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Moral decisions often involve dilemmas: cases of conflict between competing obligations. In two studies (N = 204), we ask whether children appreciate that reasoning through dilemmas involves acknowledging that there is no single, simple solution. In Study 1, 5- to 8-year-old US children were randomly assigned to a Moral Dilemma condition, in which story characters face dilemmas between two prosocial actions, or a Personal Cost control, in which story characters face decisions between a matched prosocial action and a self-interested action. Children were then presented with two reasoners who made the same judgment, but one confidently endorsed one moral action, and the other hesitantly acknowledged both actions. As they aged, children became more likely to prefer the uncertain reasoner's "way of thinking" in the Moral Dilemma compared to the Personal Cost condition. They also inferred that the uncertain reasoner was nicer and more trustworthy than the confident one. In Study 2, when both reasoners acknowledged the dilemma and differed only in their level of uncertainty, 5-year-olds preferred the acknowledgment to be accompanied by a confident decision, 6- and 7-year-olds preferred it be accompanied by uncertainty, and 8-year-olds showed no preference. These results show that, before the age at which children can resolve dilemmas successfully on their own, they recognize and value others who approach dilemmas with appropriate humility.

As adults, we might understand that beliefs often spread because people are strongly influenced by their friends, family, and other social connections. However, do we think those influences are strong enough to overrule direct evidence of a friend's unreliability? And do preschoolers expect people to show such biases toward friends and to privilege friendship over reliability? Across three experiments, we explored whether friendship influences the evaluations of trust when others learn labels for novel objects as well as personal opinions. After watching scenes involving a main character, her best friend, and a stranger, preschoolers and adults judged who would be trusted for information from the main character's perspective (third person) as well as their own (first person). Adults (n = 128, 55 female, recruited online from across the United States) expected the main character to trust information from her friend even if she had been previously inaccurate, while basing their own first-person judgments on accuracy. In contrast, 4- and 5-year-olds (n = 128, 62 female, from the United States) thought that the main character would be like themselves and prioritize accuracy over friendship. Further, preschoolers expected the main character to trust her (inaccurate) friend and (accurate) stranger equally when forming personal opinions. Thus, young children, unlike adults, do not expect others' epistemic trust to privilege friendship with the speaker over accuracy information.

To address the problems of low accuracy by the CONWEP model and poor efficiency by the Coupled Eulerian-Lagrangian (CEL) method in predicting close-range air blast loads of cylindrical charges, a neural network-based simulation (NNS) method with higher accuracy and better efficiency was proposed. The NNS method consisted of three main steps. First, the parameters of blast loads, including the peak pressures and impulses of cylindrical charges with different aspect ratios (L/D) at different stand-off distances and incident angles were obtained by two-dimensional numerical simulations. Subsequently, incident shape factors of cylindrical charges with arbitrary aspect ratios were predicted by a neural network. Finally, reflected shape factors were derived and implemented into the subroutine of the ABAQUS code to modify the CONWEP model, including modifications of impulse and overpressure. The reliability of the proposed NNS method was verified by related experimental results. Remarkable accuracy improvement was acquired by the proposed NNS method compared with the unmodified CONWEP model. Moreover, huge efficiency superiority was obtained by the proposed NNS method compared with the CEL method. The proposed NNS method showed good accuracy when the scaled distance was greater than 0.2 m/kg1/3. It should be noted that there is no need to generate a new dataset again since the blast loads satisfy the similarity law, and the proposed NNS method can be directly used to simulate the blast loads generated by different cylindrical charges. The proposed NNS method with high efficiency and accuracy can be used as an effective method to analyze the dynamic response of structures under blast loads, and it has significant application prospects in designing protective structures.

Abstract Background Cancer-associated fibroblasts (CAFs) are key components of tumor microenvironment and have been identified to be involved in modulating drug resistance in cancers by secreting molecules. Pancreatic cancer (PC) is a leading cause of cancer mortality with high aggressiveness. Gemcitabine (GEM) is one of primary antineoplastic drugs for PC. Collagen XVII (COL17A1) expression was found to be upregulated in GEM-resistant CAFs. Here, this study focused on investigating whether CAFs affected GEM resistance in PC by secreting COL17A1 and its associated mechanisms. Methods In total, 60 newly diagnosed PC patients only with GEM-based chemotherapy were recruited. Normal fibroblasts (NFs) and CAFs were isolated using fresh normal and resistant PC tissues. Human pancreatic duct epithelial (HPDE) cells were used for functional analyses. Levels of COL17A1 and Actinin Alpha 4 (ACTN4) were measured by using qRT-PCR and western blotting. Functional analyses were conducted using MTT, 5-ethynyl-2ʹ-deoxyuridine, transwell, and sphere formation assays, respectively. The interaction between COL17A1 and ACTN4 was analyzed by Co-immunoprecipitation and immunofluorescence assays. Animal models were established for in vivo analysis. Results CAF incubation promoted GEM resistance and enhanced the proliferation, invasion and stemness in GEM-resistant PC cells. COL17A1 was highly expressed in resistant CAFs and GEM-resistant PC cells, and CAF incubation could increase COL17A1 expression in resistant PC cells. Moreover, COL17A1 silencing in GEM-resistant PC cells or the incubation of COL17A1-decreased CAF with GEM-resistant PC cells could suppress GEM resistance and cell oncogenic phenotype progression. Mechanistically, COL17A1 interacted with ACTN4 protein, and the anticancer effects mediated by COL17A1-decreased CAFs in resistant PC cells were reversed by ACTN4 overexpression. In vivo assay also showed that COL17A1-decreased CAFs suppressed the growth and GEM resistance in PC by ACTN4. Conclusion CAFs-derived COL17A1 promoted GEM resistance and tumorigenesis in PC by interacting with ACTN4, suggesting a new method for overcoming GEM resistance in PC.

ABSTRACT Objectives Lumbar disc herniation (LDH) is a common degenerative spinal disease in clinical practice. This study aims to investigate the impact of Modic changes (MCs) on postoperative recovery and disease recurrence following percutaneous endoscopic lumbar disc discectomy (PELD), providing important insights for improving the management of chronic low back pain. This study investigates the 1‐year progression rate of MCs after PELD and their impact on surgical outcomes and recurrence. Methods This retrospective cohort study analyzed data from 419 patients with single‐segment lumbar disc herniation who underwent PELD between January 2019 and December 2022. Lumbar MRI assessed preoperative and postoperative MCs. Pain levels and surgical outcomes were evaluated using the visual analog scale, Oswestry Disability Index, and Macnab criteria. Univariate analysis explored the relationship between postoperative MCs and pain, while subgroups investigated the associations between postoperative efficacy, recurrence, and MCs type and area. Results One‐year follow‐up revealed that the probability of MCs postsurgery was 24.8%. Patients with postoperative MCs had significantly lower pain scores compared with the control group (p

The energy storage is an effective solution for the current imbalance between energy supply and demand. In particular, the cascaded storage method can enhance the heat exchange temperature difference and heat storage efficiency. Previous research mainly focused on the combination of different phase change materials, while there was rare research on efficient cascaded conversion pathways for electrothermal direct conversion coupled thermal storage devices. This study investigated the influence of sensible and latent heat storage materials on the thermal performance, and identified the optimal volume ratios and materials types. When the volume share of Mg-Al:PW-EG=1:1, the heat storage performance was the optimal with a quantity/efficiency of heat stored as 7328.7 kJ/97.3 %, leading to an increase of 458.5 kJ/6.6 % than the sensible heat storage condition (Mg-Al:PW-EG=1:0) and 630.18 kJ/8.5 % than the latent heat storage condition (Mg-Al:PW-EG=0:1). When the melting point and latent heat of phase change materials increased from 68.9∼79.1 °C and 224.8 kJ/kg to 118.0 °C and 344.9 kJ/kg respectively, the heat storage temperature rose by 162.7 °C, quantity of heat stored rose by 7535.5 kJ. While materials with large subcooling were not recommended for short-term heat storage, as approximately 25.6 % (3309.3 kJ) of stored heat and 22.4 % (2505.2 kJ) of exergy were wasted when the subcooling degree was 70 °C. The findings provided solutions to support the synergistic enhancement of heat storage/release performance of the composite energy storage heat sink.

Following the initial treatment of nasopharyngeal carcinoma (NPC), tumor progression often portends an adverse prognosis for these patients. MicroRNAs (miRNAs) have emerged as critical regulators of tumor immunity, yet their intricate mechanisms in NPC remain elusive. Through comprehensive miRNA sequencing, tumor tissue microarrays and tissue samples analysis, we identified miR-142-3p as a significantly upregulated miRNA that is strongly associated with poor prognosis in recurrent NPC patients. To elucidate the underlying molecular mechanism, we employed RNA sequencing, coupled with cellular and tissue assays, to identify the downstream targets and associated signaling pathways of miR-142-3p. Our findings revealed two potential targets, CFL2 and WASL, which are directly targeted by miR-142-3p. Functionally, overexpressing CFL2 or WASL significantly reversed the malignant phenotypes induced by miR-142-3p both in vitro and in vivo. Furthermore, signaling pathway analysis revealed that miR-142-3p repressed the RIG-I-mediated immune defense response in NPC by inhibiting the nuclear translocation of IRF3, IRF7 and p65. Moreover, we discovered that ADAR1 physically interacted with Dicer and promoted the formation of mature miR-142-3p in a dose-dependent manner. Collectively, ADAR1-mediated miR-142-3p processing promotes tumor progression and suppresses antitumor immunity, indicating that miR-142-3p may serve as a promising prognostic biomarker and therapeutic target for NPC patients.

The effect of alkali lignin on laccase activity and mycelial biomass of Flammulina velutipes was investigated under different fermentation temperature. The secretion of laccase by F. velutipes has certain specificity. Specifically, laccase activity could not be detected by F. velutipes CCMSSC 00103 under most fermentation medium, but could be detected by F. velutipes FL 19 under more fermentation medium. Among the three strains of F. velutipes, the laccase secretion capacity of F. velutipes FL 19 was obviously better than that of F. velutipes CCMSSC 05331 and F. velutipes CCMSSC 00103. Maximum laccase activity with the value of 73.42 ± 4.74 U/L was secreted by F. velutipes FL 19 in fermentation medium 2 appeared at 2th day. The presence of alkali lignin was useful for improving laccase activity secreted by F. velutipes and the effect of alkali lignin on improving laccase activity exceeded that of Populus beijingensis. F. velutipes were more suitable for secreting laccase at 26 ℃ due to the maximum laccase activity measured at 26 ℃ (73.42 ± 4.74 U/L) higher than that measured at 33 ℃ (70.71 ± 6.89 U/L). The results were useful for selecting suitable medium and temperature of F. velutipes strains to produce low-cost laccase.

Time synchronization networks are vital infrastructures for numerous applications. We introduce an innovative architecture addressing the high-precision requirements of national time networks. This scheme combines DCV (distributed common-view) time transfer in the backbone with TDM-based (time division multiplex-based) PTP in metro networks. It enables flexible designation of time servers as national primaries. All the time servers are interconnected via a centralized data center. Theoretical analysis and extensive experiments validate successful high-precision national synchronization over large-scale transport networks. Notably, we achieved end-to-end accuracy of 36 ns across 2150 km spanning 3 provinces/cities, marking a milestone. This solution paves the way for future networks and applications requiring ultra-high time synchronization precision.

Abstract Metabolic and neurological disorders commonly display dysfunctional branched-chain amino acid (BCAA) metabolism, though it is poorly understood how this leads to neurological damage. We investigated this by generating Drosophila mutants lacking BCAA-catabolic activity, resulting in elevated BCAA levels and neurological dysfunction, mimicking disease-relevant symptoms. Our findings reveal a reduction in neuronal AMP-activated protein kinase (AMPK) activity, which disrupts autophagy in mutant brain tissues, linking BCAA imbalance to brain dysfunction. Mechanistically, we show that excess BCAA-induced mitochondrial reactive oxygen species (ROS) triggered the binding of protein phosphatase 2 A catalytic subunit (PP2Ac) to AMPK, suppressing AMPK activity. This initiated a dysregulated feedback loop of AMPK-mitochondrial interactions, exacerbating mitochondrial dysfunction and oxidative neuronal damage. Our study identifies BCAA imbalance as a critical driver of neuronal damage through AMPK suppression and autophagy dysfunction, offering insights into metabolic-neuronal interactions in neurological diseases and potential therapeutic targets for BCAA-related neurological conditions.

ABSTRACT Purpose Previous studies have shown higher cardiovascular mortality risk with higher monocyte–lymphocyte ratio levels in general population. However, the levels of oxidative stress in individuals with type 2 diabetes are higher than those in the general population, which may affect the link between monocyte‐to‐lymphocyte ratio and cardiovascular disease deaths. And the association between the monocyte‐to‐lymphocyte ratio and mortality risk in people with type 2 diabetes still be unknown. This study aimed to investigate the prognostic significance of monocyte‐to‐lymphocyte ratio in type 2 diabetes. Methods This analysis involved 2,954 individuals with type 2 diabetes from the National Health and Nutrition Examination Survey 1999–2010. The National Death Index records through December 31, 2019, was used to determine all‐cause and cardiovascular mortality. The prognostic roles were determined using Cox regression models, restricted cubic spline analysis, and time‐dependent receiver operating characteristic curve analysis. Results During an average follow‐up period of 12.4 years, a total of 1,007 deaths occurred, while 252 were due to cardiovascular disease. An elevated monocyte‐to‐lymphocyte ratio level exhibited a significant dose–response relationship with an increased risk of all‐cause mortality (1.34 [95% CI 1.12, 1.60] for all‐cause mortality [P trend = 0.001]). The multivariable‐adjusted HR was 1.81 (95% CI 1.25, 2.63) (P trend = 0.001) for cardiovascular mortality indicating a U‐shaped relationship (P nonlinear = 0.013). Conclusions The results of this study indicate a U‐shaped relationship between the monocyte‐to‐lymphocyte ratio and cardiovascular mortality in individuals with diabetes. Both very low and high monocyte‐to‐lymphocyte ratio monocyte‐to‐lymphocyte ratio values were found to be associated with increased cardiovascular mortality risk.

Abstract Chronic heart failure (CHF) poses a significant threat to human health. The stress hyperglycemia ratio (SHR) is a novel metric for accurately assessing stress hyperglycemia, which has been correlated with adverse outcomes in various major diseases. However, it remains unclear whether SHR is associated with 28-day mortality in patients with pre-existing CHF who were admitted to intensive care units (ICUs). This study retrospectively recruited patients who were admitted to ICUs with both acute critical illness and pre-existing CHF from the Medical Information Mart for Intensive Care (MIMIC) database. Characteristics were compared between the survival and non-survival groups. The relationship between SHR and 28-day all-cause mortality was analyzed using restricted cubic splines, receiver operating characteristic (ROC) curves, Kaplan–Meier survival analysis, and Cox proportional hazards regression analysis. The importance of the potential risk factors was assessed using the Boruta algorithm. Prediction models were constructed using machine learning algorithms. A total of 913 patients were enrolled. The risk of 28-day mortality increased with higher SHR levels (P 0.05). The area under the ROC (AUC) curve for SHR was larger than those for admission blood glucose and HbA1c; the cut-off for SHR was 0.57. Patients with SHR higher than the cut-off had a significantly lower 28-day survival probability (P

Abstract Introduction This study protocol specifies the primary research line and theoretical framework of the 2023 Survey of the Psychology and Behavior of the Chinese Population. It aims to establish a consistent database of Chinese residents' psychological and behavioral surveys through multi‐center and large‐sample cross‐sectional surveys to provide robust data support for developing research in related fields. It will track the public's physical and psychological health more comprehensively and systematically. Methods The study was conducted from June 20, 2023 to August 31, 2023, using stratified and quota sampling methods. A total of 150 cities across 800 communities/villages were surveyed, selected from China (Despite extensive coordination, we have been unable to contact our counterparts in the Taiwan region of China to obtain relevant statistical data). The questionnaires were distributed to the public one‐on‐one and face‐to‐face by trained surveyors. The questionnaires included basic information about the individual, personal health status, basic information about the family, the social environment in which the individual lives, psychological condition scales, behavioral level scales, other scales, and attitudes towards topical social issues. Supervisors conducted quality control during the distribution process and returned questionnaires, logically checked and cleaned for data analysis. Discussion Data collection has been finished, and scientific outputs based on this data will support the development of health promotion strategies in China and globally. In the aftermath of the pandemic, it will guide policymakers and healthcare organizations to improve their existing policies and services to maximize the physical and mental health of the Chinese population. Trial Registration This study was filed in the National Health Security Information Platform (Record No.: MR‐37‐23‐017876) and officially registered in the China Clinical Trials Registry (Registration No.: ChiCTR2300072573).

Abstract Objective This study aimed to examine the levels of physical activity (PA), sleep, and mental health (MH), specifically depression, anxiety, and stress, among Chinese university students. It also aimed to analyze the influencing factors of MH, providing a theoretical foundation for developing intervention programs to improve college students’ mental health. Methods A stratified, clustered, and phased sampling method was employed. In September 2022, a survey was conducted among 36,756 university students from 104 higher education institutions across 31 provinces, autonomous regions, and municipalities in China. The participants’ PA behaviors, sleep patterns, depressive symptoms (use the CES-D), anxiety symptoms (use the GAD-7), smoking and drinking behaviors, and demographic information were assessed through an online questionnaire using Questionnaire Star software. Results A total of 30,475 valid questionnaires were completed. The proportion of university students engaging in light-intensity PA was 77.6%. The prevalence of insufficient sleep was 39.5%, whereas the prevalence of poor sleep quality was 16.7%. The prevalence of depressive symptoms was 10%, and the prevalence of anxiety symptoms was 23.3%. Binary logistic regression analysis revealed that engaging in moderate to high-intensity PA and having sufficient and high-quality sleep were associated with a lower likelihood of depressive symptoms (OR = 0.207–0.800, P

Abstract Financing sources for urban construction have garnered significant attention globally. Among various financing methods, the urban construction investment bond (UCIB) is unique to China. The UCIB credit spread, which represents the compensation for credit risk, has become a focal point for researchers. However, owing to shortcomings of previous approaches, few scholars have accurately assessed the impact of implicit government guarantees on credit spreads. This study introduces an innovative approach that uses orthogonal decomposition to extract proprietary information from credit ratings, reflecting implicit government guarantees. After accounting for bond factors, local government financing vehicle factors, and macroeconomic conditions, the implicit government guarantee substantially reduces the UCIB's credit spread. This conclusion remains robust when controlling for investor attention, regional factors, or duration.

The diagnosis of cancer is typically based on histopathological sections or biopsies on glass slides. Artificial intelligence (AI) approaches have greatly enhanced our ability to extract quantitative information from digital histopathology images as a rapid growth in oncology data. Gynecological cancers are major diseases affecting women's health worldwide. They are characterized by high mortality and poor prognosis, underscoring the critical importance of early detection, treatment, and identification of prognostic factors. This review highlights the various clinical applications of AI in gynecological cancers using digitized histopathology slides. Particularly, deep learning models have shown promise in accurately diagnosing, classifying histopathological subtypes, and predicting treatment response and prognosis. Furthermore, the integration with transcriptomics, proteomics, and other multi-omics techniques can provide valuable insights into the molecular features of diseases. Despite the considerable potential of AI, substantial challenges remain. Further improvements in data acquisition and model optimization are required, and the exploration of broader clinical applications, such as the biomarker discovery, need to be explored.

Mycobacteria are causative agents of tuberculosis (TB), which is a global health concern. Drug-resistant TB strains are rapidly emerging, thereby necessitating the urgent development of new drugs. Two-component signal transduction systems (TCSs) are signaling pathways involved in the regulation of various bacterial behaviors and responses to environmental stimuli. Applying specific inhibitors of TCSs can disrupt bacterial signaling, growth, and virulence, and can help combat drug-resistant TB. We conducted a comprehensive pharmacophore-based inhibitor screening and biochemical and biophysical examinations to identify, characterize, and validate potential inhibitors targeting the response regulators PhoP and MtrA of mycobacteria. The constructed pharmacophore model Phar-PR-n4 identified effective inhibitors of formation of the PhoP–DNA complex: ST132 (IC50 = 29 ± 1.6 µM) and ST166 (IC50 = 18 ± 1.3 µM). ST166 (KD = 18.4 ± 4.3 μM) and ST132 (KD = 14.5 ± 0.1 μM) strongly targeted PhoP in a slow-on, slow-off manner. The inhibitory potency and binding affinity of ST166 and ST132 for MtrAC were comparable to those of PhoP. Structural analyses and molecular dynamics simulations revealed that ST166 and ST132 mainly interact with the α8-helix and C-terminal β-hairpin of PhoP, with functionally essential residue hotspots for structure-based inhibitor optimization. Moreover, ST166 has in vitro antibacterial activity against Macrobacterium marinum. Thus, ST166, with its characteristic 1,2,5,6-tetrathiocane and terminal sulphonic groups, has excellent potential as a candidate for the development of novel antimicrobial agents to combat pathogenic mycobacteria.

The increasing interest in multilineage differentiating stress-enduring (Muse) cells within the field of regenerative medicine is attributed to their exceptional homing capabilities, prolonged viability in adverse conditions, and enhanced three-germ-layer differentiate ability, surpassing their parent mesenchymal stem cells. Given their abundant sources, non-invasive collection procedure, and periodic availability, human menstrual blood-derived endometrium stem cells (MenSCs) have been extensively investigated as a potential resource for stem cell-based therapies. However, there is no established modality to isolate Muse cells from MenSCs and disparity in gene expression profiles between Muse cells and MenSCs remain unknown. In this study, Muse cells were isolated from MenSCs by long-time trypsin incubation method. Muse cells expressed pluripotency markers and could realize multilineage differentiation in vitro. Compared with MenSCs, Muse cells showed enhanced homing ability and superior therapeutic efficacy in animal models of acute liver injury (ALI) and intracerebral hemorrhage (ICH). Furthermore, the RNA-seq analysis offers insights into the mechanism underlying the disparity in trypsin resistance and migration ability between Muse and MenSCs cells. This research offers a significant foundation for further exploration of cell-based therapies using MenSCs-derived Muse cells in the context of various human diseases, highlighting their promising application in the field of regenerative medicine.