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Supplementary Material 1 Table S1. The characteristics of patients from 2017 to 2019.

Jun Zhou, Wenhan Huang, Feifeng Ren, Lei Luo, Dongmei Huang, Lin Tang Department of Rheumatology and Immunology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Lin TangDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing, 400010, People’s Republic of ChinaEmail tanglin1217@163.comObjective: The aim of our study was to elucidate the potential prognostic factors in anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive patients.Methods: We divided anti-MDA5-positive patients into death and survival groups. The differences in clinical characteristics were analyzed.Results: A total of 56 cases were included. The death group comprised 10 (17.9%) cases, and the survival group comprised 46 (82.1%) cases. Median age of the death group was greater than the survival group, 59.50 years vs 39.25 years, p< 0.05. The death group had lower lymphocyte count and albumin and higher erythrocyte sedimentation rate, ferritin and lactate dehydrogenase initially (p< 0.05, respectively). Ground-glass opacity on chest computed tomography was found more often in the death group (p< 0.05), in which there was an absence of honey-combed shadow initially. The diagnosis of interstitial pneumonia with autoimmune features was higher in the death group than the survival group (70% vs 13%, p< 0.05). The median dose of maximum daily methylprednisolone in the death group (160 mg/d) was higher than that in the survival group (48 mg/d) (p< 0.05).Conclusion: Advanced age, low lymphocyte count and albumin, and increased levels of inflammatory markers may portend poor prognosis in anti-MDA5-positive patients. Extra-large doses of glucocorticoid may have no additional benefit in these patients.Keywords: anti-melanoma differentiation-associated gene 5 antibody, interstitial lung disease, clinical manifestation, prognosis

Wenhan Huang, Feifeng Ren, Lei Luo, Jun Zhou, Dongmei Huang, Lin Tang Department of Rheumatology and Immunology of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Lin TangDepartment of Rheumatology and Immunology of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of ChinaEmail hopetang@163.comObjective: Clinical characterization of lipid metabolism in untreated patients with anti-melanoma differentiation-associated gene 5 antibodies-positive (anti-MDA5+).Methods: Body-mass index (BMI), autoantibodies, lipid levels, and serum ferritin levels in 57 anti-MDA5+ patients were determined in the Department of Rheumatology and Immunology of the Second Affiliated Hospital of Chongqing Medical University.Results: Plasma high-density lipoprotein (HDL) and apolipoprotein A1 (ApoA1) levels were significantly lower in deceased group than in the survival group (P < 0.05). Plasma levels of HDL and ApoA1 were significantly lower in patients who were simultaneously anti-MDA5+ and anti-Ro-52+ than in patients who were anti-MDA5+ alone (P < 0.05). Plasma levels of total cholesterol, low-density lipoprotein, HDL, and ApoA1 were significantly decreased in patients with high levels of serum ferritin compared with patients with low levels (P < 0.05). There were no significant differences in blood lipid levels between patients grouped according to BMI.Conclusion: 1) HDL and ApoA1 levels are important indicators of poor prognosis in anti-MDA5+ patients; 2) Dysregulated lipid metabolism in anti-MDA5+ patients is closely associated with anti-Ro-52 antibody and ferritin levels but independent of BMI; 3) HDL involvement in inflammation and immune regulation merits close attention by rheumatologists.Keywords: anti-melanoma differentiation-associated gene 5 antibodies, anti-Ro-52 antibody, lipid, high-density lipoprotein, apolipoprotein A1

The effective utilization of manure in cropland systems is essential to sustain yields and reduce reactive nitrogen (Nr) losses. However, there are still uncertainties regarding the substitution of mineral nitrogen (N) fertilizer with manure in terms of its effects on crop yield and Nr losses. We conducted a comprehensive meta-analysis of wheat, maize, and rice applications in China and discovered that substituting mineral N fertilizer with manure increased wheat and maize yields by 4.9 and 5.5 %, respectively, but decreased rice yield by 1.7 %. The increase of yield is larger at low N application and low mineral N substitution rates ((SR) ≤30 %) for silt soils, warm regions, and acidic soils. High SR (>70 %) decreased rice yield as well as the N use efficiency of wheat and maize. Substitution of mineral N fertilizer with manure resulted in lower NH3 volatilization for wheat (48.7 %), lower N2O and NH3 emissions, and N runoff for maize (12.8, 49.6, and 66.7 %, respectively), and lower total Nr losses for rice (11.3–26.5 %). The loss of Nr was significantly and negatively correlated with soil organic carbon content. The rate of N application, soil properties, and climate were critical factors influencing N2O and NH3 emissions and N leaching, whereas climate or soil properties were the dominant factors influencing response in N runoff. We concluded that in silt soils, warm regions, and neutral soils, a ≤ 50 % substitution of mineral N fertilizer with manure can sustain crop yields while mitigating Nr losses.

Lichuan Zeng,1 Huaqiang Liao,1 Fengchun Ren,1 Yudong Zhang,1 Qu Wang,2 Mingguo Xie1 1Department of Radiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Ultrasound, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of ChinaCorrespondence: Mingguo Xie; Qu WangHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of ChinaEmail 767030837@qq.com; 444028177@qq.comAbstract: Percutaneous computed tomography (CT)-guided transthoracic needle biopsy (TTNB) is a valuable procedure for obtaining tissue or cells for diagnosis, which is especially indispensable in thoracic oncology. Pneumothorax and hemoptysis are the most common complications of percutaneous needle biopsy of the lung. According to reports published over the past decades, pneumothorax incidence in patients who underwent TTNB greatly varies. The morbidity of pneumothorax after CT-guided TTNB depends on several factors, including size and depth of lesions, emphysema, the number of pleural surfaces and fissure crossed, etc. Attention to biopsy planning and technique and post-biopsy precautions help to prevent or minimize potential complications. Many measures can be taken to help prevent the progression of a pneumothorax, which in turn might reduce the number of pneumothoraces requiring chest tube placement. A multitude of therapeutic options is available for the treatment of pneumothorax, varying from observation and oxygen treatment, simple manual aspiration, to chest tube placement. When a pneumothorax develops during the biopsy procedure, it can be manually aspirated after the needle is retracted back into the pleural space or by inserting a separate needle into the pleural space. Biopsy side down positioning of the patient after biopsy significantly reduces the incidence of pneumothorax and the requirement of chest tube placement. Aspiration in biopsy side down position is also recommended for treating pneumothorax when simple manual aspiration is unsuccessful or delayed pneumothorax occurred. Chest tube placement is an important treatment strategy for patients with a large or symptomatic pneumothorax. Clinicians are encouraged to understand the development, prevention, and treatment of pneumothorax. Efforts should be made to reduce the incidence of pneumothorax in biopsy planning and post-biopsy precautions. When pneumothorax occurs, appropriate treatment should be adopted to reduce the risk of worsening pneumothorax.Keywords: pneumothorax, lung biopsy, aspiration, chest tube placement, computed tomography, CT

Feifei Ren,1 Rongjuan Guo2 1Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2Department of Neurology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078, People’s Republic of ChinaCorrespondence: Rongjuan GuoDepartment of Neurology, Dongfang Hospital, Beijing University of Chinese Medicine, No. 6, 1st Section, Fangxingyuan, Fangzhuang, Fengtai District, Beijing City, People’s Republic of ChinaTel/Fax +86 10-6768-9655Email 381160563@qq.comAbstract: Depression is a major disease that can affect both mental and physical health, limits psychosocial functioning and diminishes the quality of life. But its complex pathogenesis remains poorly understood. The dynamic changes of synaptic structure and function, known as synaptic plasticity, occur with the changes of different cellular microenvironment and are closely related to learning and memory function. Accumulating evidence implies that synaptic plasticity is integrally involved in the pathological changes of mood disorders, especially in depressive disorder. However, the complex dynamic process of synaptic plasticity is influenced by many factors. Here, we reviewed and discussed various factors affecting synaptic plasticity in depression, and proposed a specific framework named synaptic microenvironment, which may be critical for synaptic plasticity under pathological conditions. Based on this concept, we will show how we understand the balance between the synaptic microenvironment and the synaptic plasticity network in depression. Finally, we point out the clinical significance of the synaptic microenvironment in depression.Keywords: depression, synaptic plasticity, synaptic microenvironment, glia, influence factors

Fang Ren, Christina Shrestha, Huirong Shi, Fangfang Sun, Minghui Zhang, Yuan Cao, Gailing Li Department of Gynecology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Fang RenDepartment of Gynecology, First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, People’s Republic of ChinaTel +8613849115866Email renfang@foxmail.comPurpose: The retinoblastoma binding protein RBP2 (KDM5A) is a histone demethylase that promotes cell growth in many human cancers. A series of functional experiments were conducted to explore the role of miR-421/KDM5A in ovarian cancer cells and their underlying molecular mechanisms.Materials and Methods: Public microarray databases were analyzed to assess KDM5A and miR-421 expression in ovarian cancer. KDM5A was predicted to be a target of miR-421 using software analysis. The expression of the miR-421/KDM5A regulatory axis in ovarian cancer and the mechanisms of its effects on proliferation, migration, and invasion of ovarian cancer cell lines were investigated.Results: Compared with normal ovarian tissues, the expression of KDM5A mRNA and protein was elevated (P< 0.05), and miR-421 expression was reduced in ovarian cancer tissue (P< 0.05). miR-421 was found to bind specifically to the KDM5A gene. Silencing KDM5A or overexpressing miR-421 significantly inhibited proliferation, migration, and invasion of OVCAR-8 and SKOV-3 cells. Similarly, compared with nude mice injected with cells transfected with empty capsids, the in vivo proliferation rate of OVCAR-8 cells after miR-421 overexpression was reduced significantly.Conclusion: The miR-421/KDM5A regulatory axis plays an important role in the development and progression of ovarian cancer cells.Keywords: ovarian cancer, KDM5A/RBP2, miR-421, progression

Pan Wang,1,* Honglin Zhao,1,* Qingchun Zhao,1,* Fan Ren,1 Ruifeng Shi,1 Xingyu Liu,1 Jinghao Liu,1 Hongyu Liu,2 Gang Chen,1 Jun Chen1,2 1Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Chen Email huntercj2004@yahoo.comBackground: The incidence of venous thromboembolism (VTE) is higher in patients with lung cancer. The aim of this study was to investigate the risk factors associated with postoperative VTE and explore the VTE predication capacity of D-dimer kinetics.Patients and Methods: Six hundred patients who had lung tumor surgery were analyzed retrospectively between January 2018 and August 2019, and venous ultrasound imaging and D-dimer examination before and after surgery were recommended to all operative patients. Of these 600 patients, 523 patients had venous thromboembolism after surgery, and 77 patients had not found. The general clinical data, postoperative prophylactic anticoagulant therapy, early systemic thromboprophylaxis, 50% increment of D-dimer, 100% increment of D-dimer, and perioperative (preoperative and days 1, 3, and 5 after surgery) D-dimer levels were collected. Logistic regression analysis was used to analyze the independent risk factors of postoperative VTE.Results: VTE developed in 77 (12.8%) patients. In a univariate analysis, age, surgical approach, tumor size, histology, postoperative preventive anticoagulation, postoperative limb compression therapy, postoperative hemostasis, duration of operation, early systemic thromboprophylaxis, 100% increment of D-dimer, preoperative and postoperative D-dimer level, intraoperative blood loss, and time spent in the hospital were significantly different between the thrombus group and nonthrombus group (P < 0.05). Multivariate analysis showed that age > 60 years (P = 0.006) and D-dimer level on 5 days after surgery (P =  0.000) were significant independent risk factors for VTE. Postoperative D-dimer was significantly higher than the preoperative level (P < 0.001). Postoperative D-dimer level was significantly different between benign and malignant tumor groups (P < 0.05) and between the thrombus group and nonthrombus group (P < 0.001). Preventive anticoagulation and limb compression therapy starting from the first day after surgery was statistically significant between the thrombus group and the nonthrombus group (P < 0.05).Conclusion: Continuous detection of D-dimer level after pulmonary tumor surgery combined with thrombotic-related risk factors can better evaluate the occurrence of VTE. Preventive anticoagulant therapy and limb compression therapy starting from the first day after surgery can effectively reduce the incidence of VTE.Keywords: anticoagulants, D-dimer, lung neoplasms, risk factors venous thromboembolism

Shuhan Liu,1 Rongjuan Guo,2 Fei Liu,3 Qingjie Yuan,4 Yao Yu,1 Feifei Ren1 1Second Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 2Department of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 100078, People’s Republic of China; 3College of Acupuncture and Massage, Changchun University of Chinese Medicine, Changchun 130117, People’s Republic of China; 4Department of Traditional Chinese Medicine, Tsinghua University Yuquan Hospital, Beijing 100040, People’s Republic of ChinaCorrespondence: Rongjuan GuoDepartment of Neurology, Dongfang Hospital Beijing University of Chinese Medicine, No. 6 Fangxingyuan 1st Block, Fengtai District, Beijing City, People’s Republic of ChinaTel +86 1 861 137 7633Fax +86 1064286498Email dfguorongjuan@163.comPurpose: Gut microbiota affects various physiological functions in the host and has crucial effects on the nervous system. There is increasing evidence of a correlation between gut microbiota and depression; however, the mechanisms underlying the regulation of depression-like behavior by gut microbiota remain unclear. In this study, we assessed the regulatory mechanism of gut microbiota on depression-like behavior in rats.Methods: We transplanted fecal microbiota obtained from patients with depression and healthy individuals into germ-free (GF) rats (n=18) through fecal microbiota transplantation technology. Next, we assessed the affective behavior in the rats using the forced swimming test and a sucrose preference test. We used enzyme-linked immunosorbent assay (ELISA) to determine the hippocampal levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and noradrenaline (NE) and the serum levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-1 (IL-1), interleukin-1 (IL-4), and interleukin-1 (IL-10). The mitochondrial morphology of small intestinal epithelial cells was observed through transmission electron microscopy.Results: Rats that received fecal microbiota from patients with depression (depression microbiota) exhibited depression-like behavior. They presented decreased levels of hippocampal neurotransmitters, serum CORT levels, and anti-inflammatory cytokine levels, as well as increased ACTH, CRH, and serum levels of multiple pro-inflammatory cytokines. Observation of the mitochondria ultrastructure showed damaged mitochondria in the intestinal epithelial cells, significant endoplasmic reticulum expansion, and border aggregation of nuclear chromatin.Conclusion: Our findings suggested that the depression-like behaviors induced by the depression microbiota through the neuroendocrine-immune-mitochondrial pathway, which were associated with neuroendocrine disorders, inflammatory responses, and mitochondrial damage.Keywords: gut microbiota, depression, neurotransmitter, HPA axis, immune, mitochondrial

Saixu Huang, 1–3,* Zhiyong Huang, 1–3,* Zhiqin Fu, 3,* Yamin Shi, 3, 4 Qi Dai, 1, 2 Shuyan Tang, 3 Yongwei Gu, 3 Youfa Xu, 3 Jianming Chen, 3, 4 Xin Wu, 3 Fuzheng Ren 1, 2 1Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of China; 2Engineering Research Centre of Pharmaceutical Process Chemistry, Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China; 3Shanghai Weier Biological Medicine Science and Technology Co. Ltd., Shanghai, People’s Republic of China; 4Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fuzheng RenSchool of Pharmacy, East China University of Science and Technology, No. 130, Meilong Road, Shanghai 200237, People’s Republic of ChinaTel/Fax +86 21 6425 3255Email fzren@ecust.edu.cnXin WuShanghai Weier Biological Medicine Science and Technology Co. Ltd., No. 358, Tian Chen Road, Shanghai 201799, People’s Republic of ChinaTel/Fax +86 21 3119 8947Email xinwu007@126.comPurpose: Nimodipine (NIMO) is used clinically to treat ischemic damage resulting from subarachnoid hemorrhage. However, clinical application of NIMO is limited by poor aqueous solubility and low safety. To overcome these limitations, a novel two-vial NIMO-loaded nanoemulsion (NIMO-TNE) was designed in this study.Methods: NIMO-TNE was prepared by mixing a nimodipine-polyethylene glycol 400 (NIMO-PEG400) solution and a commercially available 20% injectable blank nanoemulsion (BNE). Drug distribution in NIMO-TNE, physical stability, and dilution stability were evaluated in vitro, and pharmacokinetics and pharmacodynamics were evaluated in vivo. Safety was assessed using the hemolysis test and the intravenous irritation test, and acute toxicity of NIMO-TNE was compared with that of commercial Nimotop injection.Results: Drug loading (DL) in NIMO-TNE was enhanced 5-fold compared with that in Nimotop injection. The mean particle size of NIMO-TNE was 241.53 ± 1.48 nm. NIMO-TNE and NIMO-TNE diluted in 5% glucose injection and 0.9% sodium chloride was stable for a sufficient duration to allow for clinical use. In addition, NIMO-TNE exhibited a similar pharmacokinetic profile and similar brain ischemia reduction in a rat middle cerebral artery occlusion (MCAO) model compared to Nimotop injection. Furthermore, NIMO-TNE did not induce hemolysis at 37°C, and NIMO-TNE induced less intravenous irritation than Nimotop injection. Moreover, NIMO-TNE could be injected at a 23-fold higher dose than the LD 50 of Nimotop injection with no obvious toxicity or side effects.Conclusion: NIMO-TNE is a promising formulation suitable for intravenous injection, is easy to prepare, and exhibits excellent safety.Keywords: nimodipine, nanoemulsion, pharmacokinetics, MCAO, LD50

We present a numerical study on swift ion induced effects in crystalline 3C silicon carbide (SiC) by the two-temperature model, which considering the electronic stopping and electronic-phonon coupling effects simultaneously. Given the results of overlapping radiation, there is only a minority of defects formed in the system during the ionization dominance stage. When the incident energy is braked from 20 MeV to 500 keV by ionization after the first 0.91 ps, the system enters the nuclear stopping stage, the incident energy decreases to 50 keV in 0.44 ps, accomplished with a dramatic increase of damage. In addition, for the low-energy ion implantation process, the sparse atomic arrangement perpendicular to the implantation direction will reduce the response of the atomic subsystem. Insights into the complex correlations between electronic and atomic response may pave the way to elucidate the mechanism behind the experimentally observed defect formation and evolution under extreme energy deposition. (c) 2021 Elsevier B.V. All rights reserved.

Background Plants have evolved a panoply of specialized metabolites that increase their environmental fitness. Two examples are caffeine, a purine psychotropic alkaloid, and crocins, a group of glycosylated apocarotenoid pigments. Both classes of compounds are found in a handful of distantly related plant genera (Coffea, Camellia, Paullinia, and Ilex for caffeine; Crocus, Buddleja, and Gardenia for crocins) wherein they presumably evolved through convergent evolution. The closely related Coffea and Gardenia genera belong to the Rubiaceae family and synthesize, respectively, caffeine and crocins in their fruits. Results Here, we report a chromosomal-level genome assembly of Gardenia jasminoides, a crocin-producing species, obtained using Oxford Nanopore sequencing and Hi-C technology. Through genomic and functional assays, we completely deciphered for the first time in any plant the dedicated pathway of crocin biosynthesis. Through comparative analyses with Coffea canephora and other eudicot genomes, we show that Coffea caffeine synthases and the first dedicated gene in the Gardenia crocin pathway, GjCCD4a, evolved through recent tandem gene duplications in the two different genera, respectively. In contrast, genes encoding later steps of the Gardenia crocin pathway, ALDH and UGT, evolved through more ancient gene duplications and were presumably recruited into the crocin biosynthetic pathway only after the evolution of the GjCCD4a gene. Conclusions This study shows duplication-based divergent evolution within the coffee family (Rubiaceae) of two characteristic secondary metabolic pathways, caffeine and crocin biosynthesis, from a common ancestor that possessed neither complete pathway. These findings provide significant insights on the role of tandem duplications in the evolution of plant specialized metabolism.

BackgroundInfectious mononucleosis (IM) is an infectious clinical entity commonly seen in adolescence and early adulthood. It is caused in the majority of cases by Epstein-Barr virus (EBV) and it presents as pharyngitis, fever, and lymphadenopathy. As the viruses mainly target the lymphocytes and reticuloendothelial system of the body, leading to the proliferation of the lymphatic tissues, it is often mistaken as lymphoma. Most cases of IM can be easily distinguished from lymphoma by clinical presentations and laboratory findings. However, atypical clinical presentations or laboratory findings occasionally occur, including the ages of patients over 30, generalized or isolated lymphadenopathy at unusual sites, negative heterophile antibody tests, absence of atypical lymphocytosis in the peripheral blood smear, etc. These atypical cases may lead to confused diagnosis. Therefore, IM should be differentiated from malignant lymphoma. In this paper, we reported a case of atypical IM in the cervical region of an adult, with elder age and longer disease course than typical IM.Case presentationIn this paper, we reported a case of IM in the cervical region of a 31-year-old man, and reviewed the recent literatures on the pathogenesis, as well as differential diagnosis of IM.ConclusionWhen facing enlarged tonsil or cervical lymph nodes, the pathologists should increase vigilance to the differential diagnosis between infectious diseases and lymphomas. Especially in ambiguous cases, it is essential to test for EBER by in situ hybridization to rule out IM before making a preliminary diagnosis of lymphoma.

Fangping Ren,1,* Tian Zhao,2,* Bing Liu,3 Lei Pan11Department of Respiratory, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, People’s Republic of China; 2Department of Clinical Laboratory, The 161st Hospital of PLA, Wuhan, 430010, People’s Republic of China; 3Department of Disease Control and Prevention, PLA Rocket Force Characteristic Medical Center, Beijing, People’s Republic of China*These authors contributed equally to this workPurpose: The aim of this study was to identify the prognostic value of blood neutrophil–lymphocyte ratio (NLR) in patients with advanced non-small-cell lung cancer (NSCLC) who received immune checkpoint blockade (ICB) therapy.Materials and methods: 147 advanced NSCLC patients were enrolled in this study from June 30, 2013, to August 30, 2017. Survival analysis used the Kaplan and Meier methodology. The mean follow-up time was 2.6 years. The phenotypic T cells subtypes were evaluated by flow cytometry.Results: Of these patients, receiver operating characteristic (ROC) curves analysis were used to confirm the cut-off value, and patients were stratified into NLR>2.5 (n=88) and NLR≤2.5 (n=59) groups. Survival analysis showed that patients with NLR≤2.5 had significantly favorable overall survival (OS) and progression-free survival (PFS) compared with patients with NLR>2.5. After stratified with the tumor mutational burden (TMB), we further found that patients with NLR≤2.5 had significantly favorable OS and PFS compared with patients with NLR>2.5 in the group of patients with TMB>10, while in group patients with TMB≤10, patients with NLR≤2.5 had no significantly favorable OS and PFS compared with patients with NLR>2.5. The CD3+and CD8+/CD28+T cell subsets were significantly increased in patients with NLR≤2.5 (P

Fan Ren,* Minghui Liu,* Xiaoqian Xu, Hongbing Zhang, Xin Li, Jinghao Liu, Jun Chen Department of Lung Cancer Surgery, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China *These authors contributed equally to this work Abstract: Lung cancer is one of the most common causes of cancer-related death. Most of them already have distant metastasis at the time of diagnosis, but ureteral metastasis is extremely rare. Herein, we reported a lung cancer patient with a metastatic lesion from lung cancer at the distal end of the ureter. The patient is a 61-year-old male diagnosed with invasive adenocarcinoma after the right upper lobe resection and system lymph node dissection surgery. After 12 months of surgery, during routine physical examination, lower abdominal enhanced computed tomography showed there was a soft mass with uneven continuous enhancement at the distal end of the ureter. After the surgery of ureter, the mass was histologically considered to be a metastatic lesion arising from the primary lung cancer. Keywords: non-small-cell lung cancer, ureteral metastasis, prognosis, treatment

Weiwei Zhu,1,2,* Hongqiang Li,1,2,* Yan Yu,1,2 Jianan Chen,1,2 Xiaolong Chen,1,2 Fang Ren,2 Zhigang Ren,1,2 Guangying Cui1,2 1Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; 2Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China *These authors contributed equally to this work Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy with high incidence rate and poor prognosis. Enolase-1 (ENO1), a key glycolytic enzyme, has been implicated in the tumorigenesis of various cancers. However, its diagnostic value and clinical significance in HCC are unclear.Methods: Data of 374 HCC tissues and 50 nontumor tissues were retrieved from The Cancer Genome Atlas database, and the expression level of ENO1 mRNA in HCC was evaluated. In addition, a meta-analysis of 12 HCC cohorts deposited in the Gene Expression Omnibus database was conducted to determine ENO1 expression levels. The diagnostic power of ENO1 in distinguishing HCC tissues from non-HCC tissues was confirmed by receiver operating characteristic (ROC) curve analysis. A tissue microarray comprising 93 HCC specimens and 87 adjacent normal specimens was used to validate ENO1 expression, and its prognostic value in HCC was ascertained by Kaplan–Meier analysis and Cox regression models. In addition, the gene set enrichment analysis was performed to predict the molecular mechanism of ENO1 action in HCC.Results: ENO1 was overexpressed in HCC tissues and associated with worse outcomes in terms of overall survival (OS) (P

Yue Lu,1 Wenjun Jiang,1 Xin Wu,2 Saixu Huang,1 Zhiyong Huang,1 Yamin Shi,3 Qi Dai,1 Jianming Chen,2 Fuzheng Ren,1 Shen Gao4 1Shanghai Key Lab New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of China; 2Shanghai Weier Biological Medicine Science and Technology Co. Ltd., Shanghai, People’s Republic of China; 3Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China; 4Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China Background: Vectors are essential for successful gene delivery. In the present study, a tumor-targeting cationic gene vector, known as the disulfide cross-linked arginine-aspartic acid peptide modified by HAIYPRH (T7) peptide (CRD-PEG-T7), was designed for targeted delivery of plasmid DNA (pDNA) for gene therapy of prostate cancer (PCa). Methods: The structure of CRD-PEG-T7 was determined and the cellular uptake efficacy, gene transfection efficacy, cytotoxicity, and the targeting effect of the CRD-PEG-T7–plasmid DNA complex were examined. Results: The results demonstrated that the CRD-PEG-T7–plasmid DNA complex was nanosized and had a positively charged surface, good cellular uptake efficacy, minimal cytotoxicity, and a dual-targeting effect as compared with the CRD-PEG–plasmid DNA complex. The peptide T7-modifed new delivery system was able to target the highly expressed transferrin receptor (TfR) on tumor cells with an efficiency four-fold higher than that of the non-modified system. Conclusion: The results above indicatd that the CRD-PEG-T7–plasmid DNA complex may prove to be a promising gene delivery system targeting bone-metastatic tumor. Keywords: arginine peptide, aspartic acid peptide, tumor targeting, DNA delivery, bone metastasis prostate cancer

Chen Xue,1,2,* Yuting He,1,2,* Qiuyue Hu,1,2 Yan Yu,1,2 Xiaolong Chen,1,2 Jianan Chen,1,2 Fang Ren,2 Juan Li,1,2 Zhigang Ren,1,2 Guangying Cui,1,2 Ranran Sun1–3 1Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; 2Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; 3National Engineering Laboratory for Internet Medical Systems and Applications, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China *These authors contributed equally to this work Background: PIM1, a serine/threonine kinase, plays an essential role in tumorigenesis of multiple types of tumors. However, the expression pattern and functions of PIM1 in gallbladder cancer (GBC) remain largely unknown. Materials and methods: Immunohistochemistry, quantitative real-time PCR, and western blot analysis were performed to measure the expression of PIM1. Tissue microarray analysis was used to confirm the relationship between PIM1 expression and clinical outcomes of GBC patients. Finally, in vivo and in vitro functional studies were performed to detect the inhibition of PIM1 by RNAi or specific inhibitor in GBC cells. Results: We observed that PIM1 was dramatically overexpressed in GBC tissues, and its expression levels were positively related with clinical malignancies and a poor prognosis. Inhibition of PIM1 via RNAi or enzyme-specific inhibitor could suppress GBC cell proliferation, migration, and invasion both in vitro and vivo. Additionally, flow cytometry assays and cell cycle assays indicated that PIM1 inhibition promoted cell apoptosis and induced cell cycle arrest. Remarkably, inhibition of PIM1 could drive a metabolic shift from aerobic glycolysis to oxidative phosphorylation. We found that inhibition of PIM1 mechanistically reduced glucose consumption by regulating key molecules in aerobic glycolysis. Conclusion: PIM1 may serve as an oncogene in GBC and be involved in the regulation of glycolysis. PIM1 is a promising therapeutic target for the treatment of human GBC. Keywords: PIM1, gallbladder cancer, aerobic glycolysis, tumor progression

The evaluation of the soil contaminated by heavy metals can help to judge whether the soil meets the standard and whether the pollution will threaten human health and the ecological environment. In this study, the farmland soil from eight districts in Beijing was used as the research object, and the concentration of heavy metal elements, Pb, As and Cd in the soils and agricultural products were analyzed. The analysis results showed that: (1) The evaluation based on the improved Hakanson method suggested that the crops exhibit a significantly higher ability to absorb Cd than to absorb Pb and As. Pb, As and Cd are all at normal level of ecological risk; among them, Cd is mainly in a moderate ecological risk, without strong ecological risk. (2) Based on the Improved analytic hierarchy process(AHP) of evaluation, 0.2317 is the average value of the integrated index of heavy metal pollution of soil in the study area, which is a mild level of pollution. (3) Through the calculation of various parameters in the Influence index of comprehensive quality(IICQ) of soil and agricultural products, it was found that 0＜IICQS＜1, suggesting that the environmental quality of soil is at a clean level. In summary, the pollution of heavy metals Pb, As and Cd in the farmland soils and crops in the eight districts of Beijing, including Fangshan, Daxing, Shunyi, and Shijingshan is at a low level, and no significant impact has been brought to the surrounding environment.

Zhu Y, Ren F, Zhu Y, et al. Nat Sci Sleep. 2020;12:1067–1074. The authors have advised that the name of last author on page1067 is incorrect. Mingwen Zheng should be Minwen Zheng. The authors apologize for this error. Read the original article

Data-driven predictive models are increasingly used in education to support students, instructors, and administrators. However, there are concerns about the fairness of the predictions and uses of these algorithmic systems. In this introduction to algorithmic fairness in education, we draw parallels to prior literature on educational access, bias, and discrimination, and we examine core components of algorithmic systems (measurement, model learning, and action) to identify sources of bias and discrimination in the process of developing and deploying these systems. Statistical, similarity-based, and causal notions of fairness are reviewed and contrasted in the way they apply in educational contexts. Recommendations for policy makers and developers of educational technology offer guidance for how to promote algorithmic fairness in education., Forthcoming in W. Holmes & K. Porayska-Pomsta (Eds.), Ethics in Artificial Intelligence in Education, Taylor & Francis

Predictive models for identifying at-risk students early can help teaching staff direct resources to better support them, but there is a growing concern about the fairness of algorithmic systems in education. Predictive models may inadvertently introduce bias in who receives support and thereby exacerbate existing inequities. We examine this issue by building a predictive model of student success based on university administrative records. We find that the model exhibits gender and racial bias in two out of three fairness measures considered. We then apply post-hoc adjustments to improve model fairness to highlight trade-offs between the three fairness measures., FATED (Fairness, Accountability, and Transparency in Educational Data) Workshop at EDM 2020

Recent breakthroughs in bulk crystal growth of beta-Ga2O3 by the edge-defined film-fed technique has led to the commercialization of large-area beta-Ga2O3 substrates. Standard epitaxy approaches are being utilized to develop various thin-film beta-Ga2O3 based devices including lateral transistors. This article will discuss the challenges for metal organic chemical vapor deposition (MOCVD) of beta-Ga2O3 and the design criteria for use of this material system in power electronic device structures.

Thermomechanical deformation is one of the most efficient and facile routes to tailor microstructure in structural materials for mechanical property enhancement. Herein, the Ce‐modified SAF2507 super duplex stainless steel (Ce‐SAF2507) is deformed at different levels from 30% to 90% at a cryogenic temperature (–196 °C) to achieve superior mechanical performances. Cryogenic rolling increase fiber texture and induce ultra‐fine grain refinement which brings grains to ≈10 nm in the selected steel. The high‐density dislocations and deformation twins in the cryogenically rolled Ce‐SAF2507 lead to the nucleation and growth of martensite. Increases in the martensite volume fraction and nanoscale grain refinement occur at higher deformation levels. Cryogenically rolled deformation results in the overall increase in the Ce‐SAF2507 hardness. A higher hardness increment of austenite–martensite dual‐phase compared to that of ferrite is attributed to the austenite–martensite‘s higher work hardening ability. Furthermore, the ultimate tensile strength and yield strength increase with the deformation level, but the elongation decrease. Observed microstructural evolutions induced by cryogenic rolling enunciate the superiority of the present method over conventional ones to promote steel’ mechanical properties.

Yuting He,1,2,* Chen Xue,1,2,* Yan Yu,1,2 Jianan Chen,1,2 Xiaolong Chen,1,2 Fang Ren,2 Zhigang Ren,1,2 Guangying Cui,1,2 Ranran Sun1,2 1Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; 2Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China *These authors contributed equally to this work Background: Gallbladder cancer (GBC) is a highly lethal disease and the most common biliary tract malignant tumor with poor prognosis. Accumulating evidence indicates that cluster of differentiation 44 (CD44) is overexpressed in several malignancies and has a crucial role in the development of cancer. However, its expression and function in GBC are unclear. The aim of this study was to explore CD44 expression and its role in GBC. Materials and methods: The expression of CD44 was measured by immunohistochemistry. Tissue microarray analysis was used to confirm the relationship between CD44 expression and clinical outcomes of GBC patients. EDU assay, colony formation assay, cell migration and invasion assay were performed to detect the functions of CD44 in GBC-SD and NOZ transfected with si-RNA. Results: CD44 was overexpressed and associated with poor outcomes in GBC patients. The univariate and multivariate analyses confirmed that elevated CD44 was an independent prognostic factor for the OS of GBC patients. Silencing CD44 could suppress the GBC cell proliferation, migration and invasion in vitro, as well as attenuated cancer stem cell functions. Conclusion: CD44 markedly correlated with aggressive tumor behaviors and contributed to the progression of GBC, which could represent a novel prognostic marker and potential therapeutic target for GBC patients. Keywords: CD44, gallbladder cancer, cancer stem cells, tumor progression

© Copyright 2019 American Chemical Society. A central topic in single-atom catalysis is building strong interactions between single atoms and the support for stabilization. Herein we report the preparation of stabilized single-atom catalysts via a simultaneous self-reduction stabilization process at room temperature using ultrathin two-dimensional Ti 3-x C 2 T y MXene nanosheets characterized by abundant Ti-deficit vacancy defects and a high reducing capability. The single atoms therein form strong metal-carbon bonds with the Ti 3-x C 2 T y support and are therefore stabilized onto the sites previously occupied by Ti. Pt-based single-atom catalyst (SAC) Pt 1 /Ti 3-x C 2 T y offers a green route to utilizing greenhouse gas CO 2 , via the formylation of amines, as a C 1 source in organic synthesis. DFT calculations reveal that, compared to Pt nanoparticles, the single Pt atoms on Ti 3-x C 2 T y support feature partial positive charges and atomic dispersion, which helps to significantly decrease the adsorption energy and activation energy of silane, CO 2 , and aniline, thereby boosting catalytic performance. We believe that these results would open up new opportunities for the fabrication of SACs and the applications of MXenes in organic synthesis.

Controlled cold rolling impacts on microstructure and mechanical properties of the rare earth Ce-modified SAF 2507 super duplex stainless steel (SDSS) are investigated towards a better application and development prospective over the pristine SDSS. Rolling was performed at room temperature with the deformation level in a range of 30%–90%. A large amount of dislocations into the ferrite phase turned out, and their density increased with the deformation. While, emergence of dislocation plugs group, ferrite grains get refined to nanometer scale during the deformation process. In addition to deformed bands within austenite, formation of α′-martensitic phases and significant increment in their volume fraction are detected and attributed to deformation-induced martensitic transformation. Elongation of the ferrite and austenite microstructures along the deformation direction under the action of high strain also resulted in fibers formation gradually. Correspondingly, significant increase in the strength index while decrement in the plasticity index are observed. Moreover, cold rolling deformation not only affects the tensile fracture morphology but also switches it from a typical ductile to a ductile and quasi-cleavage mixed fracture.

A method of producing a silicon film includes: forming a deposition composition comprising silicon dioxide dispersed in a molten salt; placing a metal substrate and a counter electrode in the composition; and passing a reducing current between the metal substrate and the counter electrode, wherein the reducing current causes reduction of silicon dioxide particles to form a silicon film on the metal substrate.

Yanhong Zheng,1 Yunlan Tang,2 Zhirong Bao,1 Hui Wang,1 Feng Ren,1 Mingxiong Guo,2 Hong Quan,1 Changzhong Jiang11Key Laboratory of Artificial Micro- and Nano-structures of the Ministry of Education and Center for Electronic Microscopy and Department of Physics, Wuhan University; 2College of Life Sciences, Wuhan University, Wuhan, People’s Republic of ChinaAbstract: Nanomaterials have an advantage in “personalized” therapy, which is the ultimate goal of tumor treatment. In order to investigate the potential ability of FePt nanoparticles (NPs) in the diagnosis and chemoradiotherapy treatment of malignant tumors, superparamagnetic, monodispersed FePt (~3 nm) alloy NPs were synthesized, using cysteamine as a capping agent. The NPs were characterized by means of X-ray diffraction; transmission electron microscopy, Physical Property Measurement System, and Fourier transform infrared spectroscopy. The cytotoxicity of FePt NPs on Vero cells was assessed using an MTT assay, and tumor cell proliferation inhibited by individual FePt NPs and FePt NPs combined with X-ray beams were also collected using MTT assays; HeLa human cancer cell lines were used as in vitro models. Further confirmation of the combined effect of FePt NPs and X-rays was verified using HeLa cells, after which, the cellular uptake of FePt NPs was captured by transmission electron microscopy. The results indicated that the growth of HeLa cells was significantly inhibited by FePt NPs in a concentration-dependent manner, and the growth was significantly more inhibited by FePt NPs combined with a series of X-ray beam doses; the individual NPs did not display any remarkable cytotoxicity on Vero cells at a concentration

Aluminum (Al) is the most abundant metal in the Earth’s crust and is not an essential element for plant growth. In contrast, nitrogen (N) is the most important mineral element for plant growth, but this non-metal is often present at low levels in soils, and plants are often N deficient. Aluminum toxicity is dominant in acid soils, and so plants growing in acid soils have to overcome both Al toxicity and N limitation. Because of low N-use efficiency, large amounts of N fertilizers are applied to crop fields to achieve high yields, leading to soil acidification and potential Al toxicity. Aluminum lowers plant N uptake and N-use efficiency because Al inhibits root growth. Although numerous studies have investigated the interactions between Al and N, a complete review of these studies was lacking. This review describes: (1) the link between plant Al tolerance and ammonium/nitrate (NH4+/NO3-) preference; (2) the effects of NH4+/NO3- and pH on Al toxicity; (3) the effects of Al on soil N transformations; and (4) the effects of Al on NH4+/NO3- uptake and assimilation by plants. Acid soils are characterized chemically by a relatively high ratio of NH4+ to NO3- and high concentrations of toxic Al. Aluminum-tolerant plants generally prefer NH4+ as an N source, while Al-sensitive plants prefer NO3-. Compared with NO3-, NH4+ increases the solubilization of toxic Al into soil solutions, but NH4+ generally alleviates Al phytotoxicity under solution culture because the protons from NH4+ compete with Al3+ for adsorption sites on the root surface. Plant NO3- uptake and nitrate reductase activity are both inhibited by Al, while plant NH4+ uptake is inhibited to a smaller degree than NO3-. Together, the results of numerous studies indicate that there is a synergistic interaction between plant Al tolerance and NH4+ nutrition. This has important implications for the adaptation of plants to acid soils that are dominated chemically by toxic Al as well as NH4+. Finally, we discuss how this knowledge can be used to increase plant Al tolerance and N-use efficiency in acid soils.

Multiple laser shock processing (LSP) impacts on microstructures and mechanical properties were investigated through morphological determinations and hardness testing. Microscopic results show that without equal channel angular pressing (ECAP), the LSP-treated lamellar pearlite was transferred to irregular ferrite matrix and incompletely broken cementite particles. With ECAP, LSP leads to refinements of the equiaxed ferrite grain in ultrafine-grained microduplex structure from 400 to 150 nm, and the completely spheroidized cementite particles from 150 to 100 nm. Consequentially, enhancements of mechanical properties were found in strength, microhardness and elongations of samples consisting of lamellar pearlite and ultrafine-grained microduplex structure. After LSP, a mixture of quasi-cleavage and ductile fracture was formed, different from the typical quasi-cleavage fracture from the original lamellar pearlite and the ductile fracture of the microduplex structure.

Microstructure evolution and mechanical properties of AISI 316 LN austenitic stainless steel (SS) after cryorolling with different strains were investigated by means of optical, scanning and transmission electron microscopy, X-ray diffractometer, microhardness tester, and tensile testing system. The deformation-induced martensite transition and the deformation microstructure occurred during cryorolling process were always composed of high-density dislocations, deformation twins, and deformation-induced martensites. Following the strain, the dislocation density in deformation microstructure approached saturation state and the volume fraction of deformation twins combined with deformation-induced martensites increased significantly. At the 70% strain, original austenite was transformed into martensite completely. Further increasing the strain to 90% would refine the martensitic lamellae to nanoscale. The deformation degree also led to remarkable increase of the strength and hardness of the cryorolled SS, and drastic reductions of the elongation. Due to the cryorolling, the tensile fracture morphology changed from typical ductile rupture to a mixture of quasi-cleavage and ductile fracture.

To obtain ideal implant materials, we hot extruded Mg-2.0Zn-0.5Zr-3.0Gd solid-solution alloys, and studied extrusion temperature impacts on materials properties. Fine dynamic recrystallized (DRXed) grains (∼5 μm) and elongated coarse un-dynamic recrystallized (unDRXed) deformed grains turned out at the range of 470–490 °C, but changed to bigger ones (∼8 μm) and abnormal growth (30–40 μm) at 490–510 °C. Precipitated phases consist of rod-like (Mg, Zn)₃Gd particles and newly precipitated Mg₂Zn₁₁ rectangles. The alloy extruded at 490 °C meets all mechanical and anticorrosive requirements for biomaterials, thanks to evenly distributed second phases via the solid solution, and the grain refinements through the hot extrusion.

Adhesive joints are widely used in many industrial sectors since the numerous advantages over other traditional joints. However the mismatch of different materials may cause debonding of the joints. Since few studies are available for evaluating the bonded strength, this study will focuses on the solutions for the intensity of the singular stress for several typical adhesive joints, such as bonded plate and butt joint in plane stress state, bonded cylinder/pipe under axial-symmetric state. In this research, an effective numerical method combined with FEM results is used to obtain the SIFs at corner of adhesive joints in arbitrary material combinations. Here the simple bonded plate, which has already been solved accurately in our previous study, is used as the reference problem. We will discuss the effect of the adhesive thickness in a butt joint, and defined a new parameter for semi-infinite structure; and for the bonded joints in axial-symmetric, the nonsingular terms are derived so that the SIFs can be obtained, and it is found that the axial-symmetric problem are quite different since the SIFs cannot be dominated by the Dunders’ parameters. And at last, the SIFs for several problems are discussed and compared with each other., Proceedings of 4th International Conference on Fracture Fatigue and Wear, FFW 2015, Ghent University, Belgium, 27-28 August 2015

Intestinal regeneration and tumorigenesis are believed to be driven by intestinal stem cells (ISCs). Elucidating mechanisms underlying ISC activation during regeneration and tumorigenesis can help uncover the underlying principles of intestinal homeostasis and disease including colorectal cancer. Here we show that miR-31 drives ISC proliferation, and protects ISCs against apoptosis, both during homeostasis and regeneration in response to ionizing radiation injury. Furthermore, miR-31 has oncogenic properties, promoting intestinal tumorigenesis. Mechanistically, miR-31 acts to balance input from Wnt, BMP, TGFb signals to coordinate control of intestinal homeostasis, regeneration and tumorigenesis. We further find that miR-31 is regulated by the STAT3 signaling pathway in response to radiation injury. These findings identify miR-31 as a critical modulator of ISC biology, and a potential therapeutic target for a broad range of intestinal regenerative disorders and cancers.

Automated negotiation has been gained a mass of attention mainly because of its broad application potential in many fields. This work studies a prominent class of automated negotiations – multi-lateral multi-issue negotiations under real-time constraints, where the negotiation agents are given no prior information about their opponents’ preferences over the negotiation outcome space. A novel negotiation approach is proposed that enables an agent to obtain efficient agreements in this challenging multi-lateral negotiations. The proposed approach achieves that goal by, (1) employing sparse pseudo-input Gaussian processes (SPGPs) to model opponents, (2) learning fuzzy opponent preferences to increase the satisfaction of other parties, and (3) adopting an adaptive decision-making mechanism to handle uncertainty in negotiation.

Fuqiang Ren,1,2,* Mingyu Fan,1,2,* Jiandong Mei,1,2 Yongqiang Wu,3 Chengwu Liu,1,2 Qiang Pu,1,2 Zongbing You,4–9 Lunxu Liu1,2 1Department of Thoracic Surgery, West China Hospital, 2Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, 3Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Department of Structural and Cellular Biology, 5Department of Orthopaedic Surgery, 6Tulane Cancer Center, 7Louisiana Cancer Research Consortium, 8Tulane Center for Stem Cell Research and Regenerative Medicine, 9Tulane Center for Aging, Tulane University Health Sciences Center, New Orleans, LA, USA *These two authors contributed equally to this study Abstract: Tumor-associated macrophages play an important role in tumor growth and progression. These macrophages are heterogeneous with diverse functions, eg, M1 macrophages inhibit tumor growth, whereas M2 macrophages promote tumor growth. In this study, we found that IFNγ and/or celecoxib (cyclooxygenase-2 inhibitor) treatment consistently inhibited tumor growth in a mouse lung cancer model. IFNγ alone and celecoxib alone increased the percentage of M1 macrophages but decreased the percentage of M2 macrophages in the tumors, and thus the M2/M1 macrophage ratio was reduced to 1.1 and 1.7 by IFNγ alone and celecoxib alone, respectively, compared to the M2/M1 macrophage ratio of 4.4 in the control group. A combination of IFNγ and celecoxib treatment reduced the M2/M1 macrophage ratio to 0.8. Furthermore, IFNγ and/or celecoxib treatment decreased expression of matrix metalloproteinase (MMP)-2, MMP-9, and VEGF, as well as the density of microvessels in the tumors, compared to the control group. This study provides the proof of principle that IFNγ and/or celecoxib treatment may inhibit lung-tumor growth through modulating the M2/M1 macrophage ratio in the tumor microenvironment, suggesting that IFNγ and celecoxib have potential to be further optimized into a new anticancer therapy. Keywords: tumor-associated macrophages, M1 macrophages, M2 macrophages, lung cancer, interferon-γ, celecoxib

The use of tantalum as a highly effective dopant for hematite photoelectrochemistry (PEC) has shown contradictory results in previous reports. We show here through screening of different compositions by scanning electrochemical microscopy that Ta doping significantly improves the PEC performance of dropcast films on fluorine-doped tin oxide (FTO). In studies with larger electrodes, a 2% Ta-doped hematite photoanode fabricated at 500 °C shows the highest improvement of photoactivity, which is ∼32 times higher than pure hematite even under visible light. At fabrication temperature higher than 500 °C (e.g., 600, 680 °C), the substrate FTO becomes more resistive and the dopant Ta prefers to segregate from the bulk phase (α-Fe2O3) and forms tantalum fluoride oxide (TaO2F), which may act as charge-carrier recombination centers, and the corresponding Ta-doped samples show much lower photoactivities. Ta-doped hematite samples show stronger (110) diffraction as compared with the pure α-Fe2O3. We show that the dopi...

+ toxicity abstract The viability of living fibroblast cells cultured on a Petri dish was determined by scanning electrochem- ical microscopy (SECM). Three kinds of feedback modes for single living cells were derived with different redox couples: positive, negative and consumptive. The consumptive feedback was unique and distin- guished uptake from the response caused by cell deformation. The toxicity of Ag + ion on the living fibro- blast cells was investigated by using both ferrocenemethanol (FcMeOH) and oxygen (O2 )a s electrochemical mediators. The results showed that Ag + ions could be taken up and then reduced to form sub-micrometer and micrometer sized metal silver particles. The metal silver particles stained fibroblast cells and give a positive feedback with FcMeOH. These were also identified by the results of both SECM and energy dispersive X-ray spectroscopy (EDX). The amount of consumption of dissolved O2 decreased with time, showing the cell status as the cells died. Since O2 is directly involved in cell metabolism and the products of O2 reduction are not re-oxidized by metal silver particles trapped on fibroblast cells, it is a good SECM mediator to characterize drug effects on cell viability. The results suggest the importance of choice of redox mediator in characterizing cell viability.

Silicon is a widely used semiconductor for electronic and photovoltaic devices because of its earth-abundance, chemical stability, and the tunable electrical properties by doping. Therefore, the production of pure silicon films by simple and inexpensive methods has been the subject of many investigations. The desire for lower-cost silicon-based solar photovoltaic devices has encouraged the quest for solar-grade silicon production through processes alternative to the currently used Czochralski process or other processes. Electrodeposition is one of the least expensive methods for fabricating films of metals and semiconductors. Electrodeposition of silicon has been studied for over 30 years, in various solution media such as molten salts (LiF-KF-K2SiF6 at 745 8C and BaO-SiO2-BaF2 at 1465 8C ), organic solvents (acetonitrile, tetrahydrofuran), and room-temperature ionic liquids. Recently, the direct electrochemical reduction of bulk solid silicon dioxide in a CaCl2 melt was reported. [7] A key factor for silicon electrodeposition is the purity of silicon deposit because Si for the use in photovoltaic devices is solargrade silicon (> 99.9999% or 6N) and its grade is even higher in electronic devices (electronic-grade silicon or 11N). In most cases, the electrodeposited silicon does not meet these requirements without further purification and, to our knowledge, none have been shown to exhibit a photoresponse. In fact, silicon electrodeposition is not as straightforward as metal deposition, since the deposited semiconductor layer is resistive at room temperature, which complicates electron transfer through the deposit. In many cases, for example in room-temperature aprotic solvents, the deposited silicon acts as an insulating layer and prevents a continuous deposition reaction. In some cases, the silicon deposit contains a high level of impurities (> 2%). Moreover, the nucleation and growth of silicon requires a large amount of energy. The deposition is made even more challenging if the Si precursor is SiO2, which is a very resistive material. We reported previously the electrochemical formation of silicon on molybdenum from a CaCl2 molten salt (850 8C) containing a SiO2 nanoparticle (NP with a diameter of 5– 15 nm) suspension by applying a constant reduction current. However this Si film did not show photoactivity. Here we show the electrodeposition of photoactive crystalline silicon directly from SiO2 NPs from CaCl2 molten salt on a silver electrode that shows a clear photoresponse. To the best of our knowledge, this is a first report of the direct electrodeposition of photoactive silicon. The electrochemical reduction and the cyclic voltammetry (CV) of SiO2 were investigated as described previously. [8] In this study, we found that the replacement of the Mo substrate by silver leads to a dramatic change in the properties of the silicon deposit. The silver substrate exhibited essentially the same electrochemical and CV behavior as other metal substrates, that is, a high reduction current for SiO2 at negative potentials of 1.0 V with the development of a new redox couple near 0.65 V vs. a graphite quasireference electrode (QRE) (Figure 1a). Figure 1b shows a change in the reduction current as a function of the reduction potential, and the optical images of silver electrodes before and after the electrolysis, which displays a dark gray-colored deposit after the reduction. Figure 2 shows SEM images of silicon deposits grown potentiostatically ( 1.25 V vs. graphite QRE) on silver. The amount of silicon deposit increased with the deposition time, and the deposit finally covered the whole silver surface (Figure 2). High-magnification images show that the silicon deposit is not a film but rather platelets or clusters of silicon crystals of domain sizes in the range of tens of micrometers. The average height of the platelets was around 25 mm after a 10000 s deposition (Figure 2b), and 45 mm after a 20000s deposition (Figure 2c), respectively. The edges of the silicon crystals were clearly observed. Contrary to other substrates, silver enhanced the crystallization of silicon produced from silicon dioxide reduction and it is known that silver induces the crystallization of amorphous silicon. Energy-dispersive spectrometry (EDS) elemental mapping (images shown in the bottom row of Figure 2) revealed that small silver islands exist on the top of the silicon deposits, which we think is closely related to the growth mechanism of silicon on silver. The EDS spectrum of the silicon deposit (Figure 3a) suggested that the deposited silicon was quite pure and the amounts of other elements such as C, Ca, and Cl were below the detection limit (about 0.1 atom%). Since the oxygen signal was probably from the native oxide formed on exposure of the deposit to air and silicon does not form an alloy with silver, the purity of silicon was estimated to be at least 99.9 atom%. The successful reduction of Si(4+) in silicon dioxide to elemental silicon (Si) was confirmed by Xray photoelectron spectroscopy (XPS) of the silicon deposit [*] Dr. S. K. Cho, Dr. F.-R. F. Fan, Prof. A. J. Bard Center for Electrochemistry, Department of Chemistry and Biochemistry, The University of Texas at Austin Austin, TX 78712 (USA) E-mail: ajbard@mail.utexas.edu

Melamine is commonly used in the chemical industry, and it has been found to exist on food processing equipment and utensils. Previous investigations suggested that melamine alone or its combination with cyanuric acid appears to be toxic to immune system in animals. The objective of this study is to investigate the potential effects of melamine with or without cyanuric acid on immune function in ovalbumin- sensitized mice. Our data indicated that melamine-related administration caused a significant decreasing in the content of IL-4 in mice in comparison to negative control group. Significant increasing in the content of histamine (HIS) was recorded in almost all treated groups. The co-administration of melamine and cyanuric acid with high dose (each at 16mgkg-12d-1) led to a significantly lower contents of IL-10, IL-16 and monocyte chemoattractant protein-1 (MCP-1) in mouse serum in comparison to negative control group. Moreover, our data indicated that the number of Th1 and Th2 cells, and the ratio of Th1/Th2 spleen lymphocytes were significantly changed after treatment. Also, our results demonstrated that the profiles of both CD40 and CD40L were significantly altered in spleen lymphocytes after treatment.

Geographers and others have long since examined the distribution of paid work, childcare and housework within households and have more recently begun to explore the various effects of Internet use on everyday life and digital inequalities along lines of gender and other social markers. These lines of inquiry have so far remained largely separate and this paper brings them together by analysing the interrelations between the Internet and the gender division of household labour. Multi-group structural equation modelling is applied to dedicated survey data collected among heterosexual couples in Columbus (Ohio, USA). The results demonstrate that Internet use is gendered in many ways. Variations in Internet use are explained by a broader range of factors for women than for men, and an unequal division of domestic responsibilities within the household constrains women's Internet use but not men's. Overall, however, the relations between Internet use and the gender division of household labour are modest. The latter is related in different ways for women and men to the residential location, the household situation, the employment situation and gender-specific interactions among paid work, childcare and housework.

A nanostructured particulates formed from a redox active, luminescent phenyl substituted polycyclic aromatic hydrocarbon are provided herein. The nanostructured particulates may be used for determining the presence of an analyte of interest in a sample by detecting the emitted electromagnetic radiation generated by exposing a reagent mixture, which includes the nanostructured particulates and the sample, to electrochemical energy.

Experimental dog model of spinal cord shortening. To clarify the relationship between the amount of shortening of the spinal cord and the degree of injury it may induce, and to determine the safe range of the shortening. Xi’an Jiaotong University, China. Thirty adult dogs were randomly allocated to five groups. Dogs in Group A (sham operation control) underwent spondylectomy to have two-thirds of the thirteenth thoracic segment (T13) resected, without bone-to-bone contact of the adjacent vertebral bodies. Those in Group B, C, D and E had one-third, half, two-thirds and total of their T13 resected, respectively, with bone-to-bone contact. Somatosensory-evoked potentials (SEP) and spinal cord blood flow (SCBF) were detected. The histopathologic changes of spinal cord tissue were observed by hematoxylin and eosin stain and electron microscope. The shortening of the spinal cord < half of a vertebral segment height caused a reversible change of SEP. Whereas, the changes resulted from the shortening of more than two-thirds of a vertebral segment height did not return to the normal level. SCBF increased temporarily when the shortening was within two-thirds of a vertebral segment height; whereas, it decreased progressively when the length of the shortening was equal to one vertebral segment height. More serious hemorrhage occurred as the shortening increased. Shortening of half of a vertebral segment height will not induce spinal cord injury (SCI), while that between half and two-thirds of a vertebral segment may lead to incomplete SCI.