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Abstract Papillary thyroid cancer (PTC) is often characterized by indolent behavior, small tumors with slow cell proliferation and a tendency to metastasize to cervical lymph node simultaneously, and the molecular mechanisms underlying that remain poorly understood. In this study, FN1 was the hottest gene of PTC and distinctive expression in PTC cells. FN1 deficiency severely inhibited the p53 signaling pathway, especially cyclin proteins, resulting in increased cell growth but hampered invasion. The alternatively splicing EDB region of FN1 was exclusively expressed in tumors, which impacted integrin β1 (ITGB1) bonding FN1 and its secretion process, resulting in completely distinct roles of two isoforms that FN1 including and skipping EDB domain. The isoform EDB(–)FN1 intracellularly inhibited tumor proliferation by upregulating p21 expression, whereas extracellular EDB(+)FN1 promoted lymph node metastasis via the VEGF signaling pathway in vitro and in vivo. Moreover, the alternative splicing EDB region of FN1 was modulated by p53-targeted protein ZMAT3 which activated cell migration and lymphoangiogenesis. Collectively, combined with p53-induced proteins, FN1 played both anti- and pro-cancer roles owing to EDB domain alternative splicing. FN1 is a potential determinant behind the characteristic behavior of PTC, which may contribute to a deeper understanding of the peculiarity of PTC and provide a promising target for regional lymph node metastasis.

Abstract The development of tumor vaccines represents a significant focus within cancer therapeutics research. Nonetheless, the efficiency of antigen presentation in tumor vaccine remains suboptimal. We introduce an innovative mRNA-lipid nanoparticle platform designed to express tumor antigenic epitopes fused with the transmembrane domain and cytoplasmic tail of the neonatal Fc receptor (FcRn). This novel design exploits FcRn trafficking signals to direct the epitope-FcRn fusion toward endolysosomal degradation, thereby generating epitopes capable of eliciting targeted T cell responses and establishing immune memory. The FcRn-directed presentation of epitopes enhances MHC class I and II antigen presentation, thereby robustly inducing CD4+ and CD8+ T cell responses, which translates to the inhibition of tumor growth and extension of survival in preclinical mouse models. In summary, the deliberate incorporation of FcRn trafficking signals into vaccine design markedly boosts T cell responses, underscoring the promise of this novel strategy in advancing the efficacy of tumor vaccines.

Abstract We explore the decay of bound neutrons in the JUNO liquid scintillator detector into invisible particles (e.g., $$n\rightarrow 3 \nu $$ n → 3 ν or $$nn \rightarrow 2 \nu $$ n n → 2 ν ), which do not produce an observable signal. The invisible decay includes two decay modes: $$ n \rightarrow { inv} $$ n → inv and $$ nn \rightarrow { inv} $$ n n → inv . The invisible decays of s-shell neutrons in $$^{12}\textrm{C}$$ 12 C will leave a highly excited residual nucleus. Subsequently, some de-excitation modes of the excited residual nuclei can produce a time- and space-correlated triple coincidence signal in the JUNO detector. Based on a full Monte Carlo simulation informed with the latest available data, we estimate all backgrounds, including inverse beta decay events of the reactor antineutrino $${\bar{\nu }}_e$$ ν ¯ e , natural radioactivity, cosmogenic isotopes and neutral current interactions of atmospheric neutrinos. Pulse shape discrimination and multivariate analysis techniques are employed to further suppress backgrounds. With two years of exposure, JUNO is expected to give an order of magnitude improvement compared to the current best limits. After 10 years of data taking, the JUNO expected sensitivities at a 90% confidence level are $$\tau /B( n \rightarrow { inv} ) > 5.0 \times 10^{31} \, \textrm{years}$$ τ / B ( n → inv ) > 5.0 × 10 31 years and $$\tau /B( nn \rightarrow { inv} ) > 1.4 \times 10^{32} \, \textrm{years}$$ τ / B ( n n → inv ) > 1.4 × 10 32 years .

Yitong Zhang,1 Liang Zhou,2 Simin Zhu,1 Yanuo Zhou,1 Zitong Wang,1 Lina Ma,1 Yuqi Yuan,1 Yushan Xie,1 Xiaoxin Niu,1 Yonglong Su,1 Haiqin Liu,1 Xinhong Hei,2 Zhenghao Shi,2 Xiaoyong Ren,1 Yewen Shi1 1Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 2School of Computer Science and Engineering, Xi’an University of Technology, Xi’an, Shaanxi Province, People’s Republic of ChinaCorrespondence: Xiaoyong Ren; Yewen Shi, Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, Address: NO. 157 Xi Wu Road, Xi’an, Shaanxi Province, Email cor_renxiaoyong@126.com; shiyewen59@outlook.comPurpose: To develop a deep learning (DL) model for obstructive sleep apnea (OSA) detection and severity assessment and provide a new approach for convenient, economical, and accurate disease detection.Methods: Considering medical reliability and acquisition simplicity, we used electrocardiogram (ECG) and oxygen saturation (SpO2) signals to develop a multimodal signal fusion multiscale Transformer model for OSA detection and severity assessment. The proposed model comprises signal preprocessing, feature extraction, cross-modal interaction, and classification modules. A total of 510 patients who underwent polysomnography were included in the hospital dataset. The model was tested on hospital and public datasets. The hospital dataset was utilized to demonstrate the applicability and generalizability of the model. Two public datasets, Apnea-ECG dataset (consisting of 8 recordings) and UCD dataset (consisting of 21 recordings), were used to compare the results with those of previous studies.Results: In the hospital dataset, the accuracy (Acc) values of per-segment and per-recording detection were 91.38 and 96.08%, respectively. The Acc values for mild, moderate, and severe OSA were 90.20, 88.24, and 92.16%, respectively. The Bland‒Altman plots revealed the consistency of the true apnea–hypopnea index (AHI) and the predicted AHI. In the public datasets, the per-segment detection Acc values of the Apnea-ECG and UCD datasets were 95.04 and 90.56%, respectively.Conclusion: The experiments on hospital and public datasets have demonstrated that the proposed model is more advanced, accurate, and applicable in OSA detection and severity assessment than previous models.Keywords: obstructive sleep apnea, multimodal signals fusion, deep learning, detection model

Abstract The cultivation and differentiation of human embryonic stem cells (hESCs) into organoids are crucial for advancing of new drug development and personalized cell therapies. Despite establishing of chemically defined hESC culture media over the past decade, these media's reliance on growth factors, which are costly and prone to degradation, poses a challenge for sustained and stable cell culture. Here, we introduce an hESC culture system(E6Bs) that facilitates the long-term, genetically stable expansion of hESCs, enabling cells to consistently sustain high levels of pluripotency markers, including NANOG, SOX2, TRA-1–60, and SSEA4, across extended periods. Moreover, organoids derived from hESCs using this medium were successfully established and expanded for at least one month, exhibiting differentiation into cortical organoids, GABAergic precursor organoids and heart-forming organoids. This innovative system offers a robust tool for preserving hESC homeostasis and modeling the nervous system in vitro.

Abstract The frequency-modulated continuous-wave (FMCW) technology combined with optical phased array (OPA) is promising for the all-solid-state light detection and ranging (LiDAR). We propose and experimentally demonstrate a silicon integrated OPA combined with an optical frequency microcomb for parallel LiDAR system. For realizing the parallel wavelengths emission consistent with Rayleigh criterion, the wide waveguide beyond single mode region combined with the bound state in the continuum (BIC) effect is harnessed to obtain an ultra-long optical grating antenna array. The single soliton comb, generating about multiple distinct wavelength channels and combined with the high performance integrated OPA, is also demonstrated for coherent three-dimensional (3D) imaging by utilizing FMCW method. The modulation bandwidth of parallel modulation of the microcomb is beyond the modulation region of single soliton microcomb. The result paves the way for developing all-solid-state and ultrahigh-frame-rate coherent LiDAR systems.

Abstract The rapid advancements in artificial intelligence (AI) are catalyzing transformative changes in atomic modeling, simulation, and design. AI-driven potential energy models have demonstrated the capability to conduct large-scale, long-duration simulations with the accuracy of ab initio electronic structure methods. However, the model generation process remains a bottleneck for large-scale applications. We propose a shift towards a model-centric ecosystem, wherein a large atomic model (LAM), pre-trained across multiple disciplines, can be efficiently fine-tuned and distilled for various downstream tasks, thereby establishing a new framework for molecular modeling. In this study, we introduce the DPA-2 architecture as a prototype for LAMs. Pre-trained on a diverse array of chemical and materials systems using a multi-task approach, DPA-2 demonstrates superior generalization capabilities across multiple downstream tasks compared to the traditional single-task pre-training and fine-tuning methodologies. Our approach sets the stage for the development and broad application of LAMs in molecular and materials simulation research.

Abstract Background Minor salivary gland (MSG) biopsy is a critical but invasive method for the classification of primary Sjögren’s disease (pSjD). Here we aimed to identify salivary proteins as potential biomarkers and to establish a non-invasive prediction model for pSjD. Methods Liquid chromatography-tandem mass spectrometry was conducted on whole saliva samples from patients with pSjD and non-Sjögren control subjects (non-pSjD). Proteins involved in immune processes were upregulated in the pSjD group, such as complement C3 (C3), complement factor B (CFB), clusterin (CLU), calreticulin (CALR), and neutrophil elastase (NE), which were further confirmed by ELISA. Multivariate logistic regression analyses were performed to identify markers that differentiated pSjD from non-pSjD; receiver operating characteristic (ROC) curves were constructed. A diagnostic model based on the combination of salivary biomarkers (CFB, CLU, and NE), serum autoantibodies (anti-SSA /Ro60 and anti-SSA/Ro52), and Schirmer’s test was evaluated in 186 patients (derivation cohort) with replication in 72 patients (validation cohort). Results In multivariate analyses, CFB, CLU, and NE were independent predictors of pSS. A model based on the combination of salivary biomarkers (CFB, CLU, and NE), serum autoantibodies (anti-SSA and anti-Ro52), and Schirmer’s test achieved significant discrimination of pSS. In the derivation cohort, the area under curve (AUC) of the ROC was 0.930 (95% CI 0.877–0.965, P

Abstract A randomized double-blind phase 3 trial (CHOICE-01, NCT03856411) demonstrated that combining toripalimab with chemotherapy substantially improves progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients without pretreatment. This study presents the prespecified final analysis of overall survival (OS) and biomarkers utilizing circulating tumor DNA (ctDNA) and tissue-based sequencing. Additionally, the analysis revealed a higher median overall survival (OS, 23.8 months) in the toripalimab group than that in the control group (17.0 months). (HR = 0.69, 95%CI: 0.57–0.93, nominal P = 0.01). This survival benefit was particularly notable in the non-squamous subgroup. As the first phase 3 study to perform both baseline tissue whole-exome sequencing (WES) and peripheral blood ctDNA testing, we investigated efficacy predictive biomarkers based on both tissue and ctDNA, Genomic sequencing of ctDNA showed high concordance with tumor tissue independently confirmed that individuals exhibiting a high tumor mutational burden, as well as mutations in the FA-PI3K-Akt and IL-7 signaling pathways benefited more from the toripalimab treatment. Furthermore, a ctDNA response observed on cycle 3 day 1, was associated with improved clinical outcomes for patients treated with the combination therapy. In conclusion, Toripalimab plus chemotherapy yields significant improvements in OS as a first-line treatment. The study highlights the utility of ctDNA as a proxy for tumor tissue, providing novel prospects for predicting efficacy of immuno-chemotherapy through continuous ctDNA monitoring.

Abstract CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045. HB0045 is a 1:1 mixture of two humanized monoclonal IgG1 antibodies (mAbs), HB0038 and HB0039. The cocktail not only harnesses the advantages of its parental mAbs in enzyme inhibition but also shows a significantly greater capability of promoting T cell proliferation in vitro. Structural analyses show that HB0045 effectively locks the CD73 dimer in a “partially open” non-active conformation through a double lock mechanism. In various animal models of syngeneic and xenograft tumors, HB0045 inhibits tumor growth more potently than the single mAbs. Collectively, our findings provide functional and structural insights into the mechanism of a CD73-targeting antibody cocktail.

Abstract The solid-state integration of molecular electron spin qubits could promote the advancement of molecular quantum information science. With highly ordered structures and rational designability, microporous framework materials offer ideal matrices to host qubits. They exhibit tunable phonon dispersion relations and spin distributions, enabling optimization of essential qubit properties including the spin-lattice relaxation time (T 1) and decoherence time. In this study, through spin dynamic and vibrational spectroscopic characterizations of two radical-embedded framework materials, we show that hydrogen-bonded networks give rise to a low Debye temperature of acoustic phonons and generates sub-terahertz optical phonons, both of which facilitate spin-lattice relaxation. Whereas deuterating hydrogen-bonded networks reduces both phonon frequencies and T 1, eliminating such flexible structural motifs raises phonon dispersions and improves the T 1 by one to two orders of magnitude. The phononic tunability of spin-lattice relaxation in molecular qubit frameworks would facilitate the development of solid-state qubits operating at elevated temperatures.

Flavonoid glycosides are widespread in plants, and are of great interest owing to their diverse biological activities and effectiveness in preventing chronic diseases. Periploca forrestii, a renowned medicinal plant of the Apocynaceae family, contains diverse flavonoid glycosides and is clinically used to treat rheumatoid arthritis and traumatic injuries. However, the mechanisms underlying the biosynthesis of these flavonoid glycosides have not yet been elucidated. In this study, we used widely targeted metabolomics and full-length transcriptome sequencing to identify flavonoid diversity and biosynthetic genes in P. forrestii. A total of 120 flavonoid glycosides, including 21 C-, 96 O-, and 3 C/O-glycosides, were identified and annotated. Based on 24,123 full-length coding sequences, 99 uridine diphosphate sugar-utilizing glycosyltransferases (UGTs) were identified and classified into 14 groups. Biochemical assays revealed that four UGTs exhibited O-glycosyltransferase activity toward apigenin and luteolin. Among them, PfUGT74B4 and PfUGT92A8 were highly promiscuous and exhibited multisite O-glycosylation or consecutive glycosylation activities toward various flavonoid aglycones. These four glycosyltransferases may significantly contribute to the diversity of flavonoid glycosides in P. forrestii. Our findings provide a valuable genetic resource for further studies on P. forrestii and insights into the metabolic engineering of bioactive flavonoid glycosides.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Abstract Aim Metabolic dysfunction-associated steatotic disease (MASLD) and chronic hepatitis B (CHB) are prevalent liver disorders. Ongoing discussions investigate the impact of MASLD on the therapeutic outcomes of CHB. Methods A cohort of 320 CHB patients on antiviral therapy (including NAs and PEG IFNα) were included and categorized into CHB + MASLD (n = 125) and CHB group (n = 195). The treatment response rates, Kaplan–Meier survival analysis, and Cox regression were assessed between the two groups to investigate the impact of MASLD on antiviral responses in patients with CHB. Results At weeks 24 and 48, the CHB + MASLD group displayed a higher HBsAg response rate than the CHB group (24 weeks: 11.5% vs. 3.8%, p = 0.026; 48 weeks: 24.4% vs. 8.4%, p = 0.001). The pgRNA response was also higher in the CHB + MASLD group at both time points (24 weeks: 30.9% vs. 19.7%, p = 0.163; 48 weeks: 48.8% vs. 28.3%, p = 0.049). Kaplan–Meier survival analysis revealed a shorter median time to HBsAg response at 48 weeks for the CHB + MASLD group (HR = 3.251, 40 weeks vs. 42.5 weeks, p = 0.002). This is particularly evident among individuals who are negative for HBeAg (48w: 24.2% vs 12.2%, p = 0.005). KM survival analysis demonstrated that the CHB + MASLD group was more likely to achieve HBsAg response (HR = 2.428, p = 0.039).COX regression analysis identified age (HR = 0.948, p = 0.005), antiviral regimen (NAs + PEG IFNα: HR = 5.33, p

Abstract Abnormal angiogenesis is a key process associated with ischaemic retinopathies such as diabetic retinopathy, for which the underlying pathological mechanisms are still poorly understood. Here, we confirm that angiogenic factor 1 with a G patch and FHA domain (AGGF1) is elevated in the diabetics and induces retinal angiogenesis. Mechanistic investigations demonstrate that HIF-1α directly regulates AGGF1 expression. AGGF1 upregulates the expression of cell cycle proteins by increasing the binding of tumour necrosis factor ligand superfamily member 12 (TNFSF12) to fibroblast -growth -factor-inducible 14 (FN14, TNFRSF12A). Furthermore, targeting AGGF1 attenuates pathological neovascularisation in ischaemic retinopathy. Additionally, we discover that sodium-glucose cotransporter 2 inhibitors (SGLT2i) could inhibit the AGGF1 signalling pathway early to achieve therapeutic effects. Overall, we elucidate the mechanism underlying pathological retinal angiogenesis involved in endothelial AGGF1-dependent events and highlight a therapy for the effective treatment of ischaemic retinopathy.

Abstract Aberrant release of mitochondrial reactive oxygen species (mtROS) in response to cellular stress is well known for promoting cancer progression. However, precise molecular mechanism by which mtROS contribute to epithelial cancer progression remains only partially understood. Here, using colorectal cancer (CRC) models, we show that upon sensing excessive mtROS, phosphatase PGAM5, which normally localizes to the mitochondria, undergoes aberrant cleavage by presenilin-associated rhomboid-like protein (PARL), becoming released into the cytoplasm. Cytosolic PGAM5 then directly binds to and dephosphorylates MST3 kinase. This, in turn, prevents STK25-mediated LATS1/2 phosphorylation, leading to YAP activation and CRC progression. Importantly, depletion of MST3 reciprocally promotes accumulation of cytosolic PGAM5 by inducing mitochondrial damage. Taken together, these findings demonstrate how mtROS promotes CRC progression by activating YAP via a post-transcriptional positive feedback loop between PGAM5 and MST3, both of which can serve as potential targets for developing next-generation anti-colon cancer therapeutics.

Jing Xue,1 Tianyun Qu,1 Zhigang Li,1 Bo Shi,1 Guang Yang,1 Xiaocui Rong,1 Yazhou Li,1 Guoquan Lin,2 Yong Ping1 1Department of Radiology; Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2Department of General Surgery; Botou Hospital, Cangzhou City, Hebei Province, 062150, People’s Republic of ChinaCorrespondence: Yong Ping, Email Ulrica150sci@163.comObjective: To evaluate the association between background parenchymal enhancement (BPE) level and extent on contrast-enhanced mammography (CEM) with age, menopausal status, breast density, and menstrual cycle phase in women. Additionally, to characterize the dynamic changes in BPE during CEM.Methods: This retrospective study included 103 women who underwent CEM at a single institution between September 2019 and November 2021 for screening or diagnostic purposes. Menopausal status and menstrual cycle phase were recorded for all patients. BPE on subtracted CEM images was assessed quantitatively (region of interest [ROI] analysis of pixel values) and qualitatively (subjective classification). Statistical analysis was performed to determine the relationship between BPE (level and extent) and age, menopausal status, breast density, and menstrual cycle phase. Dynamic changes in BPE level over time were also analyzed.Results: Both BPE level and extent were negatively correlated with age (P=0.004, r=− 0.280; P=0.001, r=− 0.318). Postmenopausal women exhibited lower BPE level and extent compared to premenopausal women (P=0.003, Z=− 2.958; P=0.042, 2=4.123). No significant association was observed between BPE and breast density or menstrual cycle phase (P> 0.05). BPE level increased significantly from 3 to 9 minutes post-contrast injection (P< 0.001, t=− 10.7).Conclusion: BPE in CEM is significantly associated with age and menopausal status. Further research is needed to clarify the relationship between BPE and breast density and menstrual cycle phase. BPE demonstrates a dynamic increase in level over time, this relates to post-contrast injection, rather than to the age of the woman.Keywords: Mammography, Breast, Female Patients

Yunfu Chen,1,&ast; Guangling Tang,1,&ast; Jun Lu,1,&ast; Sijie Tang,1 Xinglong Xiong,1 Chao Chen,1 Lijian Pei,2 Jing Shi1 1Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guizhou, People’s Republic of China; 2Department of Anesthesiology, Peking Union Medical College Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Shi, Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China, Tel +86-18685034016, Email shijing81@gmc.edu.cn Lijian Pei, Department of Anesthesiology, Peking Union Medical College Hospital, Beijing, People’s Republic of China, Email hazelbeijing@vip.163.comBackground: The neuropathic pain side induced by Vincristine severely limit its clinical application. However, the mechanism of neuropathic pain is not clear. This study aims to clarify the mechanism of C/EBP-β regulating TGF-β 1 mediated spinal astrocyte A1/A2 polarization in the neuropathic pain caused by vincristine.Methods: Neuropathic pain model was established in rats by intraperitoneal injection of Vincristine (VCR). In vitro experiment, the astrocyte model was constructed by Vincristine, and si-C/EBP-β was regulated before VCR administration. Pain threshold of rats was measured by thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT), Elisa was used to detect the expression level of inflammatory factors, qRT PCR and Western blotting were used to detect astrocyte polarization markers, C/EBP-β, TGF-β 1, p-smad2 and p-smad3.Results: Following Vincristine administration, the TWL and MWT of rats exhibited a decrease. Additionally, there was an increase in A1 polarization of astrocytes, while A2 polarization remained relatively unchanged. Furthermore, the expression levels of pro-inflammatory factors were elevated, whereas no significant alterations were observed in anti-inflammatory factors. Notably, Vincristine promoted the expression of C/EBP-β and TGF-β 1. TGF-β 1 inhibitor alleviated VCR induced astrocyte A1 polarization and release of proinflammatory factors, ameliorated abnormal pain. Moreover, silencing C/EBP-β reversed the enhanced expression of TGF-β 1 induced by Vincristine, attenuated astrocyte A1 polarization and proinflammatory factor release.Conclusion: Vincristine induced spinal cord inflammation by promoting A1 polarization of astrocytes via upregulating the C/EBP-β/TGF-β 1 signal pathway, thus leading to neuropathic pain. It was different from the traditional signal pathway, this study shown a new signal pathway for astrocyte A1 polarization, which may provide a possibility for clinical treatment of neuropathic pain.Keywords: neuropathic pain, astrocytes, C/EBP-β, TGF-β 1, neuroinflammation

Gang Zeng,1,2,&ast; Rongyu Liang,2,3,&ast; Lingxian Xiao,2,4,&ast; Weiye Cao,5 Wenqing Zhou,2,6 Wen Wang,5 Cuixia Liu,2,7 Huarong Zhou,1,2 Xiaolei Shi,1,2 Ben Chen,1,2 Wanhua Chen2,4 1Geriatric Neuroscience Center, The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Department of Geriatric Psychiatry, The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Department of Nursing, The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 5School of Nursing, Guangzhou Medical University, Guangzhou, People’s Republic of China; 6Adult Psychiatry Department, The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 7Chronic Psychiatry Department, The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenqing Zhou, Adult Psychiatry Department, Affiliated Brain Hospital of Guangzhou Medical University, 36 mingXin Road, Liwan District, Guangzhou, People’s Republic of China, Tel +86 15918636953, Email 996459134@qq.com Weiye Cao, School of Nursing, Guangzhou Medical University, 195 Dongfeng West Road, Yuexiu District, Guangzhou, People’s Republic of China, Tel +86 13149399874, Email 1271932456@qq.comObjective: Negative symptoms significantly impair daily functioning and worsen clinical outcomes. Meanwhile, these symptoms are closely linked to anxiety and depression, further complicating prognosis. The mechanisms underlying these relationships remain unclear. This study aims to identify the factors influencing negative symptoms in schizophrenia and examine their relationship with anxiety and depression to guide more effective interventions and improve patient outcomes.Methods: This study recruited 300 inpatients with schizophrenia from October 2022 to May 2023. Sociodemographic data and clinical characteristics were collected via a self-designed questionnaire. Negative symptoms, depression, and anxiety were assessed using the SANS, HAMD, and HAMA scales, respectively.Results: Multiple regression analysis indicated that familial support (β = − 1.285, P = 0.005), friend support (β = − 0.797, P = 0.032), sleep quality (β = 2.307, P < 0.001), anxiety (β = 0.264, P = 0.004), and depression (β = 0.324, P = 0.007) were the main factors influencing negative symptoms. After adjusting for the duration of psychiatric disorder and type of antipsychotic medication as covariates, the above factors remained primary contributors to negative symptoms.Conclusion: Enhancing familial support, friend support, and addressing emotional health and sleep disturbances are strategies that may alleviate negative symptoms in patients with schizophrenia.Keywords: negative symptoms, anxiety, depression, schizophrenia, mental health

Zhan Wang,1,&ast; Pengpeng Zhang,2,&ast; Run Shi,3,&ast; Shuai Yang,1 Kui Liu,4 Zhaokai Zhou,1 Qi Li5 1Pediatric Urodynamic Center, Department of Urology, The First Affiliated Hospital of Zhengzhou University, Henan Joint International Pediatric Urodynamic Laboratory, Zhengzhou, 450052, People’s Republic of China; 2Department of Lung Cancer, Tianjin Lung Cancer Center, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Pediatric Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471000, People’s Republic of China; 5Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaokai Zhou, Pediatric Urodynamic Center, Department of Urology, The First Affiliated Hospital of Zhengzhou University, Henan Joint International Pediatric Urodynamic Laboratory, Zhengzhou, 450052, People’s Republic of China, Email 13526278113@163.com Qi Li, Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China, Email siloam1994@163.comBackground: Nocturnal enuresis (NE) and obstructive sleep apnea (OSA) are common diseases in children, which often cause various social and psychological problems. The coexistence of both seriously affects the physical and mental health of children. However, whether OSA can directly lead to NE and the specific pathogenesis is still unclear. Moreover, the benefits of surgical and non-surgical treatments for OSA on NE symptoms remain controversial. This review summarizes the relationship between NE and OSA and how to treat them, aiming to provide a reference for the clinical treatment of OSA and NE in children.Methods: All pertinent original publications to this point from PubMed database have been collected, including investigations on the connection between OSA and NE as well as studies on the mechanism and therapeutic strategy of NE in children with OSA.Results: There is a bidirectional relationship between OSA and NE in children. NE increases with the incidence of OSA, and children with NE often have sleep-disordered respiratory disease. Children with OSA may be susceptible to NE due to aberrant humoral factors secretion, sleep-wake disorder, bladder dysfunction, obesity, and psychosomatic factors. It has been suggested that adenotonsillectomy (AT) may be the best treatment option for children suffering from OSA with NE. The benefits of positive airway pressure (PAP) therapy in children with NE remain to be further studied.Conclusion: NE and OSA comorbidity seriously affect the physical and mental health of children. AT can benefit children with OSA and NE. A comprehensive multidisciplinary evaluation of children with NE and OSA is needed, and the mechanism and treatment of NE in children with OSA need to be further explored.Keywords: obstructive sleep apnea, nocturnal enuresis, children, atrial natriuretic peptide, sleep-wake disorder, adenotonsillectomy

Abstract Orbits of celestial objects, especially the geocentric and heliocentric ones, have been well explored to constrain new long-range forces beyond the Standard Model (SM), often referred to as fifth forces. In this paper, for the first time, we apply the motion of a spacecraft around Jupiter to probe fifth forces that don’t violate the equivalence principle. The spacecraft is the Juno orbiter, and ten of its early orbits already allow a precise determination of the Jovian gravitational field. We use the shift in the precession angle as a proxy to test non-gravitational interactions between Juno and Jupiter. Requiring that the contribution from the fifth force does not exceed the uncertainty of the precession shift inferred from data, we find that a new parameter space with the mass of the fifth-force mediator around 10−14 eV is excluded at 95% C.L.

Zhaoming Guo,1,2,&ast; Guqing Li,2,&ast; Lanjun Shen,2 Jiawei Pan,2 Danni Dou,2 Yuwei Gong,2 Wanwan Shi,2 Yuhua Sun,2 Yi Zhang,2 Kun Ma,2 Changhao Cui,2 Wenxin Li,3,4 Qiang Liu,5 Xudong Zhu1,4,6 1Department of General Surgery, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, 110042, People’s Republic of China; 2School of Chemical Engineering, Marine and Life Sciences, Dalian University of Technology, Panjin, Liaoning, 124221, People’s Republic of China; 3The second Department of Hepatopancreatobiliary Surgery, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, 110042, People’s Republic of China; 4Liaoning Provincial Key Laboratory of Precision Medicine for Malignant Tumors, Shenyang, Liaoning, 110042, People’s Republic of China; 5Faculty of Medicine, Dalian University of Technology, Dalian, Liaoning, 116024, People’s Republic of China; 6Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xudong Zhu, Department of General Surgery, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, 110042, People’s Republic of China, Tel +86 13354204706, Email xdzhu@cmu.edu.cn; XudongZhu@uky.edu Qiang Liu, Faculty of Medicine, Dalian University of Technology, Dalian, Liaoning, 116024, People’s Republic of China, Email andyliu_1844@dlut.edu.cnPurpose: Phototherapy has remarkable advantages in cancer treatment, owing to its high efficiency and minimal invasiveness. Indocyanine green (ICG) plays an important role in photo-mediated therapy. However, it has several disadvantages such as poor stability in aqueous solutions, easy aggregation of molecules, and short plasma half-life. This study aimed to develop an efficient nanoplatform to enhance the effects of photo-mediated therapy.Methods: We developed a novel bio-nanoplatform by integrating edible ginger-derived exosome-like nanoparticles (GDNPs) and the photosensitizer, ICG (GDNPs@ICG). GDNPs were isolated from ginger juice and loaded with ICG by co-incubation. The size distribution, zeta potential, morphology, total lipid content, and drug release behavior of the GDNPs@ICG were characterized. The photothermal performance, cellular uptake and distribution, cytotoxicity, anti-tumor effects, and mechanism of action of GDNPs@ICG were investigated both in vitro and in vivo.Results: GDNPs@ICG were taken up by tumor cells via a lipid-dependent pathway. When irradiated by an 808 nm NIR laser, GDNPs@ICG generated high levels of ROS, MDA, and local hyperthermia within the tumor, which caused lipid peroxidation and ER stress, thus enhancing the photo-mediated breast tumor therapy effect. Furthermore, in vivo studies demonstrated that engineered GDNPs@ICG significantly inhibited breast tumor growth and presented limited toxicity. Moreover, by detecting the expression of CD31, N-cadherin, IL-6, IFN-γ, CD8, p16, p21, and p53 in tumor tissues, we found that GDNPs@ICG substantially reduced angiogenesis, inhibited metastasis, activated the anti-tumor immune response, and promoted cell senescence in breast tumor.Conclusion: Our study demonstrated that the novel bio-nanoplatform GDNPs@ICG enhanced the photo-mediated therapeutic effect in breast tumor. GDNPs@ICG could be an alternative for precise and efficient anti-tumor phototherapy.Keywords: ginger-derived exosome-like nanoparticles, phototherapy, indocyanine green, lipid peroxidation, ER stress

Ni Cui,1,&ast; Qiuxia Li,1,&ast; Jing Cheng,2,&ast; Tianhua Xing,1 Peiyao Shi,3 Yingmei Wang,2 Min Luo,2 Yaoshan Dun,1,4 Suixin Liu1,4 1Division of Cardiac Rehabilitation, Department of Physical Medicine & Rehabilitation, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China; 2Department of Cardiovascular medicine, Shenzhen District Yantian People’s Hospital, Shenzhen, Guangdong, 518081, People’s Republic of China; 3Department of Experimental Diagnosis, Shenzhen District Yantian People’s Hospital, Shenzhen, Guangdong, 518081, People’s Republic of China; 4National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Suixin Liu; Yaoshan Dun, Division of Cardiac Rehabilitation, Department of Physical Medicine & Rehabilitation, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China, Email liusuixin@csu.edu.cn; dunyaoshan@csu.edu.cnBackground: Delayed heart rate recovery (HRR) after exercise, an indicator of cardiac autonomic nervous function (CANF), has been found to be associated with metabolic syndrome (MetS) in general populations. However, this relationship has not been extensively studied in older adults. The present study aimed to investigate the association between MetS and HRRs at 1, 2, 3 and 6 minutes after exercise and cardiorespiratory fitness (CRF) in Chinese dwelling older adults.Methods: This retrospective, observational study consecutively enrolled participants aged 60 years or older who underwent physical examinations in Shenzhen District Yantian People’s Hospital from September 2019 to July 2021. The participants were categorized into MetS and non-MetS groups according to the International Diabetes Federation criteria. Logistic regression analysis was applied to assess the association between MetS and CANF and CRF. Propensity score overlap weighting was used to adjust the covariates.Results: A total of 987 eligible participants were included (mean age±SD, 66± 4 years; male, 47.1%), of whom, 506 were diagnosed with MetS. MetS group showed significantly lower peak heart rate, HRR1-3, HRR6, peak metabolic equivalents, and peak oxygen consumption compared to the non-MetS group. Furthermore, peak systolic and diastolic blood pressures in the MetS group were significantly higher. Logistic regression analysis showed that MetS was significantly associated with HRR2, HRR3 (odds ratio [95% CI], 0.997 [0.995,0.999], both; P=0.009 and 0.005, respectively) and HRR6 (0.996 [0.994,0.998], P< 0.001). The association between MetS and CRF was significant (0.98 [0.97,0.98], P< 0.001).Conclusion: Elderly Chinese with MetS tend to exhibit reduced CANF and lower CRF. It is recommended that they boost physical activity and closely monitor heart rate and blood pressure during exercise to mitigate exercise-related risks.Keywords: aging population health, heart rate recovery, systolic blood pressure recovery, geriatric cardiology, autonomic regulation, fitness evaluation

Luya Shi,1,2 Xinxin Zhao,3 Jing Wu,3 Caidi He1 1Department of Nursing, Municipal Hospital Affiliated to Taizhou University, Taizhou, Zhejiang, 318000, People’s Republic of China; 2Department of Post Graduate School of Nursing, Sehan University, Yeonggam, 58447, South Korea; 3Department of Nursing, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250001, People’s Republic of ChinaCorrespondence: Caidi He, Municipal Hospital Affiliated to Taizhou University, Taizhou, Zhejiang, 318000, People’s Republic of China, Email hcdeye@gmail.comPurpose: Sleep disorders are prevalent non-motor symptoms in patients with Parkinson’s disease (PD), significantly diminishing the overall quality of life for patients and potentially accelerating the deterioration of motor and cognitive functions, accelerating disease progression. Despite increasing research on sleep disorders in PD, a comprehensive analysis of the knowledge structure and key issues in this field are still lacking. This study aims to identify research hotspots and emerging trends related to sleep disorders in PD through a detailed bibliometric analysis.Patients and Methods: On October 1, 2024, an extensive search was conducted in the Web of Science Core Collection (WOSCC) database to gather relevant literature on sleep disorders in PD. Bibliometric and knowledge mapping analyses were performed using CiteSpace, VOSviewer, and bibliometrix.Results: Between January 1, 2004, and October 1, 2024, a total of 3,655 publications on sleep disorders in PD were published by 3,387 institutions across 87 countries. The volume of publications has shown a steady increase, a trend projected to continue. Current research is primarily centered on Neurosciences, Pharmacology, and Clinical Neurology. Emerging trends involve comprehensive evaluations of sleep, early diagnosis and prevention of various sleep disorder subtypes in PD, and advancing research through animal models to develop effective therapies. Emerging keywords include machine learning, sleep quality, biomarkers, covid-19, and mouse model.Conclusion: This bibliometric analysis sheds light on the global landscape of PD-related sleep disorder research over the past two decades, highlighting key countries, institutions, authors, and journals driving advancements in the field. Moreover, it uncovers pivotal research hotspots and emerging trends, offering valuable insights and guidance for scholars engaged in this area.Keywords: bibliometric analysis, CiteSpace, Parkinson’s disease, REM sleep behavior disorder, restless leg syndrome, sleep disorder

Spermatogonial cells are capable of transmitting genetic information to the next generation and have the potential for self-renewal. However, research on spermatogonial cells is generally limited by the paucity of cell surface markers, which are not universal among species. In this study, we developed a systematic screening strategy for germline regulatory pathways and spermatogonial surface markers in non-model organisms. This was achieved by combining weighted gene co-expression network analysis (WGCNA), differential expressed gene (DEG) overrepresentation analysis, and functional annotation. This strategy was employed to identify a spermatogonia-related module, which was found to be enriched with stem cell-related pathways in the scallop Patinopecten yessoensis. This module contained a transmembrane protein, fibroblast growth factor receptor (FGFR). A single copy of Fgfr (PyFgfr) was confirmed in the P. yessoensis genome, which exhibited the canonical functional domains of FGFRs. PyFgfr was universally expressed in multiple tissues, including the testis. The highest expression was observed at the resting stage of the testis, with exclusive localization in spermatogonia. To obtain antibodies that recognize the cell surface region, the extracellular domains of PyFGFR were used as an antigen to prepare antiserum. Western blotting, immunohistochemical, and immunofluorescent analyses demonstrated that the antiserum specifically detected PyFGFR in the spermatogonia. This study demonstrates the feasibility of this strategy for screening spermatogonial surface markers in the scallop. This approach will facilitate the culture and manipulation of spermatogonia in non-model organisms, which may contribute to genetic improvement in aquaculture.

Fengjuan Shi,1,2 Yumei Wei,2 Yingmei Huang,2 Desheng Yao1 1Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of China; 2Department of Gynecology, the Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Desheng Yao, Email yaodesheng@gxmu.edu.cnPurpose: Cervical cancer is the fourth leading cause of cancer-related death in women. Furthermore, owing to its significant risk of recurrence or metastasis, the overall prognosis of patients with cervical cancer remains poor. Activating transcription factor 5 (ATF5) plays a crucial role in cell proliferation, survival, and apoptosis, and has been implicated in the progression of various types of cancer. However, the biological function and precise mechanism of ATF5 in cervical cancer remain unclear. This study, aimed to explore the function of ATF5 and its potential mechanisms in cervical cancer.Patients and Methods: Quantitative real-time PCR, Western blot and immunohistochemistry were used to detect the expression of ATF5 in cervical cancer tissues and cell lines. Knockdown ATF5 expression in cervical cancer cell lines was constructed using lentivirus-mediated shRNA to explore the role of ATF5 in cervical cancer through cell viability, transwell, and wound healing experiments. The expression of Wnt3a and β-catenin were investigated using quantitative real-time PCR and Western blot.Results: ATF5 was overexpressed in cervical cancer, and upregulation of ATF5 expression was associated with a poor prognosis. ATF5 knockdown inhibited the proliferation, migration and invasion abilities of cervical cancer cells. Furthermore, the downregulation of ATF5 led to the suppression of Wnt3a and β-catenin expression, which are key molecules in the Wnt/β-catenin signaling pathway.Conclusion: ATF5 promotes tumorigenic capability in cervical cancer through the Wnt/β-catenin signaling pathway. ATF5 may be a potential prognostic biomarker and therapeutic target in the management of cervical cancer.Keywords: activating transcription factor 5, cervical cancer, Wnt/β-catenin signaling pathway, tumorigenicity, prognosis

Xingxiang Ji,1,&ast; Yanyan Li,2,&ast; Jingsheng Wang,3,&ast; Gang Wang,3,&ast; Bin Ma,4 Jingfei Shi,5 Chao Cui,6,7 Ruiming Wang1 1State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan, Shandong, 250353, People’s Republic of China; 2Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, People’s Republic of China; 3Department of Cardiovascular Medicine, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, 271000, People’s Republic of China; 4Department of Cardiovascular Medicine, Taian City Taishan District People’s Hospital, Taian, Shandong, 271000, People’s Republic of China; 5Department of Clinical and Basic Medicine, Shandong First Medical University, Jinan, Shandong, 250000, People’s Republic of China; 6Scientific Research Department, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, Shandong, 253000, People’s Republic of China; 7Department of Pharmacy, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, 271000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Cui, Scientific Research Department, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, Shandong, 253000, People’s Republic of China, Email hbkjcuichao@126.com Ruiming Wang, State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan, Shandong, 250353, People’s Republic of China, Email ruiming3k@163.comAbstract: Silk protein, as a natural polymer material with unique structures and properties, exhibits tremendous potential in the biomedical field. Given the limited production and restricted properties of natural silk proteins, molecular biotechnology has been extensively applied in silk protein genetic engineering to produce novel silk proteins with specific properties. This review outlines the roles of major model organisms, such as silkworms and spiders, in silk protein production, and provides a detailed introduction to the applications of gene editing technologies (eg, CRISPR-Cas9), transgenic expression technologies, and synthetic biology techniques in silk protein genetic engineering. By analyzing the genetic factors influencing silk protein expression, this review further elaborates on the innovative applications of silk proteins in drug delivery systems, tissue engineering and regenerative medicine (eg, skin, bone, cartilage, and vascular repair), as well as antibacterial immune strategies. Notably, modified silk proteins expressed by transgenic silkworms demonstrate significant advantages in enhancing drug bioavailability and promoting cell proliferation and differentiation. In conclusion, silk protein gene engineering, through continuous innovations in molecular biotechnology, has provided an effective pathway for the production of high-performance silk protein materials. The extensive applications of these modified silk proteins in the biomedical field have not only expanded the functionality of silk proteins but also offered new approaches to address medical challenges. In the future, the development of silk protein gene engineering will further rely on interdisciplinary integration to promote in-depth research and the expansion of industrial applications of silk proteins.Keywords: silk protein, genetic engineering, molecular biotechnology, performance optimization, biomedical applications, tissue engineering, regenerative medicine

Xianning Dai,1 Kai Xu,1 Yu Tong,1 Jing Li,2 Liya Dai,1 Jianyou Shi,1 Haibin Xie,3 Xi Chen3 1Department of Clinical Laboratory, Wenzhou People’s Hospital, Wenzhou Maternal and Child Health Care Hospital, Zhejiang, People’s Republic of China; 2Department of PCCM, Wenzhou People’s Hospital, Wenzhou Maternal and Child Health Care Hospital, Zhejiang, People’s Republic of China; 3Department of Immunization Planning, Prevention and Health Care, Centers for Disease Control of Luchen, Zhejiang, People’s Republic of ChinaCorrespondence: Xi Chen, Department of Immunization Planning, Prevention and health care,Centers for Disease Control of Luchen, No. 3320 Guojing Road, Wenzhou, Zhejiang, 325005, People’s Republic of China, Tel +86 577 56760657, Fax +86 577 56760654, Email cxbrook0577@163.comObjective: This study aims to evaluate the utility of targeted next-generation sequencing (tNGS) in bronchoalveolar lavage fluid (BALF) for hospitalized patients with pulmonary infections.Methods: A cohort of 358 patients who received diagnosis and treatment for respiratory infections in the department of Respiratory Medicine at Wenzhou People’s hospital from January 2023 to April 2024 were selected for this study. The BALF of the patients was analyzed using tNGS, and the diagnostic efficacy of tNGS was subsequently compared with that of conventional testing methods (CTs) for pathogen detection.Results: Through the analysis of tNGS from the cohort, the pathogen detection rate in BALF using tNGS was significantly higher than that of CTs (90.22% VS 57.26%, P=0.001). Among them, Tropheryma Whipplei (6.15%), Bordetella pertussis (2.51%), Non-tuberculous mycobacteria (1.96%), Mycobacteria tuberculosis (1.40%), Chlamydia pneumoniae (1.96%), Chlamydia psittaci (0.56%), Legionella pneumophila (0.28%) were detected using tNGS alone, and the CTs results of these microorganisms were all negative. Among the various types of mixed infections observed, concurrent presence of bacteria and viruses was the most common, accounting for 37.15%. The detection rates of tNGS and CTs have statistical significance (66.87% VS 35.12%, P=0.001). Furthermore, a total of 61 cases of antimicrobial resistance genes were detected, including 34 cases of 23S rRNA A2063G, 6 cases of KPC, 5 cases of OXA, 2 cases of CTX-M, 3 cases of IMP, 1 case of NDM and 13 cases of mecA. Using the clinical diagnosis as references, the positive coincidence rate of the tNGS was significantly higher compared to that of the CTs (P=0.012).Conclusion: Compared to CTs, the application of tNGS enables the identification of a greater diversity of organisms and exhibits superior accuracy, effectively identifying pathogens that are undetectable by CTs, especially fastidious and atypical organisms. Consequently, it holds immense potential in pathogen diagnosis and offers valuable clinical guidance for patients with pulmonary infections.Keywords: bronchoalveolar lavage fluid, targeted next-generation sequencing, pneumonia, pathogen, culture, antimicrobial resistant

Since 2022, generative artificial intelligence technology and industry have been developing rapidly. This paper focused on the generative algorithms used in generative AI technology, and proposed the "Three Laws of Generative Algorithms" ethical principles in combination with relevant regulations. Combined with its technical characteristics, it analyzed the ethical difficulties that exist in practice, and then explored some preliminary solution frameworks.

Abstract Background Spermatogenesis is a complex process of cellular differentiation that commences with the division of spermatogonia stem cells, ultimately resulting in the production of functional spermatozoa. However, a substantial gap remains in our understanding of the molecular mechanisms and key driver genes that underpin this process, particularly in invertebrates. The dwarf surfclam (Mulinia lateralis) is considered an optimal bivalve model due to its relatively short generation time and ease of breeding in laboratory settings. Results In this study, over 4,600 testicular cells from various samples were employed to identify single-cell heterogeneity on a more comprehensive scale. The four germ cell populations (spermatogonia, primary spermatocytes, secondary spermatocytes, and round spermatids/spermatozoa) and three somatic populations (follicle cell, hemocyte, and nerve cell) were characterized. The four types of germ cells exhibited disparate cell cycle statuses and an uninterrupted developmental trajectory, progressing from spermatogonia to spermatids/spermatozoa. Pseudotime analysis indicates that gene expression, translation, ATP metabolic process, and microtubule-based process are involved in the transition of germ cell types. Weighted gene coexpression network analysis (WGCNA) identified four modules corresponding to the four types of germ cells, as well as key transcription factors (e.g., MYC, SREBF1, SOXH) that may play a critical role in these cell types. Furthermore, our findings revealed that there is extensive bidirectional communication between the somatic cells and the germline cells, including the FGF and TGF-β signaling pathways, as well as other ligand-receptor pairs, such as NTN1-NEO1 and PLG-PLGRKT. Conclusions This study provides a comprehensive single-cell transcriptome landscape of the gonad, which will contribute to the understanding of germ cell fate transition during spermatogenesis, and the development of germ cell manipulation technologies in mollusks.

Abstract The development of an efficient and durable photoelectrode is critical for achieving large-scale applications in photoelectrochemical water splitting. Here, we report a unique photoelectrode composed of reconfigured gallium nitride nanowire-on-silicon wafer loaded with Au nanoparticles as cocatalyst that achieved an impressive applied bias photon-to-current efficiency of 10.36% under AM 1.5G one sun illumination while exhibiting stable PEC hydrogen evolution over 800 h at a high current density. Specifically, by tailoring the GaN nanowires via a simple alkaline-etching step to expose the inner (10 $$\bar{1}\bar{1}$$ 1 ¯ 1 ¯ ) facets, we achieve a highly coupled semiconductor nanowire-cocatalyst heterointerface with strong electron interaction. The strongly coupled reconfigured GaN nanowire/Au heterointerface not only optimizes the electronic structure of Au nanoparticles to form abundant highly active interfacial regions, eventually realizing superior hydrogen evolution activity but also enables GaN nanowires to provide a stronger anchoring effect for Au nanoparticles, preventing the detachment of Au nanoparticles during the intense hydrogen evolution process. The proposed photoelectrode offers a feasible structure for overcoming the efficiency-reliability bottleneck of PEC devices for producing clean hydrogen fuel.

Abstract Ordered intermetallic alloys are renowned for their impressive mechanical, chemical, and physical properties, making them appealing for various fields. However, practical applications of them have long been severely hindered due to their severe brittleness and poor fabricability. It is difficult to fabricate such materials into components with complex geometries through traditional subtractive manufacturing methods. Here, we proposed a strategy to solve these long-standing issues through the additive manufacturing of chemically complex intermetallic alloy (CCIMA) based on laser powder bed fusion (LPBF). The developed CCIMA exhibits good printability, enabling a crack-free microstructure with a low porosity of 0.005%. More importantly, a good combination of high tensile strength (~1.6 GPa) and large uniform elongation (~35%) can be achieved, which has not been reported in the existing additive-manufactured alloys. Such properties are attributed to the structural and chemical features of highly ordered superlattice grain decorated with disordered interfacial nanolayer, as well as dynamic evolutions and interactions of multiple dislocation substructures. These findings could provide references for developing high-performance intermetallic alloys and accelerating their practical applications.

Abstract Holographic multiple-input multiple-output (MIMO) method leverages spatial diversity to enhance the performance of wireless communications and is expected to be a key technology enabling for high-speed data services in the forthcoming sixth generation (6G) networks. However, the antenna array commonly used in the traditional massive MIMO cannot meet the requirements of low cost, low complexity and high spatial resolution simultaneously, especially in higher frequency bands. Hence it is important to achieve a feasible hardware platform to support theoretical study of the holographic MIMO communications. Here, we propose a near-field holographic MIMO communication architecture based on programmable digital coding metasurface (PDCM) and electromagnetic theory. The orthogonal holographic patterns on the transmitting and receiving apertures are firstly obtained using the Hilbert-Schmidt decomposition of the radiation operator. Then the information to be transmitted is pre-encoded on PDCM following the principle of direct digital modulations. A PDCM-based holographic MIMO prototype is designed and experimentally verified in microwave frequencies. The measured results of constellations show that the prototype can realize dual-channel signal transmissions under quadrature-phase shift keying scheme. The proposed paradigm features low complexity, low cost and low power consumption, and may become a valuable technique in beyond fifth generation and 6G wireless communications.

Abstract Background The onset of the COVID-19 pandemic has had a detrimental impact on the healthcare system. Patients with kidney failure and related kidney disease are notably vulnerable to the COVID-19 pandemic. However, it remains unclear how mortality trends associated with kidney failure have evolved over the past three years. In this study, we investigated temporal trends in excess kidney failure-related mortality during the first three years of the pandemic in the United States. Methods We aim to estimate time-varying excess kidney failure-related mortality, which is defined as the difference between observed mortality and expected mortality predicted by a Poisson log-linear regression model, in the United States (March 2020—March 2023). Results Our findings revealed two distinct peaks in excess kidney failure-related mortality during the first year (March 2020—February 2021) and the second year (February 2021—March 2022), whereas a notable decline in excess mortality was observed in the third year (March 2022—March 2023). Additionally, disparities in mortality were evident among various demographic groups, including age, sex, racial/ethnic subgroups, and geographic regions. Across all age subgroups, an increase in kidney failure-related mortalities was observed, with individuals aged 85 years and above experiencing the most substantial relative increase, reaching 9595.8 per million persons (95% CI: 9438.8, 9752.9). Moreover, excess kidney failure-related mortalities were recorded at 510.3 per million persons (95% CI: 502.6, 517.9) and 721.8 per million persons (95% CI: 713.4, 730.1) for women and men, respectively. Notably, non-Hispanic Blacks exhibited the highest excess mortality within the racial/ethnic group, registering at 772.6 per million persons (95% CI: 756.3, 788.9). Conclusions Our study observed high levels of excess kidney failure-related mortality during the first two years of the pandemic, followed by a notable decline in the third year. This highlights the effectiveness of current policies and prevention measures implemented to mitigate the impact of the pandemic.

Xiao Sun,1 Xue Wang,2 Rongrong Zhou,3 Wei Deng,4 Jinxia Jiang,2 Yan Shi5 1Department of Nursing, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 2Department of Emergency, Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 3School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 4Department of Colorectal Disease, Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 5Department of Nursing, Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of ChinaCorrespondence: Jinxia Jiang; Yan Shi, Email jiangjinxia99@163.com; 2080153@tongji.edu.cnBackground: This study sought to explore the interrelationship between diabetes-related distress, patient evaluations of chronic illness management, and self-management practices among older adults diagnosed with T2DM and associated chronic complications.Methods: This was a cross-sectional study including 264 older adults with T2DM in Shanghai, China. Chinese version of Problem Areas in Diabetes Scale (PAID-C), Patient Assessment of Chronic Illness Care (PACIC) and Diabetes Self-Management Behaviour for Older (DSMB-O) were employed. Student’s t-test, one-way ANOVA or the nonparametric analysis (Mann–Whitney U-test), Pearson correlation coefficient and structural equation model (SEM) were used to analyse the data.Results: A total of 264 participants (157 males [59.47%], with an average age of 71.07± 6.47 years) were included in the study; their duration of T2DM ranged from 5 to 30 years, with a mean duration of 11.19± 6.96 years. The DSMB-O scores exhibited a negative correlation with the PAID-C scores (r=− 0.250, p< 0.01), while showing a positive correlation with PACIC scores (r=0.348, p< 0.01). Additionally, PAID-C scores demonstrated a negative correlation with PACIC scores (r=− 0.182, p< 0.01). The indirect effect of PAID-C on DSMB-O through PACIC was calculated as (− 0.70&ast;-0.39=0.27). Furthermore, the total effect of PAID-C on DSMB-O via PACIC was determined to be (0.27+0.22=0.49). Notably, the mediating effect accounted for 54.99%.Conclusion: Psychological distress is intricately linked to self-management behaviour among elderly patients suffering from T2DM and chronic complications. Our findings carry significant implications for T2DM healthcare, indicating that addressing psychological distress may enhance the quality of chronic illnesses, ultimately fostering improved self-management practices and yielding better health outcomes.Keywords: psychological distress, chronic illness care, self-management behaviors, elderly, type 2 diabetes mellitus

Shuaiyou Wang,1 Dingding Li,1 Chenjun Liu,1 Xueting Sun,1 Yage Shi,1 Hongru Wang,2 Huimin Zhang3 1School of Nursing, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 2Nursing of Department, Xinxiang First People’s Hospital, Xinxiang, Henan, People’s Republic of China; 3School of Nursing, Ningxia Medical University, Yinchuan, People’s Republic of ChinaCorrespondence: Huimin Zhang, School of Nursing, Ningxia Medical University, No.1160 Shengli South Street, Xingqing District, Yinchuan, 750001, People’s Republic of China, Email 35290915@qq.comBackground: Community integration (CI) is the ultimate goal of rehabilitation for individuals with disabilities. It plays a significant role in restoring their social functioning and facilitating their reintegration into community and family life. However, no studies have utilized bibliometric methods to explore community integration.Objective: To conduct a review about community integration of disabilities and to clarify the knowledge, hotspots, and trends through the bibliometric method.Methods: Studies on community integration from 1990 to 2023 were retrieved from the Web of Science Core Collection (WOSCC). CiteSpace 6.2.R4 and Microsoft Office Excel 2019 were applied. The CiteSpace node types involved in this study include keyword, reference, cited author, cited Journal, and the dual-map overlay of journals. CiteSpace presented the keyword cluster map, keywords timeline view map, keywords bursts map, and overlay map of journals. Microsoft Office Excel 2019 was used to present the trend of annual publications and draw up related tables and figures.Results: A total of 2239 hits were included. The number of publications related to community integration is increasing gradually. The three most frequent keywords is Brain Injury (571, 13%), Individuals (488, 11%), Quality of Life (434, 10%). Keyword cluster map and timeline map with eight clusters were obtained, and the current strongest citation burst keywords are social participation, substance use, experiences, interventions, and Afghanistan. Willer is the author with the most citations. McColl has the largest centrality in the first ten cited authors. The most cited reference is published by the World Health Organization (WHO). Archives of Physical Medicine and Rehabilitation is the journal with the highest co-citation frequency. The overlay map of journals presented four distinct paths: the journals in “psychology education, health” and “neurology, sports, ophthalmology” often cite journals in “health, nursing, medicine” and “psychology, education, social”.Conclusion: Community integration for individuals with disabilities is gradually becoming a hot topic. Research on community integration related to traumatic brain injury (TBI), stroke, children, and spinal cord injuries is current focus of community integration. Future research should explore the experiences and feelings of different groups of disabilities regarding community integration and develop more effective interventions for their community integration. Community integration is complex, and future research on community integration for individuals with disabilities needs to be explored more specifically.Keywords: community integration, community reintegration, disability, rehabilitation, quality of life, CiteSpace, bibliometric

Hongping Liu,&ast; Xiaofei Qiao,&ast; Xuliang Shi College of Education, Hebei University, Baoding, Hebei Province, 071002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuliang Shi, Associate Professor at the College of Education, Hebei University, Baoding, 071002, People’s Republic of China, Email shixl163@163.comObjective: The present study aims to analyze the heterogeneous trajectories of sleep disturbance (SD) among college students and to examine whether self-control mediates the association between sleep disturbance trajectories and Internet gaming disorder (IGD).Methods: A total of 4352 students were initially invited to participate, and 4191 (Mage = 19.12, SD = 0.98; 46.9% females) students were included as valid respondents at the first time-point. This study spanned six waves (from 2019 to 2022) with a six-month interval between each wave. Sleep disturbance was measured from Time 1 to Time 4, self-control was measured at Time 5, and Internet gaming disorder was measured at Time 6. Growth mixture modeling (GMM) was applied to identify latent classes of sleep disturbance over the four waves. Mediation analysis was conducted to examine the mediating role of self-control between sleep disturbance trajectories and IGD.Results: The results of growth mixture modelling yielded a four-class solution for sleep disturbance: a stable-low group, an increasing group, a decreasing group, and a stable-high group. Additionally, the results of mediation models showed that increased sleep disturbance is associated with a higher likelihood of individuals becoming more addicted to Internet games due to decreased self-control. Conversely, improved sleep quality may decrease the likelihood of engaging in Internet games via by promoting higher levels of self-control.Conclusion: Future prevention and intervention programs targeted at improving self-control may decrease the possibility of developing IGD.Keywords: Internet gaming disorder, sleep disturbance trajectories, self-control, college students, longitudinal cohort

GuangYuan Ma,1,&ast; ShiQin Tian,1,&ast; Yang Song,1 Yi Chen,1 Hui Shi,1 JingChi Li2 1School of Humanities and Management Science, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Orthopedics, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Song; Yi Chen, Email fookyuen666@163.com; chenyiswmu@163.comObjective: This study aims to examine the relationships between social anxiety, learning adaptability, AI technology usage, and behavioral problems among primary school students, with a focus on the mediating role of learning adaptability and the moderating role of AI usage.Methods: A cross-sectional survey was conducted among 1240 primary school students aged 8– 15 in Luzhou, Sichuan Province. Social anxiety was measured using the Social Anxiety Scale for Children (SASC), learning adaptability was assessed with the Children’s Learning Adaptability Questionnaire (CSAQ), behavioral problems were evaluated using the Child Behavior Checklist (CBCL), and AI tool usage was gauged through a self-developed questionnaire. Data analysis involved correlation and multiple regression analyses using SPSS, with the moderated mediation effect analyzed through Process Model 59.Results: Social anxiety was found to significantly and positively predict behavioral problems, indicating that higher levels of social anxiety were associated with more behavioral problems. Learning adaptability partially mediated this relationship, suggesting that social anxiety not only directly impacts behavioral problems but also indirectly heightens the risk by reducing learning adaptability. Additionally, AI usage moderated the relationship between learning adaptability and behavioral problems, with a stronger effect of learning adaptability on behavioral problems observed at higher levels of AI usage. Specifically, the positive influence of learning adaptability on behavioral problems became more pronounced as AI usage increased, indicating that frequent AI use can amplify the impact of learning adaptability on behavioral outcomes.Conclusion: Social anxiety increases the risk of behavioral problems in primary school students by diminishing learning adaptability. AI technology plays a moderating role in the relationship between learning adaptability and behavioral problems, with its effects becoming more pronounced at higher levels of AI usage. This highlights the need for educators to focus on improving students’ learning adaptability, judiciously incorporate AI technology, and consider individual differences, particularly mental health, to foster comprehensive and healthy student development.Keywords: social anxiety, learning adaptability, AI usage, behavioral problems, primary school students

Abstract This study investigates pilot perspectives on the use of Flight Simulation Training Devices (FSTDs) in Canada’s general aviation (GA) sector, which, despite their longstanding adoption, remain underutilized. It also examines pilot perspectives on the potential of Augmented Reality (AR) technology as an assistive tool in GA pilot training. An online survey gathered views on FSTD use for routine flight operations and emergency training, as well as AR’s potential to support learning. Responses from 197 participants show a strong interest (average rating above 4 on a 5-point scale) in incorporating FSTDs and AR technology into the GA pilot training framework. The findings suggest that immersive, technology-driven training environments have the potential to better address modern aviation demands and enhance pilot proficiency.

Abstract Osteoporotic vertebral compression fractures (OVCFs) can be painful. Percutaneous kyphoplasty (PKP) aims at strengthening the vertebra and reducing pain, but efficacy can vary among patients. The purpose of this study was to establish a risk prediction model for pain relief following PKP in patients with OVCF. This retrospective study included 208 (training set) and 54 (validation set) OVCF patients who underwent bone cement treatment between January 2018 and October 2023. Based on postoperative VAS scores, patients were divided into two groups (0–2 and 3–6). Univariable and multivariable logistic regression identified significant factors affecting VAS scores, leading to the creation of a nomogram model. Internal validation was performed using the bootstrap method. The model’s performance and clinical value were evaluated using the area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and calibration curves. Four predictors were identified: number of segments, PMMA dose, comorbidities, and central nervous system (CNS) medications. The AUC, DCA, and calibration curves demonstrated good model discrimination and accuracy. The clinical impact plot highlighted the model’s practical value. We developed and validated an intuitive nomogram model for predicting a postoperative VAS score ≤ 2, reflecting therapeutic efficacy in OVCF patients treated with PMMA. The model could be used for a more careful selection of patients suitable for PKP and who would benefit the most from PKP. The other patients should at least be advised of the risk of suboptimal pain control or directed toward other treatments.

Abstract Background National Medical Licensing Examination (NMLE) is the entrance exam for medical practice in China, and its general medical knowledge test (GMKT) evaluates abilities of medical students to comprehensively apply medical knowledge to clinical practice. This study aimed to identify nonacademic predictors of GMKT performance, which would benefit medical schools in designing appropriate strategies and techniques to facilitate the transition from medical students to qualified medical practitioners. Methods In 1202 medical students, we conducted the deletion-substitution-addition (DSA) and structural equation model (SEM) analyses to identify nonacademic predictors of GMKT performance from 98 candidate variables including early life events, physical conditions, psychological and personality assessments, cognitive abilities, and socioeconomic conditions. The candidate variables were assessed using psychometrically or cognitively validated and accepted instruments. Results We identified seven nonacademic predictors for GMKT performance. Body mass index (BMI) and working memory reaction time showed direct negative effects on GMKT performance. Psychological and personality features (conscientiousness, state anxiety, and openness to experience) indirectly affected GMKT performance via BMI, while socioeconomic conditions (father’s education and mother’s occupation) indirectly affected GMKT performance by influencing psychological and personality features and further BMI. Conclusion The identified nonacademic predictors for GMKT performance and their pathways may be useful for improving medical education by strengthening favorable and weakening, rectifying, or compensating unfavorable factors that are modifiable.

Abstract The attainment of white emission from a light-emitting electrochemical cell (LEC) is important, since it enables illumination and facile color conversion from devices that can be cost-efficient and sustainable. However, a drawback with current white LECs is that they either employ non-sustainable metals as an emitter constituent or are intrinsically efficiency limited by that the emitter only converts singlet excitons to photons. Organic compounds that emit by thermally activated delayed fluorescence (TADF) can address these issues since they can harvest all excitons for light emission while being metal free. Here, we report on the first white LEC based on solely metal-free TADF emitters, as accomplished through careful tuning of the energy-transfer processes and the electrochemically formed doping structure in the single-layer active material. The designed TADF-LEC emits angle-invariant white light (color rendering index = 88) with an external quantum efficiency of 2.1 % at a luminance of 350 cd/m2.

Abstract Brain glymphatic activity, as indicated by diffusion-tensor imaging analysis along the perivascular space (ALPS) index, is involved in developmental neuropsychiatric and neurodegenerative diseases, but its genetic architecture is poorly understood. Here, we identified 17 unique genome-wide significant loci and 161 candidate genes linked to the ALPS-indexes in a discovery sample of 31,021 individuals from the UK Biobank. Seven loci were replicated in two independent datasets. Genetic signals located at the 2p23.3 locus yielded significantly concordant effects in both young and aging cohorts. Genetic correlation and polygenic overlap analyses indicate a common underlying genetic mechanism between the ALPS-index, ventricular volumes, and cerebrospinal fluid tau levels, with GMNC (3q28) and C16orf95 (16q24.2) as the shared genetic basis. Our findings enhance the understanding of the genetics of the ALPS-index and provide insight for further research into the neurobiological mechanisms of glymphatic clearance activity across the lifespan and its relation to neuropsychiatric phenotypes.

Abstract Digestive and psychiatric disorders tend to co-occur, yet mechanisms remain unclear. Leveraging genetic and transcriptomic data integration, we conduct multi-trait analysis of GWAS (MTAG) and weighted gene co-expression network analysis (WGCNA) to explore shared mechanism between psychiatric and gastrointestinal disorders. Significant genetic correlations were found between these disorders, especially in irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), depression (DEP), and neuroticism (NE). MTAG identify 60 novel pleiotropic loci for IBS and 14 for GERD, predominantly located near genes associated with neurological pathways. Further WGCNA identifies multiple co-expression modules enriched with genes involved in neurological pathways in digestive tissues, with some modules strongly preserved across brain and digestive tissues. Moreover, our network analysis suggests BSN, CELF4, and NRXN1 as central players in the regulation of the gut-brain axis (GBA). This study enhances our understanding of the GBA and underscores BSN, CELF4, and NRXN1 as crucial targets for future research.

Chi Zhang,1,2,&ast; Chao Yang,3,&ast; Qingming Shi1,2 1Department of Oncology, Anhui Chest Hospital, Hefei, 230022, People’s Republic of China; 2Anhui Medical University Clinical College of Chest, Hefei, 230022, People’s Republic of China; 3Department of Urology, Anhui Provincial Children’s Hospital, Hefei, 230022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingming Shi, Email shqm0324@163.com, shqm0324@hotmail.comAbstract: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Mutations within the TP53 gene represent critical molecular events in NSCLC, contributing to the tumorigenesis in the pulmonary epithelial tissues. TP53 is a widely researched prognostic indicator in NSCLC, and pathological investigations have revealed a weak to mild negative predictive effect for TP53. Mutated p53 protein may have some pro-oncogenic impact, and the variations may change tumor inhibitors into oncogenes. The diverse mutational spectrum of TP53 in NSCLC with different mutations is linked to varied treatment responses. In contrast, first-line chemotherapeutics to this progress are limited, however, randomized trials with new chemotherapeutics have shown significant survival benefits. This review highlighted the critical influence of TP53 gene mutations on pathological-sensitivity and overall survival outcomes in NSCLC. Further research is needed to explore TP53 mutation-specific pathways and their effects on NSCLC progression and treatment effectiveness. Keywords: non-small cell lung cancer, TP53 gene, treatment, survival analysis, mutations

Jiaqi Leng,1 Huilin Cai,1 Fei Liu,2 Xiaoli Shi,3 Zhiguang Fan4 1School of English, Jilin International Studies University, Changchun, 130117, People’s Republic of China; 2Section of Student Affair, ChangChun Vocational School of Technology, Changchun, 130117, People’s Republic of China; 3Department of Psychology, University of Exeter, Exeter, EX4 4 QG, UK; 4Department of Psychology, Shaoxing University, Shaoxing, 312000, People’s Republic of ChinaCorrespondence: Zhiguang Fan, Department of Psychology, Shaoxing University, Shaoxing, 312000, People’s Republic of China, Tel +86-0431-84924101, Fax +86 1 594-831-4623, Email fanyqm@126.comBackground: Stigma can not only threaten the self-identity of secondary vocational students, but also have negative effects on their mental health and behavior.Objective: This study aimed to develop the Self-Stigma Scale for Secondary Vocational Students (SSS-SVS) and test its reliability and validity.Patients and Methods: This study formed a scale based on the stigma conceptualization model and open questionnaire. The formal survey was divided into two stages. In the first stage, a preliminary questionnaire was administered to 328 secondary vocational students to develop a formal SSS-SVS according to the results of the data check. In the second stage, the SSS-SVS, Social Recognition of Secondary Vocational Students (SR-SVS), Intensity of Willingness to Become a Secondary Vocational Student (IWB-SVS), Stigma-Consciousness Scale (SCS), Learning Adjustment Scale (LAS), Professional Identity Scale for Secondary Vocational Students (PIS-SVS), and the Self-Compassion Scale (SCoS) were administered to 1079 vocational secondary school students.Results: The SSS-SVS consisted of 21 items which were divided into three dimensions of negative characteristics, self-deprecation, and opportunity loss, reflecting secondary vocational students’ perception of negative public evaluation, self-feeling under the influence of stigma, and cognition of negative impact on their identity. The confirmatory factor analysis (CFA) shows that the three-factor model has good fit indices. The total score and the scores of each dimension of the SSS-SVS were significantly and positively correlated with Stigma Consciousness; they were significantly and negatively correlated with SA-SVS, IDB-SVS, SVS-PIS, Learning Adjustment, and Self-Compassion. Both the Cronbach’s α coefficients of the total scale and each dimension and the McDonald’s ω coefficients were satisfactory. Additionally, the scale had measurement equivalence across gender and grade levels. The SSS-SVS has limitations and may be affected by cultural background. Future studies should expand the sample and conduct cross-cultural verification.Conclusion: The SSS-SVS is a reliable and valid instrument for assessing secondary vocational students’ self-stigma, providing support for developing relevant programs and policies. It also advances secondary vocational education and enhances students’ mental health.Keywords: secondary vocational students, self-stigma, reliability, validity

Qiu Dong,1,&ast; Jiayang Wu,2,3,&ast; Huaguo Zhang,4,&ast; Xinhui Chen,2,3 Xi Xu,2,3 Jifeng Chen,3 Changzheng Shi,2,3,5 Liangping Luo,3,5 Dong Zhang2,3 1Department of Bone and Joint Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2Medical Imaging Centre, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 3The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 4Department of Ultrasonography, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 5Medical Imaging Centre, the Fifth Affiliated Hospital of Jinan University, Heyuan, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Zhang, Email lbzhangdong@126.comPurpose: Immunometabolism is pivotal in rheumatoid arthritis (RA) pathogenesis, yet the intricacies of its pathological regulatory mechanisms remain poorly understood. This study explores the complex immunometabolic landscape of RA to identify potential therapeutic targets.Patients and Methods: We integrated genome-wide association study (GWAS) data involving 1,400 plasma metabolites, 731 immune cell traits, and RA outcomes from over 58,000 participants. Mendelian randomization (MR) and mediation analyses were applied to evaluate causal relationships among plasma metabolites, immune cells, and RA. We further analyzed single-cell and bulk transcriptomes to investigate differential gene expression, immune cell interactions, and relevant biological processes. Machine learning models identified hub genes, which were validated via quantitative real-time PCR (qRT-PCR). Then, potential small-molecule drugs were screened using the Connectivity Map (CMAP) and molecular docking. Finally, a phenome-wide association study (PheWAS) was conducted to evaluate potential side effects of drugs targeting the hub genes.Results: Causalities were found between six plasma metabolites, five immune cells and RA in genetically determined levels. Notably, DC mediated 18% of the protective effect of PE on RA. Autophagy-related scores were elevated in both RA and DC subsets in PE-associated biological processes. Through observation in the functional differences in cellular interactions between the identified clusters, DCs with high autophagy scores may process such as necroptosis and the activation of the Jak-STAT signaling pathway in contributing the pathogenesis of RA. Explainable machine learning, PPI network analysis, and qPCR jointly identified four hub genes (PFN1, SRP14, S100A11, and SAP18). CMAP, molecular docking, and PheWAS analysis further highlighted vismodegib as a promising therapeutic candidate.Conclusion: This study clarifies the key immunometabolic mechanisms in RA, pinpointing promising paths for better prevention, diagnosis, and treatment.Keywords: rheumatoid arthritis, dendritic cells, single-cell sequencing, bulk transcriptome, explainable machine learning, drug repositioning