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Yanling Liao,1,&ast; Siyu Xie,2,&ast; Yifen Zhuo,3,&ast; Sisi Chen,1 Yuxin Luo,1 Ying Wei,4 Yusheng Yao1 1Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 2Department of Anesthesiology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, People’s Republic of China; 3Department of Anesthesiology, Xiamen Haicang Hospital, Xiamen, People’s Republic of China; 4Department of Anesthesiology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Wei, Department of Anesthesiology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, 350025, People’s Republic of China, Email whm444@fjmu.edu.cn Yusheng Yao, Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, 134 Dongjie Street, Fuzhou, 350001, People’s Republic of China, Email fjslyys@126.comPurpose: Emergence delirium and postoperative negative behavioral changes (PNBC) are common complications in pediatric anesthesia. This study evaluated whether intranasal premedication combining dexmedetomidine and esketamine more effectively reduces these complications compared to either drug alone in children undergoing tonsillectomy and/or adenoidectomy with sevoflurane anesthesia.Patients and Methods: This randomized, double-blind trial involved 198 children aged 2− 5 years undergoing tonsillectomy and/or adenoidectomy. Participants received intranasal premedication with either dexmedetomidine (2 μg/kg), esketamine (1 mg/kg), or their combination (dexmedetomidine 1 μg/kg plus esketamine 0.5 mg/kg). The primary outcome was the incidence of emergence delirium, defined as a Pediatric Anesthesia Emergence Delirium (PAED) scale score ≥ 10. Secondary outcomes included the incidence of PNBC, sedation depth, easiness of separation from parents, acceptance of the mask for induction, emergence time, postoperative pain score, parental satisfaction, and adverse events.Results: The combination premedication significantly reduced emergence delirium incidence (9.4%) compared to esketamine alone (38.1%; relative risk [RR] 0.25, 95% confidence interval [CI] 0.11– 0.57, p < 0.001), but not compared to dexmedetomidine alone (17.2%; RR 0.55, 95% CI 0.21– 1.39, p = 0.193). PNBC incidence at day 7 was lower with the combination (28.1%) versus dexmedetomidine (48.4%; RR 0.58, 95% CI 0.36– 0.93, p = 0.018), but not significantly different from esketamine alone (20.6%; RR 1.38, 95% CI 0.74– 2.58, p = 0.326). The combination also provided significantly superior sedation, improved ease of separation from parents, better acceptance of the mask for induction, shorter emergence time, and higher parental satisfaction than both monotherapies.Conclusion: In children undergoing tonsillectomy and/or adenoidectomy with sevoflurane anesthesia, intranasal dexmedetomidine-esketamine premedication more effectively reduces emergence delirium compared to esketamine alone and PNBC compared to dexmedetomidine alone. This combination also improves sedation, shortens emergence times, and enhances parental satisfaction compared to monotherapy without significant adverse effects.Trial Registration: The Chinese Clinical Trial Registry, ChiCTR2300076709. Keywords: adenoidectomy, dexmedetomidine, emergence delirium, esketamine, intranasal administration, pediatric anesthesia, postoperative complications, tonsillectomy

Deyi Huang,1 Xingan Yang,2 Hongbiao Ruan,3 Yushui Zhuo,1 Kai Yuan,4 Bowen Ruan,1 Fang Li1 1Department of Ultrasound, The People’s Hospital of Yuhuan, Yuhuan City, Zhejiang Province, People’s Republic of China; 2Department of Ultrasound, Taizhou Hospital of Zhejiang Province, Linhai City, Zhejiang Province, People’s Republic of China; 3Department of Cardiology, The People’s Hospital of Yuhuan, Yuhuan City, Zhejiang Province, People’s Republic of China; 4Department of Clinical Laboratory, The People’s Hospital of Yuhuan, Yuhuan City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Fang Li, Department of Ultrasound, The People’s Hospital of Yuhuan, No. 18, Changle Road, Yuhuan City, Zhejiang Province, 317600, People’s Republic of China, Tel +8613967672898, Email 3260772796@qq.comIntroduction: Chronic coronary artery disease (CAD) management often relies on myocardial contrast echocardiography (MCE), yet its effectiveness is limited by subjective interpretations and difficulty in distinguishing hibernating from necrotic myocardium. This study explores the integration of machine learning (ML) with radiomics to predict functional recovery in dyskinetic myocardial segments in CAD patients undergoing revascularization, aiming to overcome these limitations.Methods: This prospective study enrolled 55 chronic CAD patients, dividing into training (39 patients, 205 segments) and testing sets (16 patients, 68 segments). Dysfunctional myocardial segments were identified by initial wall motion scores (WMS) of ≥ 2 (hypokinesis or higher). Functional recovery was defined as a decrease of ≥ 1 grade in WMS during follow-up echocardiography. Radiomics features were extracted from dyssynergic segments in end-systolic phase MCE images across five cardiac cycles post- “flash” impulse and processed through a five-step feature selection. Four ML classifiers were trained and compared using these features and MCE parameters, to identify the optimal model for myocardial recovery prediction.Results: Functional improvement was noted in 139 out of 273 dyskinetic segments (50.9%) following revascularization. Receiver Operating Characteristic (ROC) analysis determined that myocardial blood flow (MBF) was the most precise clinical predictor of recovery, with an area under the curve (AUC) of 0.770. Approximately 1.34 million radiomics features were extracted, with nine features identified as key predictors of myocardial recovery. The random forest (RF) model, integrating MBF values and radiomics features, demonstrated superior predictive accuracy over other ML classifiers. Validation of the RF model on the testing dataset demonstrated its effectiveness, evidenced by an AUC of 0.821, along with consistent calibration and clinical utility.Conclusion: The integration of ML with radiomics from MCE effectively predicts myocardial recovery in CAD. The RF model, combining radiomics and MBF values, presents a non-invasive, precise approach, significantly enhancing CAD management.Keywords: coronary artery disease, myocardial contrast echocardiography, radiomics, machine learning, myocardial recovery prediction, random forest

Wenjie Xie,1,2,&ast; Yixun Zhang,1,2,&ast; Qianfeng Xu,1,2,&ast; Guowei Zhong,1,2 Jundong Lin,2,3 Huichan He,3 Qiuling Du,2 Huijing Tan,1,2 Muqi Chen,1,2 Zhenjie Wu,1– 3 Yulin Deng,1,2 Zhaodong Han,1– 3 Jianming Lu,1,2,4 Jianheng Ye,1,2,4 Fen Zou,1,2 Yangjia Zhuo,1,2 Weide Zhong1– 4 1Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 2Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 3Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, People’s Republic of China; 4State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, 999078, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangjia Zhuo; WeideZhong, Email eyyangjiazhuo@scut.edu.cn; zhongwd2009@live.cnPurpose: Current treatment approaches for Prostate cancer (PCa) often come with debilitating side effects and limited therapeutic outcomes. There is urgent need for an alternative effective and safe treatment for PCa.Methods: We developed a nanoplatform to target prostate cancer cells based on graphdiyne (GDY) and a copper-based metal-organic framework (GDY-CuMOF), that carries the chemotherapy drug doxorubicin (DOX) for cancer treatment. Moreover, to provide GDY-CuMOF@DOX with homotypic targeting capability, we coated the PCa cell membrane (DU145 cell membrane, DCM) onto the surface of GDY-CuMOF@DOX, thus obtaining a biomimetic nanoplatform (DCM@GDY-CuMOF@DOX). The nanoplatform was characterized by using transmission electron microscope, atomic force microscope, X-ray diffraction, etc. Drug release behavior, antitumor effects in vivo and in vitro, and biosafety of the nanoplatform were evaluated.Results: We found that GDY-CuMOF exhibited a remarkable capability to load DOX mainly through π-conjugation and pore adsorption, and it responsively released DOX and generated Cu+ in the presence of glutathione (GSH). In vivo experiments demonstrated that this nanoplatform exhibits remarkable cell-killing efficiency by generating lethal reactive oxygen species (ROS) and mediating cuproptosis. In addition, DCM@GDY-CuMOF@DOX effectively suppresses tumor growth in vivo without causing any apparent side effects.Conclusion: The constructed DCM@GDY-CuMOF@DOX nanoplatform integrates tumor targeting, drug-responsive release and combination with cuproptosis and chemodynamic therapy, offering insights for further biomedical research on efficient PCa treatment. Keywords: graphdiyne, biomimetic nanoplatform, cuproptosis, chemotherapy, prostate cancer

Hai Feng,1,&ast; Yunhui Zhuo,2,&ast; Xuemei Zhang,2 Yuyao Li,1 Yue Li,1 Xiangjuan Duan,2 Jia Shi,1 Chengbin Xu,3 Yueqiu Gao,1,2 Zhuo Yu2 1Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Informatics, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yueqiu Gao, Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Tel +86 21 20256507, Fax +86 21 20256699, Email gaoyueqiu@shutcm.edu.cn Zhuo Yu, Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Tel +86 21 20256507, Fax +86 21 20256699, Email zhuoyu@shutcm.edu.cnAbstract: Hepatocellular carcinoma (HCC) remains a serious medical therapeutic challenge as conventional curative avenues such as surgery and chemotherapy only benefit for few patients with limited tumor burden. Immunotherapy achieves clinical progress in the treatment of this prevalent malignant disease by virtue of the development of tumor immunology; however, most patients have experienced minimal or no clinical benefit in terms of overall survival. The complexity and diversity of tumor microenvironment (TME) built by immune and stromal cell subsets has been considered to be responsible for the insufficiency of immunotherapy. The advance of bioanalytical technology boosts the exploration of the composition and differentiation of these infiltrated cells, which reflect the immune state of the TME and impact the efficacy of the antitumor immune response. Targeting these cells to remodel the TME is one of the important immunotherapeutic approaches to improve HCC treatment. In this review, we focused on the role of these non-cancerous cells in the tumor progression, and elaborated their function on cancer immunotherapy when manipulating them as potential targets.Keywords: immune cells, stromal cells, tumor microenvironment, hepatocellular carcinoma, immunotherapy

Weimin Dong,1 Yong Luo,2 Guian Zhang,1 Hui Zhang,1 Yuxiang Liang,1 Yangjia Zhuo,1 Yingke Liang,1 Fen Zou,1 Weide Zhong1,3,4 1Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510180, People’s Republic of China; 2Department of Urology, The Second People’s Hospital of Foshan, Affiliated Foshan Hospital of Southern Medical University, Foshan 528000, People’s Republic of China; 3Department of Urology, Huadu District People’s Hospital, Southern Medical University, Guangzhou 510800, People’s Republic of China; 4Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510230, People’s Republic of ChinaCorrespondence: Weide Zhong; Fen ZouDepartment of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, People’s Republic of ChinaTel +86 20-81048312Fax +86 20-8337332Email zhongwd2009@live.cn; zoufen2008@126.comIntroduction: Although carbon nanospheres (CNPs) are promising nanomaterials in cancer treatment, how they affect prostate cancer (PCa) remains unclear.Methods: In this study, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Raman spectroscopy were used to confirm the successful synthesis of CNPs. CCK-8, flow cytometry, Transwell, wound healing, Western blot and immunohistochemistry (IHC) assays were performed to evaluate the antitumor effect of CNPs toward the two kinds of prostate cancer cell lines PC3 and DU145.Results: Our results showed that CNPs inhibited cell growth, invasion, and migration and induced apoptosis and autophagy in PCa cells. Multifactor detection of a single Akt phosphorylation pathway and Western blot results suggested the suppression of 4E-BP1 in PCa cells after incubation with CNPs. The results from animal experiments also suggested the antitumor effect of CNPs and reduced 4E-BP1 expression in PCa tissue samples from BALB/c nude mice administered a local subcutaneous injection of CNPs.Keywords: carbon nanosphere, prostate cancer, antitumor, 4E-BP1

Zhiduan Cai,1,* Yulin Deng,1,* Jianheng Ye,2 Yangjia Zhuo,3 Zezhen Liu,2 Yingke Liang,3 Hui Zhang,3 Xuejin Zhu,2 Yong Luo,3 Yuanfa Feng,4 Ren Liu,2 Guo Chen,5 Yongding Wu,3 Zhaodong Han,3 Yuxiang Liang,3 Funeng Jiang,3 Weide Zhong1– 4,6 1Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou 510180, People’s Republic of China; 3Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, People’s Republic of China; 4Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510230, People’s Republic of China; 5Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, People’s Republic of China; 6School of Medicine, Jinan University, Guangzhou, Guangdong 510632, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weide ZhongGuangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of ChinaEmail zhongwd2009@live.cnPurpose: Citrate synthase (CS) is a rate-limiting enzyme in the citrate cycle and is capable of catalyzing oxaloacetate and acetyl-CoA to citrate. CS has been uncovered to be upregulated in a variety of cancers, and its expression and clinical significance in prostate cancer (PCa) remain unknown.Methods: In this study, we examined the association between CS expression level and clinicopathological features of prostate cancer patients in a TMA cohort and the public cancer database (The Cancer Genome Atlas-Prostate Adenocarcinoma, TCGA-PRAD). The CS knockdown cell lines were constructed to study the effects of CS downregulation on proliferation, colony formation, migration, invasion, and cell cycle of prostate cancer cells in vitro. And the effect of CS downregulation on tumor growth in mice was studied in vivo. In addition, the metabolomics and mitochondrial function were detected in the CS knockdown cell lines.Results: CS expression level in PCa tissues was higher than that in normal tissues (P < 0.05). CS upregulation was significantly associated with high Gleason score (P < 0.05), advanced pathological stage (P < 0.001), and biochemical recurrence (P < 0.001). Functionally, decreased expression of CS inhibited PCa cell proliferation, colony formation, migration, invasion and cell cycle in vitro, and inhibited tumor growth in vivo. In addition, CS downregulation exerted potential inhibitory effects on the lipid metabolism and mitochondrial function of PCa cells.Conclusion: In conclusion, these findings suggested that CS upregulation may contribute to the aggressive progression and poor prognosis of PCa patients, which might be partially associated with its influences on the cell lipid metabolism and mitochondrial function.Keywords: prostate cancer, citrate synthase, prognosis, lipid metabolism

Yujia Deng,1 Lei Wang,1,2 Lite Ge,1,3 Da Duan,1 Yi Zhuo,1 Ting Yuan,1 Weiping Yan,1 Peiqi Huang,1 Xiaohua Teng,1 Ming Lu1,3 1Department of Neurosurgery, The Second Affiliated Hospital of Hunan Normal University (163 Hospital of the People’s Liberation Army), Changsha, 2Department of Neurosurgery, Affiliated Haikou Hospital, Xiangya School of Central South University, Haikou, 3Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, People’s Republic of China Objective: Insulin-like growth factor binding protein-2 (IGFBP-2), a member of a highly conserved family of six insulin-like growth factor binding proteins (IGFBPs), can regulate several cellular processes through IGF-dependent or IGF-independent pathway. Recent studies have provided solid evidence for the importance to delineate that olfactory ensheathing cells (OEC)-conditioned medium (OCM) can not only facilitate the differentiation of neural stem cell line (C17.2) into neurons, but also promote the survival and proliferation. We have previously reported that IGFBP-2 was detected in OCM. This study is designed to investigate the roles of IGFBP-2 for the regulation of C17.2 differentiation and proliferation.Methods and results: IGFBP-2 was identified and upregulated in OCM to compare with astrocytes-conditioned medium by shotgun proteomics and semiquantitative proteomic analysis. In order to investigate whether exogenous IGFBP-2 could stimulate proliferation in C17.2 cells and differentiate it into glia or neuron, we used various concentrations of IGFBP-2 to induce C17.2 cells which were cultured in DMEM/F12. The results showed that exogenous IGFBP-2 can promote proliferation in C17.2 cells, but had little effect on differentiation. Interestingly, we also found that IGFBP-2 could induce C17.2 cells to differentiate into astrocytes, while inhibiting their differentiation into neurons in a dose-dependent manner when cultured C17.2 cells in OCM. Changes in cell morphology were imaged under a light microscope, and proliferating cells were counted. Cell viability was determined by MTT. In addition, Western blot, immunofluorescence, and flow cytometry analysis were performed to detect protein expression patterns of proliferation-related antigen, proliferating cell nuclear antigen, neuroectodermal stem cell marker, neuron specific class III beta tubulin, and glial fibrillary acidic protein.Conclusion: Exogenous IGFBP-2 could stimulate proliferation in C17.2 cells, and promote the differentiation of C17.2 cells into astrocytes induced by OCM. Its mechanism is related to activation of the extracellular signal-regulated kinase 1/2 pathway. Keywords: IGFBP-2, C17.2 cells, proliferation, differentiation

Ting Yuan,1* Yi Zhuo,1* Chaying Su,2 Xuan Li,1 Da Duan,1 Lite Ge,1 Pei Wu,1 Hao Wang,1 Yujia Deng,1 Ming Lu1 1Department of Neurosurgery, Second Affiliated Hospital of Hunan Normal University (163 Hospital of the People’s Liberation Army), Changsha, 2Department of Pediatrics, 169 Hospital of the People’s Liberation Army, Hengyang, Peoples’ Republic of China * These authors contributed equally to this work Abstract: Human olfactory mucosa mesenchymal-like stem cells (hOM-MSCs) secrete paracrine factors that may exert a protective effect on the cerebral ischemia. This study was done to determine the hypoxic and ischemic effects on the mRNA and protein expression level of paracrine factors by hOM-MSCs. The hOM-MSCs were cultured with 5% or 20% serum and under either normoxic (21% O2) or hypoxic (3% O2) conditions. Expression levels of mRNA and protein for vascular endothelial growth factor (VEGF), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and matrix metalloproteinase-2 (MMP-2) were determined by quantitative reverse transcription polymerase chain reaction and Western blot, respectively. Hypoxia reduced gene expression for VEGF (5% serum), GDNF, BDNF (5% serum) and NGF (5% serum) and increased it for BDNF (20% serum), MMP-2 (5% serum) and NGF (20% serum). Ischemia lowered gene expression for VEGF (hypoxia), GDNF, BDNF (hypoxia), MMP-2 (normoxia) and NGF (hypoxia) and increased it for VEGF (normoxia), BDNF (normoxia), MMP-2 (hypoxia) and NGF (normoxia).The protein level of these factors was almost in line with the gene level. These data demonstrate that serum and oxygen levels have a significant effect on the gene and protein expression levels of paracrine factors by hOM-MSCs, which will affect how hOM-MSCs interact in vivo during cerebral ischemia. Keywords: human olfactory mucosa mesenchymal-like stem cells, paracrine factors, hypoxia, ischemia, cerebral ischemia

City parks and green space are vital in coordinating urban space and improving the urban ecological environment. Park and green space accessibility is an essential indication of urban livability. Recently, Hefei has become the city with the fastest GDP growth rate in China, little is known about the accessibility and landscape patterns of parks and green spaces in Hefei. We used GIS network analysis and landscape pattern indices to explore the parks and green spaces in the main urban area of Hefei. The results showed that the accessibility to parks and green spaces in the main urban area of Hefei is poor in walking mode, with less than 50% of people able to reach parks and green spaces within 15 minutes. Contrastingly, the accessibility to parks and green spaces in the main urban area of Hefei is good in cycling mode, with 98.06% of people able to reach parks and green spaces within 15 minutes. Furthermore, the parks and green spaces in Hefei have low dimensional indices, indicating high human intervention and regular landscape shapes, which are not conducive to maintaining urban biodiversity and creating natural green landscapes. The spread indices and fragmentation indices of each administrative district are high, indicating a uniform distribution of parks and green spaces. Our study analyzes the accessibility and landscape patterns of parks and green spaces in Hefei, and it will provide a scientific reference for park and green space planning in Hefei. [ABSTRACT FROM AUTHOR]

Glaucoma, a blinding neurodegenerative disease, whose risk factors include elevated intraocular pressure (IOP), age, and genetics, is characterized by accelerated and progressive retinal ganglion cell (RGC) death. Despite decades of research, the mechanism of RGC death in glaucoma is still unknown. Here, we demonstrate that the genetic effect of the SIX6 risk variant (rs33912345, His141Asn) is enhanced by another major POAG risk gene, p16INK4a (cyclin-dependent kinase inhibitor 2A, isoform INK4a). We further show that the upregulation of homozygous SIX6 risk alleles (CC) leads to an increase in p16INK4a expression, with subsequent cellular senescence, as evidenced in a mouse model of elevated IOP and in human POAG eyes. Our data indicate that SIX6 and/or IOP promotes POAG by directly increasing p16INK4a expression, leading to RGC senescence in adult human retinas. Our study provides important insights linking genetic susceptibility to the underlying mechanism of RGC death and provides a unified theory of glaucoma pathogenesis. Zhang et al. report p16INK4a as a downstream integrator of diverse signals, such as inherited genetic risk, age, and intraocular pressure, in the pathogenesis of glaucoma. They demonstrate that upregulation of SIX6 upon stress directly increases p16INK4a, leading to retinal ganglion cell senescence and death.

Abstract Saposhnikovia divaricata is commonly used in clinical practice as a heat-clearing and detoxifying traditional Chinese medicine. Current research on Saposhnikovia divaricata has mostly focused on chromones, while studies on its lipophilic parts remain scarce. In this study, samples of the lipophilic components of Saposhnikovia divaricata (SDL) from different regions in China were collected to establish an HPLC fingerprint. The quality of SDL was evaluated through chemical pattern recognition and multi-component content determination. Furthermore, using the Caenorhabditis elegans (C. elegans) model, the anti-aging ability of SDL was preliminarily studied. In the HPLC fingerprints of 11 batches of SDL, 19 common peaks were identified, and 4 components were characterized as follows: peak 14, linolenic acid (ALA); peak 15, docosahexaenoic acid (DHA); peak 16, linoleic acid (LA); peak 17, oleic acid (OA). The similarity of the fingerprint ranged from 0.704 to 0.929. The results indicate that the content of ALA, DHA, LA, and OA are 0.040–0.440 mg/g, 0.003–0.116 mg/g, 1.047–6.460 mg/g, and 0.040–0.294 mg/g, respectively. HCA analysis divided 11 batches of SDL into two categories, and PCA analysis extracted 6 principal components with a cumulative contribution rate of 85.91%. The anti-aging ability of the SDL was proved by measuring the lifespan, reproductive capacity, body length, mobility, lipofuscin content, and heat stress resistance of C. elegans. The combination of high-performance liquid chromatography fingerprint and chemical pattern recognition for multi-component content determination is a reliable, comprehensive, and promising evaluation of the quality of SDL. The confirmation of SDL’s anti-aging ability provides the possibility for the research of Saposhnikovia divaricata in the field of healthy food and cosmetics.

Abstract Background Human Papillomavirus (HPV) DNA screening was a crucial element in the fight against cervical cancer and had been adopted in many countries, including China. However, the onset of the COVID-19 pandemic in March 2020 disrupted this program significantly. Methods The aim of this study is to investigate the prevalence and distribution of HPV genotypes among the population undergoing cervical cancer screening during the pandemic period. From January 2017 to December 2022, Peking Union Medical College Hospital gathered 45,496 cervical swabs from individuals undergoing cervical cancer screening. These samples were analyzed to detect fifteen high-risk HPV (HR-HPV) DNA types and a combination of two low-risk HPV (LR-HPV) types. Results The study revealed an overall infection rate of 11.24% (5,114/45,496), with 11.06% (5,032/45,496) of individuals infected with HR-HPV. The number of HPV screening patients and the infection rates of HPV, HR-HPV, LR-HPV, multiple genotype HPV (M-HPV), and single genotype HPV (S-HPV) during the pandemic were lower than those observed before the pandemic. Moreover, the age group with the highest percentage of infected individuals was under 45–49 years, with HPV52, HPV58, HPV16, and HPV51 being the most prevalent genotypes. Notably, HPV66 emerged as the fifth most commonly detected genotype during the pandemic. Additionally, among the eleven age groups examined, women under 25 exhibited the highest detection rate, with HPV52 and HPV16 infection rates exceeding those observed in the pre-pandemic period. Conclusions The findings of this study offer significant insights for shaping HPV prevention strategies and enhancing cervical cancer screening initiatives in China following the epidemic.

Abstract In the present work, we investigate the productions of $$X_0(2900)$$ X 0 ( 2900 ) and its spin partners in the $$B^+$$ B + decay processes, where $$X_0(2900)$$ X 0 ( 2900 ) is regarded as a $$\bar{D}^*K^*$$ D ¯ ∗ K ∗ molecular state. We infer that the initial $$B^+$$ B + meson and the final $$D^+ X_0(2900)$$ D + X 0 ( 2900 ) are connected through the $$D_{s1}^{\prime +}(2460) \bar{D}^{*0} $$ D s 1 ′ + ( 2460 ) D ¯ ∗ 0 mesons by exchanging a $$K^{*0}$$ K ∗ 0 meson. The contributions of such a meson loop to the process $$B^+ \rightarrow D^+ X_0(2900)$$ B + → D + X 0 ( 2900 ) are evaluated and our estimations indicate that the measured branching fraction of $$B^+\rightarrow D^+ X_0(2900)$$ B + → D + X 0 ( 2900 ) could be well reproduced in a reasonable range of model parameters, indicating that $$X_0(2900)$$ X 0 ( 2900 ) could be interpreted as a $$\bar{D}^*K^*$$ D ¯ ∗ K ∗ molecular state. In addition, the production processes $$B^+ \rightarrow D^+ \tilde{X}_{1,2}$$ B + → D + X ~ 1 , 2 , $$B^+ \rightarrow D^{*+} X_0(2900)$$ B + → D ∗ + X 0 ( 2900 ) , and $$B^+ \rightarrow D^{*+}\tilde{X}_{1,2}$$ B + → D ∗ + X ~ 1 , 2 are investigated, and we find that the fit fraction of $$\tilde{X}_1$$ X ~ 1 in the process $$B^+ \rightarrow D^{*+} D^{*-} K^+$$ B + → D ∗ + D ∗ - K + is about 6%, which should be accessible by the LHCb and Belle II Collaborations.

Abstract The mixed-valence compound YbB12 displays paradoxical quantum oscillations in electrical resistivity and magnetic torque in a regime with a well-developed insulating charge gap and in the absence of an electronic Fermi surface. However, signatures of such unusual fermionic quasiparticles in other bulk thermodynamic observables have been missing. Here we report the observation of a series of sharp double-peak features in the specific heat as a function of the magnetic field. The measured Hall resistivity evolves smoothly across the field values at which the characteristic anomalies appear in the thermodynamic response and rules out the possibility of conventional electrons as their origin. Our observations of thermodynamic anomalies in a bulk three-dimensional electrical insulator provide the evidence for the presence of emergent dispersing fermionic excitations within the insulating bulk, which sets the stage for further investigation of electron fractionalization in other correlated mixed-valence compounds.

ObjectivesIn this paper, an orthogonal braided glass fiber composite sandwich panel with a PVC foam core and dimensions of 150 mm×100 mm×26 mm is selected as the research object in order to study the impact mechanical properties of composite sandwich panels. The dynamic response and residual compressive strength of the panel under single-point low-velocity impact are then analyzed.MethodsFirst, a series of drop hammer impact tests are conducted to study the failure mode, impact force-displacement response and energy absorption characteristics of the panel under different impact energies. Next, quasi-static compression experiments are conducted to investigate the maximum compression load capacity and residual compressive strength under impact damage.ResultsThere are significant differences in the failure modes and impact force-displacement characteristics of the sandwich panel under different impact energies. The core mainly absorbs impact energy through compression deformation. As the impact energy increases, the maximal impact force, dent depth and absorbed energy of panel gradually increase, while the maximum compression load capacity and residual strength decrease after impact. The damage degree of the impacted composite sandwich panel determines its residual compressive strength. ConclusionThe findings of this study can provide valuable references for the impact resistance design of naval ship structures.

Abstract Although multiple myeloma (MM) responds well to immunotherapeutic treatment, certain portions of MM are still unresponsive or relapse after immunotherapy. Other immune molecules are needed for the immunotherapy of MM. Here, we revealed that leukocyte immunoglobulin-like receptor B4 (LILRB4) was highly expressed in multiple myeloma cell lines and patient samples and that the expression of LILRB4 was adversely correlated with the overall survival of MM patients. Knockdown of LILRB4 efficiently delayed the growth of MM cells both in vitro and in vivo. Mechanistically, IKZF1 transactivated LILRB4 expression to trigger the downstream of STAT3-PFKFB1 pathways to support MM cell proliferation. Blockade of LILRB4 signaling by blocking antibodies can effectively inhibit MM progression. Our data show that targeting LILRB4 is potentially an additional therapeutic strategy for the immunotherapeutic treatment of MM.

Abstract As one of the significant challenges to human health, cancer has long been a focal point in medical treatment. With ongoing advancements in the field of medicine, numerous methodologies for cancer therapy have emerged, among which oncolytic virus therapy has gained considerable attention. However, oncolytic viruses still exhibit limitations. Combining them with various therapies can further enhance the efficacy of cancer treatment, offering renewed hope for patients. In recent research, scientists have recognized the promising prospect of amalgamating oncolytic virus therapy with diverse treatments, potentially surmounting the restrictions of singular approaches. The central concept of this combined therapy revolves around leveraging oncolytic virus to incite localized tumor inflammation, augmenting the immune response for immunotherapeutic efficacy. Through this approach, the patient's immune system can better recognize and eliminate cancer cells, simultaneously reducing tumor evasion mechanisms against the immune system. This review delves deeply into the latest research progress concerning the integration of oncolytic virus with diverse treatments and its role in various types of cancer therapy. We aim to analyze the mechanisms, advantages, potential challenges, and future research directions of this combination therapy. By extensively exploring this field, we aim to instill renewed hope in the fight against cancer.

Abstract Due to the increasing power system capacity, the interruption of large fault currents has gradually become a major challenge in power systems. At the moment, such currents are interrupted mainly via circuit breakers based on the method of active current commutation. However, these types of circuit breakers tend to be costly and oversized. One possible alternative—a fuse‐based circuit breaker with current commutation process enhanced by an external transverse magnetic field (ETMF)—is proposed by the authors. Its main advantage lies in the fast current commutation achieved by an ETMF‐enhanced three‐stage increase of the vacuum arc voltage. The study of the current commutation process is mainly represented by the authors, and the influencing factors of the current commutation—contact opening speed and ETMF current—are discussed. At last, the proposed circuit breaker is verified by an experiment, whose results show that a short‐circuit current of 42 kA can be interrupted within just 2 ms.

IntroductionThe elevation of the intraocular and extraocular pressures is associated with various visual conditions, including glaucoma and traumatic retinal injury. The retina expresses mechanosensitive channels (MSCs), but the role of MSCs in retinal physiology and pathologies has been unclear.MethodsUsing immunocytochemistry, confocal microscopy, and patch-clamp recording techniques, we studied the co-expression of K+-permeable (K-MSCs) TRAAK and big potassium channel BK with the epithelial sodium channel ENaC and transient receptor potential channel vanilloid TPRV4 and TRPV2 favorably permeable to Ca2+ than Na+ (together named N-MSCs), and TRPV4 activity in the mouse retina.ResultsTRAAK immunoreactivity (IR) was mainly located in Müller cells. Photoreceptor outer segments (OSs) expressed BK and ENaCα intensively and TRAAK, TRPV2, and TRPV4 weakly. Somas and axons of retinal ganglion cells (RGCs) retrograde-identified clearly expressed ENaCα, TRPV4, and TRPV2 but lacked TRAAK and BK. Rod bipolar cells (RBCs) showed TRPV4-IR in somas and BK-IR in axonal globules. Horizontal cells were BK-negative, and some cone BCs lacked TRPV4-IR. TRPV4 agonist depolarized RGCs, enhanced spontaneous spikes and excitatory postsynaptic currents, reduced the visual signal reliability (VSR = 1-noise/signal) by ~50%, and resulted in ATP crisis, which could inactivate voltage-gated sodium channels in RGCs.ConclusionIndividual neurons co-express hyperpolarizing K-MSCs with depolarizing N-MSCs to counterbalance the pressure-induced excitation, and the level of K-MSCs relative to N-MSCs (RK/N ratio) is balanced in the outer retina but low in RGCs, bringing out novel determinants for the pressure vulnerability of retinal neurons and new targets for clinical interventions.

Renewable energy serves as an effective alternative to traditional fossil fuels, reducing reliance on energy imports from specific countries, thereby alleviating geopolitical risks and ensuring national energy security. The development and utilization of renewable energy have profound implications for the global energy consumption structure and geopolitical landscape. This paper utilizes time-series and panel data from 1990 to 2020 to examine the causal relationship between renewable energy consumption and geopolitical risks. Focusing primarily on the United States and the United Kingdom, a multivariate regression model was developed for empirical analysis, with a comparative analysis conducted against other Group of Seven (G7) member countries. Subsequent robustness checks were performed to further validate the model's robustness. Additionally, this study explores the role of military strength as a moderating variable in the relationship between renewable energy and geopolitics. Lastly, a vector autoregression model was constructed to analyze the dynamic relationships between renewable energy and related variables. The findings reveal that (1) consumption of clean renewable energies, such as solar, wind, and tidal energy, significantly reduces geopolitical risks in the United States and the United Kingdom, with differing empirical results for France, Canada, and Japan, interpreted according to their developmental contexts and (2) increased defense expenditure in the US and the UK significantly enhances the positive impact of renewable energy consumption on mitigating geopolitical risks. Utilizing renewable energy not only diversifies national energy options but also reduces reliance on fossil fuels and fosters international cooperation, thereby easing geopolitical tensions. This research enriches the literature on the relationship between renewable energy consumption and national energy security in key global nations and offers theoretical insights for the formulation and implementation of national energy development strategies in the new world development paradigm.

Abstract Liquid–liquid phase separation (LLPS) has emerged as a pivotal biological phenomenon involved in various cellular processes, including the formation of membrane‐less organelles and the regulation of biomolecular condensates through precise spatiotemporal coordination of signaling pathways in cells. Dysregulation of LLPSs results in aberrant biomolecular condensates, which are widely implicated in tumorigenesis and cancer progression. Here, we comprehensively summarize the multifaceted roles of LLPS in tumor biology from the perspective of cancer hallmarks, including genomic stability, metabolic reprogramming progression, ferroptosis, and metastasis, to unveil the intricate mechanisms by which LLPS occurs in tumorigenesis. We discuss current discoveries related to therapeutic involvement and potential clinical applications of LLPS in cancer treatment, highlighting the potential of targeting LLPS‐driven processes as novel therapeutic strategies. Additionally, we discuss the challenges associated with new approaches for cancer treatment based on LLPS. This in‐depth discussion of the impact of LLPS on fundamental aspects of tumor biology provides new insights into overcoming cancer.