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IntroductionThe factors that determine the growth and spread advantages of an alien plant during the invasion process remain open to debate. The genetic diversity and differentiation of an invasive plant population might be closely related to its growth adaptation and spread in the introduced range. However, little is known about whether phenotypic and genetic variation in invasive plant populations covary during the invasion process along invaded geographic distances.MethodsIn a wild experiment, we examined the genetic variation in populations of the aggressively invasive species Erigeron annuus at different geographical distances from the first recorded point of introduction (FRPI) in China. We also measured growth traits in the wild and common garden experiments, and the coefficient of variation (CV) of populations in the common garden experiments.Results and discussionWe found that E. annuus populations had better growth performance (i.e., height and biomass) and genetic diversity, and less trait variation, in the long-term introduced region (east) than in the short-term introduced region (west). Furthermore, population growth performance was significantly positively or negatively correlated with genetic diversity or genetic variation. Our results indicate that there was parallel genetic and phenotypic differentiation along the invaded geographic distance in response to adaptation and spread, and populations that entered introduced regions earlier had consistently high genetic diversity and high growth dominance. Growth and reproduction traits can be used as reliable predictors of the adaptation and genetic variation of invasive plants.

Heavy metal (HM) contamination resulting from industrialization and urbanization during the Anthropocene along with plant invasion can severely threaten the growth and adaptation of local flora. Invasive alien plant species generally exhibit a growth pattern consistent with their functional traits in non-contaminated environments in the introduced range. However, it remains unclear whether invasive alien plants have an advantage over native plants in contaminated environments and whether this growth pattern is dependent on the adaptation of their leaf functional traits. Here, we selected two congeneric pairs of invasive alien and native grasses that naturally co-exist in China and are commonly found growing in contaminated soil. To evaluate the effect of cadmium (Cd) on the structural and physiological leaf traits, we grew all four species in soil contaminated without or with 80 mg/kg Cd. Invasive plants contained significantly higher concentrations of Cd in all three organs (leaf, stem, and root). They displayed a higher transfer factor and bioconcentration factor (BCF) of shoot and root than natives, indicating that invasive species are potential Cd hyperaccumulators. Invasive plants accumulated polyphenol oxidase (PPO) to higher levels than natives and showed similar patterns of leaf structural and physiological traits in response to changes in Cd bioconcentration. The quantifiable leaf structural traits of invasive plants were significantly greater (except for stomatal density and number of dead leaves) than native plants. Leaf physiological traits, chlorophyll content, and flavonoid content were also significantly higher in invasive plants than in natives under Cd stress conditions after 4 weeks, although nitrogen balance index (NBI) showed no significant difference between the two species. Chlorophyll fluorescence parameters decreased, except for the quantum yield of photosystem II (ΦPSII) and the proportion of open photosystem II (qP), which increased under Cd stress conditions in both species. However, invasive plants exhibited higher fluorescence parameters than natives under Cd stress, and the decrement observed in invasive plants under Cd stress was greater than that in natives. High Cd adaptation of invasive grasses over natives suggests that invasive plants possess optimal leaf structural and physiological traits, which enable them to adapt to stressful conditions and capture resources more quickly than natives. This study further emphasizes the potential invasion of alien plants in contaminated soil environments within the introduced range. To a certain extent, some non-invasive alien plants might adapt to metalliferous environments and serve as hyperaccumulator candidates in phytoremediation projects in contaminated environments.

Abstract AB209371 gene has been characterized as an oncogenic lncRNA in liver cancer. However, its involvement in ovarian carcinoma (OC) is unknown. In the present study, we analyzed the roles of AB209371 in OC. We found that AB209371 gene and Survivin gene were up-regulated in OC and positively correlated with OC development. AB209371 over-expression led to up-regulated Survivin in OC cells, while Survivin over-expression failed to affect AB209371. In addition, AB209371 over-expression led to down-regulated miR-203. However, miR-203 over-expression failed to affect AB209371, but down-regulated the expression of Survivin. In addition, over-expressions of AB209371 and Survivin resulted in the increased proliferation rate of OC cells. Over-expression MiR-203 played the opposite role and attenuated the effects of AB209371 over-expression. Therefore, AB209371 may down-regulate miR-203 to up-regulate Survivin, thereby promoting OC cell proliferation. Our study provided novel insights into the pathogenesis of OC.

Pancreatic cancer is a lethal malignancy with relatively few effective therapies. Recent investigations have highlighted the role of microRNAs (miRNAs) as crucial regulators in various tumor processes including tumor progression. Hence the current study aimed to investigate the role of bone marrow mesenchymal stem cell (BMSC)-derived exosomal microRNA-126-3p (miR-126-3p) in pancreatic cancer. Initially, miRNA candidates and related genes associated with pancreatic cancer were screened. PANC-1 cells were transfected with miR-126-3p or silenced a disintegrin and a metalloproteinase-9 (ADAM9) to examine their regulatory roles in pancreatic cancer cells. Additionally, exosomes derived from BMSCs were isolated and co-cultured with pancreatic cancer cells to elucidate the effects of exosomes in pancreatic cancer. Furthermore, the effects of overexpressed miR-126-3p derived from BMSCs exosomes on proliferation, migration, invasion, apoptosis, tumor growth, and metastasis of pancreatic cancer cells were analyzed in connection with lentiviral packaged miR-126-3p in vivo. Restored miR-126-3p was observed to suppress pancreatic cancer through downregulating ADAM9. Notably, overexpressed miR-126-3p derived from BMSCs exosomes inhibited the proliferation, invasion, and metastasis of pancreatic cancer cells, and promoted their apoptosis both in vitro and in vivo. Taken together, the key findings of the study indicated that overexpressed miR-126-3p derived from BMSCs exosomes inhibited the development of pancreatic cancer through the downregulation of ADAM9, highlighting the potential of miR-126-3p as a novel biomarker for pancreatic cancer treatment. Keywords: bone marrow mesenchymal stem cells, exosomes, microRNA-126-3p, a disintegrin and a metalloproteinase-9, pancreatic cancer, invasion, metastasis

Abstract Background Innate immune dysfunction contributes to the development and progression of nonalcoholic fatty liver disease (NAFLD), however, its pathogenesis is still incompletely understood. Identifying the key innate immune component responsible for the pathogenesis of NAFLD and clarifying the underlying mechanisms may provide therapeutic targets for NAFLD. Recently, F-box- and WD repeat domain-containing 7 (FBXW7) exhibits a regulatory role in hepatic glucose and lipid metabolism. This study aims to investigate whether FBXW7 controls high-mobility group box 1 protein (HMGB1)-mediated innate immune signaling to improve NAFLD and the mechanism underlying this action. Methods Mice were fed a high-fat diet (HFD) for 12 or 20 weeks to establish NAFLD model. Hepatic overexpression or knockdown of FBXW7 was induced by tail-vein injection of recombinant adenovirus. Some Ad-FBXW7-injected mice fed a HFD were injected intraperitoneally with recombinant mouse HMGB1 to confirm the protective role of FBXW7 in NAFLD via inhibition of HMGB1. Results FBXW7 improves NAFLD and related metabolic parameters without remarkable influence of body weight and food intake. Moreover, FBXW7 markedly ameliorated hepatic inflammation and insulin resistance in the HFD-fed mice. Furthermore, FBXW7 dramatically attenuated the expression and release of HMGB1 in the livers of HFD-fed mice, which is associated with inhibition of protein kinase R (PKR) signaling. Thereby, FBXW7 restrains Toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE) signaling in HFD-fed mouse livers. In addition, exogenous HMGB1 treatment abolished FBXW7-mediated inhibition of hepatic inflammation and insulin resistance in HFD-fed mouse livers. Conclusions Our results demonstrate a protective role of FBXW7 in NAFLD by abating HMGB1-mediated innate immune signaling to suppress inflammation and consequent insulin resistance, suggesting that FBXW7 is a potential target for therapeutic intervention in NAFLD development.

Abstract Background Liver cancer stem cells (LCSCs) are a small subset of cells characterized by unlimited self-renewal, cell differentiation, and uncontrollable cellular growth. LCSCs are also resistant to conventional therapies and are thus believed to be held responsible for causing treatment failure of hepatocellular carcinoma (HCC). It has been recently found that long non-coding RNAs (lncRNAs) are important regulators in HCC. This present study aims to explore the underlying mechanism of how lncRNA DLX6-AS1 influences the development of LCSCs and HCC. Methods A microarray-based analysis was performed to initially screen differentially expressed lncRNAs associated with HCC. We then analyzed the lncRNA DLX6-AS1 levels as well as CADM1 promoter methylation. The mRNA and protein expression of CADM1, STAT3, CD133, CD13, OCT-4, SOX2, and Nanog were then detected. We quantified our results by evaluating the spheroid formation, proliferation, and tumor formation abilities, as well as the proportion of tumor stem cells, and the recruitment of DNA methyltransferase (DNMT) in LCSCs when lncRNA DLX6-AS1 was either overexpressed or silenced. Results LncRNA DLX6-AS1 was upregulated in HCC. The silencing of lncRNA DLX6-AS1 was shown to reduce and inhibit spheroid formation, colony formation, proliferation, and tumor formation abilities, as well as attenuate CD133, CD13, OCT-4, SOX2, and Nanog expression in LCSCs. Furthermore, downregulation of lncRNA DLX6-AS1 contributed to a reduction in CADM1 promoter methylation via suppression of DNMT1, DNMT3a, and DNMT3b in LCSCs and inactivating the STAT3 signaling pathway. Conclusion This study demonstrated that down-regulated lncRNA DLX6-AS1 may inhibit the stem cell properties of LCSCs through upregulation of CADM1 by suppressing the methylation of the CADM1 promoter and inactivation of the STAT3 signaling pathway.

Climate change and human activities have continuously decreased productivity, carbon storage and soil fertility of global plantations under continuous planting. However, this situation can be largely reversed through appropriate planting density and thinning management. We evaluated the effects of initial planting density and selective thinning management on biomass accumulation and carbon stocks in different plantation compartments, on soil carbon stocks in different stand stages of a chronosequence of evergreen (Cunninghamia lanceolata) plantations in typical hilly and mountainous areas of Jiangxi Province, Southeast China.The result showed that biomass components and carbon storage of tree, understory and the whole ecosystem in C. lanceolata plantations were significantly higher with than without selective thinning treatment, in the low (1150 trees ha−1) than in the high (2460 trees ha−1) initial density in our study. Aboveground vegetation biomass and carbon storage in C. lanceolata plantations increased with stand stages. However, carbon storage of 0–10 cm and 20–40 cm soil depth decreased with stand stages, which indicated certain degraded characteristics of soil carbon in the C. lanceolata plantations. Interestingly, low initial density increased the biomass and carbon storage of trees, shrubs, herbs and 0–20 cm soil depth greater in the pre-mature and mature stands compared to high initial density. Furthermore, these positive effects of low density increased with selective thinning. According to regressions and Detrended Correspondence Analysis (DCA), increment in carbon of trees and 0–10 cm soil with the stand age were significantly higher in the low initial density and with selective thinning than in other three treatments.Therefore, selected thinning and relatively appropriate density might have a significantly positive role in carbon storage of the ecosystem in different stand ages, especially showing a increasing trend of soil carbon. Our results provide the important evidence for selective thinning management of C. lanceolata plantations with regeneration, which plays an important role in improving the carbon storage of degraded C. lanceolata plantations.

High speed development of the mining industry has lead to serious heavy metal pollution problems around mining areas in China, such as contaminating soil, and threatening the health of ecosystems and local residents. Plants long-term grown in mining areas largely show high adaptive capacity to the environment and facilitate the reclamation of degraded lands. In this study, we tested whether and how nitrogen form affect the adaptive capacity to soil contamination between legume (Robinia pseudoacacia) and nonlegume (Rhus chinensis) plants, typical phytoremediation species for soil environments polluted by heavy metals in China. All growth parameters and leaf catalase (CAT) and peroxidase (POD) of plant species were significantly greater in control than in contamination soil, in legume than in nonlegume, and in 50% NO3− (nitrate)+ 50% NH4+ (ammonium) and 100% NH4+ than in without and 100% NO3− treatments. The negative effect of soil contamination on all growth parameters was significantly stronger in nonlegume than in legume plant. Legume plant produced greater total mass, root mass and leaf mass in 50% NO3− + 50% NH4+ and 100% NH4+. Furthermore, the positive effect was not influenced by soil contamination. The greater physiological response to soil contamination in nonlegume plant and mixed addition of NO3− and NH4+ greatly relieved heavy metal stress on plants, especially in nonlegume plant. Mixed addition of NO3− and NH4+ greatly increased transfer factor for Pb and Zn and the positive effect significantly greater in nonlegume than in legume plant. Mixed addition of NO3− and NH4+ greatly increased the performance and adaptation of legume in contamination environment. To some extent, multiple N form addition in soil contamination environment may facilitate high plant adaption in phytoremediation, and using legume plants with mixed addition of NO3− and NH4+ is largely an important restoration mode for degraded mining areas.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-019-1239-3.

Background/Aims: Parkinson’s disease (PD) is a neurodegenerative movement disease with a high annual incidence. Accumulating evidence demonstrates that microRNAs play important roles in the pathogenesis of multiple neurological disorders, including PD. This study aims to investigate how microRNA-200a (miR-200a) regulates striatal dopamine receptor D2 (DRD2) to affect apoptosis of striatum in rats with PD and to explore the associated mechanism. Methods: After successfully establishing a PD model by 6-hydroxydopamine injections, PD rats were mainly treated with miR-200a mimics, inhibitors, Forskolin or a combination of miR-200a inhibitors and Forskolin. High-performance liquid chromatography-electrochemical detection (HPLC-ECD) was employed to detect the levels of dopamine, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and chemistry colorimetric methods were applied to detect the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). A TUNEL assay and immunocytochemical staining were performed to observe apoptosis and tyrosine hydroxylase (TH)-positive cells in the striatum. The expression of miR-200a, DRD2, Bad, Bax, Bcl-2, cAMP and PKA was determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays. Results: In the cellular experiments, after transfection with the inhibitor of miR-200a, decreased levels of Bax, GSH-Px, SOD, dopamine, DOPAC and HVA but increased levels of MDA and Bcl-2 were found along with a reduced apoptosis rate and increased TH-positive cell number. In addition, downregulating miR-200a resulted in lower expression of AKT, cAMP and PKA but higher expression of DRD2 and CREB, indicating that the downregulation of miR-200a increases DRD2 expression, which blocks the cAMP/PKA signaling pathway. Conclusion: This study provides evidence that the inhibition of miR-200a can repress apoptosis in the striatum via inhibition of the cAMP/PKA signaling pathway by upregulating DRD2 expression in PD rats.

Background/Aims: Spinal cord glioma is a highly aggressive malignancy that commonly results in high mortality due to metastasis, high recurrence and limited treatment regimens. This study aims to elucidate the effects of long non-coding RNA LINC01260 (LINC01260) on the proliferation, migration and invasion of spinal cord glioma cells by targeting Caspase recruitment domain family, member 11 (CARD11) via nuclear factor kappa B (NF-κB) signaling. Methods: The Multi Experiment Matrix (MEM) website was used for target gene prediction, and the DAVID database was used for analysis of the relationship between CARD11 and the NF-κB pathway. In total, 60 cases of glioma tissues and adjacent normal tissues were collected. Human U251 glioma cells were grouped into blank, negative control (NC), LINC01260 vector, CARD11 vector, siRNA-LINC01260, siRNA-CARD11, LINC01260 vector + CARD11 vector and LINC01260 + siRNA-CARD11 groups. A dual-luciferase reporter assay was conducted to verify the target relationship between LINC01260 and CARD11. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were employed to assess expression of LINC01260, E-cadherin, p53, CARD11, Ki67, N-cadherin, matrix metalloproteinase (MMP)-9, NF-κBp65 and NF-κBp50. MTT, flow cytometry, wound-healing and Transwell assays were performed to examine cell viability, the cell cycle, apoptosis, invasion and migration. Tumor growth was assessed through xenografts in nude mice. Results: CARD11 was confirmed to be a target gene of LINC01260 and was found to be involved in regulating the NF-κB pathway. Compared with adjacent normal tissues, glioma tissues showed reduced expression of LINC01260 and elevated expression of CARD11 and genes related to apoptosis, invasion and migration; activation of NF-κB signaling was also observed. In contrast to the blank and NC groups, an elevated number of cells arrested in G1 phase, increased apoptosis and reduced cell proliferation, invasion and number of cells arrested in S and G2 phases, as well as tumor growth were found for the LINC01260 vector and siRNA-CARD11 groups. Conclusions: Our findings demonstrate that overexpression of LINC01260 inhibits spinal cord glioma cell proliferation, migration and invasion by targeting CARD11 via NF-κB signaling suppression.

Background/Aims: MiRNAs are involved in phenotype modulation of neural cells after peripheral nerve injury. However, the roles of miRNAs on the survival of dorsal root ganglion (DRG) neurons have not yet been fully understood. Methods: In this study, the expression of miR-142-3p was measured in rat DRGs (L4-L6) during the initial 24 hours post sciatic nerve transection by microarray profiling and quantitative PCR. The functional assays including the cell viability, colony formation, cell cycle and apoptosis assays were performed in miR-142-3p mimic or inhibitor transfected cell lines. Results: MiR-142-3p was identified to be siginificantly upregulated in rat DRGs (L4-L6) during the initial 24 hours post sciatic nerve transection. MiR-142-3p mimic enhanced cell viability by promoting cell cycle and inhibiting cell apoptosis in cultured DRG neurons. In addition, cyclin-dependent kinase inhibitor 1B (CDKN1B, also known as p27/Kip1) and tissue inhibitor of metalloproteinase 3 (TIMP3) were identified as targets of miR-142-3p. Furthermore, knockdown of CDKN1B or TIMP3 by specific siRNAs could reverse the effect of miR-142-3p. Conclusions: In the conclusion, the results showed that miR-142-3p could promote neuronal cell cycle and inhibit apoptosis at least partially through suppressing CDKN1B and TIMP3 after peripheral nerve injury.

Abstract Background As a form of dementia primarily affecting the elderly, vascular dementia (VD) is characterized by changes in the supply of blood to the brain, resulting in cognitive impairment. The aim of the present study was to explore the effects involved with cyclic adenosine monophosphate (cAMP) response element-binding (CREB)1 gene silencing on cognitive dysfunction through meditation of the protein kinase A (PKA)-CREB signaling pathway in mice with VD. Methods Both the Morris water maze test and the step down test were applied to assess the cognitive function of the mice with VD. Immunohistochemical and TUNEL staining techniques were employed to evaluate the positive expression rates of the protein CREB1 and Cleaved Caspase-3, as well as neuronal apoptosis among hippocampal tissues in a respective manner. Flow cytometry was applied to determine the proliferation index and apoptosis rate of the hippocampal cells among each group. Reverse transcription quantitative polymerase chain reaction and Western blot analysis methods were applied to detect the expressions of cAMP, PKA and CREB in hippocampal cells. Results Compared with the normal group, all the other groups exhibited impaired cognitive function, reduced cell numbers in the CAI area, positive expressions of CREB1 as well as positive optical density (OD) values. Furthermore, increased Cleaved Caspase-3 positive expression, OD value, proliferation index, apoptosis rate of hippocampal cells and neurons, were observed in the other groups when compared with the normal group, as well as lower expressions of cAMP, PKA and CREB1 and p-CREB1 (the shCREB1–1, H89 and shCREB1–1 + H89 groups < the VD group). Conclusion The key findings of the present study demonstrated that CREB1 gene silencing results in aggravated VD that occurs as a result of inhibiting the PKA-CREB signaling pathway, thus exasperating cognitive dysfunction.

Background/Aims: Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease, and recent studies suggested that oxidative stress (OS) contributes to the cascade that leads to dopamine cell degeneration in PD. In this study, we hypothesized that salidroside (SDS) offers protection against OS injury in 6-hydroxydopamine (6-OHDA) unilaterally lesioned rats as well as the underlying mechanism. Methods: SDS and LiCl (activators of the Wnt/β-catenin signaling pathway) administration alone and in combination with 6-OHDA injection in rats was performed 3 days before modeling for 17 consecutive days to verify the regulatory mechanism by which SDS affects the Wnt/β-catenin signaling pathway as well as to evaluate the protective effect of SDS on PD in relation to OS in vivo. In addition, pheochromocytoma 12 (PC12) cells were incubated with 10 µmol/L SDS or LiCl alone or with both in combination for 1 h followed by a 24-h incubation with 100 µmol/L 6-OHDA to obtain in vitro data. Results: In vivo the administration of LiCl was found to ameliorate behavioral deficits and dopaminergic neuron loss; increase superoxide dismutase (SOA) activity, glutathione peroxidase (GSH-Px) levels, and glycogen synthase kinase 3β phosphorylation (GSK-3β-Ser9); reduce malondialdehyde (MDA) accumulation in the striatum and the GSK-3β mRNA level; as well as elevate β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-injected rats. This SDS treatment regimen was found to strengthen the beneficial effect of LiCl on 6-OHDA-injected rats. In vitro LiCl treatment decreased the toxicity of 6-OHDA on PC12 cells and prevented apoptosis. Additionally, LiCl treatment increased SOA activity, GSH-Px levels, and GSK-3β-Ser9 phosphorylation; decreased MDA accumulation in the striatum and GSK-3β mRNA levels; as well as increased β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-treated PC12 cells. Additionally, SDS treatment increased the protective effect of LiCl on 6-OHDA-treated PC12 cells. Conclusion: Evidence from experimental models suggested that SDS may confer neuroprotection against the neurotoxicity of 6-OHDA in response to OS injury and showed that these beneficial effects may be related to regulation of the Wnt/β-catenin signaling pathway. Therefore, SDS might be a potential therapeutic agent for treating PD.

Abstract Background To evaluate the risk factor associated with total or subtotal meniscectomy for respective medial and lateral meniscus injury. Methods The data of all the meniscus injured patients undergoing arthroscopy in our institute between January 15th, 2000 and December 31st, 2008 was collected and 6034 patients with 7241 injured menisci met the inclusion criteria. The mean patient age was 33.6 ± 14.9 years and there were 4785 males and 2456 females with 3568 medial and 3673 lateral menisci. The decision tree approach was applied to investigate the correlation of the tear type, the duration of complaint, age, gender, ACL rupture and total/subtotal meniscectomy for respective medial and lateral meniscus. Results The tear type was associated with both medial (χ2 = 70.901, P

Long non-coding RNAs (lncRNAs) are an emerging class of RNA species that may play a critical regulatory role in gene expression. However, the association between lncRNAs and atrial fibrillation (AF) is still not fully understood. In this study, we used RNA sequencing data to identify and quantify the both protein coding genes (PCGs) and lncRNAs. The high enrichment of these up-regulated genes in biological functions concerning response to virus and inflammatory response suggested that chronic viral infection may lead to activated inflammatory pathways, thereby alter the electrophysiology, structure, and autonomic remodeling of the atria. In contrast, the downregulated GO terms were related to the response to saccharides. To identify key lncRNAs involved in AF, we predicted lncRNAs regulating expression of the adjacent PCGs, and characterized biological function of the dysregulated lncRNAs. We found that two lncRNAs, ETF1P2, and AP001053.11, could interact with protein-coding genes (PCGs), which were implicated in AF. In conclusion, we identified key PCGs and lncRNAs, which may be implicated in AF, which not only improves our understanding of the roles of lncRNAs in AF, but also provides potentially functional lncRNAs for AF researchers.

The existing iOS platform is lacking ofsystematic assessment methods of privacy leak detection.To solve this problem,a multi-dimensional iOSprivacy disclosure evaluation model was presented.This model combined static analysis,dynamic analysis and network data analysis method to extract the features of the application’s pri-vacy disclosure behavior and evaluate it form multiple dimensions way.The model on 30 different types of apps from the iOS App Store and found out that more than 50% of all investigated apps aretracking users’ locations were evaluated,almost 40% of all send data to a server without the user’s consent.The model makes up for the limitations of single static analysis or dynamic analysis methods,solves the quantization problem of privacy disclosure effectively.

Purpose: Gastric cancer is mainly treated by gastrectomy, the results of which were unsatisfactory without any adjuvant treatments. This study aimed to examine the performance of radiotherapy, chemotherapy, and chemoradiotherapy after surgery in order to acquire the optimal adjuvant treatment.Method: Embase and PubMed were retrieved to conduct a systematic research. Hazard ratios (HR) of overall survival (OS) and progression-free survival (PFS) as outcomes were calculated by synthesizing direct and indirect evidence to evaluate the efficacy of three treatments against surgery alone. The P-score ranking was utilized to rank the therapies. Consistency was assessed by heat plot. Begg's test was performed to evaluate publication bias.Results: A total of 35 randomized controlled studies (RCTs) with 8973 patients were included in our network meta-analysis (NMA). As for efficacy outcomes, OS and PFS of 1, 2, 3, and 5 years, all revealed chemoradiotherapy (CRT) as the best of three adjuvant therapies. Meanwhile, P-score ranking results also displayed that CRT was the optimal regimen. Additionally, radiotherapy (RT) and chemotherapy (CT) were two alternative options following CRT since RT performed well in short-term survival while CT could improve the long-term survival.Conclusion: CRT was the most recommended therapy to accompany surgery according to our results. However, no analysis about the safety of these three treatments was mentioned in our study. Further studies including safety outcomes were required to draw a more comprehensive conclusion.

For the key leak problem in identity-based blind signature, a blind signature scheme based on the trusted plat-form control module (TPCM) was presented. The message which will be signed is unknown to the signer, and the infor-mation of the signature cannot be tracked. In the blind signature scheme, the secret share distribution center and the TPCM cooperate to generate the user's signature key, and the user's private key is not alone to be produced. So it solves the key escrow problem, and can also be effective to prevent disclosure of the user's key and protect the user's anonymity and the no track of the signature. Finally random oracle was used to prove the security of the scheme. Compared with the traditional scheme, the proposed scheme has better computational efficiency.

The multiple transmembrane protein Niemann-Pick C1 like1 (NPC1L1) is essential for intestinal cholesterol absorption. Ezetimibe binds to NPC1L1 and is a clinically used cholesterol absorption inhibitor. Recent studies in cultured cells have shown that NPC1L1 mediates cholesterol uptake through vesicular endocytosis that can be blocked by ezetimibe. However, how NPC1L1 and ezetimibe work in the small intestine is unknown. In this study, we found that NPC1L1 distributed in enterocytes of villi and transit-amplifying cells of crypts. Acyl-CoA cholesterol acyltransferase 2 (ACAT2), another important protein for cholesterol absorption by providing cholesteryl esters to chylomicrons, was mainly presented in the apical cytoplasm of enterocytes. NPC1L1 and ACAT2 were highly expressed in jejunum and ileum. ACAT1 presented in the Paneth cells of crypts and mesenchymal cells of villi. In the absence of cholesterol, NPC1L1 was localized on the brush border of enterocytes. Dietary cholesterol induced the internalization of NPC1L1 to the subapical layer beneath the brush border and became partially colocalized with the endosome marker Rab11. Ezetimibe blocked the internalization of NPC1L1 and cholesterol and caused their retention in the plasma membrane. This study demonstrates that NPC1L1 mediates cholesterol entering enterocytes through vesicular endocytosis and that ezetimibe blocks this step in vivo.

Ammonia oxidation dominated by ammoniaoxidizing bacteria (AOB) is the main driving factor in the earth's nitrogen cycle. It is of great practical significance to understand the community structure of AOB in different habitats and their response to environmental factors. In order to explore the diversity and influencing factors of AOB community in urban river environment which is greatly affected by human activities, the surface water and its corresponding sediment were collected from Fuyang River (Handan section). Perform physico-chemical properties analysis and molecular biology research on samples. The results showed that: (1) The eutrophication degree of Fuyang River gradually increased in the process of flowing through Handan, which affected the community structure of ammonia-oxidizing bacteria to a certain extent. (2) Proteobacteria is the main group of ammonia-oxidizing microorganisms in the sediment of urban rivers. (3) The effect of overlying water quality on the microbial community in the sediment is significant, and the surface and middle sediment environments are more suitable for the growth and reproduction of AOB than the bottom. (4) The impact of different environmental factors on the AOB communities in the sediments of different river sections varies significantly. [ABSTRACT FROM AUTHOR]