Search

The Facility for Rare Isotope Beams (FRIB) began operation with 1 kW beam power for scientific users in May 2022 upon completion of 8 years of project construction. The ramp-up to the ultimate beam power of 400 kW, planned over a 6-year period, will enable the facility to reach its full potential for scientific discovery in isotope science and applications. In December 2023, a record-high beam power of 10.4 kW uranium was delivered to the target. Technological developments and accelerator improvements are being made over the entire facility and are key to completion of the power ramp-up. Major technological developments entail the phased deployment of high-power beam-intercepting systems, including the charge strippers, the charge selection systems, the production target, and the beam dump, along with support systems, including non-conventional utilities (NCU) and remote handling facilities. Major accelerator improvements include renovations to aging legacy systems associated with experimental beam lines and system automation for improved operational efficiency and better machine availability. Experience must be gained to safely handle the increased radiological impacts associated with high beam power; extensive machine studies and advanced beam tuning procedures are needed to minimize uncontrolled beam losses for the desired operating conditions. This paper discusses the technological developments and accelerator improvements with emphasis on major R&D efforts.

Zaifeng Si,1,2,&ast; Shengmei Zhao,3,&ast; Yingying Hao,3 Qian Wang,3 Yanfa Zhong,2 Yue Liu,3 Ran Chen,3 Yan Jin,3 Zhiming Lu1,3 1Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Clinical Laboratory, Dezhou Municipal Hospital of Traditional Chinese Medicine, Dezhou, Shandong, People’s Republic of China; 3Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Jin; Zhiming Lu, Email sdjinyan@163.com; luzhiming@sdu.edu.cnBackground: Enterobacter cloacae complex (ECC), which includes major nosocomial pathogens, causes urinary, respiratory, and bloodstream infections in humans, for which colistin is one of the last-line drugs.Objective: This study aimed to analyse the epidemiology and resistance mechanisms of colistin-resistant Enterobacter cloacae complex (ECC) strains isolated from Shandong, China.Methods: Two hundred non-repetitive ECC strains were collected from a tertiary hospital in Shandong Province, China, from June 2020 to June 2022. Whole-genome sequencing and bioinformatics analyses were performed to understand the molecular epidemiology of the colistin-resistant ECC strains. The nucleotide sequences of heat shock protein (hsp60) were analyzed by using BLAST search to classify ECC. The gene expression levels of ramA, soxS, acrA, acrB, phoP, and phoQ were assessed using RT-qPCR. MALDI-TOF MS was used to analyse the modification of lipid A.Results: Twenty-three colistin-resistant strains were detected among the 200 ECC clinical strains (11.5%). The hsp60 cluster analysis revealed that 20 of the 23 ECC strains belonged to heterogeneous resistance clusters. Variants of mgrB, phoPQ, and pmrAB, particularly phoQ and pmrB, were detected in the 23 ECC strains. The soxS and acrA genes were significantly overexpressed in all 23 colistin-resistant ECC strains (P < 0.05). Additionally, all 23 ECC strains contained modified lipid A related to colistin resistance, which showed five ion peaks at m/z 1876, 1920, 1955, 2114, and 2158. Among the 23 ECC strains, 6 strains possessed a phosphoethanolamine (pETN) moiety, 16 strains possessed a 4-amino-4-deoxy-L-arabinose (−L-Ara4N) moiety, and one strain had both pETN and −L-Ara4N moieties.Conclusion: This study suggests that diverse colistin resistance existed in ECC, including unknown resistance mechanisms, exist in ECC. Mechanistic investigations of colistin resistance are warranted to optimise colistin use in clinical settings and minimise the emergence of resistance.Keywords: Enterobacter cloacae complex, ECC, epidemiology, colistin, resistance mechanism

Yujie Hao, Runmin Liu, Hao Wang, Tao Rui, Junfang Guo Division of Cardiology, Department of Medicine, the Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of ChinaCorrespondence: Junfang Guo, Email zjyyxngjf@163.comAbstract: Sepsis is a syndrome of organ dysfunction caused by a dysregulated immune response to infection, with high morbidity and mortality. At present, there have been many advances in the study of its pathogenesis, especially the cardiac dysfunction caused by sepsis, namely sepsis-induced myocardial dysfunction, SIMD, which has received widespread attention. The mechanisms of SIMD mainly include excessive release of inflammatory mediators, impaired mitochondrial function, autophagy, apoptosis and myocardial dysfunction. This article reviews the pathogenesis of SIMD and elaborates on the progress in its treatment, aiming to improve the prognosis of patients with SIMD and sepsis.Keywords: sepsis, sepsis-induced myocardial dysfunction, pathogenesis, treatment

Yukai Hao,1 Baoling Zhao,1 Dongchao Wu,1 Xuejun Ge,1 Jianmin Han2 1Department of Endodontics, Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China; 2Central Laboratory, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, People’s Republic of ChinaCorrespondence: Xuejun Ge, The Department of Endodontics, Shanxi Medical University School and Hospital ofStomatology, 63 Xinjian South Road, Yingze District, Taiyuan, 030001, People’s Republic of China, Tel +8613834568537, Email gxj19722003@163.com Jianmin Han, Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguan Cun South Street, Beijing, 100081, People’s Republic of China, Tel +8613810459668, Email hanjianmin@bjmu.edu.cnIntroduction: Recombinant humanized collagen, as a novel biomaterial, exhibits multiple excellent biological functions, such as inhibition of inflammation, promotion of cell proliferation and vascular proliferation, and promotion of tissue healing. However, there is a lack of conclusive evidence regarding the specific role of recombinant humanized collagen type 17 (rhCol 17) in oral ulcer healing. This study explored whether rhCol 17 could promote the proliferation of human gingival fibroblasts (HGFs) and inhibit its inflammation, and whether it could promote the healing of oral ulcers in rats by inhibiting inflammation and accelerating tissue healing.Methods: At the cellular level, we investigated the effect of rhCol 17 on the proliferation of (HGFs) by CCK8; HGFs were mixed with lipopolysaccharide (LPS) to investigate the effect of rhCol 17 on HGFs in an inflammatory state. Eighteen adult male Sprague-Dawley rats were randomly distributed into three groups: blank control group, carbomer group (carbomer sprayed only), and rhCol 17 group (carbomer containing rhCol 17 sprayed), 1 time/day. The samples were collected at D3 and D5. At completion, histological staining and PCR were carried out to study its effect on the healing of oral ulcers in rats.Results: Through cellular experiments, we found that rhCol 17 possesses good biocompatibility and anti-inflammatory properties, and can effectively promote the proliferation and migration of HGFs, as well as significantly reduce the inflammation level of the cells. The animal experimental results showed that rhCol 17 could significantly reduce the inflammation level, promote collagen deposition and angiogenesis at the ulcer site, thus effectively accelerating the healing of oral ulcers in rats.Conclusion: In summary, the collagen sprays containing rhCol 17 have excellent anti-inflammatory effects and could accelerate tissue healing and are expected to provide a new effective treatment for patients with recurrent oral ulcers.Keywords: oral ulcer, inflammation, wound healing, recombinant humanized collagen

Yanting Hao,1 Hua Zhang,2 Fan Zhang1 1Department of Geriatrics, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Fan Zhang, Department of Geriatrics, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, People’s Republic of China, Email zfpuh3@126.comPurpose: It has been shown that lower Barthel’s index (BI) at admission is associated with a higher in-hospital mortality. There is a lack of evidence regarding the association between the change in BI during hospitalization and mortality after discharge. Our purpose was to determine whether the BI change during hospitalization is associated with all-cause mortality in older adults with COVID-19 pneumonia.Patients and Methods: We conducted a retrospective cohort study of 330 participants at Peking University Third Hospital during the COVID-19 pandemic period. In order to analyze the time to death data, a Kaplan-Meier survival curve was used. We used restricted cubic splines to analyze the association between BI change and all-cause mortality among COVID-19 pneumonia patients aged over 80 years old. Threshold effect analysis was used to assess the ability of BI change score to predict all-cause mortality.Results: Our study included 330 patients aged over 80 years with COVID-19 pneumonia. The Kaplan-Meier curve for mortality showed significantly worst survival with reduced BI among three groups (χ2= 6.896, P < 0.05). There was a non-linear association between the BI change and all-cause mortality (P for all over < 0.001). The effect sizes on the left and right sides of the inflection point were 0.958 (HR: 0.958, 95% CI 0.932– 0.958, P < 0.05) and 1.013 (HR: 1.013, 95% CI 0.967– 1.062, P > 0.05), respectively.Conclusion: Reduced BI during hospitalization was associated with the highest mortality risk. It is crucial to monitor BI change among COVID-19 pneumonia patients aged over 80 years old.Keywords: COVID-19 pneumonia, activities of daily living, mortality, older adult

Yongzhi Xu,1,2,&ast; Yuanping Hao,2,&ast; Muhammad Arif,3 Xiaodong Xing,4 Xuyang Deng,1 Danyang Wang,1 Yang Meng,2 Shuai Wang,1 Mohamed Sayed Hasanin,5 Wanchun Wang,2 Qihui Zhou3,6 1School of Stomatology, Qingdao University, Qingdao, People’s Republic of China; 2Department of Stomatology, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, People’s Republic of China; 3Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, People’s Republic of China; 4School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing, People’s Republic of China; 5Cellulose and Paper Department, National Research Centre, Dokki, Cairo, Egypt; 6Hubei Key Laboratory of Biomass Fibers and Eco-Dyeing & Finishing, Wuhan Textile University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wanchun Wang; Qihui Zhou, Email kqwwch@126.com; qihuizhou@uor.edu.cnIntroduction: Persistent endodontic infections (PEIs) mediated by bacterial biofilm mainly cause persistent periapical inflammation, resulting in recurrent periapical abscesses and progressive bone destruction. However, conventional root canal disinfectants are highly damaging to the tooth and periodontal tissue and ineffective in treating persistent root canal infections. Antimicrobial materials that are biocompatible with apical tissues and can eliminate PEIs-associated bacteria are urgently needed.Methods: Here, &epsiv;-poly (L-lysine) derived carbon quantum dots (PL-CQDs) are fabricated using pyrolysis to remove PEIs-associated bacterial biofilms.Results: Due to their ultra-small size, high positive charge, and active reactive oxygen species (ROS) generation capacity, PL-CQDs exhibit highly effective antibacterial activity against Enterococcus faecalis (E. faecalis), which is greatly dependent on PL-CQDs concentrations. 100 μg/mL PL-CQDs could kill E. faecalis in 5 min. Importantly, PL-CQDs effectively achieved a reduction of biofilms in the isolated teeth model, disrupting the dense structure of biofilms. PL-CQDs have acceptable cytocompatibility and hemocompatibility in vitro and good biosafety in vivo.Discussion: Thus, PL-CQDs provide a new strategy for treating E. faecalis-associated PEIs. Keywords: carbon quantum dots, Enterococcus faecalis, bacterial biofilm, persistent endodontic infections

Xin Huang,1,&ast; Meng Wang,1,&ast; Baochen Zhu,1,&ast; Yu Hao,2 Ruoyu Gao,2 Wenhui Liu,2 Jiaojiao Cheng,1 Guodong Hua,1 Chunmiao Xue1 1Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guodong Hua; Chunmiao Xue, Email zhaojhuagd@126.com; xuechunmiao9501@163.comIntroduction: Non-small cell lung cancer (NSCLC) stands as one of the most prevalent malignancies, and chemotherapy remains the primary treatment for advanced stages. However, the high expression of ABC binding cassette transporters, including MRP, P-gp, and LRP, along with multidrug resistance proteins, has been identified as a significant factor contributing to decreased chemotherapy drug sensitivity. This study aims to explore the impact and underlying mechanisms of Curculiginis Rhizoma [Hypoxidaceae; Curculigo orchioides Gaertn.] (CR) in combination with cisplatin on improving chemoresistance mediated by ABC binding cassette transporters and multidrug resistance proteins in NSCLC.Methods and Results: To unravel the relationship between JNK, MRP, P-gp, and LRP in NSCLC and gain insights into the regulatory mechanism of CR, this study employs an integrated approach encompassing bioinformatics, molecular docking, molecular dynamics, animal and cellular experiments. Bioinformatics analysis revealed a significant increase in the expression levels of JNK, MRP, P-gp, and LRP subtypes in multidrug-resistant non-small cell lung cancer. Subsequent animal experiments have shown that the combination of CR with cisplatin can improve the survival rate of lung cancer mice. Molecular docking and molecular dynamics analyses demonstrated favorable binding interactions between curculigoside and the aforementioned subtypes of JNK, MRP, P-gp, and LRP. In cellular experiments, the combination of cisplatin with both curculigoside and CR extract resulted in a notable decrease in cell viability and downregulation of the expression of JNK1, JNK2, MRP1, MRP2, MRP4, P-gp, and LRP1 in A549/cis cells.Conclusion: Remarkably, curculigoside exerted a significant downregulation effect on the expression levels of JNK1, MRP1, MRP2, MRP4, and LRP1. CR, particularly its main effective metabolite, curculigoside, has the potential to enhance the sensitivity of non-small cell lung cancer to cisplatin by regulating levels of JNK/MRP/LRP/P-gp and mitigating multidrug resistance.Keywords: non-small cell lung cancer, curculiginis rhizoma, CR, curculigoside, multidrug resistance, cisplatin resistance, ABC binding cassette transporter, multidrug resistance proteins

Wang L, Li D, Hao Y, et al. Int J Nanomedicine. 2017;12:3059-3075. The authors have advised Figures 9 and 11 on pages 3070 and 3071, respectively, are incorrect. The H&E staining image of tumor tissue in the PLGA/DTX@MnO2 group in Figure 9C and the X-ray CT images in Figure 11C were inadvertently misused during data acquisition. The correct Figure 9 is as follows. Figure 9 Inhibition of tumor growth in vivo by the drug delivery system.Abbreviations: H&E, hematoxylin and eosin; AuNR, gold nanorod; DTX, docetaxel; MnO2, manganese dioxide; PLGA, poly(lactic-co-glycolic acid); RF, radiofrequency.Notes: (A) Relative volumes of tumor-bearing mice; (B) body weight of the mice models (mean ± standard deviation; n=6); (C) H&E-stained tumor tissue sections: (a) control, (b) DTX, (c) PLGA/DTX@MnO2, (d) PLGA/DTX@MnO2 + RF, (e) PLGA/AuNR/DTX@MnO2, and (f) PLGA/AuNR/DTX@MnO2 + RF. The correct Figure 11 is as follows. Figure 11 Dual-mode imaging in vivo.Abbreviations: MR, magnetic resonance; CT, computed tomography.Notes: (A, B) T1-weighted MR images; (C) X-ray CT images: (a) control; (b) 4 h; (c) 8 h. The authors apologize for these errors and advise they do not affect the results and conclusions of the paper.

Heli Li,1,&ast; Jinru Cui,1,&ast; Cong Hu,1 Hao Li,2 Xiaoping Luo,3 Yan Hao1 1Division of Child Healthcare, Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Hao, Email haoyaner@163.comObjective: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with significant genetic heterogeneity. The ZIC gene family can regulate neurodevelopment, especially in the cerebellum, and has been implicated in ASD-like behaviors in mice. We performed bioinformatic analysis to identify the ZIC gene family in the ASD cerebellum.Methods: We explored the roles of ZIC family genes in ASD by investigating (i) the association of ZIC genes with ASD risk genes from the Simons Foundation Autism Research Initiative (SFARI) database and ZIC genes in the brain regions of the Human Protein Atlas (HPA) database; (ii) co-expressed gene networks of genes positively and negatively correlated with ZIC1, ZIC2, and ZIC3, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and receiver operating characteristic (ROC) curve analysis of genes in these networks; and (iii) the relationship between ZIC1, ZIC2, ZIC3, and their related genes with cerebellar immune cells and stromal cells in ASD patients.Results: (i) ZIC1, ZIC2, and ZIC3 were associated with neurodevelopmental disorders and risk genes related to ASD in the human cerebellum and (ii) ZIC1, ZIC2, and ZIC3 were highly expressed in the cerebellum, which may play a pathogenic role by affecting neuronal development and the cerebellar internal environment in patients with ASD, including immune cells, astrocytes, and endothelial cells. (iii) OLFM3, SLC27A4, GRB2, TMED1, NR2F1, and STRBP are closely related to ZIC1, ZIC2, and ZIC3 in ASD cerebellum and have good diagnostic accuracy. (iv) ASD mice in the maternal immune activation model demonstrated that Zic3 and Nr2f1 levels were decreased in the immune-activated cerebellum.Conclusion: Our study supports the role of ZIC1, ZIC2, and ZIC3 in ASD pathogenesis and provides potential targets for early and accurate prediction of ASD.Keywords: autism, ZIC1, ZIC2, ZIC3, cerebellum, biomarkers

Xiaoqi Wang,1,2 Yuanjie Hao,3 Yujie Yin,4,5 Yunlong Hou,2,4,5 Ningxin Han,3 Yi Liu,3 Zhen Li,3 Yaru Wei,1 Kun Ma,1 Jiaojiao Gu,1 Yan Ma,1 Hui Qi,4,5 Zhenhua Jia1,4– 6 1Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050090, People’s Republic of China; 2Hebei Yiling Pharmaceutical Research Institute, Shijiazhuang, 050035, People’s Republic of China; 3Graduate School, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China; 4Hebei Academy of Integrated Traditional Chinese and Western Medicine, Shijiazhuang, Hebei, 050035, People’s Republic of China; 5National Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, People’s Republic of China; 6Department of Respiratory, Affiliated Yiling Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050091, People’s Republic of ChinaCorrespondence: Zhenhua Jia, Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050090, People’s Republic of China, Email jzhjiazhenhua@163.com Hui Qi, Hebei Academy of Integrated Traditional Chinese and Western Medicine, Shijiazhuang, Hebei, 050035, People’s Republic of China, Email qihui_qh@163.comPurpose: Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) is a sudden worsening of symptoms in patients with Chronic Obstructive Pulmonary Disease (COPD), such as cough, increased sputum volume, and sputum purulence. COPD and AECOPD are characterized by damage to cilia and increased mucus secretion. Mucociliary clearance (MCC) functions as part of the primary innate system of the lung to remove harmful particles and pathogens together with airway mucus and is therefore crucial for patients with COPD.Methods: AECOPD was induced by cigarette smoke exposure (80 cigarettes/day, 5 days/week for 12 weeks) and lipopolysaccharide (LPS) instillation (200 μg, on days 1, 14, and 84). Rats administered Lianhua Qingke (LHQK) (0.367, 0.732, and 1.465 g/kg/d) or Eucalyptol, Limonene, and Pinene Enteric Soft Capsules (ELP, 0.3 g/kg/d) intragastrically. Pulmonary pathology, Muc5ac+ goblet cell and β-tubulin IV+ ciliated cells, and mRNA levels of forkhead box J1 (Foxj1) and multiciliate differentiation and DNA synthesis associated cell cycle protein (MCIDAS) were assessed by hematoxylin and eosin staining, immunofluorescence staining, and RT-qPCR, respectively. Ciliary morphology and ultrastructure were examined through scanning electron microscopy and transmission electron microscopy. Ciliary beat frequency (CBF) was recorded using a high-speed camera.Results: Compared to the model group, LHQK treatment groups showed a reduction in inflammatory cell infiltration, significantly reduced goblet cell and increased ciliated cell proportion. LHQK significantly upregulated mRNA levels of MCIDAS and Foxj1, indicating promoted ciliated cell differentiation. LHQK protected ciliary structure and maintained ciliary function via increasing the ciliary length and density, reducing ciliary ultrastructure damage, and ameliorating random ciliary oscillations, consequently enhancing CBF.Conclusion: LHQK enhances the MCC capability of ciliated cells in rat with AECOPD by preserving the structural integrity and beating function of cilia, indicating its therapeutic potential on promoting sputum expulsion in patients with AECOPD.Keywords: goblet hyperplasia, ciliary density, ciliary length, ciliary ultrastructure, ciliary beat frequency, CBF

Xueping Ma, Zhengjun Zhang, Meihua Jin, Yu Hao, Hua Cheng, Ning Yan Heart Centre & Department of Cardiovascular Diseases, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of ChinaCorrespondence: Hua Cheng; Ning Yan, Heart Centre & Department of Cardiovascular Diseases, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China, Tel +86 15008617234 ; +86 15719591301, Email chenghzhp@126.com; yanning169@yahoo.comObjective: The study aims to reveal the association between family context and sleep trajectories in middle-aged and elderly Chinese adults.Methods: Subjects (n=7777) aged between 40 and 65 years were selected from the China Family Panel Studies (CFPS). Latent class analysis and the multi-trajectory method were used to identify the family context and sleep trajectories from 2010 to 2018. Multinomial (polytomous) logistic regression was performed to explore the relationship between family context and sleep trajectories.Results: Five family context classes were identified according to family demographic characteristics. Simultaneously, four sleep trajectories were determined based on three sleep-related indexes. Subjects from family that had only sons or multiple-child are liable to shorten or prolong sleep duration and increase midday nap ratios compare with subjects who from family that had one or more daughters, and in future public health prevention and control, more attention could be paid to such families.Conclusion: The study found that family context is associated with sleep trajectories among middle and old Chinese adults. Subjects from families with only girls seemed to have more stable sleep trajectories, while those with one or more boys’ families had unstable sleep trajectories. Further interventions would be carried out for sleep disorders, it is necessary to pay more attention to the family context, especially the number and gender of children.Keywords: family context, sleep trajectory, China Family Panel Studies, CFPS, sleep disorders

We show that the low-energy effective actions of two ten-dimensional supersymmetric heterotic strings are different by a $\mathbb{Z}_3$-valued discrete topological term even after we turn off the $E_8×E_8$ and $Spin(32)/\mathbb{Z}_2$ gauge fields. This will be demonstrated by considering the inflow of normal bundle anomaly to the respective NS5-branes from the bulk. This result will be used to show further that the $Spin(16)×Spin(16)$ non-tachyonic non-supersymmetric heterotic string has the same non-zero $\mathbb{Z}_3$-valued discrete topological term. We will also explain the relation of our findings to the theory of topological modular forms. The paper is written as a string theory paper, except for an appendix translating the content in mathematical terms. We will explain there that our finding identifies a representative of the $\mathbb{Z}/3$-torsion element of $\pi_{-32}\mathrm{TMF}$ as a particular self-dual vertex operator superalgebra of $c=16$ and how we utilize string duality to arrive at this statement.

Yanan Hao,1,&ast; Xiaodan Yang,2,&ast; Weiwei Ma,1 Xiaoling Zhang,1 Yanping Wang,1 Shuxia Qian1 1Department of Neurology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoling Zhang, Department of Neurology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, 314000, People’s Republic of China, Email zhaoxiaolingzz@126.comObjective: In this study, we assessed the awareness of cognitive dysfunction and the reasons for the lack of awareness among surgical practitioners in Jiaxing.Methods: Questionnaires were distributed to surgical practitioners covering all Class III and Class II hospitals in Jiaxing. Respondents were asked to make selections regarding the demographic data, clinical attitudes and practices of cognitive dysfunction based on Alzheimer’s Disease Assessment Scale (ADKS) of the Chinese version.Results: A total of 180 questionnaires were distributed, 12 of which were incomplete, with 168 being included for analysis. The respondents were generally under 50 years of age (150, 89.3%), predominantly males (146, 86.9%), and surgeons (153, 91.1%). They generally had a bachelor’s or master’s degrees (165, 98.2%), and served in Class III hospitals (127, 75.6%). The title of the practitioner was found to impact their attention toward their patients’ cognitive status during preoperative preparation (P< 0.05). Titles and hospital levels were found to influence decisions of surgical practitioners to invite specialist physicians for consultation and assessment when a patient was identified to have cognitive dysfunction (P< 0.05). Most surgical practitioners had little knowledge or training about Alzheimer’s disease and cognitive dysfunction. Among the 168 respondents, the mean ADKS score was 20.14± 2.40, and the awareness rate was 67.1%, indicating that the surgical practitioner’s title influenced ADKS score (P

Yanan Feng,1,2,&ast; Yongsheng Hao,3,&ast; Yuanyuan Wang,3 Weijian Song,1,4 Shanxin Zhang,1 Dong Ni,5 Fei Yan,3 Litao Sun1 1Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China; 2Department of Abdominal Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China; 3Center for Cell and Gene Circuit Design, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, People’s Republic of China; 4Bengbu Medical College, Bengbu, 233030, People’s Republic of China; 5Medical Ultrasound Image Computing (MUSIC) Laboratory, Shenzhen University, Shenzhen, 518055, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Litao Sun; Fei Yan, Tel +86 13946037056, Email litaosun1971@sina.com; fei.yan@siat.ac.cnPurpose: Ultrasound molecular imaging (UMI) has proven promising to diagnose the onset and progression of diseases such as angiogenesis, inflammation, and thrombosis. However, microbubble-based acoustic probes are confined to intravascular targets due to their relatively large particle size, greatly reducing the application value of UMI, especially for extravascular targets. Extradomain B fibronectin (ED-B FN) is an important glycoprotein associated with tumor genesis and development and highly expressed in many types of tumors. Here, we developed a gas vesicles (GVs)-based nanoscale acoustic probe (ZD2-GVs) through conjugating ZD2 peptides which can specially target to ED-B FN to the biosynthetic GVs.Materials and Methods: ED-B FN expression was evaluated in normal liver and tumor tissues with immunofluorescence and Western blot. ZD2-GVs were prepared by conjugating ZD2 to the surface of GVs by amide reaction. The inverted microscope was used to analyze the targeted binding capacity of ZD2-GVs to MB49 cells (bladder cancer cell line). The contrast-enhanced imaging features of GVs, non-targeted control GVs (CTR-GVs), and targeted GVs (ZD2-GVs) were compared in three MB49 tumor mice. The penetration ability of ZD2-GVs in tumor tissues was assessed by fluorescence immunohistochemistry. The biosafety of GVs was evaluated by CCK8, blood biochemistry, and HE staining.Results: Strong ED-B FN expression was observed in tumor tissues while little expression in normal liver tissues. The resulting ZD2-GVs had only 267.73 ± 2.86 nm particle size and exhibited excellent binding capability to the MB49 tumor cells. The in vivo UMI experiments showed that ZD2-GVs produced stronger and longer retention in the BC tumors than that of the non-targeted CTR-GVs and GVs. Fluorescence immunohistochemistry confirmed that ZD2-GVs could penetrate the tumor vascular into the interstitial space of the tumors. Biosafety analysis revealed there was no significant cytotoxicity to these tested mice.Conclusion: Thus, ZD2-GVs can function as a potential UMI probe for the early diagnosis of bladder cancer.Graphical Abstract: Keywords: ultrasound contrast agents, gas vesicles, ultrasound molecular imaging, tumor diagnosis