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This research paper investigates the intersection of the maker movement and educational innovation, using the China-U.S. Young Maker Competition as a foundational example. It examines how maker education, fueled by hands-on learning and a curiosity-driven approach, can evolve and influence. The study explores the roles and impacts of Human-Computer Interaction (HCI), Design-Driven Innovation (DDI), and Cross-Cultural Perspectives (CCP) within maker education. It highlights HCI's connection of technology with learning, DDI's focus on user-centered solutions, and the significance of CCP in enhancing cultural collaboration, vital for fostering an innovative and creative future. This paper offers a detailed perspective on the current state and future potential of maker education. It proposes a roadmap for the coming decade, emphasizing collaborative learning and creative endeavors, all set within the engaging environment of the competition.

Abstract. Background:. Renal ischemia–reperfusion (R-I/R) injury is the most prevalent cause of acute kidney injury, with high mortality and poor prognosis. However, the underlying pathological mechanisms are not yet fully understood. Therefore, this study aimed to investigate the role of N‐myc downstream‐regulated gene 2 (Ndrg2) in R-I/R injury. Methods:. We examined the expression of Ndrg2 in the kidney under normal physiological conditions and after R-I/R injury by immunofluorescence staining, real-time polymerase chain reaction, and western blotting. We then detected R-I/R injury in Ndrg2-deficient (Ndrg2–/–) mice and wild type (Ndrg2+/+) littermates in vivo, and detected oxygen and glucose deprivation and reperfusion (OGD-R) injury in HK-2 cells. We further conducted transcriptomic sequencing to investigate the role of Ndrg2 in R-I/R injury and detected levels of oxidative stress and mitochondrial damage by dihydroethidium staining, biochemical assays, and western blot. Finally, we measured the levels of mitophagy in Ndrg2+/+ and Ndrg2–/– mice after R-I/R injury or HK-2 cells in OGD-R injury. Results:. Ndrg2 was primarily expressed in renal proximal tubules and its expression was significantly decreased 24 h after R-I/R injury. Ndrg2–/– mice exhibited significantly attenuated R-I/R injury compared to Ndrg2+/+ mice. Transcriptomics profiling showed that Ndrg2 deficiency induced perturbations of multiple signaling pathways, downregulated inflammatory responses and oxidative stress, and increased autophagy following R-I/R injury. Further studies revealed that Ndrg2 deficiency reduced oxidative stress and mitochondrial damage. Notably, Ndrg2 deficiency significantly activated phosphatase and tensin homologue on chromosome ten-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy. The downregulation of NDRG2 expression significantly increased cell viability after OGD-R injury, increased the expression of heme oxygenase-1, decreased the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, and increased the expression of the PINK1/Parkin pathway. Conclusion:. Ndrg2 deficiency might become a therapy target for R-I/R injury by decreasing oxidative stress, maintaining mitochondrial homeostasis, and activating PINK1/Parkin-mediated mitophagy.

Abstract Background The Interleukin-6 (IL-6)-signal transducer and activator of transcription 3 (STAT3) pathway, along with the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, are critical contributors to neuroinflammation in Alzheimer’s disease (AD). Although previous research outside the context of AD has indicated that the IL-6-STAT3 pathway may regulate the cGAS-STING pathway, the exact molecular mechanisms through which IL-6-STAT3 influences cGAS-STING in AD are still not well understood. Methods The activation of the IL-6-STAT3 and cGAS-STING pathways in the hippocampus of 5×FAD and WT mice was analyzed using WB and qRT-PCR. To explore the effects of IL-6 deficiency, Il6 +/− mice were crossed with 5×FAD mice, and the subsequent impact on hippocampal STAT3 pathway activity, cGAS-STING pathway activation, amyloid pathology, neuroinflammation, and cognitive function was evaluated through WB, qRT-PCR, immunohistochemistry, ThS staining, ELISA, and behavioral tests. The regulatory role of STAT3 in the transcription of the Cgas and Sting genes was further validated using ChIP-seq and ChIP-qPCR on hippocampal tissue from 5×FAD and Il6 −/− : 5×FAD mice. Additionally, in the BV2 microglial cell line, the impact of STAT3 activation on the transcriptional regulation of Cgas and Sting genes, as well as the production of inflammatory mediators, was examined through WB and qRT-PCR. Results We observed marked activation of the IL-6-STAT3 and cGAS-STING pathways in the hippocampus of AD mice, which was attenuated in the absence of IL-6. IL-6 deficiency reduced beta-amyloid deposition and neuroinflammation in the hippocampus of AD mice, contributing to cognitive improvements. Further analysis revealed that STAT3 directly regulates the transcription of both the Cgas and Sting genes. These findings suggest a potential mechanism involving the STAT3-cGAS-STING pathway, wherein IL-6 deficiency mitigates neuroinflammation in AD mice by modulating this pathway. Conclusion These findings indicate that the STAT3-cGAS-STING pathway is critical in mediating neuroinflammation associated with AD and may represent a potential therapeutic target for modulating this inflammatory process in AD.

Abstract Induced pluripotent stem cell (iPSC) technology, in combination with electrophysiological characterization via multielectrode array (MEA), has facilitated the utilization of iPSC-derived motor neurons (iPSC-MNs) as highly valuable models for underpinning pathogenic mechanisms and developing novel therapeutic interventions for motor neuron diseases (MNDs). However, the challenge of MN adherence to the MEA plate and the heterogeneity presented in iPSC-derived cultures raise concerns about the reproducibility of the findings obtained from these cellular models. We discovered that one novel factor modulating the electrophysiological activity of iPSC-MNs is the extracellular matrix (ECM) used in the coating to support in vitro growth, differentiation and maturation of iPSC-MNs. The current study showed that two coating conditions, namely, Poly-L-ornithine/Matrigel (POM) and Polyethyleneimine (PEI) strongly promoted attachment of iPSC-MNs on MEA culture dishes compared to three other coating conditions, and both facilitated the maturation of iPSC-MNs as characterized by the detection of extensive electrophysiological activities from the MEA plates. POM coating accelerated the maturation of the iPSC-MNs for up to 5 weeks, which suits modeling of neurodevelopmental disorders. However, the application of PEI resulted in more even distribution of the MNs on the culture dish and reduced variability of electrophysiological signals from the iPSC-MNs in 7-week cultures, which permitted the detection of enhanced excitability in iPSC-MNs from patients with amyotrophic lateral sclerosis (ALS). This study provides a comprehensive comparison of five coating conditions and offers POM and PEI as favorable coatings for in vitro modeling of neurodevelopmental and neurodegenerative disorders, respectively.

This paper describes our equity-driven development of a chatbot curriculum for a journalism professional development center’s massive open online courses (MOOCs). A curriculum refers to entire student experiences that occur during the whole learning process in this context. We used a sequential and iterative development process with four phases to research and develop the chatbot curriculum: experimentation, evaluation, research and development reiteration, and implementation and evaluation in an ongoing course. In Phase 1, we tested whether a chatbot interface designed to answer frequently asked questions (FAQs) could provide more equitable student support than traditional FAQ pages, considering the widespread student frustration about FAQ pages. A total of 120 diverse students participated in this phase. In Phase 2, we conducted a case study to contrast the experiences of 27 non-native English users who used the FAQ chatbot, identifying what distinguished their experiences from those of 15 native English user counterparts. Based on this phase’s findings, the chatbot was further trained using an enhanced training set to better support non-native English users. In Phase 3, using a topic analysis result of 3,645 forum discussion posts from the center’s previous 21 courses, we ensured the chatbot’s expertise to cover nine additional topic themes. Phase 4 is where we examine students’ experiences with the chatbot’s latest version as a built-in course tool in MOOCs. This study suggests that systematic research and development of a chatbot curriculum is indispensable to fostering equitable learning environments in MOOCs.

Abstract Grassland is a widely distributed land use type that provides essential resources for livestock production and serves as a crucial ecosystem component. Over the past decades, grassland has significantly degraded and shrunk due to climate change and human activities, with ongoing changes in its area. This study utilized the Google Earth Engine (GEE) and the Res-UNet++ model to analyze the phenological and spectral characteristics of grasslands in Landsat images for long-term annual monitoring. Additionally, the LandTrendr algorithm was utilized to correct long-term time series data for grasslands, yielding a map of grassland distribution in Inner Mongolia from 1991 to 2020. The results indicate that the overall spatial accuracy from 1991 to 2020 exceeded 96%, with a Kappa coefficient over 0.92, demonstrating high monitoring accuracy. In particular, the 2019 grassland monitoring area showed high consistency with data from the Third National Land Survey (TNLS), with a coefficient of determination (R^2) reaching 0.97, reflecting the high accuracy and reliability.

Abstract Background To investigate the impact of using contrast-enhanced computed tomography (CHCT) in the dosimetry of stereotactic body radiation therapy (SBRT) for liver metastases treated with MR-Linac. Methods A retrospective study was conducted on 21 liver cancer patients treated with SBRT (50 Gy in 5 fractions) using a 1.5 Tesla Unity MR-Linac. The clinical treatment plans optimised on plain computed tomography (pCT) were used as reference. The electronic density (ED) of regions of interest (ROIs) including the liver, duodenum, esophagus, spinal cord, heart, ribs, and lungs, from pCT and CHCT, was analysed. The average ED of each ROI from CHCT was used to generate synthetic CT (sCT) images by assigning the average ED value from the CHCT to the pCT. Clinical plans were recalculated on sCT images. Dosimetric comparisons between the original treatment plan (TPpCT) and the sCT plan (TPsCT) were performed using dose-volume histogram (DVH) parameters, and gamma analysis. Results Significant ED differences (p

Abstract Oncolytic virotherapy is emerging as a promising therapeutic avenue for cancer treatment, harnessing both innate and tumor-specific immune responses for targeted tumor elimination. In this study, we present a novel oncolytic virus (oHSV1-IL15B) derived from herpes simplex virus-1 (HSV-1), armed with IL-15/IL-15Rα complex, with a focus on treating colon cancer combined with oncolytic HSV-1 expressing anti-PD-1 antibody (oHSV1-aPD1). Results from our study reveal that recombinant oHSV-1 virus equipped with IL-15/IL-15Rα complex exhibited significant anti-tumor effects in a murine CT26 colon adenocarcinoma model. Notably, oHSV1-IL15B combined with oHSV-1-aPD1 demonstrates superior tumor inhibition and prolonged overall survival compared to oHSV1-mock and monotherapy groups. Further exploration highlights the impact of oHSV1-IL15B, oHSV-1-aPD1 and combined group on antitumor capacity, revealing a substantial increase in CD8+ T and CD4+ T cell proportions of CT26-bearing BALB/c mice and promoting apoptosis in tumor tissue. The study emphasizes the pivotal role of cytotoxic CD8+T cells in oncolytic virotherapy, demonstrating that recombinant oHSV1-IL15B combined with oncolytic HSV-1-aPD1 induces a robust tumor-specific T cell response. RNA sequence analysis highlighted oHSV1-IL15B combined with oHSV1-aPD1 improved tumors immune microenvironment on immune response, antiviral response-related genes and apoptosis-related genes, which contributed to anti-tumor immunotherapy. The findings underscore the promising antitumor activity achieved through the combination of IL-15/IL-15Rα complex and anti-PD-1 antibody with oHSV-1. This research opens avenues for diverse therapeutic strategies, suggesting the potential of synergistically utilizing cytokines and anti-PD-1 antibody with oncolytic viruses to enhance immunotherapy for cancer management.

Abstract Background Cancer patients’ vulnerability to QT prolongation contradicts certain anti-cancer drug usage. Until now, the QT prolongation’s impact on CV mortality in cancer patients remains unclear, potentially biasing therapeutic decisions. Methods This retrospective observational cohort included adult cancer patients with an electrocardiogram (ECG) performed in a tertiary hospital in Taiwan. The first performed ECGs after cancer diagnosis (n = 59,568) were analyzed. The corrected QT intervals by Bazett (QTcB), Fridericia (QTcFri), and Framingham (QTcFra) formulae were used to predict the 90-day and one-year CV mortality according to the Taiwan death registry. Results The AUC of QTcB (90 days: 0.70, 1 year: 0.68) for predicting CV mortality was better than QTcFri and QTcFra (90 days: 0.63 and 0.50, 1 year: 0.65 and 0.56). Using the restricted cubic spline regression model adjusted by age and comorbidities, QTcB increased a significant but trivial risk of CV mortality at 90 days (hazard ratio, 1.007, P = 0.02) and one year (1.006, P

Abstract Cisplatin (CP), a chemotherapy drug commonly used in cancers treatment, causes serious reproductive toxicity. With younger cancer patients and increasing survival rates, it is important to preserve their reproductive capacity. NME8 is highly expressed in testis and contains thioredoxin and NDPK domains, suggesting it may be a target against the CP-induced reproductive toxicity. We deleted exons 6–7 of the Nme8 in mice based on human mutation sites and observed impaired transcript splicing. In mice, Nme8 was not essential for spermatogenesis, possibly due to functional compensation by its paralog, Nme5. Nme8 expression was elevated and translocated to the nucleus in response to two weeks of CP treatment. Under CP treatment, Nme8 deficiency further impaired antioxidant capacity, induced lipid peroxidation and increased ROS level, and failed to activate autophagy, resulting in aggravated DNA damage in testes and sperm. Consequently, the proliferation and differentiation of spermatogonia and the meiosis of spermatocyte were almost completely halted, and sperm motility was impaired. Our research indicates that NME8 protects against CP-induced testis and sperm damage. This may provide new insights into the physiological functions of the Nme family and potential targets for preserving fertility in young male cancer patients.

Background/purpose: Quantitative in vitro research was conducted on the learning process of a dynamic navigation system. This study provides guidance for the promotion and application of dynamic navigation technology in the endodontic apical surgery field. Materials and methods: Standardized models were designed and 3D printed to form the approach operation of endodontic apical surgery. 6 clinicians with no experience in dynamic navigation performed the operation. The distance deviation tolerance was set as 0.6 mm, and the angle deviation tolerance was set as 5°. Fifteen mm deep approach operation was completed using dynamic navigation. Each operator performed 10 consecutive exercises on the models. The positioning deviation and operation time of each operator for each practice were recorded. Based on this, the learning curve of the dynamic navigation of every operator was mapped. The learning difficulty of dynamic navigation was evaluated. Results: The learning curves of all operators reached a stable level after the 7th practice, which can ensure that the distance and angle deviations are maintained within the deviation tolerances (0.6 mm, 5°). Conclusion: Operators with no experience in dynamic navigation technology need practice to master dynamic navigation operations. For this navigation system, operators with no operational experience can master dynamic navigation operations after 7 exercises.

新世代年輕人有獨特的習性、特質和價值觀念，即便才進入大專校院就讀，卻總是對學習顯得興趣缺缺。其實若能找到他們喜歡的教學方法，他們是樂於學習的。本研究目的即在瞭解喚起新世代年輕人的學習動機因素及其喜歡的教學方法，並探討不同科系領域和就讀地區是否有差異存在。本研究從文獻探討和六場焦點團體訪談結果自編問卷，經信度與效度檢核後，讓新世代年輕人評估相關因素的重要程度與落實程度，並且勾選喜歡的教學方法，二階段施測，回收有效問卷999份，使用相依樣本平均數t檢定、單因子多變量分析、多群組潛在結構模式等分析發現：一、喚起新世代年輕人的學習動機有實踐互動、系統講述、適性關懷、成果期待等因素，他們對這些因素大多感到非常重要或重要，至於落實程度只覺得有時如此或普通，重要程度得分均顯著高於落實程度得分。二、不同科系領域學生對於喚起學習動機因素的落實程度有顯著差異，經比較發現，人文社會領域實踐互動因素落實程度較高，而成果期待因素則是科技領域較高，至於不同就讀地區學生沒有顯著差異。三、新世代年輕人大 多喜歡「講述&專題」和「講述&小組」教學方法，且相較之下，人文社會領域較喜歡遊戲競賽和戶外參訪體驗，而科技領域則是教師講述、專題實作／個案研究／問題解決、練習法，顯示不同科系領域有不同教學需求喜好，至於不同就讀地區，學生則沒有顯著差異。 Motivation and Purpose A new generation of young people is entering tertiary institutions. These people have distinct traits and values and tend to exhibit limited interest in learning. For this population, motivation for learning is a crucial topic because it stimulates fundamental engagement in learning activities, sustaining them until successful outcomes are achieved. Taiwan’s tertiary institutions are being affected by Taiwan’s low birth rate, international competition, globalization, mobility issues, and a lack of learning motivation among students. Learning motivation is a key factor in determining whether students can adapt to higher education. Students are willing to learn when they are exposed to an engaging teaching method or when their motivation is stimulated. This study argues that the characteristics of a given subject area must be considered when developing strategies for motivating learning or implementing teaching. The research objectives of this article are as follows: (1) To assess the importance and implementation levels of various motivational factors for the new generation of young people and to further understand the differences between importance and implementation levels; (2) To explore the differences in the motivational factors within various fields and areas of study; and (3) To explore the differences in preferred teaching methods within various fields and areas of study and to compare preferences between students from different localities. Literature Review Most scholars agree that within each generation, academic goals, interests, skills, and core ideas are influenced by changes in the social environment and technological advancements. In general, the various generations can be divided into four groups: Baby Boomers, Generation X, Generation Y, and Generation Z. The current study focuses on Generation Z. According to the literature, teachers should encourage Generation Z students to take an active role in their learning. Notably, they do not want to passively accept knowledge and information, and they are easily distracted. Therefore, teachers must identify methods to attract their attention. However, learning content must be appropriately challenging (i.e., neither excessively difficult nor easy), otherwise Generation Z students will feel frustrated and bored. Finally, these students want to apply what they learn in their daily lives. Additionally, they expect teachers to adapt their teaching methods and activities in accordance with the learning levels of students. As a result, these students are often dissatisfied with traditional methods of knowledge delivery, preferring teachers who present curriculum knowledge in a systematic and specific manner. They particularly prefer interactive teaching methods, such as small group cooperative learning, thematic research, games and competitions, interviews, and the integration of technology into the teaching process. The Ministry of Education applied the SCED-F 2013 framework to classify academic subjects by intrinsic attributes. This study analyzes differences in motivational factors and preferred teaching methods between students. The International Standard Classification of Education was used to categorize students. Methodology A questionnaire was developed on the basis of a literature review and six focus group interviews. The validity and reliability of the questionnaire was evaluated. Respondents were asked to evaluate the importance and level of implementation of various initiatives, as well as their preferred methods of teaching. Generation Z individuals born between 1996 and 2012 who had attended a tertiary institution were enrolled in this study. The questionnaire was administered in two stages. The first stage involved an online questionnaire. The sampling method was based on Ministry of Education statistics, which were used to select colleges and universities in accordance with the distribution of university students across northern, central, southern, and eastern Taiwan and the outlying islands of Taiwan. Respondents were then selected in accordance with the distribution of students enrolled in various fields of studies within these institutions. In the second stage, paper-based questionnaires were administered. Teachers or students from relevant departments with low student proportions were contacted to assist in the distribution of these questionnaires. In total, 1,119 questionnaires were collected in the second stage, with 999 deemed valid. Invalid questionnaires comprised those with age inaccuracies, consecutive identical responses, or missing responses on an entire side of the questionnaire. The results were analyzed by performing the paired-samples t-test, multivariate analysis of variance, and multiple group latent class analysis. Results The learning motivation of the respondents was characterized by an interactive and practical approach, which can be leveraged to enhance their motivation for learning. The key elements of learning motivation include practical interaction, systematic presentation, tailoring to students’ needs, and the expectation of tangible results. Most of them perceived these factors as relevant and significant. However, the level of implementation was mediocre and ordinary, with the scores on the importance of these factors being notably higher relative to those on their implementation. A significant difference in implementation level was identified across disciplines. Specifically, implementation levels were significantly higher in the field of humanities and social sciences. By contrast, the level of outcome expectations was higher in the field of science and technology. The implementation level among participants from different study localities was not significantly different. The respondents preferred a combination of lectures and projects as well as lectures and group work. Humanities and social sciences students preferred games, competitions, and outdoor activities, whereas science and technology students preferred lectures by teachers, project work, case studies, and problem-solving activities. The study revealed that teaching needs varied across disciplines and that students’ preferences did not significantly differ among localities. Recommendations (1) Because of the distinct habits of the younger generation, implementing learning motivation factors that they value to effectively promote learning engagement is crucial. (2) The intrinsic characteristics of each discipline must also be considered when developing teaching activities. (3) Future research can examine the differences between awareness and implementation or expand the analysis by including additional samples or variables

Background and aim: Hepatic ischemia–reperfusion injury (IRI) is a significant challenge in liver transplantation, trauma, hypovolemic shock, and hepatectomy, with limited effective interventions available. This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2 (LECT2) in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA (shRNA) delivered through adeno-associated virus (AAV) vectors. Materials and methods: This study analyzed human liver and serum samples from five patients undergoing the Pringle maneuver. Lect2-knockout and C57BL/6J mice were used. Hepatic IRI was induced by clamping the hepatic pedicle. Treatments included recombinant human LECT2 (rLECT2) and AAV-Lect2-shRNA. LECT2 expression levels and serum biomarkers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) were measured. Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. Results: Serum and liver LECT2 levels were elevated during hepatic IRI. Serum LECT2 protein and mRNA levels increased post reperfusion. Lect2-knockout mice had reduced weight loss; hepatic necrosis; and serum ALT, AST, creatinine, and BUN levels. rLECT2 treatment exacerbated weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN). AAV-Lect2-shRNA treatment significantly reduced weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN), indicating therapeutic potential. Conclusions: Elevated LECT2 levels during hepatic IRI increased liver damage. Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage, indicating its therapeutic potential. AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI, offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

Abstract Background Previous studies only considered the impact of a single physical or psychological disorder on dementia. Our study investigated the association of physical and psychological multimorbidity with dementia among older adults using two multinational prospective cohorts to supplement the limited joint evidence. Methods We utilized the Health and Retirement Study (HRS 2012 to 2018) in the United States (US) and the Survey of Health, Ageing and Retirement in Europe (SHARE 2012 to 2018). Physical disorder was defined as any one of seven self-reported physician-diagnosed conditions. Psychological disorder was assessed using the 8-item Center for Epidemiologic Research Depression (CES-D) scale or the EURO-D. Dementia was determined through a combination of self-reported physician diagnosis of dementia or Alzheimer’s disease, or the 27-point HRS cognitive scale. Competing risk models were utilized to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CI). DerSimonian-Laird random-effects meta-analyses were conducted to obtain pooled estimates. Results The prevalence of physical and psychological multimorbidity was 17.29% (1027/5939) in continental Europe and 15.52% (1326/8543) in the US. The incidence of dementia was 6.21 per 1000 person-years in continental Europe and 8.27 per 1000 person-years in the US, respectively. It was highest among participants with physical and psychological multimorbidity in continental Europe (10.46 per 1000 person-years) and the US (14.82 per 1000 person-years), compared with the other three groups. In the univariate model, participants who reported physical and psychological multimorbidity had a higher risk of dementia compared with those who reported no physical and psychological disorders in continental Europe (HR = 2.59; 95% CI: 1.55, 4.33) and the US (HR = 4.11; 95% CI: 2.44, 6.94). After adjusting all covariates, the risk of dementia among participants who reported physical and psychological multimorbidity increased by 86% in continental Europe (aHR = 1.86; 95% CI: 1.08, 3.21) and by 176% in the US (aHR = 2.76; 95% CI: 1.61, 4.72), respectively. After pooling the outcomes, the risk of dementia among participants who reported physical and psychological multimorbidity increased by 115% (aHR = 2.15; 95% CI: 1.27, 3.03). Conclusions Physical and psychological multimorbidity was prevalent among older adults in the US and continental Europe. Given the consistent associations with dementia, it is imperative to increase awareness of the links and recognize the limitations of single-disorder care. Specific attention should be given to providing care coordination.

Abstract RNA-binding proteins (RBPs) modulate all aspects of RNA metabolism, but a comprehensive picture of RBP expression across tissues is lacking. Here, we describe our development of the method we call HARD-AP that robustly retrieves RBPs and tightly associated RNA regulatory complexes from cultured cells and fresh tissues. We successfully use HARD-AP to establish a comprehensive atlas of RBPs across mouse primary organs. We then systematically map RNA-binding sites of these RBPs using machine learning-based modeling. Notably, the modeling reveals that the LIM domain as an RNA-binding domain in many RBPs. We validate the LIM-domain-only protein Csrp1 as a tissue-dependent RNA binding protein. Taken together, HARD-AP is a powerful approach that can be used to identify RBPomes from any type of sample, allowing comprehensive and physiologically relevant networks of RNA-protein interactions.

Abstract Disruption of ciliary homeostasis in vascular endothelial cells has been implicated in the development of atherosclerosis. However, the molecular basis for the regulation of endothelial cilia during atherosclerosis remains poorly understood. Herein, we provide evidence in male mice that the accumulation of lipid droplets in vascular endothelial cells induces ciliary loss and contributes to atherosclerosis. Triglyceride accumulation in vascular endothelial cells differentially affects the abundance of free fatty acid species in the cytosol, leading to stimulated lipid droplet formation and suppressed protein S-palmitoylation. Reduced S-palmitoylation of ciliary proteins, including ADP ribosylation factor like GTPase 13B, results in the loss of cilia. Restoring palmitic acid availability, either through pharmacological inhibition of stearoyl-CoA desaturase 1 or a palmitic acid-enriched diet, significantly restores endothelial cilia and mitigates the progression of atherosclerosis. These findings thus uncover a previously unrecognized role of lipid droplets in regulating ciliary homeostasis and provide a feasible intervention strategy for preventing and treating atherosclerosis.

Abstract The parietodynamic wall, a type of dynamic insulation, has been recognized as an effective technology to reduce energy loss in buildings by recovering heat energy through forced convection. However, current research on the thermal performance of parietodynamic walls has overlooked the influence of thermal radiation, a crucial factor in energy transfer within the air layers of these walls. To bridge this gap, an innovative simulation model was developed and experimentally validated. Employing simulation methods, we investigated the impact of thermal radiation on the thermal behavior of parietodynamic walls under various influencing factors. Our findings reveal that thermal radiation markedly increases heat loss. Specifically, at an emissivity of 1, thermal radiation contributes up to 80.7% to the heat transfer coefficient (HTC) of the parietodynamic wall. Moreover, for a parietodynamic wall without insulation, the HTC of this wall will increase by more than 268% when thermal radiation is taken into account, compared to when it is not considered. These revelations deepen our comprehension of the role of thermal radiation in parietodynamic walls and offer valuable guidance for the development of more energy-efficient buildings.

Abstract Background Dental caries is still a major disease that affect the oral health of people in China. First permanent molars (FPMs) are the most caries-susceptible teeth among school-aged children. The aim of this study was to investigate the eruption and caries status of first permanent molars in children aged 6–7 years in Shijingshan District, Beijing, China, to provide information for oral health promotion. Methods The study was a cross-sectional survey conducted in 6-7-year-old first grade children from public elementary schools in Shijingshan District, Beijing. Participants were invited to receive a clinical oral examination. The eruption status and caries experience of FPMs were recorded. Questionnaires assessing children’s sociodemographic information and oral health-related behaviors were completed by the children’s parents or guardians. Results A total of 3,176 children, including 1,644 boys (51.8%) and 1,532 girls (48.2%) were included in the oral examination and questionnaire. Eruption status of FPMs was as follows: 37.5% fully erupted, 28.3% partially erupted, 34.2% not erupted. Girls had more erupted FPMs than boys (70.1% VS 61.8%, P

Abstract Background Mesenchymal stem cells (MSCs) possess powerful immunomodulatory ability. This study aimed to assess the efficacy and safety of human umbilical cord-derived mesenchymal stem cells (UMSCs) in patients with ulcerative colitis (UC) and to explore the potential mechanisms. Methods This prospective, self-controlled clinical study was conducted at Henan Provincial People’s Hospital. Patients with moderate-to-severe active UC, unresponsive to traditional drugs were continuously enrolled from September 2018 to March 2023. UMSCs were administered intravenously monthly for two months at a cell dosage of 1 × 106 per kg. The primary outcome was a clinical response at 2 months. The levels of cytokines and progerin in the plasma of the patients were analyzed using enzyme-linked immunosorbent assay kits, and longitudinal data was analyzed using generalized estimation equation. Results Forty-one patients were enrolled and received UMSC therapy. At 2 months, 73.2% (30/41) of patients achieved a clinical response, and 41.5% (17/41) achieved a clinical remission. At 6 months, 2 patients were lost to follow-up; the corresponding figures were 70.0% (25/41) and 34.2% (14/41), respectively. After UMSC therapy, the Mayo score, Mayo endoscopy score, mean and maximum values of Ulcerative Colitis Endoscopic Index of Severity and Nancy index were significantly reduced compared with baseline values. Additionally, the levels of progerin and inflammatory markers, such as interleukin (IL)-1β, IL-6, IL-8, IL-12, and IL-17 A decreased, while hemoglobin, albumin, and IL-10/IL-17 A ratio increased, particularly in the response group. Multiple stepwise logistic regression analysis showed age was an independent risk factor affecting efficacy (odds ratio, 0.875 (95% confidence interval (0.787, 0.972)); the area under the receiver operating characteristic curve for age was 0.79. No serious adverse events were observed during or after UMSC therapy. Conclusion UMSCs are safe and effective for patients with UC, with age being an independent risk factor affecting efficacy. Mechanistically, UMSC treatment may ameliorate cell senescence and suppress the secretion of pro-inflammatory cytokines. Trial registration The study was retrospectively registered at www.chictr.org.cn/ (ChiCTR1900026035) on September 18, 2019.

Abstract Background Magnetic resonance-guided adaptive radiotherapy (MRgART) at MR-Linac allows for plan optimisation on the MR-based synthetic CT (sCT) images, adjusting the target and organs at risk according to the patient’s daily anatomy. Conversely, conventional linac image-guided radiotherapy (IGRT) involves rigid realignment of regions of interest to the daily anatomy, followed by the delivery of the reference computed tomography (CT) plan. This study aims to evaluate the effectiveness of MRgART versus IGRT for rectal cancer patients undergoing short-course radiotherapy, while also assessing the dose accumulation process to support the findings and determine its usefulness in enhancing treatment accuracy. Methods Nineteen rectal cancer patients treated with a 1.5 Tesla MR-Linac with a prescription dose of 25 Gy (5 Gy x 5) and undergoing daily adapted radiotherapy by plan optimization based on online MR-based sCT images, were included in this retrospective study. For each adapted plan ( $$\:{\text{T}\text{P}}_{\text{a}\text{d}\text{a}\text{p}}$$ ), a second plan ( $$\:{\text{T}\text{P}}_{\text{I}\text{G}\text{R}\text{T}}$$ ) was generated by recalculating the reference CT plan on the daily MR-based sCT images after rigid registration with the reference CT images to simulate the IGRT workflow. Dosimetry of $$\:{\text{T}\text{P}}_{\text{a}\text{d}\text{a}\text{p}}$$ and $$\:\:{\text{T}\text{P}}_{\text{I}\text{G}\text{R}\text{T}}$$ was compared for each fraction. Cumulative doses on the first and last fractions were evaluated for both workflows. The dosimetry per single fraction and the cumulative doses were compared using dose-volume histogram parameters. Results Ninety-five fractions delivered with MRgART were compared to corresponding simulated IGRT fractions. All MRgART fractions fulfilled the target clinical requirements. IGRT treatments did not meet the expected target coverage for 63 out of 94 fractions (67.0%), with 13 fractions showing a V95 median point percentage decrease of 2.78% (range, 1.65-4.16%), and 55 fractions exceeding the V107% threshold with a median value of 15.4 cc (range, 6.0-43.8 cc). For the bladder, the median $$\:{\text{D}}_{15\text{c}\text{c}}$$ values were 18.18 Gy for the adaptive fractions and 19.60 Gy for the IGRT fractions. Similarly the median $$\:{\text{D}}_{5\text{c}\text{c}}$$ values for the small bowel were 23.40 Gy and 25.69 Gy, respectively. No statistically significant differences were observed in the doses accumulated on the first or last fraction for the adaptive workflow, with results consistent with the single adaptive fractions. In contrast, accumulated doses in the IGRT workflow showed significant variations mitigating the high dose constraint, nevertheless, more than half of the patients still did not meet clinical requirements. Conclusions MRgART for short-course rectal cancer treatments ensures that the dose delivered matches each fraction of the planned dose and the results are confirmed by the dose accumulation process, which therefore seems redundant. In contrast, IGRT may lead to target dose discrepancies and non-compliance with organs at risk constraints and dose accumulation can still highlight notable dosimetric differences.

Objective: To explore the relation between procrastination and physical activity in college students and test whether grit mediated, age and gender moderated the process. Participants: 610 college students (aged 20.07 ± 1.53; 45.2% males) in Shanghai. Methods: Procrastination, grit and physical activity were tested respectively by International Procrastination Scale, Grit-S scale and International Physical Activity Questionnaire. Results: Correlation analysis showed that procrastination, grit and physical activity were related in pairs. Procrastination was negatively correlated with physical activity. Grit mediated between procrastination and physical activity. Females showed stronger moderation effect from grit to physical activity than males, while the effect between procrastination and grit was more significant for the younger. Conclusion: The moderated mediating model provided a new strategy of improving personality traits which contributed to lack of physical activity. More psychologically relevant measures should be taken in reducing procrastination to improve physical activity via improving grit.

Background: Prelinguistic communication complexity refers to the use of different communication forms such as eye gaze, gestures and vocalisations and the degree to which these forms are coordinated and how directed to a communication partner. To date, little is known about the relationship between prelinguistic communication complexity and expressive language in minimally verbal autistic children. Aims: To test the hypothesis that prelinguistic communication complexity predicts expressive language 12 months later in autistic children and explore whether there are any differences in specific prelinguistic intentional communicative behaviours that are related to later expressive language levels. Methods & Procedures: This longitudinal study examined 37 minimally verbal autistic children (29-71 months old). The Communication Complexity Scale (CCS) was used to measure participants' prelinguistic communication behaviours, which were extracted from a semi-structured play interaction at Time 1. The Chinese Communicative Development Inventory (CCDI) was used to examine participants' expressive language at Time 1 and Time 2 (12 months later). According to Time 2 vocabulary size, participants were divided into two groups: Low CCDI, between 0 and 62 words, and High CCDI, more than 100 words. Linear regression was used to examine the relationship between early prelinguistic communication complexity and later expressive language. Binary logistic regression was used to determine which of the early communication behaviours were uniquely significantly related to later expressive language levels. Outcomes & Results: There was a significant positive relationship between prelinguistic communication complexity and expressive language 12 months later, even after controlling for age and concurrent language. Findings revealed a group difference in the frequency of gesture and vocalisation combinations between the Low and High CCDI groups at Time 1. Gesture-vocalisation combinations also predicted better expressive language levels at Time 2. Conclusions & Implications: Our findings suggest that it may be beneficial to incorporate different complex communication behaviours into prelinguistic intervention targets for minimally verbal autistic children. The CCS hierarchies can be used as a reference for the intervention goals of minimally verbal autistic children. These findings highlight the importance of targeting gesture and vocalisation combinations when autistic children transition from single prelinguistic communication behaviours to multimodal behaviours.

This study aims to document the implementation of sign bilingualism and co-enrollment education in a kindergarten in Quzhou, Zhejiang Province, China, to identify the major characteristics of the programme, and to report findings of children's language in terms of vocabulary and surveys on the views and attitudes of the stakeholders of the programme, including deaf and hard-of-hearing (DHH) as well as hearing children and teachers. The results indicate that (a) both deaf and hearing teachers enjoy working in the Sign Bilingualism and Co-enrollment (SLCO) class and believe it is beneficial for their professional development; (b) parents of both DHH children and hearing children are happy to send their children to the SLCO class; (c) the teachers and parents agree that the SLCO programme is helpful for the overall development of not only the DHH children but also the hearing children. They believe that such an environment benefits the children's language and communication skills and the development of self-confidence and social cognition; (d) both the teachers and parents believe that the DHH children and their hearing peers get along well with each other in the SLCO class and also enjoy learning sign language. Furthermore, they all agree that the SLCO programme is promising and should be continued in the current school and implemented in more schools.

Phthalate esters (PE), a significant class of organic compounds used in industry, can contaminate humans and animals by entering water and food chains. Recent studies demonstrate the influence of PE on the development and progression of heart diseases, particularly in obese people. Di-isobutyl phthalate (DIBP) was administered orally to normal and diet-induced obese mice in this research to assess cardiovascular risk. The modifications in the microbial composition and metabolites were examined using RNA sequencing and mass spectrometry analysis. Based on the findings, lean group rodents were less susceptible to DIBP exposure than fat mice because of their cardiovascular systems. Histopathology examinations of mice fed a high-fat diet revealed lesions and plagues that suggested a cardiovascular risk. In the chronic DIBP microbial remodeling metagenomics Faecalibaculum rodentium was the predominant genera in obese mice. According to metabolomics data, arachidonic acid (AA) metabolism changes caused by DIBP were linked to unfavorable cardiovascular events. Our research offers new understandings of the cardiovascular damage caused by DIBP exposure in obese people and raises the possibility that arachidonic acid metabolism could be used as a regulator of the gut microbiota to avert related diseases.

Abstract Background Hemoptysis resulting from rupture of the pulmonary artery pseudoaneurysm (PAP) is massive and fatal, while factor contributing to the rupture of pseudoaneurysm remains elusive. This study aimed to elucidate the clinical and radiological features of PAP and identify the risk factors associated with rupture. Methods Patients who developed hemoptysis with PAP were collected from January 2019 to December 2022 retrospectively. Clinical data of the demographic characteristics, radiological findings, treatment strategies, and prognosis were collected. A comparative analysis was performed on the characteristics in the ruptured and non-ruptured cases. Results A total of 58 PAPs were identified in the 50 patients. The most common causes were infection (86%) and cancer (8%). The PAPs were located predominantly in the upper lobes of both lungs, and 57 (99.3%) were distributed in the segmental or subsegmental pulmonary arteries. The median diameter was 6.1(4.3–8.7) mm. A total of 29 PAPs were identified adjacent to pulmonary cavitations, with the median diameter of the cavity being 18.9 (12.4–34.8) mm. Rupture of pseudoaneurysm occurred in 21 cases (42%). Compared to unruptured group, the ruptured group had a significantly higher proportion of massive hemoptysis (57.1% vs. 6.9%, p

Abstract Pregestational diabetes mellitus (PGDM) has an impact on fetal bone formation, but the underlying mechanism is still obscure. Although miRNAs have been extensively investigated throughout bone formation, their effects on fetal bone development caused by PGDM still need clarification. This study intends to examine the mechanism by which hyperglycemia impairs the bone formation of offspring via miR-322-5p (miR-322). In this study, miR-322 was selected by systemically screening utilizing bioinformatics and subsequent validation experiments. Using streptozotocin (STZ)-induced diabetic mice and ATDC5 cell lines, we found that miR-322 was abundantly expressed in the proliferative and hypertrophic zones of the growth plate, and its expression pattern was disturbed in the presence of hyperglycemia, suggesting that miR-322 is involved in the chondrocyte proliferation and differentiation in absence/presence of hyperglycemia. This observation was proved by manipulating miR-322 expression in ATDC5 cells by transfecting mimic and inhibitor of miR-322. Furthermore, Adamts5, Col12a1, and Cbx6 were identified as the potential target genes of miR-322, verified by the co-transfection of miR-322 inhibitor and the siRNAs, respectively. The evaluation criteria are the chondrocyte proliferation and differentiation and their relevant key gene expressions (proliferation: Sox9 and PthIh; differentiation: Runx2 and Col10a1) after manipulating the gene expressions in ATDC5 cells. This study revealed the regulative role miR-322 on chondrocyte proliferation and differentiation of growth plate by targeting Adamts5, Col12a1, and Cbx6 in hyperglycemia during pregnancy. This translational potential represents a promising avenue for advancing our understanding of bone-related complications in diabetic pregnancy and mitigating bone deficiencies in diabetic pregnant individuals, improving maternal and fetal outcomes.

Abstract Background Thyroid hormone is the key endocrine regulator of growth, development, metabolism, and other bodily functions. α-Klotho has been involved in the aging process and acts as an endocrine factor involved in the regulation of various metabolic processes in humans. However, the relationship between α-Klotho and thyroid profile has not been uniformly recognize. Objective To determine the relationship between α-Klotho and thyroid profile in adult individuals. Methods Population data of 4614 adult individuals were obtained from the NHANES database during the period of 2007–2012. Weighted multivariable regression analysis was performed using a general linear model with serum α-Klotho as the independent variable and thyroid profile as the dependent variables, respectively. The generalized additive model was used for smoothing curve fitting and threshold effect analysis. Results α-Klotho was associated with a slightly higher FT3, TT3 and TT4 level in unadjusted and adjusted regression models. However, a higher α-Klotho level was associated with a lower TSH level. After α-Klotho was grouped as quantiles with reference (Q1), α-Klotho still showed a statistically significant positive correlation with FT3 and TT3 levels in Q2, Q3 and Q4. In addition, α-Klotho was positively corrected with TT4, but negatively associated with TSH in Q4. Conclusions Serum soluble α-Klotho was positively associated with FT3, TT3 and TT4, but negatively correlated with TSH. The significant effect of α-Klotho on thyroid profile suggests its potential as a predictive marker of thyroid functions, indicating its possible involvement in the regulation of thyroid hormone secretion.

The mathematical model of the profile is complicated and the connection conditions are not easily obtained by explicit calculation because different model parameters are used for different types of curves. To address the above problems, a new scroll profile is proposed by double spiral which is the combination of algebraic spiral and Archimedes spiral. First, based on the conjugate mesh theory, the relationship between the spindle angle and the pole angle of the curve is solved to derive the normalized mathematical model of the scroll line of the spiral type. Then, based on the smooth connection conditions of the combined profiles, the constraint equations of the connection points of the double spiral scroll profiles are established, and the geometric models of the two types of double spiral scroll profiles are obtained. Afterwards, the effects of the parameters of the first type of double spiral combined profile (spiral index, spiral coefficient, and pole angle of the connection point) on the geometric performance of the scroll teeth are quantitatively analyzed. Finally, the performance advantages of the two-screw combination scroll profile are comparatively studied. The results show that the geometry of the first type of double spiral combined profile is simple and can be directly used in production without head profile correction. The stroke volume is increased by 7.61%, the compression ratio is increased by 27.42%, and the area utilization factor is increased by 7.61% compared with the conventional circular involute scroll teeth at the same radial dimension of scroll teeth.

Abstract Background Given increases in China’s aging population, the growing demand for public health services and the shortage of human resources among nurses have become more prominent. Under such a background, “Internet + Nursing Services” have received more attention. Thus, exploring the barriers to and facilitators of nurses’ willingness to participate in “Internet + Nursing Services” and utilizing internet technology to increase the supply of nursing services has become a key issue. Objective This study aimed to develop a scale for assessing the barriers to and facilitators of nurses’ willingness to participate in “Internet + Nursing Services” and to test the validity and reliability of the scale. Methods A preliminary scale was developed based on a literature review, theoretical research, semistructured qualitative interviews, and two rounds of Delphi expert inquiry. A convenient sampling method was used for the questionnaire survey. A 5-point Likert scale was used to evaluate the importance of the items. The survey data of 659 clinical nurses obtained from February to March 2023 were used for item analysis, exploratory factor analysis (EFA), and reliability and validity tests of the scale. The survey data of 538 clinical nurses obtained in April 2023 were used for confirmatory factor analysis (CFA) of the final scale. Results The final scale consists of 25 items and 4 dimensions (performance expectations, perceived risk, need for professional knowledge training, and nonprofessional knowledge training). The scale showed good structural validity and content validity: the Cronbach’s α coefficient of the scale was 0.955, the split-half reliability was 0.778, the test-retest reliability was 0.944, the kaiser-meyer-olkin(KMO) value was 0.960, and the cumulative variance contribution rate of the 4 common factors was 83.147%. The scale content validity index(S-CVI) was 0.914. The confirmatory factor analysis model had favorable fit indices: χ2/df = 4.234, RMSEA = 0.078, NFI = 0.940, IFI = 0.953, TLI = 0.947, and CFI = 0.953. Conclusion The scale for assessing the barriers to and facilitators of nurses’ willingness to participate in “Internet + Nursing Services” has good reliability and validity, and provides a reference for evaluating nurses’ willingness to participate in “Internet + Nursing Services”.

Abstract The primary cilium behaves as a platform for sensing and integrating extracellular cues to control a plethora of cellular activities. However, the functional interaction of this sensory organelle with epithelial-mesenchymal transition (EMT) during pulmonary fibrosis remains unclear. Here, we reveal a critical role for cylindromatosis (CYLD) in reciprocally linking the EMT program and ciliary homeostasis during pulmonary fibrosis. A close correlation between the EMT program and primary cilia is observed in bleomycin-induced pulmonary fibrosis as well as TGF-β-induced EMT model. Mechanistic study reveals that downregulation of CYLD underlies the crosstalk between EMT and ciliary homeostasis by inactivating histone deacetylase 6 (HDAC6) during pulmonary fibrosis. Moreover, manipulation of primary cilia is an effective means to modulate the EMT program. Collectively, these results identify a pivotal role for the CYLD/HDAC6 signaling in regulating the reciprocal interplay between the EMT program and ciliary homeostasis during pulmonary fibrosis.

Src homology-2-containing protein tyrosine phosphatase 2 (SHP2) is a promising therapeutic target for cancer therapy. In this work, we presented the structure-guided design of 5,6-fused bicyclic allosteric SHP2 inhibitors, leading to the identification of pyrazolopyrazine-based TK-642 as a highly potent, selective, orally bioavailable allosteric SHP2 inhibitor (SHP2WT IC50 = 2.7 nmol/L) with favorable pharmacokinetic profiles (F = 42.5%; t1/2 = 2.47 h). Both dual inhibition biochemical assay and docking analysis indicated that TK-642 likely bound to the “tunnel” allosteric site of SHP2. TK-642 could effectively suppress cell proliferation (KYSE-520 cells IC50 = 5.73 μmol/L) and induce apoptosis in esophageal cancer cells by targeting the SHP2-mediated AKT and ERK signaling pathways. Additionally, oral administration of TK-642 also demonstrated effective anti-tumor effects in the KYSE-520 xenograft mouse model, with a T/C value of 83.69%. Collectively, TK-642 may warrant further investigation as a promising lead compound for the treatment of esophageal cancer.

Abstract For half a century, only Bi2Te3-based thermoelectrics have been commercialized for near room temperature applications including both power generation and refrigeration. Because of the strong layered structure, Bi2Te3 in particular for n-type conduction has to be texturized to utilize its high in-plane thermoelectric performance, leaving a substantial challenge in toughness. This work presents the fabrication and performance evaluation of thermoelectric modules based on n-type Ag2Se paring with commercial p-Bi2Te3. Ag2Se mechanically allows an order of magnitude larger fracture strain and thermoelectrically secures the module efficiency quite competitive to that of commercial one for both refrigeration and power generation within ± 50 K of room temperature, enabling a demonstration of a significantly tougher alternative to n-type Bi2Te3 for practical applications.

Abstract Background Enterococcus gallinarum is an infrequently intestinal symbiotic pathogen associated with nosocomial infection in immunocompromised individuals. To date, rare cases of pulmonary infection attributable to Enterococcus gallinarum were reported. Herein, we presented the first case of empyema resulting from Enterococcus gallinarum infection. Case presentation An 81-year-old male presented with fever and dyspnea upon admission. Chest CT scan and thoracic ultrasonography confirmed the presence of right pleural effusion. Thoracoscopy revealed extensive adhesion, purulent fluid, and necrotic materials within the thoracic cavity. Enterococcus gallinarum was identified through pleural effusion culture. The patient underwent an intrathoracic injection of urokinase along with thoracic drainage. Following surgery, He took oral linezolid for over one month. Undergoing comprehensive treatment, the patient exhibited favorable recovery. Conclusions We reported the first case of empyema due to Enterococcus gallinarum infection. It should be suspected in patients with impaired immune function and invasive therapies, without responding to conventional anti-infectious treatment.

Abstract As the important factors in coronary artery thrombosis, endothelial injury and M1 macrophage polarization are closely related to the expression of miR-34a-5p. Exosomes in plasma are mainly derived from platelets and play an important role in thrombosis. Based on these facts, this study was conducted to investigate the acting mechanism of platelet-derived exosomes (PLT-exo) in the effects of endothelial injury and M1 macrophage polarization on coronary artery thrombosis. Firstly, rats were divided into the sham-operated group and the coronary microembolization (CME) group, and their plasma-derived exosomes were extracted to detect the expression of miR-34a-5p. Next, the PLT-exo were extracted from healthy volunteers and then co-cultured with ox-LDL-induced endothelial cells and LPS-induced macrophages, respectively. Subsequently, the expression of IL-1β, IL-6, TNF-α, and ICAM-1 in endothelial cells was measured, and the level of markers related to M1 macrophage polarization and Sirt1/NF-κB pathway was detected. Finally, the above indicators were examined again after PLT-exo combined with miR-34a-5p mimic were co-cultured with endothelial cells and macrophages, respectively. The results demonstrated that the expression of miR-34a-5p in the CME group was up-regulated compared with the sham-operated group. In cell experiments, PLT-exo modulated the Sirt1/NF-κB pathway by inhibiting the expression of intracellular miR-34a-5p and down-regulated the expression of IL-1β, IL-6, TNF-α, and ICAM-1 in endothelial cells and M1 macrophage polarization. After the transfection with miR-34a-5p mimic, endothelial cell inflammatory injury and M1 macrophage polarization increased to varying degrees. In conclusion, PLT-exo can alleviate coronary artery thrombosis by reducing endothelial cell inflammation and M1 macrophage polarization via inhibiting miR-34a-5p expression. In contrast, miR-34a-5p overexpression in PLT-exo may exacerbate these pathological injuries in coronary artery thrombosis.

Abstract Previous studies exploring the effects of the business cycle on sleep have mostly focused on the general population, and their results have been inconclusive. This study aimed to explore the effects of the 2008 economic crisis and personality traits on the subjective sleep quality of outpatients with mood disorders. In this cross-sectional study, patients with mood disorders were recruited from two medical centers and a psychiatric hospital. Socio-demographics, the Eysenck Personality Questionnaire-Revised, and the Pittsburgh Sleep Quality Index (PSQI) were collected through in-person interviews. Candidate predictors significantly associated with PSQI scores in univariate analysis were included in a multiple linear regression model. There were 334 participants; 29% had unipolar depression, and 71% had bipolar affective disorder. The average PSQI score was 11.0 (±4.0). A higher degree of neuroticism [β(se) = 0.49 (0.07), p

Abstract Background Associations between Helicobacter pylori infection and lifestyle factors vary greatly by geographic location. This study aims to evaluate the prevalence of Helicobacter pylori infection in the Hunan cohort of central China and analyze the associations between Helicobacter pylori infection and lifestyle factors in different occupations. Methods This was a cross-sectional study. Participants who received an annual physical examination were invited. Helicobacter pylori infection was detected by the 13 C-urea breath test. Self-reported physical examination questionnaires were used to analyze participants’ demographic information, diet, exercise status, and sleep situations. Results 23254 participants finished this study. The Helicobacter pylori infection rate in the Hunan area was 25.8%, with the lowest prevalence in students (8.5%) and the highest prevalence in business managers (29.9%). The risk factors for Helicobacter pylori infection were marital status (divorced or married) (OR:1.16, 95%CI:1.090–1.234), overeating (OR:1.105, 95%CI: 1.001–1.220), and consumption of eggs (OR:1.047, 95%CI:1.004–1.092), animal viscera (OR: 1.077, 95%CI:1.014–1.144) and coffee (OR:1.074, 95%CI:1.019–1.132). Participants’ education level (OR:0.911, 95%CI:0.881-0942), consumption of midnight snack (OR:0.926, 95%CI:0.877–0.977), and vegetable (OR:0.927, 95%CI: 0.884–0.972) were protective factors against Helicobacter pylori infection. Whether participants exercised regularly or had sleep problems had no significant effect on Helicobacter pylori infection. Different professionals showed significant differences in the rates of overeating, eating three meals on time, midnight snack, and consuming coffee, eggs, animal viscera, and vegetables > 3 times/week (P values

Abstract To solve the problem of low resolution of seismic data from granite weathering crust and difficulty in predicting effective reservoir distribution. Based on the research idea of combining geology and seismology, seismic facies characteristics and effective reservoir distribution of granite weathering crust are studied by means of frequency division reconstruction processing, seismic facies analysis and sensitive attributes interpretation. This method consists of the following four main processes: (1) Using improved Morlet wavelet function for frequency division and reconstruction processing of seismic data; (2) From the perspective of geological evolution, analyzing the geological origin of seismic facies; (3) Based on the results of well- seismic combination, clarifying the types of effective reservoirs and predicting their distribution; (4) Comprehensive research indicating favorable reservoirs distribution. The results indicate that (1) a considerably improved resolution of seismic data processed by frequency division reconstruction is obtained based on the improved Morlet wavelet function. Thus, granite reservoirs then have clearer internal reflection characteristics. (2) Affected by differences in weathering, the seismic facies in granite weathering crusts can be classified as follows: Strong-amplitude facies with amplitudes of 23,700 − 32,800, corresponding to eluvium, represents the late stage of weathering crust evolution with high-intensity weathering. Medium-amplitude facies with amplitudes of 5,250 − 24,000, corresponding to dissolution layer, represents a middle stage of weathering crust evolution with moderate weathering. And weak-amplitude-blank facies with amplitudes of 0–5,330, corresponding to disintegration layer, represents an early stage of weathering crust evolution with weak weathering. (3) Effective reservoirs can be classified according to well-seismic calibrations and combined with reservoir spaces, porosities and permeabilities, and the logging and oil-bearing characteristics of the reservoirs. Type I effective reservoir comprises medium-amplitude facies, with favorable reservoir conditions and high-yield oil-bearing properties; this type is distributed in the western slopes, with an elevation of 1,300-2,500 m. Type II effective reservoir comprises strong-amplitude facies, with poor oil-bearing properties; this type is mainly distributed in the southeast and north slopes of the study area, with a relatively limited range, and the elevation is mostly below 1,500 m. Type III effective reservoir comprises weak-amplitude-blank facies, with poor reservoir conditions and poor oil-bearing properties; this type is widely distributed at various elevations. (4) The areas where medium-amplitude facies have developed are the most favorable reservoir exploration zones for granite in Dongying Sag, Bohai Bay Basin.

Abstract Background Apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for late‐onset Alzheimer's disease, and it can aggravate depressive symptoms in non‐AD patients. However, the impact of ApoE4 on AD‐associated depression‐like behaviors and its underlying pathogenic mechanisms remain unclear. Methods This study developed a 5xFAD mouse model overexpressing human ApoE4 (E4FAD). Behavioral assessments and synaptic function tests were conducted to explore the effects of ApoE4 on cognition and depression in 5xFAD mice. Changes in peripheral and central lipid metabolism, as well as the levels of serotonin (5‐HT) and γ‐aminobutyric acid (GABA) neurotransmitters in the prefrontal cortex, were examined. In addition, the protein levels of 24‐dehydrocholesterol reductase/glycogen synthase kinase‐3 beta/mammalian target of rapamycin (DHCR24/GSK3β/mTOR) and postsynaptic density protein 95/calmodulin‐dependent protein kinase II/brain‐derived neurotrophic factor (PSD95/CaMK‐II/BDNF) were measured to investigate the molecular mechanism underlying the effects of ApoE4 on AD mice. Results Compared with 5xFAD mice, E4FAD mice exhibited more severe depression‐like behaviors and cognitive impairments. These mice also exhibited increased amyloid‐beta deposition in the hippocampus, increased astrocyte numbers, and decreased expression of depression‐related neurotransmitters 5‐HT and GABA in the prefrontal cortex. Furthermore, lipid metabolism disorders were observed in E4FAD, manifesting as elevated low‐density lipoprotein cholesterol and reduced high‐density lipoprotein cholesterol in peripheral blood, decreased cholesterol level in the prefrontal cortex, and reduced expression of key enzymes and proteins related to cholesterol synthesis and homeostasis. Abnormal expression of proteins related to the DHCR24/GSK3β/mTOR and PSD95/CaMK‐II/BDNF pathways was also observed. Conclusion This study found that ApoE4 overexpression exacerbates depression‐like behaviors in 5xFAD mice and confirmed that ApoE4 reduces cognitive function in these mice. The mechanism may involve the induction of central and peripheral lipid metabolism disorders. Therefore, modulating ApoE expression or function to restore cellular lipid homeostasis may be a promising therapeutic target for AD comorbid with depression. This study also provided a better animal model for studying AD comorbid with depression.

Abstract Background Environmental factors greatly impact infectious disease-related mortality, yet there's a lack of comprehensive global studies on the contemporary burden and trends. This study aims to evaluate the global burden and trends of infectious disease mortality caused by air pollution, unsafe water, poor sanitation, and non-optimal temperature across Socio-Demographic Index (SDI) regions from 1990 to 2019. Methods This observational study utilized data from the Global Burden of Diseases Study to examine mortality rates from infectious diseases attributed to environmental risk factors between 1990 and 2019, including air pollution, unsafe water, sanitation, handwashing facilities (UWSH), and non-optimal temperatures. Age-standardized mortality rates (ASMRs) and estimated annual percentage change (EAPC) were utilized to present infectious disease mortality, and its trajectory influenced by environmental risk factors over the years. Nonlinear regression was conducted to explore the association between the SDI and ASMRs across regions from 1990 to 2019. Results In 2019, global infectious disease deaths linked to air pollution, UWSH, and non-optimal temperature reached a startling 2,556,992. Disease mortality varied widely across SDI regions, with the highest number of deaths due to air pollution and UWSH in Low SDI regions, and deaths from non-optimal temperature primarily in High SDI regions. Age disparities emerged, with children under five and the elderly most affected. However, an increasing mortality trend was observed among seniors (65–69, 75–79, and over 80) in High SDI regions due to enteric infections linked to UWSH. Globally, a consistent decrease in ASMR was seen from 1990 to 2019 for all diseases connected to these factors, except for respiratory infections linked to non-optimal temperature. Conclusions Our study underscores the significant impact of air pollution, UWSH, and non-optimal temperatures on global infectious disease mortality, particularly among vulnerable groups such as children and the elderly. It's important to tackle these challenges with targeted interventions aiming to enhance environmental quality, improve water and sanitation systems, and control extreme temperatures. In addition, international cooperation is essential for bridging regional disparities and driving global public health initiatives forward, thereby helping achieve Sustainable Development Goals more effectively.

Abstract Protein homeostasis is predominantly governed through post-translational modification (PTM). UBE3B, identified as an oncoprotein, exhibits elevated protein levels in breast cancer. However, the impact of PTM on UBE3B remains unexplored. In this study, we show that VHL is a bona fide E3 ligase for UBE3B. Mechanistically, VHL directly binds to UBE3B, facilitating its lysine 48 (K48)-linked polyubiquitination at K286 and K427 in a prolyl hydroxylase (PHD)-independent manner. Consequently, this promotes the proteasomal degradation of UBE3B. The K286/427R mutation of UBE3B dramatically abolishes the inhibitory effect of VHL on breast tumor growth and lung metastasis. Additionally, the protein levels of UBE3B and VHL exhibit a negative correlation in breast cancer tissues. These findings delineate an important layer of UBE3B regulation by VHL.

Abstract Acute myeloid leukemia (AML) is a heterogeneous hematological tumor with poor immunotherapy effect. This study was to develop a monocyte/macrophage-related prognostic risk score (MMrisk) and identify new therapeutic biomarkers for AML. We utilized differentially expressed genes (DEGs) in combination with single-cell RNA sequencing to identify monocyte/macrophage-related genes (MMGs). Eight genes were selected for the construction of a MMrisk model using univariate Cox regression analysis and LASSO regression analysis. We then validated the MMrisk on two GEO datasets. Lastly, we investigated the immunologic characteristics and advantages of immunotherapy and potential targeted drugs for MMrisk groups. Our study identified that the MMrisk is composed of eight MMGs, including HOPX, CSTB, MAP3K1, LGALS1, CFD, MXD1, CASP1 and BCL2A1. The low MMrisk group survived longer than high MMrisk group (P

Abstract Background It’s unclear if excess visceral adipose tissue (VAT) mass in individuals with prediabetes can be countered by adherence to a Mediterranean lifestyle (MEDLIFE). We aimed to examine VAT mass, MEDLIFE adherence, and their impact on type 2 diabetes (T2D) and diabetic microvascular complications (DMC) in individuals with prediabetes. Methods 11,267 individuals with prediabetes from the UK Biobank cohort were included. VAT mass was predicted using a non-linear model, and adherence to the MEDLIFE was evaluated using the 25-item MEDLIFE index, encompassing categories such as “Mediterranean food consumption,” “Mediterranean dietary habits,” and “Physical activity, rest, social habits, and conviviality.” Both VAT and MEDLIFE were categorized into quartiles, resulting in 16 combinations. Incident cases of T2D and related DMC were identified through clinical records. Cox proportional-hazards regression models were employed to examine associations, adjusting for potential confounding factors. Results Over a median follow-up of 13.77 years, we observed 1408 incident cases of T2D and 714 cases of any DMC. High adherence to the MEDLIFE, compared to the lowest quartile, reduced a 16% risk of incident T2D (HR: 0.84, 95% CI: 0.71–0.98) and 31% for incident DMC (0.69, 0.56–0.86). Conversely, compared to the lowest quartile of VAT, the highest quartile increased the risk of T2D (5.95, 4.72–7.49) and incident any DMC (1.79, 1.36–2.35). We observed an inverse dose-response relationship between MEDLIFE and T2D/DMC, and a dose-response relationship between VAT and all outcomes (P for trend

BackgroundParticulate matter pollution (PMP) is a major global health concern, with the older adult being particularly vulnerable. This study aimed to analyze global trends in PMP-related deaths and disability-adjusted life years (DALYs) among the older adult from 1991 to 2021.MethodsUsing data from the Global Burden of Disease Study 2021, we examined the impacts of ambient particulate matter pollution (APMP) and household air pollution from solid fuels (HAP-SF). We analyzed trends across different regions, socioeconomic development levels, age groups, and genders.ResultsAPMP-related older adult deaths increased from 1,745,000 to 3,850,000, and DALYs from 32,000,000 to 70,000,000. However, age-standardized mortality rate decreased from 384 to 337 per 100,000. HAP-SF-related deaths decreased from 2,700,000 to 2,100,000, and DALYs from 54,000,000 to 42,000,000. Age-standardized mortality rate for HAP-SF declined from 580 to 188 per 100,000. High APMP burden was concentrated in Asia, Africa, and the Middle East, while high HAP-SF burden was found in parts of Africa and South Asia. East Asia had the highest APMP-related older adult deaths (1,680,000) with an age-standardized mortality rate (ASMR) of 619 per 100,000. For HAP-SF, South Asia bore the heaviest burden with 1,020,000 deaths and an ASMR of 616 per 100,000. Females consistently experienced higher age-standardized DALYs rate than males for both APMP and HAP-SF across all regions and years. APMP burden showed a weak negative correlation with the Socio-demographic Index (SDI) at the regional level (r = −0.25, p

BackgroundObservational studies have demonstrated a correlation between thyroid dysfunction and osteoporosis (OP); however, the underlying causality has yet to be fully elucidated.MethodsThe necessary dataset was sourced from public databases. Initially, instrumental variables (IVs) were selected based on three primary hypotheses. Subsequently, Cochran’s Q test was employed to exclude IVs exhibiting heterogeneity. The MR-PRESSO test and the leave-one-out sensitivity test were further applied to detect potential pleiotropy. Inverse variance was utilized for the analysis. This study primarily utilized the inverse variance weighted (IVW) model for Mendelian analysis. Since Type 1 diabetes mellitus can also contribute to the development of osteoporosis, this study additionally employed multivariate Mendelian analysis. Furthermore, 249 circulating metabolites were selected for mediation analysis in the Mendelian randomization framework.ResultsIn this study, the two-sample Mendelian randomization (MR) analysis primarily employed the random-effects IVW model and demonstrated a causal relationship between hypothyroidism (OR = 1.092, 95% CI: 1.049–1.137, p 0.05). The results of the multivariate Mendelian randomization (MVMR) analysis indicated that hyperthyroidism was no longer a risk factor for OP (OR = 0.984, 95% CI: 0.918–1.055, p = 0.657), whereas hypothyroidism persisted as a risk factor (OR = 1.082, 95% CI: 1.021–1.147, p = 0.008). The mediated Mendelian randomization analysis revealed that hypothyroidism may exert an indirect effect on OP via triglycerides in large VLDL, mediating approximately 2.47% of the effect.ConclusionThis study identifies a potential link between hypothyroidism and OP, possibly mediated indirectly via triglyceride levels in large VLDL. Further investigations are required to elucidate the direct or indirect causal mechanisms underlying this association.

Background: Zika virus (ZIKV) infection during pregnancy presents a significant health risk in women of reproductive age and their offspring due to severe neurological complications. It is meaningful to assess its global burden and temporal trends. Methods: This study extracted annual incidence cases and rates of ZIKV among women of reproductive age (15–49 years) between 2011 and 2021 from Global Burden of Diseases (GBD) 2021, including global level, 21 GBD regions, 5 socio-demographic index (SDI) regions, 7 age groups, and 204 countries and territories. Relative percent change in cases and estimated annual percentage change (EAPC) of incidence rates were used to quantify the temporal trends. Results: The incidence rate of ZIKV infection exhibited a pronounced peak in 2016 at 174.27 per 100,000 population, with an EAPC of 158.30 % from 2011 to 2016 and −51.86 % from 2016 to 2021 at 3.06 per 100,000 population. And only 5 out of the 21 GBD regions reported ZIKV infection in 2021, predominantly concentrated in Latin America and Caribbean. The outbreaks were primarily concentrated in low-middle and middle SDI regions. In 2021, at the global level, the incidence rates of ZIKV infection among women of reproductive age were similar across different age groups, ranging from 2.41 to 3.39 per 100,000 population. The proportion of ZIKV infection cases was slightly higher in women aged 25–29 and 30–34 years compared to other age groups in 2021, whereas a higher proportion of cases were observed in younger age groups in 2011 and 2016. Conclusions: Women of reproductive age in Latin America and Caribbean continue to face the threat of ZIKV. Regions with lower SDI had a disproportionately severe burden. Future public health strategies should focus on high-risk areas and populations of reproductive age, enhancing surveillance, prevention, and education efforts to further mitigate the public health threat posed by ZIKV.