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Abstract The porcine epidemic diarrhea virus (PEDV) causes diarrhea in piglets, thereby causing very significant economic losses for the global swine industry. In previous studies, it has been confirmed that microRNAs (miRNAs) play an important role in the infection caused by PEDV. However, the precise molecular mechanism of miRNAs in the regulation of PEDV infection is still not fully understood. In the present study, we utilized miRNA-seq analysis to identify ssc-miR-1343 with differential expression between PEDV-infected and normal piglets. The expression of ssc-miR-1343 was detected in isolated exosomes, and it was found to be significantly higher than that in the controls following PEDV infection. The ssc-miR-1343 mimic was found to decrease PEDV replication, whereas the ssc-miR-1343 inhibitor was observed to increase PEDV replication, and ssc-miR-1343 was delivered by exosomes during PEDV infection. Mechanistically, ssc-miR-1343 binds to the 3′UTR region of FAM131C, down-regulating its expression, and FAM131C has been shown to enhance PEDV replication through simultaneously suppressing pathways associated with innate immunity. The ssc-miR-1343/FAM131C axis was found to upregulate the host immune response against PEDV infection. In conclusion, our findings indicate that the transport of ssc-miR-1343 in exosomes is involved in PEDV infection. This discovery presents a new potential target for the development of drugs to treat PEDV.

Abstract Background The distal aspect of the second molar (d-M2) often exhibits infrabony defects due to the adjacent third molar. Although the defects can be treated by guided tissue regeneration (GTR) after removing the third molar, the optimal timing remains uncertain following third molar removal in clinical decision-making. This study aimed to compare delayed and immediate GTR treatments to assist in clinical decision-making. Methods D-M2 infrabony defects with a minimum 1-year follow-up were collected and divided into three groups: Immediate GTR group, which underwent third molar extraction and received GTR simultaneously; Delayed GTR group, which underwent delayed GTR at least 3 months after third molar extraction; and Control group, which underwent only scaling and root planing during third molar extraction. The clinical and radiographic parameters related to the infrabony defect before GTR and post-surgery were evaluated using the Kruskal-Wallis test or one-way ANOVA, followed by post-hoc Dunn’s test or the Bonferroni test for pairwise comparisons. Results A total of 109 d-M2 infrabony defects were assessed. No significant differences were found between the two GTR groups, although both of them showed significant reductions in infrabony defect depth: the immediate GTR group (2.77 ± 1.97 mm vs. 0.68 ± 1.03 mm, p

Abstract Background Parent-child separation poses a significant challenge for left-behind children (LBC). However, limited empirical evidence exists regarding the correlation between left-behind characteristics and the psychological symptoms of LBC. This study investigated psychological symptoms among LBC and explored associations between left-behind characteristics and those symptoms. Methods Using stratified cluster sampling, 1,832 LBC aged 13–18 years from three cities in East China were selected for analysis. Participants’ depression and anxiety symptoms were assessed with the Patient Health Questionnaire 9 and the General Anxiety Disorder 7, respectively. Chi-square tests were used to compare differences in detection rates of psychological symptoms among LBC in different groups. Binary logistic regression analysis was used to infer associations between left-behind characteristics and psychological symptoms. Results Depression and anxiety symptoms were detected in 32.86% and 33.24%, respectively, of participating LBC. Univariate analysis showed statistically significant differences in detection rates of depression symptoms by sex, grade, and timing of parent-child separation. Statistically significant differences were observed in anxiety symptom rates by sex, grade, type of caregiver, and timing of mother-child separation. Multivariate analysis indicated a positive association between LBC’s anxiety symptoms and mother-child separation that occurred during post-primary school, and type of caregiver (father only or mother only). Our findings confirm a positive association between left-behind characteristics and anxiety symptoms among LBC. Conclusion The timing of mother-child separation and type of caregiver are potential risk factors for the development of anxiety symptoms in this population.

Abstract Icing plays an important role in various physical-chemical process. Although the formation of two-dimensional ice requires nanoscale confinement, two-dimensional bilayer ice in coexistence with three-dimensional ice without confinement remains poorly understood. Here, a critical value of a surface energy parameter is identified to characterize the liquid-solid interface interaction, above which two-dimensional and three-dimensional coexisting ice can surprisingly form on the surface. The two-dimensional ice growth mechanisms could be revealed by capturing the growth and merged of the metastable edge structures. The phase diagram about temperature and pressure vs energy parameters is predicted to distinguish liquid water, two-dimensional ice and three-dimensional ice. Furthermore, the deicing characteristics of coexisting ice demonstrate that the ice adhesion strength is linearly related to the ratio of ice-surface interaction energy to ice temperature. In addition, for gas-solid phase transition, the phase diagram about temperature and energy parameters is predicted to distinguish gas, liquid water, two-dimensional ice and three-dimensional ice. This work gives a perspective for studying the singular structure and dynamics of ice in nanoscale and provides a guide for future experimental realization of the coexisting ice.

Abstract Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly. Experimental validations reveal that IHIHICI assemble into helical β-sheet nanotubes with acetate modulation and perform phospholipase C-like and peroxidase-like activities with Ni coordination, demonstrating high thermostability and resistance to enzymatic degradation. The assembled nanotubes demonstrate cascade antifungal actions including outer mannan docking, wall disruption, lipid peroxidation and subsequent ferroptotic death, synergistically killing >90% Candida albicans within 10 min on disinfection pad. These findings demonstrate an effective de novo design strategy for developing materials with multi-antimicrobial mode of actions.

Abstract Background Patients with sepsis with low albumin levels and high red blood cell distribution width levels have poor prognoses. Red blood cell distribution width to albumin ratio (RAR) has recently attracted attention as an innovative inflammation biomarker. We aimed to explore the association between RAR and the prognosis of patients with sepsis. Methods This retrospective observational study included 402 patients meeting the sepsis-3 standards admitted to Yantai Yuhuangding Hospital’s intensive care units (ICUs) between January 2020 and December 2022. The relationship between RAR and mortality in patients with sepsis was examined using regression analysis, Kaplan–Meier analyses, and a receiver operating characteristic curve. Subgroup and sensitivity analyses were conducted to assess the results’ robustness. Results RAR, when considered as a continuous variable, was a significant independent in-hospital mortality risk factor (adjusted odds ratio [OR]: 1.383; 95% confidence interval [CI]: 1.164–1.645; P

The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity. Here, we show that carrimycin, a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials, decreases the efficiency of programmed –1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion. Carrimycin binds directly to the coronaviral frameshift-stimulatory element (FSE) RNA pseudoknot, interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes. Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses. Because the FSE mechanism is essential in all coronaviruses, carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA. This finding may open a new direction in antiviral drug discovery for coronavirus variants.

Abstract Despite recent technological advancements in cell tumor DNA (ctDNA) mutation detection, challenges persist in identifying low-frequency mutations due to inadequate sensitivity and coverage of current procedures. Herein, we introduce a super-sensitivity and specificity technique for detecting ctDNA mutations, named HiCASE. The method utilizes PCR-based CRISPR, coupled with the restriction enzyme. In this work, HiCASE focuses on testing a series of EGFR mutations to provide enhanced detection technology for non–small cell lung cancer (NSCLC), enabling a detection sensitivity of 0.01% with 40 ng cell free DNA standard. When applied to a panel of 140 plasma samples from 120 NSCLC patients, HiCASE exhibits 88.1% clinical sensitivity and 100% specificity with 40 μL of plasma, higher than ddPCR and Super-ARMS assay. In addition, HiCASE can also clearly distinguish T790M/C797S mutations in different positions at a 1% variant allele frequency, offering valuable guidance for drug utilization. Indeed, the established HiCASE assay shows potential for clinical applications.

AIM: To evaluate the relationship of overweight and obesity with retinal and choroidal thickness in adults without ocular symptoms by swept-source optical coherence tomography (SS-OCT). METHODS: According to the body mass index (BMI) results, the adults enrolled in the cross-sectional study were divided into the normal group (18.50≤BMI

Abstract Atmospheric pollution significantly impacts the regional economy and human health, and its prediction has been increasingly emphasized. The performance of traditional prediction methods is limited due to the lack of historical data support in new atmospheric monitoring sites. Therefore, this paper proposes a two-stage attention mechanism model based on transfer learning (TL-AdaBiGRU). First, the first stage of the model utilizes a temporal distribution characterization algorithm to segment the air pollutant sequences into periods. It introduces a temporal attention mechanism to assign self-learning weights to the period segments in order to filter out essential period features. Then, in the second stage of the model, a multi-head external attention mechanism is introduced to mine the network's hidden layer key features. Finally, the adequate knowledge learned by the model at the source domain site is migrated to the new site to improve the prediction capability of the new site. The results show that (1) the model is modeled from the data distribution perspective, and the critical information within the sequence of periodic segments is mined in depth. (2) The model employs a unique two-stage attention mechanism to capture complex nonlinear relationships in air pollutant data. (3) Compared with the existing models, the mean absolute error (MAE), root mean square error (RMSE), and mean absolute percentage error (MAPE) of the model decreased by 14%, 13%, and 4%, respectively, and the prediction accuracy was greatly improved.

Abstract Hedyotis diffusa Willd (HDW) possesses heat-clearing, detoxification, anti-cancer, and anti-inflammatory properties. However, its effects on rheumatoid arthritis (RA) remain under-researched. In this study, we identified potential targets of HDW and collected differentially expressed genes of RA from the GEO dataset GSE77298, leading to the construction of a drug-component-target-disease regulatory network. The intersecting genes underwent GO and KEGG analysis. A PPI protein interaction network was established in the STRING database. Through LASSO, RF, and SVM-RFE algorithms, we identified the core gene MMP9. Subsequent analyses, including ROC, GSEA enrichment, and immune cell infiltration, correlated core genes with RA. mRNA–miRNA–lncRNA regulatory networks were predicted using databases like TargetScan, miRTarBase, miRWalk, starBase, lncBase, and the GEO dataset GSE122616. Experimental verification in RA-FLS cells confirmed HDW’s regulatory impact on core genes and their ceRNA expression. We obtained 11 main active ingredients of HDW and 180 corresponding targets, 2150 RA-related genes, and 36 drug-disease intersection targets. The PPI network diagram and three machine learning methods screened to obtain MMP9, and further analysis showed that MMP9 had high diagnostic significance and was significantly correlated with the main infiltrated immune cells, and the molecular docking verification also showed that MMP9 and the main active components of HDW were well combined. Next, we predicted 6 miRNAs and 314 lncRNAs acting on MMP9, and two ceRNA regulatory axes were obtained according to the screening. Cellular assays indicated HDW inhibits RA-FLS cell proliferation and MMP9 protein expression dose-dependently, suggesting HDW might influence RA’s progression by regulating the MMP9/miR-204-5p/MIAT axis. This innovative analytical thinking provides guidance and reference for the future research on the ceRNA mechanism of traditional Chinese medicine in the treatment of RA.

Abstract Background The key role of thrombospondin 1 (THBS1) in the pathogenesis of acute-on-chronic liver failure (ACLF) is unclear. Here, we present a transcriptome approach to evaluate THBS1 as a potential biomarker in ACLF disease pathogenesis. Methods Biobanked peripheral blood mononuclear cells (PBMCs) from 330 subjects with hepatitis B virus (HBV)-related etiologies, including HBV-ACLF, liver cirrhosis (LC), and chronic hepatitis B (CHB), and normal controls (NC) randomly selected from the Chinese Group on the Study of Severe Hepatitis B (COSSH) prospective multicenter cohort underwent transcriptome analyses (ACLF = 20; LC = 10; CHB = 10; NC = 15); the findings were externally validated in participants from COSSH cohort, an ACLF rat model and hepatocyte-specific THBS1 knockout mice. Results THBS1 was the top significantly differentially expressed gene in the PBMC transcriptome, with the most significant upregulation in ACLF, and quantitative polymerase chain reaction (ACLF = 110; LC = 60; CHB = 60; NC = 45) was used to verify that THBS1 expression corresponded to ACLF disease severity outcome, including inflammation and hepatocellular apoptosis. THBS1 showed good predictive ability for ACLF short-term mortality, with an area under the receiver operating characteristic curve (AUROC) of 0.8438 and 0.7778 at 28 and 90 days, respectively. Enzyme-linked immunosorbent assay validation of the plasma THBS1 using an expanded COSSH cohort subjects (ACLF = 198; LC = 50; CHB = 50; NC = 50) showed significant correlation between THBS1 with ALT and γ-GT (P = 0.01), and offered a similarly good prognostication predictive ability (AUROC = 0.7445 and 0.7175) at 28 and 90 days, respectively. ACLF patients with high-risk short-term mortality were identified based on plasma THBS1 optimal cut-off value (

Abstract The striatum, known as the input nucleus of the basal ganglia, is extensively studied for its diverse behavioral roles. However, the relationship between its neuronal and vascular activity, vital for interpreting functional magnetic resonance imaging (fMRI) signals, has not received comprehensive examination within the striatum. Here, we demonstrate that optogenetic stimulation of dorsal striatal neurons or their afferents from various cortical and subcortical regions induces negative striatal fMRI responses in rats, manifesting as vasoconstriction. These responses occur even with heightened striatal neuronal activity, confirmed by electrophysiology and fiber-photometry. In parallel, midbrain dopaminergic neuron optogenetic modulation, coupled with electrochemical measurements, establishes a link between striatal vasodilation and dopamine release. Intriguingly, in vivo intra-striatal pharmacological manipulations during optogenetic stimulation highlight a critical role of opioidergic signaling in generating striatal vasoconstriction. This observation is substantiated by detecting striatal vasoconstriction in brain slices after synthetic opioid application. In humans, manipulations aimed at increasing striatal neuronal activity likewise elicit negative striatal fMRI responses. Our results emphasize the necessity of considering vasoactive neurotransmission alongside neuronal activity when interpreting fMRI signal.

Background: Anti-interferon-γ autoantibodies (AIGAs) syndrome is susceptible to disseminated opportunistic infections due to increased AIGAs, but its clinical immunological characteristics remain unrecognized.Methods: We conducted a prospective cohort study between January 2021 and December 2023, recruiting patients with opportunistic infections who were categorized into AIGAs-positive and AIGAs-negative groups. Clinical immunological data and outcomes were documented. A subset of AIGAs-positive patients received glucocorticoid treatment, and its effectiveness was evaluated.Results: A total of 238 patients were enrolled, with 135 AIGAs-positive and 103 AIGAs-negative patients. AIGAs-positive patients showed higher rates of multiple pathogen dissemination, shorter progression-free survival (PFS), and increased exacerbation frequency. They also showed elevated erythrocyte sedimentation rate (ESR), globulin (GLB), immunoglobulin (Ig)G, IgE, and IgG4 levels. Among the 70 AIGAs-positive patients monitored for at least six months, three subtypes were identified: high AIGAs titer with immune damage, high AIGAs titer without immune damage, and low AIGAs titer without immune damage. Of the 55 patients followed for 1 year, decreasing AIGAs titer and immune indices (GLB, IgG, IgE, IgG4) were observed. Among the 31 patients with high AIGAs titer and immune damage treated with low-dose glucocorticoids at the stable phase, reductions were observed in immune indices and AIGAs titer in 67.74% of cases.Conclusions: AIGAs-positive patients exhibit infectious and immunological characteristics. Elevated AIGAs, IgG, IgG4, and IgE indicate abnormal immune damages. AIGAs titer generally decrease over time. Stable-phase AIGAs-positive patients can be categorized into three subtypes, with those having high AIGAs titer and increased immune indices potentially benefitting from glucocorticoid treatment.

BackgroundThis study presents real-world evidence on the clinical outcomes of the Alberta Complementary Health Integration Project (ABCHIP), which utilized acupuncture to address pain and mental health issues in two vulnerable populations in Alberta: youth (aged 24 and below) and elderly (aged 55 and above).MethodsOver 282 days, a total of 606 patients received 5,424 acupuncture treatments. Tailored to each patients’ specific pain and mental health concerns, an individualized treatment plan was selected, following a standard treatment protocol lasting 1 to 3 months. Patients were evaluated at least twice: initially and upon completing therapy. Primary treatment outcomes were assessed using various measures, including the Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire 9 (PHQ9), PROMIS Anxiety 8a and its pediatric form PROMIS Anxiety-Pediatric, PROMIS Short Form v1.0 Fatigue 8a and its pediatric counterpart PROMIS Pediatric Short Form v2.0 Fatigue 10a, PROMIS Short Form v1.1 Anger 5a and its version PROMIS SF v2.0 5a, and EQ-5D-5L. These measures gauged pain reduction, improved sleep quality, reduced depression, anxiety, fatigue, anger, and quality of life, respectively.ResultsAnalysis of data from 500 patients who received at least 6 acupuncture sessions through ABCHIP showed statistically significant improvements in clinical outcomes. Among this group, the subgroup of 235 patients who received at least 12 sessions demonstrated the most favorable treatment outcomes, including an 75.5% reduction in pain severity, a 53.1% improvement in sleep quality, a 78.4% drop in depression, a 41.1% decline in anxiety, a 43.7% decrease in fatigue, a 38.2% decrease in anger, and a 42.6% improvement in overall quality of life.ConclusionIntegrating acupuncture with usual care demonstrates promise in enhancing mental health, alleviating chronic and general pain, and improving overall quality of life. The findings suggest that integrative programs, such as ABCHIP, present an effective approach to addressing pain and mental health concerns in vulnerable populations, providing valuable insights for future healthcare interventions.

Thermal barrier coatings (TBCs) applications of yttria-stabilized (YSZ) are widely utilized on turbine blades of aviation engines due to its low thermal conductivity and high electrical conductivity. Predicting the infrared emissivity aids in monitoring blade operating temperatures, ensuring safe engine operation. This paper innovatively introduces a novel three-dimensional columnar EB-PVD coating model and utilizes the FDTD method to predict emissivity. The model exhibits strong consistency with experimental results for predicted emissivity in the short-wave infrared band (1.4–3 μm). The unique microstructure of the EB-PVD thermal barrier coatings significantly influence the infrared emissivity. The results indicate that vertically uniform arranged feathers exhibit higher emissivity levels compared to feathers with varying densities. Additionally, increasing the thickness of the ceramic top coating and reducing spherical closed porosity also enhance the emissivity levels. This research provides guidance for controlling emissivity at the microscale in the preparation of thermal barrier coatings.

Summary: Diagnosis of tuberculosis remains a challenge when microbiological tests are negative. Immune cell atlas of patients with tuberculosis and healthy controls were established by single-cell transcriptome. Through integrated analysis of scRNA-seq with microarray and bulk RNA sequencing data, a ferroptosis-related gene signature containing ACSL4, CTSB, and TLR4 genes that were associated with tuberculosis disease was identified. Four gene expression datasets from blood samples of patients with tuberculosis, latent tuberculosis infection, and healthy controls were used to assess the diagnostic value of the gene signature. The areas under the ROC curve for the combined gene signature were 1.000, 0.866, 0.912, and 0.786, respectively, in differentiating active tuberculosis from latent infection. During anti-tuberculosis treatment, the expression of the gene signature decreased significantly in cured patients with tuberculosis. In conclusion, the ferroptosis-related gene signature was associated with tuberculosis treatment efficacy and was a promising biomarker for differentiating active tuberculosis from latent infection.

Clubroot disease, which is caused by the obligate biotrophic protist Plasmodiophora brassicae, leads to the formation of galls, commonly known as pathogen-induced tumors, on the roots of infected plants. The identification of crucial regulators of host tumor formation is essential to unravel the mechanisms underlying the proliferation and differentiation of P. brassicae within plant cells. To gain insight into this process, transcriptomic analysis was conducted to identify key genes associated with both primary and secondary infection of P. brassicae in Chinese cabbage. Our results demonstrate that the k-means clustering of subclass 1, which exhibited specific trends, was closely linked to the infection process of P. brassicae. Of the 1610 differentially expressed genes (DEGs) annotated in subclass 1, 782 were identified as transcription factors belonging to 49 transcription factor families, including bHLH, B3, NAC, MYB_related, WRKY, bZIP, C2H2, and ERF. In the primary infection, several genes, including the predicted Brassica rapa probable pectate lyase, RPM1-interacting protein 4-like, L-type lectin-domain-containing receptor kinase, G-type lectin S-receptor-like serine, B. rapa photosystem II 22 kDa protein, and MLP-like protein, showed significant upregulation. In the secondary infection stage, 45 of 50 overlapping DEGs were upregulated. These upregulated DEGs included the predicted B. rapa endoglucanase, long-chain acyl-CoA synthetase, WRKY transcription factor, NAC domain-containing protein, cell division control protein, auxin-induced protein, and protein variation in compound-triggered root growth response-like and xyloglucan glycosyltransferases. In both the primary and secondary infection stages, the DEGs were predicted to be Brassica rapa putative disease resistance proteins, L-type lectin domain-containing receptor kinases, ferredoxin-NADP reductases, 1-aminocyclopropane-1-carboxylate synthases, histone deacetylases, UDP-glycosyltransferases, putative glycerol-3-phosphate transporters, and chlorophyll a-binding proteins, which are closely associated with plant defense responses, biosynthetic processes, carbohydrate transport, and photosynthesis. This study revealed the pivotal role of transcription factors in the initiation of infection and establishment of intracellular parasitic relationships during the primary infection stage, as well as the proliferation and differentiation of the pathogen within the host cell during the secondary infection stage.

Abstract Counties in China play a pivotal role in economic and social development, acting as essential leadership hubs for large and medium-sized cities, contributing to rural revitalization, and facilitating urban-rural integration. Using ArcGIS spatial analysis, this study examines the population distribution spatial and dispersion patterns in Chinese counties based on 40 years of data from the first to the seventh national population census. Results reveal noticeable growth trends and regional disparities in county populations, with an increase in large-population counties and a decrease in small-population ones. Recent population growth concentrates in urban agglomerations, metropolitan areas, and southeastern coastal regions, while reductions occur in the northeastern and Inner Mongolia border areas. Furthermore, the study identifies “high-high” agglomerations around provincial capitals and “low-low” agglomerations in economically underdeveloped western and northeastern border regions. China’s population distribution spatial agglomeration has been increasing, with acceleration toward specific areas. The first through seventh census show rapid growth at low density, followed by growth at medium density, stable growth, and eventually negative growth. This suggests a likely slowdown and potential reversal in China’s future population growth. Additionally, an Auto Regression Integrated Moving Average (ARIMA) model is employed to forecast China’s total population, projecting a decline to 1343.68 million by 2035. The emergence of “population loss counties” in contemporary China underscores the need for a rational understanding of their development status and trends to optimize population development strategies and promote economic and social progress.

Abstract Copy-number alterations (CNAs) are a hallmark of cancer and can regulate cancer cell states via altered gene expression values. Herein, we have developed a copy-number impact (CNI) analysis method that quantifies the degree to which a gene expression value is impacted by CNAs and leveraged this analysis at the pathway level. Our results show that a high CNA is not necessarily reflected at the gene expression level, and our method is capable of detecting genes and pathways whose activity is strongly influenced by CNAs. Furthermore, the CNI analysis enables unbiased categorization of CNA categories, such as deletions and amplifications. We identified six CNI-driven pathways associated with poor treatment response in ovarian high-grade serous carcinoma (HGSC), which we found to be the most CNA-driven cancer across 14 cancer types. The key driver in most of these pathways was amplified wild-type KRAS, which we validated functionally using CRISPR modulation. Our results suggest that wild-type KRAS amplification is a driver of chemotherapy resistance in HGSC and may serve as a potential treatment target.

Abstract Exploring non-genetic evolution of cell states during cancer treatments has become attainable by recent advances in lineage-tracing methods. However, transcriptional changes that drive cells into resistant fates may be subtle, necessitating high resolution analysis. Here, we present ReSisTrace that uses shared transcriptomic features of sister cells to predict the states priming treatment resistance. Applying ReSisTrace in ovarian cancer cells perturbed with olaparib, carboplatin or natural killer (NK) cells reveals pre-resistant phenotypes defined by proteostatic and mRNA surveillance features, reflecting traits enriched in the upcoming subclonal selection. Furthermore, we show that DNA repair deficiency renders cells susceptible to both DNA damaging agents and NK killing in a context-dependent manner. Finally, we leverage the obtained pre-resistance profiles to predict and validate small molecules driving cells to sensitive states prior to treatment. In summary, ReSisTrace resolves pre-existing transcriptional features of treatment vulnerability, facilitating both molecular patient stratification and discovery of synergistic pre-sensitizing therapies.

Abstract Background The roles of serum lipids on digestive system cancer (DSC) risk were still inconclusive. In this study, we systematically assessed indicative effects of signature lipidomic biomarkers (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG)) on DSC (oesophagus, stomach, colorectal, liver, gallbladder, and pancreas cancers) risk. Methods HDL-C, LDL-C, and TG concentration measurements were respectively analyzed with enzyme immunoinhibition, enzymatic selective protection, and GPO-POD methods in AU5800 supplied from Beckman Coulter. The diagnoses of DSCs were coded using International Classification of Diseases, Tenth Revision (ICD-10) codes updated until October 2022 in the UK Biobank (UKB). In this study, we assessed phenotypic association patterns between signature lipidomic biomarkers and DSC risk using restricted cubic splines (RCSs) in multivariable-adjusted Cox proportional hazards regression models. Moreover, linear and nonlinear causal association patterns of signature lipidomic biomarkers with DSC risk were determined by linear and nonlinear Mendelian randomization (MR) analyses. Results A median follow-up time of 11.8 years was recorded for 319,568 participants including 6916 DSC cases. A suggestive independent nonlinear phenotypic association was observed between LDL-C concentration and stomach cancer risk (P nonlinearity < 0.05, P overall < 0.05). Meanwhile, a remarkable independent linear negative phenotypic association was demonstrated between HDL-C concentration and stomach cancer risk (P nonlinearity > 0.05, P overall < 0.008 (0.05/6 outcomes, Bonferroni-adjusted P)), and suggestive independent linear positive associations were observed between HDL-C concentration and colorectal cancer risk, and between TG concentration and gallbladder cancer risk (P nonlinearity > 0.05, P overall < 0.05). Furthermore, based on nonlinear and linear MR-based evidences, we observed an suggestive independent negative causal association (hazard ratio (HR) per 1 mmol/L increase: 0.340 (0.137-0.843), P = 0.020) between LDL-C and stomach cancer risk without a nonlinear pattern (Quadratic P = 0.901, Cochran Q P = 0.434). Meanwhile, subgroup and stratified MR analyses both supported the category of LDL-C ≥ 4.1 mmol/L was suggestively protective against stomach cancer risk, especially among female participants (HR: 0.789 (0.637-0.977), P = 0.030) and participants aged 60 years or older (HR: 0.786 (0.638-0.969), P = 0.024), and the category of TG ≥ 2.2 mmol/L concluded to be a suggestive risk factor for gallbladder cancer risk in male participants (HR: 1.447 (1.020-2.052), P = 0.038) and participants aged 60 years or older (HR: 1.264 (1.003-1.593), P = 0.047). Conclusions Our findings confirmed indicative roles of signature lipidomic biomarkers on DSC risk, notably detecting suggestive evidences for a protective effect of high LDL-C concentration on stomach cancer risk, and a detrimental effect of high TG concentration on gallbladder cancer risk among given participants.

Abstract In recent years, deep artificial neural networks have attracted much attention and have been applied in various fields because they surpass the parameter fitting effect of traditional methods under the condition of data convergence. On the other hand, limited transmission bandwidth and storage capacity make image compression necessary in communication. Here, a compression algorithm that combines the K‐means clustering algorithm with the neural network algorithm is proposed. First, the pixel points of the image are clustered by K‐means algorithm in order to reduce the amount of data input to the neural network algorithm. Secondly, neural network is used to extract image features which realizes further compression. The experiment results show that the peak signal‐to‐noise ratio (PSNR) is 33.48 dB at most with compression ratio at 32:1. The ablation experiment shows that the run time speeds up 9.5% compared to the algorithm without K‐means clustering. Comprehensive comparison experiment shows that the average PSNR is 30.09 dB, which is larger than other baseline approaches. The proposed algorithm is an efficient solution for image compression.

With the rapid development of digital media and entertainment industry, the importance of 3D mesh animation has become increasingly prominent. However, the traditional production methods are faced with problems such as high computational complexity and unnatural effects when dealing with complex motion. To improve the production efficiency and quality of 3D mesh animation, this study innovatively integrates integer programming, nonlinear constraint optimization, and machine learning algorithms to construct a new 3D mesh animation optimization algorithm. Comparative analysis of the improved machine learning algorithm shows that the mean absolute error of the algorithm is 0.00048 and the fit degree is 98.8%, which is better than the comparison algorithm. Then, the performance of the proposed 3D mesh animation optimization algorithm is analyzed. The results show that the rendering speed and average frame rate of the proposed algorithm are 29.5 FPS and 28.7 FPS, respectively, which is superior to the comparison algorithm. The algorithm can effectively improve the efficiency and quality of animation production, and inject new vitality into the development of digital media and entertainment industry. This study not only provides new ideas and methods for optimizing 3D mesh animation, but also provides useful references for research and applications in related fields.

Abstract Adventitious root formation is a key step in vegetative propagation via cuttings. It is crucial for establishing birch plantations and preserve birch varieties. Although previous studies have highlighted role of WOX11 in controlling adventitious root formation, no such study has been conducted in birch. Understanding the mechanism of adventitious root formation is essential for improvement of rooting or survival rate using stem cuttings in birch. In this study, we cloned BpWOX11 and produced BpWOX11 overexpression (OE) transgenic lines using the Agrobacterium-mediated plant transformation. OE lines exhibited early initiated adventitious root formation, leading to increase the rooting rate of stem cuttings plants. RNA sequencing analysis revealed that OE lines induced the gene expression related to expansin and cell division pathway, as well as defense and stress response genes. These may be important factors for the BpWOX11 gene to promote adventitious root formation in birch cuttings. The results of this study will help to further understand the molecular mechanisms controlling the formation of adventitious roots in birch.

Authentication for the Internet of Vehicles (IoV) is essential for safe IoV connection. However, because of the peculiar structure of IoV, current authentication schemes heavily rely on Road Side Units (RSUs). An excessive number of RSUs will make it difficult to synchronize updates, which will make system authentication inefficient overall and prevent the reuse of authentication results. Based on this, this paper proposes a blockchain-based secure distributed authentication scheme for IoV. First, data processing and storage are decentralized to the edge of the network to reduce the communication delay and response time with the trusted authority (TA). Second, in the IoV authentication process, smart contract technology is used to achieve automatic triggering of the authentication process, and an optimized Practical Byzantine Fault Tolerant Consensus (PBFT) algorithm is designed to add the authentication information to the blockchain ledger so that the authentication results can be reused. Finally, this paper performs formal security verification and informal security analysis using and Real-Or-Random (ROR) oracle model and AVISPA tool. In addition, this paper performs a detailed evaluation of computation cost and communication cost and uses SUMO for simulation verification. The security analysis and performance evaluation show that the scheme meets the security requirements of the IoV while having less communication and computation cost.

To present a modified technique for the reconstruction of a large cyclodialysis cleft with capsular tension ring (CTR) and continuous and cerclage sutures without scleral flaps in 12 cases. The mean visual acuity was 0.75 ± 0.47 logarithm of the minimal angle of resolution (logMAR), and the average intraocular pressure (IOP) was 3.35 ± 0.41 mmHg before surgery. Ultrasound biomicroscopy (UBM) revealed a ciliary cleft of 4.3 ± 3.5 clock hours. We performed the modified technique for the reconstruction of a large cyclodialysis cleft. Postoperative visual acuity improved to 0.48 ± 0.26 logMAR, and the IOP improved to 15.88 ± 3.81 mmHg. Postoperative UBM showed that cyclodialysis disappeared in the whole circumference of 12 eyes. The postoperative complications included 42% (5 eyes) with a temporary elevation of IOP and 16% (2 eyes) with a posterior shift of the ciliary body. No other complications were detected during the follow-up. Based on the results, our modified technique might be useful for most cyclodialysis clefts.

Abstract Background Toxoplasma gondii is an intracellular protozoan parasite that can infect a wide range of warm-blooded animals, including humans. It poses significant health risks, particularly in immunocompromised individuals and during pregnancy, leading to severe disease manifestations. The liver, being a crucial organ involved in immune response and metabolic regulation, plays a critical role in the host's defense against T. gondii infection. Methods In this study, we utilized RNA sequencing to investigate the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the liver of mice infected with T. gondii. By employing this method, we obtained a comprehensive overview of the alterations in gene expression occurring in the liver during infection. Results By comparing the infected groups to the control groups, we identified numerous differentially expressed lncRNAs DElncRNAs and DEmRNAs at two stages of infection. Specifically, at the acute infection stage, we found 628 DElncRNAs, and 6346 DEmRNAs. At the chronic infection stage, we identified 385 DElncRNAs and 2513 DEmRNAs. Furthermore, we identified 1959 commonly expressed DEmRNAs, including IL27, Nos2, and Cxcr2, across two infection stages. Enrichment and co-location analyses revealed pathways linked to immune and inflammatory responses during T. gondii infection. Notably, through co-location analysis, our analysis revealed several DElncRNAs, including Gm29156, Gm29157, and Gm28644, which are potentially implicated in the progression of liver inflammation induced by T. gondii. Additionally, functional enrichment analysis disclosed stage-specific characteristics of liver inflammation and immune response, alongside changes in metabolic regulation and immunosuppression pathways. Conclusions Our findings provide valuable insights into the expression patterns of lncRNAs and mRNAs in the liver at different stages of T. gondii infection. We identified potential regulatory factors and pathways implicated in liver inflammation, thereby enhancing our understanding of the molecular mechanisms underlying liver inflammation and immune responses during T. gondii infection. These findings could contribute to the development of targeted therapeutic strategies for liver inflammation in the context of T. gondii infection. Graphical Abstract

Abstract Hepatocarcinogenesis is a multi-step process. However, the regulators of hepatocellular carcinoma (HCC) initiation are understudied. Adult liver-specific gene expression was globally downregulated in HCC. We hypothesize that adult liver-specific genes, especially adult liver-enriched transcription factors may exert tumor-suppressive functions in HCC. In this study, we identify ZBTB7B, an adult liver-enriched transcription factor as a permissive regulator of HCC initiation. ZBTB7B is highly expressed in hepatocytes in adult livers, compared to fetal livers. To evaluate the functions of ZBTB7B in hepatocarcinogenesis, we performed hepatocyte-specific ZBTB7B knockout in hydrodynamic oncogene transfer-induced mouse liver cancer models. Hepatocyte-specific knockout of ZBTB7B promotes activated Akt and N-Ras-induced HCC development. Moreover, ZBTB7B deficiency sensitizes hepatocytes to a single oncogene Akt-induced oncogenic transformation and HCC initiation, which is otherwise incompetent in inducing HCC. ZBTB7B deficiency accelerates HCC initiation by down-regulating adult liver-specific gene expression and priming livers to a fetal-like state. The molecular mechanism underlying ZBTB7B functions in hepatocytes was investigated by integrated transcriptomic, phosphoproteomic, and chromatin immunoprecipitation-sequencing analyses. Integrative multi-omics analyses identify c-Jun as the core signaling node in ZBTB7B-deficient liver cancer initiation. c-Jun is a direct target of ZBTB7B essential to accelerated liver cancer initiation in ZBTB7B-deficient livers. Knockdown of c-Jun expression or dominant negative c-Jun expression delays HCC development in ZBTB7B-deficient livers. In addition, ZBTB7B competes with c-Jun for chromatin binding. Ectopic ZBTB7B expression attenuates the tumor-promoting functions of c-Jun. Expression of ZBTB7B signature, composed of 140 genes co-regulated by ZBTB7B and c-Jun, is significantly downregulated in early-stage HCCs compared to adjacent normal tissues, correlates to liver-specific gene expression, and is associated with good prognosis in human HCC. Thus, ZBTB7B functions as a permissive regulator of HCC initiation by directly regulating c-Jun expression and function.

Abstract Objective The doctor-patient relationship (DPR) plays a crucial role in the Chinese healthcare system, functioning to improve medical quality and reduce medical costs. This study examined the psychometric properties of the Chinese version of the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ-10) among general hospital inpatients in China. Methods The research recruited 38 resident doctors responsible for 120 participants, and factor analyses were used to assess the construct validity of the scale. Convergent validity was evaluated by examining the correlation between DDPRQ-10 and depressive symptoms, burnout, and self-efficacy, using the Patient Health Questionnaire Depression Scale-9 item (PHQ-9), and the Maslach Burnout Inventory (MBI). Both multidimensional item response theory (MIRT) and unidimensional item response theory (IRT) frameworks were used to estimate the parameters of each item. Results The Chinese version of DDPRQ-10 showed satisfactory internal consistency (Cronbach's alpha = 0.931), and fitted in a modified two-factor model of positive feelings and negative feelings (χ2/df = 1.494, GFI = 0.925, RMSEA = 0.071, SRMR = 0.008, CFI = 0.985, NFI = 0.958, NNFI = 0.980, TLI = 0.980, IFI = 0.986). Significant correlations with PHQ-9 with DDPRQ-10 and both subscales were revealed (r = 0.293 ~ 0.333, p

In recent years, many studies have reported that microRNAs play an important role in the pathogenesis of a variety of diseases, and the aim of this paper is to explore the role and mechanism of miR-346 in acute respiratory distress syndrome (ARDS). A mouse model of ARDS was constructed by LPS induction, and RT-qPCR assay was used to verify that the expression level of miR-346 in lung tissue was significantly increased, and was negatively correlated with oxygenation index. Inhibiting the expression of miR-346 in mice and HPMECs by miR-346 inhibitor confirmed that decreased miR-346 expression could lead to increased oxygenation index, decreased lung index, lung water content and NO content to reduce lung injury in mice, while lung inflammation was alleviated and apoptosis was reduced in mice. The same results were obtained in cells. BCL6 was predicted to be a target of miR-346 by targetscan and miRDB; when miR-346 was inhibited, BCL6 expression was increased, and if miR-346 and BCL6 expression were inhibited at the same time, it could aggravate lung injury and reduce the proliferation of HPMECs and increase their apoptosis and inflammation in mice. This shows that miR-346 inhibits the migration of HPMECs by regulating BCL6 expression, which in turn promotes the apoptosis of HPMECs, leading to inflammation and inducing ARDS.

Background Zinc (Zn) is a vital micronutrient essential for plant growth and development. Transporter proteins of the ZRT/IRT-like protein (ZIP) family play crucial roles in maintaining Zn homeostasis. Although the acquisition, translocation, and intracellular transport of Zn are well understood in plant roots and leaves, the genes that regulate these pathways in fruits remain largely unexplored. In this study, we aimed to investigate the function of SlZIP11 in regulating tomato fruit development. Methods We used Solanum lycopersicum L. ‘Micro-Tom’ SlZIP11 (Solanum lycopersicum) is highly expressed in tomato fruit, particularly in mature green (MG) stages. For obtaining results, we employed reverse transcription-quantitative polymerase chain reaction (RT-qPCR), yeast two-hybrid assay, bimolecular fluorescent complementation, subcellular localization assay, virus-induced gene silencing (VIGS), SlZIP11 overexpression, determination of Zn content, sugar extraction and content determination, and statistical analysis. Results RT-qPCR analysis showed elevated SlZIP11 expression in MG tomato fruits. SlZIP11 expression was inhibited and induced by Zn deficiency and toxicity treatments, respectively. Silencing SlZIP11 via the VIGS technology resulted in a significant increase in the Zn content of tomato fruits. In contrast, overexpression of SlZIP11 led to reduced Zn content in MG fruits. Moreover, both silencing and overexpression of SlZIP11 caused alterations in the fructose and glucose contents of tomato fruits. Additionally, SlSWEEET7a interacted with SlZIP11. The heterodimerization between SlSWEET7a and SlZIP11 affected subcellular targeting, thereby increasing the amount of intracellularly localized oligomeric complexes. Overall, this study elucidates the role of SlZIP11 in mediating Zn accumulation and sugar transport during tomato fruit ripening. These findings underscore the significance of SlZIP11 in regulating Zn levels and sugar content, providing insights into its potential implications for plant physiology and agricultural practices.

While waiting has been a prevalent and mentally taxing experience for consumers in marketing scenarios, little research has explored situational factors that enhance consumer patience. Drawing on the priming theory, attachment theory, and conservation of resources theory, the current research examines how cuteness as a situational factor affects consumer patience. Across five experiments (N = 1030), we demonstrate that exposure to cuteness enhances consumer patience (Study 1). Moreover, we uncover that the effect is driven by perceived social support employing both mediation (Study 2) and moderation approaches (Study 3). Furthermore, we identify time pressure as the moderator, such that the effect of cuteness on consumer patience only exists among individuals under low time pressure and disappears for those under high time pressure (Study 4). Finally, we examine the downstream consequence of consumer patience for word-of-mouth positivity (Study 5). These findings contribute to the literature on cuteness, patience, and perceived social support, while also offering practical implications for companies seeking to enhance consumer patience.

Abstract Pulmonary endarterectomy (PEA) is the standard treatment for chronic thromboembolic pulmonary hypertension. However, it poses risks of perioperative vascular complications, which can lead to serious clinical outcomes. This study introduces a novel noninvasive and radiation‐free clinical imaging tool, electrical impedance tomography (EIT), for real‐time bedside assessment of lung perfusion after PEA. It identifies ventilation‐perfusion mismatches arising from postoperative complications, particularly valuable for patients with hemodynamic instability, thus eliminating risks tied to CT room transfers. The article reports a case where EIT was used to identify an in‐situ thrombosis post‐PEA, marking the first such application. The emphasis is on early detection using EIT, which offers a promising approach for therapeutic interventions and improved postoperative evaluations.

BackgroundThis study investigates the burden of chronic kidney disease attributed to type 2 diabetes (CKD-T2D) across different geographical locations and time periods from 1990 to 2019. A total of 204 countries and regions are included in the analysis, with consideration given to their socio-demographic indexes (SDI). The aim is to examine both spatial and temporal variations in CKD-T2D burden.MethodsThis research utilized data from the 2019 Global Burden of Diseases Study to evaluate the age-standardized incidence rates (ASIR), Disability-Adjusted Life Years (DALYs), and Estimated Annual Percentage Change (EAPC) associated with CKD-T2D.ResultsSince 1990, there has been a noticeable increase of CKD age-standardized rates due to T2D, with an EAPCs of 0.65 (95% confidence interval [CI]: 0.63 to 0.66) for ASIR and an EAPC of 0.92 (95% CI: 0.8 to 1.05) for age-standardized DALYs rate. Among these regions, Andean Latin America showed a significant increase in CKD-T2D incidence [EAPC: 2.23 (95% CI: 2.11 to 2.34) and North America showed a significant increase in CKD-T2D DALYs [EAPC: 2.73 (95% CI: 2.39 to 3.07)]. The burden was higher in male and increased across all age groups, peaking at 60-79 years. Furthermore, there was a clear correlation between SDI and age-standardized rates, with regions categorized as middle SDI and High SDI experiencing a significant rise in burden.ConclusionThe global burden of CKD-T2D has significantly risen since 1990, especially among males aged 60-79 years and in regions with middle SDI. It is imperative to implement strategic interventions to effectively address this escalating health challenge.

Background: To investigate the associations between retinal/choroidal microvasculature and carotid plaque in patients with CAD assessed by optical coherence tomography angiography (OCTA). Methods: This study included 127 CAD patients with and 79 without carotid plaque. Each patient had both OCTA taken and digitized to determine retinal/choroidal thickness, vessel density and flow area and carotid ultrasound for carotid plaque size and stability measurement. The superficial capillary plexus (SCP), deep capillary plexus (DCP), out retina and choriocapillaris vessel density, out retina and choriocapillaris flow area, and full retina thickness were analyzed in the fovea centered 6 × 6 mm area. The association between OCTA measurements and carotid plaque characteristics in patients with CAD were evaluated. Results: The duration of hypertension and diabetes mellitus (DM) was significantly longer in CAD patients with carotid plaque than that without (p

ObjectiveThis study aimed to assess the knowledge, attitudes and practices (KAP) among Chinese reproductive-age women toward uterine adenomyosis.MethodsThis web-based cross-sectional study was conducted between April 2023 and September 2023 at the Second Hospital of Hebei Medical University. A self-designed questionnaire was developed to collect demographic information of reproductive-age women, and assess their KAP toward uterine adenomyosis.ResultsA total of 520 valid questionnaires were collected. Among the participants, 127 (24.42%) were diagnosed with uterine adenomyosis, and 120 (23.08%) were accompanied by uterine fibroids. The mean knowledge, attitudes and practices scores were 3.54 ± 3.72 (possible range:0–10), 20.96 ± 3.19 (possible range:5–25) and 24.01 ± 4.95 (possible range:7–35), respectively. The structural equation model demonstrated that knowledge had direct effects on attitudes and practices, as indicated by a path coefficient of 0.714 (p

Introduction: The close association between cuproptosis and tumor immunity in triple-negative breast cancer (TNBC) allows its monitoring for predicting the prognosis of patients with TNBC. Nevertheless, the biological function and prognostic value of cuproptosis-related miRNAs and their target genes have not been reported. Purpose: To construct the miRNA and mRNA-based risk models associated with cuproptosis for patients with TNBC. Methods: Comparison of expression levels for genes associated with cuproptosis was executed between patients in the normal individuals and the TCGA-TNBC cohort. Conducting differential analysis resulted in the identification of differentially expressed miRNA (DE-miRNAs) and differentially expressed genes (DEGs) between the TNBC and Control samples. Screening for prognostic miRNAs and biomarkers involved employing univariate Cox analysis and least absolute shrinkage and selection operator regression analyses. These methods were utilized to construct risk models aimed at predicting the survival of patients with TNBC. Based on the median value of risk scores, patients were then stratified into low- and high-risk groups. Functional enrichment analysis was employed to explore the potential function and pathways of prognostic genes. Additionally, independent prognostic analysis was performed through univariate and multivariate Cox regression. Immune infiltration analysis was performed to examine disparities in the infiltration of immune cells between the two risk groups. Finally, the prognostic gene expression was mined in key cell types of TNBC. Results: We obtained 5213 DEGs and 204 DE-miRNAs related to cuproptosis between TNBC and Control samples. Five prognostic miRNAs (miR-203a-3p, miR-1277–3p, miR-135b-5p, miR-200c-3p, and miR-592) and three biomarkers (DENND5B, IGF1R, and MEF2C) were closely associated with TNBC. Significant differences in the functions of prognostic genes between the two risk groups were observed, encompassing adipogenesis, inflammatory response, and hormone metabolic process. The prognostic gene regulatory network revealed that miR200C-3p regulated ZFPM2 and CFL2, and miR-1277–3p regulated BMP2 and RORA. A nomogram was created based on riskScore, cancer status, and pathologic stage to predict 1/3/5-year survival of patients with TNBC. Immune infiltration analysis indicated that the immune microenvironment may be associated with the progression of TNBC. Interestingly, prognostic genes exhibited higher expression levels in T cells, fibroblasts, endothelial cells, and monocytes compared to other cells. Conclusions: Five prognostic miRNA (miR-203a-3p, miR-1277–3p, miR-135b-5p, miR-200c-3p, and miR-592) and three biomarkers (DENND5B, IGF1R, and MEF2C) were significantly associated with TNBC, it provides new therapeutic targets for the treatment and prognosis of TNBC.

Background: Since 2019, Perampanel (PER) has been endorsed in China as an adjunctive treatment for focal seizures, both with and without impaired awareness, and for the transition from focal to bilateral tonic-clonic seizures. Limited research exists regarding the efficacy of PER in treating post-stroke epilepsy (PSE) in China. Empirical studies are essential to guide treatment protocols. We conducted a retrospective study to assess the efficacy and tolerability of PER in 58 PSE patients treated between October 2019 and July 2023. Method: This study encompassed 58 patients with PSE, treated with PER either as monotherapy or as part of adjunctive therapy, and underwent follow-up for a minimum duration of 6 months. The study assessed changes in seizure frequency, adverse events (AEs), drug retention rate, maintenance dose, and adverse reactions following PER treatment. Results: The study included 58 PSE patients, with 60.3% males and 39.7% females, ranging in age from 18 to 89, mostly within the 61–70 age group. Ischemic strokes constituted 58.6% of cases, while hemorrhagic strokes accounted for 41.4%. Focal seizures, either with or without impaired awareness, were noted in 62.1% of patients, and a transition from focal to bilateral tonic-clonic seizures was seen in 32.8%. The retention rates for PER at 3 and 6 months stood at 94.8% and 84.5% respectively, and the most commonly administered maintenance dose was 4 mg/day (41.28%). In the adjunctive therapy group, efficacy rates were 66.7% at 3 months and 78.6% at 6 months, compared to 80.0% at 3 months and 85.7% at 6 months in the monotherapy group. In the efficacy analysis, with a criterion of ≥50% reduction in seizure frequency, the overall efficacy rates at 3 and 6 months were 69.1% and 79.6%, respectively. Adverse reactions occurred in 46.6% of patients, primarily involving irritability and somnolence (both 27.6%), with no marked difference in incidence between the adjunctive and monotherapy groups (P > 0.05). Conclusion: PER exhibits favorable efficacy and tolerability in Chinese PSE patients, possibly at lower doses.

Tumor suppressor PTEN was aberrant silenced in gastric cancer (GC) in our previous study. Activation of PTEN through DNA demethylation is a potential strategy for the treatment of GC. Procyanidin B2 (PB2), an effective DNMT inhibitor, exert positive effects on various diseases. In our work, PB2 suppressed cell proliferation and migration while inducing cell apoptosis in vitro, and inhibited tumorigenesis and development in vivo. PB2 hypomethylated and reactivated PTEN expression via targeting and combining with DNMTs. Targeted glucose metabolism and Seahorse analysis showed that PTEN inhibited cell proliferation via HK1-mediated G6P and PFK1-mediated F1,6-2P, and the tumor-suppressor role of PTEN was not dependent on its phosphatase activity. Furthermore, PTEN promoter methylation could be used as a potential marker to predict GC development. This work aimed to investigate whether PB2 inhibit GC by reactivating PTEN’s tumor suppressor function, providing a powerful tool in the development of medical and editable natural compounds.

Abstract Spectral emissivity is an essential and sensitive parameter to characterize the radiative capacity of the solid surface in scientific and engineering applications, which would be non-negligibly affected by surface morphology. However, there is a lack of assessment of the effect of roughness on emissivity and a straightforward method for estimating the emissivity of rough surfaces. This paper established an estimating method based on constructing random rough surfaces to predict rough surface (Geometric region) emissivity for metal solids. Based on this method, the emissivity of ideal gray and non-gray body surfaces was calculated and analyzed. The calculated and measured spectral emissivities of GH3044, K465, DD6, and TC4 alloys with different roughness were compared. The results show that the emissivity increases with the roughness degree, and the enhancement effect weakens with the increase of roughness or emissivity due to the existing limit (emissivity ε = 1.0). At the same time, the roughness would not change the overall spectral distribution characteristics but may attenuate the local features of the spectral emissivity. The estimated results are in good agreement with the experimental data for the above alloys’ rough surfaces. This study provides a new reliable approach to obtaining the spectral emissivity of rough surfaces. This approach is especially beneficial for measuring objects in extreme environments where emissivity is difficult to obtain. Meanwhile, this study promotes an understanding of surface morphology’s effect mechanism on emissivity.

The as-cast Mg–2Y-0.5Zn-0.5Ni-0.5Co alloy (MYZNC, at%) underwent composite hot working, extrusion and rolling to further improve the mechanical properties, and the corresponding microstructure and mechanical properties were also investigated. The extruded and rolled MYZNC alloy (MYZNC-R) consisted of α-Mg, a long period stacking order (LPSO) phase comprising lamellar and fine block 18R LPSO phase as well as a thin strip 14H LPSO phase, along small amounts of Mg2Y, MgY(Co,Zn,Ni)4 and Mg3(Co,Zn,Ni,Y) particle phases. After composite processing, the dispersion and amounts of LPSO phase in the alloy was significantly enhanced, accompanied by a substantial introduction of low angle grain boundaries (LAGBs) during rolling process. The MYZNC-R alloy exhibited the high mechanical properties, with an ultimate tensile strength (σb) of 350 MPa, a yield strength (σ0.2) of 305 MPa and an elongation to failure (εf) of 10.6 %. In comparison to the extruded MYZNC alloy, both σb and σ0.2 demonstrated significant improvements by 25 % and 35.6 %, respectively. The elongation to failure only decreased by mere 1 %, indicating that the alloy had a good strength-plasticity. The high tensile strengths of MYZNC-R alloy were mainly attributed to grain refinement, LPSO phase strengthening and texture strengthening. The good ductility of MYZNC-R alloy was associated with the coordinated deformed LPSO phase and the formation of a high-volume fraction (∼76.5 %) of LAGBs.

AIM: To assess the retinal thickness and fundus blood flow density changes in chest pain patients with dyslipidemia using optical coherence tomography angiography (OCTA). METHODS: All subjects with chest pain as the main symptom accepted a comprehensive ophthalmological examination. According to the serum lipid levels, the participants were divided into the control group and the dyslipidemia group. The retina thickness and fundus blood flow density were determined using OCTA. RESULTS: The study enrolled 87 left eyes from 87 adults with dyslipidemia and 87 left eyes from age- and sex-matched participants without dyslipidemia. The retina of dyslipidemia subjects was significantly thinner than that of the controls in the inferior (P=0.004 and P=0.014, respectively) and temporal (P=0.015 and P=0.019, respectively) regions, both inner and outer layers. In terms of blood flow density in the macula or optic disk, there was a decreasing trend in the dyslipidemia group compared with the control group, especially in the inferior and temporal regions. CONCLUSION: Dyslipidemia may contribute to the decrease in retinal thickness and fundus blood flow density. Further validation of the association between abnormal lipid metabolism and fundus microcirculation alterations needs to be carried out in chest pain patients.

The paper deals with the third-order quaternion tensor equation. Based on the Qt multiplication operation, we derive solvability conditions and also get the general solution, the least-squares solution, the minimum-norm solution and the minimum-norm least-squares solution of the tensor equation $ \mathcal{A} \ast_{\mathbb{Q}} \mathcal{X} = \mathcal{B} $. Finally, two numerical examples are presented.

Abstract Endometriosis is a gynecological inflammatory disease that is linked with immune cells, specifically macrophages. IL-33 secreted from macrophages is known to accelerate the progression of endometriosis. The periodic and repeated bleeding that occurs in women with endometriosis leads to excess iron in the microenvironment that is conducive to ferroptosis, a process related to intracellular ROS production, lipid peroxidation and mitochondrial damage. It is suggested that eESCs may specifically be able to inhibit ferroptosis. However, it is currently unclear whether IL-33 directly regulates ferroptosis to influence the disease course in endometriosis. In this study, eESCs co-cultured with macrophages or stimulated with IL-33/ST2 were observed to have increased cell viability and migration. Additionally, IL-33/ST2 decreased intracellular iron levels and lipid peroxidation in eESCs exposed to erastin treatment. Furthermore, IL-33/ST2 treatment resulted in a notable upregulation in SLC7A11 expression in eESCs due to the downregulation of negative transcription factor ATF3, thereby suppressing ferroptosis. The P38/JNK pathway activated by IL-33/ST2 was also found to inhibit the transcription factor ATF3. Therefore, we concluded that IL-33/ST2 inhibits the ATF3-mediated reduction in SLC7A11 transcript levels via the P38/JNK pathway. The findings reveal that macrophage-derived IL-33 upregulates SLC7A11 in eESCs through the p38/JNK/ATF3 pathway, ultimately resulting in protection against ferroptosis in eESCs. Moreover, we conducted an experiment using endometriosis model mice that showed that a combination of IL-33-Ab and erastin treatment alleviated the disease, showing the promise of combining immunotherapy and ferroptosis therapy.

Abstract Cytokinin oxidase/dehydrogenase (CKX) is a key regulatory enzyme for the irreversible degradation of the plant hormone cytokinin (CK), which is important in growth and development and response to abiotic stresses in cotton. In this study, 27, 28, 14 and 14 CKXs were screened by FAD structural domain and cytokinin binding structural domain in Gossypium hirsutum, Gossypium barbadense, Gossypium arboreum and Gossypium raimondii, respectively. Their phylogenetic relationships and expression patterns were analyzed, and most GhCKXs were found to be tissue-specific and responsive to various abiotic stresses such as cold, heat, salt and PEG. GhCKX6b-Dt was selected for gene silencing in evolutionary branch II for salt stress, because its expression increased after salt stress in cotton plants. An increase in PRO and MDA content and a decrease in SOD activity due to this gene were found after inducing salt stress, contributing to oxidative damage and decreased salt tolerance. In this study, CKXs were analyzed to reveal the possible role of GhCKXs against abiotic stresses in cotton, which provides a basis for further understanding of the biological functions of CK in plants such as growth and development and stress resistance.

Abstract Amyloid-like assembly is not only associated with pathological events, but also leads to the development of novel nanomaterials with unique properties. Herein, using Fmoc diphenylalanine peptide (Fmoc–F–F) as a minimalistic model, we found that histidine can modulate the assembly behavior of Fmoc–F–F and induce enzyme-like catalysis. Specifically, the presence of histidine rearranges the β structure of Fmoc–F–F to assemble nanofilaments, resulting in the formation of active site to mimic peroxidase-like activity that catalyzes ROS generation. A similar catalytic property is also observed in Aβ assembled filaments, which is correlated with the spatial proximity between intermolecular histidine and F-F. Notably, the assembled Aβ filaments are able to induce cellular ROS elevation and damage neuron cells, providing an insight into the pathological relationship between Aβ aggregation and Alzheimer’s disease. These findings highlight the potential of histidine as a modulator in amyloid-like assembly of peptide nanomaterials exerting enzyme-like catalysis.

Abstract To investigate the effect of evidence‐based nursing on breast cancer patients during postoperative radiotherapy care. In the sample selection, 100 breast cancer patients who received postoperative radiotherapy in our hospital from January 2020 to January 2022 were selected to participate in this study. Patients in the control group received routine nursing program, while patients in the study group applied the intervention of evidence‐based nursing philosophy, the nursing effect was compared between the two groups. According to the nursing effect of the two groups, there was a significant difference under the intervention of different protocols. The patients in the study group showed significant improvements in Self‐Rating Depression Scale and Self‐Rating Anxiety Scale scores under the evidence‐based care intervention, superior to those of the control group, and the difference was significant (p

A novel cholic acid-conjugated carboplatin (CP-CA) is developed as a liver-targeting prodrug of carboplatin (CP) for liver cancer. Instead of using CP as a raw material, CP-CA was synthesized simultaneously. This paper is focused on the comparison of CP-CA and CP with respect to their pharmacokinetic (PK) and tissue distribution profiles in rats after their intravenous administration. Additionally, their uptake by human liver tumor cell Huh7 and normal human liver cell HL7702 are investigated. The inductively coupled plasma mass spectrometry (ICP-MS) method is applied for the determination of platinum in plasma, tissues, and cells. The PK results show that both the AUC0–t and AUC0–∞ data on Pt for CP-CA are significantly higher than those for CP (p < 0.01), indicating that the plasma exposure of CP-CA is significantly higher than that of CP. The CL1, Vd1, and Vd2 data on Pt for CP-CA are significantly lower than those for CP (p < 0.01), while the MRT0–t is significantly higher (p < 0.01), which is possibly related to a higher PPBR, and can strongly support the higher AUC0–t and AUC0–∞ of Pt for CP-CA compared to for CP. The tissue distribution results show that CP-CA is mainly distributed and accumulated in the liver after its intravenous administration to rats, revealing its liver-targeting profile. Compared to CP, CP-CA is more easily taken up by human liver cancer cells and normal human liver cells. The results suggest that CP-CA has a potential for further development as a new prodrug specific to liver cancer.

Iron (Fe) toxicity is a major issue adversely affecting rice production worldwide. Unfortunately, the physiological and genetic mechanisms underlying Fe toxicity tolerance in rice remain relatively unknown. In this study, we conducted a genome–wide association study using a diverse panel consisting of 551 rice accessions to identify genetic mechanisms and candidate genes associated with Fe toxicity tolerance. Of the 29 quantitative trait loci (QTL) for Fe toxicity tolerance detected on chromosomes 1, 2, 5, and 12, five (qSH_Fe5, qSFW_Fe2.3, qRRL5.1, qRSFW1.1, and qRSFW12) were selected to identify candidate genes according to haplotype and bioinformatics analyses. The following five genes were revealed as promising candidates: LOC_Os05g40160, LOC_Os05g40180, LOC_Os12g36890, LOC_Os12g36900, and LOC_Os12g36940. The physiological characteristics of rice accessions with contrasting Fe toxicity tolerance reflected the importance of reactive oxygen species–scavenging antioxidant enzymes and Fe homeostasis for mitigating the negative effects of Fe toxicity on rice. Our findings have clarified the genetic and physiological mechanisms underlying Fe toxicity tolerance in rice. Furthermore, we identified valuable genetic resources for future functional analyses and the development of Fe toxicity–tolerant rice varieties via marker–assisted selection.