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Abstract Here, we design exotic interfaces within a flexible thermoelectric device, incorporating a polyimide substrate, Ti contact layer, Cu electrode, Ti barrier layer, and thermoelectric thin film. The device features 162 pairs of thin-film legs with high room-temperature performance, using p-Bi0.5Sb1.5Te3 and n-Bi2Te2.7Se0.3, with figure-of-merit values of 1.39 and 1.44, respectively. The 10 nm Ti contact layer creates a strong bond between the substrate and the Cu electrode, while the 10 nm Ti barrier layer significantly reduces internal resistance and enhances the tightness between thermoelectric thin films and Cu electrodes. This enables both exceptional flexibility and an impressive power density of 108 μW cm−2 under a temperature difference of just 5 K, with a normalized power density exceeding 4 μW cm−2 K−2. When attached to a 50 °C irregular heat source, three series-connected devices generate 1.85 V, powering a light-emitting diode without the need for an additional heat sink or booster.

Vascular calcification and vascular ageing are “silent” diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N6-methyladenosine (m6A)-dependent manner. Interestingly, MT alleviated vascular calcification and ageing in 5/6-nephrectomy (5/6 NTP) mice, a chronic kidney disease (CKD) induced vascular calcification and vascular ageing mouse model. MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice. ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice. Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway, dependent on m6A methylation.

Objective: This study investigated the ability of Large Language Models (LLMs) to provide accurate and consistent answers by focusing on their performance in complex gynecologic cancer cases. Background: LLMs are advancing rapidly and require a thorough evaluation to ensure that they can be safely and effectively used in clinical decision-making. Such evaluations are essential for confirming LLM reliability and accuracy in supporting medical professionals in casework. Study design: We assessed three prominent LLMs—ChatGPT-4 (CG-4), Gemini Advanced (GemAdv), and Copilot—evaluating their accuracy, consistency, and overall performance. Fifteen clinical vignettes of varying difficulty and five open-ended questions based on real patient cases were used. The responses were coded, randomized, and evaluated blindly by six expert gynecologic oncologists using a 5-point Likert scale for relevance, clarity, depth, focus, and coherence. Results: GemAdv demonstrated superior accuracy (81.87 %) compared to both CG-4 (61.60 %) and Copilot (70.67 %) across all difficulty levels. GemAdv consistently provided correct answers more frequently (>60 % every day during the testing period). Although CG-4 showed a slight advantage in adhering to the National Comprehensive Cancer Network (NCCN) treatment guidelines, GemAdv excelled in the depth and focus of the answers provided, which are crucial aspects of clinical decision-making. Conclusion: LLMs, especially GemAdv, show potential in supporting clinical practice by providing accurate, consistent, and relevant information for gynecologic cancer. However, further refinement is needed for more complex scenarios. This study highlights the promise of LLMs in gynecologic oncology, emphasizing the need for ongoing development and rigorous evaluation to maximize their clinical utility and reliability.

Abstract The growing demand for Cyber-Physical Systems (CPS) requires strong reliability. However, implementing Design for Reliability (DfR) in CPS requires a deep understanding of the components’ Physics of Failure. In this work, an autonomous braking system, a Cyber-Physical System is chosen to demonstrate the application of failure physics for DfR of CPS. The component under investigation is a crystal oscillator in the control circuit of the braking system. By subjecting it to a temperature cycling that mimics the realistic environment of the component, its degradation is found to significantly increase vehicle stopping distances, thereby posing potential safety hazards. Importantly, the relationship between the oscillator’s degradation and the stopping distance is non-linear, which is critical in avoiding simplistic extrapolations from initial degradation data to determine the time to replace the braking system. The outcomes of this study also provide essential design guidelines to enhance the reliability and safety of autonomous vehicle braking systems.

Abstract Background Powdery mildew is a disease with one of the most substantial impacts on cucumber production globally. The most efficient approach for controlling powdery mildew is the development of genetic resistance; however, few genes associated with inherent variations in cucumber powdery mildew resistance have been identified as of yet. Results In this study, we re-sequence 299 cucumber accessions, which are divided into four geographical groups. A genome-wide association study identifies 50 sites significantly associated with natural variations in powdery mildew resistance. Linkage disequilibrium analysis further divides these 50 sites into 32 linkage disequilibrium blocks containing 41 putative genes. Virus-induced gene silencing and gene expression analysis implicate CsGy5G015960, which encodes a phosphate transporter, as the candidate gene regulating powdery mildew resistance. On the basis of the resequencing data, we generate five CsGy5G015960 haplotypes, identifying Hap.1 as the haplotype most likely associated with powdery mildew resistance. In addition, we determine that a 29-bp InDel in the 3′ untranslated region of CsGy5G015960 is responsible for mRNA stability. Overexpression of CsGy5G015960 Hap.1 in the susceptible line enhances powdery mildew resistance and phosphorus accumulation. Further comparative RNA-seq analysis demonstrates that CsGy5G015960 Hap.1 may regulate cucumber powdery mildew resistance by maintaining a higher H2O2 level through the depletion of multiple class III peroxidases. Conclusions Here we identify a candidate powdery mildew-resistant gene in cucumber using GWAS. The identified gene may be a promising target for molecular breeding and genetic engineering in cucumber to enhance powdery mildew resistance.

Abstract Immune evasion represents a crucial milestone in the progression of cancer and serves as the theoretical foundation for tumor immunotherapy. In this study, we reveal a negative association between Human Papillomavirus (HPV)-encoded circular RNA, circE7, and the infiltration of CD8+ T cells in head and neck squamous cell carcinoma (HNSCC). Both in vitro and in vivo experiments demonstrate that circE7 suppresses the function and activity of T cells by downregulating the transcription of LGALS9, which encodes the galectin-9 protein. The molecular mechanism involves circE7 binding to acetyl-CoA carboxylase 1 (ACC1), promoting its dephosphorylation and thereby activating ACC1. Activated ACC1 reduces H3K27 acetylation at the LGALS9 gene promoter, leading to decreased galectin-9 expression. Notably, galectin-9 interacts with immune checkpoint molecules TIM-3 and PD-1, inhibiting the secretion of cytotoxic cytokines by T cells and promoting T cell apoptosis. Here, we demonstrate a mechanism by which HPV promotes immune evasion in HNSCC through a circE7-driven epigenetic modification and propose a potential immunotherapy strategy for HNSCC that involves the combined use of anti-PD-1 and anti-TIM-3 inhibitors.

Abstract N6-Methyladenosine (m6A) is an evolutionarily highly conserved epigenetic modification that affects eukaryotic RNAs, especially mRNAs, and m6A modification is commonly linked to tumor proliferation, progression, and therapeutic resistance by participating in RNA metabolism. Autophagy is an intracellular degradation and recycling biological process by which cells remove damaged organelles, protein aggregates, and other intracellular wastes, and release nutrients to maintain cell survival when energy is scarce. Recent studies have shown that m6A modification plays a critical role in the regulation of autophagy, affecting the initiation of autophagy, the formation and assembly of autophagosomes, and lysosomal function by regulating critical regulatory molecules involved in the process of autophagy. Moreover, autophagy can also affect the expression of the three types of regulators related to m6A, which in turn affects the levels of their target genes via m6A modification. Thus, m6A modification and autophagy form a sophisticated regulatory network through mutual regulation, which plays an important role in tumor progression and therapeutic resistance. In this manuscript, we reviewed the effects of m6A modification on autophagy as well as the effects of autophagy on m6A modification and the roles of the m6A-autophagy axis in tumor progression and therapy resistance. Additionally, we summarized the value and application prospects of key molecules in the m6A-autophagy axis in tumor diagnosis and therapy.

Abstract The norovirus (NoV) genome is diverse. Therefore, this study explored the epidemiological characteristics and genetic features of NoV in Ningxia Hui Autonomous Region, China, from 2011 to 2022 to clarify the genetic diversity in this region. Stool samples were screened for NoV and then sequenced and genotyped. In total, 1,788 of 13,083 specimens were NoV -positive (13.67%); 204 (1.56%) and 1,584 (12.11%) cases were GI and GII, respectively. Additionally, 559 were NoV infection with other viruses (4.27%), primarily with rotavirus (277/559, 49.55%). The NoV incidence rate was the highest among children aged 0–2 years (18.09%, 1054/5,828) and lowest among adults aged 45–64 years (110/1,495, 7.36%); it was also higher in the winter and spring than in the other seasons. GI.3[P3] was the dominant GI genotype. The dominant GII genotype changed roughly every two years. In the GII group, GII.4 was the most common genotype (46.79%), followed by GII.3 (21.34%), GII.2 (12.34%), and GII.17 (9.77%). There were three variants of GII.4 Den Haag, GII.4 New Orleans and GII.4 Sydney identified in the detected GII.4 strains, with GII.4 Sydney dominating. The GII.4 (87.36%), GII.3 (86.35%), and GII.2 (72.92%) strains were primarily detected in children, whereas it was the GII.17 (52.63%) strain in adults. Overall, the NoV genotypes in the Ningxia Hui Autonomous Region were diverse. Primarily, GII groups were dominant, but this changed over time.

Abstract Underrepresented populations’ participation in clinical trials remains limited, and the potential impact of genomic variants on drug metabolism remains elusive. This study aimed to assess the pharmacokinetics (PK) and pharmacogenomics (PGx) of ribociclib in self-identified Black women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2) advanced breast cancer. LEANORA (NCT04657679) was a prospective, observational, multicenter cohort study involving 14 Black women. PK and PGx were evaluated using tandem mass spectrometry and PharmacoScan™ microarray (including CYP3A5*3, *6, and *7). CYP3A5 phenotypes varied among participants: 7 poor metabolizers (PM), 6 intermediate metabolizers (IM), and one normal metabolizer (NM). The area under the curve did not significantly differ between PMs (39,230 h*ng/mL) and IM/NMs (43,546 h*ng/mL; p = 0.38). The incidence of adverse events (AEs) was also similar. We found no association between CYP3A5 genotype and ribociclib exposure. Continued efforts are needed to include diverse populations in clinical trials to ensure equitable treatment outcomes.

ObjectiveThis article investigates the relationship between common chronic diseases and depression among US adults and examines the mediating role of sleep in this relationship, using a cross-sectional study to offer recommendations for depression prevention.MethodsThis study analyzed data from 10,710 participants collected from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. Logistic regression, subgroup analysis, restricted cubic spline (RCS) analysis, and mediation analysis were employed to explore the relationship between common chronic diseases and depression, and the mediating role of sleep.ResultsThe adjusted model indicated that stroke (OR = 1.712, 95% CI: 1.399, 2.103), heart disease (OR = 1.419, 95% CI: 1.262, 1.598), diabetes (OR = 1.243, 95% CI: 1.116, 1.386), and hypertension (OR = 1.249, 95% CI: 1.160, 1.346) were associated with an increased probability of depression. Additionally, trouble sleeping (OR = 2.059, 95% CI: 1.790, 2.375) was associated with an increased probability of depression, while sleep hours (OR = 0.867, 95% CI: 0.846, 0.888) may decrease this probability. RCS analysis showed a non-linear relationship between sleep hours and the risk of depression. The final mediation analysis showed that trouble sleeping mediated 3.66% of the effect of stroke, 12.68% of heart disease, and 17.76% of diabetes on depression. Furthermore, trouble sleeping mediated 11.07% of the impact of hypertension on depression, while sleep hours mediated 5.36% of this impact.ConclusionChronic diseases and sleep problems may increase the likelihood of depression among U.S. adults, with sleep serving as a mediator between chronic diseases and depression.

ABSTRACT Introduction Depression is a prevalent and significant psychological consequence of traumatic brain injury (TBI). Ferroptosis, an iron‐dependent form of regulated cell death, exacerbates the neurological damage associated with TBI. This study investigates whether nicorandil, a potassium channel opener with nitrate‐like properties known for its antioxidative and neuroprotective effects, can mitigate depression‐like behaviors following TBI by modulating ferroptosis. Methods A controlled cortical impact (CCI) device was used to establish the TBI model. Depression‐like behaviors in rats were assessed using the sucrose preference test (SPT), the tail suspension test (TST), and the forced swimming test (FST). The antioxidant system, lipid peroxidation, and ferroptosis levels were evaluated. The SLC7A11/GPX4 axis was analyzed using quantitative real‐time PCR (qRT‐PCR) and Western blot analysis. Results Nicorandil administration significantly ameliorated depression‐like behaviors in rats with TBI. Nicorandil administration also effectively restored the antioxidant system, substantially reduced lipid peroxidation, and attenuated ferroptosis in the hippocampus of rats with TBI. Mechanistically, nicorandil administration promoted the SLC7A11/GPX4 axis in the hippocampus of rats with TBI. Crucially, knockdown of hippocampal SLC7A11 abrogated the protective effects of nicorandil on depression‐like behaviors, lipid peroxidation, and ferroptosis in the hippocampus of rats with TBI. Conclusion These findings indicate that nicorandil ameliorates depression‐like behaviors following TBI by inhibiting hippocampal ferroptosis through the activation of the SLC7A11/GPX4 axis.

Introduction: As pharmacological strategies remain limited for relieving fatigue and associated cognitive symptoms, integrative modalities such as traditional Chinese medicine (TCM) could be explored as therapeutic strategies in cancer survivors. Here, we evaluate and report the efficacy and safety of a TCM concoction, modified Xiang Bei Yang Rong Tang (XBYRT), on quality of life (QOL), cancer-related fatigue (CRF), and cognitive symptoms, compared to placebo. Methods: In a single-centered, randomized, double-blinded, placebo-controlled pilot trial conducted from 2019 to 2022, fatigued cancer survivors ≥21 years old were recruited to receive the XBYRT intervention or placebo (5% diluted) once daily for the duration of 8 weeks. Patient-reported outcomes for QOL, CRF, cognition, blood samples for biomarker testing, and adverse events were collected at baseline (T0), 4 weeks (T1), 8 weeks (T2), and 10 weeks (T3) after baseline. Linear regression was performed to evaluate differences between groups at T2 and T3. Results: A total of 1502 patients were screened, with 672 patients considered eligible. Of the eligible, 15 XBYRT and 13 placebo subjects with similar mean ages (58.5 vs 58.4) were recruited. Both groups were predominantly Chinese (93% vs 62%), breast cancer patients (87% vs 62%), and diagnosed with stage 2 cancer (60% vs 46%). Although no significant difference was found in QOL between groups, the XBYRT group exhibited improved emotional fatigue at T3 ( P = .045) and higher BDNF levels at T2 ( P = .047) and T3 ( P = .029). After baseline adjustment, XBYRT was associated with better perceived cognitive impairment at T2 ( P = .011) and T3 ( P = .017), as well as overall perceived cognitive function at T3 ( P = .028). XBYRT is well tolerated, with grade 3 adverse events reported in three XBYRT (20%) and two placebo (15%) subjects. Conclusion: In this pilot study, XBYRT as an integrative therapy is safe and generates encouraging improvements in cognitive and fatigue symptoms. Difficulties with recruitment limited the generalizability of trial findings, thus findings should be verified through a larger, multi-centered trial.

Human hepatitis B virus (HBV) infection is the major cause of acute and chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma. Although the application of prophylactic vaccination programs has successfully prevented the trend of increasing HBV infection prevalence, the number of HBV-infected people remains very high. Approved therapeutic management efficiently suppresses viral replication; however, HBV infection is rarely completely resolved. The major reason for therapeutic failure is the persistence of covalently closed circular DNA (cccDNA), which forms viral minichromosomes by combining with histone and nonhistone proteins in the nucleus. Increasing evidence indicates that chromatin-modifying enzymes, viral proteins, and noncoding RNAs are essential for modulating the function of cccDNA. Therefore, a deeper understanding of the regulatory mechanism underlying cccDNA transcription will contribute to the development of a cure for chronic hepatitis B. This review summarizes the current knowledge of cccDNA biology, the regulatory mechanisms underlying cccDNA transcription, and novel anti-HBV approaches for eliminating cccDNA transcription.

This research aims to bridge a gap in the existing literature by investigating the role of the blockchain-based metaverse in fostering decentralized sustainable management, leveraging the principles of stakeholder capitalism theory. By conducting a content analysis of thirty-two expert reports from the blockchain-based metaverse industry, the study identifies five key attributes that can potentially cultivate innovation and decentralized sustainable management within the business domain. These attributes include a creator economy, a persistent synchronous virtual environment, decentralization, an interoperable network, and a digitalized mindset. The research underscores the need for stakeholders to adopt a sustainable approach when navigating the blockchain-based metaverse, highlighting the potential benefits achievable in a decentralized, hybrid physical-digital environment. This work stands as a pioneering effort in conceptualizing a theoretical framework that encapsulates decentralized sustainable management within the blockchain-based metaverse, underpinned by the principles of stakeholder capitalism. Thus, it contributes significantly to the academic discourse on the sustainable implications of blockchain technology in new business models.

C29H26ClN3O7, monoclinic, P21 (no. 4), a = 15.5488(6) Å, b = 7.9366(3) Å, c = 22.6498(9) Å, β = 93.006(2)°, V = 2,791.24(19) Å3, Z = 4, Rgt(F) = 0.0528, wRref(F2) = 0.1391, T = 292 K.

Abstract Background The Diagnosis-Intervention Packet (DIP) payment system, initiated by China's National Healthcare Security Administration, is designed to enhance healthcare efficiency and manage rising healthcare costs. This study aims to evaluate the impact of the DIP payment reform on inpatient care in a specialized obstetrics and gynecology hospital, with a focus on its implications for various patient groups. Methods To assess the DIP policy's effects, we employed the Difference-in-Differences (DID) approach. This method was used to analyze changes in total hospital costs and Length of Stay (LOS) across different patient groups, particularly within select DIP categories. The study involved a comprehensive examination of the DIP policy's influence pre- and post-implementation. Results Our findings indicate that the implementation of the DIP policy led to a significant increase in both total costs and LOS for the insured group relative to the self-paying group. The study further identified variations within DIP groups both before and after the reform. In-depth analysis of specific disease groups revealed that the insured group experienced notably higher total costs and LOS compared to the self-paying group. Conclusions The DIP reform has led to several challenges, including upcoding and diagnostic ambiguity, because of the pursuit of higher reimbursements. These findings underscore the necessity for continuous improvement of the DIP payment system to effectively tackle these challenges and optimize healthcare delivery and cost management.

Abstract The HBV core protein (HBc) is an important viral protein of HBV that plays an indispensable role in the lifecycle of HBV, including capsid assembly and transport, reverse transcription and virus release. In recent years, evidence has shown that HBc may be involved in the malignant progression of HCC. Thus, HBc is an attractive target for antiviral agents and provides a new strategy for the treatment of HBV-related HCC. Here, we identified a novel anti‐HBc compound—colchicine, an alkaloid compound—that promoted selective autophagic degradation of HBc through the AMPK/mTOR/ULK1 signalling pathway. We further confirmed that colchicine promoted the selective autophagy of HBc by enhancing the binding of HBc to the autophagy receptor p62. Finally, we evaluated the effects of colchicine on HBV replication and HBc-mediated HCC metastasis in vitro and in vivo. Our research indicated that the inhibitory effects of colchicine on HBV and HBV-related HCC depend on the selective autophagic degradation of HBc. Thus, colchicine is not only a promising therapeutic strategy for chronic hepatitis B but also a new treatment for HBV-related HCC.

Abstract Pressing environmental challenges require focused research on sustainable solutions in the domains of energy, water, food, land, and climate. The pigment eumelanin has recently been positioned as a promising candidate for solving issues in health, sensors, and energy storage. However, the low solubility of eumelanin in aqueous solvents, difficult film processibility, and high cost have hindered the material from wide deployment. Here, we propose melanin extracted from the black soldier fly, Hermetia illucens (Mel-BSF), as a sustainable alternative for the preparation of organic electrodes in energy storage applications. Mel-BSF displays pseudocapacitive behaviour with a high potential window, good electrochemical stability, and higher maximum capacity (91.8 mAh g−1) compared to synthetic eumelanin (17.3 mAh g−1) as the working electrode material in zinc-ion hybrid capacitors using an ionic liquid electrolyte. Structural and surface investigations reveal that additional aliphatic compounds, potentially lipids present after Mel-BSF refinement, significantly increase the film stability and redox centre availability.

Abstract Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide, exhibiting unique regional prevalence. Despite advancements in diagnostics and therapy, the 5-year survival rate for patients has seen limited improvement. A deeper understanding of OSCC pathogenesis, especially its molecular underpinnings, is essential for improving detection, prevention, and treatment. In this context, noncoding RNAs, such as circular RNAs (circRNAs), have gained recognition as crucial regulators and potential biomarkers in OSCC progression. Our study highlights the discovery of previously uncharacterized circRNAs, including a SNX5 gene-derived circRNA, circSNX5, through deep sequencing of OSCC patient tissue transcriptomes. We established circSNX5’s tumor-specific expression and its strong correlation with patient survival using structure-specific and quantitative PCR analyses. In vitro and in vivo experiments underscored circSNX5 RNA’s regulatory role in cancer growth and metastasis. Further, our omics profiling and functional assays revealed that ADAM10 is a critical effector in circSNX5-mediated cancer progression, with circSNX5 maintaining ADAM10 expression by sponging miR-323. This novel circRNA-miRNA-mRNA regulatory axis significantly contributes to oral cancer progression and malignancy. Moreover, we discovered that circSNX5 RNA is produced via noncanonical sequential back-splicing of pre-mRNA, a process negatively regulated by the RNA-binding protein STAU1. This finding adds a new dimension to our understanding of exonic circRNA biogenesis in the eukaryotic transcriptome. Collectively, our findings offer a detailed mechanistic dissection and functional interpretation of a novel circRNA, shedding light on the role of the noncoding transcriptome in cancer biology and potentially paving the way for innovative therapeutic strategies.

Abstract Background Non-small cell lung cancer (NSCLC) is the most common type of tumor globally and the leading cause of cancer-related deaths. Although treatment strategies such as immune checkpoint inhibitors and chemotherapy have advanced, the heterogeneity among NSCLC patients results in significant variability in treatment outcomes. Studies have shown that certain patients respond poorly to immune checkpoint inhibitors, indicating that treatment response is closely related to multiple factors. Therefore, it is necessary to develop predictive models to stratify patients based on gene expression and clinical characteristics, aiming for precision therapy. Objective This study aims to construct a stratified prognostic model for NSCLC patients based on lysosome-dependent cell death (LDCD) scoring by integrating single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data. By analyzing the immune-related characteristics of high-risk and low-risk groups, we further explored the impact of cell death patterns on lung cancer and identified potential therapeutic targets. Methods This study obtained single-cell RNA sequencing data and gene expression data of NSCLC patients and normal lung tissues from the GEO and TCGA databases. We used R packages such as Seurat and CellChat for data preprocessing and analysis, and performed dimensionality reduction and visualization through Principal Component Analysis (PCA) and UMAP algorithms. LASSO regression analysis was used to construct the predictive model, followed by cross-validation and ROC curve analysis. The model’s effectiveness was validated through survival analysis and immune microenvironment analysis. Results The study showed a significant increase in the proportion of monocytes in NSCLC tissues, suggesting their important role in cancer progression. Cell communication analysis indicated that macrophages, smooth muscle cells, and myeloid cells exhibit strong intercellular communication during cancer progression. Using the constructed prognostic model based on 12 LDCD-related genes, we found significant differences in overall survival and immune microenvironment between the high-risk and low-risk groups.

Urolithiasis is a heat-specific disease. Exploring heat-related urolithiasis susceptibility subtypes, economic burden, and modifying factors could assist governments in targeting interventions to reduce the heat-related health risks of urolithiasis morbidity. We collected data on 23,492 patients with upper urinary tract stones (main subtypes of urolithiasis) from 2013 to 2017 in Nanjing, China. We adopted generalized additive quasi-Poisson models to examine the associations between daily mean temperatures and morbidity of upper urinary tract stones, while generalized additive Gaussian models were used to explore the relationships between temperatures and log-transformed medical costs. We examined the modification effects of disease subtypes (kidney and ureteral calculus), sex, and age through stratified analyses and the modification effects of other meteorological factors by introducing interaction terms in the models. We found that short-term summer heat exposure has a statistically significant effect on ureteral calculus morbidity but not on kidney calculus morbidity. For ureter calculus, a 1 °C temperature increase was associated with a 4.36% (95% confidence interval [CI]: 1.94%, 6.83%) increase in daily hospitalization and a 5.44% (95% CI: 2.71%, 8.25%) increase in daily medical costs. The attributable fraction associated with heat (greater than the median value of daily mean temperature, 26.8 °C) was 7.85% (95% empirical confidence interval [eCI]: 3.64%, 11.44%) for hospitalization and 9.36% (95% eCI: 4.91%, 13.14%) for medical costs. The effects of heat on ureter calculus morbidity were significantly higher among the males and those with high sunshine duration than females and those with low sunshine duration. Short-term summer heat exposure was associated with increased morbidity and medical costs of ureteral calculus. Relevant government organizations should take effective intervention measures, including community health education, to reduce the health hazards and economic losses caused by heat.

HIGHLIGHTS 1. The article highlights how Artificial Intelligence with Large Language Models (AI-LLMs) greatly improves diagnosis and treatment personalization in obstetrics & gynecology, and also enhances medical education through interactive simulations and up-to-date learning materials. 2. The article also discusses the ethical issues linked to AI, emphasizing the need for cooperation among different stakeholders to use AI responsibly in medicine, focusing on protecting data privacy and minimizing reliance on technology. ABSTRACT The introduction of Artificial Intelligence through Large Language Models (AI-LLM) into medicine holds great promise for improving patient care and medical education, especially in obstetrics and gynecology. AI-LLM can significantly improve diagnostic accuracy and treatment efficiency by utilizing large medical databases, which is especially useful for dealing with rare diseases that are difficult to document or understand by human practitioners alone. In addition, AI-LLM can provide informed patient care recommendations by analyzing large amounts of data and providing insights based on unique patient profiles, with the added benefit of being accessible 24/7 via the internet. This constant availability ensures that patients receive prompt information and assistance as needed. In the field of education, AI-LLMs enhance the learning experience by incorporating interactive simulations into the curriculum, improving medical students' and professionals' practical knowledge. They also ensure that educational materials are always up-to-date reflecting the most recent research and worldwide medical standards. This access latest information from global resources helps to bridge the educational gap, making advanced knowledge more accessible to learners regardless of their geographic location. However, the introduction of AI-LLMs is not without challenges. Ethical issues, such as data privacy and the risk of overreliance on technology, must be addressed. Effective management of these concerns necessitates collaboration among medical professionals, technological experts, academics, hospital committees, and representatives of patients. This multidisciplinary teamwork is vital for upholding ethical norms and preserving patient dignity and respect. AI-LLMs can considerably improve both patient care and medical education in obstetrics and gynecology provided they are appropriately balanced with innovation and ethics.

Abstract This study explores disparities and opportunities in healthcare information provided by AI chatbots. We focused on recommendations for adjuvant therapy in endometrial cancer, analyzing responses across four regions (Indonesia, Nigeria, Taiwan, USA) and three platforms (Bard, Bing, ChatGPT-3.5). Utilizing previously published cases, we asked identical questions to chatbots from each location within a 24-h window. Responses were evaluated in a double-blinded manner on relevance, clarity, depth, focus, and coherence by ten experts in endometrial cancer. Our analysis revealed significant variations across different countries/regions (p

Abstract In a battery pack, several lithium-ion batteries (LiBs) are connected in series and parallel so that sufficient voltage, current and power can be provided for applications. To ensure safe operation, when one of the LiB cells in a pack has its SoH below 80%, the entire pack will have to be discarded. Thus, ensuring all the LiB cells degrade similarly in a pack is crucial to maximize the potential of all the cells in a pack. There are several methods to perform screening on the LiB cells for such purpose, but there exist many practical challenges for estimating and predicting the degradation rate of the cells before they are chosen to be put in a pack which will be described in this work. This work provides solutions to some of these challenges and shows through experiments that one can screen the weak cells from production batch with just the first discharge cycle, and one can also predict the statistical distribution of the degradation rates of LiB cells in a production batch. On-line in-situ determination of the SoH of each cell connected in a pack is also made possible with a solution presented in this work, and this method is verified over many different types of LiB from various manufacturers.

Abstract Non-alcoholic fatty liver disease (NAFLD) is a chronic disease caused by hepatic steatosis. Adenosine deaminases acting on RNA (ADARs) catalyze adenosine to inosine RNA editing. However, the functional role of ADAR2 in NAFLD is unclear. ADAR2+/+/GluR-BR/R mice (wild type, WT) and ADAR2−/−/GluR-BR/R mice (ADAR2 KO) mice are fed with standard chow or high-fat diet (HFD) for 12 weeks. ADAR2 KO mice exhibit protection against HFD–induced glucose intolerance, insulin resistance, and dyslipidemia. Moreover, ADAR2 KO mice display reduced liver lipid droplets in concert with decreased hepatic TG content, improved hepatic insulin signaling, better pyruvate tolerance, and increased glycogen synthesis. Mechanistically, ADAR2 KO effectively mitigates excessive lipid production via AMPK/Sirt1 pathway. ADAR2 KO inhibits hepatic gluconeogenesis via the AMPK/CREB pathway and promotes glycogen synthesis by activating the AMPK/GSK3β pathway. These results provide evidence that ADAR2 KO protects against NAFLD progression through the activation of AMPK signaling pathways.

Background: Noroviruses, which cause epidemic acute gastroenteritis, and Plasmodium parasites, which lead to malaria, are two infectious pathogens that pose threats to public health. The protruding (P) domain of norovirus VP1 and the αTSR domain of the circumsporozoite protein (CSP) of Plasmodium sporozoite are the glycan receptor-binding domains of the two pathogens for host cell attachment, making them excellent targets for vaccine development. Modified norovirus P domains self-assemble into a 24-meric octahedral P nanoparticle (P24 NP). Methods: We generated a unique P24-αTSR NP by inserting the αTSR domain into a surface loop of the P domain. The P-αTSR fusion proteins were produced in the Escherichia coli expression system and the fusion protein self-assembled into the P24-αTSR NP. Results: The formation of the P24-αTSR NP was demonstrated through gel filtration, electron microscopy, and dynamic light scattering. A 3D structural model of the P24-αTSR NP was constructed, using the known cryo-EM structure of the previously developed P24 NP and P24-VP8* NP as templates. Each P24-αTSR NP consists of a P24 NP core, with 24 surface-exposed αTSR domains that have retained their general conformations and binding function to heparan sulfate proteoglycans. The P24-αTSR NP is immunogenic, eliciting strong antibody responses in mice toward both the norovirus P domain and the αTSR domain of Plasmodium CSP. Notably, sera from mice immunized with the P24-αTSR NP bound strongly to Plasmodium sporozoites and blocked norovirus VLP attachment to their glycan receptors. Conclusion: These data suggest that the P24-αTSR NP may serve as a combination vaccine against both norovirus and Plasmodium parasites.

Although diabetic polyneuropathy (DPN) has a very high prevalence among people with diabetes, gait analysis using cyclograms is very limited, and cyclogram research, in general, is limited to standard measures available in software packages. In this study, cyclograms (movements of the centre of pressure, COP, on and between the plantar surfaces) of diabetics and healthy individuals recorded with a smart insole were compared in terms of geometry and balance index, BI. The latter was calculated as the summed product of standard deviations of cyclogram markers, i.e., start/end points, turning points, and intersection points of the COP. The geometry was assessed by the positions of, and distances between, these points, and the distance ratios (14 parameters in total). The BI of healthy and diabetic individuals differed significantly. Of the fifteen parameters (including the BI), three were suitable as classifiers to predict DPN, namely two distances and their ratio, with false negatives ranging from 1.8 to 12.5%, and false positives ranging from 2.9 to 7.1%. The standard metric of the cyclogram provided by the software packages failed as a classifier. While the BI captures both DPN-related balance and other balance disorders, the changing geometry of the cyclogram in diabetics appears to be DPN-specific.

Background Digital technologies proliferate in many people’s lives around the world with over 65% of these technology users being online. Children and youth are among the most prominent adopters of digital technologies in forms such as video gaming, social media, and online shopping. Problematic use of digital technologies can lead to poorer school/work performance, neglect of self-care skills, and comorbidities with other mental health issues. However, when used non-problematically, digital technology can also contribute to improving health and well-being. With the abundance of literature published, many reviews have sought to collate literature on treatment and interventions for children and youth with varying results. Thus, our proposed systematic review aims to synthesize current systematic reviews and meta-analyses on interventions and treatment of problematic digital technology use in children and youth (up to 25 years old). Methods As part of a three-paper series, a systematic search was completed in PsycINFO, Web of Science, and PubMed databases. Grey literature databases of the World Health Organization (IRIS database) and ClinicalTrials.gov were also searched. Furthermore, hand-searching of reference lists was also conducted. Title and abstract screening, followed by full-text screening, were completed by at least two independent reviewers. For this review, the extractions and the quality of selected reviews will be assessed using AMSTAR 2.0 by two authors independently and reviewed by two additional authors. Results Results will be presented in narrative and tabular form. The results of this study are expected to offer insights into the populations of children and youth studied, treatments/interventions provided, outcomes, results, limitations, and conclusions of literature from the past five years. Feasibility and generalizability of the reviews will also be discussed. Conclusions Methodological strengths and weaknesses of reviewed studies will point to gaps in knowledge and can be used to inform future areas of policy and research.

Abstract Enhancing fracture toughness and self‐healing within soft elastomers is crucial to prolonging the operational lifetimes of soft devices. Herein, it is revealed that tuning the polymer chain mobilities of carboxylated‐functionalized polyurethane through incorporating plasticizers or thermal treatment can enhance these properties. Self‐healing is promoted as polymer chains gain greater mobility toward the broken interface to reassociate their bonds. Raising the temperature from 80 to 120 °C, the recovered work of fracture is increased from 2.86 to 123.7 MJ m−3. Improved fracture toughness is realized through two effects. First, strong carboxyl hydrogen bonds dissipate large energies when broken. Second, chain mobilities enable the redistribution of localized stress concentrations to allow crack blunting, enlarging the size of dissipation zones. At optimal conditions of plasticizers (3 wt.%) or temperature (40 °C) to promote chain mobilities, fracture toughness improves from 16.3 to 19.9 and 25.6 kJ m−2, respectively. Insights of fracture properties at healed soft interfaces are revealed through double cantilever beam tests. These measurements indicate that fracture mechanics play a critical role in delaying complete failure at partial self‐healing. By imparting optimal polymer chain mobilities within tough and self‐healing elastomers, effective prevention against damage and better recovery are realized.

ABSTRACT: E2F transcription factor 5 (E2F5) gene is a transcription factor, plays an important role in the development of a variety of cells. E2F5 is expressed in human and mouse adipocytes, but its specific function in adipogenesis is unclear. Krüppel-like factor 7 (KLF7) facilitates proliferation and inhibits differentiation in chicken preadipocytes. Our previous KLF7 chromatin immunoprecipitation-sequencing analysis revealed a KLF7-binding peak in the 3′ flanking region of the E2F5, indicating a regulatory role of KLF7 in this region. In the present study, we investigated E2F5 potential role, the overexpression and knockdown analyses revealed that E2F5 inhibited the differentiation and promoted the proliferation of chicken preadipocytes. Moreover, we identified enhancer activity in the 3′ flanking region (nucleotides +22661/+22900) of E2F5 and found that KLF7 overexpression increased E2F5 expression and luciferase activity in this region. Deleting the putative KLF7-binding site eliminated the promoting effect of KLF7 overexpression on E2F5 expression. Further, E2F5 reversed the KLF7-induced decrease in preadipocyte differentiation and increase in preadipocyte proliferation. Taken together, our findings demonstrate that KLF7 inhibits differentiation and promotes proliferation in preadipocytes by enhancing E2F5 transcription.

Introduction: We presented the key findings from Singapore’s Changi General Hospital Breast Centre’s lymphedema surveillance strategy that used patients’ reported symptoms, standard arm circumference measurements and clinical assessment in the diagnosis of breast cancer-related lymphedema (BCRL). Our secondary aim was to highlight and discuss important elements of a surveillance strategy that can be implemented to track this outcome measure of breast cancer treatment for future research. Method: We conducted a cross-sectional study of 511 breast cancer patients to assess the prevalence of BCRL and its associated risk factors. We defined BCRL prevalence rates based on patients’ self-reporting, objective arm circumference measure-ments and clinical diagnosis based on International Society of Lymphology (ISL) staging. Results: The median follow-up of patients was 88.8 months. The cumulative prevalence rate in the cohort was 30.9%. The cohort of BCRL patients were older (58.4 versus [vs] 54.9 years), had higher mean Body Mass Index (27.7 vs 25.2), higher proportion of mastectomy (77% vs 64.3%), axillary clearance, less likely breast reconstruction, higher-grade tumour, more lymph nodes excised, more advanced nodal disease, and had undergone adjuvant chemotherapy. However, clinically apparent BCRL was only 6.5% (33 out of 511 patients). The proportion of clinically significant BCRL in patients undergoing sentinel lymph node biopsy (SLNB) or axillary sampling was 1.7% compared to 9.9% in patients who had undergone axillary clearance. Majority of the BCRL were subclinical or mild in severity. Conclusion: Our study showed that our rates of BCRL were comparable to international rates and highlighted similar patient profiles who were at risk of developing the disease. Having a comprehensive lymphedema surveillance strategy is paramount in paving the way for future studies.

Abstract Background Progressive hepatitis B virus (HBV) infection can result in cirrhosis, hepatocellular cancer, and chronic hepatitis. While antiviral drugs that are now on the market are efficient in controlling HBV infection, finding a functional cure is still quite difficult. Identifying host factors involved in regulating the HBV life cycle will contribute to the development of new antiviral strategies. Zinc finger proteins have a significant function in HBV replication, according to earlier studies. Zinc finger protein 148 (ZNF148), a zinc finger transcription factor, regulates the expression of various genes by specifically binding to GC-rich sequences within promoter regions. The function of ZNF148 in HBV replication was investigated in this study. Methods HepG2-Na+/taurocholate cotransporting polypeptide (HepG2-NTCP) cells and Huh7 cells were used to evaluate the function of ZNF148 in vitro. Northern blotting and real-time PCR were used to quantify the amount of viral RNA. Southern blotting and real-time PCR were used to quantify the amount of viral DNA. Viral protein levels were elevated, according to the Western blot results. Dual-luciferase reporter assays were used to examine the transcriptional activity of viral promoters. ZNF148’s impact on HBV in vivo was investigated using an established rcccDNA mouse model. Results ZNF148 overexpression significantly decreased the levels of HBV RNAs and HBV core DNA in HBV-infected HepG2-NTCP cells and Huh7 cells expressing prcccDNA. Silencing ZNF148 exhibited the opposite effects in both cell lines. Furthermore, ZNF148 inhibited the activity of HBV ENII/Cp and the transcriptional activity of cccDNA. Mechanistic studies revealed that ZNF148 attenuated retinoid X receptor alpha (RXRα) expression by binding to the RXRα promoter sequence. RXRα binding site mutation or RXRα overexpression abolished the suppressive effect of ZNF148 on HBV replication. The inhibitory effect of ZNF148 was also observed in the rcccDNA mouse model. Conclusions ZNF148 inhibited HBV replication by downregulating RXRα transcription. Our findings reveal that ZNF148 may be a new target for anti-HBV strategies.

Chlorophyll is a vital component of photosynthesis and must be produced throughout the plant life cycle. Light-dependent protochlorophyllide oxidoreductase (LPOR) is a pivotal enzyme in the chlorophyll biosynthesis pathway, catalyzing the conversion of Pchlide to Chlide. The presence of different types of LPOR ensures the efficient synthesis of chlorophyll in photosynthetic organisms during the dark-light transition. In addition to the transcriptional, translational, and post-translational regulation of LPOR function under different abiotic stresses, the nature of the substrate also influences LPOR function. Here, a perspective on chlorophyll synthesis and the development of chloroplasts is offered, the importance of LPOR in safeguarding plant light energy utilization is summarized, the gene expression pattern and structural-functional features of LPOR are outlined, as well as the role of LPOR in abiotic stress tolerance response, the catalytic mechanism of LPOR as well as the modulation of LPOR by light signals and other environmental factors are discussed. The aim is to provide references for the cultivation and innovation of plant germplasm resources with stress tolerance.