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Yang Yu,1,* Wenfeng Wang,2,* Zuquan Xiong,3 Zhenyu Yang,1 Jun Li,1 Yifan Shen,1 Bin Gu1 1Urology Department, Shanghai Pudong New Area People’s Hospital, Shanghai, People’s Republic of China; 2Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China; 3Urology Department, Shanghai Huashan Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin GuUrology Department, Shanghai Pudong New Area People’s Hospital, 490 Chuanhuan South Road, Shanghai, 201200, People’s Republic of ChinaTel/Fax +86-2120509000Email ibippan3998@163.comPurpose: This study aimed to compare perioperative outcomes of open partial nephrectomy (OPN) and laparoscopic partial nephrectomy (LPN) from a retrospective single-center dataset.Patients and Methods: A retrospective single-center analysis of 210 patients who underwent open (n=91) or laparoscopic (n =119) partial nephrectomy for RCC was conducted between 2012 and 2015. All patients were grouped into low complexity, moderate complexity, and high complexity according to the R.E.N.A.L. Nephrometry Score, respectively. The rates of intraoperative and postoperative complications estimated blood loss, warm ischemia time, operative time, conversion of laparoscopic procedure to open surgery, and postoperative length of stay were assessed for both procedures.Results: In low complexity group (n=93), patients undergoing LPN (n=52) under ischemia conditions had significantly longer renal artery clamp time (p < 0.001) and operative time (p = 0.001) compared with OPN (n=41). However, patients undergoing LPN had a significantly less postoperative length of stay (p=0.005) and estimated blood loss (p < 0.001) compared with OPN. There was no statistically significant difference in the rates of complications between LPN and OPN. In the moderate complexity group (n=114), 67 and 47 patients underwent LPN and OPN, respectively. LPN had notably longer warm ischemia time (p < 0.001) and operative time (p < 0.001) compared with OPN. There were no statistically significant differences in the rates of complications, estimated blood loss, and postoperative length of stay between LPN and OPN. In the high complexity group (n=3), all patients underwent OPN.Conclusion: OPN and LPN procedures performed in patients with low and moderate complexity tumors based on the RENAL Nephrometry score offer acceptable and comparable results. When applied to low complexity tumors, our data suggest that laparoscopic NSS is an effective, minimally invasive therapeutic approach with the advantages of less blood loss, earlier hospital discharge, and more rapid convalescence.Keywords: renal cell carcinoma, open partial nephrectomy, laparoscopic partial nephrectomy, R.E.N.A.L. Nephrometry Score

Xiaoxiao Wu,1,&ast; Yongyan Chen,1,&ast; Yangheng Zhang,2,&ast; Yunjie Shan,1 Zhiyue Peng,1 Bing Gu,1,3 Huan Yang1 1Xuzhou Key Laboratory of Laboratory Diagnostics, School of Medical Technology, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 2Department of Periodontology, Nanjing Stomatological Hospital of Nanjing University School of Medicine, Nanjing, 210008, People’s Republic of China; 3Laboratory Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huan Yang; Bing Gu Email yanghuan2015@tmu.edu.cn; gb20031129@163.comBackground: Shigella infection has always been a global burden, and it particularly threatens children between the ages of 1 and 5 years. Economically underdeveloped countries are dominated by Shigella flexneri infection. The most effective method to treat Shigella is antibiotics, but with the abuse of antibiotics and the prevalence of multidrug resistance, we urgently need a relatively safe non-antibiotic treatment to replace it. Ultrasmall Au nanoclusters (NCs) have special physical and chemical properties and can better interact with and be internalized by bacteria to disrupt the metabolic balance. The purpose of this study was to explore whether Au NCs may be a substitute for antibiotics to treat Shigella infections.Methods: Au NCs and Shigella Sf301, R2448, and RII-1 were cocultured in vitro to evaluate the bactericidal ability of Au NCs. The degree of damage and mode of action of Au NCs in Shigella were clearly observed in images of scanning electron microscopy (SEM). In vivo experiments were conducted to observe the changes in body weight, clinical disease activity index (DAI) and colon (including length and histopathological sections) of mice treated with Au NCs. The effect of Au NCs was analysed by measuring the content of lipocalin-2 (LCN2) and Shigella in faeces. Next, the changes in Shigella biofilm activity, the release of reactive oxygen species (ROS), the changes in metabolism-related and membrane-related genes, and the effect of Au NCs on the body weight of mice were determined to further analyse the mechanism of action and effect.Results: Au NCs (100 μM) interfered with oxidative metabolism genes, induced a substantial increase in ROS levels, interacted with the cell membrane to destroy it, significantly killed Shigella, and effectively alleviated the intestinal damage caused by Shigella in mice. The activity of the biofilm formed by Shigella was reduced.Conclusion: The effective antibacterial effect and good safety suggest that Au NCs represent a good potential alternative to antibiotics to treat Shigella infections.Keywords: Shigella, Au nanoclusters, antibacterial effect, reactive oxygen species, oxidative stress

Shan Hu,1– 3,* Haiquan Kang,4,* Feng Gu,2,* Chongwen Wang,1,5 Siyun Cheng,3 Wenjing Gong,1 Liping Wang,1 Bing Gu,3,4 Ying Yang1 1Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing, 100850, People’s Republic of China; 2Department of Laboratory Medicine, Xuzhou Tumor Hospital, Xuzhou, 221005, People’s Republic of China; 3Xuzhou Key Laboratory of Laboratory Diagnostics, Medical Technology School of Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 4Department of Laboratory Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, People’s Republic of China; 5College of Life Sciences, Anhui Agricultural University, Hefei, 230036, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Yang; Bing Gu Email y_ying_77@163.com; gb20031129@163.comPurpose: Candidemia infection is common in the clinic and has a high mortality rate. Candida albicans, Candida tropicalis, and Candida krusei are very important and common pathogenic species. Candida is difficult to isolate from clinical samples and culture, and immunological detection cannot distinguish these related strains. Furthermore, Candida has a complex cell wall, which causes difficulties in the extraction of DNA for nucleic acid detection. The purpose of this study was to establish a protocol for the direct identification of Candida from serum.Materials and Methods: We synthesized Fe3O4@PEI (where PEI stands for polyethylenimine) magnetic nanoparticles to capture Candida and prepared positively charged silver nanoparticles (AgNPs+) as the substrate for surface-enhanced Raman scattering (SERS). Candida was directly identified from serum by SERS detection.Results: Orthogonal partial least squares discriminant analysis (OPLS-DA) was used as the multivariate analysis tool. Principal component analysis confirmed that this method can clearly distinguish common Candida. After 10-fold cross-validation, the accuracy of training data in this model was 100% and the accuracy of test data was 99.8%, indicating that the model has good classification ability.Conclusion: The detection could be completed within 40 minutes using Fe3O4@PEI and AgNPs+ prepared in advance. This is the first time that Fe3O4@PEI was used in the detection of Candida by SERS. We report the first rapid method to identify fungi directly from serum without breaking the cell wall to extract DNA from the fungi.Keywords: capture, surface-enhanced Raman scattering, positively charged silver nanoparticles, orthogonal partial least squares discriminant analysis, 10-fold cross-validation

Bo Yang,* Baoyu Gu,* Jing Zhang, Long Xu, Yong Sun Department of Ophthalmology, Shenzhen Hospital of Integrated Chinese and Western Medicine, Shenzhen 518101, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong SunDepartment of Ophthalmology, Shenzhen Hospital of Integrated Chinese and Western Medicine, 3 Shajing Street, Bao’an District, Shenzhen 518101, Guangdong Province, People’s Republic of ChinaTel +86 755-2772-2241Email wk9710@163.comBackground: CASC8 lncRNA has been proven to be oncogenic in a variety of cancers, but its role in other types of cancer remains unclear. This study was to investigate the role of CASC8 in retinoblastoma (Rb).Methods: RT-qPCR was performed to determine the expression of CASC8 and miR34a in paired Rb and nontumor tissue. Overexpression of CASC8 and miR34a in Rb cells was achieved to evaluate the interaction between them. Methylation-specific PCR was used to analyze the effect of CASC8 overexpression on MIR34A gene methylation. CCK8 assays were used to analyze cell proliferation.Results: The results showed that CASC8 expression was upregulated and miR34a expression downregulated in Rb tissue. Moreover, miR34a expression was negatively correlated with the of CASC8 expression in Rb tissue. Overexpression of CASC8 decreased expression of miR34a and increased methylation of MIR 34A in Rb cells. In addition, overexpression of CASC8 reduced the inhibitory effects of miR34a on Rb-cell proliferation.Conclusion: CASC8 may promote Rb cell proliferation by downregulating miR34a methylation.Keywords: retinoblastoma, CASC8, miR34a, methylation, proliferation

Ziyan Kong,1,2,* Xuemei Liu,3,* Chenxi Li,1,* Siyun Cheng,1 Fei Xu,3 Bing Gu1,4 1Medical Technology School, Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of China; 2Department of Laboratory Medicine, The First People’s Hospital of Lianyungang, Lianyungang, Jiangsu Province, People’s Republic of China; 3Department of Laboratory Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 4Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei XuDepartment of Laboratory Medicine, Children’s Hospital of Nanjing Medical University, Nanjing 210009, People’s Republic of ChinaEmail 350826448@qq.comBing GuDepartment of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People’s Republic of ChinaEmail gb20031129@163.comPurpose: The continuous emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a serious public health problem globally, especially for children, but data on CRKP infection in pediatric patients are limited. This study aimed to identify epidemiological and molecular patterns of CRKP among pediatric patients in Jiangsu province, China.Patients and Methods: CRKP were consecutively collected from the Children’s Hospital of Nanjing Medical University in China from July 2018 to May 2019. Then, CRKP strains were performed for further study: antimicrobial susceptibility testing, drug-resistance determinants screening and homology analysis.Results: We collected 94 CRKP from 94 children. Overall, blaKPC-2 (79.8%) was the predominant carbapenemase gene, followed by blaNDM-1(14.9%), blaIMP-4 (5.3%) and blaNDM-5(4.3%). Notably, two isolates coharbored blaKPC-2 and blaIMP-4, and two isolates coharbored blaKPC-2 and blaNDM-5. MLST analysis revealed that 14 distinct sequence types (STs) were identified, of which ST11 was the most common sequence type identified. Moreover, two novel STs, ST4854 and ST4855, were detected in this study. PFGE revealed that a predominant cluster consisting of KPC-2-producing CRKP ST11 clone isolates was identified and was distributed mainly in the pediatric intensive care unit (PICU) and cardiac intensive care unit (CCU). Moreover, this is the first report to identify the dissemination of ST716 CRKP coproducing KPC-2 and IMP-4 clones.Conclusion: Clonal dissemination of KPC-2-producing CRKP ST11 was observed in multiple departments. Moreover, two novel STs (ST4854 and ST4855) were identified, which indicates an increased diversity of CRKP strains. To our knowledge, this is the first report that identified the dissemination of Klebsiella pneumoniae coproducing KPC-2 and IMP-4 clones among children, which represents a significant health risk to pediatric patients. Active surveillance and effective control measures are urgently needed to prevent further transmission of these strains among children.Keywords: Klebsiella pneumoniae, carbapenemase, KPC-2, ST11, clonal dissemination, children

Huan Yang,1,* Rui Cai,1,* Yangheng Zhang,2,* Yongyan Chen,1 Bing Gu1,3 1Xuzhou Key Laboratory of Laboratory Diagnostics, School of Medical Technology, Xuzhou Medical University, Xuzhou 221004, People’s Republic of China; 2Department of Periodontology, Nanjing Stomatological Hospital of Nanjing University School of Medicine, Nanjing 210008, People’s Republic of China; 3Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bing GuDepartment of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People’s Republic of ChinaEmail binggu2015@xzhmu.edu.cnBackground: Clostridium difficile infection (CDI) has become one of the most important factors threatening human health, and about 20– 30% antibiotic-related diarrhea cases and almost all pseudomembranous enteritis cases are related to CDI. The high recurrence of Clostridium difficile (C. difficile) and the emergence of drug resistance make clinical treatment of CDI difficult. Therefore, there is an urgent need to develop a non-antibiotic-alternative therapy against CDI. Gold nanoclusters (AuNCs) can better interact with bacteria due to its ultrasmall size. The aim of the present study was to explore whether AuNCs could be used as an antibacterial agent to kill C. difficile.Methods: AuNCs and C. difficile were co-cultivated in an anaerobic atmosphere to evaluate the bactericidal effect of AuNCs. The bacterial growth rate was estimated by using two concentrations of AuNCs (50 and 100 μM). The damage of AuNCs to C. difficile is detected by SYTOX Green staining methods and SEM image analysis. The mechanism of AuNCs on C. difficile was explored by reactive oxygen species (ROS) detection. The toxic effect of AuNCs on human cells was evaluated by MTT method.Results: AuNCs (100 μM) killed C. difficile drastically. AuNCs increased the release of ROS by about 5 fold and destroyed the membrane integrity of C. difficile cells without causing significant toxic effect on human cells.Conclusion: AuNCs showed great potential as an alternative to traditional antibiotics in killing C. difficile and may prove to be an alternative to treat CDI.Keywords: Clostridium difficile, antibacterial effect, gold nanoclusters, reactive oxygen species

Source separation and recycling (SSR) for municipal solid waste is an important strategy for the transition to a circular economy and requires broader resident participation. How can residents’ participation in SSR be promoted? Here, we consider 13 cities in Jiangsu as microcosms of China. We quantify residents’ intentions to participate in SSR by distributing a validated questionnaire to 2,963 urban residents, analyze the results through structural equation modeling, and propose localized policy recommendations. We find that residents have positive attitudes toward SSR, although 92.6% of residents in southern Jiangsu were more willing to participate than those in northern Jiangsu (84.6%). Additionally, the influencing factors and their degree of influence on resident SSR participation intentions exhibit disparities across cities. “Accessibility of SSR facilities” simultaneously affects the 13 studied cities and is a key factor. “Environmental knowledge” and “environmental attitudes” are important impact factors, with occurrence frequencies of 84.6% and 69.2%, respectively. However, laws and regulations have no significant effect on residents’ SSR participation intentions. We recommend that the government create favorable external conditions related to facilities and services, promote extensive publicity and educational activities through various channels, and improve the effectiveness of SSR laws and regulations. Future SSR management strategies should be localized, flexible and comprehensive. This research could help decision makers in China and other countries design policy guides to promote SSR and help link current research areas to social development.

Meixian Chen,1,* Lisheng Zhou,1,* Zhaoxia Liao,1 Xijiu Ye,1 Xujun Xuan,2 Beibei Gu,1 Fuding Lu1 1Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Andrology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fuding LuDepartment of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of ChinaTel +86-13560371081Email lfd19870901@126.comBackground: Osteosarcoma is one of the most common primary bone cancers with predominant occurrence in children and adolescents. This study aimed to determine the effects of sevoflurane treatment on the osteosarcoma progression and to explore the underlying molecular mechanisms.Materials and methods: The mRNA and protein expression levels were determined by qPCR and Western blot, respectively. Osteosarcoma cell proliferation, apoptosis and invasion were determined by MTT, caspase-3 activity, colony formation and Transwell invasion assays, respectively. The interaction between miR-203 and WNT2B 3ʹ untranslated region was confirmed by luciferase reporter assay.Results: Sevoflurane treatment for 6 hrs concentration-dependently suppressed cell viability, increased caspase-3 activity and up-regulated miR-203 expression in both U2OS and MG63 cells. MiR-203 overexpression suppressed cell viability, increased caspase-3 activity and suppressed cell growth and invasion of osteosarcoma cells. In addition, miR-203 knockdown attenuated the tumor-suppressive effects of sevoflurane treatment on osteosarcoma cells. Mechanistic studies showed that miR-203 repressed the expression of WNT2B in U2OS cells, and inhibition of miR-203 attenuated the suppressive effects of sevoflurane on WNT2B expression. More importantly, WNT2B overexpression attenuated the effects of sevoflurane treatment on cell viability, caspase-3 activity, cell growth and invasion of U2OS cells. MiR-203 overexpression suppressed Wnt/β-catenin signalling. Similarly, sevoflurane suppressed the activity of Wnt/β-catenin signalling, which was partially reversed by miR-203 knockdown and WTN2B overexpression.Conclusion: Our data showed the tumor-suppressive effects of sevoflurane on osteosarcoma cells, and mechanistic studies revealed that sevoflurane inhibited osteosarcoma cell proliferation and invasion partly via targeting the miR-203/WNT2B/Wnt/β-catenin axis.Keywords: osteosarcoma, proliferation, invasion, sevoflurane, miR-203, WNT2B, Wnt/β-catenin

Chenchen Cai,1,* Haoliang Zhang,2,* Yingxing Zhu,2,* Peiming Zheng,3 Yinhai Xu,2 Jingfang Sun,2 Miaomiao Zhang,1 Ting Lan,1 Bing Gu,1,2 Shibao Li,1,2 Ping Ma1,2 1Department of Medical Technology, Xuzhou Medical University, Xuzhou 221004, People’s Republic of China; 2Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, People’s Republic of China; 3Department of Laboratory Medicine, Henan Provincial People’s Hospital, Zhengzhou 450003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shibao Li; Ping MaDepartment of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou 221002, People’s Republic of ChinaTel +8615895212960; +8613685127799Email sdjnshlb@126.com; pingm62@aliyun.comPurpose: Exosome-shuttled bioactive long non-coding RNA, as novel non-invasive biomarkers for cancer diagnosis, has received increasing attention. Here, we aimed to investigate the expression of serum exosomal long non-coding RNA pcsk2-2:1 (Exo-Lnc RNApcsk2-2:1) in patients of gastric cancer and evaluate its diagnostic value as a marker.Patients and methods: Exosomes were isolated from serum sample of gastric cancer using HiPure Exosomekits and identified via transmission electron microscopy, Western blotting, and nanoparticle tracking analysis. The total exosomal RNA was extracted and reverse transcribed to cDNA. The expression of Exo-Lnc RNA PCSK2-2:1 was detected in serum exosomes of 29 healthy people and 63 gastric cancer patients by real-time quantitative reverse transcription PCR (qRT-PCR), and the relationship between the expression level of Exo-Lnc RNA PCSK2-2:1 and clinicopathological parameters of patients was analyzed. Finally, a receiver operating characteristic curve was used to evaluate the clinical value of Exo-Lnc RNA PCSK2-2:1 as an auxiliary diagnostic marker for gastric cancer.Results: Transmission electron microscopy, nanoparticle size analysis, and Western blotting showed successful separation of serum exosomes. qRT-PCR results revealed that compared with the healthy control, Lnc RNA PCSK2-2:1 expression level in serum exosomes of gastric cancer patients was significantly downregulated (p=0.006). Moreover, the expression level of Exo-Lnc RNA PCSK2-2:1 was correlated with tumor size (p=0.0441), tumor stage (p=0.0061), and venous invasion (p=0.0367). The area under the curve of Exo-Lnc RNA PCSK2-2:1 was 0.896. At the optimal cut-off value, the diagnostic sensitivity and specificity were 84% and 86.5%, respectively.Conclusion: Our data indicate that Exo-Lnc RNA PCSK2-2:1 may perform a vital role in the progression of gastric cancer and can be used as a potential marker for the diagnosis of gastric cancer.Keywords: exosome, lncRNA, diagnose, biomarker

Ziyan Kong,1,* Rui Cai,1,* Chen Cheng,1 Chuanling Zhang,2 Haiquan Kang,3 Ping Ma,3 Bing Gu1,3 1Medical Technology School, Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of China; 2Department of Laboratory Medicine, XuZhou Children’s Hospital, Xuzhou, Jiangsu Province, People’s Republic of China; 3Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bing GuDepartment of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People’s Republic of ChinaTel +8615862163560Email gb20031129@163.comPurpose: Carbapenem-resistant Klebsiella pneumoniae (CRKP) have emerged worldwide and also being a major threat to children and neonate. In this study, we describe a nosocomial outbreak of NDM-5-producing Klebsiella pneumoniae in neonatal unit of a teaching hospital in China from September 2015 to September 2016.Patients and methods: We collected 12 carbapenem-resistant K. pneumoniae outbreak strains from 12 newborns and characterized these isolates for their antimicrobial susceptibility, clone relationships, and multi-locus sequence types using vitek-2 compact system, pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Resistant genes were detected by using PCR and sequencing. Plasmid conjugation experiment was carried out to determine the transferability of carbapenem resistance. PCR-based replicon typing (PBRT), S1 nuclease-PFGE, and southern blotting were conducted for plasmid profiling.Results: All 12 K. pneumoniae isolates were resistant to carbapenems and carried blaNDM-5, blaTEM-1 and blaSHV-11. Furthermore, PFGE analysis showed that NDM-5-producing K. pneumoniae were clonally related and MLST assigned them to sequence type 337. Conjugative assays showed that plasmids harboring blaNDM-5 gene were self-transmissible. Plasmid analysis suggested that all blaNDM-5 gene located on a ∼45 kb IncX3 type plasmid.Conclusion: To the best of our knowledge, this is the first report of a clone outbreak of blaNDM-5-carrying K. pneumoniae isolates from neonates. There is an urgent need for effective infection control measures to prevent blaNDM-5 variants from becoming epidemic in the neonates in the future.Keywords: Klebsiella pneumoniae, carbapenemases, blaNDM-5, ST337, neonate, IncX3

Yizhao Xie,1,2,* Bingxin Gu,2–5,*Xichun Hu,1,2Yingjian Zhang,2–5 Jian Zhang,1,2Zhonghua Wang,1,2Yannan Zhao,1,2Chengcheng Gong,1,2Yi Li,1,2Zhongyi Yang,2–5 Biyun Wang,1,21Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 4Center for Biomedical Imaging, Fudan University, Shanghai, People’s Republic of China; 5Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, People’s Republic of China*These authors contributed equally to this workBackground: Platinum-based chemotherapy is widely used as first-line therapy for metastatic triple-negative breast cancer (mTNBC). Intratumor heterogeneity derived from fluorine-18 fluorodeoxyglucose (18,F-FDG) positron emission tomography/computed tomography (PET/CT) is a potential predictor of treatment outcomes and the prognosis of breast cancer. However, the presence of multiple lesions and complex calculation methods leads to difficulties in the clinical use of this parameter for metastatic breast cancer. The aim of this study is to provide a convenient and effective measurement of intratumor heterogeneity to predict treatment outcomes for mTNBC patients with lung metastasis.Patients and methods: We enrolled mTNBC patients with lung metastasis who underwent 18,F-FDG PET/CT scans before first‐line therapy from three clinical trials (NCT01287624, NCT02341911 and NCT02546934). Apart from the regular FDG parameters, including standard uptake value (SUV), total lesion glycolysis (TLG) and metabolic tumor volume (MTV), we defined the lung index as the SUVmean divided by the difference between the SUVmax and SUVmean for the targeted lung lesion. The MTV was automatically exported from the manual delineation using software based on an adaptive threshold of SUV intensity >2.5 within the contouring margin. The TLG was calculated using the following formula: TLG=SUVmean×MTV. Progression‐free survival (PFS) and overall survival were estimated by the Kaplan–Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazard model.Results: The data from 31 patients were available for analysis. The median PFS of low-lung index (LI) patients was 8.1 months, which was significantly longer than that of high-LI patients (HR=3.3, 95% CI 1.5–7.3, p=0.003). Patients with low TLG had a significantly better PFS than those with high TLG (HR=2.6, 95% CI 1.2–5.8, p=0.014). Patients with low TLG had significantly longer overall survival than those with high TLG (31.2 months vs 13.9 months, HR=3.1, 95% CI 1.2–8.6, p=0.029). Multivariate analysis confirmed the predictive value of LI and TLG.Conclusions: This study proposed a new “PET biopsy” method to evaluate the intratumor heterogeneity of mTNBC on pretreatment 18,F-FDG PET/CT scans and indicated the predictive value of LI and TLG for first-line platinum-based treatment outcomes and overall survival. These findings could help clinicians recognize patients who are likely to not only have a favorable response to platinum-based therapy but also a good prognosis.Keywords: triple-negative breast cancer, chemotherapy, PET, tumor heterogeneity

Bin Gu,1 Meng Li,2 Yan Zhang,3 Lingyun Li,4 Kun Yao,5 Shizhi Wang3 1Department of Neurosurgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; 2Department of Neurosurgery, Suqian First Hospital, Suqian, China; 3Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China; 4Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, China; 5Department of Developmental Genetics, Nanjing Medical University, Nanjing, China Purpose: We previously identified human herpesvirus 6 (HHV-6) infection in the pathogenesis of glioma. Direct repeat (DR)7, encoded by HHV-6, has been reported to possess malignant transforming activity and involved in Hodgkin’s lymphoma carcinogenesis. Here, we aimed to determine the role of DR7 in the development and progression of glioma. Patients and methods: A total of 27 glioma and 30 normal brain tissues were collected for detection of DR7. Glioma cell proliferation, colony formation, cell cycle, migration, invasion and angiogenesis were evaluated by Cell Counting Kit-8 (CCK-8), soft agar, propidium iodide staining, wound healing, Transwell and chick embryo chorioallantoic membrane assays, respectively. The potential mRNA targets of DR7 were determined using mRNA microarray and validated via Western blot and ELISA. Results: DR7 could be detected in the 13 glioma tissues with a positive rate of 48.15%, but only the 5 normal brain tissues with a lower positive rate of 16.7%. The two strains of cells isolated from glioma tissues were also found to express DR7. CCK-8 and soft agar assays showed enhanced proliferation and colony formation in the cells expressing DR7 which might be in relation to acceleration of the G1/S phase transition by DR7. Further analyses showed that DR7 could promote glioma cell migration, invasion and angiogenesis. Expression profiles identified hundreds of differentially expressed mRNAs, among which P53, extracellular matrix (ECM) fibronectin, integrin receptor ITGβ5 and specific inhibitors of MMPs, tissue inhibitor of MMPs (TIMP)-2 and TIMP-4, were downregulated, whereas ECM-degrading proteinase MMP-3, proinflammatory cytokines IL-1β, IL-6 and IL-8, were upregulated by DR7, respectively. Conclusion: We observed existence of DR7 in the glioma tissues, and overexpression of DR7 could promote glioma cell development and progression, which might be through creating an inflammatory microenvironment and enhancing degradation of ECM. Keywords: HHV-6, DR7, development, progression, glioma

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The microstructure and texture development of the metastable β‑titanium alloy Ti5321 during hot-compression were investigated by electron backscatter diffraction. Above the β-transus temperature, deformation is accompanied by continuous dynamic recrystallization leading to immediate steady state flow. The deformation below the β-transus temperature is significantly affected by α-precipitation. Dynamic globularization of the α-lamellae leads to flow softening. During hot-compression, parallel to the compression axis a 〈100〉〈111〉double fiber texture develops. With increasing temperature the intensity of 〈100〉increases, while that of decreases. At all temperatures is dominant.

The effect of deformation temperature and strain rate (collectively described by the Zener-Hollomon parameter Z) on the deformation mechanism and texture formation of the metastable β-titanium alloy Ti5321 across the β-transus temperature during hot-compression was investigated by electron backscatter diffraction. In the β-phase field, it is found that the deformation behavior and texture formation varies depending on Z. With decreasing Z dynamic recovery and dynamic recrystallization become more and more important. The activation energy for steady state deformation is 240 kJ/mol and 370 kJ/mol in the β- and (α + β)-phase field, respectively. The texture developed is a double-fiber with < 100 > dominating at all deformation conditions. The fiber gets more prominent with increasing Z suggesting that it is mainly related to deformation. Flow softening behavior of Ti5321 is associated with dynamic globularization of the α-phase and promotion of β-grain formation by continuous dynamic recrystallization.

Flexible behavior requires restraint of actions that are no longer appropriate. This behavioral inhibition critically relies on frontal cortex - basal ganglia circuits. Within the basal ganglia the globus pallidus pars externa (GPe), has been hypothesized to mediate selective proactive inhibition: being prepared to stop a specific action, if needed. Here we investigate population dynamics of rat GPe neurons during preparation-to-stop, stopping, and going. Rats selectively engaged proactive inhibition towards specific actions, as shown by slowed reaction times (RTs). Under proactive inhibition, GPe population activity occupied state-space locations farther from the trajectory followed during normal movement initiation. Furthermore, the state-space locations were predictive of distinct types of errors: failures-to-stop, failures-to-go, and incorrect choices. Slowed RTs on correct proactive trials reflected starting bias towards the alternative action, which was overcome before progressing towards action initiation. Our results demonstrate that rats can exert cognitive control via strategic adjustments to their GPe network state.

© 2014 IEEE. Fog computing is an emergent computing paradigm that extends the cloud paradigm. With the explosive growth of smart devices and mobile users, cloud computing no longer matches the requirements of the Internet of Things (IoT) era. Fog computing is a promising solution to satisfying these new requirements, such as low latency, uninterrupted service, and location awareness. As a typical new computing paradigm and network architecture, fog computing raises new challenges, such as privacy, data management, data analytics, information overload, and participatory sensing. In this article, we present a fog-based hybrid recommender system to address the issue of information overload in fog computing. Our proposed system not only abstracts useful information from the fog environment but can also be considered as an optimization tool due to its ability to provide suggestions to improve system performance. In particular, we demonstrate that the proposed system provides personalized and localized recommendations to users, and also advise the system itself to precache the content to optimize the storage capacity of the fog server.

Background: The COVID-19 mortality is very low in the regions with a low transmission rate and sufficient medical resources. However, strict prevention measures greatly altered people’s social activities, diet, and hygienic habits, which had potential impact on non-COVID-19 deaths. Therefore, this study is to evaluate the impact of short-term lifestyle change on non-COVID deaths in the region with a low COVID-19 transmission rate. Methods: We performed a retropective observational study with statiscal analysis via Student’s t-test (significance defined as P-value < 0.05). The number of registered deaths among 8.8 million permanent residents with specific causes from January 2018 to June 2020 were sourced from Xuzhou Center for Disease Control and Prevention. Death rates were calculated and compared by weeks, months, and years with a focus on the period of COVID-19 pandemic from Jan 24 to March 27, 2020 in Xuzhou, Jiangsu Province, China. Findings: Within the COVID-19 timeframe, all-cause mortality (138.03/105 vs. 158.28/105 vs. 152.57/105, P < 0.001), respiratory disorders (13.99/105 vs. 24.48/105 vs. 21.22/105, P < 0.001), cerebrovascular diseases (36.35/105 vs. 38.69/105 vs. 38.61/105, P < 0.05), and cardiovascular diseases (35.70/105 vs. 42.06/105 vs. 39.55/105, P < 0.001) are consistently lower than those in the same period in 2018 and 2019. The traffic death dropped significantly, while mortalities of mental health disorders and out-of-hospital sudden death significantly increased during the pandemic time. Interpretation: Our study suggests the short-term lifestyle alteration can have significant impact on all-cause mortality. This could provide evidences for adjusting future healthcare policies to reduce specific-cause mortalities such as respiratory, cardiovascular and cerebrovascular diseases. Trial Registration: This study was registered at the ClinicalTrials.gov (NCT 04550312). Funding: Xuzhou Talent Fellowship Program 2019. Conflict of Interest: We declare no competing interests. Ethical Approval: The medical research ethics committee of the affiliated hospital of Xuzhou Medical University, Xuzhou, approved the study (9th, September 2020, No. XYFY2020-KL142-01).

The microstructure and texture evolution of a metastable Ti-5Al-3V-3Mo-2Cr-2Zr-1Nb-1Fe alloy during bar-rolling and after various thermal treatments was investigated by high-energy synchrotron diffraction and electron backscatter diffraction. Bar-rolling is applied in the (α+β)-phase field in order to achieve a bi-modal (duplex) microstructure. The effect of dynamic recrystallized and recovered zones on texture of Ti5321was analyzed separately, as well as the texture of primary α-precipitates and secondary α-lamellae. The texture of the recovered zones is characterized by a cube component ({001}) plus α- and γ-fibre with dominant {100}, {112}, {111} components, while the texture of the recrystallized zones is a strong cube texture. After aging or recrystallization plus aging, this texture component remains, while it disappears after solution treatment. The primary α-precipitates have their c-axes perpendicular to the rolling direction and do not follow the Burgers orientation relationship. This texture characteristics remains after various thermal heat treatments. Secondary α-lamellae obey the Burgers orientation relationship. Moreover, a variant selection of secondary α-lamellae occurs. The mechanism of texture formation of the β-phase and the precipitation behavior of the α-phase is discussed. The hardness increase can be attributed to size, shape and volume fraction of the α-precipitates. Different combinations of primary α- and secondary α-precipitates make an increase in hardness of about 11%.

Background: The increase of all-cause mortality in the areas with high COVID-19 transmission rate due to COVID-19 deaths and the collateral damage to other healthcare problems is well-known. However, the COVID-19 mortality is low in the regions with a low transmission rate and sufficient medical resources. In such regions, strict prevention measures altered people’s lifestyle and hygienic habits and had an impact on non-COVID-19 deaths. Yet, this aspect needs to be elucidated further. Methods: The number of registered deaths among 8.8 million permanent residents with specific causes from January 2018 to June 2020 were estimated. Death rates were calculated and compared by weeks, months, seasons and years with a focus on the period of the COVID-19 pandemic from January 24 to March 27, 2020. The numerical values of all-cause death and the death rates of non-COVID diseases were compared in various time points. Findings: During the pandemic in Xuzhou region, a total of 79 COVID-19 infected patients were diagnosed and treated. Meanwhile, stringent public health measures were taken to contain the virus transmission. Surprisingly, mortalities of all-cause casualty, respiratory disorders, cerebrovascular disease, and cardiovascular disease are consistently lower than those in the same periods in 2018 and 2019. Moreover, the first two weeks in the lunar new year presented the highest death rates from 2018–2020 and lowest in 2020 due to COVID-19 control. The traffic death dropped significantly, while mortality of mental health disorders and out-of-hospital sudden death significantly increased during the pandemic time. Interpretation: Control strategies in the region of low SARS-CoV-2 transmission rate during the COVID-19 outbreak alter the lifestyles of people and further exert an impact on non-COVID deaths, which could have a practical value in guiding clinical work and future management of chronic diseases. Funding Statement: Xuzhou Talent Fellowship Program 2019 Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the Institutional Review Board at the affiliated hospital of Xuzhou Medical University.

Bin Gu,1 Lingyun Li,2 Meng Li,3 Jinfeng Wang,4 Guofeng Zhang,4 Kun Yao,4 Shizhi Wang5 1Department of Neurosurgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China; 2Department of Developmental Genetics, Nanjing Medical University, Nanjing, China; 3Department of Neurosurgery, Suqian First Hospital, Suqian, China; 4Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, China; 5Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China Purpose: We previously found the involvement of human herpesvirus 6 (HHV-6) infection in the pathogenesis of glioma. U94/rep, encoded by HHV-6, has been identified to play a vital role in viral gene expression and latency. Recent studies have shown its inhibition of angiogenesis and tumorigenesis in endothelial cells and prostate cancer cell line PC3, respectively. Here, we aimed to investigate the role of U94/rep in the development and progression of glioma.Patients and methods: A total of 20 glioma tissues with positive HHV-6 infection were used for detection of U94/rep. MTT, soft agar, propidium iodide staining, wound healing, Transwell, and chick embryo chorioallantoic membrane assays were applied for evaluation of glioma cells’ proliferation, colony formation, cell cycle, migration, invasion, and angiogenesis, respectively.Results: U94/rep transcripts could be detected in 11 out of 20 glioma tissues with positive HHV-6 infection. Furthermore, MTT and soft agar assays revealed that overexpression of U94/rep inhibited glioma cell proliferation and colony formation, which may be attributed to the cell cycle arrest at S phase induced by U94/rep. Further analysis demonstrated that U94/rep inhibited glioma cells’ migration and invasion and ex vivo angiogenesis. Reduced expression of proangiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor, and type IV collagenases, MMP-2 and MMP-9, was detected in cells overexpressing U94/rep. These decreased factors may undermine glioma cell migration, invasion, and angiogenesis.Conclusion: Our results demonstrated that U94/rep could inhibit malignant phenotypes of glioma cells, indicating that it is a potential target for therapeutic intervention. Keywords: HHV-6, U94/rep, tumorigenesis, glioma

Heat is a major abiotic stressor seriously affects watermelon produce; however, its effects may be mitigated through grafting onto heat tolerant bottle gourd rootstock. To understand the genetic basis and select reliable markers are necessary in the variety breeding process. In this paper, the relative electric conductivity (REC) was used as a visual indicator for heat stress to study the genetics and SNP marker of heat tolerance in bottle gourd via QTL-seq approach. The results showed that recessive inheritance and a major QTL locus controlled REC related to heat tolerance. Seven heat-tolerant loci (qHT1.1, qHT2.1, qHT2.2, qHT5.1, qHT6.1, qHT7.1, andqHT8.1) exhibited high Δ(SNP-index) values (ranging from 0.19-0.38), and of these, the greatest value (0.32, P < 0.01) and greatest number of detected SNPs (9052) were found in chromosome 2 atqHT2.1region (11.03 - 19.25 Mb);qHT2.1was taken as a promising major QTL for heat tolerance in bottle gourd. A total of 34 putative candidate genes related to heat stress were detected within theqHT2.1region. Three polymorphic SNPs (BG_GLEAN_10022642, BG_GLEAN_10022727, and BG_GLEAN_10022589) that are involved in pollen sterility, intracellular transport, and signal recognition were validated and exhibited significant marker-trait association that could be used in heat tolerant molecular breeding for bottle gourd. TheqHT2.1region is an important finding can be used for fine mapping and discovering new genes associated with heat tolerance in bottle gourd.

Chongwen Wang,1,2,* Bing Gu,3,4,* Qiqi Liu,1,* Yuanfeng Pang,2,5 Rui Xiao,1 Shengqi Wang1–3 1Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China; 2College of Life Sciences and Bio-Engineering, Beijing University of Technology, Beijing, People’s Republic of China; 3Medical Technology School, Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 5Department of Toxicology, Capital Medical University, Beijing, People’s Republic of China *These authors contributed equally to this work Background: Pathogenic bacteria have always been a significant threat to human health. The detection of pathogens needs to be rapid, accurate, and convenient. Methods: We present a sensitive surface-enhanced Raman scattering (SERS) biosensor based on the combination of vancomycin-modified Ag-coated magnetic nanoparticles (Fe3O4@Ag-Van MNPs) and Au@Ag nanoparticles (NPs) that can effectively capture and discriminate bacterial pathogens from solution. The high-performance Fe3O4@Ag MNPs were modified with vancomycin and used as bacteria capturer for magnetic separation and enrichment. The modified MNPS were found to exhibit strong affinity with a broad range of Gram-positive and Gram-negative bacteria. After separating and rinsing bacteria, Fe3O4@Ag-Van MNPs and Au@Ag NPs were synergistically used to construct a very large number of hot spots on bacteria cells, leading to ultrasensitive SERS detection. Results: The dominant merits of our dual enhanced strategy included high bacterial-capture efficiency (>65%) within a wide pH range (pH 3.0–11.0), a short assay time (

Background Endophthalmitis is an uncommon and serious intraocular infection. Endophthalmitis most commonly follows on from cataract surgery or intravitreal injections. The rate of endophthalmitis has fallen in recent years with improved surgical techniques, and infection control. However, despite all precautions, cases of endophthalmitis continue to present. It is possible that poor intraocular immune function makes some patients susceptible to endophthalmitis. We propose that innate phagocytic function is one determinant of the development of endophthalmitis. In order to investigate this, we measured the innate phagocytic function and P2X7 receptor function acutely and at intervals through convalesence for patients who developed endophthalmitis, and compared it with the function of a published population control group.Methods Patients presented to a tertiary eye hospital emergency department with acute endophthalmitis. Informed consent was obtained, and peripheral blood taken. Innate phagocytosis of ethidium and fluorescent latex beads was then quantified using a validated flow cytometric-method at the Florey Institute. Patients had repeat bloods taken at 1 week and 3 months after recruitment.Results P2X7 receptor function was significantly reduced in the endophthalmitis cohort compared to controls. P2X7 function improved through convalescence as patients recovered from endophthalmitis but did not improve to the level of controls. Phagocytic function was reduced in the endophthalmitis cohort compared to controls at all time points. There was no improvement in phagocytic function observed as patients recovered from endophthalmitis.Conclusions The data from this study showed greatly lowered phagocytic function and P2X7 function in patients who developed endophthalmitis, as compared to population controls. This important finding may allow us to predict susceptibility or guide future therapeutics through enhancement of innate phagocytic function.

Thrombolytic therapy is one of the medical procedures in the treatment of acute ischaemic stroke (AIS), whereby the tissue plasminogen activator (tPA) is intravenously administered to dissolve the obstructive blood clot. The treatment of AIS by thrombolysis can sometimes be ineffective and it can cause serious complications, such as intracranial haemorrhage (ICH). In this study, we propose an efficient mathematical modelling approach that can be used to evaluate the therapeutic efficacy and safety of thrombolysis in various clinically relevant scenarios. Our model combines the pharmacokinetics and pharmacodynamics of tPA with local clot lysis dynamics. By varying the drug dose, bolus-infusion delay time, and bolus-infusion ratio, with the FDA approved dosing protocol serving as a reference, we have used the model to simulate 13 dose regimens. Simulation results are compared for temporal concentrations of fibrinolytic proteins in plasma and the time that is taken to achieve recanalisation. Our results show that high infusion rates can cause the rapid degradation of plasma fibrinogen, indicative of increased risk for ICH, but they do not necessarily lead to fast recanalisation. In addition, a bolus-infusion delay results in an immediate drop in plasma tPA concentration, which prolongs the time to achieve recanalisation. Therefore, an optimal administration regimen should be sought by keeping the tPA level sufficiently high throughout the treatment and maximising the lysis rate while also limiting the degradation of fibrinogen in systemic plasma. This can be achieved through model-based optimisation in the future.

Jing Qian,1,* Yingying Qian,1,* Jian Wang,1 Bing Gu,2,3 Dong Pei,1 Shaohua He,1 FangZhu,1 Oluf Dimitri Røe,4–7 Jin Xu,8 Lianke Liu,1 Yanhong Gu,1 Renhua Guo,1 Yongmei Yin,1 Yongqian Shu,1 Xiaofeng Chen1 1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 2Department of Laboratory Medicine, The Affiliated Hospital of Xuzhou Medical College, 3Medical Technology Institute, Xuzhou Medical College, Xuzhou, People’s Republic of China; 4Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; 5Department of Oncology, Clinical Cancer Research Center, 6Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark; 7Department of Surgery, Cancer Clinic, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway; 8Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention & Treatment, Cancer Center, Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: Gastrectomy with D2 lymphadenectomy is a standard procedure of curative resection for gastric cancer (GC). The aim of this study was to develop a simple and reliable prognostic scoring system for GC treated with D2 gastrectomy combined with adjuvant chemotherapy.Methods: A prognostic scoring system was established based on clinical and laboratory data from 579 patients with localized GC without distant metastasis treated with D2 gastrectomy and adjuvant chemotherapy.Results: From the multivariate model for overall survival (OS), five factors were selected for the scoring system: ≥50% metastatic lymph node rate, positive lymphovascular invasion, pathologic TNM Stage II or III, ≥5ng/mL preoperative carcinoembryonic antigen level, and

Thunderstorm electrification has been studied for hundreds of years. Several mechanisms have been proposed to elucidate the electrification, including convective charging, inductive precipitation charging, and ice crystal-graupel collision charging. Field observations and model studies have demonstrated the vital roles that graupel and ice crystals play in the electrification, but the mechanism of the collision charging is still unclear. The fundamental essence of relative growth rate theory used for explaining the tripole charge structure in thunderclouds also needs a further exploration. We analyze the processes of ice crystal-graupel collision charging from charge migration inside hydrometeors to charge separation between two hydrometeors. The driving effects of temperature gradient and chemical potential gradient in charge migration are clarified, as well as the applicability of the relative growth rate theory, thermoelectric effect and surface tension gradient in different humidities. Based on the understanding from these electrification mechanisms, we propose that the essence of charge separation is driven by non-thermal equilibrium, and future studies on thunderstorm electrification should focus on the dynamical non-thermal equilibrium of cloud particles.

© The Royal Society of Chemistry 2018. Paddy soils from mercury (Hg)-contaminated rice fields in Guizhou, China were studied with respect to total mercury (THg) and methylmercury (MeHg) concentrations as well as Bacterial and Archaeal community composition. Total Hg (0.25-990 μg g-1) and MeHg (1.3-30.5 ng g-1) varied between samples. Pyrosequencing (454 FLX) of the hypervariable v1-v3 regions of the 16S rRNA genes showed that Proteobacteria, Actinobacteria, Chloroflexi, Acidobacteria, Euryarchaeota, and Crenarchaeota were dominant in all samples. The Bacterial α-diversity was higher in samples with relatively Low THg and MeHg and decreased with increasing THg and MeHg concentrations. In contrast, Archaeal α-diversity increased with increasing of MeHg concentrations but did not correlate with changes in THg concentrations. Overall, the methylation gene hgcAB copy number increased with both increasing THg and MeHg concentrations. The microbial communities at High THg and High MeHg appear to be adapted by species that are both Hg resistant and carry hgcAB genes for MeHg production. The relatively high abundance of both sulfate-reducing δ-Proteobacteria and methanogenic Archaea, as well as their positive correlations with increasing THg and MeHg concentrations, suggests that these microorganisms are the primary Hg-methylators in the rice paddy soils in Guizhou, China.

Hai Liu,1 Weifang Yang,2 Huaping Gao,3 Tingting Jiang,1 Bengxin Gu,1 Qinghua Dong,4 Wenhong Xu,5 Shixiu Wu,6 Xiaonan Sun1 1Department of Radiation Oncology, Sir Run Run Shaw Hospital, Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou, People’s Republic of China; 2Department of Radiation Oncology, Laboratory of Cellular and Molecular Radiation Oncology, Taizhou Hospital, Wenzhou Medical College, Taizhou, People’s Republic of China; 3Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 5Department of Radiation Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, People’s Republic of China; 6Department of Radiation Oncology, Hangzhou Cancer Hospital, Wushan District, Hangzhou First People’s Hospital, Hangzhou, People’s Republic of China Background: Acquired radioresistance of cancer is common after repeated irradiation and often leads to treatment failure. This study aimed to examine the effects of nimotuzumab on acquired radioresistance in human esophageal carcinoma cells and to investigate its underlying mechanisms. Methods: The radioresistant human esophageal carcinoma cell line KYSE-150R was generated by using fractionated irradiation. KYSE-150R cells were pretreated with or without nimotuzumab before ionizing radiation. Cell growth and colony formation were measured to quantitate the effects of radiation. The γ-H2AX foci assay was employed to determine cellular DNA-repairing capacity. The phosphorylation of key molecules involved in the epidermal growth factor receptor (EGFR) signaling pathway and cellular DNA repair was measured by Western blot analysis. Results: Nimotuzumab enhanced radiation-induced inhibition on cell growth and clonogenic survival in KYSE-150R cells. The average number of γ-H2AX foci increased in the irradiated cells treated with nimotuzumab. Nimotuzumab inhibited phosphorylation of the EGFR and its downstream molecules AKT and ERK. Phosphorylation of the DNA repair-related proteins DNA-PKcs, ATM, and RAD51 was also inhibited by nimotuzumab. Conclusions: These results indicate that nimotuzumab can inhibit key cancer survival mechanisms, the EGFR signaling pathway, and DNA repair and thereby reverse acquired radioresistance in KYSE-150R cell line. Keywords: nimotuzumab, esophageal cancer, EGFR, radiation

Oomycetes and fungi facilitate pathogenesis via secretion of effector proteins that have apoplastic and intracellular localizations. These effector proteins have a diverse array of functions that aid in pathogenesis, including modification of defense responses. In the oomycetes, well characterized effector proteins that can translocate into the host cells share a pair of conserved N-terminal motifs known as RXLR and dEER. The RXLR motif has been shown to mediate translocation of the oomycete avirulence proteins Avr1b and Avr3a into host cells. Detailed mutagenesis of the RXLR motif of Avr1b revealed that the motif is tolerant to several amino acid substitutions while retaining functional translocation activity, resulting in the definition of a broadened RXLR-like motif, [R,K,H] X[L/M/I/F/Y/W]X. This motif has been used to identify functional translocation motifs in several fungal effector proteins, AvrL567, Avr2, and AvrLm6. Effectors with both RXLR and RXLR-like motifs bind phosphatidylinositol- 3-phosphate (PI-3-P) to mediate translocation via lipid raft mediated endocytosis. Mutations in RXLR or RXLRlike motifs result in loss of phospholipid binding and translocation by effectors. Effector entry into plant cells can be blocked by proteins and inositides that disrupt binding to PI-3-P, suggesting effector-blocking technologies that could be used in agriculturally important plant species. Borlaug Global Rust Initiative Technical Workshop true (Invited?) false (Extension publication?)

Silkworms with conjugated linoleic acid (CLA) incorporated into their lipids (designated CLA silkworms) were produced to enhance the quality of silkworms having a synergistic effect with CLA functions by dietary synthetic CLA. Silkworm larvae were fed fresh mulberry leaves (control diet) until the third instar stage and were then subjected to various levels (0%, 0.1%, 1%, 5%, and 10%) of CLA-sprayed mulberry leaves (designated CLA diet) beginning on the first day of the fourth instar stage and continuing to the third day of the fifth instar stage. CLA contents in CLA silkworms increased proportionally with increasing CLA levels of CLA diets. CLA silkworms on a 1% CLA diet contained 2.2 g CLA/100 g lipid without body weight reduction, whereas CLA silkworms on a 10% CLA diet contained 14.8 g CLA/100 g lipid with a significant reduction of body weight, relative to the control silkworms. The CLA content in the lipids of CLA silkworms on a 10% CLA diet was significantly higher than that of CLA silkworms on a 5% CLA diet. A 0.1% CLA diet was not sufficient to accumulate CLA in the silkworms. Most of the CLA (approximately 99%) of silkworm lipids was present in triglyceride (TG) with a similar ratio of c9,t11 and t10,c12 CLA isomers. These results suggest that a 1% CLA diet was suitable for the production of CLA silkworms.

Conjugated linoleic acid (CLA) inclusion complexes with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), and γ-cyclodextrin (γ-CD) (designated CLA/CDs inclusion complexes) were prepared to determine the mole ratio of CLA complexed with CDs and the oxidative stability of CLA in the CLA/CDs inclusion complexes. When measured by GC, 1H NMR, and T1 value analyses, 1 mole of CLA was complexed with 5 mol of α-CD, 4 mol of β-CD, and 2 mol of γ-CD. The oxidation of CLA induced at 35 °C for 80 h was completely prevented by the formation of CLA/CDs inclusion complexes. Keywords: Conjugated linoleic acid (CLA); cyclodextrins (CDs); inclusion complexes of CLA with CDs; oxidation

Oxidative stability of conjugated linoleic acid (CLA) encapsulated in α-, β-, and γ-cyclodextrins (designated CLA/CDs microencapsules) was studied by measuring the headspace-oxygen depletion in airtight serum bottles and by measuring the peroxide values (POV). The rate of oxygen depletion was reduced from 41.0 (control) to 21.5, 2.1, 1.2, and 1.1 μmol/L·h-1 by CLA/α-CD microencapsules at 1:1, 1:2, 1:4, and 1:6 mole ratios, respectively, indicating that CLA oxidation was completely protected by a 1:4 mole ratio of CLA/α-CD. Such a protective effect by CLA/β-CD or CLA/γ-CD microencapsules was achieved at a 1:6 mole ratio, but the effect by CLA/β-CD was slightly greater than that by CLA/γ-CD. The protective effect of α-, β-, and γ-CDs for CLA oxidation was confirmed by their POV-reducing abilities in CLA/CDs. These results suggest that α-CD was the most effective for the protection of CLA oxidation by microencapsulation, followed by β-CD and γ-CD. Keywords: Conjugated linoleic acid (CLA); cyclodextrins (CDs)...

The observation of a two dimensional electron gas (2DEG) (1, 2), superconductivity (3, 4), magnetic effects (5) and electronic phase separation (6-8) at the interfaces of insulating oxides, especially LaAlO3/SrTiO3, has further enhanced the potential of complex oxides for novel electronics. The occurrence of the 2DEG is strongly believed to be driven by the polarization discontinuity (9) at the interface between the two oxides. In this scenario, the crystal orientation plays an important role and no conductivity would be expected for e.g., the interface between LaAlO3 and (110)-oriented SrTiO3, which should not have a polarization discontinuity (10, 11). Here, we report the observation of unexpected conductivity at the LaAlO3/SrTiO3 interface prepared on (110)-oriented SrTiO3. The conductivity was further found to be strongly anisotropic, with the ratio of the conductance along the different directions parallel to the substrate surface showing a remarkable dependence on the oxygen pressure during deposition. The conductance and its anisotropy are discussed based on the atomic structure at the interface, as revealed by Scanning Transmission Electron Microscopy (STEM) and further supported by density functional theory (DFT) calculations., Comment: 17 pages, 5 figures

Symbionts, both pathogenic and beneficial, must integrate their physiology with that of their host in order to achieve a successful colonization. Effector proteins that enter the cytoplasm of host cells are widely utilized for this purpose by bacterial, fungal, oomycete, protistan, nematode, and insect symbionts. The soybean pathogen Phytophthora sojae, one of the best characterized oomycete pathogens, encodes in its genome nearly 400 potential effector proteins with the cell-entry motif RXLR. We have recently identified the mechanism by which effector proteins from pathogens and mutualists from two different kingdoms of life, Fungi and Oomycetes, enter the cells of their plant hosts. The mechanism involves the previously undetected presence of the phospholipid phosphatidylinositol-3-phosphate (PI-3-P) on the outer surface of the plasma membrane of plant cells. The virulence proteins utilize PI-3-P as a receptor to gain entry via lipid-raft mediated endocytosis. More recently, we have discovered that two diverse insect pests of plants (hessian flies and aphids) also produce proteins that can bind PI-3-P via RXLR motifs in order to enter plant cells, where they suppress host defenses while the insects feed. We are current exploring methodologies for disrupting PI-3-P-mediated effector entry in order to create new means for managing oomycete and fungal diseases and insect pests.

OBJECTIVE To investigate the effects of Tongfeng trace elements nutrient balance agent on the various growth indicators, physiological indicators, and the contents of liquiritin and glycyrrhizic acid in one-year old Glycyrrhiza uralensis. METHOD The plants of G. uralensis growing in Chifeng of Inner Mongolia and medicinal garden of Beijing University of Chinese Medicine were fertilized for two times, respectively. The photosynthetic physiological indicators were measured by LI-6400 photosynthetic instrument. The pigments and antioxidase activities of the leaves were determined. Then contents of liquiritin and glycyrrhizic acid in the plants were determined by HPLC. RESULT The application of this trace element nutrient balance agent could significantly improve the height, chla and chlb, and the photosynthetic physiology indicator such as P(n), C(i), and G(s). Similarly, it could significantly increase the fresh weight of shoots and dry weight of the roots. Compared with control block (CK), the fertilizer which was diluted by 300 times (T(1)) and 600 times (T(2)) significantly increased the content of glycyrrhizic acid by 24.72% and 20. 23%. There was significant difference between different treatments (P < 0.05). CONCLUSION The Tongfeng trace elements nutrient balance agent could promote growth, physiology and the content of active constituents of G. uralensis, especially the effect of T(1) was superior to T(2).

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This paper studies the applicability of Synthetic Environments (SE) for dynamic prototyping in the early phase of product design. For this purpose, a simple SE, built with commercial off-the-shelf (COTS) technology, was employed to support the design of the lid of an X-Ray machine. Psychological experiments, statistical analysis of questionnaires, and user interviews indicated that for the design problem concerned, the SE was a proper substitution of the physical prototype, although the participants experienced difference in sense of presence. To further improve the applicability of SE, a design strategy of intuitive user interface is proposed for dynamic prototyping in SE to facilitate the communication among stakeholders with various knowledge backgrounds.

A pilot-scale system was established for biostimulation of subsurface U(VI) reduction by injection of ethanol at the U.S. DOE's Field Research Center (FRC) in Oak Ridge, TN. After U(VI) reduction was achieved, the stability of the bioreduced area was examined by suspension of ethanol injections (resting state) and reoxidation of the area by introducing dissolved oxygen (DO) for two months. After the reoxidation, ethanol injections were resumed. Geochip 2.0, a comprehensive 50mer microarray containing probes for genes involved in the geochemical cycling of N, S, and C, metal resistance and contaminant degradation, was used to monitor the dynamics of the groundwater microbial community structure and function. The immobilized U was stable during the resting state. After DO was introduced to the reduced area, the monitoring well (FW101-2) located closest to the injection well, had a greater increase in DO (2 mg L-1) than the well located further away (FW102-3

The 4th AIST Advisory Board Meeting was held on 6 and 7 February, 2006, at the AIST Tsukuba Headquarters. The agenda of the 4th meeting was the 'second term strategy for AIST as an innovation engine'. The discussions focused on the President's presentation, entitled 'Vision for AIST's Second Mid-term Period', and on the presentation of the Director of Planning Headquarters, entitled 'Establishing the innovation hub at AIST'. A total number of fifteen people were selected for the 4th Advidory Board meeting, which went on for one and a half days. The innovative strategies discussed in the meeting include collaboration between industry and acedemia, human resource development, and venture creation. The Advisory board members and AIST executives also held active discussions on various issues regarding the operation of AIST including research management, intellectual property, safety management, security management, and public relations.

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We report the preparation of Mg1-xLixB2 compounds. Nearly single phased samples were obtained for x, 5 pages, 4 figures

We report the preparation of Mg$_{1-x}$B$_{2}$ (0$\le$x$\le$0.5) compounds with the nominal compositions. Single phase MgB$_{2}$ was obtained for x=0 sample. For 0$, Comment: 11 pages, 4 figures

In this paper we use data from the 1 Per Cent Sample of the 1990 Census of China to calculate sex ratios for the Chinese provinces that are specific not only to parity, but also to the sex composition of previously‐born children. We analyze the degree of relationship among and between the SRB's and then consider the phenomenon of son preference. We find the variation in sex ratios at birth among the Chinese provinces is related in an important way to variation among the provinces in the degree of son preference. Our analysis shows abnormally high SRB's in most of the provinces of China, especially at parities 2 and higher when the prior births were daughters. Other societies, namely Taiwan and South Korea, with rapid fertility decline and strong son preference also manifest abnormally high SRB's at parities beyond the first.

Fertility trends in rural China during the 1980s are examined in terms of the cohort and period effect of fertility. Variations in fertility among the subregions of rural China are also examined, and it is demonstrated that birth bunching characterized the decade. The implications for future fertility and family planning are discussed also. Analysis is based on the stratified, systematic, cluster and random sample from the 2/1000 Fertility Sampling Survey, 1988, in 30 provinces, autonomous regions and municipalities of China. 485,2356 households comprising 2,151,212 individuals were enumerated. 459,269 were married women 15-57 years. The total fertility rate (TFR) and the total parity progression rate (TPPR) are differentiated, and the trends revealed. Tables provide TFR and TPPR both parity and subregion for rural China for 1985-87. Fertility variation is also described for the years 1985-87 by TFR and TPPR. Birth bunching or the bunching of 1st births is also discussed at some length. High parity declined over the decade, but birth bunching existed in at least 15 of the 29 subregions. 2nd birth bunching also occurred in 11 of the 29 regions. Population planning programs overlooked the timing of marriage and childbearing, particularly in 1st marriage and 1st births. New options being proposed are the 27-4 option, which recommends 27 years of age as the minimum age for 1st childbearing and 4 years spacing between children, and granting permission to have 2 children and spacing them 8-10 years apart. Another option would be to raise the mean age of childbearing to 30 years. It is noted that except for Xinjiang and Tibet all subregions had a TFR 4.0 in the 1980s and the fertility of 3rd and higher parity had declined. The national TFR reached 2.3, but the 1-child policy tended to cluster around the eastern coastal regions. The fertility trends could be described as bunching of 1st births in the 1st part of the 1980s. The bunching of 2nd births in mid decade, and the tendency for 3rd births in rural areas at the end of the decade. Fertility decline was due to an increase in women of childbearing age, the ceiling effect of low fertility, and the onset of socioeconomic development. Reducing fertility and reaching replacement level are 2 distinct phenomena characterizing China's past trends. Socioeconomic development is ongoing and the effects on social, cultural, and economic conditions is of importance. Compared with the developing world, the death rates and natural increases are relatively low. Population problems continue, and TFR must be reduced to 2.0 by 2000. Population will exceed 1.2 billion after the mid 1990s. Migration and population movements will characterize the 1990s.