Search

Qian Gui,1,* Jingcai Meng,2,* Mingqiang Shen,1 Hongxuan Feng,1 Xiaofeng Dong,1 Daqiang Xu,3 Wenxin Zhu,2 Qingzhang Cheng,1 Linhui Wang,2 Guanhui Wu,1 Yanli Lu3 1Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, 215002, People’s Republic of China; 2Department of Physiology and Neurobiology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China; 3Department of Radiology, the Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, 215002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanli Lu, Department of Radiology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), 26 Daoqian Street, Suzhou City, Jiangsu Province, People’s Republic of China, Tel +8618251135654, Email luyanli.2009@163.com Guanhui Wu, Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), 26 Daoqian Street, Suzhou City, Jiangsu Province, People’s Republic of China, Email ghwusz26@njmu.edu.cnIntroduction: Previous studies have predominantly explored the relationship of the glymphatic system with motor symptoms in Parkinson’s disease (PD); however, research on non-motor symptoms remains limited. Therefore, this study investigated the association between glymphatic function and non-motor symptoms, including cognitive impairment and sleep disorders, in PD patients.Methods: This study recruited 49 PD patients and 38 healthy controls (HC). Glymphatic function was evaluated using enlarged perivascular spaces (EPVS) in the basal ganglia (BG) region and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Cognition, sleep, anxiety, and depression scales were assessed in all participants. According to the scale scores, PD patients were further divided into several groups to identify the presence of non-motor symptoms. Differences in EPVS numbers and ALPS index between PD subgroups and HC group were compared. Spearman correlation analysis was performed to investigate the association between the PD non-motor symptoms and ALPS index. Additionally, receiver operating characteristic (ROC) curves analysis was conducted for ALPS index to predict cognitive impairment and insomnia in PD patients.Results: PD patients with and without non-motor symptoms all showed more EPVS numbers than the controls, and the EPVS numbers in PD patients with cognitive impairment were also greater than those without. Notably, except for the depression subgroup, PD patients with non-motor symptoms showed significantly lower ALPS index than the controls. The Montreal Cognitive Assessment (MoCA) scores were positively correlated, whereas the Parkinson’s Disease Sleep Scale (PDSS)-2 and REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) scores were negatively correlated with the ALPS index in PD patients (r=0.3618, P=0.0053; r=− 0.4146, P=0.0015; r=− 0.2655, P=0.0326, respectively). The ALPS index proved to be predictive of cognitive impairment and insomnia in PD patients (AUC=0.7733, P=0.001; AUC=0.7993, P=0.0004, respectively).Conclusion: Glymphatic function is closely associated with cognition and sleep of PD patients.Keywords: glymphatic system, parkinson’s disease, non-motor symptoms, cognition, sleep

Hui Zhang,1 Minghui Li,1 Jing Zhang,1 Yanbing Shen,2 Qi Gui2 1College of Medical, Huanghuai University, Zhumadian, Henan, People’s Republic of China; 2Department of Urology, The Central Hospital of Zhumadian, Zhumadian, Henan, People’s Republic of ChinaCorrespondence: Hui ZhangCollege of Medical, Huanghuai University, No. 2628, Mountain Panlong Road, Zhumdian, 463000, Henan, People’s Republic of ChinaTel +86-0396-2853503Email cecile98@163.comBackground: Exosomal circular RNAs (circRNAs) are involved in the pathogenesis of prostate cancer (PCa) and chemotherapy resistance. This research aimed to explore the function and molecular mechanism of circRNA X-linked inhibitor of apoptosis (circ-XIAP) in docetaxel (DTX) resistance of PCa.Methods: The expression of circ-XIAP, microRNA-1182 (miR-1182), tumor protein D52 (TPD52) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were detected with transmission electron microscopy (TEM). Cluster of differentiation 63 (CD63), cluster of differentiation 9 (CD9) and TPD52 protein levels were detected by Western blot (WB). FIfty percent inhibitory concentration (IC50) of DTX and cell viability were determined using Cell Counting Kit-8 (CCK-8) assay. Colony formation assay was applied to assess colony-forming ability. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Transwell assay was used for measuring cell migration and invasion. Dual-reporter luciferase assay was performed to confirm the interaction between miR-1182 and circ-XIAP or TPD52. The role of circ-XIAP in vivo was confirmed via the mice xenograft model.Results: Circ-XIAP and TPD52 were upregulated and miR-1182 was downregulated in DTX-resistant PCa tissue specimens and cell lines. Circ-XIAP was also overexpressed in exosomes from DTX-resistant cells and could be transmitted via exosomes. Circ-XIAP knockdown enhanced DTX sensitivity by suppressing DTX-resistant cell proliferation, migration and invasion and inducing cell cycle arrest and apoptosis. Circ-XIAP directly targeted miR-1182, and the effects of circ-XIAP knockdown were reversed by downregulating miR-1182 in DTX-resistant cells. TPD52 was the target of miR-1182, and its upregulation weakened the promotive effect of miR-1182 on DTX sensitivity. Importantly, circ-XIAP depletion inhibited tumor growth and increased DTX sensitivity in vivo.Conclusion: Exosomal circ-XIAP promoted DTX resistance of PCa by regulating miR-1182/TPD52 axis, providing a promising therapeutic target for PCa chemotherapy.Keywords: prostate cancer, exosomes, circ-XIAP, miR-1182, TPD52

Jianping Liu,1 Weihua Zhao,2 Qinghong Gui,1 Ying Zhang,1 Zaiyu Guo,2 Wei Liu3 1Department of Neurology, Tianjin TEDA Hospital, Tianjin 300457, People’s Republic of China; 2Department of Neurosurgery, Tianjin TEDA Hospital, Tianjin 300457, People’s Republic of China; 3Department of Neurology, Tianjin Medical University General Hospital, Tianjin 300052, People’s Republic of ChinaCorrespondence: Zaiyu GuoDepartment of Neurosurgery, Tianjin TEDA Hospital, No. 65, The Third Avenue, Tianjin Economy Development Area, Tianjin 300457, People’s Republic of ChinaTel +86-15302100230Email guozaiyu_teda@163.comWei LiuDepartment of Neurology, Tianjin Medical University General Hospital, No. 154, An Shan Road, Heping District, Tianjin 300052, People’s Republic of ChinaTel +86-2260362255Email liuweithird@126.comPurpose: To investigate the associations between concentrations of Aβ40 and Aβ42 and vascular cognitive impairment (VCI) in cerebral small vessel disease (CSVD) patients and evaluate the value of combination of levels of Aβ40 or Aβ42 and the total CSVD score in predicting VCI.Patients and Methods: A total of 199 CSVD patients were divided into VCI group and non-VCI group according to the criteria of VCI. Demographic data, MRI markers of CSVD, blood pressure, vascular risk factors, laboratory markers, and serum Aβ40 and Aβ42 concentration were collected. Univariate analysis was performed with the Student’s t-test, Mann–Whitney U-test or Chi-square test. Variables with P< 0.10 in univariate analysis were then included in multivariate analysis that used a backward stepwise logistic regression model. The predictive values were assessed with receiver operating characteristic (ROC) curve.Results: VCI was determined in 112 CSVD patients (56.3%). Hyperlipidemia (OR: 1.618, 95% CI: 1.265– 3.049), the total CSVD score (OR: 1.414, 95% CI: 1.213– 2.278) and serum Aβ42 concentration (OR: 1.401, 95% CI: 1.212– 1.946) were independent risk factors for VCI in CSVD patients with adjustment for age, education years, diabetes and fasting blood-glucose (FBG). The area under curves (AUCs) were 0.640 (SE: 0.040, 95% CI: 0.563– 0.718), 0.733 (SE: 0.035, 95% CI: 0.664– 0.802) and 0.827 (SE: 0.030, 95% CI: 0.768– 0.887), respectively, for the total CSVD score, serum Aβ42 concentration and their combination applied in predicting VCI in CSVD patients. Z test demonstrated that the AUC of combination prediction was significantly higher than individual prediction (0.827 vs 0.640, Z=3.740, P< 0.001; 0.827 vs 0.733, Z=2.039, P=0.021).Conclusion: Combination of Aβ42 and total CSVD score could significantly elevate the predictive value of cognitive impairment in CSVD patients.Keywords: Aβ40, Aβ42, vascular cognitive impairment, cerebral small vessel disease, total cerebral small vessel disease score

Tao Lv,1,* Yunbo Chen1,* Lihua Guo,1 Qiaomai Xu,1 Silan Gu,1 Ping Shen,1 Jiazheng Quan,1 Yunhui Fang,1 Lifeng Chen,2 Qiaodi Gui,3 Guangyong Ye,4 Lanjuan Li11State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Medical Engineering Department, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Clinical Laboratory, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, People’s Republic of China; 4Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workBackground: The epidemic new strain NAP1/BI/027/ST-1 of Clostridioides difficile (C. difficile) causes more severe coliti and a higher mortality rate than historical strains. However, C. difficile NAP1/BI/027/ST-1 (C. difficile RT027) infections have been rarely reported in Asia, particularly in China.Purpose: The objective of this study was to strengthen the understanding of the molecular characterizations of C. difficile RT027 in China.Patients and methods: Two C. difficile NAP1/BI/027/ST-1 were detected from two patients, and no additional isolates were found. Whole genome sequencing (WGS) was used to characterize two C. difficile RT027 isolates and control strain CD6 (from Hong Kong), and comparative genomic analysis was performed to compare genomic differences between seven isolates from Mainland China, CD6, and 10 isolates from North America and Europe.Results: The comparative genomic analysis revealed that isolates obtained from Mainlan China were outside of the two epidemic lineages, FQR1 and FQR2, and might have decreased virulence and transmissibility for outbreak. Furthermore, unique SNP mutations were detected in isolates obtained from Mainland China, which may affect the biological function of C. difficile.Conclusion: We speculate that C. difficile RT027 isolates in Mainland China may have different features, compared to those in North America and Europe.Keywords: People’s Republic of China, multilocus sequence typing, Clostridioides difficile infection, whole genome sequencing

Abstract Evolution of SARS-CoV-2 variants emphasizes the need for multivalent vaccines capable of simultaneously targeting multiple strains. SCTV01E is a tetravalent COVID-19 vaccine derived from the spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1. In this double-blinded placebo-controlled pivotal efficacy trial (NCT05308576), the primary endpoint was vaccine efficacy (VE) against COVID-19 seven days post-vaccination in individuals without recent infection. Other endpoints included evaluating safety, immunogenicity, and the VE against all SARS-CoV-2 infections in individuals meeting the study criteria. Between December 26, 2022, and January 15, 2023, 9,223 individuals were randomized at a 1:1 ratio to receive SCTV01E or a placebo. SCTV01E showed a VE of 69.4% (95% CI: 50.6, 81.0) 7 days post-vaccination, with 75 cases in the placebo group and 23 in the SCTV01E group for the primary endpoint. VEs were 79.7% (95% CI: 51.0, 91.6) and 82.4% (95% CI: 57.9, 92.6), respectively, for preventing symptomatic infection and all SARS-CoV-2 infections 14 days post-vaccination. SCTV01E elicited a 25.0-fold higher neutralizing antibody response against Omicron BA.5 28 days post-vaccination compared to placebo. Reactogenicity was generally mild and transient, with no reported vaccine-related SAE, adverse events of special interest (AESI), or deaths. The trial aligned with the shift from dominant variants BA.5 and BF.7 to XBB, suggesting SCTV01E as a potential vaccine alternative effective against present and future variants.

Using the final state analysis method (fracture morphology analysis), it is difficult to establish the dynamic changes that would have occurred during the process of necking under tensile load. In this paper, the time-dependent observations, the critical hole expansion ratio model and the Bridgeman equation is applied to establish the relationship between the dynamics of necking and the microscopic parameters that describe fracture in samples made from the low-carbon steel. The results show that the axial (x) and radial (y) displacements observed in the necking process are described by the Gaussian function. And the curve of the neck contraction (yc) and time (t) indicates that the macroscopic deformation process behind necking can be divided into three stages, which correspond to microcrack propagation in the fiber area, the radiation area, and the shear lip area. Following, by considering the fitted model of x-y, the critical hole expansion ratio model and the Bridgeman equation, a novel model between the macroscopic deformation (parameters of yc and εt) observed in necking and the formation of micropores (parameter of Rc) is established, which can disclose the effect of macroscopic deformation on the formation of the micro-voids, and plays a role in the study of plastic deformation mechanisms in a wide range of materials.

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the COVID-19 pandemic, has profoundly impacted global healthcare systems and the trajectory of economic advancement. As nations grapple with the far-reaching consequences of this unprecedented health crisis, the administration of COVID-19 vaccines has proven to be a pivotal strategy in managing this crisis. Protein-based vaccines have garnered significant attention owing to their commendable safety profile and precise immune targeting advantages. Nonetheless, the unpredictable mutations and widespread transmission of SARS-CoV-2 have posed challenges for vaccine developers and governments worldwide. Monovalent and multivalent vaccines represent two strategies in COVID-19 vaccine development, with ongoing controversy surrounding their efficacy. This review concentrates on the development of protein-based COVID-19 vaccines, specifically addressing the transition from monovalent to multivalent formulations, and synthesizes data on vaccine manufacturers, antigen composition, pivotal clinical study findings, and other features that shape their distinct profiles and overall effectiveness. Our hypothesis is that multivalent vaccine strategies for COVID-19 could offer enhanced capability with broad-spectrum protection.

The Omicron EG.5 lineage of SARS-CoV-2 is currently on a trajectory to become the dominant strain. This phase 2 study aims to evaluate the immunogenicity of SCTV01E-2, a tetravalent protein vaccine, with a specific emphasis on its immunogenicity against Omicron EG.5, comparing it with its progenitor vaccine, SCTV01E (NCT05933512). As of 12 September 2023, 429 participants aged ≥18 years were randomized into the groups SCTV01E (N = 215) and SCTV01E-2 (N = 214). Both vaccines showed increases in neutralizing antibody (nAb) against Omicron EG.5, with a 5.7-fold increase and a 9.0-fold increase in the SCTV01E and SCTV01E-2 groups 14 days post-vaccination, respectively. The predetermined statistical endpoints were achieved, showing that the geometric mean titer (GMT) of nAb and the seroresponse rate (SRR) against Omicron EG.5 were significantly higher in the SCTV01E-2 group than in the SCTV01E group. Additionally, SCTV01E and SCTV01E-2 induced a 5.5-fold and a 5.9-fold increase in nAb against XBB.1, respectively. Reactogenicity was generally mild and transient. No vaccine-related serious adverse events (SAEs), adverse events of special interest (AESIs), or deaths were reported. In summary, SCTV01E-2 elicited robust neutralizing responses against Omicron EG.5 and XBB.1 without raising safety concerns, highlighting its potential as a versatile COVID-19 vaccine against SARS-CoV-2 variants.

Summary: Cyclic GMP-AMP synthase (cGAS) recognizes Y-form cDNA of human immunodeficiency virus type 1 (HIV-1) and initiates antiviral immune response through cGAS-stimulator of interferon genes (STING)-TBK1-IRF3-type I interferon (IFN-I) signalingcascade. Here, we report that the HIV-1 p6 protein suppresses HIV-1-stimulated expression of IFN-I and promotes immune evasion. Mechanistically, the glutamylated p6 at residue Glu6 inhibits the interaction between STING and tripartite motif protein 32 (TRIM32) or autocrine motility factor receptor (AMFR). This subsequently suppresses the K27- and K63-linked polyubiquitination of STING at K337, therefore inhibiting STING activation, whereas mutation of the Glu6 residue partially reverses the inhibitory effect. However, CoCl2, an agonist of cytosolic carboxypeptidases (CCPs), counteracts the glutamylation of p6 at the Glu6 residue and inhibits HIV-1 immune evasion. These findings reveal a mechanism through which an HIV-1 protein mediates immune evasion and provides a therapeutic drug candidate to treat HIV-1 infection.

Abstract Background Metabolic reprogramming is a hallmark of cancer. However, the roles of long noncoding RNAs (lncRNAs) in cancer metabolism, especially glucose metabolism remain largely unknown. Results In this study, we identified and functionally characterized a novel metabolism-related lncRNA, LINC00930, which was upregulated and associated with tumorigenesis, lymphatic invasion, metastasis, and poor prognosis in nasopharyngeal carcinoma (NPC). Functionally, LINC00930 was required for increased glycolysis activity and cell proliferation in multiple NPC models in vitro and in vivo. Mechanistically, LINC00930 served as a scaffold to recruit the RBBP5 and GCN5 complex to the PFKFB3 promoter and increased H3K4 trimethylation and H3K9 acetylation levels in the PFKFB3 promoter region, which epigenetically transactivating PFKFB3, and thus promoting glycolytic flux and cell cycle progression. Clinically, targeting LINC00930 and PFKFB3 in combination with radiotherapy induced tumor regression. Conclusions Collectively, LINC00930 is mechanistically, functionally and clinically oncogenic in NPC. Targeting LINC00930 and its pathway may be meaningful for treating patients with NPC.

In order to achieve sustainable development, low-carbon economic efficiency (LCEE) is particularly important in China. Therefore, this study uses SBM-DEA model to evaluate the LCEE of 30 provinces in China from 2008 to 2017. Based on the uncoordinated coupling model, this study discusses the interaction between China’s provincial LCEE and scientific and technological development level (STDL), and uses the panel VAR model to consider the interactive response relationship between China’s provincial LCEE and STDL. The research shows that the uncoordinated coupling degree (UCCD) between the STDL and LCEE in 30 provinces showed a decreasing trend as a whole during the research period. In terms of spatial distribution, the provinces with UCCD less than 0.5 mainly concentrated in the eastern and southern provinces, gradually spread to the north, and showed positive spatial autocorrelation, with significant spatial accumulation effect. From the perspective of influencing factors, patents, urbanization level, traffic level and financial development have significant positive effects on promoting the coordinated development of STDL and LCEE. From the relationship between them, the STDL has a positive promoting effect on LCEE, but the mechanism of the two is not obvious enough. Therefore, it is necessary to emphasize the coordinated development of low-carbon economy and science and technology, and promote the development of low-carbon economy through scientific innovation.

In China, online sales continue to grow against the generally adverse effects of the COVID-19 pandemic on economic development. Although advertisers favor online targeted advertising for its precision, consumers may find it intrusive and avoid it. This study constructed a conceptual model based on Stimulus-Organism-Response (SOR) theory, Approach-Avoidance Theory, and Brand Avoidance Theory to investigate the influence mechanism of consumers’ perceived risk on the avoidance behavior of online targeted advertising via an online survey. Collected 436 validated data was analyzed through structural equation method in AMOS statistical software. Results showed that the positively influenced advertising avoidance, and negative emotions mediated the relationship between perceived performance risk, time-loss risk, freedom risk, and advertising avoidance, but perceived privacy risk did not influence advertising avoidance through negative emotions. Perceived COVID-19 risk moderates the effect of negative emotions on advertising avoidance. The findings provide important insights for helping governments, advertisers and online platforms into which risk perceptions influence advertising avoidance, and suggests ways to mitigate consumers risk perceptions for the mutual benefit of brands and users.

Excessive interferon (IFN) responses often follow viral infection to induce pathology or even death. Here the authors show that a signaling adaptor, β-arrestin 2, enhances the cGAS/STING innate immunity signaling pathway to promote IFN-β production, but may be degraded in infected cells to serve as a target of viral immune evasion.

Introduction To improve the efficacy of anterior cervical decompression and fusion (ACDF) and reduce postoperative complications in degenerative cervical myelopathy, our team established a set of perioperative care of enhanced recovery guidelines of ACDF based on the concept of enhanced recovery after surgery. In addition, a prospective, multicentre, randomised clinical trial was designed.Methods and analysis A total of 260 patients aged 18–65 years will be included. Preoperative MRI and CT will be used to confirm the typical manifestations of cervical spondylosis, such as cervical disc herniation and spinal cord compression. The patient presents with neck and shoulder pain, numbness of upper limbs, weakened grip strength and cotton sense of foot tread. Patients received normal conservative treatment for 3 months with no obvious relief or even aggravation of symptoms. Patients will be assigned to the group in strict accordance with the random allocation table. Patients in groups A and B will receive conventional perioperative care and perioperative care for enhanced recovery, respectively. The main outcome indicators are the Karnofsky Performance Scale score and the Japanese Orthopaedic Association scale. Secondary outcome indicators are pain assessment by Numeric Rating Scale, Neck Disability Index, quality of life index (QL-Index) and postoperative complications. Follow-up will be conducted at 3, 6 and 12 months postoperatively.Ethics and dissemination Ethical approval has been granted by the Ethics Committee of Fujian Medical University Union Hospital, Fuzhou, China (2020YF034-01). Results of the research will be published in an international peer-reviewed scientific journal and disseminated through presentation at scientific conferences.Trial registration number ChiCTR2000040508.

OBJECTIVE: To analyze the efficacy of open nephron-sparing surgery (NSS) in the treatment of complex renal cell carcinoma. PATIENTS AND METHODS: A total of 118 patients with complex renal cell carcinoma (T1N0M0, clear cell carcinoma) were included in this study, and assigned into open radical nephrectomy (RN) group (35 patients), open NSS group (45 patients) and laparoscopic NSS group (38 patients). After 3 years of follow-up, the clinical efficacy was analyzed. RESULTS: Both the mean surgery time and ischemia blocking time in the open NSS group were comparable to those in the RN group, and significantly shorter than the laparoscopic NSS group, p < 0.05.The rate of positive margin in the open NSS group was significantly lower than the laparoscopic NSS group. The occurrence of total complications in the open NSS group was comparable to that in the laparoscopic NSS group and significantly lower than the RN group. The successful rate of surgery in the open NSS group was significantly higher than the laparoscopic NSS group, p < 0.05. The 75% survival was 30.0 months in the RN group, > 35.0 months in the open NSS group and 34.0 months in the laparoscopic NSS group, the difference was significant (p < 0.001). The mortality was similar in the open NSS group and the laparoscopic NSS group, and significantly smaller than the RN group, p < 0.05. CONCLUSIONS: Open NSS was more safe and effective in the treatment of complex renal cell carcinoma than RN and laparoscopic NSS. [ABSTRACT FROM AUTHOR]

Copyright of Geostandards & Geoanalytical Research is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The room-temperature d0 ferromagnetism in black phosphorous (BP) oxide is investigated experimentally and theoretically. Electrochemical oxidation does not alter the single-crystal structure of BP and the degree of oxidation depends on the oxidation time, thereby resulting in changeable d0 ferromagnetism caused by surface P-O bonds. First-principles calculation reveals that different surface P-O bonds have different binding energies and contributions to the ferromagnetism and the bridge and dangling oxygen atoms are responsible for the observed ferromagnetism which stems from p orbital spin polarization of the oxygen and phosphorus atoms. [ABSTRACT FROM AUTHOR]