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Background: The pathogenesis of multiple sclerosis (MS) is mediated primarily by T cells, but most studies of MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have focused on CD4 T cells. The aims of the current study were to determine the pathological interrelationship between CD4 and CD8 autoreactive T cells in MS/EAE., Methods: Female C57BL/6 mice (n = 20) were induced by myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. At 14 days after immunization, T cells were isolated from the spleen and purified as CD4 and CD8 T cells by using CD4 and CD8 isolation kits, and then the purity was determined by flow cytometric analysis. These cells were stimulated by MOG35-55 peptide and applied to proliferation assays. The interferon-gamma (IFN-γ) and interleukin (IL)-4 secretion of supernatant of cultured CD4 and CD8 T cells were measured by enzyme-linked immunosorbent assays (ELISA). For adoptive transfer, recipient mice were injected with MOG35-55-specific CD8 or CD4 T cells. EAE clinical course was measured by EAE score at 0-5 scale and spinal cord was examined by staining with hematoxylin and eosin and Luxol fast blue staining., Results: CD8CD3 and CD4CD3 cells were 86% and 94% pure of total CD3 cells after CD8/CD4 bead enrichment, respectively. These cells were stimulated by MOG35-55 peptide and applied to proliferation assays. Although the CD8 T cells had a generally lower response to MOG35-55 than CD4 T cells, the response of CD8 T cells was not always dependent on CD4. CD8 T cell secreted less IFN-γ and IL-4 compared with CD4 T cells. EAE was induced in wildtype B6 naïve mice by adoptive transfer of MOG35-55-specific T cells from B6 active-induced EAE (aEAE) mice. A similar EAE score and slight inflammation and demyelination were found in naive B6 mice after transferring of CD8 T cells from immunized B6 mice compared with transfer of CD4 T cells., Conclusion: Our data suggest that CD8 autoreactive T cells in EAE have a lower encephalitogenic function but are unique and independent on pathogenic of EAE rather than their CD4 counterparts.

Purpose : To examine the hidden blood loss (HBL) in treatment of AO type A1-A3 thoracolumbar fractures with three different approaches and to explore the influential factors of HBL among patients after the surgery of internal fixation for thoracolumbar fractures. Methods : We retrospectively studied 85 patients in treatment of thoracolumbar fractures: 25 patients via percutaneous approach (Group A), 33 patients via paraspinal approach (Group B), and 27 patients via conventional open approach (Group C). The demographic information of the patients was collected. Each patient's preoperative and postoperative hematocrit were recorded and used for calculating the blood loss according to the Gross's formula. The difference of blood loss between the three groups was measured by ANOVA. And influential factors were further analyzed by multivariate linear regression analysis in each group. Results : The average HBL was 240.0 ± 65.1 mL in Group A, 313.7 ± 138.1 mL in Group B, and 382 ± 153.8 mL in Group C. There was statistical difference in the HBL between three groups ( P = 0.000). However, multivariate linear regression analysis revealed that HBL of three approaches was not associated with age, gender, body mass index (BMI), percentage of height loss, percentage of height restoration, fracture type, or operation time. Conclusion : There was a substantial HBL in the treatment of thoracolumbar fractures, which was neglected by surgeons. Further investigation is necessary to study the risk factors for surgery on HBL in treatment of thoracolumbar fractures.

Objective: To investigate the gene mutation types and gene carrying rate of common thalassemia in patients with thalassemia in Quanzhou, and to analyze its molecular epidemiological characteristics in Quanzhou., Methods: 546 patients with thalassemia diagnosed at the first hospital of Quanzhou from January 2017 to October 2018 were collected and retrospectively analyzed for their types of mutations and carrier rates., Results: Among the 4226 samples submitted, 546 positive samples were detected, the total carrying rate of the thalassaemia genes was 12.92%; the carrier rate of α-thalassemia was 8.16%; the carrier rate of β-thalassemia was 4.76%; There were more α-thalassemia missing patients than non-deleted patients. The Southeast Asian deletion type (-- SEA /αα) was the most common one, with a composition ratio of 68.98%, which was followed by 22.61% (-α 3.7 /αα), 2.61% (α WS α/αα), and 2.32% (αα CS /αα), 2.32% (α QS α/αα), 1.16% (-α 4.2 /αα); 9 types of β-thalassemia gene mutations were detected. The most common three mutations were IVSII-654 (C→T, 42.29%), CD41-42 (-TTCT, 33.83%), CD17 (A→T, 12.94%). 2 cases of -- THAI /αα , 1 case of αα/ααα anti3.7 and 1 case of HKαα were detected., Conclusion: This study shows that the gene carrying rate of thalassemia in Quanzhou is high and has diversity, which can provide some reference for the prevention and control of thalassemia in Quanzhou.

Thirteen new species are formally described: Cortinarius brunneocarpus from Pakistan, C. lilacinoarmillatus from India, Curvularia khuzestanica on Atriplex lentiformis from Iran, Gloeocantharellus neoechinosporus from China, Laboulbenia bernaliana on species of Apenes , Apristus , and Philophuga (Coleoptera, Carabidae) from Nicaragua and Panama, L. oioveliicola on Oiovelia machadoi (Hemiptera, Veliidae) from Brazil, L. termiticola on Macrotermes subhyalinus (Blattodea, Termitidae) from the DR Congo, Pluteus cutefractus from Slovenia, Rhizoglomus variabile from Peru, Russula phloginea from China, Stagonosporopsis flacciduvarum on Vitis vinifera from Italy, Strobilomyces huangshanensis from China , Uromyces klotzschianus on Rumex dentatus subsp. klotzschianus from Pakistan. The following new records are reported: Alternaria calendulae on Calendula officinalis from India; A. tenuissima on apple and quince fruits from Iran; Candelariella oleaginescens from Turkey; Didymella americana and D. calidophila on Vitis vinifera from Italy; Lasiodiplodia theobromae causing tip blight of Dianella tasmanica ' variegata ' from India; Marasmiellus subpruinosus from Madeira, Portugal, new for Macaronesia and Africa; Mycena albidolilacea , M. tenuispinosa , and M. xantholeuca from Russia; Neonectria neomacrospora on Madhuca longifolia from India; Nothophoma quercina on Vitis vinifera from Italy; Plagiosphaera immersa on Urtica dioica from Austria; Rinodina sicula from Turkey; Sphaerosporium lignatile from Wisconsin, USA; and Verrucaria murina from Turkey. Multi-locus analysis of ITS, LSU, rpb1 , tef1 sequences revealed that P. immersa , commonly classified within Gnomoniaceae (Diaporthales) or as Sordariomycetes incertae sedis , belongs to Magnaporthaceae (Magnaporthales). Analysis of a six-locus Ascomycota-wide dataset including SSU and LSU sequences of S. lignatile revealed that this species, currently in Ascomycota incertae sedis , belongs to Pyronemataceae (Pezizomycetes, Pezizales).

Control of lipid digestibility by various food components has received great attention in recent decades. However, there is limited literature on investigating the synergistic effect of exogenous emulsifiers and endogenous sodium cholate (SC) on lipid digestion in a simulated physiological crowded medium. In this work, the synergistic interaction of Tween80 and SC according to the regular solution theory, and the hydrolysis of lipid emulsions containing tricaprylin, glyceryltrioleate or soybean oil in crowding medium was studied. The results show that emulsions stabilized by a combination of Tween80 and SC showed higher digestion rate and transformation than those with Tween80 or SC. The digestion rate could be increased by polyethylene glycols (PEGn) with varying crowding degree. The denaturation temperature of the lipase was increased in macromolecular crowded medium. This work allows for better understanding of the interaction between the amphiphiles and the macromolecular crowding effect on lipase digestion in the physiological environment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Study Design: In vitro biomechanical evaluation of a novel self-adaptive unidirectional ratchet growing rod (RGR) system., Objective: The aim of this study was to propose and biomechanically validate a novel RGR construct in vitro using porcine thoracic spines and calculate the tensile force required to elongate the RGR with springs, without springs, and with soft tissue encapsulation (induced in vivo in rabbits)., Summary of Background Data: Literature lacks clear consensus regarding the implant of choice for early-onset scoliosis. Multiple systems are currently available, and each has its own advantages and disadvantages. Therefore, studying novel designs that can credibly accommodate growth and curb deformity progression is of principle importance., Methods: In vitro biomechanical motion tests were done using six porcine thoracic spines with pedicle screws at T3 and T8. A pure moment of ±5 Nm was loaded in lateral bending (LB) and flexion-extension. Range of motion (ROM) and neutral zone (NZ) of each specimen was determined after connecting the free movable growing rods (FGRs), RGRs, and standard rods (SRs). Tensile tests were done to measure the force required to elongate the RGR with springs, without springs, and with soft tissue encapsulation (induced in vivo in rabbits)., Results: Global ROM, implanted T3-T8 ROM, and the NZ of specimens with FGRs and RGRs were significantly higher than that with SRs. The RGRs favored unidirectional elongation in both LB and flexion. The tensile forces required for elongating the RGR without springs, with springs, and with soft tissue capsulation (by a scaled unit of 3 mm) were 3 ± 1.3 N, 10.5 ± 0.4 N, and 48.4 ± 14.4 N, respectively., Conclusion: The RGR could stabilize and favor unidirectional elongation of the implanted spinal column when appropriate forces were present. There was no device failure as far as we have studied and it is anticipated that, with further safety and feasibility assessment, RGRs could be adapted for clinical use., Level of Evidence: N/A.

Apoptosis (programmed cell death) is a systematic and coordinated cellular process that occurs in physiological and pathophysiological conditions. Sidestepping or resisting apoptosis is a distinct characteristic of human cancers including childhood malignancies. This review dissects the apoptosis pathways implicated in pediatric tumors. Understanding these pathways not only unraveled key molecules that may serve as potential targets for drug discovery, but also molecular nodes that integrate with other signaling networks involved in processes such as development. This review presents current knowledge of the complex regulatory system that governs apoptosis with respect to other processes in pediatric cancers, so that fresh insights may be derived regarding treatment resistance or for more effective treatment options., Competing Interests: The authors declare no conflict of interest.

Background: Complications of Crohn's disease such as intestinal obstruction, fistula or perforation often need surgical treatment. Nearly 70%-80% patients with Crohn's disease would receive surgical treatment during the lifetime. However, surgical treatment is incurable for Crohn's disease. The challenge of recurrence postoperatively troubles both doctors and patients. Over 50% patients would suffer recurrence postoperatively. Some certain risk factors are associated with recurrence of Crohn's disease., Aim: To evaluate the risk factors for endoscopic recurrence and clinical recurrence after bowel resection in Crohn's disease., Methods: Patients diagnosed Crohn's disease and received intestinal resection between April 2007 and December 2013 were included in this study. Data on the general demographic information, preoperative clinical characteristics, surgical information, postoperative clinical characteristics were collected. Continuous data are expressed as median (inter quartile range), and categorical data as frequencies and percentages. Kaplan-Meier method was applied to estimate the impact of the clinical variables above on the cumulative rate of postoperative endoscopic recurrence and clinical recurrence, then log-rank test was applied to test the homogeneity of those clinical variables. Multivariate Cox proportional hazard regression analysis was performed to identify the risk factors of postoperative endoscopic recurrence and clinical recurrence., Results: A total of 64 patients were included in this study. The median follow-up time for the patients was 17 (9.25-25.75) mo. In this period, 41 patients (64.1%) had endoscopic recurrence or clinical recurrence. Endoscopic recurrence occurred in 34 (59.6%) patients while clinical recurrence occurred in 28 (43.8%) patients, with the interval between the operation and recurrence of 13.0 (8.0-24.5) months and 17.0 (8.0-27.8) mo, respectively. In univariate analysis, diagnosis at younger age ( P < 0.001), disease behavior of penetrating ( P = 0.044) and preoperative use of anti-tumor necrosis factor (TNF) ( P = 0.020) were significantly correlated with endoscopic recurrence, while complication with perianal lesions ( P = 0.032) and preoperative use of immunomodulatory ( P = 0.031) were significantly correlated with clinical recurrence. As to multivariate analysis, diagnostic age ( P = 0.004), disease behavior ( P = 0.041) and preoperative use of anti-TNF ( P = 0.010) were independent prognostic factors for endoscopic recurrence, while complication with perianal lesions ( P = 0.023) was an independent prognostic factor for clinical recurrence., Conclusion: Diagnostic age, disease behavior, preoperative use of anti-TNF and complication with perianal lesions were independent risk factors for postoperative recurrence in Crohn's disease., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ageratum conyzoides L. is an important Chinese medicinal plant. In this study, we reported the complete chloroplast genome of A . conyzoides . The chloroplast genome sequence is 151,309 bp in length and consisted of a large single copy (LSC) region (83,884 bp), a small single copy (SSC) region (17,771 bp), and two inverted repeats (IRs) (24,827 bp). It was composed of 126 genes and they were 81 protein-coding genes, 30 tRNA genes, 8 rRNA genes, and 7 pseudogene. Phylogenetic analysis with reported chloroplast genomes can not only show that A. conyzoides has a close genetic relationship with Centaurea diffusa and Carthamus tinctorius , but also provide new evidence for the identification of Praxelis clematidea and A. conyzoides ., Competing Interests: The authors declare no conflicts of interest and are responsible for the content., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Torilis scabra (Thunb.) DC. is widely distributed in China and Japan and has been introduced to North America. In this study, the complete chloroplast genome sequence of the T . scabra was obtained by de novo assembly using the NGS data. The chloroplast genome of T. scabra was 157,855 bp in length and divided into four distinct regions, such as large single-copy region (85,362 bp), small single-copy region (17,993 bp), and a pair of inverted repeat regions (27,250 bp). The genome annotation predicted a total of 127 genes, including 82 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis with reported chloroplast genomes showed that T. scabra has a close genetic relationship with Anthriscus cerefolium ., Competing Interests: The authors declare no conflicts of interest and are responsible for the content., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Osteoarthritis (OA) is the most prevalent form of human arthritis which is characterized by the degradation of cartilage and inflammation. As a rare Sirt6 activator, cyanidin is the major component of anthocyanins commonly found in the Mediterranean diet, and increasing evidence has shown that cyanidin exhibits anti-inflammatory effects in a variety of diseases. However, the anti-inflammatory effects of cyanidin on OA have not been reported. In the present study, we identified that cyanidin treatment could strongly suppress the expression of NO, PGE2, TNF-α, IL-6, iNOs, COX-2, ADAMTS5 and MMP13, and reduce the degradation of aggrecan and collagen II in IL-1β-induced human OA chondrocytes, indicating the anti-inflammatory effect of cyanidin. Further investigation of the mechanism involved revealed that cyanidin could upregulate the Sirt6 level in a dose-dependent manner and Sirt6 silencing abolished the effect of cyanidin in IL-1β-stimulated human OA chondrocytes, indicating a stimulatory effect of cyanidin on Sirt6 activation. Meanwhile, we found that cyanidin could inhibit the NF-κB pathway in IL-1β-stimulated human OA chondrocytes and its effect may to some extent depend on Sirt6 activation, suggesting that cyanidin may exert a protective effect through regulating the Sirt6/NF-κB signaling axis. Moreover, the in vivo study also proved that cyanidin ameliorated the development of OA in surgical destabilization of the medial meniscus (DMM) mouse OA models. In conclusion, these results demonstrate that cyanidin may have therapeutic potential for the treatment of OA.

Callicarpa nudiflora,which is a big brand of Li nationality medicine with Hainan characteristics,has the effects of dissolving stasis,hemostasis,anti-inflammatory and antibacterial. At present,there is a lack of information about the reference genome of C. nudiflora. The study of the genome size,heterozygosity rate and characteristics of SSR of C. nudiflora,can provide an effective basis for the formulation of the whole genome de novo sequencing strategy and development of SSR molecular markers of C. nudiflora. To realize this purpose,high throughput sequencing platform Illumina Hiseq was used to sequence the genome structure of C. nudiflora and K-mer analysis was applied to estimate genome size,repeat sequences and heterozygosity rate. Simple-sequence repeat( SSR) loci that are suitable as markers were identified by MISA software. The results showed the estimated genome size of C. nudiflora was 822. 43 Mb,with a 0. 85% heterozygosity rate and 71. 67% repeats,and the GC content of genome was about 49. 20%. Therefore,C. nudiflora belongs to a complex genome with high heterozygosity and repetition. SSR molecular genetic markers were analyzed in the genome sequence,and a total of 206 049 SSRs were identified,among which mono-nucleotide,di-nucleotide and tri-nucleotide repetitive motifs summed up to 198 993,accounting for 96. 57% of the total SSRs. Among the 2-6 nucleotide repeats,AT/AT,AAT/ATT,AGCC/CTGG,AAAAT/ATTTT and AGATAT/ATATCT have the largest number,respectively. This report represents the first genome-wide characterization of C. nudiflora,and provides a reference for the construction of the library for the fine sequencing of the genome,and a molecular basis for the development of SSR molecular markers as well as for the protection and utilization of gene resources.

Glucocorticoids are the most common cause of glucocorticoid‑induced osteoporosis (GIOP). Moreover, the role of circular RNAs (circRNAs) in the regulation of bone metabolism remains unclear. Therefore, in the present study, it was hypothesized that hsa&#95;circ&#95;0006393 may play an important role in GIOP. To investigate the role of circRNAs in GIOP, treatment with dexamethasone or transfection with a vector overexpressing hsa&#95;circ&#95;0006393 were performed using in vitro cell and in vivo mouse models. Reverse transcription‑quantitative PCR, fluorescence in situ hybridization and western blotting were performed to investigate the function of hsa&#95;circ&#95;0006393 in vitro. In addition, the effects of hsa&#95;circ&#95;0006393 on osteogenesis were investigated. Dual‑energy X‑ray absorptiometry analysis was performed to examine the osteogenic potential of hsa&#95;circ&#95;0006393 in vivo. Moreover, the mechanism underlying hsa&#95;circ&#95;0006393‑mediated bone metabolism regulation via the microRNA (miR)‑145‑5p/forkhead box O1 (FOXO1) pathway was investigated. The present results suggested that the expression level of hsa&#95;circ&#95;0006393 was decreased in patients with GIOP. Furthermore, the overexpression of hsa&#95;circ&#95;0006393 increased the expression level of genes associated with osteogenesis. Moreover, hsa&#95;circ&#95;0006393 was identified to be localized mainly in the cytoplasm and nucleus of bone marrow mesenchymal stem cells. miR‑145‑5p was found to be directly targeted by hsa&#95;circ&#95;0006393. Collectively, hsa&#95;circ&#95;0006393 increases the expression levels of osteogenic genes during bone remodeling by sponging miR‑145‑5p and upregulating FOXO1.

Objective: Transarterial chemoembolization (TACE) is recommended to treat intermediate/advanced stage of hepatocellular carcinoma (HCC). However, the overall survival among initially TACE-treated patients varies significantly. The clinical characterization of long-term survival following TACE remains uncertain. We sought to identify clinical parameters and treatment requirements for long-term survival among patients with hepatitis B-related HCC who were initially treated with TACE., Materials and Methods: The included patients with HCC were admitted to our cancer center between December 2009 and May 2015. Patients who survived for >3 years were compared with those who died within 3 years. The clinical and laboratory findings that were associated with the survival were also analyzed., Results: One in six (17.9%) patients with HCC in this cohort survived for > 3 years after TACE. Body mass index (BMI) ≥ 23kg/m 2 , aspartate aminotransferase levels ≤ 40 U/L, an activated partial thromboplastin time ≤ 34 seconds, α-fetoprotein (AFP) levels ≤ 25 ng/mL, antiviral therapy, tumor size ≤ 8 cm, solitary nodule, and the absence of vascular invasion were independently favorably associated with a 3-year survival. An absence of vascular invasion was the only independent factor associated with 3-year survival in patients who received resection and/or ablation after TACE., Conclusion: In this cohort, a 3-year survival was associated with BMI, antivirus treatment, tumor status, hepatic function, and AFP level. Distant metastasis did not negatively impact the long-term survival among patients with hepatitis B-related HCC initially treated with TACE. Vascular invasion was the single impediment to long-term survival in patients who received add-on resection and/or ablation after TACE., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: The aim of the present study was to investigate the relationship between vacuum facet phenomena and lumbar instability in patients with degenerative spondylolisthesis (DS) in L4-L5., Methods: Patients with L4-L5 DS who had both lumbosacral flexion-extension radiographs and computed tomography (CT) scans available for review from January 2016 to December 2017 were eligible for the present study. The dynamic motion index (DMI) of each patient was used to represent the percentage of slippage of L-L4 on the L5 vertebral disks on the flexion radiographs minus the percentage on the extension radiographs. The facet vacuum index refers to the average width of the facet vacuum on the left and right sides., Results: A total of 67 patients with L4-L5 DS were included in the present study. Of the 67 patients, 35 had a vacuum facet phenomenon on their CT scan and 32 patients did not. The incidence of lumbar instability in the patients with a vacuum facet phenomenon was significantly greater than that in the patients without a vacuum facet phenomenon (P = 0.015). The mean DMI for the patients with a vacuum facet phenomenon was significantly greater than that for the patients without a vacuum facet phenomenon (P < 0.001). A positive linear correlation was found between the facet vacuum index and DMI for patients with a vacuum facet phenomenon (Pearson correlation coefficient, 0.597; P < 0.001)., Conclusions: A linear correlation was found between the degree of segmental motion and the width of the vacuum facet phenomenon in patients with DS at L4-L5. Our study has shown that vacuum facet phenomena detected on the CT images of patients with DS are highly predictive of segmental instability., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The effects of overweightness and weight loss on the development and prognosis of hepatocellular carcinoma (HCC) remain unclear. In this study, we aimed to evaluate the impact of overweightness and weight loss on the survival of patients with intermediate/advanced HCC receiving chemoembolization as initial treatment., Methods: We examined 1,170 patients who underwent chemoembolization as initial treatment for Barcelona-Clínic Liver Cancer stages B and C HCC at Sun Yat-sen University Cancer Center (Guangzhou, China) between December 2009 and May 2015. A baseline body mass index (BMI) of ≥23 kg/m 2 was defined as overweight, and body-weight loss of ≥5.0% from baseline was defined as critical weight loss (CWL). Cox regression analysis was used to determine the association between overweightness or CWL and overall survival (OS)., Results: The median survival time was 16.8 (95% confidence interval, 13.9-19.7) months and 11.1 (95% confidence interval, 10.0-12.2) months in the overweight and non-overweight groups (log-rank test, P  <   0.001), respectively. Cox multivariate analysis identified overweightness as an independent protective prognostic factor for OS ( P  <   0.001). Subgroup stratification analysis revealed a significant association between overweightness and survival among patients receiving further treatment ( P  =   0.005), but not in those not receiving further treatment ( P  =   0.683). Multivariate analysis showed that both overweightness and CWL were independent prognostic factors for OS among patients receiving further treatment., Conclusion: Among patients with intermediate- or advanced-stage HCC initially treated with chemoembolization, overweightness was associated with longer OS. Furthermore, CWL was an independent adverse prognostic factor for OS in patients receiving additional treatment., (© The Author(s) 2019. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Background: The role of nucleos(t)ide analogs (NAs) therapy in intermediate and advanced hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unclear., Aims: The aim was to evaluate the effect of NAs therapy on survival of intermediate- and advanced-stage HBV-related HCC patients initially treated with chemoembolization., Methods: A total of 1016 Barcelona Clinic Liver Cancer (BCLC) stage B/C HBV-related HCC patients initially treated with chemoembolization were included. Propensity score matching (PSM) was performed to decrease heterogeneity between the antiviral and non-antiviral groups. Kaplan-Meier and Cox regression analysis were performed to evaluate the effects of NAs therapy on overall survival (OS)., Results: Antiviral group (n = 394) significantly prolonged OS compared with non-antiviral group (n = 622) (p = 0.003). NAs therapy (p < 0.001) along with tumor size (p = 0.002), tumor number (p = 0.001), gross vascular invasion (p < 0.001), metastasis (p < 0.001), α-fetoprotein (p < 0.001), Child-Pugh score (p = 0.008), aspartate aminotransferase (p < 0.001), and HBV DNA (p = 0.018) were identified as independent prognostic factors for OS. After PSM processing, deducting the influence of subsequent treatments for HCC, NAs therapy was still identified as an independent protective factor (p = 0.009) for OS in patients who survived ≥ 7 months, regardless of BCLC stage B or C HCC., Conclusion: NAs therapy prolongs OS in intermediate- and advanced-stage HBV-related HCC patients initially treated with chemoembolization. After PSM processing, patients who survived ≥ 7 months still benefited from NAs therapy.

Background: 12-Lipoxygenase (12-LOX) plays a major role in the progression and metastasis of various types of cancer. In gastric cancer (GC), the expression level of 12-LOX is significantly up-regulated; however, its function, and underlying mechanism of action remain unclear., Methods: The mRNA and protein expression levels of 12-LOX were assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses, respectively, in GC cell lines. 12-LOX expression was stably up-regulated using lentiviral vector in BGC823 and MGC803 cells, and cell-counting kit-8 (CCK8), colony formation, and invasion assays were performed to verify the function of 12-LOX in proliferation and metastasis. In addition, the expression levels of epithelial-mesenchymal transition (EMT) differentiation markers and downstream targets of the Wnt/β-catenin signaling pathway were examined by Western blotting. A nude mouse model of tumor growth and metastasis was established to investigate the role of 12-LOX in vivo., Results: Our findings demonstrate that 12-LOX mRNA and protein were highly expressed in GC cell lines. 12-LOX overexpression promoted GC cell proliferation, migration, and invasion both in vitro and in vivo. In addition, up-regulation of 12-LOX promoted the EMT in GC cells, as reflected by a decrease in E-cadherin expression and an increase in N-cadherin and Snail expression. 12-LOX overexpression in GC cells also increased the expression of multiple downstream targets of the Wnt/β-catenin signaling pathway., Conclusion: These findings revealed that 12-LOX functions as an oncogene in promoting GC cell proliferation and metastasis in vitro and in vivo. In addition, 12-LOX might regulate the EMT via the Wnt/β-catenin signaling pathway, indicating a potential role for 12-LOX as a target in GC treatment., Competing Interests: The authors report no conflicts of interest in this work.

Molecular geometries and electronic structure calculations and spectroscopic assignments for metallonaphthalocyanines NiNc, CuNc and ZnNc are performed on the optimized geometries at B3LYP/6-31G* level. The order of the bond lengths of the NM bonds is computed to be NiNc < CuNc < ZnNc. The Mulliken atomic charges of the central M vary in the same order as the bond lengths. The metal dependent frequencies of IR-active and Raman-active vibrational modes decrease in the order of NiNc > CuNc > ZnNc, which is in reverse sequence of the N-M bond length. The strongest Raman lines predicted at 1570 (NiNc), 1546 (CuNc) and 1525 (ZnNc) cm -1 are highly sensitive to the metal ion. Comparison of the calculated properties of MNcs and MPcs (metallphthalocyanines) compounds reveals some interesting and meaningful results due to extension of the conjugated systems., (Copyright © 2019. Published by Elsevier B.V.)

The oriental fruit fly, Bactrocera dorsalis, is one of the most destructive pests worldwide. The frequent use of chemical insecticides has led B. dorsalis to develop resistance to many insecticides in recent decades. New high-throughput-sequenced transcriptomes, as well as genomes, have revealed a large number of reference genes for functional target identification. Here, we performed digital gene expression profiling of ovary and testis of B. dorsalis adults. Various genes were identified to be highly expressed in B. dorsalis ovary. The genes encoding components of eggshell, vitelline membrane proteins (Vmps) and chorion-related proteins, were identified to be tissue-specifically expressed in ovary. Five cytochrome P450 genes were also identified to be highly expressed in ovary. Three of them were ecdysone synthesis pathway genes indicating the ovary as a potential synthesis site of female. The up-regulated expression of Vmps by exogenous 20-hydroxyecdysone implied the hormonal regulation of eggshell formation during ovarian development. Many other genes with potential functions in ovarian development were also identified, including vitellogenin receptor, insulin receptor, NASP protein, and odorant binding protein. These findings should promote our understanding of the regulation of vitellogenesis and eggshell formation and enable exploration of potentially novel pest control targets., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Carbon monoxide (CO) is regarded as a potential therapeutic agent with multiple beneficial functions for biomedical applications. In this study, a versatile CO nanogenerator (designated as PPOSD) was fabricated and developed for tumor therapy and anti-inflammation. Partially oxidized tin disulfide (SnS 2 ) nanosheets (POS NSs) were decorated with a tumor-targeting polymer (polyethylene glycol-cyclo(Asp-d-Phe-Lys-Arg-Gly), PEG-cRGD), followed by the loading of chemotherapeutic drug doxorubicin (DOX) to prepare polymer@POS@DOX, or PPOSD. After injected intravenously, PPOSD could selectively accumulate in tumor tissue via the cRGD-mediated tumor recognition. Upon 561 nm laser irradiation, the POS moiety in PPOSD can photoreduce CO 2 to CO, which significantly sensitized the chemotherapeutic effect of DOX. The POS in PPOSD can also act as a photothermal agent for effective photothermal therapy (PTT) of the tumor upon 808 nm laser irradiation. Furthermore, the generated CO can simultaneously decrease the inflammatory reaction caused by PTT. Blood analysis and hematoxylin-eosin staining of major organs showed that no obvious systemic toxicity was induced after the treatment, suggesting good biosafety of PPOSD. This versatile CO nanogenerator will find great potential for both enhanced tumor inhibition and anti-inflammation.

Poly(methyl methacrylate) (PMMA) is the most frequently used bone void filler in orthopedic surgery. However, the interface between the PMMA-based cement and adjacent bone tissue is typically weak as PMMA bone cement is inherently bioinert and not ideal for bone ingrowth. The present study aims to improve the affinity between the polymer and ceramic interphases. By surface modifying nano-sized hydroxyapatite (nHAP) with ethylene glycol and poly(ɛ-caprolactone) (PCL) sequentially via a two-step ring opening reaction, affinity was improved between the polymer and ceramic interphases of PCL-grafted ethylene glycol-HAP (gHAP) in PMMA. Due to better affinity, the compressive strength of gHAP/PMMA was significantly enhanced compared with nHAP/PMMA. Furthermore, PMMA with 20 wt.% gHAP promoted pre-osteoblast cell proliferation in vitro and showed the best osteogenic activity between the composites tested in vivo . Taken together, gHAP/PMMA not only improves the interfacial adhesion between the nanoparticles and cement, but also increases the biological activity and affinity between the osteoblast cells and PMMA composite cement. These results show that gHAP and its use in polymer/bioceramic composite has great potential to improve the functionality of PMMA cement., Competing Interests: We declare we have no competing interests.

Background & Aims: Little is known about the composition and generation of plasma cell subsets in patients with hepatocellular carcinoma (HCC) and how these associate with outcomes. We investigated whether, or how, plasma cells differentiate and function in patients with HCC and mice with liver tumors., Methods: We analyzed subset composition and distribution of plasma cells in HCC samples from 342 patients who underwent curative resection at the Cancer Center of Sun Yat-sen University in China; samples of non-tumor liver tissue were used as controls. We associated plasma cell profiles with patient outcomes. Tissue-derived leukocytes were analyzed by flow cytometry and real-time polymerase chain reaction. The ability of macrophages to regulate plasma cell differentiation was determined in ex vivo cultures of cells from human HCC tissues. C57BL/6 and BALB/c mice were given injections of Hepa1-6 cells, which formed hepatomas, or H22 cells, which formed ascitic hepatomas. Gene expression patterns were analyzed in human HCC, mouse hepatoma, and non-tumor tissues by real-time polymerase chain reaction. Mice with hepatomas were given injections of GSK126 (an inhibitor of histone H3 lysine 27 methyltransferase [EZH2]) and 5-AZA-dC (an inhibitor of DNA methyltransferases); tumor tissues were analyzed by immunofluorescence and immunohistochemistry for the presence of immune cells and cytokines., Results: B cells isolated from HCCs had somatic hypermutations and class-switch recombinations to the IgG phenotype that were not observed in non-tumor tissues. Increased level of plasma cells correlated with poor outcomes of patients. Activated CD4 + T cells from HCCs stimulated C-X-C motif chemokine 10 (CXCL10) production by macrophages. CXCL10 bound CXC chemokine receptor 3 on B cells and signaled via extracellular signal-regulated kinase to cause them to become IgG-producing plasma cells. IgG activated Fc receptors on macrophages and induced them to produce interleukin 6, interleukin 10, and C-C motif chemokine ligand 20 (CCL20). In mice with hepatomas, depletion of B cells prevented generation of these macrophage, increased the anti-tumor T cell response, and reduced growth of hepatomas. However, these effects were lost after injection of CXC chemokine receptor 3-positive plasma cells. Human HCC and mouse hepatoma tissues had increased expression of DNA methyltransferase 1 and EZH2 compared with non-tumor tissues. Injection of mice with GSK126 and 5-AZA-dC induced expression of CXCL10 by tumor cells and caused plasma cell polarization, suppression of the anti-tumor T cell response, and hepatoma growth., Conclusions: Human HCC tissues contain B cells with class-switch recombinations to the IgG phenotype. Activated CD4 + T cells from HCCs stimulate CXCL10 production by macrophages; CXCL10 binds CXC chemokine receptor 3 on B cells and causes them to become IgG-producing plasma cells. IgG activates Fc receptor in macrophages to produce cytokines that reduce the anti-tumor immune response. In mice with hepatomas, depletion of B cells prevented generation of these macrophages, increased the anti-tumor T cell response, and reduced growth of hepatomas. This pathway involves increased expression of DNA methyltransferase 1 and EZH2 by HCC and hepatoma cells., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The aim of the study is to present the clockwise, modularized lymphadenectomy model of laparoscopic gastrectomy for gastric cancer patients, which is based on our clinical practice experience in laparoscopic gastric cancer surgery., Methods: From Jan 2015 to July 2017, 116 patients who underwent laparoscopic gastrectomy were retrospectively collected and analyzed. According to the different resection models, patients were divided into two groups: traditional laparoscopic lymphadenectomy group (63 patients) and clockwise, modularized lymphadenectomy group (53 patients). Operation-related parameters were compared between the two groups., Results: The clockwise, modularized lymphadenectomy group had less dissection time (119.8 ± 19.1 min vs. 135.3 ± 23.8 min, p < 0.001) and less intraoperative blood loss (81.7 ± 42.9 ml vs. 91.4 ± 28.7 ml, p = 0.016) compared with the traditional laparoscopic lymphadenectomy group. Meanwhile, the clockwise, modularized lymphadenectomy group had more numbers of examined lymph nodes (40.5 ± 14.3 vs. 33.9 ± 11.0, p = 0.007) than the traditional laparoscopic lymphadenectomy group. Besides, there was no statistically significant difference in the postoperative complication rates between the two groups. The clockwise, modularized lymphadenectomy group had shorter postoperative hospital stay than the traditional laparoscopic lymphadenectomy group (8.7 ± 3.2 days vs. 10.4 ± 3.9 days, respectively, p < 0.001)., Conclusions: Through the adoption of the fixed sequence of lymphadenectomy, requirements and standard of lymphadenectomy of each lymph node station, and specific surgical skills for intraoperative exposure by the clockwise and modularized lymphadenectomy model, we can optimize and facilitate the laparoscopic gastric cancer surgery.

The uncertainty relation, as one of the fundamental principles of quantum physics, captures the incompatibility of noncommuting observables in the preparation of quantum states. In this work, we derive two strong and universal uncertainty relations for N(N ≥ 2) observables with discrete and bounded spectra, one in multiplicative form and the other in additive form. To verify their validity, for illustration, we implement in the spin-1/2 system an experiment with single-photon measurement. The experimental results exhibit the validity and robustness of these uncertainty relations, and indicate the existence of stringent lower bounds.

Background: Zanthoxylum bungeanum originating in different places varies in alkylamide content and pungency intensity., Results: The pungency intensity of 19 Zanthoxylum bungeanum samples was first determined with Scoville pungency units (SPUs). The SPUs were found to range from 3.80E + 04 to 5.40E + 05. The chemical compositions and contents were measured next, using the ultra-performance liquid chromatography-mass spectrometry/ mass spectrometry (UPLC-MS/MS) method. The total alkylamide content ranged from 9.83 ± 0.15 to 89.98 ± 1.35 g kg -1 . Hydroxy-ϵ-sanshool, hydroxy-α-sanshool, hydroxy-β-sanshool, hydroxy-γ-sanshool, bungeanool, and isobungeanool were found to be the key pungent compounds, ranging in proportion from 92.65% to 97.69%. The relationship between alkymide compound content and pungency intensity was also analyzed by ridge regression, and it was found that the β values of independent variables were stable when k was more than 0.6. The regression coefficients of hydroxy-ϵ-sanshool, hydroxy-α-sanshool, hydroxy-β-sanshool, hydroxy-γ-sanshool, bungeanool, isobungeanool, and other alkylamides were 0.105, 0.177, 0.386, -0.166, -0.006, 0.005, and -0.018, respectively., Conclusion: Hydroxy- sanshool compounds were important in determinant the pungency intensity of Z. bungeanum. Knowledge of the relationship between alkymide compound content and pungency intensity will assist in the creation of new methods to determine pungency intensity and provide a scientific basis for flavor design, development of pungent food products, and consumer choice evaluations. © 2018 Society of Chemical Industry., (© 2018 Society of Chemical Industry.)

Previous studies support a critical role of hippocampus in contextual fear memory. Structural and functional alterations of hippocampus occur frequently in posttraumatic stress disorders (PTSD). Recent reports reveal that knockout of CLC-3, a member of the CLC family of anion channels and transporters, leads to neuronal degeneration and loss of hippocampus. However, the role of CLC-3 in contextual fear memory remains unknown. Using adenovirus and adeno-associated virus gene transfer to knockdown CLC-3 in hippocampal CA1, we investigate the role of CLC-3 in contextual fear memory. CLC-3 expression is increased in hippocampal CA1 after formation of long-term contextual fear memory. Knockdown of CLC-3 by adenovirus infusion in hippocampal CA1 significantly attenuates the contextual fear memory, reduces spine density, induces defects of excitatory synaptic ultrastructure showed by the decreased PSD length, PSD thickness and active zone length, and impairs L-LTP induction and maintenance. Knockdown of CLC-3 also induces the synaptic NMDAR subunit composition to an increased GluN2A/GluN2B ratio pattern and reduces the activity of CaMKII-α. Furthermore, selectively knockdown of CLC-3 in excitatory neurons by adeno-associated virus driven from CaMKII-α promoter is sufficient to impair long-term contextual fear memory. These findings highlight that CLC-3 in hippocampal CA1 is necessary for contextual fear memory., (Copyright © 2018. Published by Elsevier Inc.)

Three red cyclometalated iridium(iii) complexes (4tfmpq) 2 Ir(dipdtc), (4tfmpq) 2 Ir(dpdtc) and (4tfmpq) 2 Ir(Czdtc) (4tfmpq = 4-(4-(trifluoromethyl)phenyl)quinazoline, dipdtc = N , N -diisopropyl dithiocarbamate, dpdtc = N , N -diphenyl dithiocarbamate, and Czdtc = N -carbazolyl dithiocarbamate) containing the unique four-membered Ir-S-C-S backbone ring were synthesized in five minutes at room temperature with good yields, and the Gibbs free energy calculation results indicate that all reactions are exothermic and thermodynamically favorable processes. The emission colors ( λ peak = 641-611 nm), photoluminescence quantum efficiencies ( Φ P = 58.3-93.0%) and bipolar properties can be effectively regulated by introducing different electron-donating substituents into the dithiocarbamate ancillary ligands. Employing these emitters, organic light emitting diodes (OLEDs) with double emissive layers exhibit excellent performances with a maximum brightness over 60 000 cd m -2 , a maximum current efficiency of 40.68 cd A -1 , a maximum external quantum efficiency (EQE max ) of 30.54%, and an EQE of 26.79% at the practical luminance of 1000 cd m -2 . These results demonstrate that Ir(iii) complexes with sulfur-containing ligands can be rapidly synthesized at room temperature, which is key to the production of metal luminescent materials for large-scale application in highly efficient OLEDs.

Borneol, a natural product in the Asteraceae family, is widely used as an upper ushering drug for various brain diseases in many Chinese herbal formulae. The blood-brain barrier (BBB) plays an essential role in maintaining a stable homeostatic environment, while BBB destruction and the increasing BBB permeability are common pathological processes in many serious central nervous system (CNS) diseases, which is especially an essential pathological basis of cerebral ischemic injury. Here, we aimed to conduct a systematic review to assess preclinical evidence of borneol for experimental ischemic stroke as well as investigate in the possible neuroprotective mechanisms, which mainly focused on regulating the permeability of BBB. Seven databases were searched from their inception to July 2018. The studies of borneol for ischemic stroke in animal models were included. RevMan 5.3 was applied for data analysis. Fifteen studies investigated the effects of borneol in experimental ischemic stroke involving 308 animals were ultimately identified. The present study showed that the administration of borneol exerted a significant decrease of BBB permeability during cerebral ischemic injury according to brain Evans blue content and brain water content compared with controls ( P < 0.01). In addition, borneol could improve neurological function scores (NFS) and cerebral infarction area. Thus, borneol may be a promising neuroprotective agent for cerebral ischemic injury, largely through alleviating the BBB disruption, reducing oxidative reactions, inhibiting the occurrence of inflammation, inhibiting apoptosis, and improving the activity of lactate dehydrogenase (LDH) as well as P-glycoprotein (P-GP) and NO signaling pathway.

Gastric adenocarcinoma (GAC) is a challenging disease with dim prognosis even after surgery; hence, novel treatments for GAC are in urgent need. The aim of the present study was to explore new potential compounds interfering with the key pathways related to GAC progression. The differentially expressed genes (DEGs) between GAC and adjacent tissues were identified from The Cancer Genome Atlas (TCGA) and Genotype‑Tissue Expression (GTEx) database. Connectivity Map (CMap) was performed to screen candidate compounds for treating GAC. Subsequently, pathways affected by compounds were overlapped with those enriched by the DEGs to further identify compounds which had anti‑GAC potential. A total of 843 DEGs of GAC were identified. Via Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, 13 pathways were significantly enriched. Moreover, 78 compounds with markedly negative correlations with DEGs were revealed in CMap database (P<0.05 and Enrichment <0). Subpathways of cell cycle and p53 signaling pathways, and core genes of these compounds, cyclin B1 (CCNB1) and CDC6, were identified. This study further revealed seven compounds that may be effective against GAC; in particular methylbenzethonium chloride and alexidine have never yet been reported for GAC treatment. In brief, the candidate drugs identified in this study may provide new options to improve the treatment of patients with GAC. However, the biological effects of these drugs need further investigation.

Purpose: To explore the hidden blood loss (HBL) in treatment of extra-articular tibial fractures with plate and intramedullary nail fixation., Methods: We conducted a retrospective study including 209 consecutive patients treated by plate (Group LCP) or intramedullary nail fixation (Group IMN) for extra-articular tibial fractures between January 2015 to December 2017. Demographics, intraoperative data, perioperative laboratory values, transfusion rate, and early complications were collected and analyzed., Results: Of 209 patients, 96 patients fixed with IMN and 113 fixed with LCP. The average HBL was 272.71 ± 57.88 ml in Group LCP and 507.66 ± 109.81 ml in Group IMN, and there was statistical difference in the HBL between two groups (p < 0.001). The Hb and Hct loss, surgical duration, and postoperative number of anemic patients in Group IMN were significantly higher than in Group LCP (p < 0.001), and IMN fixation has a significantly higher rate of transfusion (p = 0.027), whereas patients in group IMN has significantly less VBL (p < 0.001), shorter postoperative hospital stay (p < 0.001), and less superficial infection (p = 0.014)., Conclusions: There was a significant amount of hidden blood loss after reamed intramedullary nail fixation for extra-articular tibial fractures, which was much higher than expected. In view of the morbidity of acute anaemia and transfusion, we suggest that for patients who suffer from extra-articular tibial fractures with multiple injuries, or those with low haemoglobin preoperatively, plates might be more suitable than nail fixation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: Hepatobiliary system cancer, which includes hepatocellular carcinoma (HCC), cholangiocarcinoma, and gallbladder carcinoma, has an increase of incidence and mortality due to various risk factors. Epstein-Barr virus (EBV) is associated with various types of lymphomas and carcinomas, which is also acknowledged as the first-discovered human tumor virus. Despite this, there is no systematic analysis about the relationship between the infection of EBV and hepatobiliary system cancer. The aim of this meta-analysis is to explore the significance of EBV infection in the development of hepatobiliary system cancer by evaluating the EBV infection ratio., Methods: A systematic search of PubMed, Embase, Cochrane Library, as well as China National Knowledge Infrastructure (CNKI), Chongqing VIP, Wan Fang, and China Biology Medicine databases was conducted. The EBV infection ratio and 95% confidence intervals (CIs) in hepatobiliary system cancer was evaluated. The I 2 statistic was used to represent heterogeneity. Through meta-regression, stratified analyses were applied to find out heterogeneity's sources. Odds ratios (ORs), 95% CIs of EBV infection in case-control studies were calculated., Results: Altogether, 15 studies were included containing a total of 918 cases and 157 controls. The whole infection ratio of EBV was 23% (95% CI: 13%, 33%, I 2  = 95.7%, P < 0.001) among all the patients. Comparable EVB infection ratios were observed in hepatobiliary system cancer as divided into different subtypes. The five case-control studies were epitomized to a pooled OR of 9.35 (95%CI: 2.95, 29.61, I 2  = 20.1%, P < 0.286)., Conclusion: EBV may be a potentially risk factor in the process of hepatobiliary system cancer. The prospective molecular mechanism remains to be explored., (Copyright © 2018. Published by Elsevier GmbH.)

Perovskite solar cells are strong competitors for silicon-based ones, but suffer from poor long-term stability, for which the intrinsic stability of perovskite materials is of primary concern. Herein, we prepared a series of well-defined cesium-containing mixed cation and mixed halide perovskite single-crystal alloys, which enabled systematic investigations on their structural stabilities against light, heat, water, and oxygen. Two potential phase separation processes are evidenced for the alloys as the cesium content increases to 10% and/or bromide to 15%. Eventually, a highly stable new composition, (FAPbI 3 ) 0.9 (MAPbBr 3 ) 0.05 (CsPbBr 3 ) 0.05 , emerges with a carrier lifetime of 16 μs. It remains stable during at least 10 000 h water-oxygen and 1000 h light stability tests, which is very promising for long-term stable devices with high efficiency. The mechanism for the enhanced stability is elucidated through detailed single-crystal structure analysis. Our work provides a single-crystal-based paradigm for stability investigation, leading to the discovery of stable new perovskite materials.

An innovative tungsten-based multifunctional nanoplatform composed of polyethylene glycol (PEG)-modified tungsten nitride nanoparticles (WN NPs) is constructed for tumor treatment. The PEG-WN NPs not only possess strong near-infrared (NIR) absorbance, high photothermal conversion efficiency, and excellent photothermal stability, but also effectively inhibit tumor cells upon 808 nm laser irradiation. After coating with thiolated (2-hydroxypropyl)-β-cyclodextrin (MUA-CD) on the surface, such a nanoplatform can also be used for drug delivery (such as DOX) and presents a synergistic tumor inhibition effect both in vitro and in vivo. Furthermore, the PEG-WN NPs present good contrasting capability for X-ray computed tomography (CT) and photoacoustic (PA) imaging. With PA/CT imaging, the tumor can be accurately positioned for precise treatment. It is worth mentioning that PEG-WN NPs are biodegradable and could be effectively excreted from the body with no appreciable toxicity in vivo. It is expected that this biocompatible multifunctional nanoplatform can serve as a potential candidate for tumor treatment in future clinical applications.

Many animal species present sex differences. Sex-associated genes (SAGs), which have female-biased or male-biased expression, have major influences on the remarkable sex differences in important traits such as growth, reproduction, disease resistance and behaviors. However, the SAGs resulting in the vast majority of phenotypic sex differences are still unknown. To provide a useful resource for the functional study of SAGs, we manually curated public RNA-seq datasets with paired female and male biological replicates from the same condition and systematically re-analyzed the datasets using standardized methods. We identified 27,793 female-biased SAGs and 64,043 male-biased SAGs from 2,828 samples of 21 species, including human, chimpanzee, macaque, mouse, rat, cow, horse, chicken, zebrafish, seven fly species and five worm species. All these data were cataloged into SAGD, a user-friendly database of SAGs (http://bioinfo.life.hust.edu.cn/SAGD) where users can browse SAGs by gene, species, drug and dataset. In SAGD, the expression, annotation, targeting drugs, homologs, ontology and related RNA-seq datasets of SAGs are provided to help researchers to explore their functions and potential applications in agriculture and human health.

The trends of and relationships among the plant community, soil nutrients, and four soil enzymes were investigated after being abandoned for 10, 15, 20, 30, and 45 years to reveal the soil properties during the restoration in the Loess Hilly Region. The results indicate the following ranking of dominant plant community species: Artemisia scoparia → Lespedeza dahurica + Artemisia sacrorum → Artemisia giraldii +irons Artemisia annua → Bothriochloa flaccidum + Artemisia selengensis . The ranking reflects an increase along the chronosequence of abandoned land. Moreover, the ratio of the total species of Compositae, Poaceae, and Leguminosae decreases from 66.67% to 50% and then increases up to 75%. The SOC, TN, TP, AN, AP, and four enzyme activity types (ALP, CAT, UE, and SC) increase but respond differently to restoration, while the stoichiometric ratio fluctuates. In contrast to the number of plant families, genus, species, and plant diversity, Compositae, Poaceae, and Leguminosae have major effects on the soil nutrient and enzyme activity, which explains the total variation of 72.8%, 69.1%, and 66.0%, respectively. The effects of these three families on the soil enzymes are greater than that on soil nutrients. Poaceae and Leguminosae have a positive effect on the nutrient and enzyme activity, while the family Compositae has a negative effect. Overall, the changes of dominant species of grassland communities during restoration significantly affect the soil enzyme and thereby are responsible for the soil nutrient dynamics.

Previous studies on the pathogenesis of myelodysplastic syndrome (MDS) have identified multiple associated gene mutations, including mutations of tetmethylcytosinedioxygenase 2, isocitrate dehydrogenase [NADP(+)] 1 cytosolic, isocitrate dehydrogenase [NADP(+)] 2 mitochondrial and additional sex combs like 1 transcriptional regulator, all of which may be considered epigenetic regulators. Furthermore, mutations of RAS type GTPase family genes have been identified in 10-15% patients with MDS. The authors' previous study on the gene expression profile of cluster of differentiation 34 + cells using microarray analysis identified elevated expression of RAP1GTPase activating protein 1 (Rap1GAP) in patients with MDS compared with that in non-malignant blood diseases (NM) control group. To further investigate the mechanism of increased Rap1GAP expression, the methylation pattern of the promoter of this gene was determined in 86 patients with MDS (n=29), acute myeloid leukemia (AML) (n=31) or NM (n=26) using bisulfite-specific polymerase chain reaction and DNA sequencing. The results demonstrated that the methylation of Rap1GAP occurred in all 29 patients with MDS at multiple CpG sites. The methylation level of Rap1GAP in patients with MDS was decreased compared with that in patients with NM. Significant differences at 4CpG sites (5,7,8 and 12) of Rap1GAP promoter were identified between MDS and NM. Furthermore, based on the present clinical records of the patient cohort, the methylation status of Rap1GAP promoter did not appear to be associated with the clinicopathological characteristics of patients with MDS, including age, gender and International Prognosis Score System. The difference in methylation level at CpG site 8 of Rap1GAP promoter was identified to be significantly increased in patients with MDS-refractory anemia with ring sideroblasts compared with that in the MDS-refractory cytopenia with multilineage dysplasia or MDS-unclassified groups. The results of the present study suggest that patients with MDS exhibit a lower overall methylation level within Rap1GAP promoter compared with patients with NM or AML. In addition, the methylation level at the four identified CpG sites can distinguish between MDS and NM.

Ephemeral gully erosion is an important erosion type in hilly and gully regions of Loess Plateau. While previous studies mainly focused on ephemeral gullies in agricultural land, little is known about the effects of naturally restored grassland on ephemeral gully erosion. In this study, taking the bare ephemeral gullies as the baseline, we conducted in-situ flushing tests to explore runoff and sediment yield characteristics and erosion mechanism of grassland ephemeral gullies under the runoff conditions of 5, 10, 15, 20 and 25 L·min -1 . Compared to the bare ephemeral gully, average flow velocity, stable runoff rate, Reynolds number and Froude number of grassland ephe-meral gullies was reduced by 25.4%-67.3%, 8.4%-26.6%, 54.9%-80.5%, 18.6%-65.1%, respectively, whereas resistance coefficient was increased by 0.09-7.18 folds. Compared to the bare ephemeral gully, the maximum sediment yield rate, stable sediment yield rate, average sediment yield rate of grassland ephemeral gullies was decreased by 55.1%-90.9%, 61.8%-95.4%, and 64.8%-92.4%, respectively. The sediment yield reduction benefit of the naturally restored grassland under the discharge flow rate of 5-25 L·min -1 could reach 65.9%-88.8%, which decreased with increasing discharge flow rate. Compared to the bare ephemeral gully, average stream power and average shear stress of grassland ephemeral gullies was reduced by 54.9%-80.5% and 12.4%-51.1%, respectively, whereas the critical stream power and critical shear stress was increased by 1.43 folds and 33.7%, respectively. The average sediment yield of grassland and bare ephemeral gullies was signifi-cantly linearly related to average stream power and shear stress. Naturally restored grassland significantly increased the erosion resistance and reduced runoff erosion potential of ephemeral gullies.

To achieve sufficient blood-brain barrier (BBB), penetration is one of the biggest challenges in the development of diagnostic and therapeutic for central nervous system (CNS) disorders. Here, we conducted a systematic review and meta-analysis to assess the preclinical evidence and possible mechanisms of borneol for improving co-administration of CNS drug delivery in animal models. The electronic literature search was conducted in six databases. Fifty-eight studies with 63 comparisons involved 1137 animals were included. Among 47 studies reporting the assessments of CNS drug concentration, 45 studies showed the significant effects of borneol for improving CNS drug delivery (p<.05), whereas 2 studies showed no difference (p>.05). Nineteen comparisons showed borneol up-regulated BBB permeability (p<.05) using brain EB content (n = 8), Rh 123 content (n = 4), brain imaging agent content (n = 2), brain water content (n = 1) and observing ultrastructure of BBB (n = 4), whereas three studies showed no difference or unclear results. Seven studies reported the safety, in which one study showed borneol was reversible changes in the BBB penetration; six studies showed borneol did not increase co-administration of blood drugs concentration of peripheral tissues (p > .05). Effects of borneol are closely associated with inhibition of efflux protein function, releasement of tight junction protein, increasement of vasodilatory neurotransmitters, and inhibition of active transport by ion channels. In conclusion, borneol is a promising candidate for CNS drug delivery, mainly through mediating a multi-targeted BBB permeability.

Regulation of prostate cancer by androgen and androgen receptor (AR), and blockade of AR signaling by AR antagonists and steroidogenic enzyme inhibitors have been extensively studied. G protein-coupled receptors (GPCRs) are a family of membrane receptors that regulate almost all physiological processes. Nearly 40% of FDA-approved drugs in the market target GPCRs. A variety of GPCRs that mediate reproductive function have been demonstrated to be involved in the regulation of prostate cancer. These GPCRs include gonadotropin-releasing hormone receptor, luteinizing hormone receptor, follicle-stimulating hormone receptor, relaxin receptor, ghrelin receptor, and kisspeptin receptor. We highlight here GPCR regulation of prostate cancer by these GPCRs. Further therapeutic approaches targeting these GPCRs for the treatment of prostate cancer are summarized., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Although studies have reported an increased risk for mood disorders in Hashimoto's thyroiditis (HT) patients even in the euthyroid state, the mechanisms involved remain unclear. Neuroinflammation may play a key role in the etiology of mood disorders in humans and behavioral disturbances in rodents. Therefore, this study established a euthyroid HT model in mice and investigated whether HT itself was capable of triggering neuroinflammation accompanied by emotional alterations., Methods: Experimental HT was induced by immunizing NOD mice with thyroglobulin and adjuvant twice. Four weeks after the last challenge, mice were tested for anxiety-like behavior in the open field and elevated plus maze tests and depression-like behavior in the forced swimming and tail suspension tests. Then, animals were sacrificed for thyroid-related parameter measure as well as detection of cellular and molecular events associated with neuroinflammation. The changes in components of central serotonin signaling were also investigated., Results: HT mice showed intrathyroidal monocyte infiltration and rising serum thyroid autoantibody levels accompanied by normal thyroid function, which defines euthyroid HT in humans. These mice displayed more anxiety- and depressive-like behaviors than controls. HT mice further showed microglia and astrocyte activation in the frontal cortex detected by immunohistochemistry, real-time RT-PCR, and transmission electron microscopy (TEM). These observations were also accompanied by enhanced gene expression of proinflammatory cytokines IL-1β and TNF-α in the frontal cortex. Despite this inflammatory response, no signs of neuronal apoptosis were visible by the TUNEL staining and TEM in the frontal cortex of HT mice. Additionally, IDO1 and SERT, key serotonin-system-related genes activated by proinflammatory cytokines, were upregulated in HT mice, accompanied by reduced frontal cortex serotonin levels., Conclusions: Our results are the first to suggest that HT induces neuroinflammation and alters related serotonin signaling in the euthyroid state, which may underlie the deleterious effects of HT itself on emotional function.

Background: The efficacy of intravenous acetaminophen in multimodal pain management in patients undergoing total knee arthroplasty (TKA) is controversial. The purpose of this meta-analysis was to compare the efficacy of intravenous acetaminophen versus placebo in TKA., Methods: Randomized controlled trials (RCTs) or retrospective cohort studies (RCSs) concerning related topics were retrieved from PubMed (1996-June 2018), Embase (1980-June 2018), and the Cochrane Library (CENTRAL June 2018). Any studies comparing intravenous acetaminophen with a placebo were included in this meta-analysis. Meta-analysis results were collected and analyzed by Stata 12.0. Subgroup analysis was performed according to the general characteristics of the patients., Results: In total, the patients from six studies met the inclusion criteria. Our meta-analysis results indicated that compared with a control group, intravenous acetaminophen was associated with reductions in total morphine consumption and visual analogue scale (VAS) score at postoperative day (POD) 3. However, there was no significant difference in morphine consumption at POD 1 or in VAS at POD 1 or POD 2. Moreover, there was no significant difference in the length of hospital stay., Conclusions: Based on our results, intravenous acetaminophen in multimodal management has shown better efficacy in pain relief at POD 3 and has morphine-sparing effects. High-quality studies with more patients are needed in the future.

The effect of attapulgite (magnesium aluminium phyllosilicate) and its modified materials on the extractability of soil Cd and the accumulation of Cd in lettuce ( Lactuca sativa ) were investigated using a pot-culture experiment, and the immobilization mechanism of attapulgite and its modified materials was explored through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The results showed that attapulgite and its modified materials could significantly reduce the Cd concentration in Lactuca sativa , with maximum reductions of 41.0% and 56.5%, respectively, and attapulgite modified materials treatments appeared more efficient than attapulgite treatments in reducing Cd uptake of Lactuca sativa . The saturated adsorption capacity for the adsorption of Cd 2+ on attapulgite rose distinctly after being modified. Attapulgite and its modified materials could significantly reduce Cd content in soil CaCl 2 extract at the dosage of 1%, with the maximum reduction rates of 34.2% and 34.3%, respectively. The attapulgite formed a complex to immobilize Cd mainly through the surface silanol and Cd 2+ complexation reaction, while the modified attapulgite formed a complex mainly through the complexation of Cd 2+ with carboxyl groups which existed in addition to the complexation with surface hydroxyl, thus reducing the mobility of Cd 2+ and achieving remediation of Cd-contaminated soil. In summary, attapulgite and its modified materials can both be used for remediation of Cd-contaminated soil, and the mechanisms for this function were found to be different.

Endometriosis is an estrogen-dependent disease associated with pain and infertility. The objective of this study was to determine the expression of ZEB1 in endometriosis and its role in 17β-estradiol (E2)-induced epithelial-mesenchymal transition (EMT). 25 patients with endometriosis and 16 endometriosis-free patients were recruited for the study. Tissue expression of EMT makers was investigated by immunohistochemistry, then the expression of ZEB1 was quantified by qRT-PCR, immunohistochemistry, and western blot. The proliferation, DNA replication, and migration and invasion in ZEB1 knockdown Ishikawa cells were further respectively performed by MTS, Edu, wound healing and transwell assays. Luciferase assay was used to measure the ZEB1 promoter activity. Our results show that protein levels of E-cadherin and Keratin 18 decreased in endometriotic tissues. Meanwhile the expressions of ZEB1, Vimentin, and N-cadherin were significantly increased in endometriotic tissues. Down-regulation of ZEB1 inhibited Ishikawa cells proliferation, migration, invasion and EMT. E2 promoted the expression of ZEB1 through the ER genomic pathway, which contributed to the EMT process. The -1401 bp - -1901 bp region in the ZEB1 promoter was the main target of the E2 activity. The present results suggest that a high expression of ZEB1 plays an important role in the pathogenesis of endometriosis, and it may serve as a potential therapeutic target for endometriosis., Competing Interests: None., (IJCEP Copyright © 2018.)

Objective: To investigate the gene prevalence and spectrum of thalassemia in the women of childbearing age in quanzhou area., Methods: Venous blood of the women were collected for study, all subjects were registered in each county of quanzhou area by using cluster sampling. Both the mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were used for screening thalassemia．Genotyping of the screened positive samples was performed by gap single polymerase chain reaction (gap-PCR) and reverse dot blot (RDB) hybridization．Unknown positive samples were analyzed with DNA sequencing., Results: Out of all 7 082 samples, Three hundred and eighty four were identified as thalassemia gene carriers with a carrying rate of 5.42 %. The α and β thalassemia were 3.21% and 2.15% respectively. -- SEA /αα was the most common genotype with 68.72 % in mutation types of α thalassemia, In addition gene, 2 cases of -- THAI /αα and 1 case of αα/ααα anti3.7 were also detected. IVS-Ⅱ-654/N and CD41-42/N were the most common gentypes with 75.00 % in mutation types of β thalassemia gene, 5 cases were found to be α β compogite thalassemia., Conclusion: The carrying rate of thalassemia gene in quanzhou area is higher, and with the most common gentypes including -- SEA /αα、IVSⅡ-654(C→T)/N and CD41-42(-TTCT)/N. The study results are beneficial for the screening of thalassemia in the genetic consultation and the prenatal gene diagnosis.