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The challenge posed by academic ghostwriting extends beyond education, affecting moral and meritocratic expectations of learners. Through a sociological lens of the "accounts theory," we analyzed the marketing language of 102 academic ghostwriting websites in English and Chinese to explore their legitimization of services in diverse cultures and contexts. Our research focused on how ghostwriting sites legitimize their services across diverse cultures and linguistic contexts while navigating the stigma associated with academic ghostwriting. We identified five neutralization techniques used by ghostwriting sites, including "Denial of responsibility," "Denial of injury," "Denial of the victim," "Condemnation of the condemners," and "Appeal to higher loyalties." Our findings suggest that the marketing of academic ghostwriting is customized to appeal to potential clients' cultural backgrounds, with Chinese ghostwriting sites emphasizing the authority of ghostwriters and English sites prioritizing empathy with users. The ghostwriting industry has diversified to meet the needs of diverse consumers and online environments. Our research provides insights into how ghostwriting sites devise market strategies based on cultural predispositions, shedding light on the complexities of the ghostwriting industry and its impact on the moral and educational landscape. It sheds light on how the dynamics of this market evolve, adapt, and ultimately influence the educational landscape, emphasizing the need for a holistic perspective on the forces at play in higher education.

The integration of education and robotics has emerged as a crucial development in the technological landscape. This study focuses on the use of a robot teaching assistant to enhance the learning efficiency of 8th-grade students in hands-on STEM activities centered around the theme of "Smart City." It explores the impact of educational robots on students' learning outcomes and their development of hands-on skills through diverse learning methods. Conducted over 12 weeks with 103 participants, the study employed a quasi-experimental design. Students were split into two groups: The Experimental Group (EG), using the 6E model with robot teaching assistants, and the Control Group (CG), using only the 6E model. The analysis of covariance revealed that the EG exhibited superior performance in STEM knowledge, motivation, and hands-on skills compared to the CG. Further analysis indicated that learning motivation significantly influenced hands-on performance in the EG, particularly in high-scoring subgroups. The findings suggest that combining the 6E model with educational robots effectively enhances STEM learning and student engagement. Educational robots as teaching assistants not only aid in knowledge acquisition but also significantly boost students' motivation and hands-on skill development. This implies a promising direction for integrating advanced technology in educational practices to foster more effective learning environments.

Adolescence is a critical period during which youth develop and shape their behaviors. Because differences between youths are strongly connected to environmental factors, we aimed to elucidate possible pathways from home-school regulation and atmosphere to youths' prosocial and antisocial behaviors. Data were derived from the China Education Panel Survey. This study involved a total of 9291 students aged 14-15 years (4834 boys, 4457 girls). We used structural equation modeling (SEM) with LISREL 8.80 and Monte Carlo resampling with R to conduct the analysis strategy. In the home-school regulation, parental supervision on the one hand and teacher criticism on the other hand have direct positive and negative predictive effects on youths' prosocial behaviors, respectively, while their direct effects on antisocial behavior are the opposite; teachers praise does not directly affect adolescents' prosocial and antisocial behaviors. In the home-school atmosphere, family interaction and perceived good class climate directly positively affect youths' prosocial behaviors, while the direct effects of both on antisocial behavior are not significant. The SEM results reveal that academic self-efficacy and depressive symptoms may be underlying mediating mechanisms through which home-school regulation and atmosphere during adolescence affect students' prosocial and antisocial behaviors. Intervention programs targeting home-school supportive environments and prevention programs targeting positive emotion and self-awareness may yield benefits for proper social behavior in adolescents. For example, by enhancing the way and frequency of parent-child interaction, teachers and students jointly create a good class climate of care and friendship to strengthen a home-school supportive environment. Improve adolescents' positive emotions such as contentment, optimism, and hope to reduce the possibility of depression.

Abstract Various pathogens from oomycete, fungi, and bacteria kingdoms can infect potato and significantly reduce potato yield. The early diagnosis of potato pathogens is important for tracing disease epidemics and the subsequent disease management. Loop-mediated isothermal amplification (LAMP) is a critical technique for pathogen detection, but available LAMP assays do not effectively meet the requirement of field diagnoses due to complexities including co-infection of different pathogens. Hence, this study aims to develop integrated-LAMP assays (iLAMPs) for simultaneous detection of eight common potato pathogens and apply iLAMPs to pathogen detection in field samples from the four main potato-growing regions of China in 2023. Therefore, eight sets of primers showing gene- and genus-specificity were designed and used for iLAMPs to determine their specificity, sensitivity, and visualization. Subsequently, iLAMPs-mediated pathogen detection revealed that 72.82% of 206 diseased leaves and 84.94% of 239 diseased tubers carry more than one pathogen. The detection rate for each pathogen significantly varies from 1.94 to 65.53% in diseased leaves, and ranges from 26.78 to 52.72% in diseased tubers, respectively. In addition, the detection rate of Phytophthora infestans and Alternaria solani positively correlates in both leaves and tubers, especially for those samples from the southwestern and southern regions. Taken together, iLAMPs developed in this study enables simultaneous detection of eight common potato pathogens from field samples and may have broad applications in early management of potato diseases.

Abstract Background TAF1L may play an important role in the occurrence and development of gastric cancer (GC), but the correlation between the expression of TAF1L and the clinicopathological factors and prognosis of GC is still unclear. Methods A total of 1053 GC patients in Zhejiang Cancer Hospital between January 1st, 2018 to December 31th, 2019 were screened. Finally, 120 patients met the inclusion criteria. TAF1L expression was detected by immunohistochemistry, and the correlations of TAF1L in clinicopathological characteristics and prognosis were analyzed. TCGA GC dataset was used to perform further bioinformatics analysis. Results In this study, TAF1L expression was evaluated in 120 clinical samples of GC. TAF1L expression was higher in tumor tissues and was associated with tumor differentiation (p = 0.046), signet-ring cells (p = 0.043), dMMR status (p = 0.011), lympho-vascular invasion (p = 0.038), and neural invasion (p = 0.005) in our cohort. Cases with high expression of TAF1L presented worse mean OS than those with low expression (40.3 months vs. 51.8 months, p = 0.019), and the difference was also significant in HER2-positive cases (20.9 months vs. 51.2 months, p = 0.007) as well as pMMR cases (38.8 months vs. 51.6 months, p = 0.006). Multivariate Cox regression analysis showed that TAF1L (HR = 2.044, 95%CI = 1.007–4.147, p = 0.048) and HER2 status (HR = 2.383, 95%CI = 1.087–5.222, p = 0.030) were independent prognosis factors of these patients. In subgroup analysis, TAF1L was the independent prognostic risk factor in HER2-positive patients (HR = 6.736, 95%CI = 1.373–33.032, p = 0.019). and pMMR patients (HR = 2.291, 95%CI = 1.126–4.660, p = 0.022). Besides, HER2 status was the independent prognostic risk factor in TAF1L-H patients (HR = 4.832, 95%CI = 1.908–12.239, p = 0.001). TCGA dataset also indicated the higher expression of TAF1L in tumors than normal tissues (p

Abstract Background Allergic rhinitis (AR) subjects might have their microenvironment changed due to pathogenesis and living environment. Whether the nasal microbe in AR children differs from healthy subjects and how it interplays with dermal, oral and indoor dust microbe needs to be elucidated. Methods In this case–control study, we analyzed and compared the bacterial characterization and associations in nasal, dermal, oral swab samples and dust samples in 62 children with physician-diagnosed AR(cases) and 51 age- and gender-matched healthy ones with no history of allergic diseases(controls). Full-length 16S rRNA sequencing(swabs) and shotgun metagenomics(dust) were applied. Bacterial diversity, composition, abundance difference characteristics and fast expectation–maximization for microbial source tracking(FEAST) analysis were performed and compared between cases and controls. Results The α-diversity of dust microorganisms in AR was lower than that in control group (P = 0.034), and the β-diversity indices of microorganisms in nasal cavity (P = 0.020), skin (P = 0.001) and dust (P = 0.004) were significantly different from those in control group. At species levels, a total of 10, 15, 12, and 15 bacterial species were differentially enriched in either cases or controls in nasal, dermal, oral, and dust samples, respectively(Linear Discriminant Analysis(LDA) score > 2, P

Fuscoporia is a polypore genus of Hymenochaetaceae that causes wood decay, although some species in the genus have medicinal values. Phylogenetic analyses of concatenated ITS1-5.8S-ITS2-nLSU sequence data and morphological features identified three new species, F. eucalypticola, F. resupinata and F. subtropica from Australia, China and Malaysia, and these new species derived from the Fuscoporia ferrea group. These three species are illustrated and described. A key to resupinate species of Fuscoporia without mycelial setae in the world is provided.

Abstract Background Evidence for the efficacy of pharmacological therapies for heart failure with reduced ejection fraction (HFrEF) is growing. However, there is no consensus on the most effective treatment for HFrEF. This study aimed to evaluate the most effective combination of pharmacological therapy in patients with HFrEF. Methods We systematically searched Medline, Embase, and CENTRAL up to Feb 2022, to include randomized controlled trials (RCTs) that evaluated the efficacy of pharmacological treatment among adults (≥ 18 years) with a diagnosis of HFrEF (defined by a left ventricular ejection fraction ≤ 45%). The outcomes of interest included all-cause death, cardiovascular (CV) death, and hospitalization for heart failure (HHF). A random network meta-analysis using a frequentist framework model was employed to calculate the pooled risk ratio (RR) with 95% confidence interval (CI) and rank the treatments. Results We included 49 RCTs involving 90,529 participants with HFrEF. For reducing all-cause mortality, the combination of angiotensin-converting enzyme inhibitors (ACEI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose co-transporter-2 inhibitors (SGLT2i) was most effective (RR, 0.46; 95% CI, 0.32–0.66). For CV death, the combination of ACEI, BB, MRA, and Vericiguat showed the highest efficacy (RR, 0.34; 95% CI, 0.12–0.90). Regarding reducing HHF, the combination of ACEI, BB, MRA, and SGLT2i as well as the combination of ACEI, BB, MRA, and Ivabradine were equally the most effective (both RR, 0.27; 95% CI, 0.18–0.39). Conclusion This study provides robust evidence supporting the use of combination therapies in HFrEF management, with newer agents offering incremental benefits when added to established guideline-directed medical therapy.

Abstract Understanding the genetics of kidney function decline, or trait change in general, is hampered by scarce longitudinal data for GWAS (longGWAS) and uncertainty about how to analyze such data. We use longitudinal UK Biobank data for creatinine-based estimated glomerular filtration rate from 348,275 individuals to search for genetic variants associated with eGFR-decline. This search was performed both among 595 variants previously associated with eGFR in cross-sectional GWAS and genome-wide. We use seven statistical approaches to analyze the UK Biobank data and simulated data, finding that a linear mixed model is a powerful approach with unbiased effect estimates which is viable for longGWAS. The linear mixed model identifies 13 independent genetic variants associated with eGFR-decline, including 6 novel variants, and links them to age-dependent eGFR-genetics. We demonstrate that age-dependent and age-independent eGFR-genetics exhibit a differential pattern regarding clinical progression traits and kidney-specific gene expression regulation. Overall, our results provide insights into kidney aging and linear mixed model-based longGWAS generally.

Abstract Grey mullet (Mugil cephalus) aquaculture is economically vital due to the high value of its roe. However, it faces significant risks from disease outbreaks, particularly from Nocardia seriolae. Current reliance on antibiotics has drawbacks, highlighting the potential of probiotics as a promising alternative. Despite this, no studies have focused on the effects and mechanisms of probiotics in disease prevention and treatment in grey mullet. This study, therefore, investigates the efficacy of probiotics in enhancing disease resistance and promoting growth in grey mullet. Three strains of probiotics, Lacticaseibacillus rhamnosus FS3051, Limosilactobacillus reuteri FS3052, and Bacillus subtilis natto NTU-18, were selected to evaluate their anti-N. seriolae activity and hydrolytic enzyme secretion in vitro. Then, 144 grey mullet were randomly divided into four groups: control, L. rhamnosus FS3051, L. reuteri FS3052, and B. subtilis natto NTU-18. After being fed the corresponding diet for 28 days, fish were measured for immune gene expression and short-term growth followed by challenge of N. seriolae. Survival rates were recorded for 35 days post challenge. Additionally, the gut microbiota of the control and probiotic groups with effects on both growth and protection against N. seriolae were analyzed to investigate the potential role of gut microbiota. Results demonstrated that L. rhamnosus FS3051 and L. reuteri FS3052 inhibited N. seriolae, while B. subtilis natto NTU-18 did not inhibited N. seriolae. Probiotics also had the ability to secrete hydrolytic enzymes. Probiotic-fed grey mullet showed significant improvements in weight gain ratio, feed efficiency, and specific growth rate, particularly in the B. subtilis natto NTU-18 group. Immune gene expression was enhanced by probiotics, especially L. rhamnosus, FS3051, which induced IL-8, IL-1β, TNF-α, IFN-γ, and MHCI. Survival rates post-N. seriolae challenge improved significantly for L. rhamnosus FS3051-fed fish. L. rhamnosus FS3051 also altered the gut microbiota, enriching beneficial genera like Lactobacillus, which correlated positively with immune responses and growth, while reducing Mycoplasma and Rhodobacter, which were negatively correlated with immune responses. This study underscores the potential of probiotics in enhancing disease resistance and growth via regulating gut microbiota in grey mullet.

Abstract MDM4 is one of the major regulators of p53. The biological effect of MDM4 on tumor is controversial, its role and molecular mechanism in colon cancer progression and prognosis are still unclear. In this study, we identify that MDM4 is significantly overexpressed in human colon cancer and high MDM4 expression was associated with poor prognosis of colon cancer with mutant p53. MDM4 inhibits the ubiquitination of the ferroptosis marker protein GPX4 at K167 and K191 by upregulating the protein expression level of the E3 ubiquitin ligase TRIM21, which promotes the polyubiquitination of GPX4 transfer from K48- to K63- linked ubiquitination. Thereby, MDM4 enhances the stability of GPX4 protein, inhibiting ferroptosis, increasing the resistance of colon cancer patients to chemotherapy, and promoting colon cancer progression. These findings elucidate the ferroptosis inhibition effect of MDM4 via regulating TRIM21/GPX4 on p53-mutated colon cancer and provide a potential therapeutic strategy for colon cancer therapy.

More than 600 Chinese specimens of Armillaria were identified by mating tests, Genealogical Concordance Phylogenetic Species Recognition (GCPSR), and comparison of morphological characteristics. Sixteen Chinese Biological Species (CBS) of Armillaria were identified by 30,340 mate pair combinations. Fifteen Chinese Phylogenetic Species (CPS) were recognised based on Independent Evolutionary Lineage (IEL) recognition and concatenated six-gene analysis (actin, h3h, hisps, LSU rDNA, rpb1, and tef1α). All the biological species and phylogenetic species were identical and possessed the same species boundary, except for CBS K (A. mellea) and CBS G (A. mellea ssp. nipponica) which were the same phylogenetic species. On the basis of CBS and CPS, eight new species of Armillaria in China were distinguished using macro and micro morphology, and they are described as A. algida, A. amygdalispora, A. bruneocystidia, A. luteopileata, A. pungentisquamosa, A. sinensis, A. tibetica, and A. violacea. This study indicates that the GCPSR approach provides the same resolution as mating tests in identification of Armillaria species.

As international capitals keep flowing into Asia, in particular China, it experienced rapid development on both economy and financial market during the last three decades. While more and more financial products are introduced, the government also loosens the leash on investment, so that the approaches to investment in the Chinese market are diversified enough to attract more and more investors to invest in it. This study will thus explore in depth what have affected Chinese ETF performance. For empirical analysis, the daily data on total ETF transactions and related economic indices during a period from February 24, 2005 to December 31, 2015 were used with multiple regression models. Our findings indicated that the amount of international capital inflow to China, the stock market, and interest rates affected the investment performance of Chinese ETFs.

With the popularization of high-resolution thin-layer CT, the detection rate of early asymptomatic lung cancer that manifests as solitary pulmonary nodules has significantly increased. The differentiation of benign from malignant nodules and histopathological classification are the keys to and challenges of clinical diagnoses, the accuracy of which is of great significance for treatment decision-making. Traditional CT evaluates nodules based on their size, density, and morphological characteristics with single modal imaging. Dual-energy CT achieves material separation based on attenuation differences in the same tissue at two different energy levels, which allows CT imaging to evolve from a single-parameter to multi-parameter measurements. This not only provides more valuable information for the early and accurate diagnosis of nodules but also facilitates measurements of tumor progression and heterogeneity. In addition, the combination of radiomics based on artificial intelligence and multi-parameter images by dual-energy CT has shown great potential in diagnosis, and the related investigations are in exploratory stages. This review will cover the application of dual-energy CT in the diagnosis of solitary pulmonary nodules, with a focus on the meaning of multi-parameter images for the ccurate diagnosis of pulmonary nodules. Further, the future directions of this diagnostic imaging technique are discussed as well.

Background/Objective: The perceived benefits and barriers to physical activity play crucial roles in determining daily physical activity levels. However, previous studies have employed tools lacking adequate validation, leading to inconsistent conclusions about the impact of these two factors. Therefore, this national, population-based study was conducted to assess the psychometric properties, measurement invariance, and predictive validity of the Chinese versions of the perceived benefits (C-PBEPA) and barriers to physical activity (C-PBAPA) scales. Methods: The final sample (N = 2942, 49.3 % for boys) was randomly split into two subsamples. The first subsample was used for exploratory factor analysis and the second subsample was used for confirmatory factor analysis. Measurement invariance across gender and age groups were examined. Structural equation models were developed to examine the predictive validity of the revised C-PBEPA and C-PBAPA on moderate to vigorous PA. Results: The results showed that both scales were unidimensional, had excellent model fit (e.g., X2/df 0.9, RMSEA 0.01) and supported the predictive validity of both scales (p

The unsupervised enhancement technology for underwater images is mainly oriented towards specific distortion factors and exhibits limited adaptability towards various underwater distorted images. The content attribute(structure) of the image will migrate and change with the style attribute(appearance), resulting in an uncontrolled enhancement effect and affecting the stability and accuracy of subsequent environmental perception and processing. To address this issue, an unsupervised controllable enhancement method of underwater images based on multi-domain attribute representation disentanglement(MARD) was proposed in the paper. First, a framework of multi-domain unified representation disentanglement cycle-consistent adversarial translations was designed, thereby enhancing the algorithm’s adaptability to multiple distortion factors. Subsequently, a dual-encoding and conditional decoding network structure was constructed. Finally, a series of losses for MARD was designed to enhance the independence and controllability of quality, content, style, and other attribute representations. Experimental results demonstrate that the proposed algorithm not only eliminates various distortions such as color aberration, blur, noise, and low illumination in underwater images but also quantify the image style codes by linear interpolation for controllable enhancement of underwater images.

Abstract We consider a version of the typical state firewall setup recently reintroduced by Stanford and Yang, who found that wormholes may create firewalls. We examine a late-time scaling limit in JT gravity in which one can resum the expansion in the number of wormholes, and we use this to study the exact distribution of interior slices at times exponential in the entropy. We consider a thermofield double with and without early perturbations on a boundary. These perturbations can appear on interior slices as dangerous high energy shockwaves. For exponentially late times, wormholes tend to teleport the particles created by perturbations and render the interior more dangerous. In states with many perturbations separated by large times, the probability of a safe interior is exponentially small, even though these would be safe without wormholes. With perturbation, even in the safest state we conceive, the odds of encountering a shock are fifty-fifty. One interpretation of the phenomenon is that wormholes can change time-ordered contours into effective out-of-time-ordered folds, making shockwaves appear in unexpected places.

Abstract Mangroves can retain both autochthonous and allochthonous marine and/or terrestrial organic carbon (OC) in sediments. Accurate quantification of these OC sources is essential for the proper allocation of blue C credits. Here, we conduct a global-scale analysis of sediments autochthonous and allochthonous OC contributions in estuarine and marine mangroves using stable isotopes. Globally, mangrove-derived autochthonous OC was the main contributor to estuarine and marine mangrove top-meter soil organic carbon (SOC) (49% and 62%, respectively). Less marine allochthonous OC (21%) was deposited than terrestrial allochthonous OC (30%) in estuarine mangrove sediments. Estuarine mangroves accumulated more SOC in sediments than marine mangroves (282 ± 8.1 Mg C ha−1 and 250 ± 5.0 Mg C ha−1, respectively), primarily due to the additional terrestrial OC inputs. Globally, marine mangroves held 67% of the total mangrove SOC, reaching 3025 ± 345 Tg C, while 1502 ± 154 Tg C was stored in estuarine mangrove sediments. The findings emphasize the substantial influence of coastal environmental settings on OC contributions, underlining the necessity of accurate OC source quantification for the effective allocation of blue carbon credits.

Abstract. Background:. Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury. Methods:. This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes (n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group (n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls (n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. Results:. The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH. Conclusions:. The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Abstract Background In recent years, ophthalmology has emerged as a new frontier in medical artificial intelligence (AI) with multi-modal AI in ophthalmology garnering significant attention across interdisciplinary research. This integration of various types and data models holds paramount importance as it enables the provision of detailed and precise information for diagnosing eye and vision diseases. By leveraging multi-modal ophthalmology AI techniques, clinicians can enhance the accuracy and efficiency of diagnoses, and thus reduce the risks associated with misdiagnosis and oversight while also enabling more precise management of eye and vision health. However, the widespread adoption of multi-modal ophthalmology poses significant challenges. Main text In this review, we first summarize comprehensively the concept of modalities in the field of ophthalmology, the forms of fusion between modalities, and the progress of multi-modal ophthalmic AI technology. Finally, we discuss the challenges of current multi-modal AI technology applications in ophthalmology and future feasible research directions. Conclusion In the field of ophthalmic AI, evidence suggests that when utilizing multi-modal data, deep learning-based multi-modal AI technology exhibits excellent diagnostic efficacy in assisting the diagnosis of various ophthalmic diseases. Particularly, in the current era marked by the proliferation of large-scale models, multi-modal techniques represent the most promising and advantageous solution for addressing the diagnosis of various ophthalmic diseases from a comprehensive perspective. However, it must be acknowledged that there are still numerous challenges associated with the application of multi-modal techniques in ophthalmic AI before they can be effectively employed in the clinical setting.

Abstract Racial and ethnic minorities bear a disproportionate burden of type 2 diabetes (T2D) and its complications, with social determinants of health (SDoH) recognized as key drivers of these disparities. Implementing efficient and effective social needs management strategies is crucial. We propose a machine learning analytic pipeline to calculate the individualized polysocial risk score (iPsRS), which can identify T2D patients at high social risk for hospitalization, incorporating explainable AI techniques and algorithmic fairness optimization. We use electronic health records (EHR) data from T2D patients in the University of Florida Health Integrated Data Repository, incorporating both contextual SDoH (e.g., neighborhood deprivation) and person-level SDoH (e.g., housing instability). After fairness optimization across racial and ethnic groups, the iPsRS achieved a C statistic of 0.71 in predicting 1-year hospitalization. Our iPsRS can fairly and accurately screen patients with T2D who are at increased social risk for hospitalization.

Tissue engineering technology has advanced rapidly in recent years, offering opportunities to construct biologically active tissues or organ substitutes to repair or even enhance the functions of diseased tissues and organs. Tissue-engineered scaffolds rebuild the extracellular microenvironment by mimicking the extracellular matrix. Fibrin-based scaffolds possess numerous advantages, including hemostasis, high biocompatibility, and good degradability. Fibrin scaffolds provide an initial matrix that facilitates cell migration, differentiation, proliferation, and adhesion, and also play a critical role in cell-matrix interactions. Fibrin scaffolds are now widely recognized as a key component in tissue engineering, where they can facilitate tissue and organ defect repair. This review introduces the properties of fibrin, including its composition, structure, and biology. In addition, the modification and cross-linking modes of fibrin are discussed, along with various forms commonly used in tissue engineering. We also describe the biofunctionalization of fibrin. This review provides a detailed overview of the use and applications of fibrin in skin, bone, and nervous tissues, and provides novel insights into future research directions for clinical treatment.

Many uncertainties arise during the manufacturing process, such as changes in the working environment, traffic transportation delays, machine breakdowns, and worker performance instabilities. These factors can cause job processing times and ready times to change. In this study, we address a scheduling model for a single machine where both job release dates and processing times are scenario dependent. The objective is to minimize the total completion time across the worst-case scenarios. Even without the uncertainty factor, this problem is NP-hard. To solve it, we derive several properties and a lower bound used in a branch-and-bound method to find an optimal solution. We propose nine heuristics based on a linear combination of scenario-dependent processing times and release times for approximate solutions. Additionally, we offer an iterated greedy population-based algorithm that efficiently solves this problem by taking advantage of the diversity of solutions. We evaluate the performance of the proposed nine heuristics and the iterated greedy population-based algorithm.

Intelligent reflecting surface (IRS) is a promising enabler for achieving communication quality of service (QoS) and enhancing sensing QoS in Integrated Sensing and Communication (ISAC) systems. It has been regarded as one of the most attractive solutions for facilitating vehicle applications in internet of vehicles (IoV) by utilizing ISAC technologies. In this paper, the trajectory of target vehicle goes through no obstacle blocking stage and obstacle blocking stage successively in ISAC systems. And the performance trad-off is pursued in the sensing QoS and the communication QoS of the target vehicle. The achievable rate and posterior Cramer-Rao lower bounds (PCRLBs) are defined to reflect communication QoS and sensing QoS, respectively. In this process, the trade-off strategy on QoS for communication and IRS assisted sensing is explored in IoV. Hence, an optimization problem is designed to ensure communication capability of the target while ensuring its sensing ability. The joint semidefinite relaxation (SDR) and alternating optimization (AO) method is proposed to obtain the optimal solution on resource allocation (RA) and IRS phase shift. Simulation results verify the effectiveness of the proposed method in terms of performance trade-off between communication QoS and sensing QoS.

Abstract The spalt (Sal) gene family has four members (Sall1-4) in vertebrates, all of which play pivotal roles in various biological processes and diseases. However, the expression and function of SALL2 in development are still less clear. Here, we first charted SALL2 protein expression pattern during mouse embryo development by immunofluorescence, which revealed its dominant expression in the developing nervous system. With the establishment of Sall2 deficient mouse embryonic stem cells (ESCs), the in vitro neural differentiation system was leveraged to interrogate the function of SALL2, which showed impaired neural differentiation of Sall2 knockout (KO) ESCs. Furthermore, neural stem cells (NSCs) could not be derived from Sall2 KO ESCs and the generation of neural tube organoids (NTOs) was greatly inhibited in the absence of SALL2. Meanwhile, transgenic expression of E1 isoform of SALL2 restored the defects of neural differentiation in Sall2 KO ESCs. By chromatin immunoprecipitation sequencing (ChIP-seq), Tuba1a was identified as downstream target of SALL2, whose function in neural differentiation was confirmed by rescuing neural phenotypes of Sall2 KO ESCs when overexpressed. In sum, by elucidating SALL2 expression dynamics during early mouse development and mechanistically characterizing its indispensable role in neural differentiation, this study offers insights into SALL2’s function in human nervous system development, associated pathologies stemming from its mutations and relevant therapeutic strategy.

Abstract Background There is currently a lack of comprehensive evidence regarding the correlation between Alternate Mediterranean Diet (AMED) and the survival of patients with ovarian cancer (OC). This prospective cohort study first assessed the association of AMED, not only pre-diagnosis and post-diagnosis but also the change from pre-diagnosis to post-diagnosis with OC survival. Methods A total of 560 OC patients were included in the study, and their dietary intake was assessed using a reliable 111-item food frequency questionnaire. The overall survival (OS) of the patients was monitored through active follow-up and review of medical records until February 16th, 2023. Cox proportional hazard regression models were utilized to compute the hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). Results Out of the total 560 patients with OC, 211 (37.68%) succumbed during a median follow-up period of 44.40 months (interquartile range: 26.97–61.37). Comparative analysis indicated a significant association between the highest tertiles of pre-diagnosis (HR = 0.59; 95% CI 0.38–0.90; P trend

Abstract Cardiac biological pacing (BP) is one of the future directions for bradyarrhythmias intervention. Currently, cardiac pacemaker cells (PCs) used for cardiac BP are mainly derived from pluripotent stem cells (PSCs). However, the production of high-quality cardiac PCs from PSCs remains a challenge. Here, we developed a cardiac PC differentiation strategy by adopting dual PC markers and simulating the developmental route of PCs. First, two PC markers, Shox2 and Hcn4, were selected to establish Shox2:EGFP; Hcn4:mCherry mouse PSC reporter line. Then, by stepwise guiding naïve PSCs to cardiac PCs following naïve to formative pluripotency transition and manipulating signaling pathways during cardiac PCs differentiation, we designed the FSK method that increased the yield of SHOX2+; HCN4+ cells with typical PC characteristics, which was 12 and 42 folds higher than that of the embryoid body (EB) and the monolayer M10 methods respectively. In addition, the in vitro cardiac PCs differentiation trajectory was mapped by single-cell RNA sequencing (scRNA-seq), which resembled in vivo PCs development, and ZFP503 was verified as a key regulator of cardiac PCs differentiation. These PSC-derived cardiac PCs have the potential to drive advances in cardiac BP technology, help with the understanding of PCs (patho)physiology, and benefit drug discovery for PC-related diseases as well.

Abstract Transforming growth factor (TGF)-β signaling is critical for epithelial-mesenchymal transition (EMT) and colorectal cancer (CRC) metastasis. Disruption of Smad-depednent TGF-β signaling has been shown in CRC cells. However, TGF-β receptor remains expressed on CRC cells. Here, we investigated whether the cooperation between tumor-associated N-glycosylation and a glycan-binding protein modulated the TGF-β-driven signaling and metastasis of CRC. We showed that galectin-8, a galactose-binding lectin, hampered TGF-β-induced EMT by interacting with the type II TGF-β receptor and competing with TGF-β binding. Depletion of galectin-8 promoted the migration of CRC cells by increasing TGF-β-receptor-mediated RAS and Src signaling, which was attenuated after recombinant galectin-8 treatment. Treatment with recombinant galectin-8 also induces JNK-dependent apoptosis in CRC cells. The anti-migratory effect of galectin-8 depended on β4-galactosyltransferase-I (B4GALT1), an enzyme involved in N-glycan synthesis. Increased B4GALT1 expression was observed in clinical CRC samples. Depletion of B4GALT1 reduced the metastatic potential of CRC cells. Furthermore, inducible expression of galectin-8 attenuated tumor development and metastasis of CRC cells in an intra-splenic injection model. Our results thus demonstrate that galectin-8 alters non-canonical TGF-β response in CRC cells and suppresses CRC progression.

In this work, we report a counter-intuitive activation of abnormal grain growth (AGG) in randomly-oriented fine grains (FGs) in an L-PBF Al–Mg–Sc–Zr alloy, which is unlikely from perspectives of curvature-driven grain growth, crystallographic texture or strain-induced boundary migration. The observed spontaneous AGG is understood in light of the growth instability of an arbitrary grain in an evolving particle-pinned polycrystalline aggregation. A generalized criterion for AGG is hence proposed, which efficaciously explains the observed susceptibility of FGs to AGG, the presence of multiple AGG activation sites, and the asynchrony of AGG activation.

Objectives: Campylobacter is a significant zoonotic pathogen primarily transmitted through poultry. Our study aimed to assess antimicrobial resistance and genetic relationships among Campylobacter isolates from retail chicken meat and humans in Taiwan. Methods: Campylobacter isolates were analysed using whole-genome sequencing to investigate their antimicrobial resistance, genetic determinants of resistance, and genotypes. Results: Campylobacter coli and Campylobacter jejuni accounted for 44.9% and 55.1% of chicken meat isolates, and 11.4% and 88.6% of human isolates, respectively. C. coli displayed significantly higher resistance levels. Furthermore, isolates from chicken meat exhibited higher levels of resistance to most tested antimicrobials compared to isolates from humans. Multidrug resistance was observed in 96.3% of C. coli and 43.3% of C. jejuni isolates from chicken meat and 80.6% of C. coli and 15.8% of C. jejuni isolates from humans. Macrolide resistance was observed in 85.5% of C. coli isolates, primarily attributed to the erm(B) rather than the A2075G mutation in 23S rRNA. Among the 511 genomes, we identified 133 conventional MLST sequence types, indicating significant diversity among Campylobacter strains. Notably, hierarchical Core-genome multilocus sequence typing clustering, including HC0, HC5, and HC10, revealed a significant proportion of closely related isolates from chicken meat and humans. Conclusions: Our research highlights significant associations in antimicrobial resistance and genetic relatedness between Campylobacter isolates from chicken meat and humans in Taiwan. The genetic analysis data suggest that campylobacteriosis outbreaks may occur more frequently in Taiwan than previously assumed. Our study emphasizes the need for strategies to control multidrug-resistant strains and enhance outbreak prevention.

Abstract Tin-lead halide perovskites with a bandgap near 1.2 electron-volt hold great promise for thin-film photovoltaics. However, the film quality of solution-processed Sn-Pb perovskites is compromised by the asynchronous crystallization behavior between Sn and Pb components, where the crystallization of Sn-based perovskites tends to occur faster than that of Pb. Here we show that the rapid crystallization of Sn is rooted in its stereochemically active lone pair, which impedes coordination between the metal ion and Lewis base ligands in the perovskite precursor. From this perspective, we introduce a noncovalent binding agent targeting the open metal site of coordinatively unsaturated Sn(II) solvates, thereby synchronizing crystallization kinetics and homogenizing Sn-Pb alloying. The resultant single-junction Sn-Pb perovskite solar cells achieve a certified power conversion efficiency of 24.13 per cent. The encapsulated device retains 90 per cent of the initial efficiency after 795 h of maximum power point operation under simulated one-sun illumination.

Abstract The global burden of hepatitis B virus (HBV) infection remains high, with chronic hepatitis B (CHB) patients facing a significantly increased risk of developing cirrhosis and hepatocellular carcinoma (HCC). The ultimate objective of antiviral therapy is to achieve a sterilizing cure for HBV. This necessitates the elimination of intrahepatic covalently closed circular DNA (cccDNA) and the complete eradication of integrated HBV DNA. This review aims to summarize the oncogenetic role of HBV integration and the significance of clearing HBV integration in sterilizing cure. It specifically focuses on the molecular mechanisms through which HBV integration leads to HCC, including modulation of the expression of proto-oncogenes and tumor suppressor genes, induction of chromosomal instability, and expression of truncated mutant HBV proteins. The review also highlights the impact of antiviral therapy in reducing HBV integration and preventing HBV-related HCC. Additionally, the review offers insights into future objectives for the treatment of CHB. Current strategies for HBV DNA integration inhibition and elimination include mainly antiviral therapies, RNA interference and gene editing technologies. Overall, HBV integration deserves further investigation and can potentially serve as a biomarker for CHB and HBV-related HCC.

This study investigated antimicrobial resistance in Salmonella enterica serovar Choleraesuis (S. Choleraesuis) isolates from diseased pigs in Taiwan (2015–2020). Among 272 isolates, florfenicol (96.7%), enrofloxacin (96.3%), doxycycline (91.2%), gentamicin (84.6%), and tiamulin (80.5%) exhibited high resistance. 99.3% of the isolates were resistant to at least one antibiotic, and 97.8% of the isolates were multidrug resistant. This study illustrated that S. Choleraesuis isolates exhibited high resistance to antimicrobials currently used in the Taiwanese swine industry.

Background: Hepatitis C virus (HCV) eradication with sofosbuvir/velpatasvir (SOF/VEL) represents a significant advancement, offering hope for eliminating the virus in diverse patient populations. But real-world data on its effectiveness and safety remains scarce for patients with chronic hepatitis C (CHC) in China, especially those with HCV GT3b, cirrhosis, hepato-cellular carcinoma (HCC), or HCV/hepatitis B (HBV), HCV/HIV, or HCV/HBV/HIV coinfection. Methods: In this real-world prospective observational study, we recruited patients from the West China Hospital and Public Health Clinical Center of Chengdu in China. Patients included adults with with CHC and any genotype (GT), with or without cirrhosis, hepatocellular carcinoma (HCC), HCV/HBV, HCV/HIV, or HCV/HBV/HIV coinfection. Patients were administered SOF/VEL (400/100 mg) ± ribavirin (RBV) once daily for 12 weeks. The primary efficacy endpoint was sustained virological response at post-treatment week 12 (SVR12). Adverse events (AEs) were evaluated during treatment. Results: The study included 483 patients with HCV genotypes 1, 2, 3, 6 and uncertain ones. Among them, 35.4 % (171/483, ITT) and 36.7 % (166/452, mITT) received SOF/VEL + RBV. At the end of treatment , 99.2 % (ITT, 479/483) and 99.1 % (mITT, 448/452) of patients had undetectable HCV RNA. SVR12 rates were 92.8 % [intention to treat (ITT), 448/483] and 99.1 % [modified ITT (mITT), 448/452]. In the mITT analysis, SVR12 for patients with HCV GT3b, those with cirrhosis or HCC, and those coinfected with HBV/HIV was 99.2 % (130/131), 99.4 % (168/169), and 97.6 % (40/41), respectively. The albumin-bilirubin (ALBI) (−3.01 vs. −3.18 P

BackgroundDiabetic retinopathy (DR) is a major complication of diabetes, leading to severe vision impairment. Understanding the molecular mechanisms, particularly PANoptosis, underlying DR is crucial for identifying potential biomarkers and therapeutic targets. This study aims to identify differentially expressed PANoptosis-related genes (DE-PRGs) in DR, offering insights into the disease’s pathogenesis and potential diagnostic tools.MethodsDR datasets were obtained from the Gene Expression Omnibus (GEO) database, while PANoptosis-related genes were sourced from the GeneCards database. Differentially expressed genes (DEGs) were identified using the DESeq2 package, followed by functional enrichment analysis through DAVID and Metascape tools. Three machine learning algorithms—LASSO regression, Random Forest, and SVM-RFE—were employed to identify hub genes. A diagnostic nomogram was constructed and its performance assessed via ROC analysis. The CIBERSORT algorithm analyzed immune cell infiltration. Hub genes were validated through RT-qPCR, Western blotting, immunohistochemistry, and publicly available datasets. Additionally, the impact of FASN and PLSCR3 knockdown on HUVECs behavior was validated through in vitro experiments.ResultsDifferential expression analysis identified 1,418 DEGs in the GSE221521 dataset, with 39 overlapping DE-PRGs (29 upregulated, 10 downregulated). Functional enrichment indicated that DE-PRGs are involved in apoptosis, signal transduction, and inflammatory responses, with key pathways such as MAPK and TNF signaling. Machine learning algorithms identified six PANoptosis-related hub genes (BEX2, CASP2, CD36, FASN, OSMR, and PLSCR3) as potential biomarkers. A diagnostic nomogram based on these hub genes showed high diagnostic accuracy. Immune cell infiltration analysis revealed significant differences in immune cell patterns between control and DR groups, especially in Activated CD4 Memory T Cells and Monocytes. Validation confirmed the diagnostic efficiency and expression patterns of the PANoptosis-related hub genes, supported by in vitro and the GSE60436 dataset analysis. Furthermore, experiments demonstrated that knocking down FASN and PLSCR3 impacted HUVECs behavior.ConclusionThis study provides valuable insights into the molecular mechanisms of DR, particularly highlighting PANoptosis-related pathways, and identifies potential biomarkers and therapeutic targets for the disease.