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Kailian He,1,2,&ast; Xiashuang Zhang,1,2,&ast; Dong Yang,3 Xiaofeng Fu,3 Yulu Chen,1,2 Ziqi Chen,1,2 Jinglin Mo,3 Lingmi Zhou,3 Fang Xu,3 Xiuli Jiang,3 Wuxiang Shi,4 Liang Cao,1,5 You Li1,2 1Department of Environmental Health and Occupational Medicine, School of Public Health, Guilin Medical University, Guilin, Guangxi, 541199, People’s Republic of China; 2Guangxi Health Commission Key Laboratory of Entire Lifecycle Health and Care (Guilin Medical University), Guilin, Guangxi, 541199, People’s Republic of China; 3Department of AIDS Control and Prevention, Guilin Center for Disease Control and Prevention, Guilin, Guangxi, 541000, People’s Republic of China; 4Health Management Unit, Faculty of Humanities and Management, Guilin Medical University, Guilin, Guangxi, 541199, People’s Republic of China; 5Department of Experimental Teaching Center, School of Public Health, Guilin Medical University, Guilin, Guangxi, 541199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: You Li; Liang Cao, Email liyou121300@163.com; caoliang00552@163.comPurpose: The purpose of our study is to understand the current status of depression and medical social support in elderly HIV/AIDS, as well as the role of social support on depression, so as to provide a certain reference for reducing the occurrence of depression in the population.Methods: A total of 115 participants with PLWHA (people living with HIV/AIDS) aged 50 years or older were collected in Guilin from December 2021 to July 2022. Depression and medical social support were assessed using the Center for Streaming Depression Scale (CES-D) and the Medical Social Support Scale (MOS-SSS). The structural equation model was used to examine the relationship between medical social support and depression.Results: Sixty-one of 115 participants developed depressive symptoms with a prevalence of 53.0%. The results of univariate analysis showed that ethnicity, health status, mean monthly income, antiviral treatment status, and medical social support influenced PLWHA depression (P< 0.05). Simple linear regression showed that health status (95% CI: − 9.901~-2.635), and antiviral treatment status (95% CI: − 12.969~-3.394) influent depression (P< 0.05). There were associations between total medical social support, practical support dimension, message and emotional support dimension, social interactive cooperation dimension, emotional support dimension and depression (unadjusted and adjusted for contextual factors) (P < 0.05). Using multiple linear regression analyses, we found that medical-social support was negatively associated with depression with a standardized effect value of − 0.223. PLWHA with higher medical social support had lower prevalence of depression.Conclusion: The results indicate that the prevalence of depression among HIV/AIDS patients in Guilin is high. So the joint efforts of individuals, families, and society are needed to improve the physical and mental health of the PLWHA.Keywords: older people living with HIV/AIDS, medical social support, depression, structural equation model, SEM

Supplementary Figures 1-5 from A Genome-Wide Screen Reveals Functional Gene Clusters in the Cancer Genome and Identifies EphA2 as a Mitogen in Glioblastoma

Supplementary Table 1 from A Genome-Wide Screen Reveals Functional Gene Clusters in the Cancer Genome and Identifies EphA2 as a Mitogen in Glioblastoma

A novel genome-wide screen that combines patient outcome analysis with array comparative genomic hybridization and mRNA expression profiling was developed to identify genes with copy number alterations, aberrant mRNA expression, and relevance to survival in glioblastoma. The method led to the discovery of physical gene clusters within the cancer genome with boundaries defined by physical proximity, correlated mRNA expression patterns, and survival relatedness. These boundaries delineate a novel genomic interval called the functional common region (FCR). Many FCRs contained genes of high biological relevance to cancer and were used to pinpoint functionally significant DNA alterations that were too small or infrequent to be reliably identified using standard algorithms. One such FCR contained the EphA2 receptor tyrosine kinase. Validation experiments showed that EphA2 mRNA overexpression correlated inversely with patient survival in a panel of 21 glioblastomas, and ligand-mediated EphA2 receptor activation increased glioblastoma proliferation and tumor growth via a mitogen-activated protein kinase–dependent pathway. This novel genome-wide approach greatly expanded the list of target genes in glioblastoma and represents a powerful new strategy to identify the upstream determinants of tumor phenotype in a range of human cancers. (Cancer Res 2006; 66(22): 10815-23)

Supplementary Table 2 from A Genome-Wide Screen Reveals Functional Gene Clusters in the Cancer Genome and Identifies EphA2 as a Mitogen in Glioblastoma

Surface integrity is a critical factor to assess the quality of mechanical products, which has a significant impact on the service performance. In this work, the surface integrity of coating, such as roughness, hardness and residual stress, are changed by micro-blasting. The high-speed sliding wear experiments and cutting experiments are carried out with the TiAlN coated tool with different levels of surface integrity. The influence of the surface integrity of the coating on the high-speed sliding wear and cutting performance is investigated. The result shows that the low surface roughness of the coating can effectively reduce the friction coefficient. The high surface hardness and compressive residual stress (absolute value) can reduce the fluctuation range of friction coefficient. The cutting performance of coated tool is mainly influenced by the surface hardness and surface residual stress. The high wear resistance of the TiAlN coated tool in sliding wear process or cutting process can be obtained at the low surface roughness, the medium hardness and residual stress. It has practical significance to improve the surface integrity and the wear resistance of the coated tools.

The application of polyetheretherketone (PEEK) in additive manufacturing (AM) can effectively reduce material and energy waste in the manufacturing process and help achieve lightweight parts. As a result, AM PEEK is considered an emerging technology in line with green manufacturing concepts. However, 3D-printed PEEK parts often suffer from low mechanical strength and poor surface quality due to the immaturity of the manufacturing process. Therefore, this research investigates the feasibility of improving the surface quality of 3D-printed parts by dry milling post-processing. Meanwhile, the mechanical strength of the parts is improved by optimizing the printing process parameters, and the effects of mechanical strength on milling quality are investigated. The novelty of this research is to design experiments based on the anisotropy of 3D-printed parts. For the first time, the delamination of the milling post-processing surface of 3D-printed PEEK parts is investigated. The results show that the milled surfaces of 3D-printed PEEK parts are prone to delamination problems. The printing direction has a significant effect on the quality of milling post-processing, whereas the milling directions have little effect on milling post-processing quality. The delamination problem can be significantly improved by a side milling process where the specimen is printed at 90° and then milled. Milling surface delamination is caused by the poor mechanical strength (internal bonding) of 3D-printed PEEK parts. By improving the mechanical strength of 3D-printed PEEK parts, the delamination of its milled surfaces can be significantly improved.

Due to the high-efficiency, environmental protection the low cost, the micro sandblasting technology is used in the surface treatment of the coated tools. The simulation and application of micro sandblasting of the coated tool are carried out to reveal the surface treatment mechanism and analyze the influence of sandblasting parameters on the tool surface integrity. The flow field erosion simulation model of abrasive-water-air three-phase flow is established. The results show that the maximum velocity and pressure are obtained at the center of jet flow. The pressure distribution on the target surface has little correlation with the distance to the nozzle. The surface morphology of the AlTiN coated tool changes obviously after micro sandblasting. Moreover, the low surface roughness Ra of the blasted tool can be obtained at the small sandblasting pressure and time. Additionally, the residual compressive stress on the surface of the AlTiN coated tool is enhanced after micro sandblasting. This work has practical significance for optimizing micro sandblasting process and improving the surface integrity of coated tools.

Colorectal cancer (CRC) is a common cause of cancer-related deaths worldwide. MicroRNA-935 (miR-935) has been reported to be involved in several cancers. In the present study, we aimed to investigate the role of miR-935 in the progression of CRC. The expression levels of miR-935 in CRC tissues and cells were detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The prognostic significance of miR-935 was identified using Kaplan-Meier survival analysis and Cox regression assay. Cell proliferation capacity was detected by Cell Counting Kit-8 (CCK-8) assay. Cell migration and invasion capacities were determined by Transwell assay in CRC cells. Bioinformatics analysis and luciferase reporter assays were used to confirm the direct target of miR-935. The expression of miR-935 was increased in CRC tissues and cells. Overexpression of miR-935 was significantly associated with lymph node metastasis and TNM stage. Overexpression of miR-935 in patients predicted shorter overall survival compared to low miR-935 expression. The expression of miR-935 was indicated to be an independent prognostic factor for CRC patients. In addition, overexpression of miR-935 in CRC cells promoted cell proliferation, migration, and invasion, whereas inhibition of miR-935 suppressed cell proliferation, migration, and invasion. Bioinformatics and luciferase assays revealed that INPP4A is a direct target of miR-935. Our findings suggest that miR-935 functions as an oncogene and promotes CRC progression. INPP4A is a potential target of miR-935. And miR-935 may represent a prognostic biomarker and potential therapeutic strategy for CRC treatment.

This work presents a novel design of long period fiber grating (LPFG) refractive index sensor based on mode transition near phase-matching turning point (PMTP). The dual peaks can approach to PMTP by adjusting the fiber radius, and LPFG can operate in the mode transition range by choosing the optimal film thickness. Through experiments, the LPFG based on mode transition near PMTP was fabricated by the aforesaid design, and a glycerol solution concentration monitoring test was performed to analyze its sensing properties. The results show that if the dual peaks are close to PMTP and the overlay thickness stays within the mode transition range, the sensitivity to surrounding refractive index (SRI) will be greatly improved. Compared with the regular LPFG sensors based on dual peaks resonance or the LPFG sensors based on mode transition, this LPFG has a higher sensitivity to SRI which can reach to 4900nm/RIU in the SRI range of 1.34 ∼ 1.39.

Long non-coding RNAs (lncRNAs) are known as crucial regulators in the development of OC. In the current study, we aim to explore the function and molecular mechanism of lncRNA DLEU1 in OC. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine the expression of DLEU1, miR-429, and TFAP2A in OC cells and tissues. The relationship among DLEU1, miR-429, and TFAP2A was tested by dual-luciferase reporter (DLR) assay. Besides, the proliferative, migratory and invasive abilities of OC cells were analyzed by MTT, wound healing, and transwell assays, respectively. Western blot was performed to determine the protein expression of TFAP2A. The expression of lncRNA DLEU1 and TFAP2A were upregulated, and miR-429 was downregulated in OC tissues. Silencing of DLEU1 inhibited the proliferation, migration, and invasion of OC cells. Bioinformation and DLR assay showed that DLEU1 acted as the sponge for miR-429. Moreover, miR-429 could directly target TFAP2A and inhibit the proliferation, migration, and invasion of OC cells. Moreover, we observed a negative correlation between miR-429 and DLEU1, and between miR-429 and TFAP2A in OC tissues. The transfection of miR-429 inhibitor or pcDNA-TFAP2A reversed the inhibitory effects of si-DLEU1 on the proliferation, migration, and invasion of OC cells. Silencing of DLEU1 inhibited the proliferation, migration, and invasion of OC cells by regulating miR-429/TFAP2A axis, indicating a potential therapeutic target for OC.

MicroRNAs are crucial regulators for the development, mass and function of pancreatic β-cells. MiRNA dysregulation is associated with β-cell dysfunction and development of diabetes. The members of let7 family are important players in regulating cellular growth and metabolism. In this study we investigated the functional role of let7b-5p in the mouse pancreatic β-cells. We generated pancreatic β-cell-specific let7b-5p transgenic mouse model and analyzed the glucose metabolic phenotype, β-cells mass and insulin secretion in vivo. Luciferase reporter assay, immunofluorescence staining and western blot were carried out to study the target genes of let7b-5p in β-cells. Let7b-5p overexpression impaired the insulin production and secretion of β-cells and resulted impaired glucose tolerance in mice. The overexpressed let7b-5p inhibited pancreatic β-cell proliferation and decreased the expression of cyclin D1 and cyclin D2. Our findings demonstrated that let7b-5p was critical in regulating the proliferation and insulin secretion of pancreatic β-cells.

Background Effective targeting therapies for common chronic liver disease nonalcoholic steatohepatitis (NASH) are in urgent need. MicroRNA-targeted therapeutics would be potentially an effective treatment strategy of hepatic diseases. Here we investigated the functional role of miR-221/222 and the therapeutic effects of antimiRs-221/222 in NASH mouse models. Methods We generated the miR-221/222flox/flox mice on a C57BL/6 J background and the hepatic miR-221/222 knockout (miR-221/222-LKO) mice. The mice were challenged with the methionine and choline deficient diet (MCDD) or chronic carbon tetrachloride (CCl4) treatment to generate experimental steatohepatitis models. Adenovirus-mediated re-expression of miR-221/222 was performed on the MCDD-fed miR-221/222-LKO mice. The MCDD and control diet-fed mice were treated with locked nucleic acid (LNA)-based antimiRs of miR-221/222 to evaluate the therapeutic effects. Histological analysis, RNA-seq, quantitative PCR and Western blot of liver tissues were carried out to study the hepatic lipid accumulation, inflammation and collagen deposition in mouse models. Findings Hepatic deletion of miR-221/222 resulted in significant reduction of liver fibrosis, lipid deposition and inflammatory infiltration in the MCDD-fed and CCl4-treated mouse models. The hepatic steatosis and fibrosis were dramatically aggravated by miR-221/222 re-expression in MCDD-fed miR-221/222-LKO mice. AntimiRs of miR-221/222 could effectively reduce the MCDD-mediated hepatic steatosis and fibrosis. Systematically mechanistic study revealed that hepatic miR-221/222 controlled the expression of target gene Timp3 and promoted the progression of NASH. Interpretation Our findings demonstrate that miR-221/222 are crucial for the regulation of lipid metabolism, inflammation and fibrosis in the liver. LNA-antimiRs targeted miR-221/222 could reduce steatohepatitis with prominent antifibrotic effect in NASH mice. Fund This work is supported by the Natural Science Foundation of China (81530020, 81390352 to Dr. Ning and 81522032 to Dr. Cao and 81670793 to Dr. Jiang); National Key Research and Development Program (No. 2016YFC0905001 and 2017YFC0909703 to Dr. Cao); the Shanghai Rising-Star Program (15QA1402900 to Dr. Cao); Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (20171905 to Dr. Jiang).

Layered double hydroxides (LDHs) intercalated with amino acids such as methionine (Met) were synthesized as new adsorbents to remediate arsenic-polluted water. This Zn2Al-Met-LDHs, identified with the formula of Zn0.7Al0.3(OH)2(Met)0.3·0.32H2O, has good thermal stability. Adsorption experiments with Zn2Al-Met-LDHs showed that the residual arsenic in solution could be reduced below the regulation limit, and this adsorption process fitted Langmuir isotherm and the pseudo-second-order kinetics well. A remarkably high removal efficiency and the maximum adsorption capacity for As(III) were achieved, 96.7% and 94.1 mg/g, respectively, at 298 K. The desorption efficiency of As(III) from the arsenic-saturated Zn2Al-Met-LDHs (

Anthraquinone-2,6-disulphonate (AQDS) and reduced Graphene Oxide (rGO) were selected to prepare the AQDS–rGO composites for investigating the bioreduction performance of As(V)/Fe(III) from the flooded arsenic-rich soil. The addition of AQDS–rGO composites coupled with acetate helped release more 849.87 ± 97.05 μg L−1 of As(III) and 144.02 ± 10.02 mg L−1 of Fe(II) from soil, compared to acetate control at 208.17 ± 35.97 μg L−1 of As(III) and 85.75 ± 4.80 mg L−1 of Fe(II). Meanwhile, the performance was also perceived to be better than the amendments with the mixture of gradient AQDS and acetate, as well as the incorporation of gradient AQDS, rGO and acetate (identified by the maximal levels of Fe(II) and As(III), less than 130.74 ± 22.01 mg L−1 and 675.15 ± 67.06 μg L−1, respectively). Because metal-reducing or metal-oxidizing bacteria in the soil are susceptible to the soluble AQDS level, it would in turn influence the bioreduction performance of As(V)/Fe(III). The mediated strategies of AQDS-composites positively correlated with the loaded contents of AQDS, electrical conductivity and increasing abundance of metal-reducing bacteria (e.g., Desulfitobacterium, Clostridium, Pseudomonas, Geobacter, and Anaeromyxobacter) derived from the AQDS–rGO composites amendments, favor the bioreductive dissolution of As(V)/Fe(III) from the soil. This insight will encourage the application of a promising tool as an alternative technology for remediating arsenic-polluted soil.

Microribonucleic acids (miRNAs) are essential for the regulation of development, proliferation, and functions of pancreatic β-cells. The conserved miR-221/222 cluster is an important regulator in multiple cellular processes. Here we investigated the functional role of miR-221/222 in the regulation of β-cell proliferation and functions in transgenic mouse models. We generated 2 pancreatic β-cell-specific–miR-221/222 transgenic mouse models on a C57BL/6J background. The glucose metabolic phenotypes, β-cell mass, and β-cell functions were analyzed in the mouse models. Adenovirus-mediated overexpression of miR-221/222 was performed on β-cells and mouse insulinoma 6 (MIN6) cells to explore the effect and mechanisms of miR-221/222 on β-cell proliferation and functions. Luciferase reporter assay, histological analysis, and quantitative polymerase chain reaction (PCR) were carried out to study the direct target genes of miR-221/222 in β-cells. The expression of miR-221/222 was significantly upregulated in β-cells from the high-fat diet (HFD)–fed mice and db/db mice. Overexpression of miR-221/222 impaired the insulin production and secretion of β-cells and resulted in glucose intolerance in vivo. The β-cell mass and proliferation were increased by miR-221/222 expression via Cdkn1b and Cdkn1c. MiR-221/222 repressed insulin transcription activity through targeting Nfatc3 and lead to reduction of insulin in β-cells. Our findings demonstrate that miR-221/222 are important regulators of β-cell proliferation and insulin production. The expression of miR-221/222 in β-cells could regulate glucose metabolism in physiological and pathological processes.

Investigations were performed on the determination of the main components in

Investigations were performed on the determination of the main components in Berchemia lineata (L.) DC. (BL) and its metabolism with human liver microsomes (HLM). A total of 35 compounds were detected in BL extracts and 25 of them including 6 naphthopyrones, 10 flavonoids, 2 phenolic acids, 2 phenols, 4 fatty acids and 1 quinone were unambiguously or tentatively identified by UPLC-QTOF-MS/MS. Among them, naphthopyrones were first identified in BL extracts and labelled in chromatography. In addition, the weak inhibitory effects of BL extracts (IC50＝149.25 μg/mL) and rubrofusarin-6-O-α-L-rhamnosyl-(1-6)-O-β-D-glu-copyranside (the main component of BL extracts, M0; IC50＝82.14 μM) on CYP3A4 were also proved using testosterone as specific probe drug. The main metabolic pathway of M0 by HLM was hydroxylation in its aglycone, the metabolite was tentatively identified as 10-hydroxy-rubrofusarin-6-O-α-L-rhamnosyl-(1-6)-O-β-D-glucopyranside. Components characterisation and the metabolism with HLM could help the further development and application of BL.

Biochars prepared from biogas residue using different chemical activators were investigated for their As(III) adsorption properties. The results indicated that the original biochars did not exhibit significant As(III) adsorption. However, ZnCl 2 -activated biochar, which possessed the largest specific surface area, 516.67 cm 2 /g, and exhibited a perfectly porous texture, showed excellent performance in a 500 μgL −1 solution of As(III). Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy were utilized to identify the mechanism of As(III) adsorption by ZnCl 2 -activated biochar. Adsorption was found to occur mainly through ligand exchange of the hydroxyl in Zn-OH to form Zn-O-As(III), as well as through porous adsorption. As a low-cost adsorbent, the adsorption process was well fitted using a pseudo-second-order model, with an R 2 > 0.993. The adsorption process was fast, requiring nearly 90 min to reach adsorption equilibrium. Batch adsorption experimental results indicated that ZnCl 2 -activated biochar has a maximum adsorption capacity of 27.67 mg/g at pH 7.0, and the adsorption process followed the Freundlich isotherm model well, with an R 2 > 0.994. In addition, the current work demonstrated the efficiency of using ZnCl 2 -activated biochar adsorbent to treat As(III)-contaminated water.

Background The transcription factor YY1 is an important regulator for metabolic homeostasis. Activating mutations in YY1 lead to tumorigenesis of pancreatic β-cells, however, the physiological functions of YY1 in β-cells are still unknown. Here, we investigated the effects of YY1 ablation on insulin secretion and glucose metabolism. Methods We established two models of β-cell-specific YY1 knockout mice. The glucose metabolic phenotypes, β-cell mass and β-cell functions were analyzed in the mouse models. Transmission electron microscopy was used to detect the ultrastructure of β-cells. The flow cytometry analysis, measurement of OCR and ROS were performed to investigate the mitochondrial function. Histological analysis, quantitative PCR and ChIP were performed to analyze the target genes of YY1 in β-cells. Results Our results showed that loss of YY1 resulted in reduction of insulin production, β-cell mass and glucose tolerance in mice. Ablation of YY1 led to defective ATP production and mitochondrial ROS accumulation in pancreatic β-cells. The inactivation of YY1 impaired the activity of mitochondrial oxidative phosphorylation, induced mitochondrial dysfunction and diabetes in mouse models. Conclusion Our findings demonstrate that the transcriptional activity of YY1 is essential for the maintenance of mitochondrial functions and insulin secretion in β-cells.

BACKGROUND Interleukin-1 receptor-associated kinases (IRAKs) are crucial mediators in the signaling pathways of Toll-like receptors (TLRs)/IL1Rs. Targeting the IRAK4/IRAK1/TRAF6 axis and its associated pathway has therapeutic benefits in liver fibrosis. However, the function of IRAK1 itself in the development of liver fibrosis remains unknown. MATERIAL AND METHODS Irak1 global knockout (KO) mice were generated to study the functional role of Irak1 in liver fibrosis. Male Irak1 knockout and control mice were challenged with chronic carbon tetrachloride (CCl4) or fed a methionine- and choline-deficient diet (MCDD) to generate models of nonalcoholic steatohepatitis (NASH). Liver inflammation and collagen deposition were assessed by histological examination, quantitative real-time PCR (qRT-PCR), and western blotting of hepatic tissues. RESULTS The mRNA expression of the downstream inflammatory gene Il1b was significantly lower in Irak1-KO than in control mice. Irak1 ablation had little effect on inflammatory cell infiltration into livers of mice with NASH. Collagen deposition and the expression of genes related to fibrogenesis were similar in the livers of Irak1-KO and control mice exposed to CCl4 and MCDD. The loss of Irak1 did not affect lipid or glucose metabolism in these experimental models of steatohepatitis. CONCLUSIONS Irak1 knockout reduced the expression of inflammatory genes but had no effect on hepatic fibrogenesis. The Irak1-related pathway may regulate liver fibrosis via other pathways or be compensated for by other factors.

China is a massive mercury emitter, responsible for a quarter of the world’s mercury emissions, which transit the atmosphere and accumulate throughout its watercourses. The Changjiang (Yangtze) River is the third largest river in the world, integrating mercury emissions over its 1.8 × 106 km2 catchment and channelling them to the East China Sea where they can be buried. Despite its potential global significance, the importance of the East China Sea as a terminal mercury sink remains poorly known. To address this knowledge gap, total mercury and methylmercury concentrations were determined from 51 surface sediment samples revealing their spatial distribution, whilst demonstrating the overall pollution status of the East China Sea. Sedimentary mercury distributions beneath the East China Sea are spatially heterogeneous, with high mercury concentrations (> 25 ng g−1) corresponding to areas of fine-grained sediment accumulation. In contrast, some sites of fine-grained sediment deposition have significantly lower values of methylmercury (< 15 ng g−1), such as the Changjiang estuary and some isolated offshore areas. Fine-grained particles and organic matter availability appear to exert the dominant control over sedimentary mercury distribution in the East China Sea, whereas in situ methylation serves as an additional control governing methylmercury accumulation. Estimated annual sedimentary fluxes of mercury in the East China Sea are 51 × 106 g, which accounts for 9% of China’s annual mercury emissions.

To investigate the factors associated with the anastomotic leakage after anterior resection in rectal cancer.From January 2014 to January 2017 471 patients underwent Dixon procedure for rectal cancer in The Affiliated Hospital of Qingdao University. The data of those patients was collected and reviewed retrospectively. Inclusion criteria included: 1) rectal cancer confirmed by preoperative electron colonoscopy; 2) the standard of total mesorectal excision followed by the surgeon during the surgery; and 3) elective surgery. Exclusion criteria included multi-primary rectal cancer, secondary surgery for tumor recurrence, palliative surgery, Miles procedure, Hartmann procedure, hormone drugs used, presence of rheumatic and immune diseases, and distant metastasis of rectal cancer. The variables, including demograpic characteristics, ASA score, diabetes mellitus, preoperative radiochemotherapy, histopathologic grade, pathological T stage, laparoscopic or open surgery, distance of the tumor from the anal verge ≤5 cm, were analyzed to identify the risk factors for anastomotic leakage.Of 471 patients, 285 and 186 were men and women, respectively, with a mean age of 61 years (range, 31-92) years. Symptomatic clinically anastomotic leakage occurred in 31 patients (6.6%, 31/471) after Dixon procedure for rectal cancer. On univariate analysis, the occurrence of anastomotic leakage was associated with diabetes (χFor patients with rectal cancer with diabetes, undergoing neoadjuvant chemoradiotherapy, or distance ≤5 cm between the tumor and anal edge, anastomotic leakage after anterior resection of rectal cancer must be paid attention. When necessary, preventive colostomy or use of double-perfusion cannula for abdominal flushing should be considered.

Receptor for advanced glycation end products (RAGE) is a multiligand receptor belonging to the immunoglobulin superfamily and plays crucial roles in the development of many human diseases such as neurodegenerative diseases, diabetes, cardiovascular diseases, osteoarthritis and cancer. RAGE involves in a number of cell processes such as neuroinflammation, apoptosis, proliferation and autophagy. In CNS, RAGE was primarily expressed in neurons, microglia and vascular endothelial cells. Interacting with ligands, RAGE induces a series of signal transduction cascades and leads to the activation of transcription factor NF-κB as well as increased expression of cytokines like TNF-α, IL-1. Moreover, binding to RAGE can also stimulate the generation of reactive oxygen species (ROS), which is implicated in neuron death. It was reported that RAGE were highly expressed in PD patients when compared to age-matched controls. And RAGE ablation protected nigral dopaminergic neurons against cell death in MPTP treated mice. Here we review this article to elucidate the role of RAGE in PD pathogenesis and highlight the anti-RAGE strategies in the treatment of PD.

In this study, macroscopic and spectroscopic experimental methods accurately modeled the sorption process of arsenate on ferrihydrite. EXAFS, X-ray diffraction and infrared (IR) spectroscopy indicated that the behavior of As(V) adsorption onto ferrihydrite took place mainly via surface complexation and surface precipitation at acidic pH (3.0–6.0), while the surface precipitation was dominated at longer time intervals and higher Fe3+ concentration. The macroscopic competitive adsorption experiment between arsenate with phosphate indicated two types of adsorption sites existing on the surface of ferrihydrite, i.e., non-exchangeable sites, which are responsible for a rapid surface complex formation; and exchangeable sites for a slow build-up of surface precipitates. In the slow build-up precipitates, the As(V) surface coverage (mmol/g) exhibited a good linear relationship (R2 = 0.952) with the amount of dissolved Fe3+. Three steps are involved during the process of surface precipitation, i.e., (1) an initial uptake of As(V) via surface complexation; (2) re-adsorption of Fe3+ leaching from ferrihydrite on the surface complex; and (3) As(V) adsorption via surface complexation again and finally forming the surface precipitate.

The tumor suppressor menin is recognized as a key regulator of β-cell proliferation. To induce tumorigenesis within the pancreatic β-cells, floxed alleles of Men1 were selectively ablated using Cre-recombinase driven by the insulin promoter. Despite the β-cell specificity of the RipCre, glucagon-expressing tumors as well as insulinomas developed in old mutant mice. These glucagon-expressing tumor cells were menin deficient and expressed the mature α-cell-specific transcription factors Brain-specific homeobox POU domain protein 4 (Brn4) and v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B (MafB). Moreover, the inactivation of β-cell-specific transcription factors was observed in mutant β-cells. Our work shows that Men1 ablation in the pancreatic β-cells leads to the inactivation of specific transcription factors, resulting in glucagon-expressing tumor development, which sheds light on the mechanisms of islet tumorigenesis.

We reported a long period grating (LPG) written in specially designed photonic crystal fiber (PCF) for refractive index (RI) sensing by interrogating the transmitted light power. The outermost ring of clad holes of the PCF is enlarged where the analyte is filled. We showed that the leakage loss of the clad mode increases with the RI in the larger holes. By numerically analyzing the complex couple mode equations for the core mode and the first clad mode, we found the depth of attenuation band in the transmitted spectra and the total transmitted power is sensitive to the leakage loss of the clad mode or the RI in the larger holes. We also demonstrated that the transmitted power is sensitive to the RI even less than that of the silica, which just avoids the limitation that the transmitted light power of LPG in conventional fiber is only sensitive to the RI of the external media higher than that of fiber clad.

Dysregulation of ribosome biogenesis or translation can promote cancer, but the underlying mechanisms remain unclear. UTP18 is a component of the small subunit processome, a nucleolar multi-protein complex whose only known function is to cleave pre-ribosomal RNA to yield the 18S ribosomal RNA component of 40S ribosomal subunits. Here, we show that UTP18 also alters translation to promote stress resistance and growth, and that UTP18 is frequently gained and overexpressed in cancer. We observed that UTP18 localizes to the cytoplasm in a subset of cells, and that serum withdrawal increases cytoplasmic UTP18 localization. Cytoplasmic UTP18 associates with the translation complex and Hsp90 to upregulate the translation of IRES-containing transcripts such as HIF1a, Myc and VEGF, thereby inducing stress resistance. Hsp90 inhibition decreases cytoplasmic UTP18 and UTP18-induced increases in translation. Importantly, elevated UTP18 expression correlates with increased aggressiveness and decreased survival in numerous cancers. Enforced UTP18 overexpression promotes transformation and tumorigenesis, whereas UTP18 knockdown inhibits these processes. This stress adaptation mechanism is thus co-opted for growth by cancers, and its inhibition may represent a promising new therapeutic target.

The correlation between tuberous sclerosis complex 1 (TSC1) gene polymorphism and epilepsy was studied. In total, 38 patients with epilepsy treated in People's Hospital of Rizhao from May 2015 to June 2016 were selected as study subjects, as the observation group, 38 healthy people in the same period were selected as the control group. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to study the polymorphism of TSC1 gene in the above study subjects. The mRNA expression of TSC1 gene in the observation group and the control group was measured by fluorescence quantitative PCR, the expression of TSC1 protein in the control and observation group was measured by western blotting and ELISA. The polymorphisms of TSC1 gene in control group and observation group were analyzed by PCR-RFLP. There were three genotypes of TCS1 gene locus 142 in healthy population: CC (79.3%), CA (13.9%) and AA (6.8%), there were also three genotypes at locus 142 in the observation group: CC (21.3%), CA (26.4%) and AA (52.3%), there was significant difference in the genotypes at locus 142 between healthy population and the patients with epilepsy (P0.05). The expression of TSC1 gene was detected by western blot method. Western blotting showed no significant difference in TSC1 protein expression between the two groups (P>0.05). However, by determining the activity of TSC1 protein in the observation group and the control group by ELISA, it was found that TSC1 activity in healthy human body (8.95±2.41 U/ml) was much lower than that in the patients with epilepsy (29.27±4.06 U/ml), the difference was statistically significant (P

BACKGROUND Previous studies have clearly demonstrated that metformin inhibits cell proliferation and cell growth in many types of human cancers. Increased survival rates in patients with breast and lung cancer receiving metformin have also been observed. However, the effect of metformin on pheochromocytoma cells remains unexplored. MATERIAL AND METHODS Rat pheochromocytoma cells (PC12 cells) were cultured and treated with metformin or vehicle control. Cell proliferation, cell-cycle, apoptosis, genes expression, and the signaling pathways involved were analyzed in PC12 cells. RESULTS The metformin treatment reduced cell viability and proliferation in rat pheochromocytoma PC12 cells in a dose- and time-dependent manner. Furthermore, metformin exposure led to an increased apoptosis rate and cell-cycle arrest accompanied with downregulation of Ccna2 and Ccnb2. At the molecular level, the AMPK signaling pathway was activated, whereas the mTOR and ERK1/2 signaling pathways were inhibited by metformin. CONCLUSIONS Our data suggest an antiproliferative role of metformin in pheochromocytoma development, which may provide a novel option for future cancer therapy.

Adrenal Cushing’s syndrome is caused by excess production of glucocorticoid from adrenocortical tumors and hyperplasias, which leads to metabolic disorders. We performed whole-exome sequencing of 49 blood-tumor pairs and RNA sequencing of 44 tumors from cortisol-producing adrenocortical adenomas (ACAs), adrenocorticotropic hormone–independent macronodular adrenocortical hyperplasias (AIMAHs), and adrenocortical oncocytomas (ADOs). We identified a hotspot in the PRKACA gene with a L205R mutation in 69.2% (27 out of 39) of ACAs and validated in 65.5% of a total of 87 ACAs. Our data revealed that the activating L205R mutation, which locates in the P+1 loop of the protein kinase A (PKA) catalytic subunit, promoted PKA substrate phosphorylation and target gene expression. Moreover, we discovered the recurrently mutated gene DOT1L in AIMAHs and CLASP2 in ADOs. Collectively, these data highlight potentially functional mutated genes in adrenal Cushing’s syndrome.

Increased expression of S100A6 in many cancer tissues and its association with tumor behavior and patient prognosis were demonstrated, and there are no studies analyzing the serum levels of S100A6 in patients with gastric cancer (GC). Serum S100A6 levels were investigated as a marker of tumor aggressiveness in patients with GC, and the S100A6 gene was examined as a potential therapeutic target in GC. Serum S100A6 levels were detected in 103 GC patients and 72 healthy subjects by ELISA. Clinicopathological features of GC patients were analyzed in correlation to serum S100A6 levels. Two small interfering RNAs against S100A6 (siRNA1-S100A6 and siRNA2-S100A6) were generated and transfected into SGC7901 cells using pSUPER gfp-neo vector, and the effects of S100A6 knockdown on cell proliferation, invasion and apoptosis were evaluated in vitro. The effects of S100A6 silencing on tumor growth and metastasis were evaluated in vivo in a pseudo-metastatic GC nude mouse model. Serum S100A6 levels were significantly higher in GC patients than in healthy controls (P

The mechanism underlying the increased susceptibility of type 2 diabetes in offspring of maternal malnutrition is poorly determined. Here we tested the hypothesis that functional microRNAs (miRNAs) mediated the maternal low-protein (LP) isocaloric diet induced pancreatic β-cell impairment. We performed miRNA profiling in the islets from offspring of LP and control diet mothers to explore the potential functional miRNAs responsible for β-cell dysfunction. We found that LP offspring exhibited impaired glucose tolerance due to decreased β-cell mass and insulin secretion. Reduction in the β-cell proliferation rate and cell size contributed to the decreased β-cell mass. MiR-15b was up-regulated in the islets of LP offspring. The up-regulated miR-15b inhibited pancreatic β-cell proliferation via targeting cyclin D1 and cyclin D2. Inhibition of miR-15b in LP islet cells restored β-cell proliferation and insulin secretion. Our findings demonstrate that miR-15b is critical for the regulation of pancreatic β-cells in offspring of maternal protein restriction, which may provide a further insight for β-cell exhaustion originated from intrauterine growth restriction.

Each part of smart grid system is supported by communications network. The amount of smart grid data is developing larger and more complex so that the network faces a lot of challenges to acquire stable and efficient communication in smart grid. The application of cognitive radio can effectively alleviate the shortage of spectrum resources in the smart grid communication network. In this paper, the spectrum allocation scheme of matching algorithm is proposed based on channel idle time and users' priority. Firstly, hidden Markov-model (HMM) is established to predict the idle time of channels in spectrum pool. Baum-Welch, which is the HMM training algorithm of the most commonly used, is formulated to train HMM parameter for each channel to get the most suitable HMM. Secondly, the data of smart grid is divided considering real-time priority, making the higher priority second user (SU) can occupy the channel with longer idle time. Finally, the system total throughput is calculated based on the two factors above. Simulation results show that the total throughput is improved effectively employing the matching algorithm and the stability and the reliability of communication network is obtained. The utilization of spectrum resources is also improved in smart grid.

Microbially-mediated arsenic (As) metabolism and iron (Fe) bioreduction from sediments play crucial roles in global As/Fe cycle, and their mobilization is associated with the various effects within the alliance of “mediator-bacteria-DOM (Dissolved Organic Matter)”. The gradient levels (0.05, 0.10 and 1.00 mM) of sodium anthraquinone-2,6-disulphonate (AQDS) as a mediator were investigated for their impact on reductive dissolution of As(V) and Fe(III) from arsenic-rich sediment. For the overall performance of AQDS-mediated reductive dissolution on As(V) and Fe(III), a more positive effect resulting from 0.05 mM AQDS was observed compared to 0.10 mM, whereas an inhibitory effect was observed with 1.00 mM. Compared to the biotic supplementation with acetate as electron donors, approximately 13- and 6-fold increased levels of As(III) were released with 0.05 and 0.10 mM, respectively, compared to 1.00 mM AQDS (107.51 μg/L), and approximately 4- and 3-fold increased Fe(II) levels (40.72 mg/L) were observed during the same conditions. Multiple-dynamic effects of “bacteria-AQDS-DOM”, which result from AQDS, shifted the microbial community and synchronously derived terrestrial DOM, which potentially changes the DOM substrate and complex formation of As(III)-Fe(II)-humic DOM. High-throughput sequencing results indicated an increase in the abundance of metal-reducing bacteria (e.g., Bacillus (> 16%), Lactococcus (> 13%), Pseudomonas (> 4%) and Geobacter (> 3%)) when supplemented with 0.05 and 0.10 mM of AQDS. However, a boost increasing the abundance of metal oxidizing bacteria was observed with Alicyclobacillus (> 16%), Burkholderia (> 7%), and Bradyrhizobium (> 5%) upon supplementation with 1.00 mM AQDS. These novel insights have profound environmental implications and significance in terms of engineering, not only for understanding the cycle of As/Fe in sediment biochemical processes but for considering future alternative bioremediation treatments.

Objective Thymic neuroendocrine tumor is the second-most prevalent cause of ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS), which is a rare disease characterized by ectopic ACTH oversecretion from nonpituitary tumors. However, the genetic abnormalities of thymic neuroendocrine tumors with EAS remain largely unknown. We aim to elucidate the genetic abnormalities and identify the somatic mutations of potential tumor-related genes of thymic neuroendocrine tumors with EAS by whole exome sequencing. Design and methods Nine patients with thymic neuroendocrine tumors with EAS who were diagnosed at Shanghai Clinical Center for Endocrine and Metabolic Diseases in Ruijin Hospital between 2002 and 2014 were enrolled. We performed whole exome sequencing on the DNA obtained from thymic neuroendocrine tumors and matched peripheral blood using the Hiseq2000 platform. Results We identified a total of 137 somatic mutations (median of 15.2 per tumor; range, 1–24) with 129 single-nucleotide mutations (SNVs). The predominant substitution in these mutations was C:G > T:A transition. Approximately 80% of detected mutations resulted in amino acid changes. However, we failed to discover any recurrent mutations in these nine patients. By functional predictions, HRAS, PAK1 and MEN1, previously reported in neuroendocrine tumors, were identified as candidate tumor-related genes associated with thymic neuroendocrine tumors. Conclusions Using whole exome sequencing, we identified genetic abnormalities in thymic neuroendocrine tumors with EAS. Thereby, this study acts as a further supplement of the genetic features of neuroendocrine tumors. Somatic mutations of three potential tumor-related genes (HRAS, PAK1 and MEN1) might contribute to the tumorigenesis of thymic neuroendocrine tumors with EAS.

Glioblastoma contains a hierarchy of stem-like cancer cells, but how this hierarchy is established is unclear. Here, we show that asymmetric Numb localization specifies glioblastoma stem-like cell (GSC) fate in a manner that does not require Notch inhibition. Numb is asymmetrically localized to CD133-hi GSCs. The predominant Numb isoform, Numb4, decreases Notch and promotes a CD133-hi, radial glial-like phenotype. However, upregulation of a novel Numb isoform, Numb4 delta 7 (Numb4d7), increases Notch and AKT activation while nevertheless maintaining CD133-hi fate specification. Numb knockdown increases Notch and promotes growth while favoring a CD133-lo, glial progenitor-like phenotype. We report the novel finding that Numb4 (but not Numb4d7) promotes SCFFbw7 ubiquitin ligase assembly and activation to increase Notch degradation. However, both Numb isoforms decrease epidermal growth factor receptor (EGFR) expression, thereby regulating GSC fate. Small molecule inhibition of EGFR activity phenocopies the effect of Numb on CD133 and Pax6. Clinically, homozygous NUMB deletions and low Numb mRNA expression occur primarily in a subgroup of proneural glioblastomas. Higher Numb expression is found in classical and mesenchymal glioblastomas and correlates with decreased survival. Thus, decreased Numb promotes glioblastoma growth, but the remaining Numb establishes a phenotypically diverse stem-like cell hierarchy that increases tumor aggressiveness and therapeutic resistance.

Biochar derived from the pyrolysis at 500 °C with fresh biogas slurry and residue, was conducted to investigate its potential role in mediating the speciation and mobilization of As(V) and Fe(III) from arsenic-contaminated tailing mine sediment, with consideration of the changes in microbial populations and dissolved organic matter (DOM). The reduction of As(V) (10-13%) and Fe(III) (12-17%) were partly in response to biochar abiotically causing desorption and reduction effect, but were predominantly (87-90% and 83-88% for As(V) and Fe(III)) attributed to biochar stimulating biological reduction. The level of As(III) released from sediment upon biochar amendment (656.35±89.25 μg L(-1)) was significantly higher than the level released without biochar amendment (98.06±19.38 μg L(-1)) after 49 days incubation. Although a low level of Fe(II) (0.81±0.07 mg L(-1)) was determined in the solution when amending with biochar, most of released Fe(II) (166.25±40.25 mg L(-1)) was formed as biochar-Fe(II)minerals composite. More importantly, biochar stimulated the DOM bioavailability in association with bacterial activities mediating As(V) and Fe(III) reduction. High-throughput sequencing results indicated biochar application shifted the soil microbial community and increased the relative abundance of As(V)-/Fe(III)-reducing bacteria, mostly Geobacter, Anaeromyxobacter, Desulfosporosinus and Pedobacter. The discovery of biochar-bacteria-DOM consortium may broaden new understanding into speciation and mobilization of metals, which arouses attention to exploit feasible bioremediation for metal-contaminated sediment.

The imprinted gene PEG3 confers parenting and sexual behaviors, alters growth and development, and regulates apoptosis. However, a molecular mechanism that can account for the diverse functions of Peg3/Pw1 is not known. To elucidate Peg3-regulated pathways, we performed a functional screen in zebrafish. Enforced overexpression of PEG3 mRNA during zebrafish embryogenesis decreased beta-catenin protein expression and inhibited Wnt-dependent tail development. Peg3/Pw1 also inhibited Wnt signaling in human cells by binding to beta-catenin and promoting its degradation via a p53/Siah1-dependent, GSK3beta-independent proteasomal pathway. The inhibition of the Wnt pathway by Peg3/Pw1 suggested a role in tumor suppression. Hypermethylation of the PEG3 promoter in primary human gliomas led to a loss of imprinting and decreased PEG3 mRNA expression that correlated with tumor grade. The decrease in Peg3/Pw1 protein expression increased beta-catenin, promoted proliferation, and inhibited p53-dependent apoptosis in human CD133(+) glioma stem cells. Thus, mammalian imprinting utilizes Peg3/Pw1 to co-opt the Wnt pathway, thereby regulating development and glioma growth.