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Abstract Background New graduate nurses often have certain potential safety hazards for patients due to insufficient knowledge and lack of clinical practice ability. To address these challenges, China has implemented a standardized training strategy. The improvements in the quality of this training involve not only the intervention of teaching methods but also the consideration of personality traits. Methods The application software based on the BFI-2 Chinese scale was utilized to administer personality tests to nursing students; nursing students were invited to scan the QR code and voluntarily fill in a questionnaire, including basic information, personality test results, and a professional self-efficacy test scale; offline paper-based theoretical examination results of nursing students were collected before and after training. The data was then analyzed using SPSS software version 26.0, which involved descriptive analysis, one-way between-groups analysis of variance (ANOVA) and Spearman correlation analysis. Results Based on the data, there were no observable differences in the theoretical results before and after training across different personality traits. In terms of skill assessment, conscientiousness exhibited the highest score at 78.91 ± 2.98 points, while negative emotionality showed the lowest score at 74.59 ± 2.12 points. These differences between different personality traits are statistically significant (P

Abstract Water content and primary fractures can change the mechanical characteristics of rock, making it easy to induce geological disasters. Therefore, direct shear tests of red sandstone under the action of water-fracture were carried out in this paper. The results show that shear strength of rock samples with fractures is less than that of intact rock samples. With the increase of primary fracture dip angle, shear strength and macroscopic crushing area of the rock sample increases first and then decreases with 20° as the boundary. It shows that the primary fractures weaken the shear mechanical properties and change the macroscopic failure mode. The shear performance of water-bearing rock samples is weaker than that of intact rock samples, and the weakening degree of water-saturated on shear performance of rock samples is lower than that of unsaturated water state. The fracture surfaces of rock samples are divided into 'shortest path single through type', 'longest path single through type' and 'cross path through type'. The failured rock samples are divided into 'single through type' and 'cross through type'. The research results can provide reference for geological disaster management under relevant conditions.

Abstract Tumor spread through air spaces (STAS) is a distinctive metastatic pattern affecting prognosis in lung adenocarcinoma (LUAD) patients. Several challenges are associated with STAS detection, including misdetection, low interobserver agreement, and lack of quantitative analysis. In this research, a total of 489 digital whole slide images (WSIs) were collected. The deep learning-based STAS detection model, named STASNet, was constructed to calculate semi-quantitative parameters associated with STAS density and distance. STASNet demonstrated an accuracy of 0.93 for STAS detection at the tiles level and had an AUC of 0.72–0.78 for determining the STAS status at the WSI level. Among the semi-quantitative parameters, T10S, combined with the spatial location information, significantly stratified stage I LUAD patients on disease-free survival. Additionally, STASNet was deployed into a real-time pathological diagnostic environment, which boosted the STAS detection rate and led to the identification of three easily misidentified types of occult STAS.

Abstract Breast cancer remains a significant global health challenge, and its mechanisms of progression and metastasis are still not fully understood. In this study, analysis of TCGA and GEO datasets revealed a significant increase in CCT2 expression in breast cancer tissues, which was associated with poor prognosis in breast cancer patients. Functional analysis revealed that CCT2 promoted breast cancer growth and metastasis through activation of the JAK2/STAT3 signaling pathway. Additionally, the E3 ubiquitin ligase Trim21 facilitated CCT2 ubiquitination and degradation, significantly reversing the protumor effects of CCT2. Most interestingly, we discovered that exosomal CCT2 derived from breast cancer cells suppressed the activation and proinflammatory cytokine secretion of CD4+ T cell. Mechanistically, exosomal CCT2 constrained Ca2+-NFAT1 signaling, thereby reducing CD40L expression on CD4+ T cell. These findings highlight CCT2 upregulation as a potential driver of breast cancer progression and immune evasion. Our study provides new insights into the molecular mechanisms underlying breast cancer progression, suggesting that CCT2 is a promising therapeutic target and prognostic predictor for breast cancer.

Abstract Proto-oncogenic MYC is frequently dysregulated in colorectal cancer (CRC). In the past decades, long noncoding RNAs (lncRNAs) have emerged as important regulators in cancers, acting as scaffolds, molecular decoys, post-transcriptional regulators, and others. Interestingly, lncRNAs are able to control MYC expression both at transcriptional and post-transcriptional levels. It is suggested that the reciprocal interaction of MYC and lncRNAs often occurs in CRC. MYC can affect the cell fate by promoting or inhibiting the transcription of some lncRNAs. At the same time, some lncRNAs can also affect MYC expression or transcriptional activity, and in turn decide the cell fate. In this review we summarized the current knowledge about the MYC and lncRNA axis, focusing on its mutual regulation, roles in CRC, and proposed potential therapeutic prospects for CRC treatment.

Abstract Spinal cord injury (SCI) leads to fibrotic scar formation at the lesion site, yet the heterogeneity of fibrotic scar remains elusive. Here we show the heterogeneity in distribution, origin, and function of fibroblasts within fibrotic scars after SCI in mice and female monkeys. Utilizing lineage tracing and single-cell RNA sequencing (scRNA-seq), we found that perivascular fibroblasts (PFs), and meningeal fibroblasts (MFs), rather than pericytes/vascular smooth cells (vSMCs), primarily contribute to fibrotic scar in both transection and crush SCI. Crabp2 + /Emb+ fibroblasts (CE-F) derived from meninges primarily localize in the central region of fibrotic scars, demonstrating enhanced cholesterol synthesis and secretion of type I collagen and fibronectin. In contrast, perivascular/pial Lama1 + /Lama2+ fibroblasts (LA-F) are predominantly found at the periphery of the lesion, expressing laminin and type IV collagen and functionally involved in angiogenesis and lipid transport. These findings may provide a comprehensive understanding for remodeling heterogeneous fibrotic scars after SCI.

Background: Ginsenoside Rg1 (Rg1) is one of the main active components in Chinese medicines, Panax ginseng and Panax notoginseng. Research has shown that Rg1 has a protective effect on the cardiovascular system, including anti-myocardial ischemia-reperfusion injury, anti-apoptosis, and promotion of myocardial angiogenesis, suggesting it a potential cardiovascular agent. However, the protective mechanism involved is still not fully understood. Methods: Based on network pharmacology, ligand-based protein docking, proteomics, Western blot, protein recombination and spectroscopic analysis (UV–Vis and fluorescence spectra) techniques, potential targets and pathways for Rg1 against myocardial ischemia (MI) were screened and explored. Results: An important target set containing 19 proteins was constructed. Two target proteins with more favorable binding activity for Rg1 against MI were further identified by molecular docking, including mitogen-activated protein kinase 1 (MAPK1) and adenosine kinase (ADK). Meanwhile, Rg1 intervention on H9c2 cells injured by H2O2 showed an inhibitory oxidative phosphorylation (OXPHOS) pathway. The inhibition of Rg1 on MAPK1 and OXPHOS pathway was confirmed by Western blot assay. By protein recombination and spectroscopic analysis, the binding reaction between ADK and Rg1 was also evaluated. Conclusion: Rg1 can effectively alleviate cardiomyocytes oxidative stress injury via targeting MAPK1 and ADK, and inhibiting oxidative phosphorylation (OXPHOS) pathway. The present study provides scientific basis for the clinical application of the natural active ingredient, Rg1, and also gives rise to a methodological reference to the searching of action targets and pathways of other natural active ingredients.

Abstract Clean fire extinguishing systems applicable to the pottery jar liquor warehouse are in demand. In this study, taking 53vol% liquor as the research subject, fire models of various clean fire extinguishing systems comprising water mist, liquid carbon dioxide (LCO2) and liquid nitrogen (LN2) were established using a fire dynamic simulator to determine their fire extinguishing effect. A feasibility assessment of systems was performed under different fire source types, fire source sizes, and ventilation conditions. The fire extinguishing efficiency was analyzed in terms of the fire extinguishing time, oxygen concentration, and space temperature. The results showed that the success rate of the LCO2 and LN2 fire extinguishing systems was 100%, whereas the success rate of the water mist fire extinguishing system was 95%. In terms of reducing the oxygen concentration at the bottom of the space and the temperature in the space, the LCO2 system exhibited the best performance, followed by the LN2 system, and lastly the water mist. Under different ventilation conditions and fire source types, the LCO2 fire extinguishing system was least affected, whereas the effectiveness of the water mist fire extinguishing system reduced under natural ventilation conditions, and the extinguishing efficiency of the LN2 fire extinguishing system was affected by the fire source type. Overall, the LCO2 system presented more advantages in extinguishing fires in pottery jar liquor warehouses and can provide a new idea for the development and application of clean and efficient fire extinguishing systems.

Abstract Background Breast cancer is the most common malignant tumor, and metastasis remains the major cause of poor prognosis. Glucose metabolic reprogramming is one of the prominent hallmarks in cancer, providing nutrients and energy to support dramatically elevated tumor growth and metastasis. Nevertheless, the potential mechanistic links between glycolysis and breast cancer progression have not been thoroughly elucidated. Methods RNA-seq analysis was used to identify glucose metabolism-related circRNAs. The expression of circSIPA1L3 in breast cancer tissues and serum was examined by qRT-PCR, and further assessed its diagnostic value. We also evaluated the prognostic potential of circSIPA1L3 by analyzing a cohort of 238 breast cancer patients. Gain- and loss-of-function experiments, transcriptomic analysis, and molecular biology experiments were conducted to explore the biological function and regulatory mechanism of circSIPA1L3. Results Using RNA-seq analysis, circSIPA1L3 was identified as the critical mediator responsible for metabolic adaption upon energy stress. Gain- and loss-of-function experiments revealed that circSIPA1L3 exerted a stimulative effect on breast cancer progression and glycolysis, which could also be transported by exosomes and facilitated malignant behaviors among breast cancer cells. Significantly, the elevated lactate secretion caused by circSIPA1L3-mediated glycolysis enhancement promoted the recruitment of tumor associated macrophage and their tumor-promoting roles. Mechanistically, EIF4A3 induced the cyclization and cytoplasmic export of circSIPA1L3, which inhibited ubiquitin-mediated IGF2BP3 degradation through enhancing the UPS7-IGF2BP3 interaction. Furthermore, circSIPA1L3 increased mRNA stability of the lactate export carrier SLC16A1 and the glucose intake enhancer RAB11A through either strengthening their interaction with IGF2BP3 or sponging miR-665, leading to enhanced glycolytic metabolism. Clinically, elevated circSIPA1L3 expression indicated unfavorable prognosis base on the cohort of 238 breast cancer patients. Moreover, circSIPA1L3 was highly expressed in the serum of breast cancer patients and exhibited high diagnostic value for breast cancer patients. Conclusions Our study highlights the oncogenic role of circSIPA1L3 through mediating glucose metabolism, which might serve as a promising diagnostic and prognostic biomarker and potential therapeutic target for breast cancer.

Summary: RNA splicing is a critical process governing gene expression and transcriptomic diversity. Despite its importance, a detailed examination of transcript variation at the splicing junction level remains scarce. Here, we perform a thorough analysis of RNA splicing junctions in 34,775 samples across multiple sample types. We identified 29,051 tumor-specific transcripts (TSTs) in pan-cancer, with a majority of these TSTs being unannotated. Our findings show that TSTs are positively correlated with tumor stemness and linked to unfavorable outcomes in cancer patients. Additionally, TSTs display mutual exclusivity with somatic mutations and are overrepresented in transposable-element-derived transcripts possessing oncogenic functions. Importantly, TSTs can generate putative neoantigens for immunotherapy. Moreover, TSTs can be detected in blood extracellular vesicles from cancer patients. Our results shed light on the intricacies of RNA splicing and offer promising avenues for cancer diagnosis and therapy.

E-learning platform (ELP) provides economic and efficient channels to share and learn knowledge online without time and location restrictions. Earlier studies have identified determinants that impact students’ intention to use new technologies in different learning contexts, yet few have tried to investigate the effect of students’ satisfaction of basic psychological needs during the adoption process. Based on the framework of UTAUT2, this study has tested the mediating role of satisfaction of basic psychological needs to better comprehend the relationships between the antecedents and intention. The partial least square structural equation modeling was used for data analysis, findings indicate that performance expectancy, learning value, hedonic motivation, and habit significantly impact students’ willingness to adopt ELP for college English study. As for the mediating effect of students’ satisfaction of basic psychological needs, it fully mediates the relationship between effort expectancy, facilitating conditions, and intention while partially mediating the relationship between performance expectancy, learning value, hedonic motivation, habit, and intention. The study aids in grasping the key factors to increase students’ adoption of ELP and offers recommendations to increase students’ participation, learning efficiency, and their satisfaction of basic psychological needs for competence, autonomy, and relatedness during college English study with ELP.

An extensive network of cutaneous nerves, neuropeptides, and specific receptors richly innervates the skin and influences a variety of physiological and pathological processes. The sensory and autonomic nerve fibers secrete a variety of neuropeptides that are essential to the different phases of wound healing. In addition to initiating a neurogenic inflammatory response in the early stages of healing, neuropeptides also control wound healing by influencing immune cells, repair cells, and the growth factor network. However, the precise mechanism by which they accomplish these roles in the context of cutaneous wound healing is still unknown. Investigating the mechanisms of action of neuropeptides in wound healing and potential therapeutic applications is therefore urgently necessary. The present review discusses the process of wound healing, types of neuropeptides, potential mechanisms underlying the role of neuropeptides in cutaneous wound healing, as well as some neuropeptide-derived treatment strategies, such as hydrogels, new dressings, electro stimulation, and skin-derived precursors. Future in-depth mechanistic studies of neuropeptides in cutaneous wound healing may provide opportunities to develop therapeutic technologies that harness the roles of neuropeptides in the wound healing process.

BackgroundPrimary immune thrombocytopenia (ITP) is an immune-mediated hematologic disorder characterized by a reduction in platelet count, increasing the risk of bleeding. Recent studies have indicated a close association between alterations in gut microbiota and the development of ITP. However, the mechanisms by which gut microbiota influence the occurrence and progression of ITP through plasma metabolites remain poorly understood. Evidence suggests extensive interactions between gut microbiota and plasma metabolites, implying a potential role for gut microbiota in influencing ITP through alterations in plasma metabolites, which requires further investigation.MethodsIn this study, summarized GWAS data (including 211 gut microbiota taxa, 1,400 plasma metabolites or ratios, and an ITP patient cohort) were retrieved from the MiBioGen and GWAS Catalog databases. Using a two-sample Mendelian randomization (MR) approach, we screened gut microbiota and plasma metabolites potentially causally related to ITP. We further identified plasma metabolites serving as mediators through which gut microbiota affect ITP and calculated the strength of the mediation effect. To ensure result stability, we primarily used the inverse variance weighted (IVW) method as the main judgment index. We also utilized MR Egger and inverse variance weighted methods to detect heterogeneity in the results, and employed MR-Egger and MR-PRESSO methods to assess the presence of pleiotropy.ResultsThough two-sample MR analysis, 8 gut microbiota taxa were found to have causal relationships with ITP. After excluding six plasma metabolites with pleiotropy, 39 plasma metabolites were found to be causally related to ITP (P < 0.05). Eleven plasma metabolites were identified as having causal relationships between gut microbiota and plasma metabolites. Finally, using the delta method, it was calculated that Sphingomyelin levels (8.0%, 95%CI: 0.9% to 11.5%, P = 0.047) and Glucose-to-mannose ratio (6.5%, 95%CI: 0.7% to 9.5%, P = 0.039) are intermediates for Intestinimonas influencing ITP, while Bilirubin (Z,Z) to etiocholanolone glucuronide ratio (5.6%, 95%CI: 4.7% to 6.9%, P = 0.043) is an intermediate for Senegalimassilia influencing ITP.ConclusionGut microbiota can influence the development of ITP through changes in plasma metabolites. Sphingomyelin levels, Glucose-to-mannose ratio, and Bilirubin (Z,Z) to etiocholanolone glucuronide ratio are newly discovered intermediates through which gut microbiota influence ITP, providing potential indicators and targets for clinical diagnosis and treatment. This study highlights the intricate relationship between gut microbiota and plasma metabolites in the context of ITP, suggesting new avenues for clinical diagnosis and treatment.

Abstract Cognitive dysfunction is not only a common symptom of major depressive disorder, but also a more common residual symptom after antidepressant treatment and a risk factor for chronic and recurrent disease. The disruption of hypocretin regulation is known to be associated with depression, however, their exact correlation is remains to be elucidated. Hypocretin‐1 levels are increased in the plasma and hypothalamus from chronic unpredictable mild stress (CUMS) model mice. Excessive hypocretin‐1 conducted with hypocretin receptor 1 (HCRTR1) reduced lactate production and brain‐derived neurotrophic factor (BDNF) expression by hypoxia‐inducible factor‐1α (HIF‐1α), thus impairing adult hippocampal neuroplasticity, and cognitive impairment in CUMS model. Subsequently, it is found that HCRTR1 antagonists can reverse these changes. The direct effect of hypocretin‐1 on hippocampal lactate production and cognitive behavior is further confirmed by intraventricular injection of hypocretin‐1 and microPET‐CT in rats. In addition, these mechanisms are further validated in astrocytes and neurons in vitro. Moreover, these phenotypes and changes in molecules of lactate transport pathway can be duplicated by specifically knockdown of HCRTR1 in hippocampal astrocytes. In summary, the results provide molecular and functional insights for involvement of hypocretin‐1‐HCRTR1 in altered cognitive function in depression.

ABSTRACT The number of pediatric respiratory tract infection cases in China has significantly increased this year, and Mycoplasma pneumoniae is one of the main pathogens. This study aimed to investigate the epidemiological characteristics of M. pneumoniae in children in the Anhui region and to provide evidence for the prevention and control strategies of M. pneumoniae in children in this region. A total of 66,488 pediatric patients with respiratory tract infection were enrolled from January 2015 to November 2023 in this study. The results of this study exhibited that M. pneumoniae infection in the Anhui region was characterized by a high positive rate during 2021–2023, especially this year is considered a year of pandemic for M. pneumoniae infection. Moreover, the positive rate of M. pneumoniae in female children is significantly higher than in male children, and the infection rate of M. pneumoniae in children increases significantly with age, particularly in school-aged children.IMPORTANCEThe number of pediatric respiratory tract infection cases in China has significantly increased this year, and Mycoplasma pneumoniae is one of the main pathogens. This study aimed to investigate the epidemiological characteristics of M. pneumoniae in children in the Anhui region and provide evidence for the prevention and control strategies of M. pneumoniae in children in this region.

IntroductionResearch on the relationship between microscale built environments and physical activity among older adults in densely populated old urban areas with high aging rates is scarce. Particularly, the relationship between urban block land-use pattern and older adults’ walking activities have not yet been completely understood.MethodsThis study examined the daily walking habits and socioeconomic attributes of older adults in 17 blocks with different built environment characteristics in Nanjing City, China. A multi-layer linear model was used to quantitatively analyse the mechanism underlying the effects of various factors on the health of older adults.ResultsThe result shows significant positive correlation between neighborhood walkability and the enhancement of walking frequency and activity. For every 10% increase in pedestrian road connectivity and land use, the walking activity volume increased by 22.4 and 12%, and the BMI increased by 9.1 and 7.3% toward the standard range, respectively. For every 10% increase in distance between residence and plaza and park, the walking activity volume decreased by 5.4 and 3.2%, and BMI decreased by 9.9 and 6.3%, respectively.DiscussionFor every 10.4% increase in land mixed-use rate and per capita green area, BMI increased by 19.4%. Furthermore, higher household income and number of family members have significant correlation with walking activities and health effects. Moreover, the block-scale built environment and walking activities jointly affected health, with a cross-functional relationship between multiple factors.

Abstract Triple‐negative breast cancer (TNBC) is the most malignant subtype of breast cancer. TP53, which has a mutation rate of ≈70%–80% in TNBC patients, plays oncogenic roles when mutated. However, whether circRNAs can exert their effects on TNBC through regulating mutant TP53 has not been well evaluated. In this study, circCFL1, which is highly expressed in TNBC cells and tissues and has prognostic potential is identified. Functionally, circCFL1 promoted the proliferation, metastasis and stemness of TNBC cells. Mechanistically, circCFL1 acted as a scaffold to enhance the interaction between HDAC1 and c‐Myc, further promoting the stability of c‐Myc via deacetylation‐mediated inhibition of K48‐linked ubiquitylation. Stably expressed c‐Myc further enhanced the expression of mutp53 in TNBC cells with TP53 mutations by directly binding to the promoter of TP53, which promoted the stemness of TNBC cells via activation of the p‐AKT/WIP/YAP/TAZ pathway. Moreover, circCFL1 can facilitate the immune escape of TNBC cells by promoting the expression of PD‐L1 and suppressing the antitumor immunity of CD8+ T cells. In conclusion, the results revealed that circCFL1 plays an oncogenic role by promoting the HDAC1/c‐Myc/mutp53 axis, which can serve as a potential diagnostic biomarker and therapeutic target for TNBC patients with TP53 mutations.

The autogenous self-sealing model has been researched in previous work, which could help to characterize the self-sealing process with crystalline products. The model outcome was presented in the form of leakage water flow, which demonstrates the self-sealing capacity or the recovery of watertightness. While in the research area of cement-based material self-sealing, the expansive agent cannot be neglectable, for example the superabsorbent polymer (SAP). Especially for the building components exposed to free water, an efficient water flow blockage after cracking is crucial to ensure stable service. Hence in this study, the self-sealing process of a granular expansive agent inside the crack of cement-based material was simulated. The model outputs were compared with experimental results to verify the reliability. Additionally, the autogenous self-sealing model was incorporated into this model to simulate the “crystallization-expansion” synergetic self-sealing. The contribution of crystalline product and expanded EA to water flow blockage were compared during the crystallizing process. Overall, this model is of great use to evaluate the role of expansive agent on water flow blockage after the cement-based material cracking in hydraulic engineering or engineering components exposed to water.

The following Key Messages comprise the salient findings of this study:1. Ambient energy (from sun, air, ground, and sky) can heat and cool buildings; provide hot water, ventilation, and daylighting; dry clothes; and cook food. These services account for about three-quarters of building energy consumption and a third of total US demand. Biophilic design (direct and indirect connections with nature) is an intrinsic adjunct to ambient energy systems, and improves wellness and human performance.2. The current strategy of electrification and energy efficiency for buildings will not meet our climate goals, because the transition to an all-renewable electric grid is too slow. Widespread adoption of ambient energy is needed. Solar-heated buildings also flatten the seasonal demand for electricity compared to all-electric buildings, reducing required production capacity and long-term energy storage. In addition, ambient-conditioned buildings improve resilience by remaining livable during power outages.3. National policies, incentives, and marketing should be enacted to promote ambient energy use. Federal administrative priorities should reflect the importance of ambient energy for buildings. Use of ambient energy should be encouraged through existing and new building codes and standards.4. Ambient energy system design tools are needed for architects, engineers, builders, building scientists, realtors, appraisers, and consumers. PVWatts is used over 100 million times per year for photovoltaic system design. A similar, simple, and accessible tool for ambient design is crucial.5. Training on ambient energy is needed throughout secondary, post-secondary, and continuing education for workforce development. Currently, only about 10% of colleges teach courses on passive heating and cooling systems.6. Ambient-conditioned buildings should be demonstrated in all US climate zones. Performance should be monitored and reported, with quantitative case studies made widely available.7. While current technology is sufficient to build high-performance ambient buildings now, research is needed to develop new technologies to harness ambient energy more effectively and more economically. Such advancements will facilitate adoption of ambient energy technologies in a wider range of buildings, including retrofits. Examples include windows with much lower thermal losses, use of the building shell for thermal storage, alternative light-weight thermal storage systems, sky-radiation cooling systems, automated controls for solar gains and passive cooling, and ground coupling.

Highlights The formation of peptide nanocapsules is facilitated by a gradient interface, where the differential solvent concentration drives the peptides to preferentially localize and assemble. The peptide nanocapsules, characterized by their hollow structures, demonstrated potential as carriers for targeted drug delivery.

In response to the inadequacy of existing defense methods for backdoor attacks in federated learning to effectively remove embedded backdoor features from models, while simultaneously reducing the accuracy of the primary task, a federated learning backdoor defense method called ContraFL was proposed, which utilized contrastive training to disrupt the clustering process of backdoor samples in the feature space, thereby rendering the global model classifications in federated learning independent of the backdoor trigger features.Specifically, on the server side, a trigger generation algorithm was developed to construct a generator pool to restore potential backdoor triggers in the training samples of the global model.Consequently, the trigger generator pool was distributed to the participants by the server, where each participant added the generated backdoor triggers to their local samples to achieve backdoor data augmentation.Experimental results demonstrate that ContraFL effectively defends against various backdoor attacks in federated learning, outperforming existing defense methods.

Abstract Background The incidence of male reproductive dysfunction is increasing annually, and many studies have shown that obesity can cause severe harm to male reproductive function. The mechanism of male reproductive dysfunction caused by obesity is unclear, and there is no ideal treatment. Identification of effective therapeutic drugs and elucidation of the molecular mechanism involved in male reproductive health are meaningful. In this study, we investigated the effects of the GLP-1 receptor agonist liraglutide on sex hormones, semen quality, and testicular AC3/cAMP/PKA levels in high-fat-diet-induced obese mice. Methods Obese mice and their lean littermates were treated with liraglutide or saline for 12 weeks. Body weight was measured weekly. Fasting blood glucose (FBG) was measured using a blood glucose test strip. The serum levels of insulin (INS), luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), free testosterone (F-TESTO), estradiol (E2), and sex hormone binding globulin (SHBG) were detected using ELISA. The sperm morphology and sperm count were observed after Pap staining. The mRNA and protein expression levels of testicular GLP-1R and AC3 were measured by RT-qPCR and Western blot, respectively. Testicular cAMP levels and PKA activity were detected using ELISA. Results Liraglutide treatment can decrease body weight, FBG, INS, HOMA-IR, E2 and SHBG levels; increase LH, FSH, T, and F-TESTO levels; increase sperm count; decrease the sperm abnormality rate; and increase GLP-1R and AC3 expression levels and cAMP levels and PKA activity in testicular tissue. Conclusions Liraglutide can improve the sex hormone levels and semen quality of obese male mice. In addition to its weight loss effect, liraglutide can improve the reproductive function of obese male mice, which may also be related to the upregulation of AC3/cAMP/PKA pathway in the testis. This work lays the groundwork for future clinical studies.

Abstract Active pulmonary tuberculosis (PTB) poses challenges in rapid diagnosis within complex clinical conditions. Given the close association between neutrophils and tuberculosis, we explored differentially expressed long non-coding RNAs (lncRNAs) in neutrophils as potential molecular markers for diagnosing active PTB. We employed a gene microarray to screen for lncRNA alterations in neutrophil samples from three patients with active PTB and three healthy controls. The results revealed differential expression of 1457 lncRNAs between the two groups, with 916 lncRNAs upregulated and 541 lncRNAs down-regulated in tuberculosis patients. Subsequent validation tests demonstrated down-regulation of lncRNA ZNF100-6:2 in patients with active PTB, which was restored following anti-tuberculosis treatment. Our findings further indicated a high diagnostic potential for lncRNA ZNF100-6:2, as evidenced by an area under the receiver operating characteristic (ROC) curve of 0.9796 (95% confidence interval: 0.9479 to 1.000; P

Abstract Moyamoya disease (MMD) remains a chronic progressive cerebrovascular disease with unknown etiology. A growing number of reports describe the development of MMD relevant to infection or autoimmune diseases. Identifying biomarkers of MMD is to understand the pathogenesis and development of novel targeted therapy and may be the key to improving the patient’s outcome. Here, we analyzed gene expression from two GEO databases. To identify the MMD biomarkers, the weighted gene co-expression network analysis (WGCNA) and the differential expression analyses were conducted to identify 266 key genes. The KEGG and GO analyses were then performed to construct the protein interaction (PPI) network. The three machine-learning algorithms of support vector machine-recursive feature elimination (SVM-RFE), random forest and least absolute shrinkage and selection operator (LASSO) were used to analyze the key genes and take intersection to construct MMD diagnosis based on the four core genes found (ACAN, FREM1, TOP2A and UCHL1), with highly accurate AUCs of 0.805, 0.903, 0.815, 0.826. Gene enrichment analysis illustrated that the MMD samples revealed quite a few differences in pathways like one carbon pool by folate, aminoacyl-tRNA biosynthesis, fat digestion and absorption and fructose and mannose metabolism. In addition, the immune infiltration profile demonstrated that ACAN expression was associated with mast cells resting, FREM1 expression was associated with T cells CD4 naive, TOP2A expression was associated with B cells memory, UCHL1 expression was associated with mast cells activated. Ultimately, the four key genes were verified by qPCR. Taken together, our study analyzed the diagnostic biomarkers and immune infiltration characteristics of MMD, which may shed light on the potential intervention targets of moyamoya disease patients

Background: Determining when to recommend a change in treatment regimen due to insufficient improvement is a common challenge in therapeutics. Methods: In a sample of 7215 patients with major depressive disorder treated with transcranial magnetic stimulation (TMS) and with PHQ-9 scores before, during and after the course, 3 groups were identified based on number of acute course sessions: exactly 36 sessions (N = 3591), more than 36 sessions (N = 975), and less than 36 sessions (N = 2649). Two techniques were used to determine thresholds for percentage change in PHQ-9 scores at assessments after 10, 20, and 30 sessions that optimized prediction of endpoint response status: the Youden index and fixing the false positive rate at 10%. Positive and negative predictive values were calculated to assess the accuracy of identifying final nonresponders and responders, respectively. Results: There was greater accuracy in predicting final response than nonresponse, especially in the groups that had at least 36 sessions. Substantial proportions of patients with low levels of early improvement were classified as responders at the end of treatment. Limitations: The findings should be validated with clinician ratings using a more comprehensive depression severity scale. Conclusions: Manifesting clinical improvement early in the TMS course is strongly predictive of final status as a responder, while lack of early improvement is a relatively poor indicator of final nonresponse status. The predictive value of lack of early symptomatic improvement is too low to make reliable recommendations regarding changes in treatment regimen.

High-entropy alloy coatings show great potentiality in improving elevated temperature oxidation and wear resistance. In this study, Fe20Co20Ni20Cr8Mo12B10Si10 high-entropy alloy coating was prepared on 42CrMo alloy structural steel by laser cladding. The elevated temperature oxidation and wear resistance were investigated at room temperature and elevated temperature (600 °C). The crystal structure of the coating changed from a dual-phase structure consisting of BCC (dominant phase) and FCC phase to a single FCC structure with the production of SiO2, MoO3, Cr2O3 and NiCr2O4 after 600 °C oxidation for 200 h. The oxidation rate of the coating was 1.21 × 10−3 mg/(mm2·h), one fifth that of 42CrMo steel. The tribological properties of the coating shown no significant difference at room and elevated temperature with an average coefficient of friction and the wear rate about 0.46 and 0.02 mm3/N·m, respectively. The oxide film generated on the surface of the coating was dense and uniform, providing excellent oxidation and wear resistance at elevated temperature.

ABSTRACTObjective: To investigate the relationship between 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) related parameters and the prognosis of multiple myeloma and to establish and validate a prediction model regarding the progression-free survival (PFS) of multiple myeloma.Methods: A retrospective analysis of 126 newly diagnosed multiple myeloma patients who attended Nanjing Drum Tower Hospital from 2014–2021. All patients underwent PET/CT before treatment and were divided into a training cohort (n = 75) and a validation cohort (n = 51). Multivariate Cox proportional hazard regression analysis incorporated PET/CT-related parameters and clinical indicators. A nomogram was established to individually predict PFS in MM patients. The model was evaluated by calculating the C-index and calibration curve.Results: Here, 4.2 was used as the cut-off value of SUVmax to divide patients into high and low groups. PFS significantly differed between patients in the high-SUVmax group and low-SUVmax group, and SUVmax was an independent predictor of PFS in newly diagnosed multiple myeloma (NDMM) patients. Univariate and multivariate cox regression analysis suggested that lactate dehydrogenase (LDH), bone marrow plasma cell (BMPC), and SUVmax affected PFS. These factors were incorporated to construct a nomogram model for predicting PFS at 1 and 2 years in NDMM patients. The C-index and calibration curves of the nomogram exhibited good accuracy and consistency, and the DCA curves suggested that the model had good clinical utility.Conclusion: The PET/CT parameter SUVmax is closely related to the prognosis of myeloma patients. The nomogram constructed in this study based on PET/CT-related parameters and clinical indicators individually predicts the PFS rate of NDMM patients and enables further risk stratification of NDMM patients.

Abstract The quest for mechanoluminescence (ML) in zinc sulfide (ZnS) spans more than a century, initially sparked by observations of natural minerals. There has been a resurgence in research into ML materials in recent decades, driven by advances in optoelectronic technologies and a deeper understanding of their luminescent properties under mechanical stress. ZnS, in particular, has garnered attention owing to its remarkable ability to sustain luminescence after more than 100,000 mechanical stimulations, positioning it as a standout candidate for optoelectronic applications. In contrast to conventional photoluminescent and electroluminescent light sources, ZnS composite elastomers have emerged as flexible, stretchable self‐powered light sources with considerable practical implications. This review introduces the development history, ML mechanisms, prototype ML devices, ZnS‐based ML material preparation methods, and their diverse applications spanning environmental mechanical‐to‐optical energy conversion, E‐signatures, anti‐counterfeiting, wearable information sensing devices, advanced battery‐free displays, biomedical imaging, and optical fiber sensors for human–computer interactions, among others. By integrating insights from ML‐optics, mechanics, and flexible optoelectronics, and by summarizing pertinent perspectives on current scientific challenges, application technology hurdles, and potential solutions for emerging scientific frontiers, this review aims to furnish fundamental guidance and conceptual frameworks for the design, advancement, and cutting‐edge application of novel mechanoluminescent materials.

The orexin system regulates a variety of physiological functions, including the sleep-wake cycle, addiction, foraging behavior, stress and cognitive functioning. Orexin levels in central and peripheral are related to the pathogenesis of many diseases, most notably the narcolepsy, eating disorders, stress-related psychiatric disorders, and neurodegenerative diseases. Recently, it has been reported that the orexin system is distinctly sexually dimorphic, and is strongly associated with neuropsychiatric disorders. In this review, we analyzed advancements in the sex differences in the orexin system and their connection to psychoneurological conditions. Considering the scarcity of research in this domain, more research is imperative to reveal the underlying mechanisms.

Purpose: This study elucidates the relationship between similarity and ethnic psychological compatibility and its underlying psychological mechanisms. According to kin selection theory, similarity can promote ethnic psychological compatibility by enhancing psychological kinship and intergroup contact. Participants: and methods: A questionnaire survey was administered to 1523 participants from 25 ethnic groups in China. Data analysis was carried out via conditional process modelling. A multigroup comparison of mediation models between the ethnic majority and minorities was detected via the Stats Tools Package. Results: Our findings demonstrated that: (1) cultural and attitude similarity both showed a significant positive correlation with ethnic psychological compatibility; (2) psychological kinship and intergroup contact served as mediators in the relationship of attitude and cultural similarity with ethnic psychological compatibility and psychological kinship and intergroup contact were independent mediators, while psychological kinship–intergroup contact showed a significant serial mediation effect; (3) there were no significant differences in mediation effects between different ethnic groups. Conclusion: Our findings expand on kin selection theory and provide valuable paths for psychologically supporting ethnic psychological compatibility.

AimsMultiple myeloma (MM) remains a challenging condition to cure, with persistent drug resistance negating the benefits of treatment advancements. The unraveling complexities in programmed cell death (PCD), inclusive of apoptosis, autophagy, and ferroptosis, have highlighted novel therapeutic avenues. Our study focuses on deciphering how adapalene (ADA), a small molecule compound, accelerates the demise of MM cells via targeting their compensatory survival mechanisms.MethodsTo assess the impact of ADA on MM, we employed flow cytometry and trypan blue exclusion assays to determine cell viabilities across MM cell lines and primary patient samples post-treatment. To delineate ADA’s therapeutic targets and mechanisms, we conducted RNA sequencing (RNA-seq), gene set enrichment analysis (GSEA), molecular docking, and molecular dynamics simulations. We further designed pre-clinical trials emphasizing MM, exploring the efficacy of ADA as a standalone and in combination with bortezomib (BTZ).ResultsADA elicited a dose-responsive induction of MM cell death. Building upon ADA’s anti-MM capabilities as a single agent, we proposed that ADA-BTZ co-treatment might amplify this lethality. Indeed, ADA and BTZ together greatly potentiated MM cell death. ADA proved beneficial in restoring BTZ susceptibility in BTZ-resistant relapsed or refractory MM (RRMM) patient cells. Molecular simulations highlighted ADA’s high affinity (−9.17 kcal/mol) for CD138, with MM-GBSA revealing a binding free energy of −27.39 kcal/mol. Detailed interaction analyses indicated hydrogen-bonding of ADA with CD138 at the Asp35 and Gln34 residues. Additionally, ADA emerged as a versatile instigator of both ferroptosis and apoptosis in MM cells. Furthermore, ADA disrupted activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway triggered by BTZ, fostering cell death in BTZ-resistant MM subsets.ConclusionADA demonstrates a comprehensive capability to orchestrate MM cell death, exerting pronounced anti-MM activity while disrupting NF-κB-related drug resistance. ADA sensitization of MM cells to BTZ unravels its potential as a novel therapeutic drug for MM management.

The intestinal tract plays an important role in digestion and absorption, nutrient metabolism, and immune anti-stress. At the same time, the intestine is also the major site for pathogens and various harmful substances to invade. Probiotics, as living microbial agents, improve animal health by maintaining the microecological balance of the host's intestinal flora. To explore the protective effect of Clostridium butyricum (CB) on the gut, we investigated the changes in digestion, antioxidant, and gut microbiota in juvenile largemouth bass. The fish were fed with diets containing 0 (control, CB0), 4.3×108 (CB1), 7.5×108 (CB2), 1.5×109 (CB3), and 3.2×109 (CB4) CFU/kg Clostridium butyricum for 56 days. After 56 days of dietary supplementation with 4.3×108 and 3.2×109 CFU/kg of CB, significant growth promotion and feed utilization improvement were observed in largemouth bass (P < 0.05). The activities of digestive enzymes (trypsin, protease and amylase) and intestinal functional indicators (sodium-potassium ATP, γ-GT and CK) were significantly increased in the intestine of largemouth bass (P < 0.05). The contents of intestinal short-chain fatty acids (acetic acid, propionic acid, isobutyric acid, N-butyric acid and isovaleric acid) in largemouth bass were significantly increased (P < 0.05). CB significantly increased the activities of antioxidant enzymes (T-AOC, CAT, POD, GSH-Px and SOD) and decreased the content of MDA in the intestine of largemouth bass (P < 0.05). It was also observed that CB significantly increased the activities of immune-related markers lysozyme and alkaline phosphatase (P < 0.05). High-throughput sequencing of the 16 S rRNA gene in largemouth bass revealed a significant increase in gut microbial richness. KEGG pathway analysis showed that CB had significant effects on intestinal microbiota functions, such as nutrient metabolism and energy conversion. The results showed that CB could stimulate intestine to produce the organic product butyric acid, which was customized in the gut to enhance digestive performance, promote nutrient metabolism, and protect microbial homeostasis in the intestinal tract of largemouth bass. These results provide new insights into the protective effects of CB on the intestinal tract of aquatic animals.

Abstract With 75 known species, the freshwater fish genus Sinocyclocheilus is the largest cavefish radiation in the world and shows multiple adaptations for cave‐dwelling (stygomorphic adaptations), which include a range of traits such as eye degeneration (normal‐eyed, micro‐eyed and eyeless), depigmentation of skin, and in some species, the presence of “horns”. Their behavioural adaptations to subterranean environments, however, are poorly understood. Wall‐following (WF) behaviour, where an organism remains in close contact with the boundary demarcating its habitat when in the dark, is a peculiar behaviour observed in a wide range of animals and is enhanced in cave dwellers. Hence, we hypothesise that wall‐following is also present in Sinocyclocheilus, possibly enhanced in eyeless species compared to eye bearing (normal‐/micro‐eyed species). Using 13 species representative of Sinocyclocheilus radiation and eye morphs, we designed a series of assays, based on pre‐existing methods for Astyanax mexicanus behavioural experiments, to examine wall‐following behaviour under three conditions. Our results indicate that eyeless species exhibit significantly enhanced intensities of WF compared to normal‐eyed species, with micro‐eyed forms demonstrating intermediate intensities in the WF distance. Using a mtDNA based dated phylogeny (chronogram with four clades A–D), we traced the degree of WF of these forms to outline common patterns. We show that the intensity of WF behaviour is higher in the subterranean clades compared to clades dominated by normal‐eyed free‐living species. We also found that eyeless species are highly sensitive to vibrations, whereas normal‐eyed species are the least sensitive. Since WF behaviour is presented to some degree in all Sinocyclocheilus species, and given that these fishes evolved in the late Miocene, we identify this behaviour as being ancestral with WF enhancement related to cave occupation. Results from this diversification‐scale study of cavefish behaviour suggest that enhanced wall‐following behaviour may be a convergent trait across all stygomorphic lineages.

The electroplating industry is the main source of 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) pollution, which presents risks to human health and the environment. It is therefore crucial to develop effective 6:2 Cl-PFESA degradation techniques. Persulfate oxidation is a potential treatment method for 6:2 Cl-PFESA due to its outstanding oxidative degradability following the generation of the sulfate radical (SO4•−) and hydroxyl radical (•OH). It has proven difficult to acquire a full understanding of the reaction mechanism and formation of intermediate (IM) products through conventional experimental studies because they are costly and time-consuming. Therefore, a theoretical analysis method based on density functional theory (DFT) calculations was applied. The DFT results showed that electron transfer for the degradation of 6:2 Cl-PFESA could be initiated by the protonated sulfate radical (HSO4•, ΔG≠SET = 9.16 kcal/mol), rather than SO4•− (ΔG≠SET = 41.60 kcal/mol). After desulfonation, the reaction underwent stepwise decarboxylation cycles under the action of •OH, leading to the elimination of the CF2 units until there was complete mineralization into HCl, HF, and CO2. Furthermore, the IMs and the end products of 6:2 Cl-PFESA were evaluated using ECOSAR and TEST software. The low bioaccumulation of the short-chain IMs meant that they could be considered safe in terms of ecotoxicity and health effects. This research determined the theoretical and mechanistic basis of the effects of persulfate in the treatment of water containing 6:2 Cl-PFESA, and its structural analogues.

Abstract Lung adenocarcinoma (LUAD) is a prevalent form of non-small cell lung cancer with a rising incidence in recent years. Understanding the mutation characteristics of LUAD is crucial for effective treatment and prediction of this disease. Among the various mutations observed in LUAD, KRAS mutations are particularly common. Different subtypes of KRAS mutations can activate the Ras signaling pathway to varying degrees, potentially influencing the pathogenesis and prognosis of LUAD. This study aims to investigate the relationship between different KRAS mutation subtypes and the pathogenesis and prognosis of LUAD. A total of 63 clinical samples of LUAD were collected for this study. The samples were analyzed using targeted gene sequencing panels to obtain sequencing data. To complement the dataset, additional clinical and sequencing data were obtained from TCGA and MSK. The analysis revealed significantly higher Ki67 immunohistochemical scores in patients with missense mutations compared to controls. Moreover, the expression level of KRAS was found to be significantly correlated with Ki67 expression. Enrichment analysis indicated that KRAS missense mutations activated the SWEET_LUNG_CANCER_KRAS_DN and CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_2 pathways. Additionally, patients with KRAS missense mutations and high Ki67 IHC scores exhibited significantly higher tumor mutational burden levels compared to other groups, which suggests they are more likely to be responsive to ICIs. Based on the data from MSK and TCGA, it was observed that patients with KRAS missense mutations had shorter survival compared to controls, and Ki67 expression level could more accurately predict patient prognosis. In conclusion, when utilizing KRAS mutations as biomarkers for the treatment and prediction of LUAD, it is important to consider the specific KRAS mutant subtypes and Ki67 expression levels. These findings contribute to a better understanding of LUAD and have implications for personalized therapeutic approaches in the management of this disease.

Abstract Background Social distancing policies were of utmost importance during the early stages of the COVID-19 pandemic. These policies aimed to mitigate the severity of local outbreaks by altering public behavior. However, if the severity of the pandemic reduces, the impact of these policies on actual behavior may decrease. This study aims to examine, from a global perspective, whether the impact of social distancing policies on actual mobility is moderated by local pandemic severity and whether this moderating effect varies across cultural value contexts. Methods We combined multiple publicly available global datasets for structural equation model analysis. 17,513 rows of data from 57 countries included in all databases were analyzed. Multilevel moderated moderation models were constructed to test the hypotheses. Results More stringent policies in a region mean less regional mobility (β = -0.572, p

Computing-In-Memory (CIM) is widely applied in neural networks due to its unique capability to perform multiply-and-accumulate operations within a circuit array. This process directly obtains the current value through the product of voltage and conductance, accumulating it on the bit line, thus realizing storage and computing functionalities simultaneously within a single array. This significantly reduces the power consumption and time delay in data processing. Unfortunately, implementing general-purpose logic computations in large-scale memory arrays with CIM remains a challenge. This paper introduced a novel device concept, the programmable diode—a special type of memristor with a high switching window, ideally suited for memory arrays to reduce power consumption. A compact SPICE model was developed to enable circuit-level simulations in EDA tools. We also proposed a method to efficiently control the programmable diode for logic operations in memory arrays, and in this way, we constructed a parallel 8-bit full adder to verify the feasibility of the proposed method. Finally, based on the 8-bit full adder, we built a 5KB in-memory logic array capable of executing logic computations and simulated it using EDA tools. The simulation results demonstrated that the 5KB in-memory logic array can perform fundamental Boolean logic and arithmetic operations with high repeatability and parallelism, perfectly realizing the functionality of in-memory logic computation. Our work can provide a feasible scheme for realizing large-scale general logic computation systems based on CIM.

Abstract Background Primary aldosteronism (P.A.) is the most common form of secondary hypertension, accounting for 5% of hypertensive patients and 17–23% of patients with resistant hypertension. Compared to primary hypertension, P.A. is more prone to cause severe organ damage and even early death. Adrenal venous sampling (AVS) is a practical confirmatory test for subtyping aldosterone-producing adenoma and bilateral adrenal hyperplasia, helping physicians to make an accurate decision between surgery or medication. According to guidelines, supine in bed before AVS is recommended for a desirable result of AVS. However, investigations about the most optimal preoperative supine time before AVS are lacking. Methods/design This is a multi-center prospective randomized controlled study. One hundred twenty patients diagnosed as P.A. and willing for AVS examination will be included. Participants will be randomly allocated to a 15-min supine time group or 2-h supine time group. The primary outcome is the degree of biochemical remission (serum potassium and orthostatic ARR). The secondary outcomes are degrees of clinical remission (blood pressure, type and dose of antihypertensive drugs), the technical success rate, and the adverse event of AVS (selective index ≥ 2 is considered successful surgery without corticotropin stimulation). Discussion P.A. is an intractable public health problem, and many techniques including AVS have been developed to identify this disease correctly. This study will help to understand whether the length of preoperative supine time would affect the diagnostic efficacy of AVS and thus help to formulate a more reasonable AVS procedure. Trial registration ClinicalTrials.gov NCT05658705. Registered on 10 September 2022.

In this work, an accurate temperature-dependent drain current $I_{\mathrm { D}}$ fluctuation model valid from 10 to 300 K was proposed for 18 nm ultra-thin body and buried oxide (UTBB) n-channel field effect transistors (n-FETs). The temperature dependence of $I_{\mathrm { D}}$ fluctuation was characterized and investigated from 300 K down to 10 K. In moderate inversion mode, $I_{\mathrm { D}}$ fluctuation is more severe at sub-100 K while in the strong inversion mode, it still can be overshadowed by the charge screening effect. Cryogenic virtual source (CVS) device model was used to extract and analyze the carrier density and mobility which are used in the current fluctuation model. The current fluctuation model was experimentally verified under different inversion conditions, showing it can be used to analyze and optimize the flicker noise in the low temperature (LT) circuit applications.

Abstract Through the uniaxial compression test of double parallel fissured layered rock mass, the mechanical properties of layered rock mass with different fissure dip angle, and the characteristics of acoustic emission (AE) parameters in the process of fracture are studied. The influence of fissure dip angle on the progressive damage, and macroscopic fracture of layered rock mass is explored. The fracture mode, local stress variation characteristics, and stress field evolution law of fissured layered rock mass are analyzed from a mesoscopic point of view. The results show that with the increase of the fissure dip angle α, the peak strength and the elastic modulus of the layered rock mass decrease first and then increase. The low frequency-high amplitude (LF-HA) signals of AE all appear in the crack propagation stage. With the increase of fissure dip angle α, the LF-HA signal ratio increases first, then decreases and then increases, and shows significant stage characteristics. The cracks are mainly generated around the relatively low strength A rock and prefabricated fissures, and all pass through the interface between A rock and B rock. Eight types mesoscopic displacement field models are found, and the final failure mode of the model is tensile-shear mixed failure. The upper and lower regions of the fissure are tensile stress areas, while the left and right regions are compressive shear stress areas, which are distributed in a “butterfly” type. The stress difference at the fissure tip is negatively correlated with the mechanical parameters of the layered rock mass.

Abstract Background Parkinson’s disease (PD), a chronic and severe neurodegenerative disease, is pathologically characterized by the selective loss of nigrostriatal dopaminergic neurons. Dopamine (DA), the neurotransmitter produced by dopaminergic neurons, and its metabolites can covalently modify proteins, and dysregulation of this process has been implicated in neuronal loss in PD. However, much remains unknown about the protein targets. Methods In the present work, we designed and synthesized a dopamine probe (DA-P) to screen and identify the potential protein targets of DA using activity-based protein profiling (ABPP) technology in combination with liquid chromatography-tandem mass spectrometry (LC–MS/MS). In situ pull-down assays, cellular thermal shift assays (CETSAs) and immunofluorescence were performed to confirm the DA modifications on these hits. To investigate the effects of DA modifications, we measured the enzymatic activities of these target proteins, evaluated glycolytic stress and mitochondrial respiration by Seahorse tests, and systematically analyzed the changes in metabolites with unbiased LC–MS/MS-based non-targeted metabolomics profiling. Results We successfully identified three glycolytic proteins, aldolase A, α-enolase and pyruvate kinase M2 (PKM2), as the binding partners of DA. DA bound to Glu166 of α-enolase, Cys49 and Cys424 of PKM2, and Lys230 of aldolase A, inhibiting the enzymatic activities of α-enolase and PKM2 and thereby impairing ATP synthesis, resulting in mitochondrial dysfunction. Conclusions Recent research has revealed that enhancing glycolysis can offer protection against PD. The present study identified that the glycolytic pathway is vulnerable to disruption by DA, suggesting a promising avenue for potential therapeutic interventions. Safeguarding glycolysis against DA-related disruption could be a potential therapeutic intervention for PD.

The exploitation of shear dilatation behavior exhibited by natural rock fractures can serve as an effective strategy for stimulating reservoirs in the enhanced geothermal systems (EGS). However, few studies have considered the shear dilatation characteristics of rock fractures treated by real-time high temperature. Firstly, the self-developed Mechanical(M)-Thermal(T) coupling shear test cell and the MTS816.01 rock shear test system were used to carry out the direct shear tests of granite fractures. The M-T coupling effect on granite's physical properties such as cohesion, the mechanical properties such as shear strength, and strain energy characteristics such as dissipated strain energies were analyzed. On these Base, the shear dilatation mechanism of granite fractures treated by real-time high temperature is further revealed. Subsequently, based on the dynamic changes in the area degradation degree of granite fractures, the shear dilatation model of rock fractures treated by real-time high temperature were improved and verified. The results reveal that the M-T coupling effect can considerably impair the shear dilatation behavior of granite fractures. The temperature undermines the shear dilatation behavior of granite fractures by negatively affecting their physical and mechanical properties, while the normal stress deteriorates their shear dilatation behavior by constraining the normal displacement of the rock fractures. The modified shear dilatation model of rock fractures exhibits high accuracy and can accurately represent the shear dilatation behavior of rock fractures under M-T coupling effects. The novel insights provided in this paper contribute to a more comprehensive understanding of the wellbore stability and permeability improvement mechanism of EGS.

Abstract The use of titanium implants as fixed supports following fractures in patients with OP can often result in sterile loosening and poor osseointegration. Oxidative stress has been shown to play a particularly important role in this process. While TSA has been reported to facilitate in vivo osteogenesis, the underlying mechanisms remain to be clarified. It also remains unclear whether TSA can improve the osseointegration of titanium implants. This study investigated whether TSA could enhance the osseointegration of titanium rods by activating AKT/Nrf2 pathway signaling, thereby suppressing oxidative stress. MC3T3-E1 cells treated with CCCP to induce oxidative stress served as an in vitro model, while an OVX-induced OP rat model was employed for in vivo analysis of titanium rod implantation. In vitro, TSA treatment of CCCP-treated MC3T3-E1 cells resulted in the upregulation of osteogenic proteins together with increased AKT, total Nrf2, nuclear Nrf2, HO-1, and NQO1 expression, enhanced mitochondrial functionality, and decreased oxidative damage. Notably, the PI3K/AKT inhibitor LY294002 reversed these effects. In vivo, TSA effectively enhanced the microstructural characteristics of distal femur trabecular bone, increased BMSCs mineralization capacity, promoted bone formation, and improved the binding of titanium implants to the surrounding tissue. Finally, our results showed that TSA could reverse oxidative stress-induced cell damage while promoting bone healing and improving titanium rods' osseointegration through AKT/Nrf2 pathway activation.

Background Mechanical ventilation, particularly one-lung ventilation (OLV), can cause pulmonary dysfunction. This meta-analysis assessed the effects of dexmedetomidine on the pulmonary function of patients receiving OLV. Methods The Embase, PubMed, MEDLINE, Cochrane Library, ClinicalTrials.gov, and Chinese Clinical Trial Registry databases were systematically searched. The primary outcome was oxygenation index (OI). Other outcomes including the incidence of postoperative complications were assessed. Results Fourteen randomized controlled trials involving 845 patients were included in this meta-analysis. Dexmedetomidine improved the OI at 30 (mean difference [MD]: 40.49, 95% CI [10.21, 70.78]), 60 (MD: 60.86, 95% CI [35.81, 85.92]), and 90 min (MD: 55, 95% CI [34.89, 75.11]) after OLV and after surgery (MD: 28.98, 95% CI [17.94, 40.0]) and improved lung compliance 90 min after OLV (MD: 3.62, 95% CI [1.7, 5.53]). Additionally, dexmedetomidine reduced the incidence of postoperative pulmonary complications (odds ratio: 0.44, 95% CI [0.24, 0.82]) and length of hospital stay (MD: −0.99, 95% CI [−1.25, −0.73]); decreased tumor necrosis factor-α, interleukin (IL)-6, IL-8, and malondialdehyde levels; and increased superoxide dismutase levels. However, only the results for the OI and IL-6 levels were confirmed by the sensitivity and trial sequential analyses. Conclusions Dexmedetomidine improves oxygenation in patients receiving OLV and may additionally decrease the incidence of postoperative pulmonary complications and shorten the length of hospital stay, which may be related to associated improvements in lung compliance, anti-inflammatory effects, and regulation of oxidative stress reactions. However, robust evidence is required to confirm these conclusions.

The two directly substituted pentazoles, N5NH2 and N5COOH, were designed to theoretically study the relationships between substituents, aromaticity and kinetic stability thereof. Analysis shows their kinetic stability order described by the energy separations between the highest occupied molecule orbital (HOMO) and the lowest unoccupied molecule orbital (LUMO), viz. HOMO-LUMO gap, is line with the aromaticity orders obtained from nucleus-independent chemical shift (NICS), harmonic oscillator measure of aromaticity (HOMA), Bird aromaticity index (I) and isochemical shielding surface (ICSS), which is N5NH2 > N5COOH. But this order is contrary to the heat stability order according to Ref [1] The inconsistency between heat stability and kinetic stability reveals the fact that stability of compounds is a complex character and different according to the compound property of the study. The consistency of kinetic stability order with the aromaticity orders described by NICS, NICSSZZ, HOMA, I and ICSS indicates these widely accepted methods for aromaticity estimating are reliable for the two given compounds. As for the effect on aromaticity of pentazole ring from substituent, electron-donating substituent have stronger effect than electron-withdrawing substituent.

Underground mining involves numerous risks, such as collapses, gas leaks, and explosions, posing significant threats to worker safety. In this work, we develop an indoor localization system that uses Bluetooth for coarse positioning and ultrasonic arrays for precision calibration. This system is particularly useful for automated mining operations in underground environments where satellite positioning signals are unavailable. The indoor localization system consists of ultrasonic receiver arrays and an improved multi-transmitter-multi-receiver algorithm, enabling accurate localization within the mining environment. Geometric Dilution of Precision (GDOP) analysis is incorporated to optimize the network layout, and an inertial navigation module is integrated to track the posture of moving objects, enabling precise trajectory determination over large areas, such as coal mines. In the experiment, three traditional methods were compared, and the proposed tracking approach demonstrated a positioning accuracy within 10 cm, reducing error by 20% compared to conventional techniques. This high-precision indoor localization method proves beneficial for underground mining applications.

Cyberspace has evolved into a hub for the dissemination of large amounts of tendentious information, posing significant challenges to the role of mainstream value information. As netizens’ are the main recipients of tendentious information, their personal cognition, attitude, and behavioral ability affect their willingness to re-disseminate information, making them an inalienable force in the promotion of information dissemination. Exploring the dissemination mechanism of tendentious information in cyberspace can help to understand the law of information dissemination and predict the trend of information diffusion, which is of great significance to maintaining information security and social stability. However, the existing research has overlooked the potential influence of the attribute characteristics of information in terms of content, and has failed to overcome the methodological constraints of traditional statistical analysis to accurately describe the variables and mechanisms influencing the dissemination of tendentious information at the cognitive level. Therefore, using structural equation modeling, we propose a research index system based on the Theory of Planned Behavior and the characteristics of tendentious information. To this end, confirmatory factor and model fitting analyses were conducted to develop a tendentious information dissemination mechanism model, which we validated through testing and comparative experiments. Path analysis revealed that Attitude Toward Dissemination, Information Dissemination Intention, and Information Dissemination Behavior are the main links in the information dissemination process. Moreover, Information Sentiment Orientation was found to strongly promote the dissemination of tendentious information, while Subject Norm of Dissemination had a minor inhibiting effect.

Bandsaw blades are typical band-shaped cutting tools that are characterized by their low stiffness and micro-level cutting depth, resulting in distinct wear mechanisms compared to rigid cutting tools. In this study, the wear curve and wear mechanisms of the bandsaw tooth during the bandsawing of Cr12MoV cold-working steel were investigated. The tool life was divided into two stages: a rapid wear stage (Stage I) and a homogeneous wear stage (Stage II). In Stage I, the wear was dominated by chipping, although multiple wear mechanisms were found due to their relatively low manufacturing accuracy compared to rigid cutting tools, which resulted in remarkable differences in the cutting depth of each tooth. In Stage II, abrasive and adhesive wear were the primary wear mechanisms instead of chipping, which was related to the microstructure of Cr12MoV. Furthermore, methods for increasing bandsaw performance were proposed, based on the tooth wear mechanisms.

Bluetooth devices have been widely used for pedestrian positioning and navigation in complex indoor scenes. Bluetooth beacons are scattered throughout the entire indoor walkable area containing stairwells, and pedestrian positioning can be obtained by the received Bluetooth packets. However, the positioning performance is sharply deteriorated by the multipath effects originating from indoor clutter and walls. In this work, an ultra-wideband (UWB)-assisted Bluetooth acquisition of signal strength value method is proposed for the construction of a Bluetooth fingerprint library, and a multi-frame fusion particle filtering approach is proposed for indoor pedestrian localization for online matching. First, a polynomial regression model is developed to fit the relationship between signal strength and location. Then, particle filtering is utilized to continuously update the hypothetical location and combine the data from multiple frames before and after to attenuate the interference generated by the multipath. Finally, the position corresponding to the maximum likelihood probability of the multi-frame signal is used to obtain a more accurate position estimation with an average error as low as 70 cm.

The evaluation of the wave-induced pore pressures around the offshore piles has attracted great attentions among coastal engineers, because they have been commonly used as foundations of numerous marine infrastructures. This paper presents comparative studies of the random wave-induced transient seabed response around single and double piles in a sandy seabed through a series of wave flume experiments. The influences of relative spacing ratios, wave incidence angles, and front pile diameters under different random wave parameters on oscillatory pore pressures in the vicinity of double piles are examined. In addition, variations in wave profiles and dynamic wave pressures surrounding single and double piles are quantitatively analyzed. Based on the experimental results, the following conclusions can be drawn: (1) under the influence of random waves, the wave profiles around the double piles exhibit obvious irregularity and nonlinearity; (2) the shielding effect existing in the tandem piles results in lower dynamic wave pressures around the rear pile compared to the front pile; (3) the pore pressures on the front surface of the double piles decrease with increasing soil depth, with a decreasing attenuation rate at each layer; (4) when the relative spacing ratio G/D2=3, the group-pile effect weakens, leading to an increase in the pore pressures around the rear pile, approaching the results of a single pile under conditions of lower significant wave heights or periods; (5) the intense disturbance effect caused by large wave incidence angles exacerbates the pore pressure response around the double piles; (6) when the diameter of the front pile in the tandem piles increases, it enhances the shielding effect, thus suppressing the seabed response around the rear pile. In contrast, it causes an increase in the wave surface around the double piles, exacerbating the pore pressure response in the seabed. The latter effect becomes more pronounced when the significant wave height is larger.