disturbance effect, and the remodeled and saturated loess is more prone to buckling and yielding under hydraulic action. It is revealed that the microstructure of shear deformation and failure of loess is mainly manifested in the dissolution of intergranular cement, the collapse and filling of pores, and the rotation, fragmentation and slip of particles. The test results can provide a basis for the mechanism of shear strength reduction and collapsibility of loess.

Abstract Uncontrolled microglial activation is pivotal to the pathogenesis of Parkinson’s disease (PD), which can secrete Cathepsin L (CTSL) to affect the survival of neurons in the PD patients; however, the precise mechanism has yet to be determined. We demonstrated for the first time that CTSL was mostly released by exosomes derived from α-Syn-activated microglia, resulting in neuronal damage and death. The elevation of CTSL activity was blocked by GW4869, suggesting a critical role for exosomes in mediating CTSL release. Furthermore, the P2X7R/PI3K/AKT signalling pathway was identified as the underlying molecular mechanism since specific antagonists of this signalling pathway, P2X7R knockdown and exosome release inhibitors significantly reduced the injury to cultured mouse cortical neurons. Our study suggests that increased extracellular release of CTSL from α-Syn-activated microglia through exosomes amplifies and aggravates of the neurotoxic effect of microglia, implying that CTSL may be involved in a fresh mechanism of PD pathogenesis, and serve as a potential biomarker and a target for PD drug development.

Regulatory elements in DNA sequences, such as promoters, enhancers, terminators and so on, are essential for gene expression in physiological and pathological processes. A promoter is the specific DNA sequence that is located upstream of the coding gene and acts as the "switch" for gene transcriptional regulation. Lots of promoter predictors have been developed for different bacterial species, but only a few are designed for Pseudomonas aeruginosa, a widespread Gram-negative conditional pathogen in nature. In this work, an ensemble model named SPREAD is proposed for the recognition of promoters in Pseudomonas aeruginosa. In SPREAD, the DNA sequence autoencoder model LSTM is employed to extract potential sequence information, and the mean output probability value of CNN and RF is applied as the final prediction. Compared with G4PromFinder, the only state-of-the-art classifier for promoters in Pseudomonas aeruginosa, SPREAD improves the prediction performance significantly, with an accuracy of 0.98, recall of 0.98, precision of 0.98, specificity of 0.97 and F1-score of 0.98.

Abstract Wuliangye‐flavor liquor (WLFL), a specific Chinese traditional liquor, one of the major type of global distilled spirits, offers a unique flavor system acquired across thousands of years of development. Free amino acids (FAAs), as major health factors, are considered to be primarily derive from the hydrolysis of protein from the Zaopeis (ZPs) by microbial populations during fermentation. Here, we investigated the changes of microbial communities in ZPs and FAAs in raw liquor (RL) directly related ZPs from different ages of WLFL fermentation pits by phospholipid fatty acid fingerprint (PLFA) and high performance liquid chromatography method. Results indicated that the total PLFAs of 20‐ and 50‐year ZPs were significantly higher (p 1; p

A novel polysaccharide, HSP80-2, with an average molecular weight of 13.8 kDa, was successfully isolated by the gradient ethanol precipitation (GEP) method from Huangshui (HS), the by-product of Chinese Baijiu. It was mainly composed of arabinose, xylose, and glucose with a molar ratio of 4.0:3.1:2.4, which was completely different from the previous reported HS polysaccharides (HSPs). Morphological observations indicated that HSP80-2 exhibited a smooth but uneven fragmented structure. Moreover, HSP80-2 exerted prebiotic activity evaluated by in vitro fermentation. Specifically, HSP80-2 was utilized by gut microbiota, and significantly regulated the composition and abundance of beneficial microbiota such as Phascolarctobacterium, Parabacteroides, and Bacteroides. Notably, KEGG pathway enrichment analysis illustrated that HSP80-2 enriched the pathways of amino sugar and nucleotide sugar metabolism (Ko00520), galactose metabolism (ko00052), and the citrate cycle (TCA cycle) (ko00020). Meanwhile, the contents of short-chain fatty acids (SCFAs) mainly including acetic acid, propionic acid, and butyric acid in the HSP80-2 group were remarkably increased, which was closely associated with the growth of Lachnoclostridium and Parabacteroides. These results showed that HSP80-2 might be used as a potential functional factor to promote human gut health, which further extended the high value utilization of HS.

A straightforward and convenient protocol was established for the synthesis of thiophosphates and 3-sulfenylated indoles via low-valent-tungsten-catalyzed aerobic oxidative cross-dehydrogenative coupling reactions. These reactions occur under mild conditions and simple operations with commercially available starting materials, processing the advantage of excellent atom and step economy, broad substrate scope, and good functional groups tolerance. Moreover, this transformation could be practiced on the gram scale, which exhibits great potential in the preparation of drug-derived or bioactive molecules.

Chorea is a movement disorder involving involuntary movements of muscles of the face, neck, and limbs, usually caused by basal ganglia lesions. As an important part of the presentation of many neurological diseases, chorea is also an unusual manifestation of endocrine diseases and can be challenging to diagnose. Although the most common etiology of chorea is genetic, it is vital to identify acquired or symptomatic chorea, as these are potentially treatable conditions. This review summarizes the latest developments in various endocrine disease-related chorea, which will help clinicians to correctly identify and accurately treat it.

BackgroundSingle nucleotide polymorphisms (SNPs) interfere with the function of certain genes and thus may influence the probability of skin cancer. The correlation between SNPs and skin cancer (SC) lacks statistical power, however. Therefore, the purpose of this study was to identify the gene polymorphisms involved in skin cancer susceptibility using network meta-analysis and to determine the relationship between SNPs and SC risk.MethodsPubMed, Embase, and Web of Science were searched for articles including “SNP” and different types of SC as keywords between January 2005 and May 2022. The Newcastle-Ottawa Scale was used to assess bias judgments. The odds ratio (ORs) and their 95% confidence intervals (CIs) were determined to estimate heterogeneity within and between studies. Meta-analysis and network meta-analysis were carried out to identify the SNPs associated with SC. The P-score of each SNP was compared to obtain the rank of probability. Subgroup analyses were performed by cancer type.ResultsA total of 275 SNPs from 59 studies were included in the study. Two subgroup SNP networks using the allele model and dominant model were analyzed. The alternative alleles of rs2228570 (FokI) and rs13181 (ERCC2) were the first-ranking SNPs in both subgroups one and two of the allele model, respectively. The homozygous dominant genotype and heterozygous genotype of rs475007 in subgroup one and the homozygous recessive genotype of rs238406 in subgroup two were most likely to be associated with skin cancer based on the dominant model.ConclusionsAccording to the allele model, SNPs FokI rs2228570 and ERCC2 rs13181 and, according to the dominant model, SNPs MMP1 rs475007 and ERCC2 rs238406 are closely linked to SC risk.

BackgroundThe exponential growth of the cancer burden attributable to metabolic factors deserves global attention. We investigated the trends of cancer mortality attributable to metabolic factors in 204 countries and regions between 1990 and 2019.MethodsWe extracted data from the Global Burden of Disease Study (GBD) 2019 and assessed the mortality, age-standardized death rate (ASDR), and population attributable fractions (PAFs) of cancers attributable to metabolic factors. Average annual percentage changes (AAPCs) were calculated to assess the changes in the ASDR. The cancer mortality burden was evaluated according to geographic location, SDI quintiles, age, sex, and changes over time.ResultsCancer attributable to metabolic factors contributed 865,440 (95% UI, 447,970-140,590) deaths in 2019, a 167.45% increase over 1990. In the past 30 years, the increase in the number of deaths and ASDR in lower SDI regions have been significantly higher than in higher SDI regions (from high to low SDIs: the changes in death numbers were 108.72%, 135.7%, 288.26%, 375.34%, and 288.26%, and the AAPCs were 0.42%, 0.58%, 1.51%, 2.36%, and 1.96%). Equatorial Guinea (AAPC= 5.71%), Cabo Verde (AAPC=4.54%), and Lesotho (AAPC=4.42%) had the largest increase in ASDR. Large differences were observed in the ASDRs by sex across different SDIs, and the male-to-female ratios of ASDR were 1.42, 1.50, 1.32, 0.93, and 0.86 in 2019. The core population of death in higher SDI regions is the age group of 70 years and above, and the lower SDI regions are concentrated in the age group of 50-69 years. The proportion of premature deaths in lower SDI regions is significantly higher than that in higher SDI regions (from high to low SDIs: 2%, 4%, 7%, 7%, and 9%). Gastrointestinal cancers were the core burden, accounting for 50.11% of cancer deaths attributable to metabolic factors, among which the top three cancers were tracheal, bronchus, and lung cancer, followed by colon and rectum cancer and breast cancer.ConclusionsThe cancer mortality burden attributable to metabolic factors is shifting from higher SDI regions to lower SDI regions. Sex differences show regional heterogeneity, with men having a significantly higher burden than women in higher SDI regions but the opposite is observed in lower SDI regions. Lower SDI regions have a heavier premature death burden. Gastrointestinal cancers are the core of the burden of cancer attributable to metabolic factors.

Fatty acid ethyl esters are important flavor chemicals in strong-flavor Baijiu. Monascus purpureus YJX-8 is recognized as an important microorganism for ester synthesis in the fermentation process. Enzyme LIP05 from YJX-8 can efficiently catalyze the synthesis of fatty acid ethyl esters under aqueous phase, but the key catalytic sites affecting esterification were unclear. The present work combined homology modeling, molecular dynamics simulation, molecular docking and site-directed mutation to analyze the catalytic mechanism of LIP05. Protein structure modeling indicated LIP05 belonged to α/β fold hydrolase, contained a lid domain and a core catalytic pocket with conserved catalytic triad Ser150-His215-Asp202, and the oxyanion hole composed of Gly73 and Thr74. Ile30 and Leu37 of the lid domain were found to affect substrate specificity. The π-bond stacking between Tyr116 and Tyr149 played an important role in stabilizing the catalytic active center of LIP05. Tyr116 and Ile204 determined the substrate spectrum by composing the substrate-entrance channel. Residues Leu83, Ile204, Ile211 and Leu216 were involved in forming the hydrophobic substrate-binding pocket through steric hindrance and hydrophobic interaction. The catalytic mechanism for esterification in aqueous phase of LIP05 was proposed and provided a reference for clarifying the synthesis of fatty acid ethyl esters during the fermentation process of strong-flavor Baijiu.

Abstract Aims/Introduction To explore the relationship between handgrip strength per weight (HGS/W), triglyceride glucose index (TyG) and diabetes, and whether lower HGS levels precede TyG in the Chinese elderly population. Materials and Methods Two linear regression models were used to explore the association of whether baseline HGS/W predicted follow‐up variation of TyG or baseline TyG predicted follow‐up variation of HGS/W. The logistic regression model was used to examine the relationship between baseline HGS/W and future diabetes. Results A total of 4,561 participants in the China Health and Retirement Longitudinal Study were enrolled, of which 47.0% were men, and the mean age was 58.7 years (standard deviation 8.68 years). A lower baseline HGS/W significantly correlated with a higher level of follow‐up TyG (β = −0.173, P = 0.002). The baseline level of HGS/W was significantly negatively associated with the incidence risk of diabetes (rate ratio 0.375, P = 0.004). However, in sex stratification, the statistical association between HGS/W and TyG and diabetes was only in men. Conclusions Our results showed that HGS/W was inversely associated with TyG and diabetes, and lower HGS/W levels preceded TyG levels in the elderly population. However, the effect was inconsistent between men and women, and the possible mechanism would require further clarification.

Usually asymmetric hydrogenation of olefins is enantiodivergent and thus requires isomerically pure olefins, which is a considerable drawback. Here, the authors show a general iridium-catalyzed enantioconvergent hydrogenation of a broad range of functionalized trisubstituted olefins.

As one of the most significant protein post-translational modifications (PTMs) in eukaryotes, ubiquitylation plays an essential role in regulating diverse cellular functions, such as apoptosis, cell division, DNA repair and replication, intracellular transport and immune reactions. Traditional experimental methods have the defect of being time-consuming, costly and labor-intensive. Therefore, it is highly desired to develop automated computational methods that can recognize potential ubiquitylation sites rapidly and accurately. In this study, we propose a novel predictor, named UPFPSR, for predicting lysine ubiquitylation sites in plant. UPFPSR is developed using multiple physicochemical properties of amino acids and sequence-based statistical information. In order to find a suitable classification algorithm, four traditional algorithms and two deep learning networks are compared, and the random forest with superior performance is selected ultimately. An extensive benchmarking shows that UPFPSR outperforms the most advanced ubiquitylation prediction tool on each measurement indicator, with the accuracy of 77.3%, precision of 75%, recall of 81.7%, F1-score of 0.7824, and AUC of 0.84 on the independent test dataset. The results indicate that UPFPSR can provide new guidance for further experimental study on ubiquitylation. The data sets and source code used in this study are freely available at https://github.com/ysw-sunshine/UPFPSR.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects millions of people worldwide. Positron emission tomography/magnetic resonance (PET/MR) imaging is a promising technique that combines the advantages of PET and MR to provide both functional and structural information of the brain. Deep learning (DL) is a subfield of machine learning (ML) and artificial intelligence (AI) that focuses on developing algorithms and models inspired by the structure and function of the human brain’s neural networks. DL has been applied to various aspects of PET/MR imaging in AD, such as image segmentation, image reconstruction, diagnosis and prediction, and visualization of pathological features. In this review, we introduce the basic concepts and types of DL algorithms, such as feed forward neural networks, convolutional neural networks, recurrent neural networks, and autoencoders. We then summarize the current applications and challenges of DL in PET/MR imaging in AD, and discuss the future directions and opportunities for automated diagnosis, predictions of models, and personalized medicine. We conclude that DL has great potential to improve the quality and efficiency of PET/MR imaging in AD, and to provide new insights into the pathophysiology and treatment of this devastating disease.

Intracerebral hemorrhage (ICH) is the most lethal type of stroke. Secondary injury from ICH determines the recovery, but there is still a lack of effective treatment. The identification of new therapeutic targets may address the current dilemma. The process of autophagy is mediated through the lysosomal pathway and is used to maintain cell homeostasis. Recent studies have advanced our knowledge of autophagy, and in particular its involvement in cell physiology and pathology. Autophagy involves multiple targets and signaling pathways and occurs in many brain cells. It also regulates oxidative stress and inflammation after ICH, both of which are important factors in secondary brain injury. An appropriate level of autophagy is protective in ICH, whereas excessive autophagy may be detrimental. In this review, we discuss the signaling pathways for autophagy in ICH and related factors that provide a theoretical basis for the discovery of new treatment targets.