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Abstract Nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme in cellular redox reactions, is closely associated with age-related functional degeneration and metabolic diseases. NAD exerts direct and indirect influences on many crucial cellular functions, including metabolic pathways, DNA repair, chromatin remodeling, cellular senescence, and immune cell functionality. These cellular processes and functions are essential for maintaining tissue and metabolic homeostasis, as well as healthy aging. Causality has been elucidated between a decline in NAD levels and multiple age-related diseases, which has been confirmed by various strategies aimed at increasing NAD levels in the preclinical setting. Ovarian aging is recognized as a natural process characterized by a decline in follicle number and function, resulting in decreased estrogen production and menopause. In this regard, it is necessary to address the many factors involved in this complicated procedure, which could improve fertility in women of advanced maternal age. Concerning the decrease in NAD+ levels as ovarian aging progresses, promising and exciting results are presented for strategies using NAD+ precursors to promote NAD+ biosynthesis, which could substantially improve oocyte quality and alleviate ovarian aging. Hence, to acquire further insights into NAD+ metabolism and biology, this review aims to probe the factors affecting ovarian aging, the characteristics of NAD+ precursors, and the current research status of NAD+ supplementation in ovarian aging. Specifically, by gaining a comprehensive understanding of these aspects, we are optimistic about the prominent progress that will be made in both research and therapy related to ovarian aging.

The flexible pressure sensor has been credited for leading performance including higher sensitivity, faster response/recovery, wider detection range and higher mechanical durability, thus driving the development of novel sensing materials enabled by new processing technologies. Using atomic layer infiltration, Pt nanocrystals with dimensions on the order of a few nanometers can be infiltrated into the compressible lamellar structure of Ti3C2Tx MXene, allowing a modulation of its interlayer spacing, electrical conductivity and piezoresistive property. The flexible piezoresistive sensor is further developed from the Pt-infiltrated MXene on a paper substrate. It is demonstrated that Pt infiltration leads to a significant enhancement of the pressure-sensing performance of the sensor, including increase of sensitivity from 0.08 ​kPa−1 to 0.5 ​kPa−1, extension of detection limit from 5 ​kPa to 9 ​kPa, decrease of response time from 200 ​ms to 20 ​ms, and reduction of recovery time from 230 ​ms to 50 ​ms. The mechanical durability of the flexible sensor is also improved, with the piezoresistive performance stable over 1000 cycles of flexure fatigue. The atomic layer infiltration process offers new possibilities for the structure modification of MXene for advanced sensor applications.

Abstract Background Estrogen receptor-positive and progesterone receptor-negative (ER + /PR-) breast cancer comprise a special type. More than 10% breast cancer patients belonged to ER + /PR-. Methods In order to better understand this patient population, we utilized a unique dataset from China, examining the clinicopathological features and genomic profiles of ER + /PR- breast cancers. Our study involved three cohorts: Cohort 1 included 2120 unselected ER-positive female patients with re-evaluated clinicopathological and survival data; Cohort 2 comprised 442 ER-positive females who underwent genetic testing; and Cohort 3 consisted of 77 ER-positive/HER2-negative females tested with MammaPrint and BluePrint. Results Patients were stratified into four categories based on the PR/ER ratio. Clinically, ER + /PR- tumors (PR/ER ratio = 0) showed the lowest proportion of T1 tumors (10.88%) and highest proportion of HER2-positive tumors (28.36%) than did other ER + /PR + tumors groups. The ER + /PR- group contained a higher number of underweight patients (20.20%). Independently of HER2 status, ER + /PR- patients demonstrated the poorest prognosis. Genomically, the most prevalent mutations were PIK3CA (50%) in ER + /PR + tumors and TP53 (65%) in ER + /PR- tumors. ER + /PR- tumors presented more frequent mutations in TP53, ERBB2, CDK12, SPEN, and NEB, with mutation rates of 65%, 42%, 27%, 13%, and 10%, respectively. Additionally, the Tumor Mutational Burden (TMB) was higher in the ER + /PR- group compared to the ER + /PR + group. The MammaPrint score for the ER + /PR-/HER2- group was significantly lower than that of other groups. In the BluePrint analysis, only four patients were classified as Basal-Type, all of whom were ER + /PR-/HER2-. Conclusions In this study, we identified the clinical and genetic characteristics of ER + /PR- breast cancer patients in China. Distinct PR statuses indicated different biological processes of ER + breast cancer and survival outcomes. Future treatment strategies may need to be tailored for ER + /PR- patients.

ABSTRACTHepatocellular carcinoma (HCC) is a frequently occurring malignant gastrointestinal cancer. The 5-year survival rate of HCC is still below 8%, and thus, identifying more effective therapeutic methods is needed. Here, we evaluated the effects of Stigmast-4-en-6β-ol-3-one (S463) on the viability and colony formation of liver cancer cells. S463 treatment decreased the viability and induced apoptosis and ferroptosis in liver cancer cells, and also increased cellular malondialdehyde (MDA) and lipid peroxidation levels. In S463 treated cells, the expression level of Bax was increased, and the expression level of GPX4 was reduced, and the cleavage of PARP was improved. We also found that S463 treatment downregulated E2F1 and upregulated p53 at both the mRNA and protein levels. Importantly, rescue experiments revealed that overexpression of E2F1 partially restored S463-induced Bax and p53 upregulation and GPX4 downregulation and counteracted the S463-induced decrease in cell viability and colony formation and the S463-induced increase in MDA and lipid peroxidation levels. Our findings suggest that S463 significantly inhibits viability and colony formation and induces apoptosis and ferroptosis in liver cancer cells via E2F1.

Urban population size dynamic adjustment has been widely studied for a long time; however, the dynamic adjustment at the urban hierarchy level remains unknown. This study utilises China’s urban population data to investigate the dynamic adjustment. Specifically, we utilise methods of the Gini coefficient, linear regression, and coefficients of Spearman, and Moran’s I to explore the dynamic adjustment tendency, adjustment rate and correlation of urban population size distribution of different urban hierarchies and groups of different urban hierarchies. We find that the urban population size spatial distribution is gradually even within the same urban hierarchy. The adjustment rate to be even of Megacity II is the highest, and Megacity I is the bottom. We also find the population size spatial distribution of the whole urban system is gradually uneven. We explore the dynamic process by sorting urban hierarchies into six groups. Furthermore, we find there is a complex correlation between different urban hierarchies and global spatial correlation among China cities. These results are valuable as references for Chinese policy-makers and practitioners and will enable them to adopt sustainable land use and urban population management measures. The study outcomes will also benefit future studies on spatial population size distribution in international communities.

Abstract As one of the most common ferrous (Fe2+)-containing oxide minerals in the Earth’s crust, ilmenite (FeTiO3) is a potential low-cost heterogeneous Fenton-like catalyst for organic wastewater treatment via catalytic wet peroxide oxidation (CWPO). However, it suffers from low activity and long induction time. Herein anisotropic FeTiO3/C nanocomposite with rich Fe2+ ions on large surface area of 159.0 m2 g−1 (surface Fe/Ti and Fe2+/Fe3+ ratios were respectively 2.1 and 2.0) was prepared via cetyltrimethylammonium (CTA+)-assisted sol-gel synthesis. CTA+ modulated the growth of FeTiO3 nanoparticles with more exposed metallic sites by preferential adsorption on its (104) plane via electrostatic attraction, provided the carbon source and facilitated the generation of more Fe2+ ions at the interface of FeTiO3/C via carbothermal reduction of FeTiO3. FeTiO3/C efficiently catalyzed CWPO removal of six aromatic pollutants with different charges (25 mg L−1 each) at 25 oC and pH 3.0 without an induction period owing to rich Fe2+ content on neutral surface (pHpzc ~3.3)—three dye solutions completely decolorized in 1 h and three antibiotics degraded by >90% in 3 h. Reusability of FeTiO3/C was demonstrated with cationic rhodamine B and anionic orange G dyes in five consecutive runs. Scavenging tests and spin-trapping EPR spectra confirmed the generation of dominant ·OH and minor O2 •− species for organic degradation via catalytic decomposition of H2O2 on FeTiO3/C as a heterogeneous Fenton-like catalyst.

This research examines the content as well as underlying psychological motives of ideology in East Asia. Adopting a mixed methods approach utilizing data from national samples in mainland China (N = 509) and Taiwan (N = 417), qualitative content analysis and correlation analysis results reveal that in both samples: (a) overall, participants had some understanding of the left-right ideological spectrum; (b) notwithstanding, most participants placed themselves at the Center; and (c) elective affinities between epistemic motives and political ideology exhibited the most consistent association. Findings shed light on the political psychology of ideology in authoritarian regimes as well as in new democracies. Findings were also discussed in the cross-cultural psychological context. Altogether, they contribute to our understanding of the nature of ideology beyond the West, which could be a first step toward reducing political polarization and avoiding conflict.

PLCPs (papain-like cysteine proteases) are one of the most abundant groups of cysteine proteases and play vital roles in multiple processes. The pepper (Capsicum annuum) is an important Solanaceae vegetable crop; its commercial hybrid seeds are widely used in production. Male sterility is a valuable trait for hybrid seed production. However, the function of PLCPs and the underlying mechanisms of male sterility in peppers remain unclear. In this study, we comprehensively identified the PLCP gene family in peppers, identifying 31 CaPLCPs. A phylogenetic analysis classified 31 members into eight clades. These CaPLCPs were unevenly distributed across eight chromosomes, and five segmental duplicated pairs were observed. The promoter cis-acting element analysis indicated that CaPLCP promoters contained abundant hormone-responsive and stress-responsive cis-elements, suggesting that CaPLCPs may play important roles in responding to abiotic stress, such as drought and low temperatures, as well as in plant immunity. The qRT-PCR analysis demonstrated that the expression levels of CaPLCP1, CaPLCP5, CaPLCP11, CaPLCP12, CaPLCP13, CaPLCP17, CaPLCP19, and CaPLCP21 were significantly reduced in the flowers of MS (male sterile pepper) at least at one stage, indicating their potential roles as regulatory factors in pepper male sterility. These findings provide important insights into the functional analysis of the PLCP gene family in peppers and other species, laying a crucial foundation for understanding the mechanisms of male sterility in peppers.

Rapid urbanization leads to fragmentation and reduced connectivity of urban landscapes, endangering regional biodiversity conservation and sustainable development. Constructing a red, green, and blue spatial ecological network is an effective way to alleviate ecological pressure and promote economic development. Using circuit theory, hydrological analysis, and suitability analysis, this study constructs a composite ecological network under urban–rural integration. The results show the following: (1) A total of 22 ecological corridors with a length of 349.20 km, 22 ecological pinch points, and 22 ecological barrier points are identified in the municipal area, mainly distributed in Haidong Town. There are 504 stormwater corridors, which are more evenly distributed, 502 riverfront landscape corridors, and 130 slow-moving landscape corridors. (2) A total of 20 ecological corridors, with a length of 99.23 km, 19 ecological pinch points, and 25 barrier points were identified in the main urban area, and most of them are located in the ecological corridors. There are 71 stormwater corridors, mainly located in the northwestern forest area, 71 riverfront recreation corridors, and 50 slow-moving recreation corridors. (3) Two scales of superimposed ecological source area of 3.65 km2, and eleven ecological corridors, are primarily distributed between Erhai Lake and Xiaguan Town. There are two superimposed stormwater corridors and fourteen recreational corridors. The eco-nodes are mostly distributed in the east and south of Dali City; wetland nodes are mainly situated in the eighteen streams of Cangshan Mountain; and landscape nodes are more balanced in spatial distribution. The study results can provide a reference for composite ecological network construction.

Low or insufficient testosterone levels caused by caponization promote fat deposition in animals. However, the molecular mechanism of fat deposition in caponized animals remains unclear. This study aimed to investigate the metabolomics and transcriptomic profiles of adipose tissues and study the effect of testosterone and leptin on the proliferation of adipocytes. We observed a significant enlargement in the areas of adipocytes in the abdominal fat tissues in capon, as well as increased luciferase activity of the serum leptin and a sharp decrease in the serum testosterone in caponized gander. Metabolomics and transcriptomic results revealed differentially expressed genes and differentially expressed metabolites with enhanced PARR signal pathway. The mRNA levels of peroxisome proliferators-activated receptor γ, fatty acid synthase, and suppressor of cytokine signaling 3 in goose primary pre-adipocytes were significantly upregulated with high leptin treatment and decreased significantly with increasing testosterone dose. Hence, reduced testosterone and increased leptin levels after caponization possibly promoted adipocytes proliferation and abdominal fat deposition by altering the expression of PPAR pathway related genes in caponized ganders. This study provides a new direction for the mechanism through which testosterone regulates the biological function of leptin and fat deposition in male animals.

The rapid advancement of artificial intelligence technology has significantly enhanced the intelligence of mobile robots, facilitating their widespread utilization in unmanned driving, smart home systems, and various other domains. As the scope, scale, and complexity of robot deployment continue to expand, there arises a heightened demand for enhanced computational power and real-time performance, with path planning emerging as a prominent research focus. In this study, we present an adaptive Lévy flight–rotation slime mold algorithm (LRSMA) for global robot motion planning, which incorporates LRSMA with the cubic Hermite interpolation. Unlike traditional methods, the algorithm eliminates the need for a priori knowledge of appropriate interpolation points. Instead, it autonomously detects the convergence status of LRSMA, dynamically increasing interpolation points to enhance the curvature of the motion curve when it surpasses the predefined threshold. Subsequently, it compares path lengths resulting from two different objective functions to determine the optimal number of interpolation points and the best path. Compared to LRSMA, this algorithm reduced the minimum path length and average processing time by (2.52%, 3.56%) and (38.89%, 62.46%), respectively, along with minimum processing times. Our findings demonstrate that this method effectively generates collision-free, smooth, and curvature-constrained motion curves with the least processing time.

Background and objectivesThe prognosis of liver failure treated with non-bioartificial liver support systems is poor. Detecting its risk factors and developing relevant prognostic models still represent the top priority to lower its death risk.MethodsAll 215 patients with liver failure treated with non-bioartificial liver support system were retrospectively analyzed. Potential prognostic factors were investigated, and the Nomogram and the Random Survival Forests (RSF) models were constructed, respectively. Notably, we evaluated the performance of models and calculated the risk scores to divide patients into low-risk and high-risk groups.ResultsIn the training set, multifactorial Cox regression analysis showed that etiology, hepatic encephalopathy, total bilirubin, serum alkaline phosphatase, platelets, and MELD score were independent factors of short-term prognosis. The RSF model (AUC: 0.863, 0.792) performed better in prediction than the Nomogram model (AUC: 0.816, 0.756) and MELD (AUC: 0.658, 0.700) in the training and validation groups. On top of that, patients in the low-risk group had a significantly better prognosis than those in the high-risk group.ConclusionWe constructed the RSF model with etiology, hepatic encephalopathy, total bilirubin, serum alkaline phosphatase, platelets, and MELD score, which showed better prognostic power than the Nomogram model and MELD score and could help physicians make optimal treatment decisions.

The present study investigated the effects of temperature on growth performance, slaughtering traits, meat quality and antioxidant function of Pekin ducks from 21–42 d of age. Single factor analysis of variance was used in this experiment, 144 21 d-old Pekin ducks were randomly allotted to 4 environmentally controlled chambers: T20 (20°C), T23 (23°C), T26 (26°C) and T29 (29°C), with 3 replicates in each group (12 ducks in each replicate), the relative humidity of all groups is 74%. During the 21-day trial period, feed and water were freely available. At 42 d, the BW (body weight) and ADG (average daily gain) of T26 were significantly lower than T20 (p

Alternative polyadenylation (APA) is a widespread mechanism of gene regulation that generates mRNA isoforms with alternative 3' untranslated regions (3' UTRs). Our previous study has revealed the global 3' UTR shortening of host mRNAs through APA upon viral infection. However, how the dynamic changes in the APA landscape occur upon viral infection remains largely unknown. Here we further found that, the reduced protein abundance of CPSF6, one of the core 3' processing factors, promotes the usage of proximal poly(A) sites (pPASs) of many immune related genes in macrophages and fibroblasts upon viral infection. Shortening of the 3' UTR of these transcripts may improve their mRNA stability and translation efficiency, leading to the promotion of type I IFN (IFN-I) signalling-based antiviral immune responses. In addition, dysregulated expression of CPSF6 is also observed in many immune related physiological and pathological conditions, especially in various infections and cancers. Thus, the global APA dynamics of immune genes regulated by CPSF6, can fine-tune the antiviral response as well as the responses to other cellular stresses to maintain the tissue homeostasis, which may represent a novel regulatory mechanism for antiviral immunity.

Abstract Background Immune‐related pneumonitis is a rare and potentially fatal adverse event associated with sintilimab. We aimed to develop and validate a nomogram for predicting the risk of immune‐related pneumonitis in patients treated with sintilimab. Methods The least absolute shrinkage and selection operator (LASSO) regression was used to determine risk factors. Multivariable logistic regression was used to establish a prediction model. Its clinical validity was evaluated using calibration, discrimination, decision, and clinical impact curves. Internal validation was performed against the validation set and complete dataset. Results The study included 632 patients; 59 were diagnosed with immune‐related pneumonitis. LASSO regression analysis identified that the risk factors for immune‐related pneumonitis were pulmonary metastases (odds ratio [OR], 4.015; 95% confidence interval [CI]: 1.725–9.340) and metastases at >3 sites (OR, 2.687; 95% CI: 1.151–6.269). The use of combined antibiotics (OR, 0.247; 95% CI: 0.083–0.738) and proton pump inhibitors (OR, 0.420; 95% CI: 0.211–0.837) were protective factors. The decision and clinical impact curves showed that the nomogram had clinical value for patients treated with sintilimab. Conclusions We have developed and validated a practical nomogram model of sintilimab‐associated immune‐related pneumonitis, which provides clinical value for determining the risk of immune‐related pneumonitis and facilitating the safe administration of sintilimab therapy.

The hypothesis of paternal origins of health and disease (POHaD) indicates that paternal exposure to adverse environment could alter the epigenetic modification in germ line, increasing the disease susceptibility in offspring or even in subsequent generations. p,p′-Dichlorodiphenyldichloroethylene (p,p′-DDE) is an anti-androgenic chemical and male reproductive toxicant. Gestational p,p′-DDE exposure could impair reproductive development and fertility in male offspring. However, the effect of paternal p,p′-DDE exposure on fertility in male offspring remains uncovered. From postnatal day (PND) 35 to 119, male rats (F0) were given 10 mg/body weight (b.w.) p,p′-DDE or corn oil by gavage. Male rats were then mated with the control females to generate male offspring. On PND35, the male offspring were divided into 4 groups according whether to be given the high-fat diet (HF): corn oil treatment with control diet (C-C), p,p′-DDE treatment with control diet (DDE-C), corn oil treatment with high-fat diet (C-HF) or p,p′-DDE treatment with high-fat diet (DDE-HF) for 35 days. Our results indicated that paternal p,p′-DDE exposure did not affect the male fertility of male offspring directly, but decreased sperm quality and induced testicular apoptosis after the high-fat diet treatment. Further analysis demonstrated that paternal exposure to p,p′-DDE and pre-pubertal high-fat diet decreased sperm Igf2 DMR2 methylation and gene expression in male offspring. Hence, paternal exposure to p,p′-DDE and pre-pubertal high-fat diet increases the susceptibility to male fertility impairment and sperm Igf2 DMR2 hypo-methylation in male offspring, posing a significant implication in the disease etiology.

BackgroundInflammatory cytokines play a major role in the pathogenesis of myocardial infarction (MI). Although information on the importance of interleukin 13 (IL13) in human MI is limited, it has been well documented in the mouse model. Genetic variation in the IL13 gene has been associated with the structure and expression of the IL13. In the present study, we hypothesized that IL13 common genetic variants would be associated with a predisposition to the development of MI.Materials and methodsThe present study enrolled 305 MI patients and 310 matched healthy controls. Common genetic polymorphisms in the IL13 gene (rs20541, rs1881457, and rs1800925) were genotyped using the TaqMan SNP genotyping method. Plasma levels of IL13 were measured using an enzyme-linked immunosorbent assay (ELISA).ResultsIn MI patients, minor alleles of the IL13 rs1881457 and rs1800925 polymorphisms were less common than in healthy controls [rs1881457: AC (P = 0.004, OR = 0.61), C (P = 0.001, OR = 0.66); rs1800925: CT (P = 0.006, OR = 0.59)]. Further haplotype analysis of three studied SNPs revealed a significant association with predisposition to MI. Interestingly, IL13 rs1881457 and rs1800925 were linked to plasma levels of IL13: the reference genotype had higher levels, heterozygotes were intermediate, and the alternate genotype had the lowest levels.ConclusionsIn the Chinese population, IL13 (rs1881457 and rs180092) variants are associated with different plasma IL13 levels and offer protection against MI development. However, additional research is required to validate our findings in different populations, including descent samples.

OpenStreetMap (OSM) is one of the most successful and well-known projects in the field of Volunteered Geographic Information (VGI). It has not only become supplement to basic mapping services and professional surveying data, but also a popular free spatial dataset in urban analysis. However, the completeness of OSM building data in China was relatively low in the past. As a result, there is a relatively small number of studies on OSM building data in China, especially in terms of spatial patterns and evolution of OSM building data. In response to this research gap, this article proposes an OSM building data evolution model that combines gravity model and tree model. The spatial distribution pattern and evolution trend of OSM building data in the Yangtze River Delta region of China from 2014 to 2020 were systematically studied, providing insights and references for the future development of OSM building data in China. The research results indicate: (1) From 2014 to 2020, OSM building data in various cities in the Yangtze River Delta region grew rapidly, with an average annual growth rate of 30%, but there were significant spatial differences; (2) In terms of space, due to the influence of urban economy, population, and education level, OSM buildings mainly evolve and develop along large cities, forming a local radial development structure around large cities. Shanghai-Suzhou-Wuxi-Nanjing-Xuzhou/Hefei is the main evolutionary path of OSM building data in the Yangtze River Delta region; (3) In terms of time series, the gap between cities gradually decreases with the development of time, and OSM buildings gradually expand and develop from large cities to small and medium-sized cities, with spatial differences gradually narrowing. However, when OSM buildings have a certain scale, the city size will limit the development of OSM buildings to some extent.

Rainfall has a significant impact on urban population mobility, posing great challenges to traffic management and urban planning. An understanding of this influence from multiple perspectives is urgently needed. In this study, we devised a multiscale comparative research framework to explore the spatiotemporal effects of rainfall on taxi travel patterns, aiming to provide a new perspective on the investigation of rainfall’s impact on urban human mobility. More specifically, at the macroscopic scale, we computed taxi travel indicators across the entire study area and used kernel density estimates to observe the spatiotemporal distribution patterns influenced by rainfall. Subsequently, complex traffic networks were constructed by considering urban road intersections as nodes and combined with visualization methods to understand changes in taxi travel patterns visually at the microscopic level. We selected Wuhan City, a typical urban area in southern China with frequent rainfall, as the study area and used meteorological data along with a large volume of taxi spatiotemporal trajectory data for investigation. Results indicated a 4.16% decrease in weekly travel volume due to rainfall, with a 3.96% decrease on workdays and a 4.64% decrease on weekends. However, nighttime rainfall between 19:00 and 22:00 on weekdays increased the demand for taxi travel. Furthermore, the impact of rainfall on weekends exceeded that on workdays, restricting people’s mobility and leisure activities, resulting in reduced travel to recreational tourist spots and commercial pedestrian streets. Rainfall altered residents’ travel preferences to some extent, with more residents choosing taxis during rainy weather, which led to decreased transportation efficiency and increased traffic congestion. These findings contribute to a deeper understanding of the complex relationship between population mobility patterns and the urban ecological environment, providing valuable insights for planning resident travel and taxi dispatching under adverse weather conditions.

BackgroundAlthough there is evidence that ribonucleotide reductase subunit M2 (RRM2) is associated with numerous cancers, pan-cancer analysis has seldom been conducted. This study aimed to explore the potential carcinogenesis of RRM2 in pan-cancer using datasets from The Cancer Genome Atlas (TCGA).MethodsData from the UCSC Xena database were analyzed to investigate the differential expression of RRM2 across multiple cancer types. Clinical data such as age, race, sex, tumor stage, and status were acquired to analyze the influence of RRM2 on the clinical characteristics of the patients. The role of RRM2 in the onset and progression of multiple cancers has been examined in terms of genetic changes at the molecular level, including tumor mutational burden (TMB), microsatellite instability (MSI), biological pathway changes, and the immune microenvironment.ResultsRRM2 was highly expressed in most cancers, and there was an obvious correlation between RRM2 expression and patient prognosis. RRM2 expression is associated with the infiltration of diverse immune and endothelial cells, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI). Moreover, the cell cycle is involved in the functional mechanisms of RRM2.ConclusionsOur pan-cancer study provides a comprehensive understanding of the carcinogenesis of RRM2 in various tumors.

As an on-demand mobility service, parking reservations can greatly alleviate the issue of parking challenges. There are currently three primary strategies for parking reservation: first-come-first-served, permit reservation, and auction. In contrast to the first-come-first-served and permit-reserved strategies, the auction strategy uses dynamic pricing to allocate parking supplies efficiently based on the auction, which attracts more scholars for the research. However, parking reservations based on the auction process may have an inequity issue because drivers’ age, gender, income level, and location of residence fluctuate. This inequity may limit the growth of reserved parking by influencing parking drivers’ acceptance of reserved parking. But currently, very few scholars focus on the issue of reserved parking equity, and even fewer measure this nebulous and personal issue. In consideration of this, the Lorenz curve of parking reservation and the vertical equity index of parking reservation are proposed in this paper along with the calculation method for the index, which enables the problem of reserved parking vertical equity to be visualized and made concrete. The numerical experimental method is used to analyze the vertical equity of drivers with varying income levels, utilizing the Vickrey–Clarke–Groves (VCG) auction process as an example. According to the research, loss-averse drivers are more than gain-neutral and gain-seeking drivers when the income levels of the drivers using reserved parking are the same. With the increasing number of high-income drivers involved in the parking reservation, medium to low-income drivers would lose their chances of successful reservations because of their uncompetitive bid price which leads to inequity issues when the number is less than the number of parking spaces. In contrast, the vertical equity index changes more for gain-seeking drivers while being generally steady when loss-averse and gain-neutral drivers participate. For instance, when the profit and loss coefficient is 3 and 15% of drivers with high-income levels use the parking reservation platform, the vertical equity index rises from 0.09128 to 0.45434. The reference price has a moderating influence on the vertical equity index when the number of driver participants at high-income levels remains constant. In general, within a reasonable range, the higher the reference price, the more equitable the parking reservation procedure and the lower the vertical equity index.

PurposeThis study aimed to assess the difference in prognosis of patients with early-stage liver cancer after surgery or external radiation.MethodsBetween 2010 and 2015, 2155 patients with AJCC 7th stage I liver cancer were enrolled in the SEER database. Among these, 1972 patients had undergone surgery and 183 had undergone external beam radiation. The main research endpoints were overall survival (OS) and disease-specific survival (DSS). The competitive risk model was used to calculate the risk ratio of liver cancer-specific deaths when there was a competitive risk. Propensity Score Matching (PSM) method using a 1:1 ratio was used to match confounders such as sex, age, and treatment method. Conditional survival was dynamically assessed for patient survival after surgery or external radiation.ResultsMultivariate analysis of the competitive risk model showed that age, disease diagnosis time, grade, and treatment [surgery and external beam radiation therapy (EBRT)] were independent prognostic factors for patients with hepatocellular carcinoma. Surgery had a higher survival improvement rate than that of EBRT. As the survival of patients with liver cancer increased, the survival curve of surgery declined more slowly than that of radiotherapy patients and stabilized around 3 years after surgery. The survival curve of radiotherapy patients significantly dropped within 4 years and then stabilized.ConclusionSurgery was better than EBRT for patients with stage I liver cancer. Close follow-up was required for 3 years after surgery or 4 years after external radiation. This study can help clinicians make better informed clinical decisions.

ObjectivesTo evaluate the efficacy and safety of biliary stenting implantation with iodine-125 seed strand (SI) followed by hepatic artery infusion chemotherapy (HAIC) plus lenvatinib (Len) with programmed death-1 (PD-1) inhibitor for patients diagnosed with extrahepatic cholangiocarcinoma (ECC) and malignant obstructive jaundice (MOJ).MethodsIn this single-center retrospective study, the data of ECC patients with MOJ from March 2015 to January 2023 was assessed. Using probability score matching (PSM), the selection bias of patients was reduced. Primary study outcomes included overall survival (OS) and progression-free survival (PFS). The OS and PFS were performed using the Kaplan–Meier method and evaluated with the log-rank test.ResultsA total of 104 patients were enrolled finally, including 52 patients treated with interventional therapy (SI+HAIC) plus Len with PD-1 inhibitor (SI+HAIC+Len+P group) and 52 patients treated with interventional therapy (SI+HAIC) plus lenvatinib (SI+HAIC+Len group). 26 pairs of patients were matched after PSM analysis. After PSM analysis, the median OS and PFS in the SI+HAIC+Len+P group were significantly longer compared to those in the SI+HAIC+Len group (OS:16.6 vs. 12.3 months, P = 0.001; PFS:12.6 vs 8.5 months, P = 0.004). The DCR was significantly different between groups (P = 0.039), while ORR not (P = 0.548). The addition of PD-1 inhibitor was generally well tolerated without treatment-associated mortality.ConclusionInterventional therapy (SI+HAIC) plus Len with PD-1 inhibitor was effective for ECC patients accompanied by MOJ with a manageable safety profile.

We aimed to explore the relationship between pulmonary artery distensibility obtained from computed tomography pulmonary angiography (CTPA) and short-term adverse clinical outcomes in patients with acute pulmonary embolism (APE). We included patients who underwent retrospective electrocardiogram-gated CTPA and were subsequently diagnosed with APE. Patients were categorized into good and poor outcome groups based on short-term clinical outcomes. Pulmonary artery distensibility (AD), right ventricle/left ventricle (RV/LV) ratio, and pulmonary artery obstruction index (PAOI) were measured, and the receiver operating characteristic curves were constructed. Sixty-four patients with APE (good outcome, 46; poor outcome, 18) were enrolled. AD, RV/LV ratio, and PAOI differed significantly between groups (P

ABSTRACT: Chinese herbs have been used as feed additives and are commonly utilized in domestic intensive livestock farming. However, their impact on the production performance and intestinal health of broiler breeders has yet to be thoroughly explored. This study aimed to evaluate the effects of a Chinese herbal mixture (CHM) on the production performance of broiler breeders in terms of reproductive hormones, antioxidant capacity, immunity, and intestinal health of broiler breeders. A total of 336 thirty-wk-old hens were randomly allotted to 4 groups with 6 replicates of fourteen hens each, which fed a basal diet supplemented with 0 (CON), 500 (CHM500), 1,000 (CHM1000), and 1,500 (CHM1500) mg/kg CHM for 56 days, respectively. Our results showed that dietary supplementation with CHM1000 increased the laying rate and number of SYF and decreased the feed conversion ratio (P < 0.05). All CHM groups increased oviduct and ovarian indexes, serum E2 and T-AOC levels, and decreased serum TG and MDA levels compared with CON (P < 0.05). In comparison to the CON group, the CHM1000 and CHM1500 groups increased serum ALB, IgM, and IL-10 levels, whereas the CHM1000 group also increased serum TP and SOD levels, and the CHM1500 group increased serum P and decreased serum TNF-α (P < 0.05). The addition of CHM increased FSHR expressions in the ovary, Claudin-1 expressions in the jejunum, and SOD1 expressions in the liver and ovary, but decreased the mRNA expressions of INH in the ovary as well as IL-2 and IL-6 expressions in the jejunum (P < 0.05). Moreover, CHM500 and CHM1000 groups increased CAT, GPx, and HO-1 expression in the ovary, and SOD1 and GPx expression in the jejunum, while decreasing IL-17A expression in the jejunum (P < 0.05). In addition, CHM1000 and CHM1500 groups increased villus height, VCR, and the mRNA expressions of Nrf2, HO-1, Occludin, and MUC2 in the jejunum, and IL-10 expression in the ovary, while decreasing IL-2 and IL-17A expression in the ovary, in addition to increasing GPx, Nrf2, HO-1, NQO1, and IL-10 expression in the liver (P < 0.05). Supplementation with CHM1000 increased ESR-α, ESR-β, GnRH, Nrf2, and NQO1 expression in the ovary, but decreased IFN-γ expression in the ovary as well as crypt depth in the jejunum (P < 0.05). Supplementing CHM1500 increased NQO1 and ZO-1 expression in the jejunum and decreased IL-2 in the liver (P < 0.05). The high-throughput sequencing results showed that dietary CHM1000 supplementation altered the composition of the intestinal microbiota, as evidenced by the regulation of the genera Lactobacillus, Faecalibacterium, and Phascolarctobacterium. PICRUSt analysis revealed that metabolic pathways of bacterial chemotaxis, butanoate metabolism, and synthesis and degradation of ketone bodies were enriched in the CHM1000 group. Spearman's correlation analysis indicated that the differentiated genera were significantly associated with the production performance, serum hormone, and gut barrier-related genes. Taken together, supplementation of CHM, especially at 1,000 mg/kg, could improve production performance by regulating reproductive hormones, antioxidant capacity, immunity, and intestinal health of broiler breeders, and maybe provide insights into its application as a potential feed additive to promote the performance of broiler breeders.

Classical swine fever virus (CSFV) can dampen the host innate immunity by destabilizing IRF3 upon its binding with viral Npro. High mobility group box 1 (HMGB1), a non-histone nuclear protein, has diverse functions, including inflammation, innate immunity, etc., which are closely related to its cellular localization. We investigated potential mutual interactions between CSFV and HMGB1 and their effects on virus replication. We found that HMGB1 at the protein level, but not at mRNA level, was markedly reduced in CSFV-infected or Npro-expressing IPEC-J2 cells. HMGB1 in the nuclear compartment is anti-CSFV by promoting IFN-mediated innate immune response, as evidenced by overexpression of nuclear or cytoplasmic dominant HMGB1 mutant in IPEC-J2 cells stimulated with poly(I:C). However, CSFV Npro upregulates HMGB1 acetylation, a modification that promotes HMGB1 translocation into the cytoplasmic compartment where it is degraded by lysosomes. Ethyl pyruvate could downregulate HMGB1 acetylation and prevent Npro-mediated HMGB1 reduction. Inhibition of deacetylase HDAC1 with MS275 or by RNA silencing could promote Npro-mediated HMGB1 degradation. Taken together, our study elucidates the mechanism with which HMGB1 in the nuclei initiates antiviral innate immune response to suppress CSFV replication and elaborates the pathway by which CSFV uses its Npro to evade from HMGB1-mediated antiviral immunity through upregulating HMGB1 acetylation with subsequent translocation into cytoplasm for lysosomal degradation.

Abstract Background Frailty is considered a characteristic manifestation of physiological decline in multiple organ systems, which significantly increases the vulnerability of elderly individuals with colorectal cancer (CRC) and is associated with a poor prognosis. While studies have demonstrated that the 11-factor Modified Frailty Index (mFI-11) can effectively predict adverse outcomes following radical resection of CRC, there is a lack of research on the applicability of the 5-factor Modified Frailty Index (mFI-5) within this patient population. Methods In this retrospective analysis, we examined a cohort of CRC patients aged 65 years and above who had undergone radical resection. For each patient, we calculated their mFI-5 score, considering a score of ≥ 2 as an indication of frailty. We conducted univariate and multivariate analyses to assess the association between the mFI-5 and adverse outcomes as well as postoperative complications. Results Patients with an mFI-5 score ≥ 2 exhibited a significantly higher incidence of serious postoperative complications (53% vs. 30%; P = 0.001) and experienced a longer hospital stay [19.00 (15.00–24.50) vs. 17.00 (14.00–20.00); P

Delamination is a common defect in carbon fiber reinforced polymer (CFRP) during the molding process. Accurately understanding the formation and evolution mechanisms of drilling damage in CFRP with delamination defects is helpful for effectively suppressing drilling defects with delamination. In this study, a macro-micro finite element model (FEM) of CFRP with prefabricated delamination defects during drilling is established to simulate and analyze the damage formation and evolution behavior. The circular polytetrafluoroethylene (PTFE) films are employed to simulate the delamination defects in CFRP. These samples with different sizes of prefabricated delamination defects are prepared for the drilling experiments. The results show that the maximum errors of the thrust force and the exit damage factor between the simulation and experiments are 8.75% and 4.2% respectively, indicating good reliability of the simulation model. Under the condition of CFRP with delamination defects, as the size of the delamination defects increases, the maximum thrust force decreases, while the maximum delamination propagation length and exit damage increase. Compared to the case without delamination defects, when the delamination diameter is 7 mm, the delamination propagation percentage and the maximum stress in CFRP increase by 52.17% and 155.4% respectively, and the maximum increment of the exit delamination damage factor is 38%.

Abstract Atomic-scale precision alignment is a bottleneck in the fabrication of next-generation nanoelectronics. In this study, a redox-coupled inherently selective atomic layer deposition (ALD) is introduced to tackle this challenge. The ‘reduction-adsorption-oxidation’ ALD cycles are designed by adding an in-situ reduction step, effectively inhibiting nucleation on copper. As a result, tantalum oxide exhibits selective deposition on various oxides, with no observable growth on Cu. Furthermore, the self-aligned TaOx is successfully deposited on Cu/SiO2 nanopatterns, avoiding excessive mushroom growth at the edges or the emergence of undesired nucleation defects within the Cu region. The film thickness on SiO2 exceeds 5 nm with a selectivity of 100%, marking it as one of the highest reported to date. This method offers a streamlined and highly precise self-aligned manufacturing technique, which is advantageous for the future downscaling of integrated circuits.

Abstract Background Host response to virus infection is key to the effective control and eventual elimination of viruses or infected cells; however, the underlying mechanism of Japanese encephalitis virus (JEV) infection remains unclear. Methods In the present study, short time-series expression was analyzed by R software to obtain two groups of differentially expressed genes (DEGs) [upregulated/downregulated] during the entire process of JEV infection based on the data in the Gene Expression Omnibus database. GO enrichment and KEGG pathway, protein interactions and hub genes selection were analyzed by DAVID, STRING and Cytoscape respectively. Interactions of the JEV and host proteins, and the microRNAs that target Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activating protein Eta (YWHAH) and Proteasome activator subunit 2(PSME2) were predicted by P-hipster and ENCORI, respectively. Expression levels of YWHAH and PSME2 were analyzed using the HPA database and RT-qPCR assay. Results Two groups of continuously changed DEGs during entire process of JEV infection were obtained. Continuously upregulated cluster was mainly related to regulation of transcription, immune response and inflammatory response; and the continuous downregulated group mainly including intracellular protein transport and signal transduction, several proteolysis pathways. As targets of several microRNAs, the downregulated-YWHAH and the upregulated-PSME2 were related to host and JEV proteins to affect several pathways after JEV infection. Conclusions YWHAH and PSME2 are key host factors of JEV infection based on their continuously differentially expressed pattern, interactions with multiple JEV proteins, and as members of the hub genes. Our results provide valuable information for further studies on the interactions between viruses and host.

Abstract Hepatocellular carcinoma (HCC) is common worldwide, and novel therapeutic targets and biomarkers are needed to improve outcomes. In this study, bioinformatics analyses combined with in vitro and in vivo assays were used to identify the potential therapeutic targets. Differentially expressed genes (DEG) in HCC were identified by the intersection between The Cancer Genome Atlas and International Cancer Genome Consortium data. The DEGs were evaluated by a gene set enrichment analysis as well as Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. A protein interaction network, univariate Cox regression, and Lasso regression were used to screen out hub genes correlated with survival. Increased expression of the long noncoding RNA GBAP1 in HCC was confirmed in additional datasets and its biological function was evaluated in HCC cell lines and nude mice. Among 121 DEGs, GBAP1 and PRC1 were identified as hub genes with significant prognostic value. Overexpression of GBAP1 in HCC was confirmed in 21 paired clinical tissues and liver cancer or normal cell lines. The inhibition of GBAP1 expression reduced HCC cell proliferation and promoted apoptosis by inactivating the PI3K/AKT pathway in vitro and in vivo. Therefore, GBAP1 has a pro-oncogenic function in HCC and is a candidate prognostic biomarker and therapeutic target.

Paleoenvironmental conditions significantly influence the distribution patterns and organic matter enrichment of shale. This study investigated the vertical variations of major elements, trace elements, and total organic carbon (TOC) in the Lower Carboniferous marine shale from the Yaziluo Rift Trough, South China, to understand the paleoenvironmental conditions, including redox conditions, terrigenous detrital input, paleoproductivity, and paleo-seawater depth. The Lower Carboniferous formation consists of three sedimentary facies: basin facies, lower slope facies, and upper slope facies. From the basin to the lower slope and then to the upper slope facies, TOC, quartz, and pyrite contents gradually decrease, whereas the carbonate mineral content shows an increasing trend. A continuous decline in paleo-seawater depth transformed a deep-water anoxic environment with high paleoproductivity and low detrital input in the basin facies into a semi-deep-water environment with dysoxic-oxic conditions and moderate detrital influx in the lower slope facies, evolving further into a suboxic environment with high detrital flux in the upper slope facies. The geochemistry results suggest that anoxic conditions and high paleoproductivity were the primary controls on organic matter enrichment in the siliceous shale of the basin facies. In contrast, redox conditions significantly influenced organic matter accumulation in the mixed shale of the lower slope facies, attributed to relatively low paleoproductivity in a more restricted marine setting. Additionally, the adsorption of carbon components by clay minerals facilitated the preservation of organic matter in the calcareous shale of the upper slope facies.

OVATE family proteins (OFPs) are a class of plant-specific proteins with a conserved OVATE domain that play fundamental roles in fruit development and plant growth. Mango (Mangifera indica L.) is an economically important subtropical fruit tree characterized by a diverse array of fruit shapes and sizes. Despite extensive research on OFPs across various species, there remains a scarcity of information regarding OFPs in mango. Here, we have successfully identified 25 OFP genes (MiOFPs) in mango, each of which exhibits the conserved OVATE domains. The MiOFP gene exhibit a range of 2–6 motifs, with all genes containing both motif 1 and motif 2. Phylogenetic analysis on 97 OFPs (including 18 AtOFPs, 24 SlOFPs, 25 MiOFPs, and 30 OsOFPs) indicated that MiOFPs could be divided into three main clades: clade I, II, and III. Comparative morphological analysis identified significant variations in fruit longitudinal diameter, fruit transverse diameter, and fruit shape index between two distinct shaped mango cultivars (‘Hongxiangya’ and ‘Jingpingmang’) at DAP5, DAP7, and DAP10 stages. The subsequent examination of paraffin sections revealed distinct patterns of cell elongation. The majority of MiOFP genes exhibited predominantly expressed in developing organs, specifically flowers and immature fruits, while displaying distinct expression patterns. RNA-Seq analysis revealed significant disparities in the expression levels of several OFP genes, including MiOFP5, MiOFP11, MiOFP21, MiOFP22, MiOFP23, and MiOFP25, between the two mango cultivars. These findings suggest that these six genes may play a crucial role for fruit shape in mango, especially the MiOFP22. The findings of this study have established a basis for future investigations into MiOFPs in mango, offering a solid foundation for further research in this field.

Protein palmitoylation, the most common and the only reversible post-translational lipid modification following protein translation, plays a pivotal role in the biochemical and physiological processes of both animals and plants. DHHC proteins, enriched with DHHC (Asp-His-His-Cys) domains, serve as catalyst for protein palmitoylation. However, research on DHHC in cotton remains scarce. This study conducted a systematic characterization and bioinformatics analysis on G. arboreum, G. raimondii, G. hirsutum, and G. barbadense, detecting 38, 37, 74, and 74 DHHC genes, respectively. Phylogenetic analysis categorized the DHHC gene family into six subgroups, consistent with previous evolutionary studies in Arabidopsis and rice. A further examination of protein structure revealed a correlation between genetic relatedness, structural similarity, and functional identity. Cis-element analysis identified elements predominantly associated with light response, stress, growth and development, and plant hormones. The integration of cotton seed development transcriptome, tissue expression pattern analysis, and population transcriptome data collectively suggests that Ghir_A05G027650 and Ghir_D05G027670 are promising candidate genes influencing seed development in upland cotton. Conversely, Gbar_A04G010750 and Gbar_A12G020520 emerge as potential candidates affecting both seed and fiber development in sea island cotton. These findings lay down a theoretical foundation for delving into the functional diversity of DHHC genes in cotton, thereby paving the way for the development of new breeding strategies and the optimization of cotton seed and fiber production, ultimately contributing to improved crop yield and quality.

In this research, with an aim to develop novel pyrazole oxime ether derivatives possessing potential biological activity, thirty-two pyrazole oxime ethers, including a substituted pyridine ring, have been synthesized and structurally identified through 1H NMR, 13C NMR, and HRMS. Bioassay data indicated that most of these compounds owned strong insecticidal properties against Mythimna separata, Tetranychus cinnabarinus, Plutella xylostella, and Aphis medicaginis at a dosage of 500 μg/mL, and some title compounds were active towards Nilaparvata lugens at 500 μg/mL. Furthermore, some of the designed compounds had potent insecticidal effects against M. separata, T. cinnabarinus, or A. medicaginis at 100 μg/mL, with the mortalities of compounds 8a, 8c, 8d, 8e, 8f, 8g, 8o, 8s, 8v, 8x, and 8z against A. medicaginis, in particular, all reaching 100%. Even when the dosage was lowered to 20 μg/mL, compound 8s also expressed 50% insecticidal activity against M. separata, and compounds 8a, 8e, 8f, 8o, 8v, and 8x displayed more than 60% inhibition rates against A. medicaginis. The current results provided a significant basis for the rational design of biologically active pyrazole oxime ethers in future.

A chimeric protein, formed by two fragments of the conserved nucleocapsid (N) and S2 proteins from SARS-CoV-2, was obtained as a recombinant construct in Escherichia coli. The N fragment belongs to the C-terminal domain whereas the S2 fragment spans the fibre structure in the post-fusion conformation of the spike protein. The resultant protein, named S2NDH, was able to form spherical particles of 10 nm, which forms aggregates upon mixture with the CpG ODN-39M. Both preparations were recognized by positive COVID-19 human sera. The S2NDH + ODN-39M formulation administered by the intranasal route resulted highly immunogenic in Balb/c mice. It induced cross-reactive anti-N humoral immunity in both sera and bronchoalveolar fluids, under a Th1 pattern. The cell-mediated immunity (CMI) was also broad, with positive response even against the N protein of SARS-CoV-1. However, neither neutralizing antibodies (NAb) nor CMI against the S2 region were obtained. As alternative, the RBD protein was included in the formulation as inducer of NAb. Upon evaluation in mice by the intranasal route, a clear adjuvant effect was detected for the S2NDH + ODN-39M preparation over RBD. High levels of NAb were induced against SARS-CoV-2 and SARS-CoV-1. The bivalent formulation S2NDH + ODN-39M + RBD, administered by the intranasal route, constitutes an attractive proposal as booster vaccine of sarbecovirus scope.

Class III peroxidases (CIII PRXs) are plant-specific enzymes with high activity that play key roles in the catalysis of oxidation-reduction reactions. In plants, CIII PRXs can reduce hydrogen peroxide to catalyze oxidation–reduction reactions, thereby affecting plant growth, development, and stress responses. To date, no systematic analysis of the CIII PRX gene family in litchi (Litchi chinensis Sonn.) has been documented, although the genome has been reported. In this study, a total of 77 CIII PRX (designated LcPRX) gene family members were predicted in the litchi genome to provide a reference for candidate genes in the responses to abiotic stresses during litchi growth and development. All of these LcPRX genes had different numbers of highly conserved PRX domains and were unevenly distributed across fifteen chromosomes. They were further clustered into eight clades using a phylogenetic tree, and almost every clade had its own unique gene structure and motif distribution. Collinearity analysis confirmed that there were eleven pairs of duplicate genes among the LcPRX members, and segmental duplication (SD) was the main driving force behind the LcPRX gene expansion. Tissue-specific expression profiles indicated that the expression levels of all the LcPRX family members in different tissues of the litchi tree were significantly divergent. After different abiotic stress treatments, quantitative real-time PCR (qRT-PCR) analysis revealed that the LcPRX genes responded to various stresses and displayed differential expression patterns. Physicochemical properties, transmembrane domains, subcellular localization, secondary structures, and cis-acting elements were also analyzed. These findings provide insights into the characteristics of the LcPRX gene family and give valuable information for further elucidating its molecular function and then enhancing abiotic stress tolerance in litchi through molecular breeding.

Eggplant is a highly significant vegetable crop and extensively cultivated worldwide. Sepal color is considered one of the major commercial traits of eggplant. Eggplant sepals develop from petals, and sepals have the ability to change color by accumulating anthocyanins, but whether the eggplants in sepal and their biosynthetic pathways are the same as those in petals is not known. To date, little is known about the underlying mechanisms of sepal color formation. In this study, we performed bulked segregant analysis and transcriptome sequencing using eggplant sepals and obtained 1,452,898 SNPs and 182,543 InDel markers, respectively, as well as 123.65 Gb of clean data using transcriptome sequencing. Through marker screening, the genes regulating eggplant sepals were localized to an interval of 2.6 cM on chromosome 10 by bulked segregant analysis sequencing and transcriptome sequencing and co-analysis, combined with screening of molecular markers by capillary electrophoresis. Eight possible candidate genes were then screened to further interpret the regulatory incentives for the eggplant sepal color.

Rotavirus (RV) is the main pathogen that causes severe diarrhea in infants and children under 5 years of age. No specific antiviral therapies or licensed anti-rotavirus drugs are available. It is crucial to develop effective and low-toxicity anti-rotavirus small-molecule drugs that act on novel host targets. In this study, a new anti-rotavirus compound was selected by ELISA, and cell activity was detected from 453 small-molecule compounds. The anti-RV effects and underlying mechanisms of the screened compounds were explored. In vitro experimental results showed that the small-molecule compound ML241 has a good effect on inhibiting rotavirus proliferation and has low cytotoxicity during the virus adsorption, cell entry, and replication stages. In addition to its in vitro effects, ML241 also exerted anti-RV effects in a suckling mouse model. Transcriptome sequencing was performed after adding ML241 to cells infected with RV. The results showed that ML241 inhibited the phosphorylation of ERK1/2 in the MAPK signaling pathway, thereby inhibiting IκBα, activating the NF-κB signaling pathway, and playing an anti-RV role. These results provide an experimental basis for specific anti-RV small-molecule compounds or compound combinations, which is beneficial for the development of anti-RV drugs.

As a planarization technique, chemical mechanical polishing (CMP) continues to suffer from pattern effects that result in large variations in material thickness, which can influence circuit performance and yield. Therefore, tools for predicting post-CMP chip morphology based on the layout-dependent effect (LDE) have become increasingly critical and widely utilized for design verification and manufacturing development. In order to characterize the impact of patterns on polishing, such models often require the extraction of graphic parameters. However, existing extraction algorithms provide a limited description of the interaction effect between layout patterns. To address this problem, we calculate the average density as a density correction and innovatively use a one-dimensional line contact deformation profile as a weighting function. To verify our hypothesis, the density correction method is applied to a density step-height-based high-K metal gate-CMP prediction model. The surface prediction results before and after optimization are compared with the silicon data. The results show a reduction in mean squared error (MSE) of 40.1% and 35.2% in oxide and Al height predictions, respectively, compared with the preoptimization results, confirming that the optimization method can improve the prediction accuracy of the model.

Due to the increasing amounts of textile waste, textile to textile recycling is of prime concern. Polyethylene terephthalate (PET) represents the most extensively used type of chemical fiber. Its spinnability suffers from impurities and degradation in the processing, which limits its recycling to new fibers. Here, recycled polyester is blended with a small amount of recycled nylon, and the regenerated fibers, which demonstrated good mechanical properties, were obtained via a melt spinning machine. The mechanical properties, thermal properties, rheological properties, and chemical structure of the modified recycled fibers were investigated. It was found that when compared with rPET-T fibers, the elongation at break of rPET-Ax fibers increased to 17.48%, and the strength at break decreased to 3.79 cN/dtex. The compatibility of PET and PA6 copolymer were enhanced by copolymers produced by in-situ reaction in the processing. Meanwhile, the existence of PA6 increases the crystallization temperature and improves the hydrophilicity of the fibers. This study realized the high-value recycling of waste PET fabric to new fibers, which opens a door for the large utilization of waste textiles.

Atherosclerotic cardiovascular disease (ASCVD) frequently results in sudden death and poses a serious threat to public health worldwide. The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets. Therefore, the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention. Andrographolide (AG) is a diterpenoid lactone compound extracted from Andrographis paniculata. In addition to its use in conditions such as sore throat, AG can be used to prevent and treat ASCVD. It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity, diabetes, hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis (AS) including lipid accumulation, inflammation, oxidative stress and cellular abnormalities by regulating various targets and pathways. However, the pharmacological mechanisms of AG underlying the prevention and treatment of ASCVD have not been corroborated, which may hinder its clinical development and application. Therefore, this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD. The findings support the use of the old pharmacological compound (‘old bottle’) as a novel drug (‘novel wine’) for the prevention and treatment of ASCVD. Additionally, this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG, aiming to provide more information regarding the clinical application and further research and development of AG.

Abstract Background Exploring the association of diet and indoor and outdoor environments on the gut microbiome of red-crowned cranes. We investigated the microbiome profile of the 24 fecal samples collected from nine cranes from day 1 to 35. Differences in the gut microbiome composition were compared across diet and environments. Results A total of 2,883 operational taxonomic units (OTUs) were detected, with 438 species-specific OTUs and 106 OTUs common to the gut microbiomes of four groups. The abundance of Dietzia and Clostridium XI increased significantly when the red-crowned cranes were initially fed live mealworms. Skermanella and Deinococcus increased after the red-crowned cranes were fed fruits and vegetables and placed outdoors. Thirty-three level II pathway categories were predicted. Our study revealed the mechanism by which the gut microbiota of red-crowned cranes responds to dietary and environmental changes, laying a foundation for future breeding, nutritional and physiological studies of this species. Conclusions The gut microbiome of red-crowned cranes could adapt to changes in diet and environment, but the proportion of live mealworms in captive red-crowned cranes can be appropriately reduced at the initial feeding stage, reducing the negative impact of high-protein and high-fat foods on the gut microbiome and growth and development.

Abstract Background Uterine arteriovenous malformation(AVM) refers to the abnormal direct traffic between uterine arteries and veins, which can be characterized by the imaging examination, showing increased uterine vascularity and arteriovenous shunting. However, similar imaging manifestations can also be seen in a variety of conditions including retained production of conception, gestational trophoblastic disease, placental polyp, and vascular neoplasm. Case presentation Here we present a case of a 42-year-old woman who was suspected of suffering uterine AVM indicated by Doppler sonography and magnetic resonance imaging but was finally diagnosed with a persistent ectopic pregnancy located on the right uterine corner by pathology after laparoscopy. She recovered well after surgery. Conclusion Uterine AVM is a rare and serious condition. In general, it presents special radiological manifestations. However, when complicated with other diseases it can also be distorting. Standardized diagnosis and management are important.

Prior studies examining the effects of cocaine on the dynorphin/kappa opioid receptor (Dyn/KOR) system primarily focus on non-contingent cocaine exposure, but the effects of self-administration, which more closely reflects human drug-taking behaviors, are not well studied. In this study we characterized the effects of escalated intravenous cocaine self-administration on the functional state of the Dyn/KOR system and its interaction with mesolimbic dopamine signaling. Rats self-administered cocaine in an extended access, limited intake cocaine procedure, in which animals obtained 40 infusions per day (1.5 mg/kg/inf) for 5 consecutive days to ensure comparable consumption levels. Following single day tests of cue reactivity and progressive ratio responding, quantitative real-time polymerase chain reaction was used to measure levels of Oprk and Pdyn transcripts in the ventral tegmental area and nucleus accumbens. Additionally, after self-administration, ex vivo fast-scan cyclic voltammetry in the NAc was used to examine the ability of the KOR agonist U50,488 to inhibit dopamine release. We found that KOR-induced inhibition of dopamine release was enhanced in animals that self-administered cocaine compared to controls, suggesting upregulated Dyn/KOR activity after cocaine self-administration. Furthermore, expression levels of Pdyn in the nucleus accumbens and ventral tegmental area, and Oprk in the nucleus accumbens, were elevated in cocaine animals compared to controls. Additionally, Pdyn expression in the nucleus accumbens was negatively correlated with progressive ratio breakpoints, a measure of motivation to self-administer cocaine. Overall, these data suggest that cocaine self-administration elevates KOR/Dyn system activity in the mesolimbic dopamine pathway.

Abstract Single-molecule localization microscopy (SMLM) can be used to resolve subcellular structures and achieve a tenfold improvement in spatial resolution compared to that obtained by conventional fluorescence microscopy. However, the separation of single-molecule fluorescence events that requires thousands of frames dramatically increases the image acquisition time and phototoxicity, impeding the observation of instantaneous intracellular dynamics. Here we develop a deep-learning based single-frame super-resolution microscopy (SFSRM) method which utilizes a subpixel edge map and a multicomponent optimization strategy to guide the neural network to reconstruct a super-resolution image from a single frame of a diffraction-limited image. Under a tolerable signal density and an affordable signal-to-noise ratio, SFSRM enables high-fidelity live-cell imaging with spatiotemporal resolutions of 30 nm and 10 ms, allowing for prolonged monitoring of subcellular dynamics such as interplays between mitochondria and endoplasmic reticulum, the vesicle transport along microtubules, and the endosome fusion and fission. Moreover, its adaptability to different microscopes and spectra makes it a useful tool for various imaging systems.

Abstract Background The frequently occurred chemotherapy-induced diarrhea (CID) caused by irinotecan (CPT-11) administration has been the most representative side-effects of CPT-11, resulting in the chemotherapy suspension or failure. Our previous studies indicated that Gegen Qinlian formula exhibited a significant alleviation effect on CPT-11-induced diarrhea. However, referencing to Japanese Kampo medicine, the TCM standard decoction would supply the gap between ancient preparation application and modern industrial production. Methods The LC–MS technology combined with network pharmacology was employed to identify the active ingredients and mechanisms of GQD standard decoction for CPT-11-induced diarrhea. The anti-inflammatory activities associated with intestinal barrier function of GQD standard decoction were studied by SN-38 activated NCM460 cells in vitro and CPT-11-induced diarrhea in vivo. Proteins involved in inflammation, mRNA levels, disease severity scores, and histology involved in intestinal inflammation were analysed. Results There were 37 active compounds were identified in GQD standard decoction. Network pharmacology analyses indicated that PI3K-AKT signaling pathway were probably the main pathway of GQD standard decoction in CPT-11-induced diarrhea treatment, and PIK3R1, AKT1, NF-κB1 were the core proteins. Moreover, we found that the key proteins and pathway predicted above was verified in vivo and in vitro experiments, and the GQD standard decoction could protect the cellular proliferation in vitro and ameliorate CPT-11-induced diarrhea in mice model. Conclusions This study demonstrated the molecular mechanism of 37 active ingredients in GQD standard decoction against CPT-11-induced diarrhea. And the core proteins and pathway were validated by experiment. This data establishes the groundwork for particular molecular mechanism of GQD standard decoction active components, and this research can provide a scientific reference for the TCM therapy of CID.

Abstract Moso bamboo has been shown to accumulate high concentrations of iron and zinc in the seeds. However, the bioavailablity of iron and zinc in bamboo seeds is poorly understood. Here, we evaluated the bioaccessibility and bioavailability of iron and zinc in bamboo seeds by using an in vitro digestion protocol. Our evaluations revealed that values of bioaccessibility and bioavailability of iron were 25 and 21 mg kg−1 in bamboo seeds which were 1.6- and 1.7- fold higher than in rice, respectively. Also, values of bioaccessibility and bioavailability of zinc were 20 and 13 mg kg−1 in bamboo seeds which were 1.9- and 2.6- fold higher than in rice, respectively. Boiling process reduced both the bioaccessibility and bioavailability of iron and zinc. In addition, phytic acid concentration in bamboo seeds was only 0.42 times higher than in rice. By contrast, the tannins concentration in bamboo seeds was 2.2 times higher than in rice. Cellular localization results showed that iron and zinc were mainly concentrated in the embryo and the aleurone layer. These results clearly suggest that Moso bamboo seeds are rich in iron and zinc and have potential as a food for iron and zinc biofortification.