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Nonylphenol (NP) is a widely used chemical, which has been considered a kind of endocrine-disrupting chemical and is involved in the occurrence and development of many types of cancers. Our recent studies demonstrated that NP exposure is related to colorectal cancer (CRC) progression. In this study, we also found epithelial-mesenchymal transition (EMT) promoted by NP treatment in CRC cells. However, the mechanism of NP on tumor metastasis is still unclear. In this study, we focused on the effect of the regulator of cell cycle (RGCC) induced by NP treatment. The cancer genome atlas (TCGA) analysis suggested that the expression of RGCC increased in CRC tissues, and our clinical samples showed that the expression of RGCC in tumor tissues is positively correlated with the serum level of NP in CRC patients. Further studies revealed that overexpression of RGCC could enhance the NP-induced EMT process in CRC cells and activate ERK signaling pathways. Inhibiting ERK signaling by ERK inhibitors or the knockdown of RGCC could attenuate the NP-induced EMT process. In addition, both RGCC overexpression and NP treatment could activate ERK pathways and attenuate the effect of ERK inhibitors on the EMT process in CRC cells. Altogether, this study demonstrated that NP could induce cell invasion and migration by increasing the expression of RGCC to enhance the EMT process, which might be through the activation of ERK signaling pathways. This finding supported a potential target for studying NP exposure-related colorectal cancers.

BACKGROUND Hepatic tuberculosis (TB) is uncommon clinically. Because of a lack of specific signs, characteristic symptoms and clinical manifestations and because pathological samples are difficult to obtain, hepatic TB is easily missed or misdiagnosed. CASE SUMMARY A 62-year-old Chinese man presented with jaundice for 1 wk and no abnormal laboratory tests other than elevated bilirubin, aminotransferases and C-reactive protein. Computed tomography (CT) of the abdomen showed a mass in the left lobe of the liver and hepatic hilum with striped calcified foci. Mild enhancement was visible at the edges, along with extensive intrahepatic biliary ductal dilatation in the right lobe of the liver. In the arterial phase of both CT and magnetic resonance imaging, the main trunk and right branch of the portal artery were partially visualized. Magnetic resonance cholangiopancreatography (MRCP) indicated that the left lobe of the liver and most of the bile ducts in the hilum were not visible. Pathological examination revealed coagulative necrosis, and granulomatous nodules were seen around areas of necrosis; therefore, TB was considered. CONCLUSION Hepatic tuberculosis is easily misdiagnosed or missed on imaging. Percutaneous puncture biopsy is the most useful tool for definitive diagnosis.

Angiotensin-converting enzyme 2 (ACE2) has been identified as the key receptor of SARS coronavirus that plays a key role in the pathogenesis of SARS. It is known that ACE2 mRNA can be expressed in most organs. However, the protein expression of ACE2 is not clear yet. To explore the role of ACE2 as a precipitating factor in digestive organ damage in COVID-19, this study investigated the expression of ACE2 protein in the human liver, esophagus, stomach, and colon. The result showed that ACE2 can be expressed in the liver, esophagus, stomach, and colon, which suggests SARS-CoV-2 may enter the digestive system through ACE2 and cause liver damage and gastrointestinal damage. It is hoped that the result of the study will provide a new strategy for the prevention and treatment of digestive organ damage under COVID-19.

Coronavirus disease 2019 (COVID-19) combined with liver injury has become a very prominent clinical problem. Due to the lack of a clear definition of liver injury in patients with COVID-19, the different selection of evaluation parameters and statistical time points, there are the conflicting conclusions about the incidence rate in different studies. The mechanism of COVID-19 combined with liver injury is complicated, including the direct injury of liver cells caused by severe acute respiratory syndrome coronavirus 2 replication and liver injury caused by cytokines, ischemia and hypoxia, and drugs. In addition, underlying diseases, especially chronic liver disease, can aggravate COVID-19 liver injury. In the treatment of COVID-19 combined with liver injury, the primary and basic treatment is to treat the etiology and pathogenesis, followed by support, liver protection, and symptomatic treatment according to the clinical classification and severity of liver injury. This article evaluates the incidence, pathogenesis and prevention and treatment of COVID-19 combined with liver injury, and aims to provide countermeasures for the prevention and treatment of COVID-19 combined with liver injury.

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and the third leading cause of cancer death worldwide. The incidence of HCC accounts for more than 90% of primary HCC. Like most solid malignancies, the occurrence and development of HCC are closely related to the Warburg effect. The Warburg effect of HCC is mainly manifested as increased glucose uptake by HCC cells, increased glycolysis, restricted mitochondrial oxidative phosphorylation, increased pentose phosphate pathway in HCC cells, and increased glutamine decomposition. As the contribution of glycolysis to the total ATP of tumor cells generally does not exceed 50% to 60%, oxidative phosphorylation (OXPHOS) still makes a considerable contribution to the ATP of tumor cells. In some cases, there will be an anti-Warburg effect. HCC Warburg effect is closely related to HCC cell proliferation, apoptosis, immune escape, migration and invasion, chemotherapy resistance, and treatment failure. The mechanism of the Warburg effect in HCC is complex, involving the expression of stimulating the key glycolysis enzymes by hypoxia-inducible factor-1(HIF-1), the activation of oncogenes and the inactivation of tumor suppressor genes, the continuous activation of related signaling pathways, the participation of noncoding RNA, and the rate of metabolism gene mutation of enzyme. This article synthetically discusses the characteristics of glucose metabolism in HCC cells, the mechanism of Warburg effect, clinical significance, and corresponding treatment strategies and provides new perspectives for the prevention and treatment of HCC.

It remains enigmatic why the geomagnetic polarity is frequently reversed and how geomagnetic superchrons were formed during Earth’s evolution. Here we establish a physical model to decipher the relationship among geomagnetic superchron, subducted slab and superplume. During the supercontinent’s breakup or assembly, the subducted slabs concentratively arrive at the core-mantle boundary (CMB) and form “collective graveyards”, leading to increase of radial temperature gradient of CMB. The energy accumulation by the radioactive elements and fertile components from the subducted slab facilitate the subsequent superplume activity which consumes tremendous heat supply from the outer core. The combined results of subducted slabs and superplume activity keep long-term heat supply from the liquid outer core to the “collective graveyard” and the unchanged direction of resultant velocity of the fluid across the outer core, thereby forming a geomagnetic superchron. Our results reveal that a geomagnetic superchron lags supercontinent’s assembly or breakup by 163-239 Myr.

Hepatocellular carcinoma (HCC) is one of the most common malignancies, and its treatment is limited. With the understanding of key genes and signaling pathways in the occurrence and development of HCC, targeted drugs with high selectivity and low toxicity have been developed continuously, bringing a variety of options for the treatment of advanced HCC. In this article, the research progress on representative drugs of targeted therapy and potential therapeutic targets for HCC are reviewed.

The composite bone graft materials were made of calcium sulfate (CaSO4) and sodium hyaluronate (SH). The SH was in the form of solution, with a concentration of 850 kDa 0.1% v/w. The two materials were mixed in a ratio of 2 g:1 mL to obtain the first composite bone graft material Ca_Nw. Next, CaSO4 was mixed with SH-derivative (cross-linked SH) in a ratio of 2 g:1 mL to obtain the second composite bone graft material Ca_Cn. The experiment included 80 patients with ulna and radius nonunion, who were divided into 4 groups. The included patients were treated with Ca_Nw bone graft material, Ca_Cn bone graft material, autograft, and allograft. The computed tomography (CT) data, MIMICS software, and PRO/E software were utilized to construct the finite element models of AO-typing C-type distal radius fractures treated by different bone graft materials. The fixed constraints of radial and ulnar full degree of freedom (DOF) were set. The 120 N axial pressure was given on the forearm to compare the stress and fracture displacement. The results showed excellent stress simulation effects on two groups of patients treated by composite bone graft materials than those treated by autograft and allograft (P < 0.05).

Recently, the effect of endocrine-disrupting chemicals on the cancer procession has been a concern. Nonylphenol (NP) is a common environmental estrogen that has been shown to enhance the proliferation of colorectal cancer (CRC) cells in our previous studies; however, the underlying mechanism remains unclear. In this study, we confirmed the increased concentration of NP in the serum of patients with CRC. RNA sequencing was used to explore the differentially expressed genes after NP exposure. We found 16 upregulated genes and 12 downregulated genes in COLO205 cells after NP treatment. Among these differentially expressed genes, we found that coiled-coil domain containing 80 (CCDC80) was downregulated by NP treatment and was associated with CRC progression. Further experiments revealed that the overexpression of CCDC80 significantly suppressed NP-induced cell proliferation and recovered the reduced cell apoptosis. Meanwhile, the overexpression of CCDC80 significantly inhibited the activation of ERK1/2 induced by NP treatment. ERK1/2 inhibitor (PD98059) treatment also suppressed NP-induced CRC cell growth, but the overexpression of CCDC80 did not enhance the effect of ERK1/2 inhibitor. Taken together, NP treatment significantly inhibited the expression of CCDC80, and the overexpression of CCDC80 suppressed NP-induced CRC cell growth by inhibiting the activation of ERK1/2. These results suggest that NP could induce CRC cell growth by influencing the expression of multiple genes. CCDC80 and ERK1/2 inhibitors may be suitable therapeutic targets in NP-related CRC progression.

Androgen receptor (AR) has been reported to play an important role in the development and progression of man's prostate cancer. Hepatocellular carcinoma (HCC) is also male-dominant, but the role of AR in HCC remains poorly understood. Mechanistic target of rapamycin complex 1 (mTORC1) also has been reported to be highly activated in HCC. In this study, we aimed to explore the role of AR phosphorylation and its relationship with mTORC1 in hepatocarcinogenesis.In vitro experiment, we observed that mTORC1 interacts with hepatic AR and phosphorylates it at S96 in response to nutrient and mitogenic stimuli in HCC cells. S96 phosphorylation promotes the stability, nuclear localization, and transcriptional activity of AR, which enhances de novo lipogenesis and proliferation in hepatocytes and induces liver steatosis and hepatocarcinogenesis in mice independently and cooperatively with androgen. Furthermore, high ARAR S96 phosphorylation by mTORC1 drives liver steatosis and HCC development and progression independently and cooperatively with androgen, which not only explains why HCC is man-biased but also provides a target molecule for prevention and treatment of HCC and a potential survival predictor in patients with HCC.

OBJECTIVE: Circular RNA_0004913 (circ_0004913), circular RNA_0008160 (circ_0008160), and circular RNA_0000517 (circ_0000517) are shown to be dysregulated in HCC tissues and cell lines, and also show potential in regulating hepatocellular carcinoma (HCC) pathogenesis. This current study attempted to find possible associations of circ_0004913, circ_0008160, and circ_0000517 with clinical features and prognosis of HCC patients. METHODS: A hundred and fifty HCC patients who received hepatectomy were retrospectively reviewed, and their resected specimens including tumor tissues and paired adjacent tissues were obtained, in which the circ_0004913, circ_0008160, and circ_0000517 expressions were detected. Overall survival (OS) data were collected according to the clinical visit records. RESULTS: Circ_0004913 (p 0.05). Tumor circ_0004913 high expression was associated with prolonged OS in total HCC patients (p = 0.008) and in subgroup of patients with largest tumor size

Tumor-associated macrophages contribute to cell growth, development, and metastasis in various cancers. However, the underlying mechanisms of M2 macrophage that modulate the progression of gastric cancer (GC) remain largely unknown. In this study, we detected the ratio of macrophages in GC tissues and found that the proportion of M2 macrophages was increased in GC tissues. We then co-cultured GC cells with M1 and M2 macrophages, respectively, and then assessed cell proliferation and tumorigenicity of GC cells by MTT and colony formation assay. The results indicated that M2 macrophages promoted the proliferation of GC cells, but M1 not. Besides, GW4869, an exosomes inhibitor, reduced the effects induced by M2 macrophage. Then, we isolated and identified exosomes derived from M1 and M2 macrophage, and confirmed that the exosomes could be taken up by GC cells. We demonstrated that M2 macrophage-exosomes could induce the proliferation and tumorigenesis in vitro and in vivo. Moreover, miR-487a was enriched in M2 macrophage-exosomes and further determined that miR-487a exert the functions by targeting TIA1. In conclusion, exosomal miR-487a derived from M2 macrophage promotes the proliferation and tumorigenesis in gastric cancer, and the novel findings might be helpful to the development of novel diagnostic and therapeutic methods in GC.

Dysregulated glycolysis is one of the mechanisms employed by cancer cells to facilitate growth and metastasis. Here we aimed to characterize the PPFIA4 gene, as a glycolysis-related oncogene in promoting the proliferation and migration of colon cancer cells. Using bioinformatical tools including The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA), we found that PPFIA4 expression and methylation levels were higher in colon cancer tissues of different stages than in normal tissues. Higher PPFIA4 level was also positively correlated with poorer survival of patients. PPFIA4 upregulation also correlated with poor prognosis and higher clinical stages of colon cancer patients. Colon cancer cell viability, migration and migration were enhanced after PPFIA4 overexpression. EMT markers and glycolysis were upregulated after PPFIA4 overexpression. PPFIA4 expression was found to be positively correlated with PFKFB3 and ENO2 levels, while knockdown of PFKFB3 and ENO2 reduced cell proliferation, migration, invasion and glycolysis. PPFIA4 upregulation is a potential biomarker in colon cancer which promotes proliferation, migration, invasion and glycolysis. The upregulation of PFKFB3/ENO2 signaling by PPFIA4 is a potential mechanism underlying the oncogenic effects of PPFIA4.

Cyclooxygenase-2 (COX-2) is an important rate-limiting enzyme in the synthesis of prostaglandins (PGs), which can be upregulated by various stimuli. COX-2 has been shown to be involved in the occurrence and development of hepatic fibrosis by regulating the proliferation and apoptosis of hepatic stellate cells (HSCs) in previous studies. The aims of the study are to study the mechanism of how COX-2 regulates the proliferation and apoptosis of HSCs and to provide new targets for the prevention and treatment of hepatic fibrosis. A short hairpin RNA targeting COX-2 was constructed, and the changes in proliferation and apoptosis of liver tissue cells and HSCs were observed, respectively. COX-2-shRNA-1 significantly suppressed the proliferation of HSCs in vivo. Moreover, knockdown of COX-2 significantly suppressed cell proliferation and accelerated cell cycle arrest and apoptosis in vitro. Among those differential genes related to cell proliferation and apoptosis, CDC27 and Sh3kbp1 were upregulated, but Plcd4 was suppressed. Mechanistically, the influence of COX-2 on HSCs partly depends on upregulating CDC27. Our results demonstrated that COX-2 regulates the proliferation and apoptosis of activated hepatic stellate cells through the CDC27 pathway. This study contributes to our understanding of the effect of COX-2 for the treatment of hepatic fibrosis.

BACKGROUND In December 2019, an ongoing outbreak of coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China. The characteristics of COVID-19 patients treated in local hospitals in Wuhan are not fully representative of patients outside Wuhan. Therefore, it is highly essential to analyze the epidemiological and clinical characteristics of COVID-19 in areas outside Wuhan or Hubei Province. To date, a limited number of studies have concentrated on the epidemiological and clinical characteristics of COVID-19 patients with different genders, clinical classification, and with or without basic diseases. AIM To study the epidemiological and clinical characteristics of COVID-19 patients in Hengyang (China) and provide a reliable reference for the prevention and control of COVID-19. METHODS From January 16 to March 2, 2020, a total of 48 confirmed cases of COVID-19 were reported in Hengyang, and those cases were included in this study. The diagnostic criteria, clinical classification, and discharge standard related to COVID-19 were in line with the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) released by National Health Commission and National Administration of Traditional Chinese Medicine. The presence of SARS-CoV-2 in pharyngeal swab specimens was detected by quantitative reverse transcription polymerase chain reaction. All the data were imported into the excel worksheet and statistically analyzed by using SPSS 25.0 software. RESULTS A total of 48 cases of COVID-19 were collected, of which 1 was mild, 38 were moderate, and 9 were severe. It was unveiled that there were 31 (64.6%) male patients and 17 (35.4%) female patients, with a female-to-male ratio of 1.82:1. The range of age of patients with COVID-19 was dominantly 30-49 years old [25 (52.1%) of 48], followed by those aged over 60 years old [11 (22.9%)]. Besides, 29.2% (14 of 48) of patients had basic diseases, and 57.2% (8 of 14) of patients with basic diseases were aged over 60 years old. The occupations of 48 COVID-19 patients were mainly farmers working in agricultural production [15 (31.5%) of 48], rural migrant workers from Hengyang to Wuhan [15 (31.5%)], and service workers operating in the service sector [8 (16.7%)]. The mean latent period was 6.86 ± 3.57 d, and the median was 7 [interquartile range (IQR): 4-9] d. The mean time from onset of symptoms to the first physician visit was 3.38 ± 2.98 (95%CI: 2.58-9.18) d, with a median of 2 (IQR: 1-5) d, and the mean time from hospital admission to confirmed diagnosis was 2.29 ± 2.11 (95%CI: 1.18-6.42) d, with a median of 2 (IQR: 1-3) d. The main symptoms were fever [43 (89.6%) of 48], cough and expectoration [41 (85.4%)], fatigue [22 (45.8%)], and chills [22 (45.8%)]. Other symptoms included poor appetite [13 (27.1%)], sore throat [9 (18.8%)], dyspnea [9 (18.8%)], diarrhea [7 (14.6%)], dizziness [5 (10.4%)], headache [5 (10.4%)], muscle pain [5 (10.4%)], nausea and vomiting [4 (8.3%)], hemoptysis [4 (8.3%)], and runny nose [1 (2.1%)]. The numbers of peripheral blood leukocytes, lymphocytes, and eosinophils were significantly reduced in the majority of the patients. The levels of C-reactive protein, fibrinogen, blood glucose, lactate dehydrogenase, D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GT), myoglobin (MB), and creatine kinase (CK) were increased in 64.6%, 44.7%, 43.2%, 37.0%, 29.5%, 22.9%,20.8%, 21.6%, 13.6%, and 12.8% of patients, respectively. The incidence of ALT elevation in male patients was remarkably higher than that in females (P < 0.01), while the incidences of AST, CK, and blood glucose elevations in severe patients were remarkably higher than those in moderate patients (P < 0.05, respectively). Except for the mild patients, chest computed tomography showed characteristic pulmonary lesions. All the patients received antiviral drugs, 38 (79.2%) accepted traditional Chinese medicine, and 2 (4.2%) received treatment of human umbilical-cord mesenchymal stem cells. On March 2, 2020, 48 patients with COVID-19 were all cured and discharged. CONCLUSION Based on our results, patients with COVID-19 often have multiple organ dysfunction or damage. The incidences of ALT elevation in males, and AST, CK, and blood glucose elevations in severe patients are remarkably higher.

A numerical simulation research was carried out on vortex and sound pressure level of the butterfly valve in the flow process based on FLUENT, which analyzed the variation of the vorticity and sound pressure level at different opening angles. There was an inverse pressure gradient in the orifice formed by the butterfly plate and pipe, which caused partial particle reflux on the back of butterfly plate in flowing, thus formed the vortex. The vortex formed on the back of the butterfly plate was decreased gradually, with the increasing opening angle of the valve in opening process. The noise was generated by the vortex separated and rupture in flowing. And the sound pressure level on the back of butterfly plate was decreased with the increasing opening angle. At the same time, the vorticity and the maximum sound pressure level position moved from the center to the rotation center of butterfly plate in opening process. The expanding orifice formed by butterfly plate upstream and the pipe and the tapered orifice formed by butterfly plate downstream and the pipe had the different throttling action to the fluid, which made the sound pressure level of upstream was higher than that of downstream in symmetrical position. The vortex generated by the separation of boundary layer would cause vortex excited vibration between plate and fluid, and then resonance occurred. The studies were carried out in the vorticity and the sound pressure level on the downstream of butterfly plate, and the changing law of those was found. It would provide a basis theory for reducing noise and avoiding vortex vibration of butterfly valve.

The fast response temperature sensor is an effective tool for measuring the temperature of internal combustion engine, in order to improve the performance of fast response temperature sensor, and the Coiflet wavelet finite element method is applied in analyzing the heat transfer rules of fast response temperature sensor. Firstly, the related research progress on the performance analysis of fast response and wavelet finite element method is summarized, respectively, and research significance of heat transfer of fast response sensor based on Coiflet wavelet finite element method is summarized in detail. Secondly, the basic theory of fast response sensor is studied, and the new structure of the fast response temperature sensor is analyzed. Thirdly, the Coiflet wavelet finite element model of analyzing heat transfer of fast response sensor is constructed by combing the Coiflet wavelet scale function with traditional finite element method, and the theoretical models are deduced. Finally, the heat transfer simulation of fast response temperature sensor based on Coiflet wavelet finite element method is carried out, and simulation results show that the Coiflet finite element has higher computing precision and efficiency than traditional finite element method, and the heat transfer rules of fast response temperature sensor are also obtained.

A novel carbon dioxide (CO2) gas sensor based on capillary array is presented. The capillary array is composed of 51 capillaries and modified by fluorescent dye 8-hydroxy-1,3,6-pyrenetrisulfonic acid trisodium salt (HPTS, PTS−) and tetraoctylammonium cation (TOA+) doped porous ethyl cellulose. A Y-fiber is used to transmit exciting light and fluorescence. A fiber optic pigtail-contained spectrophotometer is used to collect and deal with optical signals. Due to its structural features, each capillary has the two rolling-up layers of inner and outer sensing films, which make the 2 cm long capillary array has large sensing area about 12.81 cm2 and the fluorescence signal easily be collected. The sensing probe has advantages such as small volume, compact structure and large sensing area. The results demonstrate that the sensor has a linear response in the CO2 volume ratio range from 0 to 10%. Keywords: Carbon dioxide chemical sensor, Fluorescence sensor, Capillary array

The inhibitor of growth family, member 3 (ING3) protein may be capable of blocking the cell cycle via activating p53-transactivated promoters of p21 and Bcl2-associated X protein, and may induce apoptosis via a Fas/caspase-8-dependent signaling pathway. In the present study, immunohistochemistry was performed in order to characterize the expression profile of ING3 protein in tissue microarrays containing mouse and human normal tissue, human hepatocellular (n=62), renal clear cell (n=62), pancreatic (n=62), esophageal squamous cell (n=45), cervical squamous cell (n=31), breast (n=144), gastric (n=196), colorectal (n=96), ovarian (n=208), endometrial (n=96) and lung carcinoma (n=192). In mouse tissue, ING3 protein was positively detected in the cytoplasm of cardiomyocytes, kidney and skeletal muscle cells, and was additionally detected in the cytoplasm and nucleus of bronchial and alveolar epithelium, gastric and intestinal gland, and mammary gland cells. In human tissues, ING3 protein was principally distributed in the cytoplasm, but was observed in the cytoplasm and nucleus of tongue, esophagus, stomach, intestine, lung, skin, appendix, bladder, cervix and breast cells. ING3 immunoreactivity was strongly detected in the stomach, skin and cervical tissues, whereas a weak signal was detected in the cerebellum, brain stem, thymus, liver, skeletal muscle, testis and prostate. In total, ING3-positive specimens were identified in 424 of 1,194 tested cancer entities (35.5%). In a number of cases, ING3 expression was observed to be restricted to the cytoplasm and nucleus, excluding the cytoplasmic distribution identified in breast and hepatocellular carcinoma. Among these cases, ING3 was more frequently expressed in breast and gynecological types of cancer, including ovarian (59.2%), endometrial (47.9%), breast (38.9%) and cervical (35.5%) cancer. ING3-positive cases were more rare in renal clear cell (17.7%), hepatocellular (16.1%) and esophageal carcinoma (17.8%). It is suggested that ING3 may be involved in the repair and regeneration of organs or tissues, and may be closely associated with gynecological carcinogenesis.

// Xue-feng Yang 1 , Zhi-juan Zhao 1 , Jia-jie Liu 1 , Xiang-hong Yang 2 , Yang Gao 1 , Shuang Zhao 1 , Shuai Shi 1 , Ke-qiang Huang 3 , Hua-chuan Zheng 1, 4 1 Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China 2 Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110004, China 3 Department of Stomatology, The Second Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China 4 Life Science Institute of Jinzhou Medical University, Jinzhou 121001, China Correspondence to: Hua-chuan Zheng, email: zheng_huachuan@hotmail.com Keywords: glioma, suberoylanilide hydroxamic acid, histone acetylation, MG132, chemotherapy Received: August 23, 2016 Accepted: November 15, 2016 Published: November 29, 2016 ABSTRACT To elucidate the anti-tumor effects and molecular mechanisms of SAHA (a histone deacetylase inhibitor) and MG132 (a proteasome inhibitor) on the aggressive phenotypes of glioma cells, we treated U87 and U251 cells with SAHA or/and MG132, and detected phenotypes’ assays with phenotype-related molecules examined. It was found that SAHA or/and MG132 treatment suppressed proliferation in both concentration- and time-dependent manners, inhibited energy metabolism, migration, invasion and lamellipodia formation, and induced G 2 arrest and apoptosis in the glioma cells. The treatment with SAHA increased the expression of acetyl-histones 3 and 4, which were recruited to the promoters of p21, p27, Cyclin D1, c-myc and Nanog to down-regulate their transcriptional levels. Expression of acetyl-histones 3 and 4 was higher in gliomas than normal brain tissues. Both drugs’ exposure suppressed tumor growth in nude mice by inducing apoptosis and inhibiting proliferation, but increased serum aminotransferase and creatinine. These results indicated that SAHA and/or MG132 may suppress the aggressive phenotypes of glioma cells. They might be employed to treat the glioma if both hepatic and renal injuries are prevented.

Oil atomization is an effective enhanced heat transfer method for single screw compressor, which can make the compression process of single screw compressor be close to the isothermal process, then the working efficiency can be improved. In order to obtain optimal atomization technology effectively, the heat transfer of single screw compressor is analyzed based on fuzzy random wavelet finite element method. Firstly, the relating researching progresses are summarized. Secondly, the heat transfer governing equation of single screw compressor is constructed based on large eddy simulation technology. Thirdly, the heat transfer wavelet finite element model of single screw compressor is established through using Hermitian wavelet function, and then the fuzzy random Hermitian wavelet finite element mode is established based on λ level set theory. Finally, the heat transfer rules of single screw compressor is obtained based on simulation analysis, the effect of atomization on heat transfer of single screw compressor is obtained, results can offer effective theoretical guidance for designing the novel atomization system for single screw compressor.

// Yang Gao 1, * , Ji-feng Zhang 1, * , Qing-chang Li 2 , Jia-jie Liu 1 , Li-li Liu 1 , Xue-feng Yang 1 , Hua-mao Jiang 3 , Hua-chuan Zheng 1, 4 1 Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China 2 Department of Pathology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China 3 Department of Urology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China 4 Life Science Institute of Jinzhou Medical University, Jinzhou 121001, China * These authors have contributed equally to this work Correspondence to: Hua-chuan Zheng, email: zheng_huachuan@hotmail.com Keywords: lung cancer, clinicopathological behaviors, prognosis, China, Japan Received: May 29, 2016 Accepted: August 21, 2016 Published: September 06, 2016 ABSTRACT Here, we retrospectively compared the differences in clinicopathological behaviors and prognosis of lung cancer from the First Affiliated Hospital (CMU1, n=513), Shengjing Hospital (CMUS, n=1021), Tumor Hospital (CMUT, n=5378) of China Medical University, the First Affiliated Hospital of Dalian (DMU, n=2251) and Jinzhou (JMU, n=630) Medical University, Takaoka Kouseiren Hospital (Takaoka, n=163) of Japan. Japanese lung cancer patients showed smaller tumor size, lower TNM staging, lower ratio of squamous cell carcinoma and higher ratio of small and large cell carcinomas than Chinese patients (p

// Hang Lu 1 , Xue-feng Yang 1 , Xiao-qing Tian 1 , Shou-long Tang 1 , Lian-qian Li 2 , Shuang Zhao 1 , Hua-chuan Zheng 1, 3 1 Cancer Center, The Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China 2 Department of Surgery, Panjin Central Hospital, Panjin, China 3 Life Science Institute of Jinzhou Medical University, Jinzhou, China Correspondence to: Hua-chuan Zheng, email: zheng_huachuan@hotmail.com Keywords: gastric cancer, suberoylanilide hydroxamic acid, MG132, aggressive phenotypes, chemotherapy Received: April 17, 2016 Accepted: June 03, 2016 Published: July 18, 2016 ABSTRACT Here, we found that both SAHA and MG132 synergistically inhibited proliferation, glycolysis and mitochondrial oxidization, induced cell cycle arrest and apoptosis in MGC-803 and MKN28 cells. SAHA increased cell migration and invasionat a low concentration. SAHA induced the overexpression of acetyl histone 3 and 4, which were recruited to p21 , p27 , Cyclin D1 , c-myc and nanog promoters to transcriptionally up-regulate the former two and down-regulate the latter three. The expression of acetyl-histone 3 and 4 was increased during gastric carcinogenesis and positively correlated with cancer differentiation. SAHA and MG132 exposure suppressed tumor growth by inhibiting proliferation and inducing apoptosis in nude mice, increased serum ALT and AST levels and decreased hemaglobin level, white blood cell and neutrophil numbers. These data indicated that SAHA and MG132 in vivo and vitro synergistically induced cytotoxicity and apoptosis, suppressed proliferation, growth, migration and invasion of gastric cancer cells. Therefore, they might potentially be employed as chemotherapeutic agents if the hepatic injury and the killing effects of peripheral blood cells are avoided or ameliorated.

// Shuang Zhao 1 , Shu-rui Chen 2 , Xue-feng Yang 1 , Dao-fu Shen 1 , Yasuo Takano 3 , Rong-jian Su 4 , Hua-chuan Zheng 1, 4 1 Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China 2 Department of Science and Technology, Jinzhou Medical University, Jinzhou, China 3 School of Health Science, Tokyo University of Technology, Nishi-Kamata, Ohta-ku, Tokyo, Japan 4 Life Science Institute of Jinzhou Medical University, Jinzhou, China Correspondence to: Hua-chuan Zheng, email: zheng_huachuan@hotmail.com Keywords: colorectal cancer, BTG1, carcinogenesis, aggressive phenotypes, gene therapy Received: April 02, 2016 Accepted: June 03, 2016 Published: July 18, 2016 ABSTRACT Here, BTG1 overexpression inhibited proliferation, induced differentiation, autophagy, and apoptosis in colorectal cancer cells (p

// Shuang Zhao 1 , Xue-feng Yang 1 , Dao-fu Shen 1 , Yang Gao 1 , Shuai Shi 1 , Ji-cheng Wu 1 , Hong-xu Liu 2 , Hong-zhi Sun 1 , Rong-jian Su 3 , Hua-chuan Zheng 1, 3 1 Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, China 2 Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China 3 Life Science Institute of Jinzhou Medical University, Jinzhou, 121001, China Correspondence to: Hua-chuan Zheng, email: zheng_huachuan@hotmail.com Keywords: lung cancer, ING5, pathogenesis, aggressiveness, prognosis Received: February 06, 2016 Accepted: May 28, 2016 Published: July 09, 2016 ABSTRACT ING5 can interact with p53, thereby inhibiting cell growth and inducing apoptosis. We found that ING5 overexpression not only inhibited proliferation, migration, and invasion, but also induced G2 arrest, differentiation, autophagy, apoptosis, glycolysis and mitochondrial respiration in lung cancer cells. ING5 transfection up-regulated the expression of Cdc2, ATG13, ATG14, Beclin-1, LC-3B, AIF, cytochrome c, Akt1/2/3, ADFP, PFK-1 and PDPc, while down-regulated the expression of Bcl-2, XIAP, survivin,β-catenin and HXK1. ING5 transfection desensitized cells to the chemotherapy of MG132, paclitaxel, and SAHA, which paralleled with apoptotic alteration. ING5 overexpression suppressed the xenograft tumor growth by inhibiting proliferation and inducing apoptosis. ING5 expression level was significantly higher in normal tissue than that in lung cancer at both protein and mRNA levels. Nuclear ING5 expression was positively correlated with ki-67 expression and cytoplasmic ING5 expression. Cytoplasmic ING5 expression was positively associated with lymph node metastasis, and negatively with age, lymphatic invasion or CPP32 expression. ING5 expression was different in histological classification: squamous cell carcinoma > adenocarcinoma > large cell carcinoma > small cell carcinoma. Taken together, our data suggested that ING5 downregulation might involved in carcinogenesis, growth, and invasion of lung cancer and could be considered as a promising marker to gauge the aggressiveness of lung cancer. It might be employed as a potential target for gene therapy of lung cancer.

Signal transducer and activator of transcription 3 (STAT3) have roles in various cellular processes, including angiogenesis, apoptosis, cell cycle progression, cell migration and drug resistance. To clarify the effects of STAT3 in colorectal cancer (CRC) cells and the underlying molecular mechanisms, STAT3 was directly silenced, and the effects of STAT3 silencing on cell proliferation, apoptosis and growth with phenotype-associated molecules were examined.pSH1-Si-STAT3 was successfully transfected into the CRC HCT-116 and SW480 cell lines, which was verified by GFP tagging under a fluorescence microscope. An MTT assay revealed that the proliferation of both cell lines that were transfected with pSH1-Si-STAT3 was significantly suppressed in comparison with the control and mock (P

Motor-driven flexible manipulator systems (MDFMSs) are widely used in industry robot fields. During the dynamic modeling, the separate investigation method which neglects the dynamic behavior of the driving motor will cause an error in the dynamic analysis of the flexible manipulator, especially with high-speed operations. This paper proposes a coupled dynamic model of the MDFMS in which the driving motor and flexible manipulator are considered as an integrated system, which can clearly reflect the influence of the dynamic effect of the driving motor. Based on the proposed dynamic model, the vibration responses of the flexible manipulator under different velocities, accelerations and structure parameters, as well as the effect mechanism of the driving motor on the vibration responses, are investigated. The results obtained in this paper contribute to the structure design, motion optimization and dynamic analysis of flexible manipulators.

// Hua-chuan Zheng 1 , Jing Li 2 , Dao-fu Shen 1 , Xue-feng Yang 1 , Shuang Zhao 1 , Ya-zhou Wu 1 , Yasuo Takano 3 , Hong-zhi Sun 1 , Rong-jian Su 4 , Jun-sheng Luo 1 , Wen-feng Gou 1 1 Cancer Research Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China 2 Department of Gastroenterology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China 3 School of Health Science, Tokyo University of Technology, Ohta-ku, Tokyo, Japan 4 Experimental Center, Liaoning Medical University, Jinzhou, China Correspondence to: Wen-feng Gou, e-mail: xiaogouaeiou@163.com Keywords: gastric cancer, BTG1, pathobiological behaviors, carcinogenesis, gene therapy Received: March 11, 2015 Accepted: May 23, 2015 Published: June 05, 2015 ABSTRACT Here, we found that BTG1 overexpression inhibited proliferation, migration and invasion, induced G 2 /M arrest, differentiation, senescence and apoptosis in BGC-823 and MKN28 cells ( p < 0.05). BTG1 transfectants showed a higher mRNA expression of Cyclin D1 and Bax , but a lower mRNA expression of cdc2, p21, mTOR and MMP-9 than the control and mock ( p < 0.05). After treated with cisplatin, MG132, paclitaxel and SAHA, both BTG1 transfectants showed lower mRNA viability and higher apoptosis than the control in both time- and dose-dependent manners ( p < 0.05) with the hypoexpression of chemoresistance-related genes ( slug , CD147 , GRP78 , GRP94 , FBXW7 TOP1 , TOP2 and GST-π ). BTG1 expression was restored after 5-aza-2′-deoxycytidine treatment in gastric cancer cells. BTG1 expression was statistically lower in gastric cancer than non-neoplastic mucosa and metastatic cancer in lymph node ( p < 0.05). BTG1 expression was positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, TNM staging and worse prognosis ( p < 0.05). The diffuse-type carcinoma showed less BTG1 expression than intestinal- and mixed-type ones ( p < 0.05). BTG1 overexpression suppressed tumor growth and lung metastasis of gastric cancer cells by inhibiting proliferation, enhancing autophagy and apoptosis in xenograft models. It was suggested that down-regulated BTG1 expression might promote gastric carcinogenesis partially due to its promoter methylation. BTG1 overexpression might reverse the aggressive phenotypes and be employed as a potential target for gene therapy of gastric cancer.

Here, we found that ING5 overexpression increased autophagy, differentiation, and decreased proliferation, apoptosis, migration, invasion and lamellipodia formation in gastric cancer cells, while ING5 knockdown had the opposite effects. In SGC-7901 transfectants, ING5 overexpression caused G1 arrest, which was positively associated with 14-3-3 overexpression, Cdk4 and c-jun hypoexpression. The induction of Bax hypoexpression, Bcl-2, survivin, 14-3-3, PI3K, p-Akt and p70S6K overexpression by ING5 decreased apoptosis in SGC-7901 cells. The hypoexpression of MMP-9, MAP1B and flotillin 2 contributed to the inhibitory effects of ING5 on migration and invasion of SGC-7901 cells. ING5 overexpression might activate both β-catenin and NF-κB pathways in SGC-7901 cells, and promote the expression of down-stream genes (c-myc, VEGF, Cyclin D1, survivin, and interleukins). Compared with the control, ING5 transfectants displayed drug resistance to triciribine, paclitaxel, cisplatin, SAHA, MG132 and parthenolide, which was positively related to their apoptotic induction and the overexpression of chemoresistance-related genes (MDR1, GRP78, GRP94, IRE, CD147, FBXW7, TOP1, TOP2, MLH1, MRP1, BRCP1 and GST-π). ING5 expression was higher in gastric cancer than matched mucosa. It was inversely associated with tumor size, dedifferentiation, lymph node metastasis and clinicopathological staging of cancer. ING5 overexpression suppressed growth, blood supply and lung metastasis of SGC-7901 cells by inhibiting proliferation, enhancing autophagy and apoptosis in xenograft models. It was suggested that ING5 expression might be employed as a good marker for gastric carcinogenesis and subsequent progression by inhibiting proliferation, growth, migration, invasion and metastasis. ING5 might induce apoptotic and chemotherapeutic resistances of gastric cancer cells by activating β-catenin, NF-κB and Akt pathways.

Summary The length-weight (LWR) and length-length relationships (LLR) were estimated for three endemic fish species, including Schizothorax waltoni Regan, 1905, Schizothorax oconnori Lloyd, 1908, and Schizothorax macropogon Regan, 1905 in the Yarlung Tsangpo River. A total of 399 specimens were collected using gillnets and cast nets during February to August 2012 and March to May 2013. No information regarding length–weight and length–length relationships was reported previously in FishBase for these three endemic species.

β2-microglobulin (B2M), the light chain of major histocompatibility complex class I (MHC I) molecules, has been found to impair hippocampal neurogenesis. Based on the crucial role of hippocampal neurogenesis disturbance in the process of depression and anxiety, the aim of the present study is to investigate whether B2M leads to depressive- and anxiety-like behaviors. We found that 6 days after intracerebroventricular injection with B2M (0.3 μg), the immobility times of rats in the tail suspension test and the forced swimming test were increased, the swimming and climbing time in the forced swimming test was decreased, and the latency to feed in the novelty-suppressed feeding test was increased, indicating that B2M induces depressive-like behaviors. In addition, in the elevated plus maze test, B2M-treated rats displayed obvious decline in the number of entries into and the proportion of time spent in the open arm, while the number of total arm entries was no change, which indicated that B2M induces anxiety-like behaviors. Our present findings suggest that target B2M might represent a novel approach for treatment of depression and anxiety.

The aim of this study was to construct recombinant adenovirus vector carrying a short hairpin RNA (shRNA) that can exclusively target cyclooxygenase-2 (COX-2) gene expression and observe its inhibitory effect on hepatic fibrosis. We designed and synthesized three oligonucleotide sequences, and cloned those into a shuttle vector, pYr-1.1-hU6-EGFP, after annealing. The restriction-enzyme digestion and sequencing analyses confirmed that the constructed recombinant eukaryotic expression vector was correct. A recombination reaction using LR Clonase was performed for the pYr-1.1-hU6-EGFP COX-2shRNA and the adenovirus vector pAd/BL-DEST to form Ad-COX-2shRNA. The adenoviruses containing the recombinant plasmids were transfected into hepatic stellate cells (HSCs). The transfection efficiency of the three COX-2 shRNAs exceeded 70%. Reverse transcription PCR (RT-PCR) and western blot confirmed that the target gene expression was decreased at the level of mRNA and protein, and the interference effect of COX-2 shRNA-1 was better than that of the other two COX-2 shRNAs. COX-2 shRNA-1 recombinant adenovirus vectors (1 × 109 PFU/mL) were injected via the tail vein into rats fed a high-fat diet with a 40% carbon tetrachloride peanut oil lavage, which induced liver fibrosis. Rats were euthanized at the end of the 12th week, and their liver was removed. Liver expression of COX-2 mRNA and protein was detected by RT-PCR and immunohistochemistry, respectively. RT-PCR and immunohistochemistry showed that COX-2 shRNA-1 inhibited COX-2 expression in liver tissue. Hematoxylin/eosin and Masson staining showed that COX-2 shRNA-1 ameliorated the severity of liver fibrosis. The COX-2 shRNA eukaryotic expression vectors were constructed successfully and COX-2 shRNA-1 ameliorated liver fibrosis.

A numerically efficient broadband, range-dependent propagation model is proposed, which incorporates the Hamiltonian method into the coupled-mode model DGMCM. The Hamiltonian method is highly efficient for finding broadband eigenvalues, and DGMCM is an accurate model for range-dependent propagation in the frequency domain. Consequently, the proposed broadband model combining the Hamiltonian method and DGMCM has significant virtue in terms of both efficiency and accuracy. Numerical simulations are also provided. The numerical results indicate that the proposed model has a better performance over the broadband model using the Fourier synthesis and COUPLE, while retaining the same level of accuracy.

This paper designed a control system based on STM32 as the main core of the control system of amphibious waters, cleaning robot, the overall design including hardware module circuit and software module two parts. Designed a new multi-function remote control type amphibious water cleaning robot, the robot cleaner by the control system module, bluetooth module, solar power supply module, motor module, garbage collection, sorting system module, hull and car body in an amphibious system composition, its special ground drive system and the surface drive system can realize amphibious type movement, through the mobile terminal equipment sends commands to the STM32 control system, which can realize remote control robot cleaner to designated waters homework, such as the implementation of cleaning robot move forward, backward, turn left, turn right, such as motor control, and complete garbage collection, sorting, handling, unloading and other tasks, through the test, can effectively achieve the surface of the robot clean homework tasks[1].

d-galactose was injected into mice of ages 4–5 months, and peony seed oil was administered using an oral gavage to assess its possible anti-aging functions. The content of malondialdehyde (MDA) and the activities of monoamine oxidase (MAO), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) in the brain and liver of these mice were determined using biochemical kits. The significance of the differences in the content of the components associated with aging and anti-aging among each group was analyzed statistically. The MDA content and activities of MAO in the brain and liver of mice in the peony seed oil group were significantly lower than those in the aging group. The activities of GSH-Px, Cu/Zn-SOD, and Mn-SOD in the brain and liver of mice in the peony seed oil group were very significantly higher than those in the aging group. Peony seed oil was determined to have an obvious anti-aging function.

Objective:This study aimed to investigate the correlation of polo-like kinase 4 with clinicopathological features and survival profiles in patients with gastric cancer.Methods:This retrospective study was conducted based on the clinical data from 289 eligible patients with gastric cancer who received resection. Polo-like kinase 4 expression in adjacent tissue and tumor tissue was determined by immunohistochemical assay and semiquantified scoring method using immunohistochemical score by staining intensity score multiplying staining density score. Based on the total immunohistochemical score (ranged from 0 to 12), the polo-like kinase 4 expression was classified as low expression (immunohistochemical: 0-3) and high expression (immunohistochemical: 4-12); furthermore, high expression was divided into high+ expression (immunohistochemical: 4-6), high++ expression (immunohistochemical: 7-9), and high+++ expression (immunohistochemical: 10-12).Results:Polo-like kinase 4 expression was elevated in tumor tissue compared with adjacent tissue. Tumor polo-like kinase 4 high expression correlated with increased T stage and Tumor, Node, Metastasis (TNM) stage, while, it did not correlate with age, gender, current smoke, current drink, chronic complications, Helicobacter pylori infection, tumor location, pathological grade, or N stage. Besides, higher tumor polo-like kinase 4 expression correlated with shorter disease-free survival and overall survival. Subsequently, multivariate Cox proportional hazards regression analysis showed that higher tumor polo-like kinase 4 expression was an independent predictive factor for worse disease-free survival but not for overall survival.Conclusion:Polo-like kinase 4 possesses the clinical significance as a biomarker for aiding prognostication and facilitating postoperative tumor management in patients with gastric cancer.

Liver fibrosis is a common pathological consequence of a variety of chronic stimuli, including viral, autoimmune, drug-induced, cholestatic and metabolic diseases. Fibrosis is driven by a dynamic process involving increased synthesis of matrix components and a failure of physiological mechanisms of matrix turnover. Activation of hepatic stellate cells (HSCs) remains a central event in fibrosis. HSCs are the main source of extracellular matrix (ECM). Transforming growth factor-beta (TGF-Β), which is the fibrogenic master cytokine, can induce the activation of HSCs to produce a large amount of ECM, and is capable of inducing apoptosis of liver cells. RNA interference (RNAi) is a novel gene disruption technology. Studies have shown that small interfering RNA (siRNA) targeting TGF-Β1 may inhibit the activation and proliferation of HSCs, suppress ECM synthesis and block liver fibrosis. TGF-Β1 siRNA-mediated gene silencing therapy provides a new avenue for liver fibrosis. This review summarizes recent progresses in research on HSCs, TGF-Β1 and TGF-Β1 siRNA in liver fibrosis.