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Hongping Ge,1,2 Na Zhang,1 Xinru Chen,1,3 Meiyan Wang,1 Tianhui Ye1,3 1Department of Dermatology, Jinhua Municipal Central Hospital (Affiliated Jinhua Hospital, Zhejiang University School of Medicine), Jinhua City, Zhejiang Province, People’s Republic of China; 2Department of Dermatology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang; 3Department of Dermatology, Zhejiang Chinese Medical University, Hangzhou, ZhejiangCorrespondence: Na Zhang, Email sallyzhang1986@163.comBackground: Dyschromatosis symmetrica hereditaria (DSH) is a rare genetic skin condition characterized by pigmented macules on the hands, feet, and sometimes the face. The ADAR1 gene is responsible for this autosomal dominant disorder.Objective: This study aimed to analyze a three-generation Chinese family with DSH, identify a novel ADAR1 gene mutation, and conduct a comprehensive literature review of Chinese DSH families to enhance understanding of the genetic basis and clinical manifestations.Methods: Clinical reports, mutation analysis, and literature reviews were conducted. A literature search was performed using PubMed.Results: A novel heterozygous nonsense mutation, c.763C>T (p.Q255X), in the ADAR1 gene was identified in the proband and five other affected individuals. Literature review findings revealed prevalent mutation sites and clinical data in Chinese DSH families over the past two decades.Limitations: The number of databases searched was limited, and the treatment outcomes for patients were not deemed satisfactory.Conclusion: This study provides valuable insights into the genetic basis and clinical features of DSH in Chinese families, shedding light on prevalent mutation sites and clinical data. Further research is needed to explore the relationship between gene mutations and clinical phenotypes and advance therapeutic interventions for DSH.Keywords: dyschromatosis symmetrica hereditaria, ADAR1 gene, mutation analysis

A novel equiatomic refractory AlNbTiVY high-entropy alloy containing rare earth elements was fabricated by vacuum arc melting. AlNbTiVY alloy possesses a dual-phase structure, consisting of a B2 ordered matrix and an Orthorhombic structured Y2Al second phase. The alloy has a dendritic microstructure with a density of only 5.18 g/cm3. As the testing temperature increases, the compressive yield strength of the alloy gradually decreases from 1104 MPa at room temperature to 321 MPa at 800 °C, with improved deformability and no fracture occurring in the 800 °C environment. Based on the insights of physics, a simple calculation was conducted on the temperature-dependent model of the alloy, and the theoretical application temperature of the alloy was predicted to exceed 600 °C.

Ningkang Li,1,2,&ast; Xia Qi,2,&ast; Jiamin Bao,2 Yang Gu,1,2 Xiaohong Zhou,1,2 Ting Wang,2 Ningxiang Jiang,3 Yun Wang,2 Qingshan Ye1,2 1Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2Department of Anesthesiology, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 3Department of Breast Surgery, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingshan Ye; Yun Wang, Department of Anesthesiology, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia, 750002, People’s Republic of China, Email yeqingshan@hotmail.com; wangyun10483@126.comPurpose: Minimally invasive rotary resection (MIRR) is crucial for diagnosing and treating breast tumors, but the optimal intravenous anesthesia regimen is unclear. Esketamine, an NMDA receptor antagonist with anesthetic, analgesic, and sympathomimetic properties, may provide an ideal adjunct to propofol sedation. This study aims to compare the safety and efficacy of esketamine versus sufentanil as adjuncts to propofol for analgesia and sedation during breast MIRR.Patients and Methods: A total of 90 patients undergoing elective breast MIRR were randomly assigned to receive either sufentanil-propofol or esketamine-propofol for analgesia and sedation. The primary outcome was the occurrence of hypoxia (SpO2 < 92% for > 10s or exhibiting a persistent downward trajectory). Other outcomes included incidence of subclinical respiratory depression (92% ≤ SpO2 < 95% for > 10s), number of airway interventions, awakening time, satisfaction scores, postoperative exhaust time, hemodynamic parameters, and side events.Results: Finally, 41 patients were assigned to the sufentanil group and 40 to the esketamine group. The occurrence of hypoxia was significantly lower in the esketamine group (17.5%) than in the sufentanil group (39%) (P = 0.032). Subclinical respiratory depression occurred in 32.5% of the esketamine group and 56.1% of the sufentanil group (P = 0.033). The sufentanil group required more airway interventions than the esketamine group (P = 0.032), and patients in the sufentanil group experiencing hypoxia received more mask-assisted ventilation (P = 0.029). Hemodynamic stability was better in the esketamine group. No significant differences were observed in awakening time, satisfaction score, postoperative exhaust time, or side events between groups.Conclusion: Esketamine-propofol anesthesia significantly reduces the risk of hypoxia (SpO2 < 92%) compared to sufentanil-propofol, while maintaining similar awakening time, satisfaction, postoperative exhaust time, and side events. Its hemodynamic advantages make it valuable for clinical use, especially in procedures requiring respiratory and hemodynamic stability.Keywords: esketamine, hypoxia, respiratory depression, minimally invasive rotary resection, breast tumor

Hong Chen,&ast; Xie Wang,&ast; Nian Peng, Yue Pu, Hao Ye, Yu Gui, Rui Zhang, Juan Zhang Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, 230031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Zhang, Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, People’s Republic of China, Email zhangdoumi2019@163.comBackground: Wilson’s disease (WD) is a hereditary disorder characterized by an abnormality in copper metabolism. Liver fibrosis, and potentially cirrhosis, induced by copper accumulation are critical factors in the pathogenesis of WD. CircRNAs exhibit high stability and play crucial roles in numerous biological processes.Methods: RNA-seq technology was employed to conduct transcriptome sequencing of the liver from 12 homozygous (TX) mice in the model group (NL group) and 12 wild-type (WT) mice in the control group (N group). Differentially expressed circular RNAs (DE-circRNAs) were identified, and following GO and KEGG analysis, a competitive endogenous RNA (ceRNA) regulatory network was constructed. The identified DE-circRNAs were then randomly validated using RT-qPCR.Results: Utilizing RNA sequencing (RNA-seq), the study identified 54 DE-circRNAs in TX-j mice with WD-induced liver fibrosis model, among which 19 were up-regulated and 35 were down-regulated. GO analysis revealed multiple biological processes, including single-organism process, cellular process, and metabolic process. Further pathway identification using KEGG implicated several pathways, including the HIF-1, PI3K-Akt, AMPK, FoxO, signaling pathway regulating pluripotency of stem cells, phospholipase D, mTOR, Ras, cGMP-PKG, and MAPK signaling pathway, among others. A ceRNA regulatory network was constructed with 20 circRNAs, 7 miRNAs, and 75 mRNAs as crucial core components. Additionally, RT-qPCR validation was performed on randomly selected DE-circRNAs, yielding consistent results (P< 0.05).Conclusion: The findings provide a significant molecular biology foundation for understanding the pathogenesis of liver fibrosis in WD and offer new insights for exploring potential diagnostic and therapeutic targets.Keywords: circRNA, circRNA-miRNA-mRNA, ceRNA, Wilson’s disease, liver fibrosis

Ecological protection and restoration of territorial space is a national strategy aimed at safeguarding China's ecological security and enhancing people's well-being in the new era of ecological civilization. Establishing a legal framework for ecological protection and restoration of territorial space is a key strategic requirement for China to build the "multiple pillars" of ecological civilization. However, the legal provisions related to ecological protection and restoration are currently dispersed across various environmental laws and basic environmental legislation, making it difficult to provide robust support for the construction of a comprehensive legal system for ecological protection and restoration of territorial space. This study employs a textual analysis to systematically review the history of China's ecological protection and restoration legislation since 1978, tracing the evolution of relevant environmental laws, revealing the legislative foundations for the protection and restoration of national land space, and offering critical insights and references for building a legal framework that promotes integrated protection and systematic governance of mountains, waters, forests, fields, lakes, grasses, and sands in the new era. The evolution of legal themes related to ecological protection and restoration of territorial space in China has undergone three stages: natural resource management and utilization (1978‒2011), single-element protection (2012‒2017), and barrier zone ecological protection and restoration (2018‒2023), marking three levels of transformation. From the perspective of legislative objectives, the focus has shifted from legislation concerning individual natural resources elements, such as mountains, water, forests, grasses, and seas, to comprehensive legislation targeting key regional ecosystems. In terms of legislative goals, the shift has been from single-element governance aimed at singular objectives to multi-objective, synergistic protection and restoration of mountains, water, forests, fields, lakes, grasses, sands, and more, through an integrated approach. Additionally, the legislative framework has transitioned from managing natural resources to managing integrated ecosystems. These changes and innovations have laid a foundation for China to establish a legal system for ecological protection and restoration of territorial space, focused on integrated protection and systematic governance of mountains, water, forests, fields, lakes, grasses, and sands in the new era. However, challenges remain, such as the absence of legal norms to implement the new concepts and approaches, unclear departmental responsibilities, and insufficient public participation mechanisms. Moving forward, it is essential to fully implement the ecosystem approach, develop a management system with centralized jurisdiction, joint coordination, and step-by-step refinement centered on the "two unified" responsibilities of the natural resources departments, and deepen legislation to enhance public participation. Additionally, leveraging the combined expertise of multiple disciplines and fields will support legislative research and practical exploration, leading to the comprehensive establishment of a legal system for the ecological protection and restoration of territorial space.

Abstract Background Total en bloc spondylectomy (TES) is a recognized surgical approach for managing spinal tumors. With advancements in three-dimensional (3D) printing technology, the use of 3D-printed prosthetics for vertebral reconstruction post-tumor resection has gained traction. However, research on the clinical implications of these prosthetics remains limited. Methods This retrospective study evaluated patients who underwent TES for primary and metastatic thoracolumbar tumors at the Department of Spinal Surgery, Tianjin Hospital, between October 2017 and September 2020. These patients received anterior reconstruction with 3D-printed artificial vertebral bodies. Results 14 patients completed the surgery, with intraoperative blood loss ranging from 1,400 to 4,200 ml (mean 2,767 ± 790 ml) and operative duration between 240 and 520 min (mean 382 ± 75.9 min). The follow-up period extended from 7 to 43 months, with an average of 19.9 ± 9.5 months. Standardized prefabricated prosthetics were utilized in nine patients, while five received customized prosthetics. Throughout the follow-up, there were no reports of posterior connecting rod, 3D-printed prosthetic, or pedicle screw failures. Notably, one patient presented with significant prosthetic subsidence resulting in screw loosening, and three cases of prosthetic subsidence were observed. Conclusion The incorporation of 3D-printed prosthetics in TES procedures yielded favorable clinical outcomes. Further research is warranted to optimize these prosthetics for enhanced postoperative stability and patient-specific applications.

Abstract Multiple myeloma (MM) is an incurable disease characterized by the abnormal expansion of plasma cells in the bone marrow (BM). Numerous studies have shown that BM tumor cells can influence the tumor microenvironment (TME) through communication with extracellular vesicle circular RNAs (circRNAs), a type of noncoding RNA. Our study revealed that a circular RNA, circRFWD2 (hsa_circ_0015361), is expressed by MM cells and translated into a new protein, circRFWD2_369aa. We found that elevated levels of circRFWD2_369aa in MM peripheral blood samples were closely associated with poor outcomes in MM patients. Further investigation revealed that circRFWD2 promoted the degradation of p27 through the ubiquitination pathway, leading to increased proliferation of MM cells. We also confirmed the interaction between circRFWD2 and its downstream genes DDB1 and CUL4A, indicating that circRFWD2 could form an E3 ligase complex with other genes to mediate the ubiquitination of p27. Notably, the protein translated by a circular RNA of RFWD2 can also function as an E3 ligase. Our study highlights the potential of circRFWD2 as a biomarker for MM, which may improve the sensitivity and specificity of diagnosis and efficacy analyses.

Abstract The aim of this study is to investigate the correlation between soft drusen and the likelihood of mortality from all causes and specific ailments within a representative United States population. This cohort study encompassed 4497 individuals from the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES) cycles, and followed for survival to December 31, 2019. Data on soft drusen were obtained from fundus images. Survey-weighted Cox regression models were utilized to evaluate the hazard of soft drusen incidence and mortality. After a median follow-up of 12.33 (11.33, 12.58) years, 1014 (22.5%) patients died from all causes. Overall, individuals with soft drusen exhibited an increased risk for all-cause mortality (HR 1.41; 95% CI 1.22 to 1.64), cardiovascular disease (CVD)-related death (HR 1.53; 95% CI 1.15 to 2.04), and mortality from other causes (HR 1.48; 95% CI 1.20 to 1.83). Further stratified analysis revealed that the mortality rates were heightened in participants who had distinct soft drusen or both types of soft drusen, as well as those with soft drusen measuring 500 μm or more in diameter. The investigation revealed that soft drusen was linked to all-cause mortality, CVD mortality, and mortality resulting from non-cardiovascular and non-cancerous conditions, indicating that soft drusen may symbolize frailty and aging processes.

Abstract On the basis of the law of conservation of energy, the three stages of rock creep are analyzed. The reasons for the difficulty in studying the accelerated creep stage of rocks using the traditional creep model are expounded. The triaxial creep deformation law and critical point parameter values of rocks are obtained by carrying out rock creep tests under different confining pressures. Based on strain energy theory, the law of conservation of energy, and Perzyna viscoplastic theory, a creep constitutive model, which can describe the whole process of primary creep, steady-state creep, and accelerated creep, is established. Results show that the model can well reflect the creep characteristics of rocks, especially when the load of rocks is greater than the long-term strength. It has an obvious effect on highlighting the accelerated creep stage of rocks. The fitting degree of the creep model curve and test curve is considerably greater than that of the Nishihara model curve and test curve. The model not only describes the whole process of rock primary creep, steady-state creep, and accelerated creep thoroughly but also compensates for the shortcomings of traditional models in describing accelerated creep. This model can provide a theoretical basis for further revealing the objective law of rock creep.

Abstract Objectives To explore the impact of hepatic steatosis measured by MRI-proton density fat fraction (MRI-PDFF) on liver stiffness measurement (LSM) value and its diagnostic performance for staging liver fibrosis in patients with chronic hepatitis B (CHB). Methods A total of 914 patients with CHB who underwent liver biopsy and MRI-PDFF were retrospectively reviewed. The influence of MRI-PDFF on LSM value was assessed using univariate and multivariate linear analyses. To assess the influence of liver steatosis on the diagnostic performance of LSM, a series of ROC analyses were performed and compared by stratifying patients into non-steatosis (PDFF

Abstract Advanced biofabrication techniques can create tissue-like constructs that can be applied for reconstructive surgery or as in vitro three-dimensional (3D) models for disease modeling and drug screening. While various biofabrication techniques have recently been widely reviewed in the literature, acoustics-based technologies still need to be explored. The rapidly increasing number of publications in the past two decades exploring the application of acoustic technologies highlights the tremendous potential of these technologies. In this review, we contend that acoustics-based methods can address many limitations inherent in other biofabrication techniques due to their unique advantages: noncontact manipulation, biocompatibility, deep tissue penetrability, versatility, precision in-scaffold control, high-throughput capabilities, and the ability to assemble multilayered structures. We discuss the mechanisms by which acoustics directly dictate cell assembly across various biostructures and examine how the advent of novel acoustic technologies, along with their integration with traditional methods, offers innovative solutions for enhancing the functionality of organoids. Acoustic technologies are poised to address fundamental challenges in biofabrication and tissue engineering and show promise for advancing the field in the coming years.

Abstract Fungal communities inhabiting plant tissues are complex systems of inter-species interactions, consisting of both the “abundant biosphere” and “rare biosphere”. However, the composition, assembly, and stability of these subcommunities, as well as their contributions to productivity remain unclear. In this study, the taxonomic and functional composition, co-occurrence, and ecological assembly of abundant and rare fungal subcommunities in different tissues of three Panax species were investigated. Abundant subcommunities were dominated by potential plant pathogens belonging to Microbotryomycetes, while saprotrophic fungi like Agaricomycetes and Mortierellomycetes were more prevalent in rare subcommunities. The rare taxa played a central role in upholding the stability of the fungal networks as driven by Dothideomycetes and Sordariomycetes. Homogeneous selection played a larger role in the assembly of abundant fungal subcommunities compared to the rare counterparts, which was more dominated by stochastically ecological drift in all plant species. Rare biospheres played a larger role in the accumulation of saponin compared to their abundant counterparts, especially in the leaf endosphere, which was mainly affected by environmental factors (Mg, pH, OC, and etc.). Furthermore, we found that rare species belonging to unidentified saprotrophs were associated with saponin formation. This study provides hypotheses for future experiments to understand mechanisms accounting for the variations in the composition and function of rare fungal subcommunities across different Panax species.

Abstract We have previously found that the DAPK-DDX20 signaling axis exerts an anti-cancer activity in hepatocellular carcinoma (HCC) by inhibiting the GTPase activity of CDC42, thereby reducing the invasive and migratory capabilities of cancer cells without affecting cell proliferation. DDX20 serves as an intermediate protein regulated by DAPK in the control of CDC42. Specifically, DAPK enhances DDX20 protein levels by suppressing DDX20 degradation. However, the mechanism underlying DAPK regulation of DDX20 remains unclear. In the current study, we discovered that DDX20 is degraded through the ubiquitin–proteasome pathway and identified TRIM25 as the E3 ubiquitin ligase of DDX20. TRIM25 mediates the proteasomal degradation of DDX20 by binding to, and ubiquitinating the 1-244 amino acid region of DDX20. Moreover, DAPK interacts with this 1-244 segment of DDX20, inhibiting its ubiquitination and enhancing its stability, despite the lack of direct physical interaction between DAPK and the 1-244 region of DDX20. Remarkably, DAPK, TRIM25, and DDX20 form a ternary protein complex in cells, and knockdown of TRIM25 leads to a reduction in the cellular levels of the binary DAPK-DDX20 complex, suggesting that TRIM25 acts as an important intermediate protein linking DAPK and DDX20. TRIM25 functions as an oncogene in liver cancer, as shRNA-mediated silencing of TRIM25 inhibits cell migration and invasion. Therefore, these novel findings of the interaction among these three proteins not only enhances our knowledge of the downstream molecular network of DAPK and its possible role in the development of HCC, but also provides potential druggable targets for the future development of novel anticancer drug therapeutics.

Abstract CT is crucial for diagnosing chest diseases, with image quality affected by spatial resolution. Thick-slice CT remains prevalent in practice due to cost considerations, yet its coarse spatial resolution may hinder accurate diagnoses. Our multicenter study develops a deep learning synthetic model with Convolutional-Transformer hybrid encoder-decoder architecture for generating thin-slice CT from thick-slice CT on a single center (1576 participants) and access the synthetic CT on three cross-regional centers (1228 participants). The qualitative image quality of synthetic and real thin-slice CT is comparable (p = 0.16). Four radiologists’ accuracy in diagnosing community-acquired pneumonia using synthetic thin-slice CT surpasses thick-slice CT (p 0.99). For lung nodule detection, sensitivity with thin-slice CT outperforms thick-slice CT (p 0.05). These findings indicate the potential of our model to generate high-quality synthetic thin-slice CT as a practical alternative when real thin-slice CT is preferred but unavailable.

Abstract Background Air pollution is a major environmental risk factor. Hypertension is one of the most important modifiable risk factors for cardiovascular diseases. However, few studies have evaluated the impact of exposure to ambient air pollution on hypertension hospitalizations. Objective This study aims to explore the correlation between exposure to air pollution and hospital admissions for hypertension, to evaluate the short-term effects of air pollution on hypertension hospitalizations and its lag effects. Methods We collected air pollution concentration and hypertension hospitalization data from 2013 to 2020. Distributed lag non-linear models were employed to assess the impact of air pollution on hypertension hospitalizations in Lanzhou City. We also performed subgroup analyses and sensitivity analyses. Results A total of 47,884 cases of hypertension hospitalizations were included. Short-term exposure to NO2 and CO increased the risk of hypertension hospitalization. For each 10 µg/m3 increase in NO2 and each 1 mg/m3 increase in CO, the relative risk (RR) for hypertension hospitalization were highest at lag0-3 (RR: 1.0427; 95% CI: 1.0196, 1.0663) and lag3 (RR: 1.0986; 95% CI: 1.0350, 1.1661), respectively. SO2 at different lag structures showed opposite effects on hypertension hospitalization. O3 was significantly negatively associated with hypertension hospitalization. No correlation was observed between PM2.5 and PM10 and hypertension hospitalization. Females and individuals aged ≥ 65 were more susceptible to air pollution. The harmful effects of air pollution are greater in the cold season. Conclusion Short-term exposure to ambient air pollution increases risk of hypertension hospitalization.

Abstract Background Perinatal loss is a severe stressor that usually triggers distressing symptoms of acute grief. Moreover, acute grief can worsen with time and become a chronic debilitating state known as complicated grief. However, there is a lack of comprehensive reviews on this topic. This systematic review aims to synthesize the existing literature on complicated grief following the perinatal loss. Methods We systematically searched PubMed, Embase, Cochrane Library, CINAHL, ProQuest, and Web of Science to identify articles on complicated grief symptoms and influencing factors following perinatal loss. We performed a comprehensive, structured evaluation in full compliance with PRISMA guidelines. Results A systematic search produced 1163 results. Of these, 38 articles met the full-text screening criteria, and 10 pieces of literature met the inclusion criteria. Individuals may experience complicated grief following perinatal loss, manifesting in symptoms such as emotional reactions, physical responses, and social impairments. Furthermore, based on existing evidence, influencing factors include demographic characteristics, reproductive characteristics, marital relationships, social support, and coping strategies. Conclusions Complicated grief following perinatal loss is easily overlooked and has not been adequately studied. Further empirical research is needed to explore the symptoms and factors influencing this condition. A better understanding of complicated grief will help develop and optimize care strategies, informing future clinical practice and improving psychological support for individuals affected by perinatal loss. Trial registration PROSPERO registration number: CRD42023473510.

Chenchun Ding,1 Zhenzhen Guo,2 Quan Liao,1 Renjie Zuo,1 Junjie He,1 Ziwei Ye,2 Weibin Chen1 1Department of Thoracic Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, People’s Republic of China; 2School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, 361102, People’s Republic of ChinaCorrespondence: Weibin Chen, Department of Thoracic Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, People’s Republic of China, Email cwbxmu@163.comPurpose: Idiopathic pulmonary fibrosis (IPF) is an irreversible respiratory disease. In this study, we evaluated the efficacy of salidroside (SAL), the main component of Rhodiola rosea, in treating IPF.Methods: The pharmacological effects of SAL against epithelial-mesenchymal transition (EMT) and IPF were assessed through in vivo and in vitro experiments. Targets for SAL in treating IPF were identified from various databases and a PPI network was constructed. Functional analyses of target genes were performed using GO, KEGG, DO, and GSEA. Core target genes were identified using LASSO logistic regression and support vector machine (SVM) analysis, followed by molecular docking simulations. Predicted targets and pathways were validated through Western blotting, qRT-PCR, and IHC.Results: Our results demonstrated that SAL ameliorated alveolar epithelial cells (AECs) EMT and mitigated bleomycin -induced pulmonary fibrosis. Through network pharmacology, we identified 74 targets for SAL in the treatment of IPF (PFDR< 0.05) and analyzed their biological functions. Based on these findings, we further applied machine learning techniques to narrow down 9 core targets (PFDR< 0.05). Integrating the results from molecular docking, KEGG, and GSEA analyses, we selected three key targets—IGF1, hypoxia-inducible factor 1-alpha (HIF-1α), and MAPK (PFDR< 0.05)—for further investigation. Our study revealed that SAL inhibits the IGF1 signaling pathway, thereby improving AECs senescence and cell cycle arrest. By inhibiting the HIF-1α pathway, SAL alleviates endoplasmic reticulum stress and reduces intracellular ROS accumulation. Moreover, SAL suppresses the activation of the MAPK signaling pathway, leading to a decrease in inflammation markers in AECs and lung tissue.Conclusion: Experimental results suggest that SAL effectively ameliorates BLM-induced EMT and IPF, likely through the inhibition of IGF1, HIF-1α, and MAPK signaling pathways. This study holds potential translational prospects and may provide new perspectives and insights for the use of traditional Chinese medicine in the treatment of IPF.Keywords: salidroside, idiopathic pulmonary fibrosis, network pharmacology, machine-learning, molecular docking

Dexian Zhang,1,2,&ast; Xinxin Xu,2,3,&ast; Zhibin Ye,1,2 Zhenxing Zhang,1,2 Jing Xiao1,2 1Department of Nephrology, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China; 3Clinical Research Center for Geriatric Medicine, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenxing Zhang; Jing Xiao, Department of Nephrology, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China, Email contraindication@163.com; jingxiao13@fudan.edu.cnObjective: To develop and externally validate a nomogram to predict elevated serum uric acid (SUA) levels in older adults.Study Design: This is a longitudinal Chinese cohort study.Methods: A cohort of 2788 older adults was established at Huadong Hospital, followed-up for at least one year, and screened for risk factors for elevated SUA levels. A logistic regression model was built to predict elevated SUA, and its performance was validated.Results: The risk prediction model showed good discrimination ability in both the development cohort (area under the curve (AUC) = 0.82; 95% confidence interval (CI) =0.79~0.86) and the external validation cohort (AUC=0.76; 95% CI=0.70~0.82). The model was adequately calibrated, and the predictions correlated with the observed outcome (χ2 = 6.36, P = 0.607). Men were more prone to elevated SUA levels than women were, and a baseline SUA level ≥ 360 μmol/L was a common risk factor for both males and females. Proteinuria status was an additional risk factor for males, whereas a baseline estimated glomerular filtration rate (eGFR)< 60 mL/min· 1.73 m2 and diabetes status were additional risk factors for females.Conclusion: The externally validated nomogram, which is predictive of elevated SUA in older adults, might aid in the detection of individual diseases, the development of preventive interventions and clinical decision-making.Keywords: elevated serum uric acid, prediction nomogram, risk factor

Shu Wang,1,&ast; Chengzhong Liu,2,&ast; Ruipei Ding,2 Shumei Wang,2 Yousheng Ye,1 Maozhang He2 1Department of Geriatrics, The First People’s Hospital of Hefei, Hefei, 230061, People’s Republic of China; 2Department of Microbiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Maozhang He; Yousheng Ye, Email jnzd_hemaozhang@hotmail.com; ye.ys@qq.comBackground: Over the past years, there has been a significant increase in the incidence of Mycoplasma pneumoniae (MP) infections, particularly among pediatric patients, nationwide. An emerging body of research has established a link between dysbiosis of the host microbiome and the metabolic functioning of the host, which contributes to the development of respiratory diseases.Methods: A total of 25 children were included in the study, comprising 15 pneumonia patients and 10 healthy children. Stool samples were collected from all participants to analyze the 16S ribosomal RNA (16S rRNA) gene, while serum samples were prepared for untargeted metabolomics to qualitatively and quantitatively assess short-chain fatty acids.Results: The gut microbial composition of individuals with Mycoplasma pneumoniae pneumonia (MPP) exhibited significant differences compared to healthy children. Notably, diseased children demonstrated higher microbial diversity and an enrichment of opportunistic pathogens, such as Erysipelatoclostridium and Eggerthella. Analysis revealed elevated levels of two specific short-chain fatty acids, namely acetic acid and isobutyric acid, in the MPP group, suggesting their potential as biomarkers for predicting MP infection. Metabolomic signature analysis identified a significant increase in major classes of glycerophospholipids in the MPP group. Moreover, we identified a total of 750 significant correlations between gut microbiota and circulating serum metabolites. MPP enriched genera Erysipelatoclostridium and Eggerthella, exhibited negative associations with indole-3-butyric acid. Additionally, Eggerthella showed a positive correlation with inflammatory metabolites LPC (18:0).Discussion: Collectively, these findings provide novel insights into the selection of potential biomarkers and the pathogenesis of MPP in children based on the gut microbiota and systemic circulating metabolites.Keywords: Mycoplasma pneumoniae, gut microbiota, serum metabolomics, short-chain fatty acids, inflammation

Abstract There are significant differences in distributed generators (DGs) distribution and load characteristics between different voltage levels, which makes it difficult to match sources and loads. We focus on the problem of different consumption capacities at different voltage levels and the divergence of interests among investment entities, and propose a coordinated planning model for DGs and soft open points (SOPs) based on the Stackelberg game. Firstly, a model of a multi‐voltage level distribution networks (DNs) is constructed based on SOPs. Next, the source‐load matching degree is proposed as a measure of the degree of matching between sources and loads in the DN, and the source‐load consumption rate is selected as an indicator to evaluate the impact of the load on DG consumption. Following this, the interest demands of DG investors and distribution company (DisCo) in multi‐voltage levels DN are analyzed, a planning mode based on the Stackelberg game is proposed, and this is solved by combining the genetic algorithm with second‐order cone programming. Finally, the effectiveness of the planning model is tested and verified using an improved IEEE 28‐node system. The results show that the proposed model improves the DG consumption capacity of DNs with multiple voltage levels while protecting the interests of DG investors and DisCo.

Abstract Background Sepsis-induced myocardial dysfunction (SIMD) may contribute to the poor prognosis of septic patients. Carvacrol (2-methyl-5-isopropyl phenol), a phenolic monoterpene compound extracted from various aromatic plants and fragrance essential oils, has multiple beneficial effects such as antibacterial, anti-inflammatory, and antioxidant properties. These attributes make it potentially useful for treating many diseases. This study aims to investigate the effects of CAR on LPS-induced myocardial dysfunction and explore the underlying mechanism. Results H9c2 cells were stimulated with 10 µg/ml LPS for 12 h, and c57BL/6 mice were intraperitoneally injected with 10 mg/kg LPS to establish a septic-myocardial injury model. Our results showed that CAR could improve cardiac function, significantly reduce serum levels of inflammatory cytokines (including TNF-α, IL-1β, and IL-6), decrease oxidative stress, and inhibit cardiomyocyte apoptosis in LPS-injured mice. Additionally, CAR significantly downregulated the expression of TLR4, MyD88, and NF-κB in LPS-injured mice and H9c2 cells. It also inhibited the upregulation of inflammasome components (such as NLRP3, GSDMD, and IL-1β) in H9c2 cells triggered by LPS. Conclusion Taken together, CAR exhibited potential cardioprotective effects against sepsis, which may be mainly attributed to the TLR4/MyD88/NF-κB pathway and the NLRP3 inflammasome.

Abstract Background Dental pulp stem cells (DPSCs) have acquired noteworthy attention for their application in treating ischemic diseases and facilitating tissue regeneration. However, the host’s immune response following allogenic DPSC transplantation often handicaps the long-term survival of transplanted cells, thereby limiting the application of DPSCs in cell therapy. This study aims to investigate whether genetic modification can alleviate the immunogenicity of DPSCs. Methods Beta 2-microglobulin (B2M) and the class II histocompatibility complex transactivator (CIITA) were individually knocked down in DPSCs by lentiviral particles encoding short hairpin (sh) RNAs. The self-renewal capacity and pluripotency of DPSCs-shB2M (B2M silenced DPSCs) and DPSCs-shCIITA (CIITA silenced DPSCs) were evaluated by CCK8 and differentiation assays including osteogenesis, adipogenesis, and neurogenesis. The expression of HLA-I and HLA-II in DPSCs-shB2M and DPSCs-shCIITA after IFN-γ treatment were analyzed by western blotting, immunofluorescence, and flow cytometry. The function of genetically modified cells was assessed by leukocyte-mediated cytotoxicity and T-cell proliferation assays. Results Western blotting, immunofluorescence, and flow cytometry revealed that DPSCs-shB2M and DPSCs-shCIITA exhibited impaired IFN-γ inducible HLA-I and HLA-II expression. There were no significant differences in the self-renewal capacity and pluripotency among DPSCs-shB2M, DPSCs-shCIITA, and control groups (p > 0.05). Lower leukocyte-mediated cytotoxicity and higher cell survival rates were found in DPSCs-shB2M and DPSCs-shCIITA groups compared to the control (p

Abstract The rapid advancement of artificial intelligence and robot technology has spurred the proposal and innovation of a coal gangue sorting robot system (CGSRS) paradigm. The time-varying raw coal flow (TVRCF) with multi-scene and full working conditions affects the gangue queue. Configuring the CGSRS scheme correctly is combative. The field environment puts forward higher requirements for the time complexity of the CGSRS multi-task allocation strategy. Therefore, this paper proposes a scheme evaluation method of the CGSRS with time-varying multi-scenario based on deep learning. Firstly, the gangue queue data set of multi-scene and full-condition TVRCF was obtained according to the belt speed, the maximum coal flow, and the uncorrelated nonlinear changes of coal flow and gangue content. The CGSRS scheme is established based on robot number and rule combination, and the multi-task allocation strategy is adjusted to generate the labels of the gangue queue. Then, the RGB sample set is established based on the labels of the gangue queue. The CGSRS scheme evaluation model is trained based on DenseNet. Finally, the CGSRS scheme evaluation method was designed to realize the prediction of a random gangue queue. In this paper, the CGSRS scheme evaluation model, the stability of the solution, and the comparison of methods are carried out. Experimental results show that the solution of the CGSRS scheme evaluation model is accurate and stable. The time complexity is significantly reduced and very stable. The CGSRS scheme evaluation method is applied to the CGSRS multi-task allocation problem, and the stability of the solution is not affected by the data. It is significantly better than the multi-task allocation strategy. The proposed method is the first attempt to apply deep learning to a multi-task allocation problem in CGSRS.

Abstract Head and neck squamous cell carcinoma (HNSCC) is notorious for poor prognoses, and effective biomarkers are urgently needed for early diagnosis of HNSCC patients. We investigate the role of alkaline ceramidase 1 (ACER1) and its relationship with immune infiltration in HNSCC. The differential expression and clinical prognostic significance of ACER1 in HNSCC patients are explored using bioinformatics methods and verified in human HNSCC samples. Genetic mutation, DNA methylation and drug sensitivity linked with ACER1 are examined. The potential biological function of ACER1 co-expression genes is assessed, and a series of functional assays are performed on ACER1in vitro. The results comprehensively reveal a relationship between ACER1 and immune infiltration in HNSCC patients. ACER1 expression is significantly downregulated in HNSCC tissues and closely correlated with better prognoses for HNSCC patients, and this prognostic significance is determined by distinct clinical characteristics. Genetic alteration and promoter hypomethylation of ACER1 are involved in progression of HNSCC, and ACER1 expression is significantly related to several drug sensitivities. Functional analysis shows that ACER1 co-expression genes are mainly enriched in the sphingolipid signaling pathway associated with inhibition of tumorigenesis, leading to better prognoses for HNSCC patients. In vitro, ACER1 overexpression inhibits proliferation and migration, induces apoptosis, and promotes adhesion of Fadu and SCC9 cells. In addition, high ACER1 expression is closely linked with infiltration levels of immune cells, and strongly associated with biomarkers of immune cells in HNSCC, suggesting the important role of ACER1 in regulating tumor immunity in HNSCC patients. In summary, ACER1 may be a useful indicator for diagnosis and prognosis, and may regulate immune infiltration in HNSCC patients, thus promising targeted immunotherapy for HNSCC.

Abstract This study aims to optimize the reduction of free fatty acids (FFAs) in palm fatty acid distillate (PFAD) using hydrodynamic cavitation reactors (HCRs) in series and a solid acid catalyst for biodiesel production. Hydrodynamic cavitation is used to accelerate the esterification of FFAs using a heterogeneous acid catalyst. There are three HCRs units, and each HCR composed of a 3D-printed rotor and stator, is separated by flanges and equipped with a basket for holding Amberlyst-15 catalyst. Through response surface methodology (RSM), the esterification process is optimized by adjusting its optimal parameters, namely, methanol (2–12 wt%), circulation time (30–170 min), and rotor speed (1000–3000 rpm). The optimal conditions for achieving a maximum methyl ester purity of 89.76 wt% in converting FFA in first-step esterified oil are 9 wt% methanol (molar ratio of methanol to oil of 4:1), 133 min of circulation time, and 2000 rpm of rotor speed. An 82.48 wt% biodiesel yield is achieved from the HCRs in series under the optimal conditions. Scanning electron microscope images reveal that after the esterification process, there are minor cracks and defects on the catalyst’s resin surface, indicating the presence of residual reactants. Further examination of the catalyst after the esterification process, reveals an average absorption pore diameter of 341.41 Å and BET surface area of approximately 41.68 m2/g. Although there were slight physical changes in the catalyst, HCRs technology offers a viable FFA reduction process that could enhance biodiesel production efficiency. Moreover, the optimized conditions achieved in this study contribute to the advancement of biodiesel production processes and provide insights into the performance of the catalyst used.

Abstract Adipose stem cell-derived exosomes (ADSC-EXO) have been demonstrated to promote osteogenic differentiation of bone marrow stem cells (BMSCs) and facilitate bone regeneration. The present study aims to investigate the effect of ADSC-EXO-loaded nano-hydroxyapatite/chitosan/poly-lactide-co-glycolide (nHA/CS/PLGA) scaffolds on maxillofacial bone regeneration using tissue engineering. ADSC-EXO was isolated and co-cultured with BMSCs, and the osteogenic differentiation of BMSCs was assessed through the detection of mineralized nodule formation, alkaline phosphatase (ALP) activity, and mRNA expression of COL1A1 and runt-related transcription factor 2 (RUNX2). The nHA/CS/PLGA scaffolds were fabricated and loaded with ADSC-EXO and BMSCs, and these tissue engineering complexes were applied to the maxillofacial bone defect region of rabbits to elucidate their bone regeneration effect. The osteogenic differentiation of BMSCs was markedly enhanced when they were co-cultured with ADSC-EXO. This was evidenced by an increase in the formation of mineralized nodule formation, ALP activity, and mRNA expression of COL1A1 and runt-related transcription factor 2 (RUNX2). In vivo experiments demonstrated that the application of ADSC-EXO and BMSCs loaded nHA/CS/PLGA scaffolds effectively repaired maxillofacial bone defects in rabbits. ADSC-EXO has been demonstrated to promote the osteogenic differentiation of BMSCs. The ADSC-EXO and BMSCs loaded nHA/CS/PLGA scaffolds have been shown to facilitate the regeneration of maxillofacial bone defects. This may serve as a potential therapeutic strategy for large-scale bone defects.

Abstract The utilization of visible-near infrared (Vis–NIR) spectroscopy presents a nondestructive, fast, reliable and cost-effective approach to predicting total nitrogen (TN) and organic carbon (OC) levels. This study employed a combination of Vis–NIR spectroscopy, partial least-squares regression (PLSR), and support vector machine (SVM) models to investigate the effects of mining on TN and OC stocks in both the topsoil (0–10 cm) and subsoil (10–40 cm). 105 soil samples were collected from agricultural areas near an iron mine, polluted, moderately-polluted, and non-polluted sites. Results indicated that soils at the non-polluted site had the highest of soil OC stocks (7.5 kg m–2) and total nitrogen (2.5 kg m–2), followed by the moderately-polluted site. Furthermore, it was observed that soils from the polluted site displayed the highest spectral reflectance. The spectral bands in the range of 500–700 nm showed the strongest correlation with soil organic carbon content. Notably, the SVM method utilizing Vis–NIR spectroscopy provided superior predictions for both subsoil and topsoil organic carbon and total nitrogen compared to the PLSR methods. Additionally, SVM demonstrated better performance in predicting topsoil soil organic carbon (R2 = 0.87, RMSE = 0.13%, and RPD = 2.8) and total nitrogen (R2 = 0.91, RMSE = 0.13%, and RPD = 2.4) compared to the subsoil, owing to the larger OM content in the topsoils.

Abstract The intestine, is responsible for food digestion, nutrient absorption, endocrine secretion, food residue excretion, and immune defense. These function performances are based on the intricate composition of intestinal epithelial cells, encompassing differentiated mature cells, rapidly proliferative cells, and intestinal stem cells. Although the characteristics of these cell types are well-documented, in-depth exploration of their representative markers and transcription factors is critical for comprehensive cell fate trajectory analysis. Here, we unveiled the feature genes in different cell types of the human and mouse gut through single-cell RNA sequencing analysis. Further, the locations of some specific transcription factors and membrane proteins were determined by immunofluorescence staining, and their role in regulating the proliferation and differentiation of intestinal epithelial cells were explored by CRISPR/Cas9 knockout. Therefore, this study not only reports new markers for various intestinal epithelial cell types but also elucidates the involvement of relevant genes in the determination of epithelial cell fate and maintenance of stem cell homeostasis, which facilitates the tracing and functional elucidation of intestinal epithelial cells.

Abstract Background Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) is a treatment for preventing febrile neutropenia (FN) in patients with early breast cancer. However, the optimal injection timing of PEG-rhG-CSF after chemotherapy is obscure. The trial was designed to explore the best administration timing of PEG-rhG-CSF when breast cancer patients could benefit most. Methods Patients with early breast cancer were randomly assigned to receive a preventive injection on the 7th or 3rd day following chemotherapy. The experimental group (n = 80) received PEG-rhG-CSF treatment on day 7 after chemotherapy, whereas the control group (n = 80) received it on day 3. The occurrence of grades 3–4 neutropenia and FN in the first cycle was the primary endpoint. The secondary endpoint was the frequency of PEG-rhG-CSF dose reduction. Results In comparison to the control group, the experimental group exhibited higher white blood cell count (WBC) and absolute neutrophil count (ANC) on the 9th and 13th days following chemotherapy (P

Abstract Purpose This study explored the effectiveness of a Problem-based Learning (PBL) teaching model on the WeChat public platform for radiation oncology residency training programs. Materials and methods The WeChat PBL program was initiated in 2019. The study recruited student participants, on a voluntary basis, who were in their first and second years of standardized training in radiation oncology. We selected classic and trending issues in radiation oncology as the two main teaching topics. Students in the PBL group searched for relevant literature, summarizing PowerPoint presentations or academic speeches on specific issues published on the professional WeChat public platform after an in-depth review by teachers. The final national standardized training examination scores for resident physicians were used to evaluate teaching effectiveness. The graduation scores of the PBL and non-PBL groups were compared, and a stratified analysis was conducted based on the year of participation to assess the teaching effectiveness of this model. Moreover, questionnaires were administered to evaluate students’ experiences. Results Among the 36 students who joined the study in 2019, 16 (44.0%) voluntarily joined the PBL teaching group. Nine students started teaching PBL in their first year of residency, accounting for 47.4% of that year, and seven started in their second year, accounting for 41.2%. The average graduation scores of the PBL group were superior to those of the non-PBL-focused group for the same grade. The rate of high scores among students in the PBL group (56.3%) was higher than that of students in the non-PBL group (25%). Specifically, first-year residents who joined the PBL group had an average score of 92.3 ± 2.2, significantly higher than their non-PBL counterparts, who scored an average of 88.6 ± 4.6, showing a statistically significant advantage (p = 0.042). All students were satisfied with the PBL WeChat teaching and would recommend the PBL WeChat course to others. Conclusion The PBL residency teaching model on the WeChat platform improved residency scores and garnered student satisfaction.

Abstract A fundamental objective of genomics is to track variations in gene expression program. While metabolic RNA labeling-based single-cell RNA sequencing offers insights into temporal biological processes, its limited applicability only to in vitro models challenges the study of in vivo gene expression dynamics. Herein, we introduce Dyna-vivo-seq, a strategy that enables time-resolved dynamic transcription profiling in vivo at the single-cell level by examining new and old RNAs. The new RNAs can offer an additional dimension to reveal cellular heterogeneity. Leveraging new RNAs, we discern two distinct high and low metabolic labeling populations among proximal tubular (PT) cells. Furthermore, we identify 90 rapidly responding transcription factors during the acute kidney injury in female mice, highlighting that high metabolic labeling PT cells exhibit heightened susceptibility to injury. Dyna-vivo-seq provides a powerful tool for the characterization of dynamic transcriptome at the single-cell level in living organism and holds great promise for biomedical applications.

Abstract The membrane electrode assembly (MEA) is promising for practical applications of the electrocatalytic CO2 reduction reaction (CO2RR) to multi-carbon (C2+) compounds. Water management is crucial in the MEA electrolyser without catholyte, but few studies have clarified whether the co-feeding water in cathode can enhance C2+ formation. Here, we report our discovery of pivotal roles of a suitable nanocomposite electrocatalyst with abundant Cu2O−Cu0 interfaces in accomplishing water-promoting effect on C2+ formation, achieving a current density of 1.0 A cm−2 and a 19% single-pass C2+ yield at 80% C2+ Faradaic efficiency in MEA. The operando characterizations confirm the co-existence of Cu+ with Cu0 during CO2RR at ampere-level current densities. Our studies reveal that Cu+ works for water activation and aids C‒C coupling by enhancing formations of adsorbed CO and CHO species. This work offers a strategy to boost CO2RR to C2+ compounds in industrial-relevant MEA by combining water management and electrocatalyst design.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition and a leading cause of mortality, with acute exacerbations (AECOPD) significantly complicating its management and prognosis. Despite the development of various prognostic prediction models for patients with AECOPD, their performance and clinical applicability remain unclear, necessitating a systematic review to evaluate these models and provide guidance for their future improvement and clinical use. Method PubMed, Web of Science, CINAHL, Scopus, EMBASE, and Medline were searched for studies published from their inception until February 5, 2024. Data extraction and evaluation were conducted using the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). The Prediction model Risk Of Bias Assessment Tool (PROBAST) was employed to assess the risk of bias and applicability of the models. Results After deduplication and screening 5942 retrieved articles, 46 studies comprising 53 models were included. Of these, 17 (37.0%) studies developed from studies conducted in China. All models were based on cohort studies. Mortality was the predicted outcome in 27 (50.9%) models. Logistic regression was used in 41 (77.4%) models, while machine learning methods were employed in 9 (17.0%) models. The median (minimum, maximum) sample size for model development was 672 (106, 150,035). The median (minimum, maximum) number of predictors per model was 5 (2, 42). Frequently used predictors included age (n = 28), dyspnea severity scores (n = 12), and PaCO2 (n = 11). The pooled AUC was 0.80 for mortality prediction models and 0.84 for hospitalization-related outcomes. 52 models have a high overall risk of bias, and all models were judged to have low concern regarding applicability. Major sources of bias included insufficient sample sizes (83.0%), reliance on univariate analysis for predictor selection (73.6%), inappropriate internal and external validation methods (54.7%), inappropriate inclusion and exclusion criteria for study subjects (50.9%) and so on. The only model with low bias was the PEARL score. Conclusion Current prognostic risk prediction models for patients with AECOPD generally exhibit high bias. Future efforts should standardize model development and validation methods, and develop widely usable clinical models.

Abstract Introduction: Problematic gaming (PG) is a serious issue among adolescents worldwide, and there is evidence suggesting that school bullying behaviors may be associated with increased rates of PG. This study aimed to examine the associations between school bullying behaviors and PG among adolescents, with a focus on sex effects. Methods: A total of 20,197 participants were recruited from the 2023 School-based Chinese Adolescents Health Survey. Information about school bullying behaviors and PG was measured. Sampling weights were utilized to estimate the prevalence, and weighted logistic regression models were executed. Stratified analyses by sex were performed. Results: Among Chinese adolescents, the weighted prevalence of PG was 4.2%, 8.1% were identified as victims, 1.8% as bullies, and 3.4% as bully-victims. A higher frequency of school bullying behaviors corresponds to a higher prevalence of PG. After adjusting for covariates, victims (AOR = 1.34, 95% CI = 1.03–1.73), bullies (AOR = 2.08, 95% CI = 1.39–3.11), and bully-victims (AOR = 2.75, 95% CI = 2.09–3.61) were associated with PG. Moreover, the severity of PG tended to increase with the number of involved in school bullying behaviors. The interaction terms of bully-victims and sex were significant. Further stratified analyses by sex indicated that the association of school bullying behaviors with PG was stronger for females than males, especially those identified as bully-victims. Conclusion: School bullying behaviors are associated with PG among adolescents, with a stronger association found in female adolescents, particularly those identified as bully-victims. These findings suggest that implementing prevention and control measures for school bullying could help reduce PG among adolescents.

Abstract The Leshan Giant Buddha’s ushnisha (Head Bun) has suffered from loss of lime plaster, cracks, and biological damage, compromising its structural integrity and reducing the effectiveness of the drainage system in the Buddha's head. The infiltration of moisture has led to water damage within the statue, significantly accelerating its weathering. This situation urgently requires protection and reinforcement measures. Detecting deterioration in the ushnisha is a crucial step in the preservation process. In this study, we utilized two deep learning models for pixel-level semantic segmentation of the damage. Due to the small size of the cracks, a weighted loss function was applied to improve both the training speed of the model and the efficiency of crack identification. This weighting strategy proved effective for both models. The weighted K-Net model achieved a mean accuracy (mAcc) of 90.23% and a mean intersection-over-union (mIoU) of 69.55%, with a damage segmentation speed of 7 images per second, which is 1309 times faster than manual segmentation. By applying the trained deep learning models to re-examine the ushnisha, we successfully identified damage that had been overlooked during manual annotation. Using the model’s enhanced results, we conducted a comprehensive quantification of the damage across all ushnisha and identified the most severely affected areas. Additionally, we performed a model interpretability analysis to explain the decision-making process and principles of the deep learning models. This research provides significant practical value for detecting and quantifying damage in the Leshan Giant Buddha.

Abstract Previous reports showed that long non-coding RNA (lncRNA) participates in the development and progression of tumors. Nevertheless, the effect of LINC02139 and its mechanism on gastric cancer (GC) is still unknown. We revealed that LINC02139 is upregulated in GC cell lines and tissues and high LINC02139 expression was correlated with the advancement of GC in patients. Functionally, overexpression of LINC02139 promoted, while knockdown of LINC02139 impaired GC cell proliferation, migration, and invasion in vitro and impeded tumorigenesis in a tumor xenograft model in vivo. Mechanistically, LINC02139 directly bound to XIAP and increased the protein level by maintaining its protein stability through inhibition of the ubiquitination and proteasome-dependent degradation pathway. Importantly, the regulatory function of XIAP in LINC02139-mediated oncogenic effects was demonstrated. Both in vitro and in vivo experiments showed that LINC02139 and XIAP collaboratively modulate GC cell growth and apoptosis. Analysis of clinical GC tissues further confirmed the upregulation of XIAP and the positive association between LINC02139 and XIAP expression. These findings established LINC02139 as a driver of tumorigenesis and highlighted the crucial involvement of the LINC02139-XIAP axis in GC progression, suggesting its potential as a promising therapeutic target for combating GC advancement.

Highlights A 2.5-dimensional dynamic structural color based on nanogratings of heterogeneous materials was proposed by interweaving a pH-responsive hydrogel with IP-L photoresist. The nanogrid structures exhibit brilliant tuneable structural color, high sensitivity, and ultrafast recovery speeds in response to pH. The 4D printing-based grayscale design approach was proposed for the patterned encoding and array printing of dynamic structural colors, promoting their application in patterned printing, information encryption, and microfluidic chip sensing.

Abstract Synovial sarcoma (SS) is driven by a unique t(18;X) chromosomal translocation resulting in expression of the SS18-SSX fusion oncoprotein, a transcriptional regulator with both activating and repressing functions. However, the manner in which SS18-SSX contributes to the development of SS is not entirely known. Here, we show that SS18-SSX drives the expression of Preferentially Expressed Antigen in Melanoma (PRAME), which is highly expressed in SS but whose function remains poorly understood. The fusion protein directly binds and activates the PRAME promoter and we found that expression of SS18-SSX and PRAME are positively correlated. We provide evidence that PRAME modulates retinoic acid (RA) signaling, forming a ternary complex with the RA receptor α (RARα) and the Enhancer of Zeste Homolog 2 (EZH2). Knockdown of PRAME suppressed the response to all-trans retinoic acid (ATRA) supporting PRAME’s role in modulating RA-signaling. Notably, we demonstrate that combined pharmacological inhibition of EZH2 and treatment with ATRA reconstituted RA signaling followed by reduced proliferation and induction of cellular senescence. In conclusion, our data provides new insights on the role of the SS18-SSX fusion protein in regulation of PRAME expression and RA signaling, highlighting the therapeutic potential of disrupting the RARα-PRAME-EZH2 complex in SS. Schematic presentation of the proposed model. A The RARα-PRAME-EZH2 ternary complex in SS. The fusion SS18-SSX oncoprotein binds to the PRAME promoter and activates its expression. PRAME in turn interacts with RARα-RXR heterodimers as well as with EZH2, and the complex binds to retinoic acid response elements (RAREs) in the DNA. This results in transcriptional repression of retinoic acid (RA) responsive genes and thus inhibition of RA-signaling, allowing tumor cell proliferation. B Therapeutic strategy. Treatment with an EZH2 inhibitor, such as GSK343, or activation of RAR receptors via all-trans retinoic acid (ATRA), disrupts the RARα-PRAME-EZH2 ternary complex and restores RA-signaling. Exposure to GSK343 or ATRA results in inhibition of cell proliferation and induction of cellular senescence, where GSK343 shows a dominant effect. The Figure was created with Biorender.com.

Abstract Background Epidemiological studies investigating the association between flavonoid intake and bone mineral density (BMD) draw inconsistent conclusions. Our study aims to investigate the association between flavonoid intake and BMD and osteoporosis and the mediating role of composite dietary antioxidant index (CDAI) in their relationship using data from the National Health and Nutrition Examination Survey (NHANES). Methods The study assessed the relationship between flavonoid intake and femur BMD and osteoporosis in 10,225 individuals from NHANES 2007–2010 and 2017–2018. Multivariable linear regression analyses were used to detect the association between flavonoid intake and femur BMD in adult Americans. Restricted cubic splines (RCS) were used to examine the nonlinear relationship between flavonoid intake and their subclasses and osteoporosis risk in individuals 20 years or older. We explored the mediating role of CDAI in the association between flavonoid intake and BMD. Results In fully adjusted multivariable regression analyses, compared with people in the first quartile, people in the fourth quartile of total flavonoid intake have a higher BMD at total femur (0.013, 95% CI: 0.004, 0.022, P = 0.001), femur neck (0.010, 95% CI: 0.004, 0.017, P = 0.001), trochanter (0.010, 95% CI: 0.004, 0.017, P = 0.001), and intertrochanter (0.012, 95% CI: 0.003, 0.020, P = 0.006). The positive relationship between flavonoid intake and femur BMD was present in both sexes. Furthermore, we found that people in the fourth quartile of total flavonoid intake have a lower risk of osteoporosis compared with the first quartile (OR = 0.686, 95% CI: 0.528–0.890, P = 0.005). RCS found a linear inverse relationship between total flavonoid intake and osteoporosis in individuals ≥ 20 years (Overall P = 0.015, nonlinear P = 0.086). Moreover, CDAI partially mediates the association of total flavonoid intake with femur BMD. Conclusions Our findings suggest that higher flavonoid intake is associated with higher BMD and lower risk of osteoporosis in Americans. Furthermore, we found distinct associations between different flavonoid subclasses and osteoporosis risk. More studies with stronger evidence are needed to explore the causal association between flavonoid intake and bone health and their underlying mechanisms.

Abstract Background The study focuses on the effect of temperature and relative humidity on hospitalization for acute lower respiratory tract infections (LRTI) in children, respectively. Methods In this study, the Distributed Lag Nonlinear Model (DLNM) based on quasi-Poisson distribution was used to investigate the effect of temperature and relative humidity on LRTI hospitalization in children, and subgroup analyses were conducted to identify sensitive populations by gender and age. Results A total of 43,951 children were hospitalized for LRTI from 1 January 2014 to 31 December 2019 in Lanzhou. The mean temperature during the study period was 11.34 °C and the mean relative humidity was 51.03%. With reference to the median temperature of 12.7 °C during the study period, both low (-4.1 °C) and high (25.43 °C) temperature had a detrimental effect on LRTI hospitalization, and the maximum effect was reached at lag0-10 and lag0-9, respectively, with RR values of 1.645 (95%CI: 1.533, 1.764) and 1.098 (95%CI: 1.018, 1.184). With a reference to the median relative humidity of 51.17% during the study period, both low relative humidity (26.71%) and high relative humidity (76.70%, P95) had a detrimental effect on LRTI hospitalization, and the maximum effect was reached at lag0-21 and lag21, respectively, with RR values of 1.235 (95% CI: 1.163, 1.311) and 1.044 (95% CI: 1.036, 1.051). The results of subgroup analyses showed that changes in meteorological factors had a stronger effect on Female and children aged 5–14 years. Conclusions The meteorological factors all have different degrees of influence on LRTI hospitalization in children. Girls and the children aged 5–14 years are more sensitive. Attention to these meteorological risks can inform targeted interventions.

Abstract Object detection using UAV images is a current research focus in the field of computer vision, with frequent advancements in recent years. However, many methods are ineffective for challenging UAV images that feature uneven object scales, sparse spatial distribution, and dense occlusions. We propose a new algorithm for detecting small objects in UAV images, called ATBHC-YOLO. Firstly, the MS-CET module has been introduced to enhance the model’s focus on global sparse features in the spatial distribution of small objects. Secondly, the BHC-FB module is proposed to address the large-scale variance of small objects and enhance the perception of local features. Finally, a more appropriate loss function, WIoU, is used to penalise the quality variance of small object samples and further enhance the model’s detection accuracy. Comparison experiments on the DIOR and VEDAI datasets validate the effectiveness and robustness of the improved method. By conducting experiments on the publicly available UAV benchmark dataset Visdrone, ATBHC-YOLO outperforms the state-of-the-art method(YOLOv7) by 3.5%.

Hang Yi,1 Ruiping Ye,2 Jinfeng Wang,3 Lin Gao,4 Weiwei Zhang,4 Chao Liu4 1Department of Intensive Care Medicine, Qianjiang Central Hospital, Qianjiang City, Hubei Province, 433100, People’s Republic of China; 2Department of Intensive Care Medicine, The First People’s Hospital of Dingnan County, Ganzhou City, Jiangxi Province, 341900, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, People’s Republic of China; 4Department of Intensive Care Medicine, Ganzhou People’s Hospital, Ganzhou City, Jiangxi Province, 341000, People’s Republic of ChinaCorrespondence: Chao Liu, Department of Intensive Care Medicine, Ganzhou People’s Hospital, No. 16, Meiguan Avenue, Zhanggong District, Ganzhou City, Jiangxi Province, People’s Republic of China, Email a15116461784@126.comObjective: To investigate the diagnostic value of serum fibrinogen domain-containing lectin-3 (Ficolin-3) and galectin-3 (Gal-3) in sepsis-associated acute kidney injury (SA-AKI).Methods: This study retrospectively analyzed 126 SA-AKI patients with SA-AKI and 103 septic patients without AKI as controls. Based on the severity of renal injury, the SA-AKI patients were divided into three groups: mild (41 cases), moderate (53 cases), and severe (32 cases). Serum levels of Ficolin-3 and Gal-3 were measured using ELISA, and their correlation was determined through Pearson analysis. Multivariate logistic regression was used to identify factors associated with the occurrence of SA-AKI.Results: The serum creatinine (SCr), blood urea nitrogen (BUN), as well as the expression levels of serum Ficolin-3 and Gal-3 in the SA-AKI group were higher than those in the non SA-AKI group (P< 0.05). The expression levels of Ficolin-3 and Gal-3 in the serum of the SA-AKI group were also higher than those of the non SA-AKI group (P< 0.05). The expression levels of Ficolin-3 and Gal-3 in serum gradually increased with the severity of renal injury in SA-AKI patients (P< 0.05). The expression levels of Ficolin-3 and Gal-3 in serum were greatly positively correlated (P< 0.001). Elevated levels of BUN, Ficolin-3, and Gal-3 were risk factors affecting the occurrence of SA-AKI (P< 0.05). The area under the curve (AUC) of serum Ficolin-3 and Gal-3 for individual diagnosis of SA-AKI was 0.877 and 0.867, respectively, the AUC of their combined diagnosis was 0.953, and the diagnostic sensitivity was higher than that of their individual diagnosis (P< 0.001).Conclusion: The expression levels of serum Ficolin-3 and Gal-3 are closely related to associated with the onset and progression of SA-AKI and hold diagnostic value for its detection. Furthermore, the combined use of both markers provides a more accurate diagnosis than either marker alone.Keywords: Sepsis complicated with acute kidney injury, Fibrinogen domain-containing lectin-3, Galectin-3

Xiaorong Ye,1 Bingzhen Li,2 Fang Xu,3 Debiao Pan,4 Jing Wu1 1Department of Anorectal Surgery, Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang Province, People’s Republic of China; 2Department of Gastrointestinal Surgery, Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang Province, People’s Republic of China; 3Department of Gastroenterology, Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang Province, People’s Republic of China; 4Department of Hepatobiliary Surgery, Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang Province, People’s Republic of ChinaCorrespondence: Bingzhen Li, Department of Gastrointestinal Surgery, Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang Province, People’s Republic of China, Email 18957097838@163.comObjective: Delirium is a common complication of acute pancreatitis. Receptor-interacting protein kinase 3 (RIP3) is an activator of programmed cell necrosis. This study aimed to determine its ability to predict delirium after acute pancreatitis.Methods: In total, 297 patients with acute pancreatitis were prospectively enrolled in this study. Patients were divided into two subgroups (study and validation groups: 197 and 100 cases, respectively). Serum RIP3 levels were measured in all patients and in 100 healthy controls. Acute Physiology and Chronic Health Evaluation (APACHE) II, Ranson, and sequential organ failure assessment (SOFA) scores were used for the severity assessment. In-hospital delirium was observed as an outcome variable. Multifactorial analyses were performed to discern severity correlations and outcome associations.Results: Serum RIP3 levels were significantly higher in the patients than in the controls. Serum RIP3 levels had linear relationships under the restricted cubic spline and were independently correlated with APACHE II, Ranson, and SOFA scores. Serum RIP3 levels were linearly correlated with the likelihood of developing in-hospital delirium and exhibited a strong discrimination efficiency under the receiver operating characteristic curve. Serum RIP3 levels, coupled with APACHE II scores, Ranson scores, and SOFA scores, were the four independent predictors of in-hospital delirium. No interactions were revealed regarding its relevance to sex, age, or body mass index in subgroup analysis. These were integrated to form a model graphically represented by a nomogram that showed effective stability, clinical fit, and predictive ability for in-hospital delirium. The model was verified in the validation group.Conclusion: An incremental trend in serum RIP3 levels was notable after acute pancreatitis. Serum RIP3 levels are independently related to illness severity and occurrence of in-hospital delirium, indicating that serum RIP3 may be a potential biomarker of acute pancreatitis.Keywords: acute pancreatitis, delirium, receptor-interacting protein kinase 3, severity

Titanium alloy is a typically difficult-to-process material, and its surface state significantly impacts its applications in aerospace, ships, and other fields. To obtain high-quality surface, laser surface melting and electrochemical polishing (LSM-ECP) combined processing was presented to polish Ti6Al4V in this study. The effects of laser surface melting (LSM) on the electrochemical polishing (ECP) surface morphology and properties of Ti6Al4V alloy (LSM-ECP) was studied. The research includes microstructure evolution, surface phase and element change, microhardness, and surface corrosion resistance. The results showed that the LSM-ECP surface roughness was further reduced by 73.8%–168 nm. LSM-ECP can partially remove the remelted layer, and the generated metal oxides such as TiO2, Ti2O3, TiO, Al2O3. and other metal oxides help protect the surface of the specimen, reduce corrosion, and the surface hardness and corrosion resistance of the substrate was improved. It can be concluded that grain refinement, a large number of needle-shaped α′+β phases and dislocatiaon in the LSM Ti6Al4V alloy can provide more numbers of corrosion of grain boundaries, the oxide layer and low roughness during the ECP process. The electrode response of LSM-ECP is faster than that of direct ECP of the substrate surface, better polishing result is obtained in a shorter time.

Objective To investigate the influencing factors of early postoperative cognitive dysfunction (POCD) in elderly patients undergoing general anesthesia. Methods A total of 129 elderly patients hospitalized under general anesthesia who underwent elective surgery in Xi’an Fifth Hospital from October 2021 to October 2023 were selected as the study subjects. The preoperative general conditions, underlying disease history and hemoglobin content were recorded. The preoperative mean blood flow velocity of bilateral middle cerebral arteries and breath holding index (BHI) were assessed by transcranial doppler. The intraoperative anesthesia time, blood loss, hypothermia and hypotension were recorded. Cognitive function was assessed by the Mini-Mental State Examination (MMSE) 1 day before surgery and 1 week after surgery in elderly patients, and POCD was considered to be present if the postoperative MMSE score was lower than ≥2 points before surgery. Results A total of 36 patients who developed POCD after surgery were in the POCD group, and the remaining 93 patients who did not develop POCD were in the non-POCD group. POCD group education level was lower than non-POCD group (P

Fang Ye,1,&ast; Xiaonan Hou,1,&ast; Jie Chen,1 Hui Qin,1 Xiaojing Xu,1 Die Liu,1 Jing Liu,2 Qi Sun,1 Haiyan Liu,3 Fang Hu,4 Yuwan Zhou,5 Pengfei Xu,1,&ast; Qi Zhang1,&ast; 1Department of Pediatrics, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Pediatrics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi an, People’s Republic of China; 4Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510623, People’s Republic of China; 5Department of Prevention Care, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengfei Xu; Qi Zhang, Department of Pediatrics, China-Japan Friendship Hospital, No. 2 East Yinghua Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Email xpf@263.net; zhangqi0355@sina.comPurpose: The objective of this study was to investigate the behavioral changes in the core features and challenging behaviors of children with Autism Spectrum Disorder (ASD) during the COVID-19 Omicron wave (from December 2022 to January 2023) in China.Patients and Methods: A total of 515 caregivers of children with ASD completed an online survey. This survey was designed to assess the sociodemographic characteristics of the children and their caregivers, the clinical features of COVID-19, the manifestation of core ASD features and challenging behaviors, and the alterations in daily life following the COVID-19 Omicron variant wave.Results: The children with ASD had an average age of 5.4 years, with 79.6% being male. After the Omicron wave, the proportions of participants with worsening core ASD features and challenging behaviors were 22.9% and 37.1%, respectively. Sleep disorders (20.0%), eating problems (18.6%), and inattentive symptoms (17.5%) were the most frequently reported worsening behaviors. The factors associated with the worsening of core ASD features included infection with the Omicron variant of COVID-19, reduced outdoor activity, and a lower score of caregiver health-related quality of life (HRQoL). The worsening of challenging behaviors was associated with infection with the Omicron variant of COVID-19, a lower frequency of rehabilitation training, and a lower score of HRQoL.Conclusion: The outbreak of the COVID-19 Omicron variant had an impact on the behaviors of autistic children. The behavior changes in core ASD features and challenging behaviors differed and were associated with COVID-19 infection and other factors.Keywords: core feature, challenging behavior, behavior worsening, infection, autism spectrum disorder

Meili Xu,1,2 Hongliu Chen,1,2 Jianjing Chen,3 Rongzong Ye,4 Huan Xiao,1,2 Jingwen Li,4 Chaoqian Li1,2 1Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Guangxi University Key Laboratory of Emergency Medicine, Nanning, Guangxi, People’s Republic of China; 3Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Guangxi Medical University, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Chaoqian Li, Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email lichaoqiangood@163.comObjective: This study aimed to explore the factors influencing pulmonary fibrosis in patients with acute diquat poisoning through logistic regression analysis.Methods: A retrospective analysis was conducted on 68 cases of acute diquat poisoning due to suicidal intent admitted to our hospital from February 2020 to March 2023. Patients were divided into a combined group (28 cases with pulmonary fibrosis) and an acute diquat poisoning group (40 cases without). A healthy control group consisted of 40 individuals. General data were compared among the three groups, and laboratory indicators were analyzed. Single and multiple logistic regression analyses were performed to identify risk factors for pulmonary fibrosis.Results: There were no significant differences in gender, age, BMI, poisoning status, or treatment timing among the groups (P > 0.05). The combined group had significantly higher diquat ingestion dose, SIRS score, SOFA score, and APACHE II score compared to the poisoning group (P < 0.05). In the acute poisoning group, these scores were also higher than in the healthy controls (P < 0.05). Laboratory indicators, including Hb, PLT, ALP, DBil, ALB, BUN, Glu, BNP, and pH, showed no significant differences (P > 0.05). However, WBC, ALT, TBil, DBil, Cr, K+, Tn I, and Lac levels were significantly higher in the combined group compared to the acute poisoning group (P < 0.05). Logistic regression analysis identified factors influencing pulmonary fibrosis as diquat ingestion dose, K+, ALT, PaO2, Lac, and HCO3-.Conclusion: The factors influencing pulmonary fibrosis in acute diquat poisoning include diquat ingestion dose, K+, ALT, PaO2, Lac, and HCO3-. These findings enhance understanding of pulmonary fibrosis pathogenesis and may inform clinical management for affected patients.Keywords: acute diquat poisoning, pulmonary fibrosis, K+, ALT, PaO2