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Juan-Min Zha,1,* Mei Zhang,1,* Tao Wang,2,* Hua-Shan Li,1,2,* Quan-Yao Ban,1,* Mei Liu,1 Xue-Xue Jiang,1 Shi-Ying Guo,2 Jing Wang,2 Ya-Ru Zhou,2 Yu-Hong Liu,2 Wei-Qi He,1,2 Hong Xu1 1Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China; 2Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cambridge-Suda (CAM-SU) Genomic Resource Center, Medical College of Soochow University, Suzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei-Qi He; Hong Xu, Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-512-6588-3545, Email whe@suda.edu.cn; hongxusuda@outlook.comObjective: This cross-sectional study aimed to explore the association of overweight and inflammatory indicators with breast cancer risk in Chinese patients.Methods: Weight, height, and peripheral blood inflammatory indicators, including white blood cell count (WBC), neutrophil count (NE), lymphocyte count (LY), platelet count (PLT) and the concentration of hypersensitivity C-reactive protein (hsCRP), were collected in 383 patients with benign breast lumps (non-cancer) and 358 patients with malignant breast tumors (cancer) at the First Affiliated Hospital of Soochow University, China, from March 2018 to July 2020. Body mass index (BMI), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were determined according to the ratio equation. The correlations among overweight, inflammatory indicators, and the proportion of non-cancer or cancer cases were analyzed.Results: BMI is associated with an increased breast cancer risk. Compared with non-cancer patients, the average WBC count, NE count, NLR, and level of hsCRP were significantly higher in cancer patients. The level of hsCRP was closely associated with the size of malignant breast tumors.Conclusion: We conclude that overweight and high levels of hsCRP may serve as putative risk factors for malignant breast tumors in Chinese women.Keywords: breast cancer, body mass index, overweight, chronic inflammation, inflammatory indicator

Yan Zhang,1 Wenjie Li,1 Xiaomin Tian,1 Ruanyang Sun,1 Shidan Zhou,2 Ling Jia,1 Jian Sun,1,3,4 Xiao-Ping Liao,1,3,4 Ya-Hong Liu,1,3,4 Yang Yu1,3,4 1Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, People’s Republic of China; 2Intensive Care Unit, Huizhou Municipal Central Hospital, Huizhou, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Microbial Safety and Health, Guangdong Institute of Microbiology, Guangdong Academy of Science, Guangzhou, People’s Republic of China; 4Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, People’s Republic of ChinaCorrespondence: Yang Yu, Email graceyyu@scau.edu.cnObjective: Carbapenem-resistant Enterobacteriaceae (CRE) have become an increasingly common cause of healthcare-related infections and present a serious challenge to clinical treatment. This study examined the phenotypic, genotypic characterization, clinical, and microbiological data of CRE in the Huizhou Municipal Central Hospital.Methods: We conducted a phenotypic susceptibility evaluation and whole genome sequence analysis for 52 CRE strains isolated from 37 patients and 2 medical device-related samples during 2013– 2017 to characterize risk factors, antimicrobial resistance profiles, dominant clones and hospital transmission.Results: Long-term hospitalization, treatment time with antibiotics and use of invasive devices were linked to the risk of CRE infection. The carbapenem resistance genes (CRGs) we found included blaNDM (82.7%), blaIMP (19.2%) and blaKPC (3.8%), Escherichia coli (44.2%) and Klebsiella pneumoniae (44.2%) were the dominant species we identified, and the type of CRG carried by isolates was highly correlated with species. The coexistence of CRGs with a variety of other antibiotic resistance genes leads to an increased prevalence of high resistance levels for CRE to β-lactams and other antibiotic classes such as aminoglycosides and fluoroquinolones. These isolates were sensitive only to colistin and tigecycline. In addition to this, we observed significantly genomic diversity of CRE isolates in this hospital. Importantly, we found that long-term transmission of multiple CRE clones had occurred at this hospital between various wards.Conclusion: Evaluating and improving the current infection control strategies may be necessary, and reducing nosocomial transmission remains the primary control element for CRE infections in China.Keywords: carbapenem-resistant Enterobacteriaceae, bacteremia, carbapenem resistance genes, nosocomial transmission

Yi-Hui Liu,1 Yan Guo,2 Hong Xu,1 Hui Feng,1 Dong-Ya Chen1 1Department of Digestive Hepatology, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, 310003, People’s Republic of China; 2Department of Gastroenterology, Hangzhou Third Hospital, Hangzhou, Zhejiang, 310009, People’s Republic of ChinaCorrespondence: Yi-Hui LiuDepartment of Digestive Hepatology, Hangzhou Red Cross Hospital, No. 208 of Huancheng East Road, Xiacheng District, Hangzhou, Zhejiang, 310003, People’s Republic of ChinaTel +8613588227972Email yhl_123drsea@163.comObjective: To observe the effect of non-alcoholic simple fatty liver disease on drug-induced liver injury caused by tuberculosis.Methods: We retrospectively analyzed the incidence, characteristics, and risk factors of antituberculosis drug-induced liver injury in 104 patients with initial treatment of tuberculosis complicated with non-alcoholic simple fatty liver disease. The patients were divided into two groups according to whether there was liver injury or not. The differences in age, gender, body mass index (BMI), cholesterol, and triglycerides were studied between the two groups.Results: Among the 104 patients with initial treatment of tuberculosis complicated with non-alcoholic fatty liver disease, 24 (23%) patients developed a drug-induced liver injury. The remaining 80 (77%) patients did not develop drug-induced liver injury (χ2 = 60.308, P < 0.05). In the liver injury group, there were 20 cases of mild liver injury, two cases of moderate liver injury, two cases of severe liver injury, 22 cases of hepatocellular injury, two cases of cholestasis, and no cases of mixed liver injury. The time of abnormal liver function in antituberculosis treatment was 16.42 ± 9.18 days from the beginning of the antituberculosis treatment. There were no significant differences in gender, age, BMI, or triglyceride between the liver injury group and the non-liver injury group (χ2 = 2.063, t = 0.179, t = 0.703, t = 1.12, P > 0.05 in all), but there were significant differences in cholesterol (t = 3.08, P < 0.05). By logistic regression analysis, cholesterol was a high-risk factor for liver injury.Conclusion: Non-alcoholic simple fatty liver disease may increase the risk of antituberculosis drug-induced liver injury.Keywords: non-alcoholic simple fatty liver disease, antituberculosis drugs, drug-induced liver injury

Shao-Jie Zhang,1,2,&ast; Kun Li,2,3,&ast; Zhi-Jun Li,2,3 Xing Wang,2,3 Jia-Hui Dong,4 Jian Wang,2 Jie Chen,2 Xing-Yue Qu,2 Zi-Yu Li,2 Yu-Hang Liu2 1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Human Anatomy, Inner Mongolia Medical University, Hohhot, People’s Republic of China; 3Digital Medical Center, Inner Mongolia Medical University, Hohhot, People’s Republic of China; 4The First Clinical Medical College, Inner Mongolia Medical University, Hohhot, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Jun LiDepartment of Human Anatomy, Inner Mongolia Medical University, Hohhot, People’s Republic of ChinaTel +86 471-6636945Email zjl06_master@126.comObjective: This study aimed to investigate the safety of clival screw placement in children aged 1– 6 years.Methods: The cranial computed tomography data of 92 children aged 1– 6 years were divided into three groups, according to age, for three-dimensional reconstruction. Three clival screw placement points were defined: (1) median point A at the middle and upper third of the tripartite distance from the spheno-occipital synchondrosis to the base of the skull; (2, 3) critical points B and C on the horizontal line with point A, where the screw placement passage was parallel to the sagittal plane. Parameters such as the passage length and angle were measured for horizontal, vertical facial, and extreme screw placement.Results: The length parameters of the clival screw placement increased with age, and the screw passage length was the shortest for the vertical facial type in each age group. There were significant differences in all three groups between the length of screw placement in the vertical bone surface, the length of screw placement in the horizontal direction, and the length of screw placement on the limit at points A, B, and C (P < 0.05); the length of screw placement on the vertical bone surface was the shortest. There was no significant difference between the horizontal screw length at point A and the extreme screw length (P > 0.05). The difference between the horizontal screw length and the extreme screw length in the groups aged 1– 2 years and 5– 6 years was statistically significant (P < 0.05), and the horizontal screw length was longer.Conclusion: The cranial slope of children aged 1– 6 years has the morphological basis for the placement of 3.5 mm screws, and each placement point has a safe angle range for screw placement.Keywords: children, craniocervical junction region, clivus, internal screw fixation, spiral computed tomography scan

Kai-Ming Jhang,1,* Wen-Fu Wang,1,2,* Hao-Fang Chang,3,* Yu-Huei Liu,4– 6,* Ming-Che Chang,7 Hsin-Hung Wu3,8,9 1Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan; 2Department of Holistic Wellness, Ming Dao University, Changhua, Taiwan; 3Department of Business Administration, National Changhua University of Education, Changhua, Taiwan; 4Graduate Institute of Integrated Medicine, China Medical University, Taichung City, Taiwan; 5Drug Development Center, China Medical University, Taichung City, Taiwan; 6Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung City, Taiwan; 7Department of Nuclear Medicine, Changhua Christian Hospital, Changhua, Taiwan; 8Department of M-Commerce and Multimedia Applications, Asia University, Taichung City, Taiwan; 9Faculty of Education, State University of Malang, Malang, East Java, Indonesia*These authors contributed equally to this workCorrespondence: Hsin-Hung Wu No. 2 Shida Road, Changhua City 500, TaiwanTel +886 4 7232105 ext. 7412Fax +886 4-7211292Email hhwu@cc.ncue.edu.twPurpose: The aim of this study was to identify the care needs of male patients with vascular cognitive impairment (VCI) and their caregivers.Patients and Methods: This cross-sectional study enrolled 389 male patients with VCI and their caregivers who were cared for by the dementia collaborative care team at Changhua Christian Hospital, Taiwan. Fifteen care needs consisting of most of quality measures for people living with dementia and their caregivers were developed by the care team. Through face-to-face evaluations, individualized care needs were collected. The Apriori algorithm was used to identify care bundles for the patients and their caregivers.Results: Six basic care needs for patients and their caregivers were identified, including appropriate schedule of activities, regular outpatient follow-up treatment, introduction and referral of social resources, referral to family support groups and care skills training, care for the mood of the caregiver, and health education for dementia and behavioral and psychological symptoms of dementia. Compared to subjects with all dementia subtypes from the previous studies, care for the mood of the caregiver was an important and frequent care need for the male patients with VCI and their caregivers. A comparison among the study and similar studies was made to highlight the strength of this study concentrating on the precise selection of care needs.Conclusion: Collaborative dementia care teams should monitor for caregivers’ depression and include this care need into the care bundle when assessing male subjects with VCI.Keywords: male patients with vascular cognitive impairment, people living with dementia, behavioral and psychological symptoms of dementia, dementia collaborative care model, care need, Apriori algorithm

Li-Jun Chen,1,2 Wang Xu,1 Ya-Ping Li,3 Li-Ting Ma,1 Hui-Fang Zhang,1 Xiao-Bo Huang,1 Geng-Geng Yu,1 Xiu-Qin Ma,1 Chao Chen,1 Yan-Hong Liu,1 Jie Wu,4 Li-Jun Wang,4 Yuan Xu4 1Department of Respiratory and Critical Medicine, The First People’s Hospital of Yinchuan City, Yinchuan, Ningxia, People’s Republic of China; 2Department of Respiratory and Critical Medicine, The Second Affiliated Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 3Department of Respiratory Medicine, Weihai Municipal Hospital of Shandong Province, Weihai, Shandong, People’s Republic of China; 4Department of Clinical Institute, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of ChinaCorrespondence: Li-Jun ChenDepartment of Respiratory and Critical Medicine, The Second Affiliated Hospital of Ningxia Medical University, No. 2, Liqun West Street, Xingqing District, Yinchuan, Ningxia 750001, People’s Republic of ChinaTel +86-13895016600Fax +86-951-6192235Email ycchenlj@163.comBackground: Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory disease characterized by irreversible airflow obstruction. Pathogenic mechanisms underlying COPD remain largely unknown.Objective: The current study was designed to explore serum concentration of hypoxia-inducible factor 1α (HIF-1α) in stable COPD patients and the potential effect of Lycium barbarum polysaccharides (LBP) on HIF-1α protein expression.Methods: Serum HIF-1α was quantified by ELISA in 102 stable COPD patients before and after 2-week orally taken LBP (100 mL/time, twice daily, 5– 15 mg/mL). Correlation of serum LBP and lung function (FEV1%) or blood gas (PO2 and PCO2) was also analyzed. As a control, 105 healthy subjects were also enrolled into this study.Results: Serum concentration of HIF-1α was significantly higher in the stable COPD patients (37.34 ± 7.20 pg/mL) than that in the healthy subjects (29.55 ± 9.66 pg/mL, P< 0.001). Oral administration of LBP (5 mg/mL, 100 mL, twice daily for 2 weeks) not only relieved COPD symptoms but also significantly reduced serum HIF-1α concentration (36.94 ± 9.23 vs 30.49 ± 6.42 pg/mL, P< 0.05). In addition, level of serum HIF-1α concentration was significantly correlated with PCO2 (r = 0.283, P< 0.001), but negatively and significantly correlated with PO2 (r = − 0.490, P=0.005) or FEV1%(r = − 0.420, P=0.018).Conclusion: These findings suggested that activation of HIF-1 signaling pathway may be involved in the pathophysiology of COPD and that stabilization of serum HIF-1α concentration by LBP might benefit the stable COPD patients.Keywords: chronic obstructive pulmonary disease, COPD, hypoxia-induced factor 1, HIF-1, Lycium barbarum polysaccharides, LBP

Jie Li, Ling Bo Xue, Xiao Yi Gong, Yan Fang Yang, Bu Yong Zhang, Jian Jin, Qing Feng Shi, Yong Hong Liu Thyroid and Breast Surgery, Cangzhou Central Hospital, Cangzhou City 061000, People’s Republic of ChinaCorrespondence: Yong Hong LiuThyroid and Breast Surgery, Cangzhou Central Hospital, No. 16 Xinhua Road, Yunhe Qu, Cangzhou City 061000, People’s Republic of ChinaTel +86-15733758110Fax +86 317-207-2692Email lyh15733758110@hotmail.comObjective: Despite the expectation of normal life expectancy for thyroid cancer, there are concerns about the decreased quality of life (QoL). The present study investigated the potential risk factors of deterioration in QoL scores in thyroid cancer patients after thyroidectomy.Materials and methods: A total of 286 patients who were diagnosed with thyroid cancer after thyroidectomy were involved in this prospective, single-center, observational study from November 2018 to June 2019. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 was used to assess the QoL 3 months after thyroidectomy. We investigated the effects of demographics (age, gender, education, marital status, area of residence, and annual mean income), tumor characteristics (histology, clinical stage, presence of metastasis, surgery type, and radiotherapy), and neurological deficits induced by recurrent nerve or superior laryngeal injury on QoL.Results: The mean overall QoL in thyroid cancer survivors was 65.93 ±9.00 (on a scale of 0–100, where 100 was the best). Multivariate regression analysis confirmed that clinical stage (P < 0.010), surgery type (P < 0.001), histology (P < 0.001), neurological deficits (P < 0.001), and marital status (P < 0.001) were independent risk factors for decreased QoL 3 months after thyroidectomy.Conclusion: Our study indicated that clinical stage, surgery type, histology, neurological deficits, and marital status were independent risk factors for decreased QoL at 3 months after thyroidectomy. Further exploration and validation of these findings in larger prospective studies are warranted.Keywords: quality of life, thyroid cancer, thyroidectomy

Chiung-Chi Cheng,1,2 Wei-Ting Chao,3 Chen-Chun Liao,3 Jing-Hao Shih,3 Yih-Shyong Lai,1 Yung-Hsiang Hsu,4 Yi-Hsiang Liu1,4 1Department of Pathology, Chang Bing Show-Chwan Memorial Hospital, Changhua 505, Taiwan; 2Center for General Education, Providence University, Taichung City 433, Taiwan; 3Department of Life Science, Tunghai University, Taichung City 407, Taiwan; 4Department of Pathology, Tzu Chi University, Hualien 97004, TaiwanCorrespondence: Yi-Hsiang LiuDepartment of Pathology, Chang Bing Show-Chwan Memorial Hospital, 6 Lugong Road, Lukang Zhen, Changhua County 505, TaiwanTel +886 4 7813888 ext. 71181Fax +886 4 7073235Email ysliu53@gmail.comBackground: An increasing number of studies support cancer stem cells as the reason for chemoresistance to sorafenib therapy in hepatocellular carcinoma (HCC), but the mechanism is still unclear. In this study, the mechanism of sorafenib resistance in cancer stem cells was examined by in vitro experiments and xenograft mouse model.Methods: The expression of cancer stem cell markers in the Chang liver cell line and PLC/PRF/5 and HepG2 hepatoma cell lines were compared by immunoblot assay before and after sorafenib treatment in vitro. As a xenograft mouse model, subcutaneous injection of hepatoma cells followed by sorafenib therapy was performed in NU/NU mice. The effects of sorafenib therapy on tumor growth and cancer stem cell markers were studied. Angiogenesis associated with cancer stem cells was studied by immunoblot and immunohistochemistry assay.Results: The expression of cancer stem cell markers was higher in PLC/PRF/5 and HepG2 cells than Chang liver cells, indicating that these hepatoma cells had more stemness-related characteristics. The cancer stem cell markers were upregulated in the hepatoma cell lines following sorafenib treatment in vitro. In the xenograft model, tumors from PLC/PRF/5 and HepG2 cells with high E-cadherin expression were more resistance to sorafenib therapy. However, the expression of cancer stem cell markers was not significantly different after sorafenib therapy in these tumors. Furthermore, we found that sorafenib therapy induced angiogenesis within tumors from high E-cadherin expressing hepatoma cells.Conclusion: The mechanism of chemoresistance in sorafenib therapy in HCC may be the tumor angiogenesis associated with high E-cadherin expression in cancer stem cells.Keywords: angiogenesis, cancer stem cells, cytokeratin, E-cadherin, hepatocellular carcinoma, sorafenib

Xu-ping Gao,1,* Yan-hua Liu,2,* Ze-ying Liu,1 Li-jun Wang,3 Chun-xia Jing,1 Sui Zhu,4 Fang-fang Zeng1 1Department of Epidemiology, School of Medicine, Jinan University, Guangzhou 510632, Guangdong, China; 2Department of Nutrition, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; 3Department of Nutrition, School of Medicine, Jinan University, Guangzhou 510632, Guangdong, China; 4Department of Medical Statistics, School of Medicine, Jinan University, Guangzhou 510632, Guangdong, China *These authors contributed equally to this work Introduction: In this meta-analysis, we analyzed retrospective cohort studies that assessed the prognostic potential of the pretreatment lymphocyte-to-monocyte ratio (LMR) among patients with ovarian cancer (OC).Materials and methods: We comprehensively searched electronic databases, including PubMed and Embase, from inception through October 2018. A random-effects model was used to calculate pooled HRs and their 95% CIs for overall survival (OS) and progression-free survival (PFS). The low LMR group was treated as the reference group.Results: Twelve studies, including 3,346 OC cases at baseline, were included. Overall, our results indicated that LMR was positively associated with both OS (HR: 1.85, 95% CI: 1.50–2.28, P

Guo-Lin Hong,1 Hai-Ling Zhao,2,3 Hao-Hua Deng,3 Hui-Jing Yang,4 Hua-Ping Peng,3 Yin-Huan Liu,5 Wei Chen3 1Department of Laboratory Medicine, The First Affiliated Hospital of Xiamen University, Xiamen 361003, People’s Republic of China; 2School of Public Health, Xiamen University, Xiamen 361102, People’s Republic of China; 3Department of Pharmaceutical Analysis, Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, Fujian Medical University, Fuzhou 350004, People’s Republic of China; 4Department of Laboratory Medicine, Fujian Medical University, Fuzhou 350004, People’s Republic of China; 5Department of Laboratory Medicine, The Affiliated Fuzhou Second Hospital of Xiamen University, Fuzhou 350007, People’s Republic of China Background: The preparation and biological applications of ultra-small graphene quantum dots (GQDs) with accurate-controlled size are of great significance. Methods: Here in, we report a novel procedure involving pyrolysis of trisodium citrate and subsequent ultrafiltration for fabricating monolayer GQDs with ultra-small lateral size (1.3±0.5 nm). Results: The GQDs exhibit blue photoluminescence with peak position independent of excitation wavelength. The quantum yield of GQDs is measured to be 3.6%, and the average fluorescence lifetime is 2.78 ns. Conclusion: Because of high stability and low toxicity, GQDs are demonstrated to be excellent bioimaging agents. The ultra-small GQDs can not only distribute in the cytoplasm but also penetrate into the nuclei. We ensure that this work will add a new dimension to the application of graphene materials for nanomedicine. Keywords: graphene quantum dots, fluorescence, cell imaging, trisodium citrate, pyrolysis

Liang-Xing Fang,1,2,* Xing-Ping Li,1,2,* Liang Li,1,2 Mu-Ya Chen,1,2 Cai-Yan Wu,3 Lu-Lu Li,4 Xiao-Ping Liao,1,2 Ya-Hong Liu,1,2 Jian Sun1,2 1National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, People’s Republic of China; 3Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, People’s Republic of China; 4Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, People’s Republic of China *These authors contributed equally to this work Background: CMY-2 is the most prevalent pAmpC β-lactamase, but the chromosomal blaCMY-2 gene transfer via horizontal transmission has been seldom reported. This study aimed to describe an ISEcp1-mediated transposition of a chromosomal blaCMY-2 gene from Escherichia coli into a small endogenous ColE1-like plasmid, resulting in elevated resistance to extended-spectrum cephalosporins. Methods: Three ESCs-resistant ST641 E. coli strains EC6413, EC4103 and EC5106 harbored the blaCMY-2 gene. S1- PFGE, I-ceu I-PFGE, Southern blotting and electroporation experiments were performed to investigate the location and transferability of blaCMY-2. The genetic context and gene expression of blaCMY-2 in the original isolates and the corresponding electroporants were explored by PCR mapping, primer walking strategy and RT-qPCR. Results: The blaCMY-2-containing region (ISEcp1-blaCMY-2-∆blc-∆yggR-∆tnp1-orf7-orf8-orf9-∆tnp2-∆hsdR) was transposed into endogenous ColE1-like plasmid pSC137 in the process of electroporation at very low frequencies (10–8–10–9). The transpositions resulted in novel larger blaCMY-2-harboring ColE1-like plasmids with size of 14,845 bp, enabling increase in MICs of 2 to 8-fold for cefotaxime, ceftiofur, and ceftazidime in recipient strains over their respective original counterparts. Transcriptional level analysis revealed that the increased blaCMY-2 expression was correlated with elevated MIC values of cephalosporins. The blaCMY-2 transposition unit was identical to that in a clinical isolate E. coli TN44889 from France isolated in 2004. Conclusions: Our results firstly demonstrated that ISEcp1 mediated a transposition of chromosome-borne blaCMY-2 into an endogenous ColE1-like plasmid by electroporation. Amplification of the blaCMY-2 gene facilitates the strain adaptation to a changed environment with an elevated antibiotic pressure. Keywords: blaCMY-2, chromosome-borne, ColE1-like plasmid, ISEcp1-mediated transposition, extended-spectrum cephalosporin

Junhong Li,* Ruofei Liang,* Chen Song, Yufan Xiang, Yanhui Liu Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People’s Republic of China *These authors contributed equally to this work Purpose: There is a great controversy regarding the prognostic significance of epidermal growth factor receptor (EGFR) in glioma patients. The current meta-analysis was conducted to evaluate the effect of abnormal EGFR expression on overall survival in glioma patients.Materials and methods: A comprehensive literature search of PubMed, EMBASE, Google Scholar, Web of Science, and Cochrane Library was conducted. The combined hazard ratio (HR) and its 95% confidence intervals (CIs) were used to evaluate the association between EGFR expression and survival in glioma.Results: A total of 476 articles were screened, and 17 articles containing 1,458 patients were selected. The quality assessment of the included studies was performed by the Newcastle–Ottawa Scale. Overexpression of EGFR was found to be an indicator of poor prognosis in overall survival in glioma patients (HR =1.72, 95% CI 1.32–2.25, P=0.000, random effect) and glioblastoma multiforme patients (HR =1.57, 95% CI 1.15–2.14, P=0.004, random effect). Subgroup analysis was conducted to explore the source of high heterogeneity.Conclusion: This meta-analysis indicated that high expression of EGFR may serve as a biomarker for poor prognosis in glioma patients. Keywords: epidermal growth factor receptor, glioma, meta-analysis, prognosis

Yuh-Hwa Liu,1,2,* Yeh-Lin Lu,3,* Der-Zen Liu,4 Wen-Chi Hou5 1Division of Gastroenterology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 2Department of General Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Pharmacy, Taipei Medical University, Taipei, Taiwan; 4Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei, Taiwan; 5Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan *These authors contributed equally to this work Abstract: Advanced glycation endproducts (AGEs) can promote intracellular reactive oxygen species production, and the levels of AGEs are highly correlated with cardiovascular disease and diabetes complications. Acetohydroxamic acid (acetH) is a bacterial urease inhibitor drug used to treat kidney stones and infections in the urinary tract, and hydroxyurea (HU) is a drug used for antineoplasm and sickle cell diseases. Both acetH and HU are hydroxamic acid derivatives. It was found that acetH and HU at 2.5 or 5 mM showed anti-AGE formation by lowering the AGEs’ fluorescent intensities and Nε-(carboxymethyl)lysine formation in bovine serum albumin/galactose models, and both showed better and significant differences (P

Fei Xue,1 Yanhui Liu,2 Hongwei Zhang,1 Yu Wen,1 Lei Yan,1 Qiang Tang,1 Erhui Xiao,1 Dongyi Zhang1 1Department of Hepatobiliary and Pancreatic Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Hematology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China Background: Let-7 miRNAs are reported to play an inhibitory role in carcinogenesis, tumor progression, recurrence, and pluripotency of cancer. However, few studies have reported the relationship between let-7 and drug sensitivity, especially for let-7a (a subtype of let-7). This study aimed to investigate the function of let-7a in regulating the sensitivity of hepatocellular carcinoma (HCC) cell lines to cetuximab. Methods: The cytotoxicity of cetuximab on HCC cell lines (Huh7, Hep3B, HepG2, SNU449, and SNU387) was evaluated using a cell viability assay (the Cell Counting Kit-8 assay) and a cell proliferation assay (the Click-iT EdU Imaging Kit) in the presence of a control, a let-7a mimic, and a let-7a inhibitor. Small interfering RNA to knockdown the expression of signal transducer and activator of transcription 3 (STAT3) were employed. Protein and mRNA expression levels were determined using quantitative polymerase chain reaction and Western blot analysis. Results: It was found that let-7a enhances the sensitivity of HCC cells with an epithelial phenotype (Huh7, Hep3B, and HepG2) to cetuximab, but has no effect on cells with the mesenchymal phenotype (SNU449 and SNU387). It was determined that STAT3 was a target mRNA of let-7a using TargetScan. Expression of STAT3 and let-7a mRNA were negatively correlated in HCC cell lines. Moreover, let-7a altered the protein and mRNA expression of STAT3. Furthermore, STAT3 knockdown enhanced the function of cetuximab on HCC cell lines with epithelial phenotypes, but not on HCC cell lines with mesenchymal phenotypes. Finally, a rescue experiment confirmed that let-7a affected the sensitivity of HCC cell lines to cetuximab by interacting with STAT3. Conclusions: There is a functional link between let-7a and STAT3 in enhancing the sensitivity of HCC cells with an epithelial phenotype to cetuximab. Our results provide novel insight into new methodologies for combating HCC drug resistance. Keywords: hepatocellular carcinoma, microRNA, STAT3, let-7a

Ailing Liu,1,2,* Jinxiang Wu,1,* Aijun Li,2 Wenxiang Bi,3 Tian Liu,1 Liuzhao Cao,1 Yahui Liu,1 Liang Dong1 1Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Pulmonary Diseases, Weihai Municipal Hospital, Weihai, Shandong, People’s Republic of China; 3Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this work Objectives: Cellular senescence is a state of irreversible growth arrest induced either by telomere shortening (replicative senescence) or stress. The bronchial epithelial cell is often injured by inhaled toxic substances, such as cigarette smoke. In the present study, we investigated whether exposure to cigarette smoke extract (CSE) induces senescence of bronchial epithelial cells; and Cordyceps sinensis mechanism of inhibition of CSE-induced cellular senescence.Methods: Human bronchial epithelial cells (16HBE cells) cultured in vitro were treated with CSE and/or C. sinensis. p16, p21, and senescence-associated-galactosidase activity were used to detect cellular senescence with immunofluorescence, quantitative polymerase chain reaction, and Western blotting. Reactive oxygen species (ROS), PI3K/AKT/mTOR and their phosphorylated proteins were examined to testify the activation of signaling pathway by ROS fluorescent staining and Western blotting. Then, inhibitors of ROS and PI3K were used to further confirm the function of this pathway.Results: Cellular senescence was upregulated by CSE treatment, and C. sinensis can decrease CSE-induced cellular senescence. Activation of ROS/PI3K/AKT/mTOR signaling pathway was enhanced by CSE treatment, and decreased when C. sinensis was added. Blocking ROS/PI3K/AKT/mTOR signaling pathway can attenuate CSE-induced cellular senescence.Conclusion: CSE can induce cellular senescence in human bronchial epithelial cells, and ROS/PI3K/AKT/mTOR signaling pathway may play an important role in this process. C. sinensis can inhibit the CSE-induced senescence. Keywords: senescence, Cordyceps sinensis, ROS/PI3K/AKT/mTOR signaling pathway, COPD

Liquan Hong,1 Feng Pan,1 Huifen Jiang,2 Lahong Zhang,1 Yuhua Liu,1 Chengsong Cai,1 Chunzhen Hua,3 Xian Luo,1 Jinhua Sun,4 Zhaojun Chen1 1Department of Clinical Laboratory, Affiliated Hospital of Hangzhou Normal University, 2Zhejiang Provincial Tumor Hospital, 3Zhejiang Provincial Children’s Hospital, 4Technology Department, Hangzhou Joingenome Diagnostics, Hangzhou, Zhejiang Province, People’s Republic of China Abstract: MicroRNAs (miRNAs) play important roles in diverse biological processes and are emerging as key regulators of tumorigenesis and tumor progression. Among the differentially expressed miRNAs in breast cancer, miR-125b was revealed to be deregulated and associated with poor prognosis and chemoresistance in triple-negative breast cancer (TNBC), but the mechanism is still unknown. In our study, we showed downregulated expression of miR-125b in TNBC tissues and decreased migration and invasion in miR-125b-expressing Hs578T cells. MAP2K7 was then detected to be a novel target of miR-125b, and downregulation of MAP2K7 by miR-125b was similar to transient knockdown of MAP2K7 which hindered epithelial–­mesenchymal transition (EMT) of Hs578T cells. Upregulation of MAP2K7 in miR-125b-overexpressing Hs578T cells partly rescued the migration and invasion suppression of miR-125b. Furthermore, MAP2K7 was overexpressed in TNBC samples compared with normal tissues and negatively correlated with miR-125b expression. In light of these findings, miR-125b emerged as a tumor suppressor in TNBC by targeting MAP2K7 to inhibit EMT. Keywords: miR-125b, MAP2K7, TNBC, Hs578T, EMT

Fan Yang, Shixu Lyu, Siyang Dong, Yehuan Liu, Xiaohua Zhang, Ouchen Wang Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China Background: Human epidermal growth factor receptor 2 (HER-2)-enriched subtype breast cancer is associated with a more aggressive phenotype and shorter survival time. Long noncoding RNAs (LncRNAs) have essential roles in tumorigenesis and occupy a central place in cancer progression. Notably, few studies have focused on the dysregulation of LncRNAs in the HER-2-enriched subtype breast cancer. In this study, we analyzed the expression profile of LncRNAs and mRNAs in this particular subtype of breast cancer. Methods: Seven pairs of HER-2-enriched subtype breast cancer and normal tissue were sequenced. We screened out differently expressed genes and measured the correlation of the expression levels of dysregulated LncRNAs and HER-2 by Pearson’s correlation coefficient analysis. Gene ontology analysis and pathway analysis were used to understand the biological roles of these differently expressed genes. Pathway act network and coexpression network were constructed. Results: More than 1,300 LncRNAs and 2,800 mRNAs, which were significantly differently expressed, were identified. Among these LncRNAs, AFAP1-AS1 was the most dysregulated LncRNA, while ORM2 was the most dysregulated mRNA. LOC100288637 had the highest positive correlation coefficient of 0.93 with HER-2, while RPL13P5 had the highest negative correlation coefficient of -0.87. The pathway act network showed that MAPK signaling pathway, PI3K-Akt signaling pathway, metabolic pathways, cell cycle, and regulation of actin cytoskeleton were highly related with HER-2-enriched subtype breast cancer. Coexpression network recognized LINC00636, LINC01405, ADARB2-AS1, ST8SIA6-AS1, LINC00511, and DPP10-AS1 as core genes. Conclusion: These results analyze the functions of LncRNAs and provide useful information for exploring candidate therapeutic targets and new molecular biomarkers for HER-2-enriched subtype breast cancer. Keywords: ncRNA, breast cancer, gene ontology, pathway analysis, coexpression network

Shixu Lyu, Lechi Ye, Ouchen Wang, Guanli Huang, Fan Yang, Yehuan Liu, Siyang Dong Department of Surgical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China Abstract: IL-27, a new member of the IL-12 family, has been found to have antitumor effects in colorectal cancer (CRC); therefore, polymorphisms of this protein may modulate CRC carcinogenesis. So, we studied the association of single nucleotide polymorphisms of the IL-27 gene with the risk of CRC occurrence using a case–control using 600 CRC patients and matched healthy controls. The IL-27 rs153109 polymorphism was analyzed with polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. Data indicate that GG, GA, and combined A-variant genotypes (GG + GA) conferred significantly greater risk of CRC (P=0.034, 0.002, and 0.001, respectively), and that G alleles were associated with higher susceptibility to CRC (P=0.001). However, no correlation was found between the IL-27 rs153109 polymorphism and particular clinical features. In conclusion, our data demonstrated a clear association of IL-27 rs153109 polymorphism and the risk of CRC development. Keywords: IL-27, polymorphism, CRC

Yanmin Song, Qunfang Li, Lili Long, Ning Zhang, Yunhai Liu Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China Background: CD31, also called platelet endothelial cell adhesion molecule-1 (PECAM-1), is thought to play a role in the pathological mechanisms of atherosclerosis. Leu125Val polymorphism and elevated plasma levels of soluble PECAM-1 (sPECAM-1) were found to be associated with cerebral infarction. Our aim was to investigate the association between the Asn563Ser polymorphism of CD31/PECAM-1, plasma level of sPECAM-1, and the risk of atherosclerotic cerebral infarction (ACI) in the southern Han population of the People’s Republic of China.Subjects and methods: A total of 147 subjects with ACI and 114 controls were enrolled in the study. The Asn563Ser CD31/PECAM-1 polymorphism was detected using the polymerase chain reaction–restriction fragment length polymorphism method. The plasma spECAM-1 level was measured using the enzyme-linked immunosorbent assay method.Results: In this study, statistically significant differences in Asn563Ser genotype and allele distribution were found between the cases and controls (P

Guolin Hong,1,2,* Yinhuan Liu,1,* Wei Chen,3,5 Shaohuang Weng,3,5 Qicai Liu,4 Ailin Liu,3,5 Daoxin Zheng,1 Xinhua Lin,3,51Department of Laboratory Medicine, The Fuzhou Second Affiliated Hospital of Xiamen University, Fuzhou, China; 2Department of Laboratory Medicine, Medical Technology and Engineering College of Fujian Medical University, Fuzhou, China; 3Department of Pharmaceutical Analysis, Pharmacy College of Fujian Medical University, Fuzhou, China; 4Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China; 5Nano Medical Technology Research Institute, Fujian Medical University, Fuzhou, China*Guolin Hong and Yinhuan Liu contributed equally to the present studyAbstract: A highly sensitive and selective method for amplified electrochemical detection for hairpin-stem-loop structured target sequences was developed based on the temperature regulation of DNA hybrids on a sandwich-type electrochemical DNA sensor. Multistep hybridization was applied to promote the hybridization efficiency of each section of sandwich structure. The results showed that both multistep and temperature-controlling hybridization techniques were both especially made to fabricate the sensor for the tendency of internal hybridization of target gene sequences. This strategy provides significantly enhanced hybridization efficiency and sequence specificity of electrochemical detection.Keywords: sandwich-type biosensor, structured target, multistep temperature-controlling, DNA hybridization, tubercle bacillus

He Lian1, Jin Sun1, Yan Ping Yu1, Yan Hua Liu2, Wen Cao1, Yong Jun Wang1, Ying Hua Sun1, Si Ling Wang1, Zhong Gui He11School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 2Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Ningxia, People's Republic of ChinaBackground: Nowadays, many cytotoxic anticancer drugs exhibit low solubility and poor tumor selectivity, which means that the drug formulation is very important. For example, in the case of paclitaxel (PTX), Cremophor EL® (BASF, Ludwigshafen, Germany) needs to be used as a solubilizer in its clinical formulation (Taxol®, Bristol-Myers Squibb, New York, NY), although it can cause serious side effects. Nanomicellar systems are promising carriers to resolve the above problems, and the polymer chosen is the key element.Methods: In this study, a novel amphiphilic chitosan/vitamin E succinate (CS-VES) copolymer was successfully synthesized for self-assembling polymeric micelles. Proton nuclear magnetic resonance spectroscopy and infrared were used to characterize the molecular structure of the copolymer. The PTX-loaded CS-VES polymeric micelles (PTX-micelles) were characterized by dynamic light scattering, transmission electron microscopy, X-ray diffraction, and differential scanning calorimetry.Results: The critical micelle concentration of CS-VES was about 12.6 µg/mL, with the degree of amino group substitution being 20.4%. PTX-micelles were prepared by a nanoprecipitation/dispersion technique without any surfactant being involved. PTX-micelles exhibited a drug loading as high as 21.37% and an encapsulation efficiency of 81.12%, with a particle size ranging from 326.3 to 380.8 nm and a zeta potential of +20 mV. In vitro release study showed a near zero-order sustained release, with 51.06%, 50.88%, and 44.35% of the PTX in the micelles being released up to 168 hours at three drug loadings of 7.52%, 14.09%, and 21.37%, respectively. The cellular uptake experiments, conducted by confocal laser scanning microscopy, showed an enhanced cellular uptake efficiency of the CS-VES micelles in MCF-7 cells compared with Taxol. The PTX-micelles exhibited a comparable but delayed cytotoxic effect compared with Taxol against MCF-7 cells, due to the sustained-release characteristics of the nanomicelles. More interestingly, blank nanomicelles based on CS-VES copolymer demonstrated significant cytotoxicity against MCF-7 cells.Conclusion: The supramolecular micellar aggregates based on CS-VES copolymer is a promising nanocarrier and efficacy enhancer when used as an anticancer drug-delivery system.Keywords: nanomicelles, cellular uptake, cytotoxicity

A high precision calibration of the nonlinearity in the energy response of the Daya Bay Reactor Neutrino Experiment's antineutrino detectors is presented in detail. The energy nonlinearity originates from the particle-dependent light yield of the scintillator and charge-dependent electronics response. The nonlinearity model is constrained by γ calibration points from deployed and naturally occurring radioactive sources, the β spectrum from 12B decays, and a direct measurement of the electronics nonlinearity with a new flash analog-to-digital converter readout system. Less than 0.5% uncertainty in the energy nonlinearity calibration is achieved for positrons of kinetic energies greater than 1 MeV.

This Letter reports the first extraction of individual antineutrino spectra from ^{235}U and ^{239}Pu fission and an improved measurement of the prompt energy spectrum of reactor antineutrinos at Daya Bay. The analysis uses 3.5×10^{6} inverse beta-decay candidates in four near antineutrino detectors in 1958 days. The individual antineutrino spectra of the two dominant isotopes, ^{235}U and ^{239}Pu, are extracted using the evolution of the prompt spectrum as a function of the isotope fission fractions. In the energy window of 4-6 MeV, a 7% (9%) excess of events is observed for the ^{235}U (^{239}Pu) spectrum compared with the normalized Huber-Mueller model prediction. The significance of discrepancy is 4.0σ for ^{235}U spectral shape compared with the Huber-Mueller model prediction. The shape of the measured inverse beta-decay prompt energy spectrum disagrees with the prediction of the Huber-Mueller model at 5.3σ. In the energy range of 4-6 MeV, a maximal local discrepancy of 6.3σ is observed.

This work reports a precise measurement of the reactor antineutrino flux using 2.2 million inverse beta decay (IBD) events collected with the Daya Bay near detectors in 1230 days. The dominant uncertainty on the neutron detection efficiency is reduced by 56% with respect to the previous measurement through a comprehensive neutron calibration and detailed data and simulation analysis. The new average IBD yield is determined to be (5.91±0.09)×10-43 cm2/fission with total uncertainty improved by 29%. The corresponding mean fission fractions from the four main fission isotopes U235, U238, Pu239, and Pu241 are 0.564, 0.076, 0.304, and 0.056, respectively. The ratio of measured to predicted antineutrino yield is found to be 0.952±0.014±0.023 (1.001±0.015±0.027) for the Huber-Mueller (ILL-Vogel) model, where the first and second uncertainty are experimental and theoretical model uncertainty, respectively. This measurement confirms the discrepancy between the world average of reactor antineutrino flux and the Huber-Mueller model.

This Letter reports the first extraction of individual antineutrino spectra from ^{235}U and ^{239}Pu fission and an improved measurement of the prompt energy spectrum of reactor antineutrinos at Daya Bay. The analysis uses 3.5×10^{6} inverse beta-decay candidates in four near antineutrino detectors in 1958 days. The individual antineutrino spectra of the two dominant isotopes, ^{235}U and ^{239}Pu, are extracted using the evolution of the prompt spectrum as a function of the isotope fission fractions. In the energy window of 4-6 MeV, a 7% (9%) excess of events is observed for the ^{235}U (^{239}Pu) spectrum compared with the normalized Huber-Mueller model prediction. The significance of discrepancy is 4.0σ for ^{235}U spectral shape compared with the Huber-Mueller model prediction. The shape of the measured inverse beta-decay prompt energy spectrum disagrees with the prediction of the Huber-Mueller model at 5.3σ. In the energy range of 4-6 MeV, a maximal local discrepancy of 6.3σ is observed.

The Daya Bay Collaboration responds to comments posted by S. Parke and R.Zukanovich Funchal regarding our use of Delta(m^2_ee).

We present the results of structural and magnetic phase comparisons of the iron oxychalcogenides La2O2Fe2OM2(M=S,Se). Elastic neutron scattering reveals that M=S and Se have similar nuclear structures at room and low temperatures. Our neutron diffraction data reveals that both materials obtain antiferromagnetic ordering at a Néel temperature TN90.1±0.16 K and 107.2±0.06 K for M=Se and S, respectively. The magnetic arrangements for both M=S, Se compounds are obtained through Rietveld refinement. We find the order parameter exponent β to be 0.129±0.006 for M=Se and 0.133±0.007 for M=S. Each of these values is near the Ising symmetry value of 1/8. This suggests that although lattice and electronic structural modifications result from chalcogen replacement, the nature of the magnetic interactions is similar in these materials.

We report a measurement of electron antineutrino oscillation from the Daya Bay Reactor Neutrino Experiment with nearly 4 million reactor ν[over ¯]_{e} inverse β decay candidates observed over 1958 days of data collection. The installation of a flash analog-to-digital converter readout system and a special calibration campaign using different source enclosures reduce uncertainties in the absolute energy calibration to less than 0.5% for visible energies larger than 2 MeV. The uncertainty in the cosmogenic ^{9}Li and ^{8}He background is reduced from 45% to 30% in the near detectors. A detailed investigation of the spent nuclear fuel history improves its uncertainty from 100% to 30%. Analysis of the relative ν[over ¯]_{e} rates and energy spectra among detectors yields sin^{2}2θ_{13}=0.0856±0.0029 and Δm_{32}^{2}=(2.471_{-0.070}^{+0.068})×10^{-3}  eV^{2} assuming the normal hierarchy, and Δm_{32}^{2}=-(2.575_{-0.070}^{+0.068})×10^{-3}  eV^{2} assuming the inverted hierarchy.

A search for a time-varying νe signal was performed with 621 days of data acquired by the Daya Bay Reactor Neutrino Experiment over 704 calendar days. The time spectrum of the measured νe flux normalized to its prediction was analyzed with a Lomb-Scargle periodogram, which yielded no significant signal for periods ranging from 2 hours to nearly 2 years. The normalized time spectrum was also fit for a sidereal modulation under the Standard Model Extension (SME) framework to search for Lorentz and CPT violation (LV-CPTV). Limits were obtained for all six flavor pairs ēμ,ēτ, μτ, ēē,μμ and ττ by fitting them one at a time, constituting the first experimental constraints on the latter three. Daya Bay's high statistics and unique layout of multiple directions from three pairs of reactors to three experimental halls allowed the simultaneous constraint of individual SME LV-CPTV coefficients without assuming others contribute negligibly, a first for a neutrino experiment.

Signal amplification, performed by transistor amplifiers with its merit rated by the efficiency and noise characteristics, is ubiquitous in all electronic systems. Because of transistor thermal noise, an intrinsic signal amplification mechanism, impact ionization was sought after to complement the limits of transistor amplifiers. However, due to the high operation voltage (30-200 V typically), low power efficiency, limited scalability, and, above all, rapidly increasing excess noise with amplification factor, impact ionization has been out of favor for most electronic systems except for a few applications such as avalanche photodetectors and single-photon Geiger detectors. Here, we report an internal signal amplification mechanism based on the principle of the phonon-assisted cycling excitation process (CEP). Si devices using this concept show ultrahigh gain, low operation voltage, CMOS compatibility, and, above all, quantum limit noise performance that is 30 times lower than devices using impact ionization. Established on a unique physical effect of attractive properties, CEP-based devices can potentially revolutionize the fields of semiconductor electronics.

We report the experimental evidence of uncovering a photoresponse amplification mechanism in heavily doped, partially compensated silicon p-n junctions under very low bias voltage. We show that the observed photocurrent gain occurs at a bias that is more than an order of magnitude below the threshold voltage for conventional impact ionization. Moreover, contrary to the case of avalanche detectors and p-i-n diodes, the amplified photoresponse is enhanced rather than suppressed with increasing temperature. These distinctive characteristics lead us to hypothesize that the inelastic scattering between energetic electrons (holes) and the ionized impurities in the depletion and charge neutral regions of the p-n junction in a cyclic manner plays a significant role in the amplification process. Such an internal signal amplification mechanism, which occurs at much lower bias than impact ionization and favors room temperature over cryogenic temperature, makes it promising for practical device applications.

An abrupt cooling event in the North Atlantic region 8,200 years ago affected climate throughout the Northern Hemisphere. The event is well constrained in Greenland ice cores, but lack of resolution in records from other regions has challenged our understanding of the timing and nature of the associated teleconnections. Speleothem records from East Asia have suggested monsoonal changes associated with the 8,200 year event, but the nature of these changes remains controversial. Here we assess changes in East Asian precipitation during the event from a sub-annually resolved stalagmite record from central China. Using δ 18 O and Mg/Ca measurements of the speleothem carbonate, we show that climate dried significantly about 8,200 years ago. Based on our annual-layer-counted chronology, we show that the dry event lasted 150 years, with a central period of pronounced aridity that lasted 70 years. The duration and evolution of the event is indistinguishable from that observed in the Greenland ice cores. We therefore conclude that an effective and rapid atmospheric teleconnection exists between the North Atlantic and the monsoon system in warm climates similar to today's. © 2013 Macmillan Publishers Limited. All rights reserved.