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Three preregistered studies examined whether 5-year-old children cheat consistently or remain honest across multiple math tests. We observed high consistency in both honesty and cheating. All children who cheated on the first test continued cheating on subsequent tests, with shorter cheating latencies over time. In contrast, 77% of initially honest children maintained honesty despite repeated failure to complete the tests successfully. A brief integrity intervention helped initially honest children remain honest but failed to dissuade initially cheating children from cheating. These findings demonstrate that cheating emerges early and persists strongly in young children, underscoring the importance of early prevention efforts. They also suggest that bolstering honesty from the start may be more effective than attempting to remedy cheating after it has occurred.

Abstract With the establishment of “Dual Carbon” targets and industrial restructuring in China, the transition from the secondary industry to the tertiary industry has facilitated the rapid development of the financial sector. However, the significant CO2 emissions embodied within inter-provincial trade result in carbon leakage, posing challenges in assigning equitable carbon reduction responsibilities to the financial sectors across the 31 provinces of China. This study establishes a framework for evaluating CO2 emissions of financial sectors through 134 samples of 60 listed financial enterprises in the 31 provinces, tracking the embodied CO2 emissions within inter-provincial trade by using a multiregional input–output approach. The results reveal that the total CO2 emissions of the financial sector in China surged from 4.591 to 12.423 Tg CO2-eq between 2012 and 2020. The regions with the highest annual net CO2 emissions are Anhui (0.244 Tg), Zhejiang (0.242 Tg), and Henan (0.211 Tg). The key factors influencing net CO2 emissions are in the following order of importance: net CO2 density, per capita added value of service industry, the proportion of finances in service industries, and population size. Based on the findings, this study provides policy implications: reducing net carbon intensity, enacting tailored carbon tax policies based on embodied CO2 emissions, and fostering interdepartmental collaboration to address the impact of carbon leakage.

Abstract Nonaromatic and nonconjugated fluorescent materials have garnered increasing attention in recent years. However, most non-classical chromophores are derived from electro-rich nitrogen and oxygen atoms, which suffer from short emission wavelengths, low efficiency, limited responsiveness, and obscure luminescence mechanisms. Here we present an emission mechanism in bioactive polycysteine, an aliphatic polymer that displays polymerization- and aggregation-induced emission, high quantum yield, and multicolor emission properties. We show that the hydrogen atoms bonded to the sulfur atoms play a crucial role in luminescence. This enables reversible modulation of polymer fluorescence under reducing and oxidizing conditions, facilitating specific imaging and quantitative detection of redox species in cells and in vivo. Furthermore, the polymer exhibits better anti-inflammatory and antioxidative activities compared to first-line clinical antioxidants, offering a promising platform for in vivo theragnosis of diseases such as osteoarthritis.

Abstract Background Interleukin-10 (IL-10), a pivotal anti-inflammatory cytokine, has gotten attention for its involvement in tissue remodeling and organ fibrosis. Pleurisy and subsequent pleural remodeling are recognized as quantifiable indicators of systemic lupus erythematosus (SLE) activity. However, the role of IL-10 in SLE-associated pleural remodeling remains unknown. In this study, we investigated role of IL-10 in SLE-associated pleural remodeling and the underlying mechanism. Methods Clinical data and serum specimens were obtained from SLE patients, while pleural mesothelial cells and mouse models served as primary experimental subjects. The protein expression-related technologies, histopathological staining, and other experimental methods were used in the study. Results Our investigation got several key findings. Firstly, serum obtained from SLE patients with pleural thickening was found to induce pleural mesothelial cell remodeling. Subsequently, heightened levels of IL-10 were found in serum from SLE patients with pleural thickening compared to that of SLE patients without pleural thickening. Secondly, administration of recombinant IL-10 was confirmed its ability to induce pleural mesothelial cell remodeling, on the contrary, this remodeling was effectively mitigated by IL-10 inhibition. Notably, blockade of IL-10 significantly prevented collagen deposition and prevented thickening in pleura of SLE mouse models. Lastly, the IL-10/JAK2/STAT3/HIF1α/TMEM45A/P4HA1 signaling axis was elucidated to mediate pleural remodeling and thickening. Conclusions Our study uncovered that IL-10 mediated pleural remodeling in SLE. We suggested that serum IL-10 level exceeding 6.32 pg/mL was a potential reference threshold for predicting pleural thickening in SLE patients.

Abstract The earliest silicon-based aerogels attracted attention due to their nanoscale porous structure and high transparency. Still, they need to be more balanced with the poor mechanical properties. Their brittle structure limits the development of this promising new material. Therefore, the goal of this work is to optimize the mechanical properties of aerogels while maintaining transparency. The good mechanical properties of polymers have made them the material of choice for this work. Polyvinyl alcohol (PVA), which can undergo self-crosslinking through side-chain hydroxyl groups forming hydrogen bonds, was chosen as the raw material to simplify and expedite the production process. The production process was experimented with, analyzed, and refined. Considering the time efficiency of the experimental process, a one-step gelling method was invented to facilitate the sol-gel transition. The one-step gelling method maintained the high transparency of PVA aerogels and reduced the time required for the gelation process compared to the freeze-thawing method. This work employs carbon dioxide supercritical drying to ensure minimal structural collapse and maximize the porous structure’s retention. The transmittance of PVA aerogels can reach up to 93.67% at a wavelength of 1333 nm. The internal structure of aerogels with different PVA concentrations was observed using a Scanning electron microscope. Applying Beer-Lambert’s Law eliminated the effect of sample thickness on transparency. The relationship between the transparency of PVA aerogels, their microstructure, and macroscopic concentration was studied and analyzed for the first time. While ensuring light transmittance, the modulus of the PVA aerogel reached as high as 6.18 ± 0.56 MPa at 13 wt%.

Abstract Human–robot collaboration (HRC) is a novel manufacturing paradigm designed to fully leverage the advantage of humans and robots, efficiently and flexibly accomplishing customized manufacturing tasks. However, existing HRC systems lack the transfer and generalization capability for environment perception and task reasoning. These limitations manifest in: (1) current methods rely on specialized models to perceive scenes; and need retraining the model when facing unseen objects. (2) current methods only address predefined tasks, and cannot support undefined task reasoning. To avoid these limitations, this paper proposes a novel HRC approach based on Foundation Models (FMs), including Large Language models (LLMs) and Vision Foundation Models (VFMs). Specifically, a LLMs-based task reasoning method is introduced, utilizing prompt learning to transfer LLMs into the domain of HRC tasks, supporting undefined task reasoning. A VFMs-based scene semantic perception method is proposed, integrating various VFMs to achieve scene perception without training. Finally, a FMs-based HRC system is developed, comprising perception, reasoning, and execution modules for more flexible and generalized HRC. The superior performances of FMs in perception and reasoning are demonstrated by extensive experiments. Furthermore, the feasibility and effectiveness of the FMs-based HRC system are validated through an part assembly case involving a satellite component model.

Objective: To provide the mechanism-based pharmacotherapy of the Huatan Qushi formula (HTQS formula), for the health management and treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A rat model of NAFLD was employed to examine the efficacy and safety of the HTQS formula. In vivo active components and potential mechanisms of the HTQS formula were identified using UPLC‒MS/MS combined with network pharmacology. The influence of the HTQS formula on the dominating proteins in PI3K/Akt pathway was validated in vivo using western blot. Finally, 16S rRNA sequencing of the gut microbiome was conducted followed by targeted metabolomics detecting fecal short-chain fatty acids (SCFAs) and bile acids to determine the impact of the HTQS formula on gut microbiota. Results: The HTQS formula reduced weight gain and hepatic steatosis in NAFLD rats and decreased serum total cholesterol (TC), triglycerides, blood glucose, and insulin resistance (IR) without causing liver or kidney injury. We detected 28 components using UPLC‒MS/MS and identified 439 shared targets between NAFLD and the HTQS formula. Primarily, we focused on the PI3K/Akt signaling pathway based on protein‒protein interaction network analysis. We validated that the HTQS formula inhibited liver steatosis and inflammation by increasing the phosphorylation levels of PI3K, AKT, P27, GSK3β in the PI3K/Akt signaling pathway. 16S rRNA sequencing revealed that the HTQS formula reduced the abundance of the genus Family_XIII_AD3011_group, which was positively correlated with IR and taurodeoxycholic acid. In addition, Lachnospiraceae_UCG_010 inversely correlated with TC and five bile acids, which could be essential to the therapeutic effect of the HTQS formula against NAFLD. Conclusions: The HTQS formula proved to be an effective pharmacotherapy for NAFLD without causing liver or kidney injury. Multiple potent components of the HTQS formula could alleviate liver steatosis and lipid metabolism disorder by modulating the PI3K/Akt signaling pathway and restoring gut microbiota composition.

Abstract Extensive studies indicate that mitochondria dysfunction is pivotal for Alzheimer’s disease (AD) pathogenesis; while cumulative evidence suggests that increased mitochondrial stress response (MSR) may mitigate neurodegeneration in AD, explorations to develop a MSR-targeted therapeutic strategy against AD are scarce. We combined cell biology, molecular biology, and pharmacological approaches to unravel a novel molecular pathway by which NAD+-boosting agent nicotinamide mononucleotide (NMN) regulates MSR in AD models. Here, we report dyshomeostasis plasma UPRmt-mitophagy-mediated MSR profiles in AD patient samples. NMN restores NAD+ metabolic profiles and improves MSR through the ATF4-dependent UPRmt pathway in AD-related cross-species models. At the organismal level, NAD+ repletion with NMN supplementation ameliorates mitochondrial proteotoxicity, decreases hippocampal synaptic disruption, decreases neuronal loss, and brain atrophy in mice model of AD. Remarkably, omics features of the hippocampus with NMN show that NMN leads to transcriptional changes of genes and proteins involved in MSR characteristics, principally within the astrocyte unit rather than microglia and oligodendrocytes. In brief, our work provides evidence that MSR has an active role in the pathogenesis of AD, as reducing mitochondrial homeostasis via atf4 depletion in AD mice aggravates the hallmarks of the disease; conversely, bolstering mitochondrial proteostasis by NMN decreases protein aggregation, restores memory performance, and delays disease progression, ultimately translating to increased healthspan.

Abstract Estimating gross primary production (GPP) of terrestrial ecosystems is important for understanding the terrestrial carbon cycle. However, existed nationwide GPP datasets are primarily driven by coarse spatial resolutions (≥500 m) remotely sensed data, which fails to capture the spatial heterogeneity of GPP across different ecosystem types at land surface. This paper introduces a new GPP dataset, Hi-GLASS GPP v1, with a fine spatial resolution (30-m) and monthly temporal resolution from 2016 to 2020 in China. The Hi-GLASS GPP v1 dataset is generated from 30-m Landsat data using a process based light use efficiency model. The Hi-GLASS GPP v1 model integrates a detailed map of maize plantations, a crucial C4 crop in China known for its higher photosynthetic efficiency compared to C3 crops. This inclusion helps correct the underestimation of GPP that typically occurs when all croplands are categorized as C3. The Hi-GLASS GPP v1 dataset demonstrates a robust correlation with GPP data derived from eddy covariance towers, thereby enabling a more accurate assessment of terrestrial carbon sequestration across China.

This case study examined the current assessment practices in the math school of a large research university in the United States. After reviewing a sample of course syllabi offered in the spring 2021 semester, we descriptively summarized the use of 19 assessment methods in the school and examined the assessment patterns by subjects, class standings, and class size. Our study found that traditional homework and written tests were the most frequently used assessments in the school, while the use of learner-centered assessments was rare. Among the 19 assessment methods, we found significantly different usage of quizzes, participation scores, and projects by various course characteristics. Our case study demonstrates the gap between the recommended and actual assessment practice in U.S. higher education. We call for more future research that explores strategies to effect changes and increase the use of learner-centered assessment in higher education institutions.

The recent surge of machine learning (ML) has impacted many disciplines, including educational and psychological measurement (hereafter shortened as "measurement"). The measurement literature has seen rapid growth in applications of ML to solve measurement problems. However, as we emphasize in this article, it is imperative to critically examine the potential risks associated with involving ML in measurement. The MxML project aims to explore the relationship between measurement and ML, so as to identify and address the risks and better harness the power of ML to serve measurement missions. This paper describes the first study of the MxML project, in which we summarize the state of the field of applications, extensions, and discussions about ML in measurement contexts with a systematic review of the recent 10 years' literature. We provide a snapshot of the literature in (1) areas of measurement where ML is discussed, (2) types of articles (e.g., applications, conceptual, etc.), (3) ML methods discussed, and (4) potential risks associated with involving ML in measurement, which result from the differences between what measurement tasks need versus what ML techniques can provide.

Abstract Background The positioning error of femoral tunnel was the key factor leading to the failure of anterior cruciate ligament (ACL) reconstruction. This study aimed to propose a new femoral tunnel classification to guide revision ACL reconstruction. Methods Totals of 150 patients with ACL reconstruction failure from 2017 to 2023 were enrolled in this retrospective study. According to the tunnel diameter, shape, posterior wall and the positioning relationship with the Lateral Intercondylar Ridge on the three-dimensional CT imaging, we divided the femoral tunnels into four types: Type I off-target type, Type II straddled type, Type III anatomical type, and Type IV irregular type. Finally, explored the inter-observer reliability within two groups of doctors (Group A, 12 high seniorities; Group B, 12 low seniorities), and evaluated the intra-observer reliability within 6 doctors after two months. Clinical evaluation was performed using the Lysholm score, Tenger activity score, Pivot Shift and anterior knee laxity measurements. Results Among 150 cases of femoral tunnel three-dimensional CT reconstructed imaging, 144 cases were successfully included in the classification system, and 6 cases were confirmed as uncertain type. We measured the Kappa (κ) coefficient of group A was significantly higher than that of group B (κ 0.72 VS 0.68), and the κ coefficient of group A was still higher than group B (κ 0.69 VS 0.62) after further dividing Type III anatomical type into three subtypes. In addition, the κ coefficients of intra-observer reliability were all exceeded 0.73. Clinical follow-up showed that 9 patients had good knee joint motor function and stability after operation. Conclusion The new femoral tunnel classification was reliable and had clinical guiding significance based on three-dimensional CT imaging. Level of evidence Level III.

Abstract Metal micro/nanoparticle ink-based printed circuits have shown promise for promoting the scalable application of flexible electronics due to enabling superhigh metallic conductivity with cost-effective mass production. However, it is challenging to activate printed metal-particle patterns to approach the intrinsic conductivity without damaging the flexible substrate, especially for high melting-point metals. Here, we report a pressure-constrained sonication activation (PCSA) method of the printed flexible circuits for more than dozens of metal (covering melting points from room temperature to 3422 °C) and even nonmetallic inks, which is integrated with the large-scale roll-to-roll process. The PCSA-induced synergistic heat-softening and vibration-bonding effect of particles can enable multilayer circuit interconnection and join electronic components onto printed circuits without solder within 1 s at room temperature. We demonstrate PCSA-based applications of 3D flexible origami electronics, erasable and foldable double-sided electroluminescent displays, and custom-designed and large-area electronic textiles, thus indicating its potential for universality in flexible electronics.

Abstract Background Kiwifruit, belonging to the genus Actinidia, represents a unique fruit crop characterized by its modern cultivars being genetically diverse and exhibiting remarkable variations in morphological traits and adaptability to harsh environments. However, the genetic mechanisms underlying such morphological diversity remain largely elusive. Results We report the high-quality genomes of five Actinidia species, including Actinidia longicarpa, A. macrosperma, A. polygama, A. reticulata, and A. rufa. Through comparative genomics analyses, we identified three whole genome duplication events shared by the Actinidia genus and uncovered rapidly evolving gene families implicated in the development of characteristic kiwifruit traits, including vitamin C (VC) content and fruit hairiness. A range of structural variations were identified, potentially contributing to the phenotypic diversity in kiwifruit. Notably, phylogenomic analyses revealed 76 cis-regulatory elements within the Actinidia genus, predominantly associated with stress responses, metabolic processes, and development. Among these, five motifs did not exhibit similarity to known plant motifs, suggesting the presence of possible novel cis-regulatory elements in kiwifruit. Construction of a pan-genome encompassing the nine Actinidia species facilitated the identification of gene DTZ79_23g14810 specific to species exhibiting extraordinarily high VC content. Expression of DTZ79_23g14810 is significantly correlated with the dynamics of VC concentration, and its overexpression in the transgenic roots of kiwifruit plants resulted in increased VC content. Conclusions Collectively, the genomes and pan-genome of diverse Actinidia species not only enhance our understanding of fruit development but also provide a valuable genomic resource for facilitating the genome-based breeding of kiwifruit.

Abstract Background Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases. However, it is still not well understand about the relationship between PCDH15 variants and RP. Methods In this study, we enrolled a Chinese autosomal recessive retinitis pigmentosa (arRP) pedigree and identified the causative gene in the proband by targeted whole exome sequencing (WES). The variants were validated in the family members by Sanger sequencing and co-segregation analysis. Results Novel compound heterozygous, Frame shift variants of the PCDH15 gene, NM_001384140.1:c.4368 − 2147_4368-2131del and NM_001384140.1:c exon19:c.2505del: p. T836Lfs*6 were identified in the arRP pedigree, which co-segregated with the clinical RP phenotypes. The PCDH15 protein is highly conserved among species. Conclusion This is the first study to identify novel compound heterozygous variants c.4368 − 2147_4368-2131del and c.2505del(p.T836Lfs*6) in the PCDH15 gene which might be disease-causing variants, and extending the variant spectra. All above findings may be contribute to genetic counseling, molecular diagnosis and clinical management of arRP disease.

Abstract RHOA mutations are found at diverse residues in various cancer types, implying mutation- and cell-specific mechanisms of tumorigenesis. Here, we focus on the underlying mechanisms of two gain-of-function RHOA mutations, A161P and A161V, identified in adult T-cell leukemia/lymphoma. We find that RHOAA161P and RHOAA161V are both fast-cycling mutants with increased guanine nucleotide dissociation/association rates compared with RHOAWT and show reduced GTP-hydrolysis activity. Crystal structures reveal an altered nucleotide association in RHOAA161P and an open nucleotide pocket in RHOAA161V. Both mutations perturb the dynamic properties of RHOA switch regions and shift the conformational landscape important for RHOA activity, as shown by 31P NMR and molecular dynamics simulations. Interestingly, RHOAA161P and RHOAA161V can interact with effectors in the GDP-bound state. 1H-15N HSQC NMR spectra support the existence of an active population in RHOAA161V-GDP. The distinct interaction mechanisms resulting from the mutations likely favor an RHOAWT-like “ON” conformation, endowing GDP-bound state effector binding activity.

In the process of CO2-enhanced coalbed methane recovery, the behaviours of coal seam fractures significantly affect sequestration and extraction. To address the unclear impact of fracture roughness evolution on engineering efficiency under multi-physical field coupling effects, we developed an innovative interdisciplinary mathematical model. This model introduces a parameter to quantitatively describe coal seam fracture roughness and couples it with the gas flow control equations under multi-field effects in the coal seam. We investigated the thermo-hydro-mechanical (THM) coupling effects and fracture network characteristics in the coal seam gas extraction process. Results show that the mathematical model aligns well with field data and effectively characterizes coal seam fracture roughness. Fracture roughness significantly influences the residual gas pressure in the coal seam and the injection pressure of CO2. When the roughness parameter decreases from 0.24 to 0.18, the maximum methane content decreases by 32.5% and the maximum CO2 pressure increases by 26.7%, the maximum gas adsorption capacity of coal seam decreased by 31.7%, and the maximum CO2 adsorption capacity increased by 12.1%.

On December 18, 2023, a M6.2 earthquake occurred in Jishishan County of Gansu Province, and on January 1, 2024, a M7.6 earthquake occurred in Noto, Japan, with a short interval between the two earthquakes. They caused a large number of deaths and huge property losses with causing great concern in the seismic community. By using the mean line difference amplitude enhancement ratio method, it was found that there were significant thermal infrared anomalies before the two earthquakes. About 110 to 90 days before the Jishishan earthquake, the activity of long-wave radiant thermal infrared was 1.5 to 5 times higher than the historical average. Thermal infrared activity levels were 3 to 4 times higher than the historical average for about 140 to 100 days before the Noto earthquake in Japan. These results once again prove that there are thermal infrared anomalies before strong earthquakes, and also indicate that the mean line difference amplitude enhancement ratio method has strong ability to extract thermal infrared anomalies.

Abstract Background Electronic medical record (EMR) systems provide timely access to clinical information and have been shown to improve medication safety. However, EMRs can also create opportunities for error, including system-related errors or errors that were unlikely or not possible with the use of paper medication charts. This study aimed to determine the detection and mitigation strategies adopted by a health district in Australia to target system-related errors and to explore stakeholder views on strategies needed to curb future system-related errors from emerging. Methods A qualitative descriptive study design was used comprising semi-structured interviews. Data were collected from three hospitals within a health district in Sydney, Australia, between September 2020 and May 2021. Interviews were conducted with EMR users and other key stakeholders (e.g. clinical informatics team members). Participants were asked to reflect on how system-related errors changed over time, and to describe approaches taken by their organisation to detect and mitigate these errors. Thematic analysis was conducted iteratively using a general inductive approach, where codes were assigned as themes emerged from the data. Results Interviews were conducted with 25 stakeholders. Participants reported that most system-related errors were detected by front-line clinicians. Following error detection, clinicians either reported system-related errors directly to the clinical informatics team or submitted reports to the incident information management system. System-related errors were also reported to be detected via reports run within the EMR, or during organisational processes such as incident investigations or system enhancement projects. EMR redesign was the main approach described by participants for mitigating system-related errors, however other strategies, like regular user education and minimising the use of hybrid systems, were also reported. Conclusions Initial detection of system-related errors relies heavily on front-line clinicians, however other organisational strategies that are proactive and layered can improve the systemic detection, investigation, and management of errors. Together with EMR design changes, complementary error mitigation strategies, including targeted staff education, can support safe EMR use and development.

Abstract This review provides a comprehensive analysis of apoptotic signaling pathways in the context of bone metastatic lung cancer, emphasizing the intricate molecular mechanisms and microenvironmental influences. Beginning with an overview of apoptosis in cancer, the paper explores the specific molecular characteristics of bone metastatic lung cancer, highlighting alterations in apoptotic pathways. Focused discussions delve into key apoptotic signaling pathways, including the intrinsic and extrinsic pathways, and the roles of critical molecular players such as Bcl-2 family proteins and caspases. Microenvironmental factors, such as the tumor microenvironment, extracellular matrix interactions, and immune cell involvement, are examined in depth. The review also addresses experimental approaches and techniques employed in studying apoptotic signaling, paving the way for a discussion on current therapeutic strategies, their limitations, and future prospects. This synthesis contributes a holistic understanding of apoptosis in bone metastatic lung cancer, offering insights for potential therapeutic advancements.

Abstract Background Aripiprazole is the most frequently recommended antipsychotic for the treatment of tics in children and adolescents with Tourette’s disorder (TD). However, to date, a randomized controlled trial for aripiprazole oral solution has not been conducted despite being widely preferred by children. Therefore, we examined whether aripiprazole oral solution is effective for treating tics. Methods All patients received a flexible dose of aripiprazole oral solution (1 mg/mL, range: 2–20 mg) with a starting dose of 2 mg. The target dose for patients weighing

Abstract Background More than 50% of people who die by suicide have not been in contact with formal mental health services. The rate of people who fly ‘under the radar’ of mental health services is higher among men than women, indicating a need to improve engagement strategies targeted towards men who experience suicidal thoughts and/or behaviours. In Australia, a range of mental health support services exist, designed specifically for men, yet, a substantial proportion of men do not use these services. The aim of this study is to evaluate whether a brief online video-based messaging intervention is an effective approach for encouraging men with suicidal thoughts and/or behaviours to engage with existing support services. Methods Informed by a literature review, surveys, and consultation with men with a lived experience of suicidal thoughts and/or behaviours, we designed five video-based messages that will be used in this five-arm randomised controlled trial. A total of 380 (76 per arm) men aged 18 years or older with suicidal thoughts who are not currently accessing formal mental health services will be recruited online and randomly assigned to watch one of the five web-based video messages. After viewing the video, men will be presented with information about four existing Australian support services, along with links to these services. The primary outcome will be help-seeking, operationalised as a click on any one of the four support service links, immediately after viewing the video. Secondary outcomes include immediate self-reported help-seeking intentions in addition to self-reported use of the support services during a 1-week follow-up period. We will also use the Discrete Choice Experiment methodology to determine what aspects of support services (e.g. low cost, short appointment wait times) are most valued by this group of men. Discussion This study is the first to evaluate the effectiveness of a brief web-based video messaging intervention for promoting engagement with existing support services among men with suicidal thoughts who are not currently receiving formal help. If found to be effective, this would represent a scalable, cost-effective approach to promote help-seeking for this at-risk population. Limitations and strengths of this study design are discussed.

Objective Polycystic ovary syndrome (PCOS) is a prevalent cause of menstrual irregularities and infertility in women, impacting quality of life. Despite advancements, current understanding of PCOS pathogenesis and treatment remains limited. This study uses machine learning-based data mining to identify acetylation-related genetic markers associated with PCOS, aiming to enhance diagnostic precision and therapeutic efficacy.Methods Advanced machine learning techniques were used to improve the precision of key gene identification and reveal their biological mechanisms. Validation on an independent dataset (GSE48301) confirmed their diagnostic value, assessed through ROC curves and nomograms for PCOS risk prediction. Molecular mechanisms of acetylation-related gene regulation in PCOS were further examined through clustering, immune-environmental, and gene network analyses.Results Our analysis identified 15 key acetylation-regulated genes differentially expressed in PCOS, including SGF29, NOL6, KLF15, and INO80D, which are relevant to PCOS pathogenesis. ROC curve analyses on training and validation datasets confirmed the model’s high diagnostic accuracy. Additionally, these genes were associated with immune cell infiltration, offering insights into the inflammatory aspect of PCOS.Conclusion The identified acetylation gene markers offer novel insights into the molecular mechanisms underlying PCOS and hold promise for enhancing the development of precise diagnostic and therapeutic strategies.

The effect of legume proteins (soy protein (SP), chickpea protein (CP) and peanut protein (PP)) on the properties of wheat starch-lauric acid (WS-LA) system and its intrinsic mechanism were investigated. RVA, digestion experiment and TGA results showed that legume proteins prompted the viscosity peak formation during cooling stage and increased anti-digestion and thermal stability of WS-LA system. FT-IR, Raman, XRD and 13C NMR results indicated that legume proteins improved the long-range and short-range ordering degree and single-helix structure of WS-LA system. SP had greater influence on the properties of WS-LA system than that of CP and PP. Proteins with high solubility, emulsifying properties and β-sheet content were conducive to starch-based complexes formation. Molecular dynamics simulation results indicated that major forces for WS-LA-SP formation were hydrogen bonding and van der Waals forces. This study offered crucial information on starch-fatty acid-protein complexes formation for proteins selection in starch-based products development.

3D printed concrete (3DPC) is an essential technology for achieving efficient, precise, and sustainable construction. Nevertheless, due to limitations in materials and processes, 3DPC is prone to insufficient green strength and weakness in the interlayer area, which can result in print collapse and diminish its interlayer adhesion strength. Therefore, understanding green strength and interlayer adhesion strength of 3DPC is crucial for ensuring its structural safety. Superabsorbent polymer (SAP) serves as a novel type of concrete admixture, demonstrating the potential to promote green strength development and augment interlayer adhesion properties by facilitating the hydration process through water absorption and release. This study presents the first investigation into the effects of two commercially available SAPs on green strength and interlayer adhesion of 3D printed concrete. The role of SAP in improving interlayer adhesion performance in 3DPC is further elucidated through X-ray diffraction (XRD), Scanning electron microscopy (SEM). The results indicate that, compared to the control group, in the absence of added compensated water to SA1, the compressive strength at 15 min and splitting tensile strength of the printed specimen at 28 d increased by 282 % and 24.9 %, respectively, whereas SA2 demonstrates a relatively weaker enhancement effect. This study demonstrates that SAP promotes structural accumulation during the 3DPC printing stage, thereby presenting itself as a favorable material choice for applications involving 3DPC.

Effective utilization of waste kitchen oil (WKO) is important to environmental protection and economic development. Presently, an endophytic fungus Chaetomium globosum CGMCC 6882 polysaccharide (CGP-WKO) was successfully produced through submerged fermentation with the sole carbon source of WKO. CGP-WKO had a yield of 1.53 ± 0.27 g/L and contained 95.85 % ± 3.02 % carbohydrate and 2.94 % ± 0.62 % protein. Structural feature analysis indicated that CGP-WKO contained glucose, glucosamine, mannose, rhamnose, galactose, fructose, and glucuronic acid in a molar ratio of 30.38: 1.34: 32.22: 9.68: 1.59: 0.62: 3.73. The weight-averaged molecular weight of CGP-WKO was 26.64 kDa, and its polydispersity was 1.48. Moreover, antioxidant capacity detection in vitro demonstrated that when the concentration of CGP-WKO was 1.0 mg/mL, its scavenging effects against 1,1-diphenyl-2-picrylhydrazyl; 2,2′-azinobis-di-(3-ethyl-benzothiazolin-6-sulfonic acid) diammonium salt; and hydroxyl and superoxide radicals were 45.89 % ± 1.89 %, 55.89 % ± 1.12 %, 29.02 % ± 2.61 %, and 52.76 % ± 2.12 %, respectively; and the IC50 values were 6.4612, 0.8888, 13.8585, and 0.9398 mg/mL, respectively. CGP-WKO increased the content of superoxide dismutase, catalase, and glutathione peroxidase and reduced malondialdehyde content in H2O2-challenged HepG2 cells. Overall, the present work indicated that CGP-WKO can be used as an antioxidant agent in the food, cosmetics, and pharmaceutical industries.

Abstract In situ disc regeneration is a meticulously orchestrated process, which involves cell recruitment, proliferation and differentiation within a local inflammatory niche. Thus far, it remains a challenge to establish a multi‐staged regulatory framework for coordinating these cellular events, therefore leading to unsatisfactory outcome. This study constructs a super paramagnetically‐responsive cellular gel, incorporating superparamagnetic iron oxide nanoparticles (SPIONs) and aptamer‐modified palladium‐hydrogen nanozymes (PdH‐Apt) into a double‐network polyacrylamide/hyaluronic acid (PAAm/HA) hydrogel. The Aptamer DB67 within magnetic hydrogel (Mag‐gel) showed a high affinity for disialoganglioside (GD2), a specific membrane ligand of nucleus pulposus stem cells (NPSCs), to precisely recruit them to the injury site. The Mag‐gel exhibits remarkable sensitivity to a magnetic field (MF), which exerts tunable micro/nano‐scale forces on recruited NPSCs and triggers cytoskeletal remodeling, consequently boosting cell expansion in the early stage. By altering the parameters of MF, the mechanical cues within the hydrogel facilitates differentiation of NPSCs into nucleus pulposus cells to restore disc structure in the later stage. Furthermore, the PdH nanozymes within the Mag‐gel mitigate the harsh inflammatory microenvironment, favoring cell survival and disc regeneration. This study presents a remote and multi‐staged strategy for chronologically regulating endogenous stem cell fate, supporting disc regeneration without invasive procedures.

Interstitial lung diseases (ILDs) lead to increased morbidity and premature deaths, imposing a significant burden on public health worldwide. Recently, several studies have linked ambient air pollution with the acute exacerbation of certain ILDs, but the evidence remains limited and inconclusive. With a multicenter hospital-based case-crossover design, we investigated 9128 patients who resided in Jiangsu province, China, and were admitted for ILDs between 2019 and 2022. Residential exposure to particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5), PM10, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) was assessed using our validated grid datasets. We fitted conditional logistic regression models to examine associations of exposure to air pollutants with ILD admission. A 10 µg/m3 increment of exposure to SO2 and NO2 was positively associated with a 16.18 % (95 % confidence interval [CI]: 3.79 %, 30.03 %) and 4.06 % (0.75 %, 7.49 %) increase in odds of ILD admission, respectively. All these associations appeared to be linear and the association of SO2 exposure was significantly stronger among older adults. We estimated that over 10 % of ILD admissions could be attributable to exposure to SO2 and NO2. This study provides compelling evidence on the association of exposure to ambient air pollutants (including SO2 and NO2) with an increased odds of ILD hospitalizations. Our findings indicate that SO2 and NO2 exposures can lead to the exacerbation of ILDs, especially in elderly, and that the disease burden is considerable.

Congenital ocular malformations originate from defective morphogenesis during early eye development and cause 25% of childhood blindness. Formation of the eye is a multi-step, dynamic process; it involves evagination of the optic vesicle, followed by distal and ventral invagination, leading to the formation of a two-layered optic cup with a transient optic fissure. These tissue folding events require extensive changes in cell shape and tissue growth mediated by cytoskeleton mechanics and intercellular adhesion. We hypothesized that the Rho GTPase Cdc42 may be an essential, convergent effector downstream of key regulatory factors required for ocular morphogenesis. CDC42 controls actin remodeling, apicobasal polarity, and junction assembly. Here we identify a novel essential function for Cdc42 during eye morphogenesis in mouse; in Cdc42 mutant eyes expansion of the ventral optic cup is arrested, resulting in microphthalmia and a wide coloboma. Our analyses show that Cdc42 is required for expression of the polarity effector proteins PRKCZ and PARD6, intercellular junction protein tight junction protein 1, β-catenin, actin cytoskeleton F-actin, and contractile protein phospho myosin light chain 2. Expression of RPE fate determinants OTX2 and MITF, and formation of the RPE layer are severely affected in the temporal domain of the proximal optic cup. EdU incorporation is significantly downregulated. In addition, mitotic retinal progenitor cells mislocalize deeper, basal regions, likely contributing to decreased proliferation. We propose that morphogenesis of the ventral optic cup requires Cdc42 function for coordinated optic cup expansion and establishment of subretinal space, tissue tension, and differentiation of the ventral RPE layer.

The Japanese encephalitis virus (JEV), a zoonotic flavivirus, is Asia’s primary cause of viral encephalitis. JEV induces apoptosis in a variety of cells; however, the precise mechanisms underlying this apoptosis resulting from JEV infection remain to be elucidated. Our previous studies showed that the proapoptosis gene BAX may have a role in JEV proliferation. In this study, we constructed a PK-15 cell line (BAX.KO) with a knockout of the BAX gene using CRISPR/Cas9. The knockout of the BAX gene effectively inhibited the proliferation of JEV, resulting in a 39.9% decrease in viral protein levels, while BAX overexpression produced the opposite effect. We confirmed that JEV induces apoptosis of PK-15 using 4′,6-diamidino-2-phenylindole (DAPI) staining and Annexin V-FITC/PI staining. Furthermore, we found that the phosphorylation of P53 and the expression levels of BAX, NOXA, PUMA, and cleaved-caspase-3/9 were significantly upregulated after JEV infection. Moreover, we found that JEV infection not only caused mitochondrial damage, the release of mitochondrial cytochrome C (Cyt C), and the downregulation of the apoptosis-inhibiting protein BCL-2 but also reduced the mitochondrial membrane potential (MOMP) and the accumulation of intracellular reactive oxygen species (ROS). These factors collectively encourage the activation of the mitochondrial apoptosis pathway. In contrast, BAX gene knockout significantly reduces the apoptotic changes caused by JEV infection. Treatment with the caspase3 inhibitor attenuated JEV-induced viral proliferation and release, leading to a decrease in viral protein levels of 46% in PK-15 cells and 30% in BAX.KO cells. In conclusion, this study clarified the molecular mechanisms of JEV-induced apoptosis and provided a theoretical basis for revealing the pathogenic mechanisms of JEV infection.

Abstract Non‐healing diabetic wounds and ulcer complications, with persistent cell dysfunction and obstructed cellular processes, are leading causes of disability and death in patients with diabetes. Currently, there is a lack of guideline‐recommended hypoglycemic drugs in clinical practice, likely due to limited research and unclear mechanisms. In this study, it is demonstrated that liraglutide significantly accelerates wound closure in diabetic mouse models (db/db mice and streptozotocin‐induced mice) by improving re‐epithelialization, collagen deposition, and extracellular matrix remodeling, and enhancing the proliferation, migration, and adhesion functions of keratinocytes. However, these effects of improved healing by liraglutide are abrogated in dedicator of cytokinesis 5 (Dock5) keratinocyte‐specific knockout mice. Mechanistically, liraglutide induces cellular function through stabilization of unconventional myosin 1c (Myo1c). Liraglutide directly binds to Myo1c at arginine 93, enhancing the Myo1c/Dock5 interaction by targeting Dock5 promoter and thus promoting the proliferation, migration, and adhesion of keratinocytes. Therefore, this study provides insights into liraglutide biology and suggests it may be an effective treatment for diabetic patients with wound‐healing pathologies.