Search

Although oil and gas from coaly source rocks have been widely discovered worldwide, the role of oil generated from coal measures in marine-continental coaly deposits during the Carboniferous-Permian period in the Bohai Bay Basin has long been a subject of debate. The recent discovery of a condensate reservoir in the Wumaying buried hill within the Huanghua Depression of the Bohai Bay Basin offers new potential insights into this issue. In this study, we employed organic geochemical methods to explore the possibility of the Carboniferous-Permian coal deposit being a primary source of the condensate. The distribution of light hydrocarbons and the biomarker assemblage indicate that the condensate did not undergo significant secondary alterations such as thermal cracking, gas invasion fractionation, or biodegradation. The hydrocarbon generation potential of the Carboniferous-Permian coaly source rocks suggests that they could be an important contributor to the formation of condensate. High pristine/phytane ratios (1.0-7.5), an abundant presence of benzene series, and the dominance of C 29 steranes (>50%) within the condensate could be indicative of coaly organic matter. These features are comparable to those found in coaly source rocks. Moreover, the stable carbon isotopic compositions of n -alkanes in the condensate, ranging from -26.0 to -30.0‰, correlate well with those from coaly mudstone (-25.4 to -30.0‰). This suggests that the condensate of the Wumaying buried hill may predominantly originate from the Carboniferous-Permian coaly mudstone. When integrated with the geological background, the results distinctly demonstrate that the Carboniferous-Permian coaly source rocks have significantly contributed to the formation of the condensate reservoir in the Wumaying buried hill. This provides an essential reference for future exploration of oil and gas resources derived from the carboniferous-Permian coaly source rocks in the Bohai Bay Basin., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objective: This study analysed blood donation deferral trends, reasons and demographic/lifestyle characteristics among students in Huzhou City. The aim was to understand the health status of students and reduce the deferral rate., Methods: Data on blood donation deferral among students in Huzhou City from 2018 to 2022 were collected and analysed. Deferral trends and main reasons were investigated. Using demographic and lifestyle data from 2,619 cases in 2022, a risk prediction model for deferral was constructed., Results: The deferral rate among students in Huzhou City from 2018 to 2022 was 12.60% ( p = 0.000, 95%CI: 12.14-13.06%), showing a significant increasing trend. Temporary deferral was the main reason, with alanine aminotransferase (ALT), blood pressure (BP) and haemoglobin (Hb) as the main deferral factors. ALT had a deferral rate of 5.23% (4.92-5.53%), BP 3.30% (3.06-3.55%), and Hb 2.92% (2.68-3.15%). Demographic and lifestyle characteristics in 2022 showed no significant differences between education level, household registration and deferral rate ( p > 0.05). However, age, sex, blood donation history, sleep quality, diet and mental state had variable effects on ALT, BP, and Hb deferrals ( p < 0.05). Logistic regression showed that sex, blood donation history, sleep quality, diet and mental status were independent risk factors for ALT deferral ( p < 0.05), with odds ratios (ORs) of 5.057, 2.735, 1.594, 3.679, and 1.957, respectively. Age, blood donation history, sleep quality and mental state were independent risk factors for BP deferral ( p < 0.05), with ORs of 0.256, 3.658, 6.042, and 1.812, respectively. Gender, blood donation history and diet were independent risk factors for Hb deferral ( p < 0.05), with ORs of 0.244, 0.542, and 3.103, respectively., Conclusion: Students' health problems require attention. Effective health education should improve self-health management and pre-donation health behaviour to encourage regular blood donation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Feng, Yun, Le, Zhi-guo, Hai-ying, Shu-fang, Zhen-yan, Yi-zhu, Quan and Jing-xian.)

Objective: To investigate the epidemiological characteristics and risk factors for syphilis in Huzhou City, and to provide data to support the design of more effective health counselling and screening measures for blood donors., Methods: A retrospective study was conducted to analyse the demographic characteristics and seropositivity of syphilis among blood donors from 2019 to 2021. The differences in the serological status of syphilis among different populations under different demographic factors were compared, and conditional logistic regression analysis was used to identify the risk factors for syphilis., Results: The seropositivity rate of syphilis among blood donors in Huzhou City was 133/100,000, which decreased year by year. There were significant differences in the syphilis seropositivity rate among different groups in terms of age, education level, occupation, household registration, marital status and blood donation history (P < 0.05). The multivariate logistic regression model showed that all six factors, including age, education level, occupation, household registration, marital status and blood donation history, had significant effects on syphilis infection (P < 0.01), with OR values and 95% CIs of 2. 387 (1.381-4.127), 3.607 (1.609-8.086), 2.784 (1.657-4.679), 5.074 (1.865-13.804), 11.177 (3.481-35.888), and 11.244 (3.940-32.091), respectively., Conclusion: There is room for improvement in pre-donation health counselling and screening of high-risk populations. Timely monitoring and updating of demographic data for specific high-risk populations is essential., (Copyright © 2023 Société française de transfusion sanguine (SFTS). Published by Elsevier Masson SAS. All rights reserved.)

Cytotoxic peptides derived from spider venoms have been considered as promising candidates for anticancer treatment. The novel cell penetrating peptide LVTX-8, which is a 25-residue amphipathic α-helical peptide isolated from spider Lycosa vittata, exhibited potent cytotoxicity and is a potential precursor for further anticancer drug development. Nevertheless, LVTX-8 may be easily degraded by multiple proteases, inducing the proteolytic stability problem and short half-life. In this study, ten LVTX-8-based analogs were rationally designed and the efficient manual synthetic method was established by the DIC/Oxyma based condensation system. The cytotoxicity of synthetic peptides was systematically evaluated against seven cancer cell lines. Seven of the derived peptides exhibited high cytotoxicity towards tested cancer in vitro, which was better than or comparable to that of natural LVTX-8. In particular, both N-acetyl and C-hydrazide modified LVTX-8 (825) and the conjugate methotrexate (MTX)-GFLG-LVTX-8 (827) possessed more durable anticancer efficiency, higher proteolytic stability, as well as lower hemolysis. Finally, we confirmed that LVTX-8 could disrupt the integrity of cell membrane, target the mitochondria and reduce the mitochondrial membrane potential to induce the cell death. Taken together, the structural modifications were conducted on LVTX-8 for the first time and the stability significantly improved derivatives 825 and 827 may provide useful references for the modifications of cytotoxic peptides., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A total of 58 (eight known and 50 new) species of the subgenus Stegana (Steganina) from China were surveyed and (re)described: S. (S.) bacilla Chen & Aotsuka, 2004, S. (S.) belokobylskiji Sidorenko, 1997, S. (S.) hirticeps Wang, Gao, & Chen, 2013, S. (S.) izu Sidorenko, 1997, S. (S.) kanmiyai Okada & Sidorenko, 1992, S. (S.) masanoritodai Okada & Sidorenko, 1992, S. (S.) maymyo Sidorenko, 1997, stat. rev., S. (S.) nigripes Zhang & Chen, 2015, S. (S.) alafoliacea Zhang & Chen, sp. nov., S. (S.) baoxing Li & Chen, sp. nov., S. (S.) bibarbata Li & Chen, sp. nov., S. (S.) bimai Cui & Chen, sp. nov., S. (S.) cinereipecta Zhang & Chen, sp. nov., S. (S.) cardua Cui & Chen, sp. nov., S. (S.) cordhirsuta Wang & Chen, sp. nov., S. (S.) cornuta Li & Chen, sp. nov., S. (S.) cucullata Li & Chen, sp. nov., S. (S.) cultella Cui & Chen, sp. nov., S. (S.) curvitabulata Cui & Chen, sp. nov., S. (S.) daiya Cui & Chen, sp. nov., S. (S.) dendrophila Zhang & Chen, sp. nov., S. (S.) flabella Li & Chen, sp. nov., S. (S.) flavipes Li & Chen, sp. nov., S. (S.) formosa Zhang & Chen, sp. nov., S. (S.) fusca Li & Chen, sp. nov., S. (S.) fuscipes Li & Chen, sp. nov., S. (S.) glaucopalpula Cui & Chen, sp. nov., S. (S.) haba Zhang & Chen, sp. nov., S. (S.) hirticlavata Cui & Chen, sp. nov., S. (S.) iaspidea Zhang & Chen, sp. nov., S. (S.) idiasta Cui & Chen, sp. nov., S. (S.) kanda Cui & Chen, sp. nov., S. (S.) labao Li & Chen, sp. nov., S. (S.) lancang Li & Chen, sp. nov., S. (S.) latifoliacea Wang & Chen, sp. nov., S. (S.) liusanjieae Li & Chen, sp. nov., S. (S.) magniflava Cui & Chen, sp. nov., S. (S.) mailangang Li & Chen, sp. nov., S. (S.) marenubila Cui & Chen, sp. nov., S. (S.) menghai Zhang & Chen, sp. nov., S. (S.) menglian Li & Chen, sp. nov., S. (S.) minutiflava Li & Chen, sp. nov., S. (S.) multiprocera Li & Chen, sp. nov., S. (S.) nayun Li & Chen, sp. nov., S. (S.) nigridentata Wang & Chen, sp. nov., S. (S.) nigripalpula Cui & Chen, sp. nov., S. (S.) otphylla Cui & Chen, sp. nov., S. (S.) radiciflava Zhang & Chen, sp. nov., S. (S.) rava Cui & Chen, sp. nov., S. (S.) sciophila Li & Chen, sp. nov., S. (S.) septencolorata Li & Chen, sp. nov., S. (S.) serrata Zhang & Chen, sp. nov., S. (S.) silvestrella Zhang & Chen, sp. nov., S. (S.) simola Cui & Chen, sp. nov., S. (S.) yani Li & Chen, sp. nov., S. (S.) yixiang Zhang & Chen, sp. nov., S. (S.) zaduo Cui & Chen, sp. nov., and S. (S.) zhuoma Cui & Chen, sp. nov. We also provided a complete list of Chinese Steganina species together with their geographical distributions. In addition, the majority of currently available DNA barcode (partial sequence of the mitochondrial cytochrome c oxidase subunit I (COI) gene) sequences of this subgenus (435 sequences of 102 spp.) were employed in a molecular analysis for species delimitation. Taken together, morphology- and molecular-based species delimitation results reached a consensus for an overwhelming majority of these Steganina species (98 of 102 spp.).

Objectives: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a prominent public health issue. Furthermore, the prognosis of eosinophilic CRSwNP is poor, with a high recurrence rate. The underlying molecular mechanisms of eosinophilic CRSwNP remain unclear. Therefore, in this study, we sought to determine the crucial genes underlying eosinophil infiltration in eosinophilic CRSwNP pathogenesis., Methods: We used the Gene Expression Omnibus database (GEO) (GSE36830 and GSE23552 datasets) to mine gene expression profiles of CRSwNP patients and normal subjects. Differentially expressed genes (DEGs) between normal and CRSwNP tissues were identified and subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses. Co-expression networks were established using a weighted gene co-expression network analysis (WGCNA) and single-sample gene set enrichment analysis (GSEA). Protein-protein interaction networks were developed to detect functional protein modules. Based on the common DEGs, candidate miRNAs and related lncRNAs were predicted using the mirTarBase and StarBase databases. Finally, we generated immune cell subtypes of CRSwNP., Results: A total of 146 DEGs were identified. Of these, 131 genes were upregulated, whereas 15 were downregulated. GO analysis indicated that DEGs primarily participated in leukocyte chemotaxis and migration as well as cell chemotaxis. KEGG pathway analysis suggested that DEGs participated in the interactions between cytokines and viral proteins, osteoclast differentiation, and cytokine-cytokine receptor interactions. Real-time quantitative polymerase chain reaction analysis showed that Complement C5a Receptor 1 (C5AR1), C-C Motif Chemokine Receptor 3 (CCR3), Complement C3a Receptor 1 (C3AR1), and C-C Motif Chemokine Ligand 13 (CCL13) expression levels were significantly upregulated in nasal polyps, whereas C-C Motif Chemokine Ligand 4 (CCL4) expression levels were significantly downregulated., Conclusions: The candidate genes identified in this study may influence the activation and accumulation of eosinophils, cell chemotaxis, and inflammatory responses, thereby potentially representing molecular targets for future studies of CRSwNP., Competing Interests: None., (AJTR Copyright © 2023.)

Background and Objectives: Human epidermal cell sheet (human-ECS) is a feasible treatment option for wound injury. Traditionally, researchers often use murine 3T3 fibroblast cells as feeder layer to support human epidermal cell sheet grafts, thus increase risk to deliver animal-borne infection. To overcome the potential risks involved with xenotransplantation, we develop human foreskin fibroblast cell as feeder layer culture system and investigate the effects of human-ECS on second-degree burn wound healing in mini-pig in order to develop more effective and safer therapies to enhance wound healing in human., Materials and Methods: Human epidermal keratinocytes and fibroblasts were isolated from foreskin tissue and were co-cultured to manufacture human-ECS. The cell morphology was monitored with phase-contrast microscopy, the stem cell markers were assessed by flow cytometry, and by colony-forming efficiency (CFE) assay. The structure of human-ECS was observed by hematoxylin and eosin staining. Expression of cytokines in human-ECS was confirmed by enzyme-linked immunosorbent assay. Second-degree burn wounds were created on the dorsal of miniature pig to evaluate the effect of oil gauze, oil gauze combined with commercial epidermal growth factor (EGF) cream, and oil gauze combined with human-ECS. Wound healing rate, histological examination, and Masson staining were measured to observe the wound repair efficacy. Real-time PCR and Western blot were utilized to detect the expression level of EGF and interleukin 6 (IL-6)., Results: Stratified human-ECS with 6-7 layers of epidermal cells was successfully cultivated with human-derived feeder cells, in which epidermal cell highly expressed CD49f and CFE was 3% ± 0.45%. Application of human-ECS induced a higher wound healing rate than commerical EGF cream and oil gauze control. The expression of EGF in human-ECS group was higher than those in the other groups; however, the expression of IL-6 was significantly decreased at day 14 by human-ECS treatment group., Conclusions: Human-derived feeder cells are suitable for cultivation of human-ECS, avoiding pathogen transmission. Human-ECS could enhance second-degree burn wound healing, and its promoting effect involved secreting a variety of cytokines to regulate tissue reparative process., (© 2023 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Focusing on Hangzhou, a famous tourist city in China, in this study, four regression models were constructed through four items of tourist loyalty to investigate the influence of tourist perceptions and characteristics on male and female tourist loyalty to shared bicycles. A questionnaire survey and ordered logistic regression model techniques were used. Survey data from 467 tourists indicated that there were significant differences between male and female tourists. For male tourists, their willingness to reuse shared bicycles (Models 1 and 2) was positively correlated with ease of access to cycles, environmental awareness, psychological benefit, and management provision; however, their willingness to recommend shared bicycles (Models 3 and 4) was only affected by environmental awareness, psychological benefit, and management provision. Among female tourists, willingness to reuse shared bicycles (Models 1 and 2) was affected by ease of access to cycles, environmental awareness, and rule adherence, while their willingness to recommend shared bicycles (Models 3 and 4) was affected by ease of access to cycles, environmental awareness, psychological benefit, and managerial provision. In addition, female tourists' socio-demographic and behavioral characteristics had a significant impact on their loyalty, among which length of stay in Hangzhou and education were significant in the four regression models, and number of visits to Hangzhou had a positive impact on female tourists' willingness to reuse (Models 1 and 2). In addition, female tourists who used Hellobike had higher willingness to reuse and recommend than those who used Mobike. For male tourists, only length of stay in Hangzhou had a significant impact on their reuse intention (Model 2). The current study extends the theory of attribution to explore the factors which may affect tourist's loyalty to bicycle-sharing from the perspectives of tourists' perceptions. It will provide further support to decision makers in the development of new shared-bicycle systems at Chinese tourist destinations, with the aim of strengthening tourist loyalty to shared-bicycle programs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Xiong, Li, Wang, Yu and Jin.)

High urban temperatures affect city livability and may be harmful for inhabitants. Analyzing spatial and temporal differences in surface temperature and the thermal impact of urban morphological heterogeneity can promote strategies to improve the insulation of the urban thermal environment. Therefore, we analyzed the diurnal variation of land surface temperature (LST) and seasonal differences in the Fifth Ring Road area of Beijing from the perspective of the Local Climate Zone (LCZ) using latest ECOSTRESS data. We used ECOSTRESS LST data with a resolution of 70 m to accurately interpret the effects of urban morphology on the local climate. The study area was dominated by the LCZ9 type (sparse low-rise buildings) and natural LCZ types, such as LCZA/B (woodland), LCZD (grassland), and LCZG (water body), mainly including park landscapes. There were significant differences in LST observed in different seasons as well as day and night. During daytime, LST was ranked as follows: summer > spring > autumn > winter. During night-time, it was ranked as follows: summer > autumn > spring > winter. All data indicated that the highest and lowest LST was observed in summer and winter, respectively. LST was consistent with LCZ in terms of spatial distribution. Overall, the LST of each LCZ during daytime was higher than that of night-time during different seasons (except winter), and the average LST of each LCZ during the diurnal period in summer was higher than that of other seasons. The LST of each LCZ during daytime in winter was lower than that of the corresponding night-time, which indicates that it is colder in the daytime during winter. The results presented herein can facilitate improved analysis of spatial and temporal differences in surface temperature in urban areas, leading to the development of strategies aimed at improving livability and public health in cities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shi, Yang, Wang, Lv, Wang, Xiao and Xia.)

This study aimed to examine the effects of COVID-19 risk perception on negative destination image and self-protection behavior, and the resultant effects on tourist satisfaction. Hence, this study applied a continuous interpretive mixed-method design combining quantitative and qualitative analyses. A quantitative survey ( n = 486) in the cities of Ningbo, Huangshan, and Chengdu, China, and 19 qualitative interviews were conducted online. The results of the quantitative study show that: (1) Risk perception and negative destination image are antecedent variables influencing tourist satisfaction, and (2) there are significant positive correlations between risk perception and negative destination image, risk perception and tourist self-protection behavior, and negative destination image and tourist self-protection behavior. Moreover, (3) negative destination image had a partial mediating effect between risk perception and satisfaction. Furthermore, to supplement the research data and expand the quantitative findings, this study further examined whether the above variables are related to tourist satisfaction, through in-depth interviews with tourists. The findings showed that COVID-19 risk perception, negative destination image, and self-protection behavior all affect tourist satisfaction. The findings provide valuable crisis management suggestions for the government and should contribute to the efforts of tourist destinations to build a healthy and safe image, thereby contributing to the sustainable development of tourism industries in the post-epidemic era., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Liu, Wang, Wang and Wang.)

Conflict management in PAs (Protected Areas) is becoming increasingly important in the context of the rapid development of nature-based tourism. Literature proposes the Index of Conflict tendency between Tourism development and ecological Protection (ICTP) to analyze the tendency of conflict from a spatial perspective, but this index does not consider the factor of seasonality which is important in tourism. The current study considers seasonality and proposes the CVD (Coverage- Variation- Duration) framework to conduct a spatio-temporal analysis of the ICTP. The applied research based on the case of China's V-PAs (a specific category of PAs) reflects that the CVD framework can describe the spatial distribution of the ICTP from a seasonal perspective. The study finds that, among V-PAs in China, 42.16% of the areas with high ICTP of V-PAs have obvious seasonal variations, which shows that PAs conflict management must incorporate the factor of seasonality. The study also shows that 8.98% of V-PAs have large-scale coverage of areas with high ICTP, revealing priorities for conflict management. 3.96% of V-PAs have large-scale coverage of areas with high ICTP showing seasonal changes. Management in these areas should pay attention to seasonal changes to become more effective. The CVD framework proposed in this paper is operable and extendable and can provide analytical tools for PAs conflict management, and promote ecological protection and more sustainable tourism development in PAs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Necrotizing enterocolitis, a devastating gastrointestinal disease with high mortality, poses great threats to global health. Therefore, we conducted this study to explore the role of ANGPT2, as well as the potential mechanism, in necrotizing enterocolitis. IEC-6 cells were stimulated with lipopolysaccharide (LPS) to induce necrotizing enterocolitis model in vitro. The expression of ANGPT2 was measured by RT-qPCR. The cell viability was detected using CCK-8. Besides, the expressions of endoplasmic reticulum (ER) stress-related proteins, Notch signaling pathway-related proteins and tight junction proteins were checked by western blot. The apoptosis and inflammatory response were detected by TUNEL and ELISA, respectively. Moreover, with the adoption of TEER, the cell monolayer permeability was detected. The results showed that ANGPT2 expression was greatly increased after LPS induction. In addition, ANGPT2 knockdown significantly decreased the apoptosis, inflammatory response, barrier dysfunction and endoplasmic reticulum stress of LPS-induced IEC-6 cells. What is more, ANGPT2 knockdown could block Notch signaling pathway. Additionally, with the treatment of Jagged-1, the protective effect of ANGPT2 knockdown on LPS-induced intestinal injury was partly abolished. To sum up, silencing ANGPT2 could improve LPS-induced inflammation, barrier dysfunction and ER stress of intestinal epithelial cells via blocking Notch signaling pathway.

Background: The sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) channel is a target key mediator of brain edema. Sulfonylureas (SFUs) are blockers of the SUR1-TRPM4 channel. We made two assessments for the pretreatment of SFUs: (1) whether it associates with lower perihematomal edema (PHE) and (2) whether it associates with improved clinical outcomes in diabetic patients who have acute basal ganglia hemorrhage. Methods: This retrospective case-control study was conducted in diabetic adults receiving regular SFUs before the onset of intracerebral hemorrhage (ICH). All of the patients received the clinical diagnosis of spontaneous basal ganglia hemorrhage. The diagnosis was confirmed by a CT scan within 7 days after hemorrhage. For each case, we selected two matched controls with basal ganglia hemorrhage based on admission time (≤5 years) and age differences (≤5 years), with the same gender and similar hematoma volume. The primary outcome was PHE volume, and the secondary outcomes were relative PHE (rPHE), functional independence according to modified Rankin Scale score and Barthel Index at discharge, and death rate in the hospital. Results: A total of 27 patients (nine cases and 18 matched controls), admitted between January 1, 2009 and October 31, 2018, were included in our study. There was no significant association between SFU patients and non-SFU patients on PHE volumes [15.4 (7.4-50.2 ml) vs. 8.0 (3.1-22.1) ml, p = 0.100]. Compared to non-SFU patients, the SFU patients had significantly lower rPHE [0.8 (0.7-1.3) vs. 1.5 (1.2-1.9), p = 0.006]. After we adjusted the confounding factors, we found that sulfonylureas can significantly reduce both PHE volume (regression coefficient: -13.607, 95% CI: -26.185 to -1.029, p = 0.035) and rPHE (regression coefficient: -0.566, 95% CI: -0.971 to -0.161, p = 0.009). However, we found no significant improvement in clinical outcomes at discharge, in the event of pretreatment of SFUs before the onset of ICH, even after we adjusted the confounding factors. Conclusion: For diabetic patients with acute basal ganglia hemorrhage, pretreatment of sulfonylureas may associate with lower PHE and relative PHE on admission. No significant effect was found on the clinical outcomes when the patients were discharged. Future studies are needed to assess the potential clinical benefits using sulfonylureas for ICH patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jingjing, Jingjing, Bo, Le, Jingya, Dong, Fang and Wen.)

The mutton flavor is affected by cooking water significantly, and the flavor of mutton is delicious and widely loved by consumers through an extremely simple processing in northwest China, such as Inner Mongolia, Ningxia, and Xinjiang. The flavor shows obvious changes if get out of these areas even use the same raw meat, which may be caused by different cooking water. To determine whether and how the cooking water affect the mutton soup flavor, the elements in water, the flavor was studied by inductively coupled plasma mass spectrometry (ICP-MS), amino acid analyzer, and thermal desorption (TDS)-gas chromatography-mass spectrometry (GC-MS). Specifically, three water samples from different sources, Ningxia (NXW), Beijing (BJW), and ultrapure water from the laboratory (PUW), were used for cooking with Tan sheep's ribs to get different mutton soups. The inductively coupled plasma mass spectrometry (ICP-MS) results showed that the elements and the concentration of solutes in different water sources were significantly different. The NXW batch had the highest Na, Mg, K, and Sr concentrations, and Na in NXW water reached to 50.60 mg/L, which existed as Na + , significantly ( p  < .05) higher than BJW (8.63 mg/L) and PUW, which were important to the flavor of mutton soup. The PUW batch had the highest content of free amino acids, and the content of glutamic acid (Glu) reached to 17.89 μg/mL. The NXW batch had the highest content of taste nucleotides, and the content of 5´-IMP reached to 68.68 μg/ml. The volatiles of the three batches had significant differences, and only 40 volatiles were detected in all batches. Further flavor studies using electronic nose and electronic tongue showed significant differences in overall aroma and overall taste, especially bitterness, saltiness, and astringency. The results could provide a basis for improving the flavor quality for the mutton soup., Competing Interests: The authors declare that they have no conflicts of interest., (© 2021 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Cadmium (Cd) is a biologically non-essential and toxic heavy metal leaking to the environment via natural emission or anthropogenic activities, thereby contaminating crops and threatening human health. Metallothioneins (MTs) are a group of metal-binding proteins playing critical roles in metal allocation and homeostasis. In this study, we identified a novel function of OsMT1e from rice plants. OsMT1e was dominantly expressed in roots at all developmental stages and, to less extent, expressed in leaves at vegetative and seed filling stages. OsMT1e was mainly targeted to the nucleus and substantially induced by Cd exposure. Expression of OsMT1e in a yeast Cd-sensitive strain ycf1 conferred cellular tolerance to Cd, even though the ycf1 + OsMT1e cells accumulated more Cd than the control cells (ycf1 + pYES2). Both transgenic rice overexpressing (OX) and repressing OsMT1e by RNA interference (RNAi) were developed. Phenotypic analysis revealed that OsMT1e overexpression enhanced the rice growth concerning the increased shoot or root elongation, dry weight and chlorophyll contents, whereas the RNAi lines displayed a sensitive growth phenotype compared to wild-type. Assessment with 0.5, 2 and 10 μM Cd for two weeks revealed that the RNAi lines accumulated less Cd, while the OX lines had an increased Cd accumulation in root and shoot tissues. The contrasting Cd accumulation phenotypes between the OX and RNAi lines were further confirmed by a long-term study with 0.5 μM Cd for one month. Overall, the study unveiled a new function of OsMT1e in rice, which can be potentially used for engineering genotypes for phytoremediation or minimizing Cd in rice crops., Competing Interests: Declaration of competing interest The authors declare no any conflict of interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest.

As a neurological disorder, epilepsy has affected over 65 million people all over the world because of the unforeseeable seizures it might cause. However, in-depth understandings of the pathogenesis of epilepsy and effective treatments for the disease are still lacked. Recent discoveries suggest that autophagy, as an endogenous self-cleansing pathway in mammals, might be involved in the onset of epilepsy. Our study assumes that a non-histone DNA binding protein, high mobility group box-1 (HMGB1), formerly considered as a crucial inflammatory factor, may mediate the autophagy of neurons in epileptic mouse brain. To verify this hypothesis, pilocarpine induced epilepsy mouse model was constructed. The mice were treated with HMGB1 antibody for 4 weeks after the initial epileptic seizure. Behavioral test results suggested a recovery of learning ability and memory in epileptic mice when treated with HMGB1 antibody. Pathological changes in hippocampus were inspected under microscopes and hippocampus damages caused by seizures in mouse with epilepsy such as increased intracellular space were alleviated by HMGB1 antibody treatment. Moreover, the expressions of the proteins involved in autophagy pathways were detected by immunofluorescence staining and western blot. microtubule-associated protein 1A/1B-light chain 3 (LC3), Beclin 1, autophagy protein-5 (ATG5), and ATG7 levels were significantly decreased by HMGB1 antibody while the level of p62 was increased. TdT-mediated dUTP Nick-End Labeling (TUNEL) illustrated that cell apoptosis induced by seizures in hippocampus was mitigated by HMGB1 antibody. In conclusion, we propose that HMGB1 may induce increased autophagy in epilepsy mouse model., Competing Interests: Declaration of Competing Interest We would like to declare on behalf of our co-authors that the work entitled “High mobility group box 1 antibody represses autophagy and alleviates hippocampus damage in pilocarpine-induced mouse epilepsy model” has not been published previously, and not under consideration for publication elsewhere, in whole or in part. There is no interest conflict in this study., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Spinal cord injury (SCI) can lead to severe motor and sensory dysfunction, yet there are no effective therapies currently due to the failure of reconstructing the interruption of the neuroanatomical circuit. While neural stem cell (NSC) transplantation has been considered a potential strategy to repair the neural circuit after SCI, the efficacy of this strategy remains unproven. The main reason is that most of the transplanted NSC differentiates into astrocyte rather than neuron in the microenvironment of SCI. Our results demonstrated that Wnt4 significantly promotes the differentiation of NSC into neuron by activating both β-catenin and MAPK/JNK pathways and suppressing the activation of Notch signaling, which is acknowledged as prevention of NSC differentiation into neuron, through downregulating NICD expression, translocating and preventing the combination of NICD and RbpJ in nucleus. In addition, Wnt4 rescues the negative effect of Jagged, the ligand of Notch signaling, to promote neuronal differentiation. Moreover, in vivo study, transplantation of Wnt4-modified NSC efficaciously repairs the injured spinal cord and recovers the motor function of hind limbs after SCI. This study sheds new light into mechanisms that Wnt4-modified NSC transplantation is sufficient to repair the injured spinal cord and recover the motor dysfunction after SCI., (© 2019 Federation of American Societies for Experimental Biology.)

Increasing hotel/restaurant/café (HORECA) food consumption (HFC) has become one of the most prominent features of food consumption transformation under the background of rapid urbanization in China. Combining direct-weighing data (using 11,883 dishes in 164 restaurants) and literature data, this study, for the first time, quantitatively calculated the amount of HFC and its ecological footprint (EF) in China in 2002 and 2015 to depict the environmental effects of this transformation. The results indicated that per capita HFC tripled from 320 g/cap/meal in 2002 to 852 g/cap/meal in 2015, representing an average annual growth rate of 13%. In addition, by scaling up the HFC in 31 provinces/municipalities/autonomous regions to the national scale, HFC in China increased by 12,612 tons from 2002 to 2015. Finally, the total EF in the HORECA sector increased nearly 33 times (or 44,440 global ha), from 1348 global ha in 2002 to 45,788 global ha in 2015. The EF of Guangdong increased the most, surpassing 4000 global ha in 2015. These findings provide a scientific basis to support improved food resource spatial allocation and mitigation of regional resource pressure to achieve sustainable consumption under the current background of rapid urbanization in China., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Abdominal obesity and wall thickness of the central arteries have been associated with higher risk of cardiovascular disease. Despite the higher burden of overweight and cardiovascular disease among African Americans, limited data are available on the association of abdominal obesity with aortic wall thickness in African Americans. We assessed the cross-sectional and the longitudinal associations of abdominal obesity with aortic intima-media thickness (aIMT) in a cohort of African Americans from the Jackson Heart Study., Methods: Data on aIMT and repeated measures of waist circumference (WC) and waist to height ratio from 1,572 participants, as well as on abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and aIMT from 1,223 participants, were analyzed. aIMT was measured at proximal ascending aorta (PA-aIMT), proximal descending aorta (PD-aIMT), and distal aorta (bifurcation) using cardiac magnetic resonance. SAT and VAT were measured using computerized tomography., Results: WC and WHtR were longitudinally associated with PA-aIMT and PD-aIMT; SAT and VAT were associated with PA-aIMT only. Only WC was associated with distal aIMT., Conclusions: Abdominal obesity measures are associated with increased proximal aIMT in adult African Americans. Only WC is associated with wall thickness in all three segments of the aorta., (© 2019 The Obesity Society.)

Objective: To analyse the characteristics of the revision cochlear implantation （RCI）patients，the cause of the cochlear malfunction，and the choice of RCI operative approach. Method: A total of 39 patients with RCI were enrolled in this study. The cochlear use time, cause of failure and reoperation procedure are recorded and analyzed retrospectively. Result: There were 39 patients accepted cochlear reoperation，the ages ranges from 1 to 28，average age was 7.8 years, median age was 5 years old. The cochlear use time ranges from 1 month to 7 years，average was 2.2 years, median time was 1 year. Thirty-seven patients underwent RCI,30 cases right side and 7 cases left side. The reason of RCI contains device failure (28 cases)，infection (5 cases)，incorrect electrode implantation (3 cases)，facial nerve stimulation (2 cases)，and electrode prolapse (1 case).The choice of RCI procedure was dependent on the first operation procedure,contains facial nerve recess approach (35 cases) and mastoid approach (2 cases).Contralateral implantation was performed in 5 cases, the rest were ipsilateral. Conclusion: RCI has a variety causes and the common reason is trauma and device failure，the RCI should be completed as early as possible to avoid the ossified cochlear and hearing or speech stagnation，the electrode implantation through previous approach is the best method., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Gibberellin, a plant growth regulator, is widely used to increase the shelf life and quality of fruits and vegetables. In this study, human semen samples were exposed to different concentrations of gibberellin, which reduced spermatozoa motility in vitro . Gibberellin exposure also increased levels of reactive oxygen species and the protein levels of apoptosis markers in human sperm. Gibberellin inhibited the activity of Na + /K + -adenosine triphosphatase (ATPase) and Ca 2+ -ATPase, which maintain the stability of ions inside and outside the membranes of spermatozoa. Moreover, gibberellin exposure suppressed adenosine triphosphate production and reduced the protein levels of adenosine triphosphate synthases, which may have induced the protein expression of adenosine 5'-monophosphate-activated protein kinase (AMPK) and its phosphorylated form. These results suggest that gibberellin reduces human sperm motility in vitro by increasing reactive oxygen species levels and reducing ATPase activity, which may upregulate AMPK and consequently reduce the fertilization potential of spermatozoa.

A facile and feasible photoelectrochemical (PEC) immunoassay based on plasmon-enhanced energy transfer between gold nanoparticles (AuNPs) and CdS quantum dots (QDs)/g-C 3 N 4 nanosheets was developed for the ultrasensitive detection of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ). To construct such a sensing platform, the immunosensor was prepared by immobilizing Lp-PLA 2 on a CdS QDs/g-C 3 N 4 -modified electrode. A competitive-type immunoreaction was utilized for Lp-PLA 2 detection, with AuNP-labeled anti-Lp-PLA 2 antibody used as the competitor. Introducing AuNPs with the specific antibody for the antigen target Lp-PLA 2 led to heavy quenching of the photocurrent of CdS QDs/g-C 3 N 4 due to the plasmon-enhanced energy transfer between AuNPs and CdS QDs. The quenching efficiency decreased with increasing target Lp-PLA 2 concentration. Under optimal conditions, the PEC immunosensor presented a good photocurrent response to the target Lp-PLA 2 in the dynamic linear range of 0.01-300 ng mL -1 , with a low detection limit of 5.3 pg mL -1 . Other biomarkers and natural enzymes did not interfere with response of this system. The reproducibility and accuracy of this method for the analysis of human serum specimens were evaluated, and the results given by the method developed here were found to closely correspond to the results obtained with commercial Lp-PLA 2 ELISA kits. Importantly, this protocol offers promise for the development of exciton-plasmon interaction-based PEC detection systems. Graphical abstract ᅟ.

Objective: To evaluate the operation safety, hearing as well as speech results of cochlear implantation that were applied in patients over 75 years old. Method: A series of patients who were diagnosed as severe to profound sensorineural hearing loss and received cochlear implantation were admitted. The clinical data and rehabilitation effects of the patients who were over 75 years old were summarized. Result: During this period, in which 7(1.31%) patients aged over 75 at implantation. The age ranged from 75 to 88, with an average of 80 years old. All of the 7 patients received a safe operation under general anesthesia. No major or minor complications happened related to surgery and anesthesia. Only one 84 years old male patient suffered from a transient mild balance problem. Follow up were carried out regularly, ranging from 4-40 months. The average of categories of auditory performance and speech intelligibility rating is 4 and 5 respectively. Conclusion: The cochlear implant surgery and general anesthesia are safe for patients over 75 years old, and these patients can benefit from cochlear implantation., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Recent studies indicate that metabolic disorders such as diabetes and obesity are a major risk factor of psychiatric diseases. This relationship opens the opportunity to develop new antidepressant drugs by repurposing antidiabetic drugs. Previous research has demonstrated that GLP-1 analogs are neuroprotective in several neurological disease models including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In addition, the GLP-1 analog liraglutide has been shown to promote neurogenesis, which is seen to play important roles in memory formation and cognitive and emotional processing. However, whether liraglutide is an effective antidepressant remains unknown. Therefore, we tested this hypothesis in the depression model of chronic administration of corticosterone (CORT) in mice and treated the animals daily with liraglutide (5 or 20 nmol/kg ip.) to assess its therapeutic potential as an antidepressant. Behavioral studies showed that liraglutide administration attenuated depressive- and anxiety- like behaviors in this depression mouse model, and attenuated the hyperactivity induced by the stress hormone. Additionally, liraglutide treatment protected synaptic plasticity and reversed the suppression of hippocampal long-term potentiation induced by CORT administration, demonstrating synaptic protective effects of liraglutide. We also found that liraglutide treatment increased the cell density of immature neurons in the subgranular dentate gyrus region of the hippocampus. In addition, liraglutide prevented the CORT induced impairments and simultaneously increased the level of phosphorylated GSK3β in the hippocampus, which may be instrumental in the anti-depressant activity of liraglutide treatment. Taken together, liraglutide has the potential to act as a therapeutic treatment of depression., (Copyright © 2018. Published by Elsevier B.V.)

More than 100 counties, mainly in southwest China, report incidence rates of leprosy >1/100,000. The current study analysed the epidemiology of leprosy in southwest China to improve our understanding of the transmission pattern and improve control programs. 207 counties were selected in southwest China. Leprosy patients and their household contacts were recruited. The data from the medical interview and the serological antileprosy antibody of the leprosy patients were analysed. A total of 2,353 new cases of leprosy were interviewed. The distribution of leprosy patients was partly associated with local natural and economic conditions, especially several pocket areas. A total of 53 from 6643 household contacts developed leprosy, and the incidence rate of leprosy in the household contacts was 364/100,000 person-years. We found that NDO-BSA attained higher positive rates than MMP-II and LID-1 regardless of clinical types, disability and infection time in leprosy patients. By means of combination of antigens, 88.4% patients of multibacillary leprosy were detected, in contrast to 59.9% in paucibacillary leprosy. Household contacts should be given close attention for the early diagnosis, disruption of disease transmission and precise control. Applications of serology for multi-antigens were recommended for effective coverage and monitoring in leprosy control.

Objective: To investigate the possible causes of non dry ear after canal wall down mastoidectomy(CWD). Method: Clinical data of 42 patients undergoing revision CWD in our hospital were analyzed retrospectively,which included history,symptoms,signs,audiological examination,imaging examination, intraoperative findings and postoperative follow-up.All patients underwent CWD and tympanoplasty under general anesthesia. Result: Twenty-six cases were insufficient opened of sinodural angle,36 cases remained mastoid air cell(9 cases is mastoid tip air cell remained),13 cases were inadequate exposured of anterior epitympanic recess, 23 cases were inadequate exposured of posterior tympanum, 25 cases had high facial ridge, posterior facial nerve and labyrinth air cell were 5 cases,3 cases had granulation in round window, 5 cases had dysfunctional eustachian tube, 32 cases had narrow external acoustic meatus. During 3 months,6 months and 1 year follow-up, all 42 cases patients under revision CWD presented with dry ears. Conclusion: Insufficient opened of sinodural angle and mastoid air cell,inadequate exposured of anterior epitympanic recess and posterior tympanum, high facial ridge, narrow external acoustic meatus are all the possible causes of no-dry ear after CWD; As the location of concealment, posterior facial nerve and labyrinth air cell are difficult to clean. The dressing cavity do not be cleaned in time after operation is also the underlying cause of postoperative non-dry ear., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To summarize the clinical characteristics and therapeutic experiences of the middle ear teratoma in infants. Methods: Three cases of middle ear teratoma, from 2012-2015 in Beijing Friendship Hospital were analyzed. Results: The three cases all developed slowly and presented unilateral otorrhea and hearing loss. Otoscopy showed the granulation tissue in the external ear canal. Audiological changes varied according to the degree of severity. Imaging features showed the pocket-like occupancy lesions in the Eustachian tube area. The temporal bone CT showed mass with soft tissue density usually involved in the mastoid and tympanic cavity. MRI showed mixed signal intense on both T1 and T2 weighted imaging. All the three cases received neoplasm resection of the middle ear. Only one case received tympanoplasty surgery at the same time. And all the pathology results displayed mature teratoma. The follow-up time was 17 to 54 months. MRI showed complete removal of the tumor. Conclusions: Teratoma are rare in the head and neck neoplasm. When the infants suffer from the unilateral otorrhea, hearing loss, and granulation tissue formed in the external ear canal, it should be vigilant for teratoma. The differential diagnosis is middle ear cholesteatoma, congenital first branchial cyst or fistula, and middle ear carcinoma. Temporal bone CT combined with MRI could improve the accuracy of diagnosis. It should be totally resection as soon as possible if there is no contraindication. Postoperative follow-up and imaging examination are necessary to eliminate tumor recurrence.

Objective: To observe the clinical effect on the treatment of intractable tympanitis with reconstruction of external auditory canal wall. Method: Five cases underwent radical removel of residual lesion and reconsruction of external auditory posterior canal wall using hydroxyapatite ceramic wall with transferred pedicle temporalis fascia covering on it were analyzed. The implement of ossicular chain reconstruction depends on the probing for tympanic cavity intraoperatively. Periodic review were conducted in the 1st, 3rd, 6th, 12th month after surgery. Result: All 5 cases gained dryears within 3 months after surgery, in which hearing of 3 cases improved and ABG were within 20 dB. 1 cases showed no improvement compared to preoperation, and 1 case gained a worse audiology result. Central part of the transplant of 1 case was naked, while peripheral part had been epithelization and external auditory canal gained no accessible to mastoid cavity, the patient were also found recurrence of cholesteatom inside the mastoid cavity when received CT examination during outpatient follow-up one year postoperatively, and underwent correction surgery. 1 case underwent revision operation for a fistula between the reconstructed wall and the skin of the outer auditory canal. No surgical complications like infection or facial paralysis occurred, all patients were satisfied with surgery effect. Conclusion: HA with transferred vascularized temporalis fascia pedicle for the reconstructon of the external auditory canal wall is an effective method for the treatment of intractable tympanitis, and worth promoting., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Consumer food waste has attracted increasing public, academic, and political attention in recent years, due to its adverse resource, environmental, and socioeconomic impacts. The scales and patterns of consumer food waste, especially in developing countries, however, remain poorly understood, which may hinder the global effort of reducing food waste. In this study, based on a direct weighing method and a survey of 3557 tables in 195 restaurants in four case cities, we investigated the amount and patterns of restaurant food waste in China in 2015. Food waste per capita per meal in the four cities was 93g, consisting mainly of vegetables (29%), rice (14%), aquatic products (11%), wheat (10%), and pork (8%). This equals to approximately 11kg/cap/year and is not far from that of western countries, although per capita GDP of China is still much lower. We found also that food waste per capita per meal varies considerably by cities (Chengdu and Lhasa higher than Shanghai and Beijing), consumer groups (tourists higher than local residents), restaurant categories (more waste in larger restaurants), and purposes of meals (friends gathering and business banquet higher than working meal and private dining). Our pilot study provides a first, to our best knowledge, empirically determined scales and patterns of restaurant food waste in Chinese cities, and could help set targeted interventions and benchmark national food waste reduction targets., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study was analyzing the characteristic of the electrically evoked auditory brainstem responses (EABR) of cochlear implantation (CI) patients with absence of cochlear modiolus (ACM) and comparing the EABR results in deaf patients with normal anatomic structures. Also we assessed the auditory rehabilitation of ACM patients after cochlear implantation. Method: Twenty-eight profoundly deaf patients were contained, 14 of them were ACM (group A) and the rest were normal anatomic structures (group B). They all received Austria cochlear implants from 2004 to 2015. Postoperative EABR were measured and recorded with No. 2, 6, 11 electrodes in patients receving cochlear implantation. The lead-out rate and threshold of EABR between groups were compared and analyzed. Result: The lead-out rates of EABR in group A was 71.4% and group B was 100%. The thresholds of EABR in group A were higher than group B ( P < 0.05). In group A, there were no statistical difference in the thresholds of EABR among electrodes No.2,6 and 11. However, in group B, there were statistical difference in the thresholds of EABR between electrodes No.2 and 11 ( P < 0.05), and the thresholds of No.2 was lower than No.11 Conclusion: EABR could be used in assessing the objective auditory rehabilitation in ACM patients after cochlear implantation., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: The immune system has important roles in tumor development and outcomes after cancer treatment. We evaluated whether single-nucleotide polymorphisms (SNPs) in the gene encoding casitas B-lineage lymphoma b protein (Cbl-b), an E3 ubiquitin ligase that maintains immune tolerance by negatively regulating T-cell activation and function, were associated with outcomes after treatment of non-small-cell lung cancer (NSCLC)., Patients and Methods: Samples from 393 patients with NSCLC treated with definitive radiotherapy at a single institution between March 1998 and February 2009 were used to genotype 3 potentially functional SNPs in CBLB (rs1042852 C>T, rs2305035 G>A, and rs7649466 C>G). We evaluated associations between these SNPs and local recurrence-free survival, distant metastasis-free survival, overall survival, and risk of radiation pneumonitis (RP)., Results: Having the rs2305035 A variant genotypes (AA or AG) was associated with better local recurrence-free survival (median 15.8 vs. 15.3 months; adjusted hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.60-0.98; P = .033), distant metastasis-free survival (median 15.4 vs. 14.0 months; adjusted HR, 0.74; 95% CI, 0.57-0.96; P = .024) and overall survival (median 23.5 vs. 22.8 months; adjusted HR, 0.72; 95% CI, 0.56-0.93; P = .013) after adjustment in a Cox proportional hazard model. Patients with these genotypes were also at greater risk of developing grade 3 or higher RP than were patients with GG genotypes in an adjusted Cox proportional hazard model., Conclusion: This is the first report that rs2305035 genotypes in CBLB were associated with clinical and RP risk among patients with NSCLC treated with definitive radiotherapy. These findings could assist in generating hypothesis for further mechanistic studies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Mutagen sensitivity assay, which measures the enhanced cellular response to DNA damage induced in vitro by mutagens/carcinogens, has been used in the study of cancer susceptibility. 4-Nitroquinoline-1-oxide (4-NQO), an ultraviolet (UV) radiation-mimetic chemical, can produce chromosomal breaks in mammalian cells and induce cancer. Given the potential role of 4-NQO as the experimental mutagen substituting for UV as the etiological carcinogen of cutaneous melanoma (CM), we tested the hypothesis that cellular sensitivity to 4-NQO is associated with the risk of developing CM in a case-control study of 133 patients with primary CM and 176 cancer-free controls. Short-term blood cultures were treated with 4-NQO at a final concentration of 10 μmol/l for 24 h and scored chromatid breaks in 50 well-spread metaphases. Multivariate logistic regression was used to calculate odds ratios and 95% confidence intervals. We found that the log-transformed frequency of chromatid breaks was significantly higher in 133 patients than in 176 controls (P=0.004) and was associated with an increased risk for CM (adjusted odds ratio=1.78, 95% confidence interval: 1.12-2.84) after adjustment for age and sex. Moreover, as the chromatid break values increased, the risk for CM increased in a dose-dependent manner (P(trend)=0.003). Further analysis explored a multiplicative interaction between the sensitivity to 4-NQO and a family history of skin cancer (P(interaction)=0.004) on the risk of CM. Therefore, our findings suggest that sensitivity to 4-NQO may be a risk factor for the risk of CM, which is more sensitive than UV-induced chromotid breaks.

The synthesis, optical characterization and computational modeling of seven benzo[c][1,2,5]thiadiazole (BTD) donor-acceptor dyes are reported. These dyes have been studied using electrochemical analysis, electronic absorption, emission, and Raman and resonance Raman spectroscopies coupled with various density functional theoretical approaches. Crystal structure geometries on a number of these compounds are also reported. The optical spectra are dominated by low energy charge-transfer states; this may be modulated by the coupling between donor and acceptor through variation in donor energy, variation of the donor-acceptor torsion angle, and incorporation of an insulating bridge. These modifications result in a perturbation of the excitation energy for this charge-transfer transition of up to ∼2000 cm(-1). Emission spectra exhibit significant solvatochromisim, with Lippert-Mataga analysis yielding Δμ between 8 and 33 D. Predicted λmax, ε, and Raman cross sections calculated by M06L, B3LYP, PBE0, M06, CAM-B3LYP, and ωB97XD DFT functionals were compared to experimental results and analyzed using multivariate analysis, which shows that hybrid functionals with 20-27% HF best predict ground state absorption, while long-range corrected functionals best predict molecular polarizabilities.

The availability of data from electronic health records facilitates the development and evaluation of risk-prediction models, but estimation of prediction accuracy could be limited by outcome misclassification, which can arise if events are not captured. We evaluate the robustness of prediction accuracy summaries, obtained from receiver operating characteristic curves and risk-reclassification methods, if events are not captured (i.e., "false negatives"). We derive estimators for sensitivity and specificity if misclassification is independent of marker values. In simulation studies, we quantify the potential for bias in prediction accuracy summaries if misclassification depends on marker values. We compare the accuracy of alternative prognostic models for 30-day all-cause hospital readmission among 4548 patients discharged from the University of Pennsylvania Health System with a primary diagnosis of heart failure. Simulation studies indicate that if misclassification depends on marker values, then the estimated accuracy improvement is also biased, but the direction of the bias depends on the direction of the association between markers and the probability of misclassification. In our application, 29% of the 1143 readmitted patients were readmitted to a hospital elsewhere in Pennsylvania, which reduced prediction accuracy. Outcome misclassification can result in erroneous conclusions regarding the accuracy of risk-prediction models.

Recent investigation has identified association of IL-12p40 blood levels with melanoma recurrence and patient survival. No studies have investigated associations of single-nucleotide polymorphisms (SNPs) with melanoma patient IL-12p40 blood levels or their potential contributions to melanoma susceptibility or patient outcome. In the current study, 818,237 SNPs were available for 1,804 melanoma cases and 1,026 controls. IL-12p40 blood levels were assessed among 573 cases (discovery), 249 cases (case validation), and 299 controls (control validation). SNPs were evaluated for association with log[IL-12p40] levels in the discovery data set and replicated in two validation data sets, and significant SNPs were assessed for association with melanoma susceptibility and patient outcomes. The most significant SNP associated with log[IL-12p40] was in the IL-12B gene region (rs6897260, combined P=9.26 × 10(-38)); this single variant explained 13.1% of variability in log[IL-12p40]. The most significant SNP in EBF1 was rs6895454 (combined P=2.24 × 10(-9)). A marker in IL12B was associated with melanoma susceptibility (rs3213119, multivariate P=0.0499; OR=1.50, 95% CI 1.00-2.24), whereas a marker in EBF1 was associated with melanoma-specific survival in advanced-stage patients (rs10515789, multivariate P=0.02; HR=1.93, 95% CI 1.11-3.35). Both EBF1 and IL12B strongly regulate IL-12p40 blood levels, and IL-12p40 polymorphisms may contribute to melanoma susceptibility and influence patient outcome.

Thymidylate synthase (TYMS) plays a crucial role in folate metabolism as well as DNA synthesis and repair. We hypothesized that functional polymorphisms in the 3' UTR of TYMS are associated with gastric cancer risk and survival. In the present study, we tested our hypothesis by genotyping three potentially functional (at miRNA binding sites) TYMS SNPs (rs16430 6bp del/ins, rs2790 A>G and rs1059394 C>T) in 379 gastric cancer patients and 431 cancer-free controls. Compared with the rs16430 6bp/6bp + 6bp/0bp genotypes, the 0bp/0bp genotype was associated with significantly increased gastric cancer risk (adjusted OR = 1.72, 95% CI = 1.15-2.58). Similarly, rs2790 GG and rs1059394 TT genotypes were also associated with significantly increased risk (adjusted OR = 2.52, 95% CI = 1.25-5.10 and adjusted OR = 1.57, 95% CI = 1.04-2.35, respectively), compared with AA + AG and CC + CT genotypes, respectively. In the haplotype analysis, the T-G-0bp haplotype was associated with significantly increased gastric cancer risk, compared with the C-A-6bp haplotype (adjusted OR = 1.34, 95% CI = 1.05-1.72). Survival analysis revealed that rs16430 0bp/0bp and rs1059394 TT genotypes were also associated with poor survival in gastric cancer patients who received chemotherapy treatment (adjusted HR = 1.61, 95% CI = 1.05-2.48 and adjusted HR = 1.59, 95% CI = 1.02-2.48, respectively). These results suggest that these three variants in the miRNA binding sites of TYMS may be associated with cancer risk and survival of gastric cancer patients. Larger population studies are warranted to verify these findings., (© 2014 Wiley Periodicals, Inc.)

Objectives: Patients with oropharyngeal cancer (OPC) have distinct risk factor profiles reflected in the human papillomavirus (HPV) status of their tumor, and these profiles may also be influenced by factors related to socioeconomic status (SES). The goal of this study was to describe the socioeconomic characteristics of a large cohort of patients with OPC according to HPV status, smoking status, and sexual behavior., Materials and Methods: Patients with OPC prospectively provided information about their smoking and alcohol use, socioeconomic characteristics, and sexual behaviors. HPV status was determined by a composite of immunohistochemistry for p16 expression, HPV in situ hybridization, and PCR assay in 356 patients. Standard descriptive statistics and logistic regression were used to compare socioeconomic characteristics between patient subgroups., Results: Patients with HPV-positive OPC had higher levels of education, income, and overall SES. Among patients with HPV-positive OPC, never/light smokers had more than 5 times the odds of having at least a bachelor's degree and being in the highest level of SES compared with smokers. Patients with HPV-positive OPC and those with higher levels of education and SES had higher numbers of lifetime any and oral sex partners, although not all of these differences were significant., Conclusion: Socioeconomic differences among subgroups of OPC patients have implications for OPC prevention efforts, including tobacco cessation, behavior modification, and vaccination programs., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

CD133 is one of the most common stem cell markers, and functional single nucleotide polymorphisms (SNPs) of CD133 may modulate its gene functions and thus cancer risk and patient survival. We hypothesized that potentially functional CD133 SNPs are associated with gastric cancer (GC) risk and survival. To test this hypothesis, we conducted a case-control study of 371 GC patients and 313 cancer-free controls frequency-matched by age, sex, and ethnicity. We genotyped four selected, potentially functional CD133 SNPs (rs2240688A>C, rs7686732C>G, rs10022537T>A, and rs3130C>T) and used logistic regression analysis for associations of these SNPs with GC risk and Cox hazards regression analysis for survival. We found that compared with the miRNA binding site rs2240688 AA genotype, AC + CC genotypes were associated with significantly increased GC risk (adjusted OR = 1.52, 95% CI = 1.09-2.13); for another miRNA binding site rs3130C>T SNP, the TT genotype was associated with significantly reduced GC risk (adjusted OR = 0.68, 95% CI = 0.48-0.97), compared with CC + CT genotypes. In all patients, the risk rs3130 TT variant genotype was significantly associated with overall survival (OS) (adjusted P(trend) = 0.016 and 0.007 under additive and recessive models, respectively). These findings suggest that these two CD133 miRNA binding site variants, rs2240688 and rs3130, may be potential biomarkers for genetic susceptibility to GC and possible predictors for survival in GC patients but require further validation by larger studies., (© 2013 Wiley Periodicals, Inc.)

Background: Acne reflects hormone imbalance and is a key component of several systemic diseases. We hypothesized that diagnosis of acne as a teenager might predict subsequent risk of hormone-related cancers., Methods: We followed 99,128 female nurses in the Nurses' Health Study II cohort for 20 years (1989-2009) and used Cox proportional hazards models to estimate the hazard ratios (HRs) of 8 specific cancers (breast, thyroid, colorectal, ovarian, cervical, and endometrial cancers, melanoma, and non-Hodgkin lymphoma) for women with a history of severe teenage acne., Results: After thoroughly adjusting for the previously known risk factors for each cancer, we found that among women with a history of severe teenage acne, the relative risk increased, with a multivariable-adjusted HR of 1.44 (95% confidence interval [CI], 1.03-2.01) for melanoma. We replicated this association in an independent melanoma case-control study of 930 cases and 1026 controls (multivariable-adjusted odds ratio, 1.27; 95% CI, 1.03-1.56). We also found that in both studies the individuals with teenage acne were more likely to have moles (52.7% vs 50.1%, P < .001 in the cohort study; and 55.2% vs 45.1%, P = .004 in the case-control study)., Conclusions: Our findings suggest that a history of teenage acne might be a novel risk factor for melanoma independent from the known factors, which supports a need for continued investigation of these relationships., (© 2015 American Cancer Society.)

Purpose: To investigate the association between blood levels of C-reactive protein (CRP) in patients with melanoma and overall survival (OS), melanoma-specific survival (MSS), and disease-free survival., Patients and Methods: Two independent sets of plasma samples from a total of 1,144 patients with melanoma (587 initial and 557 confirmatory) were available for CRP determination. Kaplan-Meier method and Cox regression were used to evaluate the relationship between CRP and clinical outcome. Among 115 patients who underwent sequential blood draws, we evaluated the relationship between change in disease status and change in CRP using nonparametric tests., Results: Elevated CRP level was associated with poorer OS and MSS in the initial, confirmatory, and combined data sets (combined data set: OS hazard ratio, 1.44 per unit increase of logarithmic CRP; 95% CI, 1.30 to 1.59; P < .001; MSS hazard ratio, 1.51 per unit increase of logarithmic CRP; 95% CI, 1.36 to 1.68; P < .001). These findings persisted after multivariable adjustment. As compared with CRP < 10 mg/L, CRP ≥ 10 mg/L conferred poorer OS in patients with any-stage, stage I/II, or stage III/IV disease and poorer disease-free survival in those with stage I/II disease. In patients who underwent sequential evaluation of CRP, an association was identified between an increase in CRP and melanoma disease progression., Conclusion: CRP is an independent prognostic marker in patients with melanoma. CRP measurement should be considered for incorporation into prospective studies of outcome in patients with melanoma and clinical trials of systemic therapies for those with melanoma., (© 2015 by American Society of Clinical Oncology.)

Cytokines such as Interleukin (IL)-12p70 ("IL-12") and IL-23 can influence tumor progression. We tested the hypothesis that blood levels of IL-12p40, the common subunit of both cytokines, are associated with melanoma progression. Blood from 2,048 white melanoma patients were collected at a single institution between March 1998 and March 2011. Plasma levels of IL-12p40 were determined for 573 patients (discovery), 249 patients (Validation 1) and 244 patients (Validation 2). Per 10-unit change of IL-12p40 level was used to investigate associations with melanoma patient outcome among all patients or among patients with early or advanced stage. Among stage I/II melanoma patients in the pooled data set, after adjustment for sex, age, stage and blood draw time from diagnosis, elevated IL-12p40 was associated with melanoma recurrence [hazard ratio (HR) = 1.04 per 10-unit increase in IL-12p40, 95% CI 1.02-1.06, p = 8.48 × 10(-5) ]; Elevated IL-12p40 was also associated with a poorer melanoma specific survival (HR = 1.06, 95% CI 1.03-1.09, p = 3.35 × 10(-5) ) and overall survival (HR = 1.05, 95% CI 1.03-1.08, p = 8.78×10(-7) ) in multivariate analysis. Among stage III/IV melanoma patients in the pooled data set, no significant association was detected between elevated IL-12p40 and overall survival, or with melanoma specific survival, with or without adjustment for the above covariates. Early stage melanoma patients with elevated IL-12p40 levels are more likely to develop disease recurrence and have a poorer survival. Further investigation with a larger sample size will be needed to determine the role of IL-12p40 in advanced stage melanoma patients., (© 2014 UICC.)

Thymidylate synthase (TYMS) is involved in the folate metabolism and provision of nucleotides needed for DNA synthesis and repair. Thus, functional genetic variants in TYMS may alter cancer risk. In the study, we evaluated associations of three germline variants (rs2790 A > G, rs16430 6 bp > 0 bp, and rs1059394 C > T) in the predicted miRNA-binding sites of TYMS with risk of sporadic breast cancer in non-Hispanic white women aged ≤ 55. We found that carriers of the rs16430 0 bp variant allele had an increased risk of breast cancer [adjusted odd ratio (OR) = 1.37, 95% confidence interval (CI): 1.08-1.73; P = 0.010], compared with carriers of the 6 bp/6 bp genotype. This increased risk was more evident in older subjects (OR = 1.47, 95% CI = 1.06-2.03, P = 0.022), never smokers (OR = 1.67, 95% CI = 1.23-2.25, P < 0.001), never drinkers (OR = 1.44, 95% CI = 1.01-2.05, P = 0.043), and estrogen receptor-positive patients (OR = 1.46, 95% CI = 1.11-1.92, P = 0.006), regardless of tumor stages. The results are consistent with the functional analyses of rs16430 as previously reported, which showed that the 0 bp allele had a decrease in both luciferase activity by ∼ 70% and mRNA levels by ∼ 50% compared with the 6bp allele. Additionally, the rs16430 variant was predicted to influence the binding activity of miR-561. Taken together, these findings indicate that the TYMS rs16430 may contribute to the etiology of sporadic breast cancer in non-Hispanic white women aged ≤ 55 yr. Further validation in large population-based or cohort studies is needed., (© 2013 Wiley Periodicals, Inc.)

Cutaneous melanoma (CM) is the most lethal skin cancer. The Fanconi anemia (FA) pathway involved in DNA crosslink repair may affect CM susceptibility and prognosis. Using data derived from published genome-wide association study, we comprehensively analyzed the associations of 2,339 common single-nucleotide polymorphisms (SNPs) in 14 autosomal FA genes with overall survival (OS) in 858 CM patients. By performing false-positive report probability corrections and stepwise Cox proportional hazards regression analyses, we identified significant associations between CM OS and four putatively functional SNPs: BRCA2 rs10492396 (AG vs. GG: adjusted hazard ratio (adjHR)=1.85, 95% confidence interval (CI)=1.16-2.95, P=0.010), rs206118 (CC vs. TT+TC: adjHR=2.44, 95% CI=1.27-4.67, P=0.007), rs3752447 (CC vs. TT+TC: adjHR=2.10, 95% CI=1.38-3.18, P=0.0005), and FANCA rs62068372 (TT vs. CC+CT: adjHR=1.85, 95% CI=1.27-2.69, P=0.001). Moreover, patients with an increasing number of unfavorable genotypes (NUG) of these loci had markedly reduced OS and melanoma-specific survival (MSS). The final model incorporating with NUG, tumor stage, and Breslow thickness showed an improved discriminatory ability to classify both 5-year OS and 5-year MSS. Additional investigations, preferably prospective studies, are needed to validate our findings.

Background and Purpose: MicroRNAs (miRNAs) are small, highly conserved non-coding RNAs that regulate many biological processes. We sought to investigate whether three serum miRNAs related to immunity or inflammation were associated with esophagitis induced by chemoradiation therapy (CRT) for non-small cell lung cancer (NSCLC)., Material and Methods: We measured serum miR-155, miR-221 and miR-21, before and during week 1-2 of CRT for 101 NSCLC patients by real-time PCR. Associations between miRNA and severe radiation-induced esophageal toxicity (RIET) were analyzed by logistic regression., Results: We found that patients with stage IIIB-IV disease, higher mean esophagus dose or esophageal V50 had higher rates of severe RIET. Furthermore, high levels of miR-155 and miR-221 at week 1-2 of CRT were also risk factors for severe RIET (miR-155: OR=1.53, 95% CI: 1.04-2.25, P=0.03; miR-221: OR=2.07, 95% CI: 1.17-3.64, P=0.012). In addition, the fold change of miR-221 was also predictive of severe RIET (OR=1.18, 95% CI: 1.02-1.37, P=0.026). However, pretreatment miRNAs was not predictive of severe RIET., Conclusions: High serum miR-155 and miR-221 during the first 2 weeks of CRT were associated with the development of severe RIET, suggesting that these miRNAs may be useful as an early surrogate for this form of toxicity., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Functional genetic variants of DNA repair genes may alter the host DNA repair capacity, and thus influence efficiency of therapies. We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) in genes (i.e. ERCC1, XPA, XPC, XPD and XPG) involved in the nucleotide excision repair (NER) pathway in 496 Japanese gastric cancer patients, and assessed overall survival and recurrence-free survival. The combined effects of risk genotypes of these eight SNPs in Japanese patients were further replicated in 356 North-American gastric cancer patients. In Japanese patients, we found that the XPC rs2228000 TT genotype was associated with shorter overall survival [hazards ratio (HR) = 1.75, 95% confidence interval (95% CI) = 1.07-2.86] and recurrence-free survival (HR = 2.17, 95% CI = 1.19-3.95), compared with CC/CT genotypes, and the XPG rs17655 CC genotype was associated with shorter overall survival (HR = 1.60, 95% CI = 1.08-2.36), compared with GG/CG genotypes. The number of observed risk genotypes in the combined analysis was associated with shorter overall survival and recurrence-free survival in a dose-response manner (P(trend) = 0.006 and P(trend) < 0.000) in Japanese patients; specifically, compared with those with ≤1 risk genotypes, those with ≥2 risk genotypes showed markedly shorter overall survival (HR = 1.79, 95% CI = 1.18-2.70) and recurrence-free survival (HR = 2.80, 95% CI = 1.66-4.73). The association between ≥2 risk genotypes and shorter overall survival was not significant (HR = 1.26, 95% CI = 0.82-1.94) in North-American patients, but the trends were similar in these two groups of patients. These data show that functional SNPs in NER core genes may impact survival in Japanese gastric cancer patients., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: LIN28 is an RNA-binding protein that not only plays key roles in multiple cellular developmental processes and tumourigenesis, but also is involved in tissue inflammatory response. However, no published study has investigated associations between genetic variants in LIN28 and radiation-induced pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiation therapy., Methods: We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of LIN28A (rs11247946 T>C, rs3811464 C>T, rs11581746 T>C, and rs12728900 G>A) and LIN28B (rs314280 G>A, rs12194974 G>A, rs17065417 A>C and rs314276 C>A) in 362 patients with NSCLC, who received definitive radio(chemo)therapy. The associations between RP risk and genotypes were assessed by hazards ratio (HR) in Cox proportional hazards regression analysis with time to event considered with and without adjustment for potential confounders., Results: Multivariate analyses found that patients carrying LIN28B rs314280 AG and AA/AG or rs314276 AC and AA/AC genotypes had a higher risk of grade ⩾3 RP (for rs314280 AG and AA/AG versus GG, adjusted HR=2.97 and 2.23, 95% confidence interval (CI)=1.32-6.72 and 1.01-4.94, P=0.009 and 0.048, respectively; for rs314276 AC and AA/AC versus CC, adjusted HR=2.30 and 2.00, 95% CI=1.24-4.28 and 1.11-3.62, and P=0.008 and 0.022, respectively). Further stratified analyses showed a more consistent and profound risk in the subgroups of age <65years, males, stage III/IV, ever smokers, having radio-chemotherapy and mean lung dose (MLD) ⩾19.0Gy., Conclusion: Genetic variants of LIN28B, but not LIN28A, may be biomarkers for susceptibility to severe RP in NSCLC patients. Large, prospective studies are needed to confirm our findings., (Copyright © 2014. Published by Elsevier Ltd.)

Many studies have reported comparable risk of hard end points between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for unprotected left main coronary artery (ULMCA) stenosis. However, there are limited data regarding the morbidity associated with ULMCA revascularization. This study sought to compare the cause and risk of readmissions after PCI and CABG for ULMCA stenosis. We evaluated the unadjusted and adjusted risk of readmissions in 1,352 patients (783 PCI treated and 569 CABG treated) who were consecutively enrolled in a multicenter registry of patients with ULMCA stenosis, named the Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease trial. Overall, 206 PCI-treated patients (26.3%) experienced at least 1 readmission after the index procedure during 48.7 ± 16.0 months of follow-up compared with 84 CABG-treated patients (14.8%, p <0.001). The most frequent causes of readmission were repeat revascularization after PCI (41%) and noncardiac readmissions after CABG (48%). Through repeated events analysis, PCI was associated with more frequent readmissions than CABG (hazard ratio 2.037, 95% confidence interval 1.542 to 2.692, p <0.001), being an independent predictor of readmission (hazard ratio 1.820, 95% confidence interval 1.420 to 2.331, p <0.001). Except for the acute period, defined as the first 3 months, when there was no significant difference in readmission rate, a higher readmission rate after PCI was consistently observed over the remainder of the follow-up period. In conclusion, PCI was shown to be associated with a higher risk of readmission than CABG in treating ULMCA disease. This higher risk was attributable to more frequent revascularization in the PCI group., (Copyright © 2014 Elsevier Inc. All rights reserved.)