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Jiechu Wang,1– 3,&ast; Yao Yu,1,&ast; Ya Gao,1– 3,&ast; Tingting Wan,1– 3 Zhukai Cong,1– 3 Zhengqian Li,1– 3 Yang Zhou,1– 3 Xiaoxiao Wang,4 Luyang Feng,1– 3 Yongzheng Han,1– 3 Jing Zhang,1– 3 Yinyin Qu,1– 3 Xiangyang Guo1– 3 1Department of Anesthesiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Beijing Center of Quality Control and Improvement on Clinical Anesthesia, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 3Anesthesia and Perioperative Medicine Branch of China International Exchange and Promotive Association for Medical and Health Care (CPAM), Beijing, 100191, People’s Republic of China; 4Research Center for Clinical Epidemiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangyang Guo; Yinyin Qu, Department of Anesthesiology, Peking University Third Hospital, North Garden Road 49, Haidian District, Beijing, 100191, People’s Republic of China, Email puthmzk@hsc.pku.edu.cn; quyinyin@bjmu.edu.cnBackground: Malignant hyperthermia (MH) is a hypermetabolic syndrome with high mortality rates. Early detection and prompt intravenous administration of dantrolene are crucial for effective management of MH. However, there is currently a lack of comprehensive nationwide surveys on the availability of dantrolene and anesthesiologists’ understanding of MH in China.Methods: A nationwide survey was conducted between January 2022 and June 2022. Online questionnaires on the cognition of MH among anesthesiologists in China were sent through social platforms to anesthesiologists in mainland China. Data regarding participants’ perception of MH-related knowledge, availability of domestic dantrolene, and reported MH cases were collected in this study.Results: Responses were collected from a total of 11,354 anesthesiologists representing 31 provinces across the Chinese mainland. Among the 11 scoring questions, the highest accuracy rates were observed for the question regarding therapeutic drugs for MH (99.3%) and the characteristics of MH (98.0%). Conversely, the question pertaining to the earliest clinical signs of MH had the lowest accuracy rate (23.5%). Significant variations were observed in the scores among different professional titles (P=0.003), academic degree (P< 0.001), hospital classification (P< 0.001), and urban hierarchy (P< 0.001). Of the respondents, 919 (8.1%) anesthesiologists reported dantrolene availability in their hospitals, and 631 (5.6%) indicated unclear. A total of 136 hospitals in this survey reported at least one previous case of MH.Conclusion: Mainland China faces challenges such as insufficient experience in diagnosing and treating MH, as well as difficulty in obtaining dantrolene. To improve the public awareness of MH, it is imperative to establish and promote a refined MH training system. Additionally, a streamlined and rapid dantrolene linkage emergency system should be implemented to ensure prompt access to the drug.Keywords: malignant hyperthermia, dantrolene, China, anesthesiologists, survey

Dandan Qiu,1 Yan Zhu,1 Zhicheng Cong2 1Department of Urology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Urology, Zhejiang Hospital, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Zhicheng CongDepartment of Urology, Zhejiang Hospital, Hangzhou 310013 Zhejiang Province, People’s Republic of ChinaEmail cz111aybzz8@126.comBackground: The transcriptional regulator YAP is frequently overexpressed in human cancers, such as breast and pancreatic cancers, plays an important role in tumorigenesis and can regulate many factors affecting cancer progression. These observations encouraged us to investigate the effect of YAP expression on bladder cancer.Methods: The changes in multiple cellular functions associated with tumor progression including cell proliferation, cell migration, cell cycle, and cell apoptosis were assessed after YAP knockdown/overexpression in bladder cancer cell lines. Additionally, Western blot was developed to verify the change of proteins caused by YAP knockdown/overexpression.Results: YAP had relatively higher expression in bladder cancer tissues than in normal tissues. The proliferation and migration of bladder cancer cells were inhibited by YAP knockdown but were promoted by its overexpression. This promoting effect was accompanied by the increased activity of MAPK/ERK pathway.Conclusion: Our data established that YAP is an oncogene involved in bladder cancer and thus can be a potential target for treatment.Keywords: bladder cancer, proliferation, migration, MAPK/ERK pathway

Limei Wang,1,2 Jin Pei,1 Zhongcheng Cong,1 Yifang Zou,1 Tianmeng Sun,3 Fionán Davitt,4,5 Adrià Garcia-Gil,4,5 Justin D Holmes,4,5 Caitriona M O’Driscoll,6 Kamil Rahme,4,7 Jianfeng Guo1 1School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China; 2Department of Pharmacy, The General Hospital of FAW, Changchun 130011, China; 3The First Hospital of Jilin University, Changchun 130021, China; 4School of Chemistry and the Tyndall National Institute, University College Cork, Cork, Ireland; 5CRANN, Trinity College Dublin, Dublin, Ireland; 6Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland; 7Department of Sciences, Faculty of Natural and Applied Science, Notre Dame University (Louaize), Zouk Mosbeh 1200, Lebanon Background: Gold nanorods (AuNRs), due to the optical and electronic properties namely the surface plasma resonance, have been developed to achieve the light-mediated photothermal therapy (PTT) for cancer. However, PTT alone may suffer from inefficient tumor killing. Recently, the combination of PTT and chemotherapy has been utilized to achieve synergistic anticancer effects. Methods: In this study, AuNRs capped with hexadecyltrimethylammonium bromide (CTAB), poly(acrylic acid) (PAA), and PEGylated anisamide (a ligand known to target the sigma receptor) have been developed to produce a range of negatively charged anisamide-targeted PEGylated AuNRs (namely Au-CTAB-PAA-PEG-AA) for the combination of PTT and chemotherapy (termed as chemo-photothermal therapy [CPTT]). Epirubicin (EPI, an anthracycline drug) was efficiently loaded onto the surface of Au800-CTAB-PAA-PEG-AA via the electrostatic interaction forming Au800-CTAB-PAA-PEG-AA.EPI complex. Results: The resultant complex demonstrated pH-dependent drug release, facilitated nucleus trafficking of EPI, and induced antiproliferative effects in human prostate cancer PC-3 cells. When Au800-CTAB-PAA-PEG-AA.EPI complex was further stimulated with desired laser irradiation, the synergistic outcome was evident in PC-3 xenograft mice. Conclusion: These results demonstrate a promising strategy for clinical application of CPTT in cancer. Keywords: gold nanoparticles, non-viral drug delivery, chemotherapy, photothermal therapy, synergistic effect

Louis S Matza,1 Ze Cong,2 Karen Chung,2 Alison Stopeck,3 Katia Tonkin,4 Janet Brown,5 Ada Braun,2 Kate Van Brunt,6 Kelly McDaniel1 1Outcomes Research, United BioSource Corporation, Bethesda, MD, USA; 2Amgen, Inc, Thousand Oaks, CA, USA; 3Department of Medicine, University of Arizona, Tucson, AZ, USA; 4Department of Oncology, University of Alberta, Edmonton, Alberta, Canada; 5Leeds Institute of Molecular Medicine, St James University Hospital, Leeds, UK; 6formerly with Outcomes Research, United BioSource Corporation, Bethesda, MD, USA Introduction: Although cost-utility models are often used to estimate the value of treatments for metastatic cancer, limited information is available on the utility of common treatment modalities. Bisphosphonate treatment for bone metastases is frequently administered via intravenous infusion, while a newer treatment is administered as a subcutaneous injection. This study estimated the impact of these treatment modalities on health state preference. Methods: Participants from the UK general population completed time trade-off interviews to assess the utility of health state vignettes. Respondents first rated a health state representing cancer with bone metastases. Subsequent health states added descriptions of treatment modalities (ie, injection or infusion) to this basic health state. The two treatment modalities were presented with and without chemotherapy, and infusion characteristics were varied by duration (30 minutes or 2 hours) and renal monitoring. Results: A total of 121 participants completed the interviews (52.1% female, 76.9% white). Cancer with bone metastases had a mean utility of 0.40 on a standard utility scale (1 = full health; 0 = dead). The injection, 30-minute infusion, and 2-hour infusion had mean disutilities of −0.004, −0.02, and −0.04, respectively. The mean disutility of the 30-minute infusion was greater with renal monitoring than without. Chemotherapy was associated with substantial disutility (−0.17). When added to health states with chemotherapy, the mean disutilities of injection, 30-minute infusion, and 2-hour infusion were −0.02, −0.03, and −0.04, respectively. The disutility associated with injection was significantly lower than the disutility of the 30-minute and 2-hour infusions (P < 0.05), regardless of chemotherapy status. Conclusion: Respondents perceived an inconvenience with each type of treatment modality, but injections were preferred over infusions. The resulting utilities may be used in cost-utility models examining the value of treatments for the prevention of skeletal-related events in patients with bone metastases. Keywords: skeletal-related event, infusion, injection

Abstract Melanoma, recognized as the most aggressive type of skin cancer, has experienced a notable increase in cases, especially within populations with fair skin. This highly aggressive cancer is largely driven by UV radiation exposure, resulting in the uncontrolled growth and malignant transformation of melanocytes. The cGAS-STING pathway, an immune signaling mechanism responsible for detecting double-stranded DNA in the cytoplasm, is essential for mediating the immune response against melanoma. This pathway serves a dual purpose: it enhances antitumor immunity by activating immune cells, but it can also promote tumor growth when chronically activated by creating an immunosuppressive environment. This review comprehensively examines the multifaceted implication of the cGAS-STING pathway in melanoma pathogenesis and treatment. We explore its molecular mechanisms, including epigenetic regulation, interaction with signaling pathways such as AR signaling, and modulation by various cellular effectors like TG2 and activin-A. The therapeutic potential of modulating the cGAS-STING pathway is highlighted, with promising results from STING agonists, combination therapies with immune checkpoint inhibitors, and novel drug delivery systems, including nanoparticles and synthetic drugs. Our findings underscore the importance of the cGAS-STING pathway in melanoma, presenting it as a critical target for enhancing anti-tumor immunity. By leveraging this pathway, future therapeutic strategies can potentially convert ‘cold’ tumors into ‘hot’ tumors, making them more susceptible to immune responses.

Abstract Background The current study aimed to investigate the performances of clinical scales rated by clinicians and patients as well as cognitive function tests in distinguishing patients with affective and anxiety disorders from healthy controls (HCs). Methods We recruited a total of 122 subjects, comprising 24 patients with bipolar disorder (BD), 34 patients with major depressive disorder (MDD), 29 patients with anxiety disorder (AD), and 35 matched HCs. Three clinician-rated scales and five patient-rated scales were used to quantify clinical symptoms, while four cognitive tests were employed to measure cognitive functions in all subjects. Fisher’s discriminant analysis (FDA) was employed to distinguish patients from HCs, as well as to discriminate patient sub-groups from each other. In the FDA model, the prior probability of each group was set as 0.5 in the two-group classification and 0.25 in the four-group classification. Results The results showed that patient-rated scales achieved higher classification accuracies than clinician-rated scales in identifying MDD and AD from HCs. In contrast, cognitive tests exhibited the lowest accuracy. Conclusions These findings suggest that patient-rated scales might improve the classification accuracy for patients with MDD and AD.

Abstract While social media platforms promote people’s information exchange and dissemination, they also make rumors spread rapidly on online platforms. Therefore, how to detect rumors quickly, timely and accurately has become a hot topic for scholars in related fields. Traditional deep learning models ignore the relationship and topology between nodes in the rumor detection task and use fixed weights or mean aggregation strategies in the feature aggregation process, which fail to capture the complex interactions between nodes and the dynamics of information propagation, limiting the accuracy and robustness of the rumor detection model. To address these problems, we propose a location-aware weighted GraphSAGE rumor detection model GSMA. We first introduce an attention mechanism that dynamically assigns different attention weights to different neighboring nodes for different degrees of aggregation, improving GraphSAGE’s strategy of using mean-value aggregation for all neighboring nodes during the aggregation process; second, we introduce a modulated position encoding into the model and encode the position information of nodes into the features to improve the model’s ability to perceive the relative position and order of nodes; finally, the post text sentiment is incorporated into the features to provide additional semantic information for the model as a way to achieve rumor detection in microblogging platforms. Experiments show that the accuracy of the GSMA model on Ma-Weibo and Weibo23 reaches 97.43% and 97.55%, which is an improvement of 1.11% and 0.77% compared to the benchmark GraphSAGE, and all the evaluation metrics are also improved compared to other optimal rumor detection models.

Background/Aims Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Abstract Background Although the incidence of postoperative atelectasis could be reduced using lung recruitment manoeuvres, it remains high. We hypothesised that intraoperative visual lung recruitment guided by trans-oesophageal lung ultrasound would be more effective than the conventional method for managing postoperative atelectasis. Methods In this randomised, controlled, prospective study, 84 patients undergoing thoracoscopic lobectomy were recruited from Affiliated Chengdu Fifth People’s Hospital (teaching hospital) in China. Patients were grouped into trans-oesophageal lung ultrasound-guided (Group G, n = 42) and control (Group C, n = 42) groups. Methods Lung recruitment was performed after anaesthesia induction, before chest closure and before the endotracheal tube extubation. In Group C, recruitment pressure was controlled at 30 cm H2O for 10 s (performed thrice); in Group G, the pressure was controlled at 30 cm H2O (performed thrice), and the tidal volume did not exceed 20 ml kg−1 until no atelectasis was detected by trans-oesophageal ultrasound. The primary outcome was lung ultrasound scores measured at the post anaesthesia care unit 30 min after extubation. The secondary outcomes included the oxygenation index (30 min after extubation) and the incidence of atelectasis (30 min after extubation and 3 days after surgery). Results The final analysis included 79 patients. The lung ultrasound score was significantly higher in the control group than in the ultrasound-guided group 30 min after extubation (Group C vs. Group G, 8.6 ± 2.6 vs. 6.5 ± 2.0, P

Abstract Fullerene derivatives are extensively employed in inverted perovskite solar cells due to their excellent electron extraction capabilities. However, [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) agglomerates easily in solution and exhibits a relatively low ionization barrier, increasing charge recombination losses and charge accumulation in the interface. Here, tetramethylthiuram disulfide (TMDS) is introduced into the PCBM solution to induce the formation of reducing sulfur radicals through UV light irradiation, allowing for n doping of the PCBM material. The resulting modified PCBM layer exhibits enhanced conductivity and electron mobility, significantly suppressing charge recombination. As a result, the resulting devices incorporating TMDS achieve a champion efficiency of 26.10% (certified 25.39%) and 24.06% at a larger area (1.0 cm2) with negligible hysteresis. More importantly, the optimized devices retain 95% and 90% of their initial efficiency after 1090 h under damp heat testing (85 °C and 85% relative humidity) and after 1271 h under maximum power point-tracking conditions, respectively.

Abstract Background Anti-angiogenic, VEGF inhibitors (VEGFi) increase progression-free survival (PFS) and, in some cases, overall survival in many solid tumours. However, their use has been compromised by a lack of informative biomarkers. We have shown that plasma Tie2 is the first tumour vascular response biomarker for VEGFi in ovarian, colorectal and gall bladder cancer: If plasma Tie2 concentrations do not change after 9 weeks of treatment with a VEGFi, the patient does not benefit, whereas a confirmed reduction of at least 10% plasma Tie2 defines a vascular response with a hazard ratio (HR) for PFS of 0.56. The aim of the VALTIVE1 study is to validate the utility of plasma Tie2 as a vascular response biomarker and to optimise the Tie2-definition of vascular response so that the subsequent randomised discontinuation VALTIVE2 study can be powered optimally. Methods VALTIVE1 is a multi-centre, single arm, non-interventional biomarker study, with a sample size of 205 participants (176 bevacizumab-treated participants + 29 participants receiving bevacizumab and olaparib/PARPi), who are 16 years or older, have FIGO stage IIIc/IV ovarian cancer on treatment with first-line platinum-based chemotherapy and bevacizumab. Their blood plasma samples will be collected before, during, and after treatment and the concentration of Tie2 will be determined. The primary objective is to define the PFS difference between Tie2-defined vascular responders and Tie2-defined vascular non-responders in patients receiving bevacizumab for high-risk Ovarian Cancer. Secondary objectives include defining the relationship between Tie2-defined vascular progression and disease progression assessed according to RECIST 1.1 criteria and assessing the impact of PARPi on the plasma concentration of Tie2 and, therefore, the decision-making utility of Tie2 as a vascular response biomarker for bevacizumab during combined bevacizumab-PARPi maintenance. Discussion There is an urgent need to establish a test that tells patients and their doctors when VEGFi are working and when they stop working. The data generated from this study will be used to design a second trial aiming to prove conclusively the value of the Tie2 test. Trial registration ClinicalTrials.gov identifier: NCT04523116. Registered on 21 Aug 2020.

Introduction: Patients with acute mountain sickness (AMS) due to hypoxia at high altitudes often exhibit abnormal water metabolism. Hypoxia-inducible factors (HIFs) are major regulators of adaptive responses to hypoxia. As transcription factors, HIFs are involved in the regulation of erythropoiesis, iron metabolism, angiogenesis, energy metabolism, and cell survival by promoting the transcriptional expression of hundreds of target genes. Roxadustat, a novel drug for the treatment of anemia associated with chronic kidney disease, acts by inhibiting the degradation of HIFs to increase their protein levels. However, the clinical use of roxadustat is frequently associated with peripheral edema, suggesting the involvement of HIFs in regulating the body's water balance possibly by modulating water reabsorption in the kidney. Methods: we first evaluated the effect of hypoxia (8% O2) on mouse urine output. We then performed in vitro experiments using hypoxia (1% O2) and roxadustat on mouse primary proximal tubular cells (mPTCs). The qPCR, western blot, and immunofluorescence were used to assess AQP1 mRNA and protein expression levels. Luciferase, CHIP, and EMSA were used to investigate the transcriptional regulation of AQP1 by HIF1α. Results: We found that mice exposed to hypoxia (8% O2) had significantly reduced urine volume compared to mice exposed to normoxia (21% O2). Hypoxia significantly elevated AQP1 expression at both mRNA and protein levels. In vitro experiments using mouse primary cultured proximal tubular cells (mPTCs) revealed that both hypoxia and roxadustat increased AQP1 expression. Mechanistically, overexpression of HIF1α, but not HIF2α, markedly increased AQP1 protein expression. Furthermore, the up-regulation of AQP1 by hypoxia and roxadustat can be blocked by the HIF1α inhibitor PX-478 in mPTCs. Finally, we found that the AQP1 gene promoter contains a putative hypoxia response element (HRE) and confirmed that AQP1 is a target gene of HIF1α using Luciferase reporter, CHIP, and EMSA assays. Conclusion: This study demonstrates that hypoxia can reduce the urine volume of mice via upregulating AQP1 expression by HIF1α in the proximal tubular epithelial cells. Our findings also suggest a potential mechanism involved in water metabolism disorders in patients with AMS and in patients with chronic kidney disease (CKD) receiving roxadustat treatment.

Abstract Detecting chemical reaction dynamics at solid-liquid interfaces is important for understanding heterogeneous reactions. However, there is a lack of exploration of interface reaction dynamics from the single-molecule perspective, which can reveal the intrinsic reaction mechanism underlying ensemble experiments. Here, single-event protonation reaction dynamics at a solid-liquid interface are studied in-situ using single-molecule junctions. Molecules with amino terminal groups are used to construct single-molecule junctions. An interfacial cationic state present after protonation is discovered. Real-time electrical measurements are used to monitor the reversible reaction between protonated and deprotonated states, thereby revealing the interfacial reaction mechanism through dynamic analysis. The protonation reaction rate constant has a linear positive correlation with proton concentration, whereas the deprotonation reaction rate constant has a linear negative correlation. In addition, external mechanical forces can effectively regulate the protonation reaction process. This work provides a single-molecule perspective for exploring interface science, which will contribute to the development of heterogeneous catalysis and electrochemistry.

Abstract Skin cancer is a common disease resulting from genetic defects, and early detection is critical to improve treatment outcomes. Diagnostic programs that use computer aid especially those that use supervised learning are very useful in early diagnosis of skin cancer. This research therefore presents a new approach that integrates optimization methods with supervised learning to improve skin cancer diagnosis using machine vision approach. The presented method is initiated by data pre-processing that involves the removal of unnecessary data. Then, to segment the images, a combination of K-means clustering and social spider optimization technique is employed. The region of interest is then extracted from the segmented image and from this region a convolutional neural network extracts the significant features. To enhance the classification performance as compared with the standard classifiers, this research introduces a new concept of error correcting output codes coupled with a weighted Hamming distance in the group of gamma classifiers. The ability of the proposed approach in segmentation of skin lesions and classifying them was tested using samples from the ISIC-2017 and ISIC-2016 databases. The introduced method obtained state-of-the-art accuracy on both datasets (ISIC-2016: 97.10%, ISIC-2017: 95.17%). In particularly, the accuracy of the introduced approach for both these databases is at least 1.17% higher than the compared methods. This proves the high performance of the suggested method based on the usage of the convolutional neural networks for feature extraction and gamma classifiers with error correcting output codes for classification in skin cancer detection.

Abstract The existing deep estimation networks often overlook the issue of computational efficiency while pursuing high accuracy. This paper proposes a lightweight self-supervised network that combines convolutional neural networks (CNN) and Transformers as the feature extraction and encoding layers for images, enabling the network to capture both local geometric and global semantic features for depth estimation. First, depth-separable convolution is used to construct a dilated convolution residual module based on a shallow network to improve the shallow CNN feature extraction receptive field. In the transformer, a multidepth separable convolution head transposed attention module is proposed to reduce the computational burden of spatial self-attention. In the feedforward network, a two-step gating mechanism is proposed to improve the nonlinear representation ability of the feedforward network. Finally, the CNN and transformer are integrated to implement a depth estimation network with a local-global context interaction function. Compared with other lightweight models, this model has fewer model parameters and higher estimation accuracy. It also has better generalizability for different outdoor datasets. Additionally, the inference speed can reach 87 FPS, achieving better real-time performance and accounting for both inference speed and estimation accuracy.

Abstract Background Bipolar disorder (BPD) is a kind of manic and depressive phase alternate episodes of serious mental illness, and it is correlated with well-documented cortical brain abnormalities. Emerging evidence supports that autophagy dysfunction in neuronal system contributes to pathophysiological changes in neurological disease. However, the role of autophagy in bipolar disorder has rarely been elucidated. This study aimed to identify the autophagy-related gene as a potential biomarker Correlated to immune infiltration in BPD. Methods The microarray dataset GSE23848 and autophagy-related genes (ARGs) were downloaded. Differentially expressed genes (DEGs) between normal and BPD samples were screened using the R software. Machine learning algorithms were performed to screen the significant candidate biomarker from autophagy-related differentially expressed genes (ARDEGs). The correlation between the screened ARDEGs and infiltrating immune cells was explored through correlation analysis. Results In this study, the autophagy pathway was abundantly enriched and activated in BPD, as indicated by Pathway enrichment analysis. We identified 16 ARDEGs in BPD compared to the normal group. A signature of 4 ARDEGs (ERN1, ATG3, CTSB, and EIF2AK3) was screened. ROC analysis showed that the above genes have good diagnostic performance. In addition, immune correlation analysis considered that the above four genes significantly correlated with immune cells in BPD. Conclusions Autophagy - immune cell axis mediates pathophysiological changes in BPD. Four important ARDEGs are prospective to be potential biomarkers associated with immune infiltration in BPD and helpful for the prediction or diagnosis of BPD.

INTRODUCTION: The aim of this meta-analysis was to investigate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood glucose and weight in adolescents with overweight/obesity and/or type 2 diabetes mellitus (T2DM) aged

The phases, microstructure, and mechanical properties of Si-alloyed (Ti28Zr40Al20Nb12)100-xSix (x = 1, 3, 5, 10) high entropy alloys are studied. Although silicides were not detected in the as-cast 1 at. % Si-alloyed sample, after annealing all the four alloys have the same phase composition: the Zr5Al3-type phase, Zr5Si3-type silicides, and the BCC/B2 dual-phase matrix, indicating that 1 at. % Si addition is adequate for the formation of silicides in equilibrium. The phase morphologies show a dependence on the Si content and the cooling rate, which changed from the occurrence of columnar grain zones together with coarse dendrites of the as-cast 1 at. % Si-alloyed alloy to four different cooling-rate-related morphologies in the other three as-cast alloys. After heat treatment, differently shaped precipitates tend to aggregate and spherize, and a three-step-shaped phase morphology is observed when the Si content is above 5 at. %. All precipitates are rich in Zr due to either the strong Si–Zr pair or Al–Zr pair, but heterogeneous distributions of Si and Al exist. An increase of the Si content led to a gradual decrease of the compressive strength in both as-cast and annealed samples, yet the total fracture strain does not show monotonously decrease trend. 5 at. % Si-alloyed samples possessed a higher total fracture strain than the 3 at. % Si-alloyed samples.