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Zhiliang Zhang,1,&ast; Zhongxiang Ding,2,&ast; Fenyang Chen,2 Rui Hua,3 Jiaojiao Wu,3 Zhefan Shen,2 Feng Shi,3 Xiufang Xu1 1School of Medical Imaging, Hangzhou Medical College, Hangzhou, People’s Republic of China; 2Department of Radiology, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Shi; Xiufang Xu, Email feng.shi@uii-ai.com; 1996033011@hmc.edu.cnBackground: Cerebral small vessel disease lacks specific clinical manifestations, and extraction of valuable features from multimodal images is expected to improve its diagnostic accuracy. In this study, we used deep learning techniques to segment cerebral small vessel disease imaging markers in multimodal magnetic resonance images and analyze them with clinical risk factors.Methods and results: We recruited 211 lacunar stroke patients and 83 control patients. The patients’ cerebral small vessel disease markers were automatically segmented using a V-shaped bottleneck network, and the number and volume were calculated after manual correction. The segmentation results of the V-shaped bottleneck network for white matter hyperintensity and recent small subcortical infarction were in high agreement with the ground truth (DSC> 0.90). In small lesion segmentation, cerebral microbleed (average recall=0.778; average precision=0.758) and perivascular spaces (average recall=0.953; average precision=0.923) were superior to lacunar infarct (average recall=0.339; average precision=0.432) in recall and precision. Binary logistic regression analysis showed that age, systolic blood pressure, and total cerebral small vessel disease load score were independent risk factors for lacunar stroke (P< 0.05). Ordered logistic regression analysis showed age was positively correlated with cerebral small vessel disease load score and total cholesterol was negatively correlated with cerebral small vessel disease score (P< 0.05).Conclusion: Lacunar stroke patients exhibited higher cerebral small vessel disease imaging markers, and age, systolic blood pressure, and total cerebral small vessel disease score were independent risk factors for lacunar stroke patients. V-shaped bottleneck network segmentation network based on multimodal deep learning can segment and quantify various cerebral small vessel disease lesions to some extent.Keywords: lacunar stroke, cerebral small vessel disease, imaging markers, deep learning, quantification, image segmentation, clinical risk factors

Run Hua,1,&ast; Gangjie Qiao,2,&ast; Guoshan Chen,1,&ast; Zhaonan Sun,3 Haowen Jia,3 Peiyuan Li,1 Baotong Zhang,1 Feng Qi1 1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Department of Colorectal Surgery, Shanxi Provincial People’s Hospital, Shanxi, People’s Republic of China; 3General Surgery Department, Tianjin Medical University General Hospital Airport Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Qi, Email qifengtmu2017@163.comBackground: Ulcerative colitis (UC) is a severe threat to humans worldwide. Single-cell RNA sequencing (scRNA-seq) can be used to screen gene expression patterns of each cell in the intestine, provide new insights into the potential mechanism of UC, and analyze the development of immune cell changes. These findings can provide new ideas for the diagnosis and treatment of intestinal diseases. In this study, bioinformatics analysis combined with experiments applied in dextran sulfate sodium (DSS)-induced colitis mice was used to explore new diagnostic genes for UC and their potential relationship with immune cells.Methods: We downloaded microarray datasets (GSE75214, GSE87473, GSE92415) from the Gene Expression Omnibus and used these datasets to screen differentially expressed genes (DEGs) and conduct Weighted Gene Co-expression Network Analysis (WGCNA) after quality control. The hub genes were screened, and ROC curves were drawn to verify the reliability of the results in both training set (GSE75214, GSE87473, GSE92415) and validation cohort (GSE87466). Also, we explored the relation of diagnostic genes and immune cells by CIBERSORT algorithm and single-cell analysis. Finally, the expression of hub genes and their relation with immune cells were verified in DSS-induced colitis mice.Results: Diagnostic genes (ANXA5, MMP7, NR1H4, CYP3A4, ABCG2) were identified. In addition, we found these five genes firmly related to immune infiltration. The DSS-induced colitis mice confirm that the expression of ANXA5 mainly increased in the intestinal macrophages and had a strong negative correlation with M2 macrophages, which indicated its possible influence on the polarization of macrophages in UC patients.Conclusion: We identified ANXA5, MMP7, NR1H4, CYP3A4, and ABCG2 as diagnostic genes of UC that are closely related to immune infiltration and ANXA5 maintains a negative correlation with M2 macrophages which indicated its possible influence on the polarization of macrophage in UC patients.Keywords: ulcerative colitis, ANXA5, diagnostic genes, single-cell analysis, macrophages

Wenjing Ta, Xingyue Li, Jihong Song, Ruochen Hua, Yuting Zheng, Wen Lu School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Wen Lu, School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China, Email lvlu2004@xjtu.edu.cnPurpose: Nanotechnology-based drug delivery systems (nano-DDS) have been developed to be a promising strategy to improve the efficacy, safety, physicochemical and pharmacokinetic/pharmacodynamics properties of drugs. It is very necessary to elucidate the delivery process in vivo or in cells for the rational design and accurate preparation of nano-DDS. The aim of this study was to construct a nano-DDS to visualize and quantify the intracellular behavior of the loaded cargo and carrier in such a system.Methods: A carboxyl-terminal end of poly(lactic-co-glycolic acid) polymer was fluorescently labeled with rhodamine B by conjugation of ethylenediamine. Dual-fluorescent nanoparticles (DFPs) were prepared from this fluorescently labeled polymer to encapsulate a fluorescent cargo, coumarin 6. The carrier and cargo of DFPs were monitored by confocal fluorescence microscopy during cellular uptake. Furthermore, the transcellular transportation of DFPs was evaluated quantitatively by measuring the fluorescence intensity.Results: The obtained fluorescent polymer showed stable and quantifiable characteristics. DFPs could be customized in terms of coumarin 6 content (97.7± 1.0%), size (367.3± 1.7 nm) and dual-emission fluorescence (green cargo and red carrier). DFPs did not significantly affect cell viability, the integrity of cell monolayers and the microscopic morphology at concentrations below 0.7 mg/mL within 3 h of co-incubation with Caco-2 cells. Multichannel fluorescence monitoring revealed that the fluorescence intensity of the carrier and cargo increased with time, but not synchronously. By calculating the residual, intracellular, and transport amounts of DFPs, the material balance between the total amount of cellular transport and the dose administered was obtained.Conclusion: Based on the advantages of dual fluorescent labeling, the differential behavior of cell trafficking can be visualized and quantitatively analyzed for the cargo and carrier of DFPs. These results provide insights into the cellular transport process of holistic nanoparticles and complement our understanding of the biological behaviors of nano-DDS.Keywords: dual-fluorescent nanoparticles, tracking cellular uptake, fluorescence imaging, quantitative cell transport, drug delivery

Yimin Han1 &ast;, Boya Wang2 &ast;, Han Gao,3 Chengwei He,3 Rongxuan Hua,4 Chen Liang,4 Sitian Zhang,4 Ying Wang,5 Shuzi Xin,3 Jingdong Xu3 1Department of Oral Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Undergraduate Student of 2018 Eight Program of Clinical Medicine, Peking University People’s Hospital, Beijing, 100083, People’s Republic of China; 3Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, People’s Republic of China; 4Department of Clinical Medicine, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, People’s Republic of China; 5Department of Dermatology, Beijing Tong Ren Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingdong Xu, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No. 10, Xitoutiao, Youanmenwai, Fengtai District, Beijing, 100069, People’s Republic of China, Tel/Fax +86 10-8391-1469, Email xujingdong@163.comAbstract: The gut microbiota is the most abundant and diverse microbiota in the human body and the vagus nerve is the most widely distributed and complex nerve in the body, both of them are essential in maintaining homeostasis. The most important phenomenon is how they coordinate to regulate functions, which has attracted the great attention of scientists. The academic literature on the correlation with a host of intestinal diseases and even systemic diseases has revealed the bidirectional communication between the gut microbiota and the brain, which can be carried out via multiple patterns. In the review, firstly, we have a general overview of the gut microbiota and the gut microbiota-brain axis. Secondly, according to the distribution characteristics of the vagus nerve, we analyzed and summarized its function in the intestinal tract. At the same time, we have summarized the underlying mechanism of some behavior changes such as depressive and anxiety-like behaviors and related neurodegenerative diseases caused by the vagus nerve and intestinal microecological environment disorders, and then we also analyzed inconsistency of the experimental evidence in order to propose novel strategies for the clinical practice.Keywords: gut microbiota-brain axis, gut microbiota, brain, vagus nerve, behavior, neurodegenerative diseases

Jiaguo Huang,1,&ast; Shengcheng Tai,1,&ast; Hongxiang Ding,1 Li Xu,2 Runmiao Hua,1 Yufu Yu,1 Dikai Mao1 1Department of Urology, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, People’s Republic of China; 2School of Medicine, Hangzhou Normal University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dikai Mao, Department of Urology, Affiliated Xiaoshan Hospital, Hangzhou Normal University, No. 728 North Yucai Road, Xiaoshan District, Hangzhou, People’s Republic of China, Tel +8618967103936, Email Modikai@126.comAbstract: Herpes zoster infection in the sacral area accounts for a considerable number of all herpes zoster cases, and cases of acute urinary retention and defecation disorders caused by herpes zoster infection in the sacral area have been reported. However, no clinical case of spontaneous bladder rupture has been reported. In this report, we describe a 77-year-old male patient with severe complications of spontaneous bladder rupture caused by herpes zoster-associated urinary retention. The patient regained complete bladder function after undergoing surgery to repair the bladder and treatment with antiviral drugs.Keywords: herpes zoster, acute urinary retention, spontaneous bladder rupture, sacral area

Liwei Zhao,1,2,&ast; Ji Sun,2,&ast; Kai Wang,3 Shengcheng Tai,2 Runmiao Hua,2 Yufu Yu,2 Yi Fan,1,2 Jiaguo Huang2 1Department of Urology, School of Medicine, Hangzhou Normal University, Hangzhou, 311121, Zhejiang Province, People’s Republic of China; 2Department of Urology, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, 311202, Zhejiang Province, People’s Republic of China; 3Department of Urology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Fan; Jiaguo HuangDepartment of Urology, Affiliated Xiaoshan Hospital, Hangzhou Normal University, No. 728 North Yucai Road, Xiaoshan District, Hangzhou, 311202, Zhejiang, People’s Republic of ChinaTel +86-571-83865858Email fanyi316@sina.com; 13735526508@163.comBackground: Bladder cancer is the second most prevalent neoplasm in the urogenital system in terms of morbidity and mortality, and there is an urgent need for a more accurate assessment of individual prognosis in patients with primary non-muscle-invasive bladder cancer (NMIBC). The Controlling Nutritional Status (CONUT) score is an emerging biomarker score which has been confirmed to have prognostic value in various malignant tumors. The study attempted to systematically identify the prognostic role of preoperative CONUT score on posttreatment recurrence-free survival (RFS) in patients with NMIBC, and determine the predictive value and feasibility of the new prognostic prediction model.Methods: A total of 94 patients with NMIBC were analyzed retrospectively between January 2011 and December 2015. Statistical analysis was conducted using the nonparametric method. The Kaplan-–Meier method was used to assess recurrence-free survival (RFS), and Log rank tests was used to analyze the equivalences of survival curves. We used univariate and multivariate Cox proportional hazards regression model to identify important predictors of RFS. Discrimination of nomogram was measured by the concordance index. Predictive accuracy of the model was evaluated using the internal validation.Results: In univariate analysis, age, history of smoking, pathological T stage, tumor grade, tumor size, and CONUT score were significantly correlated with RFS. Multivariate analysis indicated that CONUT score (HR =3.855, 95% CI 1.242– 11.970, p=0.020) was an independent predictor of RFS in patients with NMIBC. Based on significant parameters in multivariate analysis and reliable recurrence predictors determined in predictive models and relevant guidelines, a new age-, history of smoking-, pathologic factors- and the CONUT score-based scoring model was developed to predict recurrence of NMBIC. In addition, we internally validated the nomogram using the consistency index and calibration plots, which demonstrated that the model has high prediction accuracy (c-index= 0.851).Conclusion: The development of a new nomogram based on CONUT score could increase the accuracy of recurrence prediction and improve individualized treatment plans for patients with NMIBC.Keywords: bladder cancer, CONUT score, nomogram, the EORTC scoring system, recurrence-free survival

Tiantian Wang,1 Lei Gao,2 Zejun Yang,3 Feifei Wang,3 Yuexin Guo,4 Boya Wang,5 Rongxuan Hua,3 Hongwei Shang,6 Jingdong Xu1 1Department of Physiology and Pathophysiology, Basic Medical College, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Department of Biomedical Informatics, School of Biomedical Engineering, Capital Medical University, Beijing, 100069, People’s Republic of China; 3Department of Clinical Medicine, Basic Medical College, Capital Medical University, Beijing, 100069, People’s Republic of China; 4Department of Oral Medicine, Basic Medical College, Capital Medical University, Beijing, 100069, People’s Republic of China; 5Eight Program of Clinical Medicine, Peking University Health Science Center, Beijing, 100081, People’s Republic of China; 6Experimental Center for Morphological Research Platform, Capital Medical University, Beijing, 100069, People’s Republic of ChinaCorrespondence: Jingdong Xu Tel +86-10-83911469Email xujingdong@ccmu.edu.cnPurpose: Hypertension (HTN) is a major risk factor for cardiovascular disease. In recent years, there were numerous studies on the function of stress in HTN. However, the gut dysbiosis linked to hypertension in animal models under stress is still incompletely understood. Purpose of this study is to use multiple determination method to determine the juvenile stage intestinal bacteria, cytokines and changes in hormone levels.Methods: Four groups of juvenile male spontaneously hypertensive rats (SHRs) and age-matched male Wistar-Kyoto (WKY) rats were randomly selected as control and experimental groups. Rats in the two stress groups were exposed to restraint stress for 3 hours per day for 7 consecutive days. In one day three times in the method of non-invasive type tail-cuff monitoring blood pressure. The detailed mechanism was illuminated based on the intestinal change using immunohistochemical and immunofluorescence staining and the stress-related hormone and inflammation factors were analyzed via ELISA method. The integrity of the epithelial barrier was assessed using FITC/HRP and the expression levels of proteins associated with the tight junction was detected by Western blot. The alteration of stress-related intestinal flora from ileocecal junction and distal colon were also analyzed using its 16S rDNA sequencing.Results: The results indicate that acute stress rapidly increases mean arterial pressure which is positive correlation to hormone concentration, especially in SHR-stress group. Meanwhile, stress promoted the enhancement of epithelial permeability accompanied with a reduced expression of the tight junction-related protein and the macrophages (M&phis;) aggregation to the lamina propria. There were remarkable significant increase of stress-related hormones and pro-inflammatory factor interleukin (IL)-6 along with a decrease in the diversity of intestinal flora and an imbalance in the F/B ratio.Conclusion: Our results reveal that stress accompanied with HTN could significantly disrupt the domino effect between intestinal flora and homeostasis.Keywords: hypertension, restraint stress, intestinal flora, juvenile rat, intestinal barrier, macrophages

Yuzhao Sun, Rui Hua Department of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People’s Republic of ChinaCorrespondence: Rui HuaDepartment of Ophthalmology, The First Affiliated Hospital of China Medical University, No. 155 Nanjingbei Street, Heping District, Shenyang, Liaoning 110001, People’s Republic of ChinaTel +86-13-840583355Fax +86-24-83282630Email woodshua@126.comPurpose: To investigate the effectiveness and safety of subconjunctival/perilesional 5-fluorouracil injections on ocular surface squamous neoplasia (OSSN) during a 3-year follow-up period.Patients and Methods: We followed up six patients with intraepithelial OSSN (in one eye each) that had regressed after subconjunctival/perilesional 5-fluorouracil injections. Conjunctival fluorescein angiography (FA) and indocyanine green angiography (ICGA), as well as anterior segment optical coherence tomography (AS-OCT), were performed to evaluate the OSSN status 3 years after initiation of treatment.Results: The mean age of patients (five males, one female) at baseline was 62.3± 11.6 years. The mean number of 5-fluorouracil injections was 17.0± 8.6, with a mean treatment duration of 13.0± 7.4 weeks. At the final visit, both intratumoral and conjunctival feeding vessels had disappeared on ICGA and FA, with no neovascularization-related leakage, in accordance with the results of AS-OCT. The period from complete tumor regression to final visit according to AS-OCT was 32.5± 4.2 months, which was longer than that according to ICGA (31.3± 3.2 months, p=0.034). The final best-corrected visual acuity was similar to that at baseline (p=0.128). No side effects were observed in any of the eyes.Conclusion: Subconjunctival/perilesional 5-fluorouracil injections are an effective and safe treatment for OSSN. Future studies with a larger sample size are warranted for confirmation of our findings, as well as investigation into the reasons for residual areas of non-perfusion in the conjunctiva.Keywords: ocular surface squamous neoplasia, subconjunctival injection, 5-fluorouracil, long-term follow-up, conjunctival angiography, optical coherence tomography

Yuzhao Sun, Rui HuaDepartment of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, People’s Republic of ChinaIntroduction: To investigate the angiographic characteristics of ocular surface squamous neoplasia (OSSN) and to evaluate the efficacy of subconjunctival/perilesional 5-fluorouracil injections in OSSN cases.Materials and methods: Six eyes of six patients with primary OSSN, received perilesional, subconjunctival, 25-mg/mL 5-fluorouracil injections at certain intervals. Anterior segment digital photography images, anterior segment optical coherence tomography (AS-OCT), and conjunctival indocyanine green angiography (ICGA) were obtained simultaneously with fluorescein angiography.Results: The mean best-corrected vision acuity significantly improved after treatment. At baseline, the median of the largest thickness of OSSN was 905.0 (interquartile range: 492.0–1592.5) μm based on AS-OCT data. There was an abrupt transition between normal and abnormal epithelium, a thickened hyper-reflective epithelium, and a sharp plane of cleavage between the lesion and underlying tissue, all indicative of OSSN. The angiographic characteristics of OSSN included focal or seafan-shaped intratumoral and conjunctival feeding vessels visible via ICGA, and abnormal vascular leakage visible with fluorescein angiography. The median time to tumor regression after treatment was 35.0 (interquartile range: 32.0–45.5) days in five eyes without recurrence, and OSSN in one eye regressed partially 40 days after treatment.Conclusion: This is the first report of the angiographic characteristics of OSSN and its response to subconjunctival/perilesional 5-fluorouracil injections by simultaneous conjunctival angiography and AS-OCT. The improved subconjunctival/perilesional 5-fluorouracil injection was an effective therapy for OSSN in both best-corrected vision acuity gain and anatomic outcomes.Keywords: ocular surface squamous neoplasia, subconjunctival 5-flourouracil injection, conjunctival angiography, anterior segment optical coherence tomography

Luping Wang,1 Canwei Zhang,2 Rui Hua3 1Department of Ophthalmology, University of Bonn, Bonn, Germany; 2Department of Ophthalmology, Weifang Eye Hospital, Weifang, People’s Republic of China; 3Department of Ophthalmology, First Hospital of China Medical University, Shenyang, People’s Republic of China Introduction: To assess the ocular efficacy of intravitreal ranibizumab and conbercept injection in patients with neovascular age-related macular degeneration. Materials and methods: We searched PubMed, Wed of Science, Cochrane Library, EMBASE, Google Scholar, Medline, China National Knowledge Infrastructure, and WANFANG DATA databases, up to June 20, 2018. We also searched abstracts and clinical study presentations at meetings as well as trial registries; we contacted authors of included studies if questions arose. Eligibility criteria for selection of studies were randomized controlled trials and retrospective trials that compared ranibizumab with conbercept for treatment of neovascular age-related macular degeneration. Results: Eight randomized controlled trials and four retrospective studies were included with a total of 853 patients. Best-corrected visual acuity after loading dosage was improved in the conbercept group, compared with the ranibizumab group (weighted mean difference: -0.04; 95% CI: -0.07 to 0.00; P=0.04). There was a significant difference between conbercept and ranibizumab therapy with respect to unchanged or recurrent leakage of choroidal neovascularization (OR: 0.46; 95% CI: 0.24–0.88; P=0.02). No significant differences were observed in central macular thickness (weighted mean difference: -2.92; 95% CI: -9.00 to 3.17; P=0.35), complete and partial closure of leakage of choroidal neovascularization (complete closure, P=0.70; partial closure, P=0.35), or number of injections (weighted mean difference: 0.42; 95% CI: -0.46 to 1.29; P=0.35) between the conbercept and ranibizumab groups at the end of the follow-up periods. Conclusion: Pooled evidence confirmed that conbercept was superior to ranibizumab with respect to visual gain after treatment. Additional studies with long-term follow-up are needed to support our conclusion. Keywords: age-related macular degeneration, best-corrected visual acuity, central macular thickness, choroidal neovascularization, vision loss

Jing He,1,* Zhen-Jian Zhuo,2,* Anqi Zhang,3,* Jinhong Zhu,4 Rui-Xi Hua,5 Wen-Qiong Xue,1 Shao-Dan Zhang,1 Jiang-Bo Zhang,1 Xi-Zhao Li,1 Wei-Hua Jia1 1State Key Laboratory of Oncology in South China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China; 2Faculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China; 3Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; 4Molecular Epidemiology Laboratory, Department of Laboratory Medicine, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China; 5Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China *These authors contributed equally to this work Background: Potentially functional polymorphisms can modulate protein activities and host’s DNA repair capacity, thereby influencing cancer susceptibility. The association of the polymorphisms in the nucleotide excision repair core pathway genes and gastric cancer susceptibility remains largely unknown. Methods: Here, we systematically analyzed the associations between nine polymorphisms in four key genes (XPA, ERCC1, ERCC2, and ERCC4) in the nucleotide excision repair pathway and gastric cancer risk in a Chinese population including 1142 patients and 1173 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the risk associations. Results: We observed that ERCC1 rs2298881 CA variant genotype was associated with an increased gastric cancer risk (CA vs. CC: adjusted OR [AOR]=1.33, 95% CI=1.09–1.62; dominant model: AOR=1.32, 95% CI=1.10–1.60). However, ERCC1 rs3212986 AA variant genotype was identified as a protective factor for gastric cancer (AA vs. CC: AOR=0.73, 95% CI=0.54–0.98; recessive model: AOR=0.72, 95% CI=0.54–0.96). Genotype-based mRNA expression analysis further indicated that the rs2298881 A allele was associated with decreased ERCC1 mRNA expression. Conclusion: In all, these results indicated that the ERCC1 polymorphisms may affect the risk of gastric cancer in the Chinese Han population. Keywords: gastric cancer, DNA repair, NER, polymorphism, susceptibility

Our understanding of the dynamics of ion collisional energy loss in a plasma is still not complete, in part due to the difficulty and lack of high-quality experimental measurements. These measurements are crucial to benchmark existing models. Here, we show that such a measurement is possible using high-flux proton beams accelerated by high intensity short pulse lasers, where there is a high number of particles in a picosecond pulse, which is ideal for measurements in quickly expanding plasmas. By reducing the energy bandwidth of the protons using a passive selector, we have made proton stopping measurements in partially ionized Argon and fully ionized Hydrogen plasmas with electron temperatures of hundreds of eV and densities in the range 1020-1021 cm-3. In the first case, we have observed, consistently with previous reports, enhanced stopping of protons when compared to stopping power in non-ionized gas. In the second case, we have observed for the first time the regime of reduced stopping, which is theoretically predicted in such hot and fully ionized plasma. The versatility of these tunable short-pulse laser based ion sources, where the ion type and energy can be changed at will, could open up the possibility for a variety of ion stopping power measurements in plasmas so long as they are well characterized in terms of temperature and density. In turn, these measurements will allow tests of the validity of existing theoretical models.

Thermal conductivity is one of the most crucial physical properties of matter when it comes to understanding heat transport, hydrodynamic evolution, and energy balance in systems ranging from astrophysical objects to fusion plasmas. In the warm dense matter regime, experimental data are very scarce so that many theoretical models remain untested. Here we present the first thermal conductivity measurements of aluminum at 0.5-2.7 g/cc and 2-10 eV, using a recently developed platform of differential heating. A temperature gradient is induced in a Au/Al dual-layer target by proton heating, and subsequent heat flow from the hotter Au to the Al rear surface is detected by two simultaneous time-resolved diagnostics. A systematic data set allows for constraining both thermal conductivity and equation-of-state models. Simulations using Purgatorio model or Sesame S27314 for Al thermal conductivity and LEOS for Au/Al release equation-of-state show good agreement with data after 15 ps. Discrepancy still exists at early time 0-15 ps, likely due to non-equilibrium conditions.

The complete mitochondrial genome of Locastra muscosalis (Walker, 1866) was sequenced and characterized in this study, which was the first reported complete mitogenome of the genus Locastra. The mitogenome of L. muscosalis has a total length of 15,177 bp, encompassing 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and an A-T rich region. Phylogenetic analysis revealed that L. muscosalis is closely associated with Orthaga euadrusalis. These data will serve as a valuable foundation for future investigations into the Epipaschiinae and Pyralidae evolutionary history.

Fish are generally classified as herbivorous, carnivorous, omnivorous, or filter-feeders according to feeding habits, including the feeding method and food content. The feeding habits of fish are reflected in their digestive organ, mainly the intestine. The intestine tract is the main site for digestion and nutritional uptake, and it is regarded as a key organ in fish nutrition. Reportedly, fish gut microbiota contributes to digestion and affect gastrointestinal tract development as well as the overall growth of the fish. The disruption of the intestinal microbiota induced by their feeding habit via diet usually affects the digestive functions of the host through disturbance in bacterial digestive enzyme production. Feeding habits determine the feed composition, which shapes the microbial communities in fish. For example, diet has been reported as a dominant cause of variation in the microbiota composition of rainbow trout. In contrast, feeding habit, which is regulated by many factors, including intrinsic and external factors, such as appetite, structure of the digestive tract, and feed palatability, is an important area of research in the intestinal microflora study. The feeding habit of fishes is one of the main factors affecting the differential colonization of fish intestinal flora. For example, the feeding habit increases the colonization of fish intestinal flora in the order omnivorous > herbivorous > carnivorous. It is also known that feeding habits influence intestinal digestion and structure. However, the influence of feeding habit on proximate composition, digestive enzyme secretion, and intestinal histomorphology is currently not well-known in fish. On the contrary, the feeding habit affects the composition and diversity of the intestinal microflora of fish. The composition and diversity of the microbiota in Carassius auratus, Ctenopharyngodon idella, Siniperca chuatsi, and Schizothorax grahami from the same environment have also not previously been studied. The present study aimed to compare and analyze the differences in the composition and diversity of the intestinal microflora of four fish species, investigating the relationship between their feeding habits and intestinal microflora as well. This study collected 12 intestine samples from each of the four fishes with different feeding habits, including omnivorous (C. auratus), herbivorous (C. idella), filter-feeder (S. chuatsi), and carnivorous (S. grahami), from the same pond. The composition and diversity of the microbial communities were determined by using high-throughput sequencing of 16S rRNA. Meanwhile, this study investigated the effects of feeding habits on the composition and diversity of the intestinal microflora of fish and predicted the potential functions of specific microflora with different nutrients. The results showed that the diversity of the intestinal microflora in fish was significantly affected by feeding habit (P < 0.05), such that higher levels occurred in the order omnivorous (C. auratus) > herbivorous (C. idella) > filter-feeder (S. grahami) > carnivorous (S. chuatsi). Proteobacteria and Firmicutes were the common dominant flora among the four fishes, although there were differences at the genera and species levels. For example, Acinetobacter and Bacteroides species were the most dominant flora in S. chuatsi and C. idella, respectively. Function prediction showed that the intestinal tract of S. chuatsi was mainly gram-negative. The disease resistance potential of C. idella was slightly higher than that of the other three fish species. Acinetobacter johnsonii, Acinetobacter lwoffii, and Pseudomonas stutzeri might help the host to digest protein, while Bacteroidetes may help the host to digest cellulose. In conclusion, feeding habit is one of the main factors affecting the differential colonization of fish intestinal flora. Analyzing the correlation between feeding habits and dominant intestinal flora as well as exploring the function of specific flora, could lay a theoretical foundation for studying the microbial effect of fish nutrition metabolism.

Path planning is a key technology for autonomous movement of inspection robot. The coal mine inspection robot has problems such as slow convergence speed and low search efficiency when planning paths using the rapidly-expanding random tree (RRT) algorithm. In order to solve the above problems, a combined force potential field guided RRT algorithm is proposed. The algorithm uses the repulsive force field in the combined force potential field to construct a dynamic step size. The coal mine inspection robot can adjust the step size near obstacles to improve the convergence speed of the algorithm. By utilizing the combined force field formed by the gravitational field in both the target node and random node directions, as well as the repulsive field generated by the nearest obstacle on the coal mine inspection robot, the generation direction of new nodes can be improved. It reduces the randomness of tree expansion and enhances the search efficiency of the algorithm. A pruning operation is performed on the paths planned based on the combined potential field guided RRT algorithm and smoothed using third-order Bessel curve. A simulation experiment is conducted in Matlab software on the path planning method of the coal mine inspection robot guided by the combined force potential field RRT algorithm. The results show that compared with the RRT algorithm and RRT* algorithm, the average path planning time of the combined potential field guided RRT algorithm in simple environments is reduced by 33.84% and 44.27%. The average path length is reduced by 15.29% and 4.42%, respectively. In complex environments, the average path planning time is reduced by 34.93% and 47.12%, and the average path length is reduced by 13.64% and 9.44%, respectively. In simulated coal mine environments, the average path planning time is reduced by 28.06% and 42.67%, and the average path length is reduced by 12.22% and 10.18%, respectively. After pruning and smoothing the path planned by the combined force potential field guided RRT algorithm, the number of turning points and angle changes in the path decrease, making the path smoother.

Objective The existing target speed planning algorithm for the automatic driving of urban rail transit train cannot handle in real time the temporary change of the line speed limit in case of emergency due to the large computational load and long computation time. With regard to the problem, a real-time target speed planning algorithm based on global optimization is proposed to generate the speed planning curve in real time. Method Based on the conditions of train current position, current speed and speed limit of the forward line, the speed planning curve is firstly generated in the shortest time through point by point calculation. Then the traction and braking levels are being adjusted to keep the train running at uniform acceleration or deceleration, optimizing the comfort index of the train running. Next, the cruising speed in the maximum speed limit section is adjusted to reduce unnecessary traction and braking time, optimizing the energy consumption index of the train running. Finally, the train speed planning curve is output. Result & Conclusion The simulation results show that the real-time speed planning curve generated by the proposed algorithm satisfies the basic constraints of safety, punctuality and accurate parking. Compared with the traditional algorithm, it improves the comfort level and reduces the energy consumption during train operation. Meanwhile, the proposed algorithm can effectively handle the temporary change of the line speed limit in emergency and optimize several operation indicators.

IntroductionSubjective cognitive decline (SCD) and mild cognitive impairment (MCI) are stages 2 and 3, respectively, of the Alzheimer’s continuum. The Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog’s) ten-words recall test is a validated method for the early detection of cognitive impairment in Alzheimer’s disease. However, limited studies have investigated its ability to differentiate between SCD and MCI.Methods203 participants with SCD and 62 participants with MCI underwent multiple neuropsychological assessments. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment-Basic (MOCA-B) served as brief global cognition tests. A binary logistic regression model was used to analyze the potential factors affecting MCI. The accuracy of the ten-words recall test was assessed using the area under the receiver operating characteristic (ROC) and the area under the curve (AUC).ResultsThe neuropsychological assessment revealed significant differences in the ten-words recall test scores between the SCD (median age 61 years; 70.44% female) and MCI (median age 64 years; 61.29% female) groups (p < 0.001), with the MCI group scoring the highest. Using a cut-off value of 3.15 for the ten-words recall test, sensitivity for distinguishing MCI from SCD reached 87%, while specificity stood at 61% (AUC 0.777, p < 0.001). DeLong’s test indicated no statistically significant difference in the ten-words recall test’s ability to distinguish between SCD and MCI compared to the total score of ADAS-Cog (AUC 0.833, p) and MMSE (AUC 0.784, p > 0.05). However, a significant difference was observed when compared to MoCA-B (AUC 0.973, p < 0.001). In the population with an education level of ≤ 9 years, the optimal cut-off value for the ten-words recall test was 3.15, yielding a sensitivity of 91% and a specificity of 45% (AUC = 0.674, p = 0.030). In the population with an education level > 9 years, the optimal cut-off value was 3.63, resulting in a sensitivity of 79% and a specificity of 71% (AUC = 0.785, p < 0.001).DiscussionThe ten-words recall test from the ADAS-cog may detect MCI early owing to its simplicity and quick administration. It is an effective and convenient tool for rapidly identifying mild cognitive impairment.

The aggregate gradation of asphalt mixture is one of the most important factors affecting the service life of asphalt pavement. In order to study the gradation of asphalt mixture with the best comprehensive performance, this study puts forward a new method of mineral aggregate gradation optimization based on the fuzzy analytic hierarchy process and comprehensive evaluation method, aiming at the multi-level and multi-index evaluation of the road performance of asphalt mixture. First, the orthogonal test design method is applied to design nine target gradations with coarse aggregate (>4.75 mm) and fine aggregate (

To reduce the noise in a pump piping system and increase the usage time of equipment, a new type of porous muffler is proposed in this paper. A water guide cone is incorporated into the muffler structure, which may help to redirect the fluid media in the piping system. The porous structure is adapted from a muffler shell, water cone wall and round bottom plate. According to this structure, the muffler sample is made, and a pump pipeline system test bench is set up. The outlet noise of the pump pipeline system is measured after installing the muffler. At the same time, the muffler is numerically simulated by combining computational fluid mechanics and Lighthill acoustic theory. The characteristics of the flow field and external sound field under three different flow conditions of 200 m³ /h, 400 m³ /h and 600 m³ /h are assessed. The numerical simulation results show the same dominant frequency and trend as the experimental results. The rationality of the numerical simulation is verified. Research shows that: the level of sound pressure at the muffler's outlet is lower than at the inlet, causing muffling, and the characteristics of a quadrupole sound source appear at the outlet. The proposed muffler has a certain effect in reducing noise in the pump pipeline system. [ABSTRACT FROM AUTHOR]

The E6 and E7 oncoproteins of human papillomavirus (HPV) are considered promising targets for HPV-related cancers. In this study, we evaluated novel T cell receptor mimic (TCRm) nanobodies targeting the E629-38 peptide complexed with human leukocyte antigen (HLA)-A∗02:01 in the chimeric antigen receptor (CAR) format. We isolated two dromedary camel nanobodies, F5 and G9, through phage display screening. F5 bound more efficiently to the complex expressed on cells, including peptide-pulsed T2, overexpressed 293E6, and cervical cancer lines CaSki and SS4050, compared to G9. CAR-T cells based on the F5 nanobody specifically killed target cells, including 293E6, CaSki, and SS4050 in vitro, through activation of nuclear factor of activated T cells (NFAT) and nuclear factor κB (NF-κB) signaling. Importantly, F5 CAR-T cells inhibited the growth of CaSki and SS4050 tumor xenografts in mice. These findings demonstrate that HPV-16+ cervical cancer can be targeted by F5 nanobody-based CAR-T cells, offering a valuable alternative strategy for treating HPV-16+ malignancies.

Currently, there is no established system for quantifying patterns of ocular ductions. This poses challenges in tracking the onset and evolution of ocular motility disorders, as current clinical methodologies rely on subjective observations of individual movements. We propose a protocol that integrates image processing, a statistical framework of summary indices, and criteria for evaluating both cross-sectional and longitudinal differences in ductions to address this methodological gap. We demonstrate that our protocol reliably transforms objective estimates of ocular rotations into normative patterns of total movement area and movement symmetry. This is a critical step towards clinical application in which our protocol could first diagnose and then track the progression and resolution of ocular motility disorders over time.

Resin monomer-induced dental pulp injury presents a pathology related to mitochondrial dysfunction. Melatonin has been regarded as a strong mitochondrial protective bioactive compound from the pineal gland. However, it remains unknown whether melatonin can prevent dental pulp from resin monomer-induced injury. The aim of this study is to investigate the effects of melatonin on apoptosis of mouse preodontoblast cells (mDPC6T) induced by triethylene glycol dimethacrylate (TEGDMA), a major component in dental resin, and to determine whether the JNK/MAPK signaling pathway mediates the protective effect of melatonin. A well-established TEGDMA-induced mDPC6T apoptosis model is adopted to investigate the preventive function of melatonin by detecting cell viability, apoptosis rate, expressions of apoptosis-related proteins, mitochondrial ROS (mtROS) production, mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) level. Inhibitors of MAPKs are used to explore which pathway is involved in TEGDMA-induced apoptosis. Finally, the role of the JNK/MAPK pathway is verified using JNK agonists and antagonists. Our results show that melatonin attenuates TEGDMA-induced mDPC6T apoptosis by reducing mtROS production and rescuing MMP and ATP levels. Furthermore, mitochondrial dysfunction and apoptosis are alleviated only by the JNK/MAPK inhibitor SP600125 but not by other MAPK inhibitors. Additionally, melatonin downregulates the expression of phosphorylated JNK and counteractes the activating effects of anisomycin on the JNK/MAPK pathway, mimicking the effects of SP600125. Our findings demonstrate that melatonin protects mDPC6T cells against TEGDMA-induced apoptosis partly through JNK/MAPK and the maintenance of mitochondrial function, offering a novel therapeutic strategy for the prevention of resin monomer-induced dental pulp injury.

Acinetobacter baumannii is a low-GC-content Gram-negative opportunistic pathogen that poses a serious global public health threat. Convenient and rapid genetic manipulation is beneficial for elucidating its pathogenic mechanisms and developing novel therapeutic methods. In this study, we report a new CRISPR-FnCpf1-based two-plasmid system for versatile and precise genome editing in A. baumannii. After identification, this new system prefers to recognize the 5′-TTN-3′ (N = A, T, C or G) and the 5′-CTV-3′ (V = A, C or G) protospacer-adjacent motif (PAM) sequence and utilize the spacer with lengths ranging from 19 to 25 nt. In direct comparison with the existing CRISPR-Cas9 system, it exhibits approximately four times the targetable range in A. baumannii. Moreover, by employing a tandem dual crRNA expression cassette, the new system can perform large-fragment deletion and simultaneous multiple gene editing, which is difficult to achieve via CRISPR-Cas9. Therefore, the new system is valuable and can greatly expand the genome editing toolbox of A. baumannii.

Abstract With the rapid development of multimedia technology and the massive accumulation of user data, a huge amount of data is rapidly generated and shared over the network, while the problems of inappropriate data access and abuse persist. Reversible data hiding in encrypted images (RDHEI) is a privacy-preserving method that embeds protected data in an encrypted domain and accurately extracts the embedded data without affecting the original content. However, the amount of embedded data has been one of the major limitations in the performance and application of RDHEI. Currently, the main approaches to improve the capacity of RDHEI are either to increase the overall capacity or to reduce the length of the auxiliary information. In this paper, we propose a novel RDHEI scheme based on multi-prediction and adaptive Huffman encoding. To increase the overall capacity, we propose a multi-prediction, called MED+GAP predictor, to generate the label map data of non-reference pixels prior to image encryption. Then, an adaptive Huffman coding is designed to compress the generated labels in order to reduce the embedding length of the auxiliary information used for the extraction and recovery. Experiments show that the proposed method with MED+GAP predictor and adaptive Huffman coding improves 0.052 bpp, 0.023 bpp, and 0.047 bpp on average over the other state-of-the-art methods on the BOSSBase, BOWS-2, and UCID datasets, respectively, while maintaining security and reversibility.