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Objective: This study aimed to investigate the outcomes of patients who had preimplantation genetic testing for chromosomal structural rearrangement (PGT-SR) or for aneuploidy screening (PGT-A) with different indications. Methods: This was a retrospective study at a single center. Pregnancy outcomes of all couples who had PGT from 2014 to 2018 were retrospectively analyzed, and the cumulative pregnancy rates (CPR) and the cumulative live birth/ongoing pregnancy rate (CLB/OPR) per patient with at least one transfer cycle were calculated. Results: A total of 313 PGT-SR cycles of 255 patients, 22 PGT-sexing cycles of 20 patients, and 190 PGT-A cycles of 168 patients were performed during the period. In PGT-SR, the overall CPR and the CLB/OPR were 68.04% and 59.79%, respectively. In PGT-A, the CPR and CLB/OPR were 67.52% and 58.12%, respectively. We also found that the CPR (93.75%) and CLB/OPR (87.50%) were highest in patients for PGT-sexing with a diagnosis of Y chromosomal microdeletion. In addition, we discovered a significant trend that aneuploidy rate significantly increased with maternal age (p = 0.000) in PGT-A population. No significant difference was found in the mosaicism rate or clinical outcomes among the age groups. Similarly, the significance was absent in the PGT-SR population. Conclusion: We reviewed the CPR and CLB/OPR for different indications since the 24-chromosome technique has been applied in the clinical setting for 4 years in our center. We hope that our results will provide some pointed guidance and a new perspective on outcomes for PGT in certain patients and clinicians.

Chinese cabbage (Brassica rapa L. ssp. pekinensis) is sensitive to high temperature, which will cause the B. rapa to remain in a semi-dormancy state. Foliar spray of GB prior to heat stress was proven to enhance B. rapa thermotolerance. In order to understand the molecular mechanisms of GB-primed resistance or adaptation towards heat stress, we investigated the transcriptomes of GB-primed and non-primed heat-sensitive B. rapa ‘Beijing No. 3’ variety by RNA-Seq analysis. A total of 582 differentially expressed genes (DEGs) were identified from GB-primed plants exposed to heat stress relative to non-primed plants under heat stress and were assigned to 350 gene ontology (GO) pathways and 69 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. The analysis of the KEGG enrichment pathways revealed that the most abundantly up-regulated pathways were protein processing in endoplasmic reticulum (14 genes), followed by plant hormone signal transduction (12 genes), ribosome (8 genes), MAPK signaling pathway (8 genes), homologous recombination (7 genes), nucleotide excision repair metabolism (5 genes), glutathione metabolism (4 genes), and ascorbate and aldarate metabolism (4 genes). The most abundantly down-regulated pathways were plant-pathogen interaction (14 genes), followed by phenylpropanoid biosynthesis (7 genes); arginine and proline metabolism (6 genes); cutin, suberine, and wax biosynthesis (4 genes); and tryptophan metabolism (4 genes). Several calcium sensing/transducing proteins, as well as transcription factors associated with abscisic acid (ABA), salicylic acid (SA), auxin, and cytokinin hormones were either up- or down-regulated in GB-primed B. rapa plants under heat stress. In particular, expression of the genes for antioxidant defense, heat shock response, and DNA damage repair systems were highly increased by GB priming. On the other hand, many of the genes involved in the calcium sensors and cell surface receptors involved in plant innate immunity and the biosynthesis of secondary metabolites were down-regulated in the absence of pathogen elicitors in GB-primed B. rapa seedlings. Overall GB priming activated ABA and SA signaling pathways but deactivated auxin and cytokinin signaling pathways while suppressing the innate immunity in B. rapa seedlings exposed to heat stress. The present study provides a preliminary understanding of the thermotolerance mechanisms in GB-primed plants and is of great importance in developing thermotolerant B. rapa cultivars by using the identified DEGs through genetic modification.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. Gemcitabine is the most commonly used chemotherapy for the treatment of PDAC, but the development of drug resistance still remains challenging. Recently, exosomes have emerged as important mediators for intercellular communication. Exosomes affect recipient cells’ behavior through the engulfed cargos, however the specific cargos responsible for gemcitabine resistance in PDAC are poorly understood. Here, we reported that exosomes could transfer gemcitabine resistance via a metalloproteinase 14 (MMP14)-dependent mechanism. MMP14 was identified as a major differentially secreted protein from the gemcitabine-resistant PDAC cells by comparative secretome. It was packaged into the exosomes and transmitted from the chemoresistant cells to the sensitive ones. The exosome-transferred MMP14 could enhance drug resistance and promotes the sphere-formation and migration abilities of the recipient sensitive PDAC cells. Mechanically, exosome-transferred MMP14 promotes the stability of CD44, the cancer stem cell marker in the recipient cells. Our results indicate that MMP14 is a key player for exosome-mediated transfer of gemcitabine resistance, thus targeting MMP14 in exosomes may represent a novel strategy to limit gemcitabine resistance in PDAC.

In the classification and typing of breast cancer, triple-negative breast cancer (TNBC) is one type of refractory breast cancer, while chemotherapy stays in the traditional treatment methods. However, the impact of chemotherapy is short-lived and may lead to recurrence due to incomplete killing of tumor cells. The occurrence, development, and relapse of breast cancer are relevant to T cell dysfunction, multiplied expression of related immune checkpoint molecules (ICIs) such as programmed death receptor 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) produce immunosuppressive effect. Immunotherapy (namely, immune checkpoint inhibitors, adoptive cellular immunotherapy, CAR-T immunotherapy and some potential treatments) provides new hope in TNBC. This review focuses on the new immune strategies of TNBC patients.

Ruyan Neixiao Cream (RUc) is a traditional Chinese herbal formula which can effectively inhibit the angiogenesis of breast precancerous lesions. In order to reveal the specific mechanism, we carried out experiments in vitro and in vivo. We found that the conditioned medium of MCF-10AT cells treated with RUc transdermal solution (RUt) could significantly inhibit the proliferation, migration, invasion, tube formation of HUVECs and the capillary formation of rat aortic rings. RUt may down-regulate the expression of VEGF, MMP2, and MMP9 in MCF-10AT medium by down-regulating miR-21 and up-regulating TIMP-3 and RECK. We further confirmed in rats that the microvascular density of precancerous lesions decreased significantly after external use of RUc, which may be related to the inhibition of Ras/Raf/MEK/ERK signaling pathway related proteins. Presumptively, RUc may inhibit the angiogenesis of breast precancerous lesions by inhibiting Ras/Raf/MEK/ERK signaling pathway, thus relieving the inhibition of miR-21 on TIMP-3 and RECK, then down-regulating the secretion of angiogenic factors.

It is usually difficult to capture strata caving and gob evolution characteristic in longwall mining at engineering scales. This paper uses bonded block modelling (BBM) approach within a distinct element method (DEM) code to simulate strata behaviour in longwall mining, which captures the caving phenomena and bulking characteristics of roof strata successfully. Many features in longwall mining, including the caving and compaction of gob strata and the associated stress evolution, are reproduced in the model. Four zones in longwall gob are identified based on its stress characteristics: voussoir influencing zone, compacted zone, compacting zone, and pilling zone. The initial bulking factor of the caved strata ranges from 1.12 to 1.25 and decreases gradually to the residual bulk factor of approximately 1.05 as the longwall face advances. The caved strata in the longwall gob present strain hardening behaviour and the load carrying capacity increases exponentially as a function of strain. Moreover, the range of the interaction between the caving strata and the overburden in gob was discussed, which provides a reference when using a continuum method to simulate longwall mining.

Objective: The objective of our study was to introduce community quarantine strategy against coronavirus disease 2019 (COVID-19) in Anhui and evaluate the effectiveness of community quarantine based on trauma center (TC) patients. Method: The structure of community quarantine strategy was illustrated. Distribution of injuries among patients in two TCs between January 24, 2020 and February 24, 2020 was described. Multiple linear regression was used to analyze the correlation between the distribution of Injuries in TCs and the number of COVID-19-associated cases. Results: A total of 757 TC patients in the two hospitals were enrolled. The number of traffic injuries and outdoor injuries showed a significant decrease in the early stage and began to increase on February 17. The number of indoor injuries neither decreased nor increased. Multiple linear regression analysis revealed a significant correlation between COVID-19-associated cases and traffic and outdoor injuries. Conclusion: From the perspective of the injuries in TCs, community quarantine strategy was effectively implemented and significantly slowed the outbreak of COVID-19 in Anhui. However, the implementation and maintenance of the strategy is costly and requires the participation of the entire population.

The molecular mechanisms that regulate intestinal Clu+ revival stem cells (revSCs) and their niche to enable regeneration in response to injury are unclear. Here, the authors show that mice without the phospholipid transport protein, TNFAIP8, causes less revSCs to be induced following injury.

Abstract Background Renal cell carcinoma (RCC) is one of the most common aggressive malignant tumors in urogenital system, and the clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinoma. Immune related long non-coding RNAs (IRlncRs) plentiful in immune cells and immune microenvironment (IME) are potential in evaluating prognosis and assessing the effects of immunotherapy. A completed and meaningful IRlncRs analysis based on abundant ccRCC gene samples from The Cancer Genome Atlas (TCGA) will provide insight in this field. Methods Based on the TCGA dataset, we integrated the expression profiles of IRlncRs and overall survival (OS) in the 611 ccRCC patients. The immune score of each sample was calculated based on the expression level of immune-related genes and used to identify the most meaningful IRlncRs. Survival-related IRlncRs (sIRlncRs) was estimated by calculating the algorithm of difference and COX regression analysis in ccRCC patients. Based on the median immune-related risk score (IRRS) developed from the screened sIRlncRs, the high-risk and low-risk components were distinguished. Functional annotation was detected by gene set enrichment analysis (GSEA) and principal component analysis (PCA), and the immune composition and purity of the tumor was evaluated by microenvironment cell population records. The expression levels of three sIRlncRs were verified in various tissues and cell lines. Results A total of 39 IRlncRs were collected by Pearson correlation analyses among immune score and the lncRNA expression. A total of 7 sIRlncRs were significantly associated with the clinical outcomes of ccRCC patients. Three sIRlncRs (ATP1A1-AS1, IL10RB-DT and MELTF-AS1) with the most significant prognostic values were enrolled to build the IRRS model in which the OS of in the high-risk group was shorter than that in the low-risk group. The IRRS was identified as an independent prognosis factor and correlated with the OS. The high-risk group and low-risk group illustrated different distributions in PCA and different immune status in GSEA. Besides, we found the more significant expression in certain ccRCC cell lines and tumor tissues of ccRCC patients compared with the HK-2 and adjacent tissues respectively. Additionally, the expression levels of lncR-MELTF-AS1 and IL10RB-DT were remarkably enhanced along the more advanced T-stages, but the lncR-ATP1A1-AS1 showed the inverse gradient. Conclusion Our results demonstrate some sIRlncRs with remark clinical relevance show the latent monitoring and prognosis values for ccRCC patients and may provide new insight in immunological researches and treatment strategies of ccRCC patients.

Low-calcium fly ash (LC-F) and high-calcium fly ash (HC-F) were used to synthesize corresponding zeolites (LC-Z and HC-Z), then for adsorption of Se(IV) in water. The results showed that c zeolites can effectively adsorb Se(IV). The optimal adsorption conditions were set at contact time = 360 min; pH = 2.0; the amount of adsorbent = 5.0 g·L−1; temperature = 25 °C; initial Se(IV) concentration = 10 mg·L−1. The removal efficiency of HC-Z was higher than the LC-Z after it had fully reacted because the specific surface area (SSA) of HC-Z was higher than LC-Z. The adsorption kinetics model of Se(IV) uptake by HC-Z followed the pseudo-second-order model. The Freundlich isotherm model agreed better with the equilibrium data for HC-Z and LC-Z. The maximum Se(IV) adsorption capacity was 4.16 mg/g for the HC-Z and 3.93 mg/g for the LC-Z. For the coexisting anions, barely affected Se(IV) removal, while significant affected it. Regenerated zeolites still had high capacity for Se(IV) removal. In conclusion, zeolites synthesized from fly ashes are a promising material for adsorbing Se(IV) from wastewater, and selenium-loaded zeolite has the potential to be used as a Se fertilizer to release selenium in Se-deficient areas.

Abstract Background MEIS2 has been identified as one of the key transcription factors in the gene regulatory network in the development and pathogenesis of human cancers. Our study aims to identify the regulatory mechanisms of MEIS2 in hepatocellular carcinoma (HCC), which could be targeted to develop new therapeutic strategies. Methods The variation of MEIS2 levels were assayed in a cohort of HCC patients. The proliferation, clone-formation, migration, and invasion abilities of HCC cells were measured to analyze the effects of MEIS2C and MEIS2D (MEIS2C/D) knockdown with small hairpin RNAs in vitro and in vivo. Chromatin immunoprecipitation (ChIP) was performed to identify MEIS2 binding site. Immunoprecipitation and immunofluorescence assays were employed to detect proteins regulated by MEIS2. Results The expression of MEIS2C/D was increased in the HCC specimens when compared with the adjacent noncancerous liver (ANL) tissues. Moreover, MEIS2C/D expression negatively correlated with the prognosis of HCC patients. On the other hand, knockdown of MEIS2C/D could inhibit proliferation and diminish migration and invasion of hepatoma cells in vitro and in vivo. Mechanistically, MESI2C activated Wnt/β-catenin pathway in cooperation with Parafibromin (CDC73), while MEIS2D suppressed Hippo pathway by promoting YAP nuclear translocation via miR-1307-3p/LATS1 axis. Notably, CDC73 could directly either interact with MEIS2C/β-catenin or MEIS2D/YAP complex, depending on its tyrosine-phosphorylation status. Conclusions Our studies indicate that MEISC/D promote HCC development via Wnt/β-catenin and Hippo/YAP signaling pathways, highlighting the complex molecular network of MEIS2C/D in HCC pathogenesis. These results suggest that MEISC/D may serve as a potential novel therapeutic target for HCC.

Despite that androgen-deprivation therapy results in long-lasting responses, the disease inevitably progresses to metastatic castration-resistant prostate cancer. In this study, we identified miR-33b-3p as a tumor suppressor in prostate cancer. miR-33b-3p was significantly reduced in prostate cancer tissues, and the low expression of miR-33b-3p was correlated with poor overall survival of prostate cancer patients. Overexpression of miR-33b-3p inhibited both migration and invasion of highly metastatic prostate cancer cells whereas inhibition of miR-33b-3p promoted those processes in lowly metastatic cells. The in vivo results demonstrate that miR-33b-3p suppresses metastasis of tail vein inoculated prostate cancer cells to lung and lymph nodes in mice. DOCK4 was validated as the direct target of miR-33b-3p. miR-33b-3p decreased the expression of DOCK4 and restoration of DOCK4 could rescue miR-33b-3p inhibition on cell migration and invasion. Moreover, downregulation of miR-33b-3p was induced by bortezomib, the clinically used proteasome inhibitor, and overexpression of miR-33b-3p enhanced the insufficient inhibition of bortezomib on migration and invasion as well as metastasis of prostate cancer cells. In summary, our findings demonstrate that miR-33b-3p suppresses metastasis by targeting DOCK4 in prostate cancer. Our results suggest that enhancing miR-33b-3p expression may provide a promising therapeutic strategy for overcoming that proteasome inhibitor’s poor efficacy against metastatic prostate cancer.

In this paper, a 5.8 GHz π-stub decoupling network is proposed to improve the performance of a receiving antenna array (RAA) in microwave wireless power transmission (MWPT) systems. A set of general design formulas was derived for determining the electric parameters of the required π-stubs. To validate the new technique, a π-stub decoupling network was combined with RAAs. The simulated and measured results show that the performance of the RAA is greatly improved by loading the π-stub decoupling network. In addition, a miniaturized MWPT system was built. System-level measurements indicate that the novel decoupling network enhances the receiving power of the RAA by up to 36.4%. An extended application also shows the scalability and effectiveness of the network, implying its huge potential in large-scale receiving arrays.

Sclerotinia stem rot caused by Sclerotinia sclerotiorum is one of the most destructive diseases in Brassica rapa. Verticillium dahliae Aspf2-like protein (VDAL) is a secretory protein of V. dahliae which has been shown to enhance the resistance against fungal infections in several plants. Nonetheless, the molecular mechanisms of VDAL-primed disease resistance are still poorly understood. In this study, we performed physiological, biochemical, and transcriptomic analyses of Brassica rapa in order to understand how VDAL confers resistance to S. sclerotiorumn infections in plants. The results showed that foliar application of VDAL significantly reduced the plaque area on leaves inoculated with S. sclerotiorum. It also enhanced antioxidant capacity by increasing activities of superoxide dismutase (SOD), peroxidase (POD), peroxidase (APX), glutathione reductase (GR), protoporphyrinogen oxidase (PPO), and defense-related enzymes β-1,3-glucanase and chitinase during the infection periods. This occurred in parallel with significantly reduced relative conductivity at different periods and lower malondialdehyde (MDA) content as compared to sole S. sclerotiorum inoculation. Transcriptomic analysis showed a total of 146 (81 up-regulated and 65 down-regulated) differentially expressed genes (DEGs) in VDAL-treated leaves compared to the control. The most enriched three Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were the mitogen–activated protein kinase (MAPK) signaling pathway, plant hormone signal transduction, and plant-pathogen interaction, all of which were associated with plant immunity. DEGs associated with MAPK and hormone signal transduction pathways were ethylene response sensor ERS2, EIN3 (Ethylene Insensitive3)-binding F-box protein 2 (EBF2), ethylene-responsive transcription factor ERF94, MAPK 9 (MKK9), protein phosphatase 2C (PP2C37), auxin-responsive proteins (AUX/IAA1 and 19), serine/threonine-protein kinase CTR1, and abscisic acid receptors (PLY 4 and 5). Among the DEGs linked with the plant–pathogen interaction pathway were calmodulin-like proteins (CML5, 24, 27), PTI1-like tyrosine protein kinase 3 (Pti13) and transcription factor MYB30, all of which are known to play key roles in pathogen-associated molecular pattern (PAMP)-triggered immunity and effector-triggered immunity (ETI) for hypersensitive response (HR), cell wall reinforcement, and stomatal closure in plants. Overall, VDLA treatment triggered repression of the auxin and ABA signaling pathways and de-repression of the ethylene signaling pathways in young B. rapa seedlings to increase plant innate immunity. Our results showed that VDAL holds great potential to enhance fungal disease resistance in B. rapa crop.

BackgroundRenal cell carcinoma (RCC) is one of the most common malignant tumors of the urinary system, of which the clear cell renal cell carcinoma (ccRCC) accounts for the most subtypes. The increasing discoveries of abundant autophagy-related long non-coding RNAs (ARLNRs) lead to a resurgent interest in evaluating their potential on prognosis prediction. Based on a large number of ccRCC gene samples from TCGA and clinics, ARLNRs analysis will provide a novel perspective into this field.MethodsWe calculated the autophagy scores of each sample according to the expression levels of autophagy-related genes (ARGs) and screened the survival-related ARLNRs (sARLNRs) of ccRCC patients by Cox regression analysis. The high-risk group and the low-risk group were distinguished by the median score of the autophagy-related risk score (ARRS) model. The functional annotations were detected by gene set enrichment analysis (GSEA) and principal component analysis (PCA). The expression levels of two kinds of sARLNRs in the renal tumor and adjacent normal tissues and cell lines were verified.ResultsThere were 146 ARLNRs selected by Pearson analysis. A total of 30 sARLNRs were remarkably correlated with the clinical outcomes of ccRCC patients. Eleven sARLNRs (AC002553.1, AC092611.2, AL360181.2, AP002807.1, AC098484.1, AL513218.1, AC008735.2, MHENCR, AC020907.4, AC011462.4, and AC008870.2) with the highest prognosis value were recruited to establish the ARRS in which the overall survival (OS) in the high-risk group was shorter than that in the low-risk group. ARRS could be treated as an independent prognostic factor and has significant correlations with OS. The distributions of autophagy genes were different between the high-risk group and the low-risk group. In addition, we also found that the expression levels of AC098484.1 in ccRCC cell lines and tumor tissues were lower than those in HK-2 and adjacent normal tissues, but AL513218.1 showed the inverse level. Furthermore, the AC098484.1 expressed decreasingly with the more advanced T-stages, but AL513218.1 gradually increased.ConclusionOur study identified and verified some sARLNRs with clinical significances and revealed their potential values on predicting prognoses of ccRCC patients, which may provide a novel perspective for autophagy-related research and clinical decisions.

Integrating the flow of supply and demand of ecosystem services (ESs) into the ecological security pattern (ESP) of coastal ecosystems with extremely fragile ecological backgrounds and contradictory human–land relationships is beneficial to the coordinated development of human–land systems. However, existing studies ignore the issue of scales of supply–demand linkages, making the ESP not properly guide sustainable development. Based on ESs delivery chain theory and landscape ecology approaches, we developed a sustainable development framework consisting of coupled microscopic natural–social systems. The method was tested using data from the Liao River Delta. In this study area, the natural supply potential and demand mapping distribution of key ESs were assessed to identify ecological sources in the Liao River Delta, a typical coastal zone in northern China. The resistance surface based on land use type assignment was modified using hydrological connectivity frequency and nighttime light intensity. Ecological corridors were extracted and optimized using a minimum cumulative resistance model and connectivity evaluation. The study found that the high supply area and the high demand reflection area are not consistent in location and supply level. Ecological source areas are evenly distributed, accounting for 12% of the total area. The ecological corridors are mainly concentrated in the west and southeast and do not cross the built-up areas in the east. This ESP framework safeguards the local demand for natural products and the natural potential to maintain services over the longer term and to a larger scale while informing the development of environmental management measures.

Myeloid-derived Suppressor Cells (MDSCs) are a sub-population of leukocytes that are important for carcinogenesis and cancer immunotherapy. During carcinogenesis or severe infections, inflammatory mediators induce MDSCs via aberrant differentiation of myeloid precursors. Although several transcription factors, including C/EBPβ, STAT3, c-Rel, STAT5, and IRF8, have been reported to regulate MDSC differentiation, none of them are specifically expressed in MDSCs. How these lineage-non-specific transcription factors specify MDSC differentiation in a lineage-specific manner is unclear. The recent discovery of the c-Rel−C/EBPβ enhanceosome in MDSCs may help explain these context-dependent roles. In this review, we examine several transcriptional regulators of MDSC differentiation, and discuss the concept of non-modular regulation of MDSC signature gene expression by transcription factors such as c-Rel and C/EBPß.

Interleukin (IL) 35 is a novel immunosuppressive heterodimeric cytokine in IL-12 family. Whether and how IL-35 regulates ischemia-induced angiogenesis in peripheral artery diseases are unrevealed. To fill this important knowledge gap, we used loss-of-function, gain-of-function, omics data analysis, RNA-Seq, in vivo and in vitro experiments, and we have made the following significant findings: i) IL-35 and its receptor subunit IL-12RB2, but not IL-6ST, are induced in the muscle after hindlimb ischemia (HLI); ii) HLI-induced angiogenesis is improved in Il12rb2−/− mice, in ApoE−/−/Il12rb2−/− mice compared to WT and ApoE−/− controls, respectively, where hyperlipidemia inhibits angiogenesis in vivo and in vitro; iii) IL-35 cytokine injection as a gain-of-function approach delays blood perfusion recovery at day 14 after HLI; iv) IL-35 spares regenerative angiogenesis at the late phase of HLI recovery after day 14 of HLI; v) Transcriptome analysis of endothelial cells (ECs) at 14 days post-HLI reveals a disturbed extracellular matrix re-organization in IL-35-injected mice; vi) IL-35 downregulates three reactive oxygen species (ROS) promoters and upregulates one ROS attenuator, which may functionally mediate IL-35 upregulation of anti-angiogenic extracellular matrix proteins in ECs; and vii) IL-35 inhibits human microvascular EC migration and tube formation in vitro mainly through upregulating anti-angiogenic extracellular matrix-remodeling proteins. These findings provide a novel insight on the future therapeutic potential of IL-35 in suppressing ischemia/inflammation-triggered inflammatory angiogenesis at early phase but sparing regenerative angiogenesis at late phase.

The gut microbiota plays an important role in a variety of physiological functions such as intestinal digestion, metabolic homeostasis, immune response, and responses to disease treatment. Whether there is a relationship between gut microbial communities and fatty acid (FA) profiles of Chinese mitten crab is unclear. Hence, we analyzed the relationship between FA profiles and the gut bacterial communities of six Chinese mitten crab (Eriocheir sinensis) populations from different lakes. The crabs were sampled from six different lakes in Jiangsu Province, China. The FA profiles of these crab populations were compared and clustered, and then used to determine the relationship between geographic location and FA composition. We also characterized the gut microbial communities of these crabs using 16S rRNA high-throughput gene sequencing. The FA profiles varied significantly (P < 0.05) between crabs from different geographical locations. A similar trend was also observed in the gut microbial communities, which also varied significantly based on their geographical origin (P < 0.05). Furthermore, alpha diversity, cluster analysis, and matching bacterial community structures with specific locations revealed patterns that significantly linked FA profiles to the gut microbiota. Further analysis of FA profiles and gut microbial community generated patterns that linked the two parameters. Hence, it was observed that the gut microbial community seems to contribute significantly to the FA composition of the Chinese mitten crab. However, further studies need to be conducted to investigate the interactions between gut microbial communities and the biochemical composition of the Chinese mitten crab, which will ultimately unravel the complexity of microbial ecosystems for potential applications in aquaculture and species conservation.

Summary: Activated macrophages must carefully calibrate their inflammatory responses to balance efficient pathogen control with inflammation-mediated tissue damage, but the molecular underpinnings of this “balancing act” remain unclear. Using genetically engineered mouse models and primary macrophage cultures, we show that Toll-like receptor (TLR) signaling induces the expression of the transcription factor Spic selectively in patrolling monocytes and tissue macrophages by a nuclear factor κB (NF-κB)-dependent mechanism. Functionally, Spic downregulates pro-inflammatory cytokines and promotes iron efflux by regulating ferroportin expression in activated macrophages. Notably, interferon-gamma blocks Spic expression in a STAT1-dependent manner. High levels of interferon-gamma are indicative of ongoing infection, and in its absence, activated macrophages appear to engage a “default” Spic-dependent anti-inflammatory pathway. We also provide evidence for the engagement of this pathway in sterile inflammation. Taken together, our findings uncover a pathway wherein counter-regulation of Spic by NF-κB and STATs attune inflammatory responses and iron metabolism in macrophages.

Truck flow plays a vital role in urban traffic congestion and has a significant influence on cities. In this study, we develop a novel model for solving regional logistics network (RLN) design problems considering the traffic status of the background transportation network. The models determine not only the facility location, initial distribution planning, roadway construction, and expansion decisions but also offer an optimal solution to the logistics network service level and truck-type selections. We first analyze the relationship between the urban transportation network and the RLN design problem using real truck data and traffic flow status in a typical city. Then, we develop the uncover degree function (UDF), which reflects the service degree of the RLN and formulates based on an impedance function. Subsequently, the integrated logistics network design models are proposed. We model the RLN design problem as a minimal cost problem and design double-layer Lagrangian relaxation heuristics algorithms to solve the model problems. Through experiments with data from the six-node problem and Sioux-Falls network, the effectiveness of the models and algorithms is verified. This study contributes to the planning of regional logistics networks while mitigating traffic congestion caused by truck flow.

In coal underground mining, situation of longwall face striding across (SAR) or passing through roadway (PTR) is very common, especially in an inclined coal seam mining. A roadway supporting design method, consisting of a model using to determine the minimal rock strata thickness and a segmental supporting scheme, is developed. In addition, to represent the mechanical behaviour of the caved material authentically, an elastic model was developed. The results showed that the elastic model has a good agreement with the caved material mechanical behaviours at a relatively lower stress condition. By using a FDEM method, a real case in Xutuan coal mine is studied. Compared with the process without backfill, the z-displacement of cross-cut roof decreased shapely after backfilling, with a maximum z-displacement, decreases from 0.76 m to 0.13 m and from 0.39 m to 0.064 m in PTR and SAR section, respectively. Therefore, the possibility of fall of ground (FOG) and crushing accidents can be reduced effectively with backfilling material of wood cribs. And the maximum subsidence (SAR section side) of face floor is 0.16 m, which is small enough to ensure normal production. The results of this study are likely to be useful as a reference for the safe and efficient mining of coal resources under similar conditions.

Gemcitabine (GEM)-based chemotherapy is the standard regimen for the treatment of pancreatic cancer (PC). However, chemoresistance is a major challenge in PC treatment. Reliable biomarkers are urgently needed to predict the response to GEM-based therapies. GEM-sensitive (GEM-S) and GEM-resistant (GEM-R) pancreatic carcinoma xenograft models were established, and GEM monotherapy and GEM plus nanoparticle albumin-bound paclitaxel (nab-PTX) doublet therapy were administered to GEM-S/R tumor-bearing mice. Metabolomic mass spectrometry (MS) analysis of serum, liver, and tumor samples was performed using an ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometer. The results showed that both GEM monotherapy and combination therapy significantly inhibited the tumor growth in GEM-S subgroup. However, in the GEM-R subgroup, tumor growth was not significantly inhibited by GEM monotherapy, but was significantly suppressed by GEM combination therapy. Metabolic profiling analysis by hierarchical cluster analysis and partial least squares discriminant analysis showed that the differences in metabolites were most significant in serum of three types of samples in the GEM-S/R subgroups, regardless of the administration of GEM monotherapy or combination therapy. The differential metabolite analysis of serum samples revealed 38 and 26 differential metabolites between the GEM-R and GEM-S subgroups treated with GEM monotherapy or combination therapy, and four common discriminating metabolites were investigated: 3-hydroxyadipic acid, d-galactose, lysophosphatidylcholine (LysoPC) (P-16:0), and tetradecenoyl-l-carnitine. The relative amounts of the four metabolites changed significantly and consistently after GEM monotherapy or combination therapy. The levels of these four metabolites were significantly different in the GEM-S and GEM-R pancreatic carcinoma xenograft models; thus, these metabolites could be effective predictive indicators of the efficacy of chemotherapy in PC patients, regardless of the administration of GEM alone or GEM plus nab-PTX.

It has been shown that anti-inflammatory cytokines interleukin-35 (IL-35) and IL-10 could inhibit acute endothelial cell (EC) activation, however, it remains unknown if and by what pathways IL-35 and IL-10 could block atherogenic lipid lysophosphatidylcholine (LPC)-induced sustained EC activation; and if mitochondrial reactive oxygen species (mtROS) can differentiate mediation of EC activation from trained immunity (innate immune memory). Using RNA sequencing analyses, biochemical assays, as well as database mining approaches, we compared the effects of IL-35 and IL-10 in LPC-treated human aortic ECs (HAECs). Principal component analysis revealed that both IL-35 and IL-10 could similarly and partially reverse global transcriptome changes induced by LPC. Gene set enrichment analyses showed that while IL-35 and IL-10 could both block acute EC activation, characterized by upregulation of cytokines/chemokines and adhesion molecules, IL-35 is more potent than IL-10 in suppressing innate immune signatures upregulated by LPC. Surprisingly, LPC did not induce the expression of trained tolerance itaconate pathway enzymes but induced trained immunity enzyme expressions; and neither IL-35 nor IL-10 was found to affect LPC-induced trained immunity gene signatures. Mechanistically, IL-35 and IL-10 could suppress mtROS, which partially mediate LPC-induced EC activation and innate immune response. Therefore, anti-inflammatory cytokines could reverse mtROS-mediated acute and innate immune trans-differentiation responses in HAECs, but it could spare metabolic reprogramming and trained immunity signatures, which may not fully depend on mtROS. Our characterizations of anti-inflammatory cytokines in blocking mtROS-mediated acute and prolonged EC activation, and sparing trained immunity are significant for designing novel strategies for treating cardiovascular diseases, other inflammatory diseases, and cancers. Keywords: Interleukin-35, Interleukin-10, Endothelial cell activation, Mitochondrial ROS, Trained immunity, Atherosclerosis

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease (CVD) which has been implicated in matochondrial (Mt) function impairment. In this study, we characterized Hcy metabolism in mouse tissues by using LC-ESI-MS/MS analysis, established tissue expression profiles for 84 nuclear-encoded Mt electron transport chain complex (nMt-ETC-Com) genes in 20 human and 19 mouse tissues by database mining, and modeled the effect of HHcy on Mt-ETC function. Hcy levels were high in mouse kidney/lung/spleen/liver (24–14 nmol/g tissue) but low in brain/heart (~5 nmol/g). S-adenosylhomocysteine (SAH) levels were high in the liver/kidney (59–33 nmol/g), moderate in lung/heart/brain (7–4 nmol/g) and low in spleen (1 nmol/g). S-adenosylmethionine (SAM) was comparable in all tissues (42–18 nmol/g). SAM/SAH ratio was as high as 25.6 in the spleen but much lower in the heart/lung/brain/kidney/liver (7–0.6). The nMt-ETC-Com genes were highly expressed in muscle/pituitary gland/heart/BM in humans and in lymph node/heart/pancreas/brain in mice. We identified 15 Hcy-suppressive nMt-ETC-Com genes whose mRNA levels were negatively correlated with tissue Hcy levels, including 11 complex-I, one complex-IV and two complex-V genes. Among the 11 Hcy-suppressive complex-I genes, 4 are complex-I core subunits. Based on the pattern of tissue expression of these genes, we classified tissues into three tiers (high/mid/low-Hcy responsive), and defined heart/eye/pancreas/brain/kidney/liver/testis/embryonic tissues as tier 1 (high-Hcy responsive) tissues in both human and mice. Furthermore, through extensive literature mining, we found that most of the Hcy-suppressive nMt-ETC-Com genes were suppressed in HHcy conditions and related with Mt complex assembly/activity impairment in human disease and experimental models. We hypothesize that HHcy inhibits Mt complex I gene expression leading to Mt dysfunction. Keywords: Database mining, Tissue expression profile, Homocysteine metabolism

Abstract Immune cells were traditionally considered as major pro-inflammatory contributors. Recent advances in molecular immunology prove that immune cell lineages are composed of different subsets capable of a vast array of specialized functions. These immune cell subsets share distinct duties in regulating innate and adaptive immune functions and contribute to both immune activation and immune suppression responses in peripheral tissue. Here, we summarized current understanding of the different subsets of major immune cells, including T cells, B cells, dendritic cells, monocytes, and macrophages. We highlighted molecular characterization, frequency, and tissue distribution of these immune cell subsets in human and mice. In addition, we described specific cytokine production, molecular signaling, biological functions, and tissue population changes of these immune cell subsets in both cardiovascular diseases and cancers. Finally, we presented a working model of the differentiation of inflammatory mononuclear cells, their interaction with endothelial cells, and their contribution to tissue inflammation. In summary, this review offers an updated and comprehensive guideline for immune cell development and subset differentiation, including subset characterization, signaling, modulation, and disease associations. We propose that immune cell subset differentiation and its complex interaction within the internal biological milieu compose a “pathophysiological network,” an interactive cross-talking complex, which plays a critical role in the development of inflammatory diseases and cancers.

A high content of asphaltene and wax in crude oil leads to difficulties in the recovery and transportation of crude oil due to the precipitation of asphaltenes and the deposition of waxes. Comb-like polymers were found to be capable of inhibiting the aggregation of asphaltenes and crystallization of waxes. In this work, comb-like bipolymers of α-olefins/ultra-long chain (C18, C22 and C28) alkyl acrylate were synthesized and characterized by FT-IR and 1H NMR spectra. The results show that, for a model oil containing asphaltene, the initial precipitation point (IPP) of asphaltene was prolonged by UV, and the asphaltene particle size was reduced after adding the biopolymers, as revealed by dynamitic light scattering (DLS). The bipolymer containing the longer alkyl chain had a better asphaltene inhibition effect. However, DSC and rheological results show that the wax appearance temperature (WAT) of the typical high asphaltene and high wax content of crude oil was obviously reduced by adding bipolymers with shorter alkyl chains. The bipolymer (TDA2024-22) with a mediate alkyl chain (C22) reduced the viscosity and thixotropy of the crude oil by a much larger margin than others. Compared with the previously synthesized bipolymer with phenyl pendant (PDV-A-18), TDA2024-22 exhibited a better performance. Therefore, bipolymers with appropriate alkyl side chains can act as not only the asphaltene inhibitors but also wax inhibitors for high asphaltene and wax content of crude oil, which has great potential applications in the oil fields.

Deep learning techniques such as convolutional neural networks have largely improved the performance of building segmentation from remote sensing images. However, the images for building segmentation are often in the form of traditional orthophotos, where the relief displacement would cause non-negligible misalignment between the roof outline and the footprint of a building; such misalignment poses considerable challenges for extracting accurate building footprints, especially for high-rise buildings. Aiming at alleviating this problem, a new workflow is proposed for generating rectified building footprints from traditional orthophotos. We first use the facade labels, which are prepared efficiently at low cost, along with the roof labels to train a semantic segmentation network. Then, the well-trained network, which employs the state-of-the-art version of EfficientNet as backbone, extracts the roof segments and the facade segments of buildings from the input image. Finally, after clustering the classified pixels into instance-level building objects and tracing out the roof outlines, an energy function is proposed to drive the roof outline to maximally align with the building footprint; thus, the rectified footprints can be generated. The experiments on the aerial orthophotos covering a high-density residential area in Shanghai demonstrate that the proposed workflow can generate obviously more accurate building footprints than the baseline methods, especially for high-rise buildings.

Abstract Background It is well established that caspase-1 exerts its biological activities through its downstream targets such as IL-1β, IL-18, and Sirt-1. The microarray datasets derived from various caspase-1 knockout tissues indicated that caspase-1 can significantly impact the transcriptome. However, it is not known whether all the effects exerted by caspase-1 on transcriptome are mediated only by its well-known substrates. Therefore, we hypothesized that the effects of caspase-1 on transcriptome may be partially independent from IL-1β, IL-18, and Sirt-1. Methods To determine new global and tissue-specific gene regulatory effects of caspase-1, we took novel microarray data analysis approaches including Venn analysis, cooperation analysis, and meta-analysis methods. We used these statistical methods to integrate different microarray datasets conducted on different caspase-1 knockout tissues and datasets where caspase-1 downstream targets were manipulated. Results We made the following important findings: (1) Caspase-1 exerts its regulatory effects on the majority of genes in a tissue-specific manner; (2) Caspase-1 regulatory genes partially cooperates with genes regulated by sirtuin-1 during organ injury and inflammation in adipose tissue but not in the liver; (3) Caspase-1 cooperates with IL-1β in regulating less than half of the genes involved in cardiovascular disease, organismal injury, and cancer in mouse liver; (4) The meta-analysis identifies 40 caspase-1 globally regulated genes across tissues, suggesting that caspase-1 globally regulates many novel pathways; and (5) The meta-analysis identified new cooperatively and non-cooperatively regulated genes in caspase-1, IL-1β, IL-18, and Sirt-1 pathways. Conclusions Our findings suggest that caspase-1 regulates many new signaling pathways potentially via its known substrates and also via transcription factors and other proteins that are yet to be identified.

To test our hypothesis that proatherogenic lysophosphatidylcholine (LPC) upregulates trained immunity pathways (TIPs) in human aortic endothelial cells (HAECs), we conducted an intensive analyses on our RNA-Seq data and histone 3 lysine 14 acetylation (H3K14ac)-CHIP-Seq data, both performed on HAEC treated with LPC. Our analysis revealed that: 1) LPC induces upregulation of three TIPs including glycolysis enzymes (GE), mevalonate enzymes (ME), and acetyl-CoA generating enzymes (ACE); 2) LPC induces upregulation of 29% of 31 histone acetyltransferases, three of which acetylate H3K14; 3) LPC induces H3K14 acetylation (H3K14ac) in the genomic DNA that encodes LPC-induced TIP genes (79%) in comparison to that of in LPC-induced effector genes (43%) including ICAM-1; 4) TIP pathways are significantly different from that of EC activation effectors including adhesion molecule ICAM-1; 5) reactive oxygen species generating enzyme NOX2 deficiency decreases, but antioxidant transcription factor Nrf2 deficiency increases, the expressions of a few TIP genes and EC activation effector genes; and 6) LPC induced TIP genes(81%) favor inter-chromosomal long-range interactions (CLRI, trans-chromatin interaction) while LPC induced effector genes (65%) favor intra-chromosomal CLRIs (cis-chromatin interaction). Our findings demonstrated that proatherogenic lipids upregulate TIPs in HAECs, which are a new category of qualification markers for chronic disease risk factors and conditional DAMPs and potential mechanisms for acute inflammation transition to chronic ones. These novel insights may lead to identifications of new cardiovascular risk factors in upregulating TIPs in cardiovascular cells and novel therapeutic targets for the treatment of metabolic cardiovascular diseases, inflammation, and cancers. (total words: 245). Keywords: Trained immunity, Human aortic endothelial cell activation, Proatherogenic lipids lysophosphatidycholine (LPC), RNA-Seq, Chromatin long range interaction

Circular RNAs (circRNAs) are non-coding RNAs that form covalently closed continuous loops, and act as gene regulators in physiological and disease conditions. To test our hypothesis that proatherogenic lipid lysophosphatidylcholine (LPC) induce a set of circRNAs in human aortic endothelial cell (HAEC) activation, we performed circRNA analysis by searching our RNA-Seq data from LPC-activated HAECs, and found: (1) LPC induces significant modulation of 77 newly characterized cirRNAs, among which 47 circRNAs (61%) are upregulated; (2) 34 (72%) out of 47 upregulated circRNAs are upregulated when the corresponding mRNAs are downregulated, suggesting that the majority of circRNAs are upregulated presumably via LPC-induced “abnormal splicing” when the canonical splicing for generation of corresponding mRNAs is suppressed; (3) Upregulation of 47 circRNAs is temporally associated with mRNAs-mediated LPC-upregulated cholesterol synthesis-SREBP2 pathway and LPC-downregulated TGF-β pathway; (4) Increase in upstream chromatin long-range interaction sites to circRNA related genes is associated with preferred circRNA generation over canonical splicing for mRNAs, suggesting that shifting chromatin long-range interaction sites from downstream to upstream may promote induction of a list of circRNAs in lysoPC-activated HAECs; (5) Six significantly changed circRNAs may have sponge functions for miRNAs; and (6) 74% significantly changed circRNAs contain open reading frames, suggesting that putative short proteins may interfere with the protein interaction-based signaling. Our findings have demonstrated for the first time that a new set of LPC-induced circRNAs may contribute to homeostasis in LPC-induced HAEC activation. These novel insights may lead to identifications of new therapeutic targets for treating metabolic cardiovascular diseases, inflammations, and cancers.

Common carp is one of the oldest and most popular cultured freshwater fish species both globally and in China. In a previous study, we used a carp strain with a long breeding tradition in China, named Huanghe, to create a new fast-growing strain by selection for fast growth for 6 years. The growth performance at 8 months of age has been improved by 20.84%. To achieve this, we combined the best linear unbiased prediction with marker-assisted selection techniques. Recent progress in genome-wide association studies and genomic selection in livestock breeding inspired common carp breeders to consider genome-based breeding approaches. In this study, we developed a 2b-RAD sequence assay as a means of investigating the quantitative trait loci in common carp. A total of 4,953,017,786 clean reads were generated for 250 specimens (average reads/specimen = 19,812,071) with BsaXI Restriction Enzyme. From these, 56,663 SNPs were identified, covering 50 chromosomes and 3,377 scaffolds. Principal component analysis indicated that selection and control groups are relatively clearly distinct. Top 1% of Fst values was selected as the threshold signature of artificial selection. Among the 244 identified loci, genes associated with sex-related factors and nutritional metabolism (especially fat metabolism) were annotated. Eighteen QTL were associated with growth parameters. Body length at 3 months of age and body weight (both at 3 and 8 months) were controlled by polygenic effects, but body size (length, depth, width) at 8 months of age was controlled mainly by several loci with major effects. Importantly, a single shared QTL (IGF2 gene) partially controlled the body length, depth, and width. By merging the above results, we concluded that mainly the genes related to neural pathways, sex and fatty acid metabolism contributed to the improved growth performance of the new Huanghe carp strain. These findings are one of the first investigations into the potential use of genomic selection in the breeding of common carp. Moreover, our results show that combining the Fst, QTL mapping and CRISPR–Cas9 methods can be an effective way to identify important novel candidate molecular markers in economic breeding programs.

In this investigation, an easily-operated and cost-effective method is utilized to synthesize biochar in ambient air, and the prepared biochar is used in a novel manner as a milling aid for fabricating Mg-biochar composites for hydrogen storage. X-ray diffractometry reveals that increasing the content of palm kernel shell biochar (PKSBC) from 5 wt.% to 20 wt.% enhances the hydrogen absorption performance by increasing the conversion of Mg into MgH2 from 83% to 93%. A 40 °C reduction in decomposition temperature of MgH2 is recorded from differential scanning calorimetry curves when the content of PKSBC is increased to 20 wt.%. Magnesium is milled and hydrided under the same experimental conditions and used as a reference material. It is proposed that these property enhancements can be attributed to the fact that PKSBC acts as an anti-sticking agent for elemental Mg powders, helping in the achievement of a more dispersed composite with reduced Mg particle size due to its layered-like carbon structure.

To investigate the efficacy and tolerability of duloxetine during short-term treatment in adults with generalized anxiety disorder (GAD).We conducted a comprehensive literature review of the PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials databases for randomized controlled trials(RCTs) comparing duloxetine or duloxetine plus other antipsychotics with placebo for the treatment of GAD in adults. Outcome measures were (1) efficacy, assessed by the Hospital Anxiety and Depression Scale(HADS) anxiety subscale score, the Hamilton Rating Scale for Anxiety(HAM-A) psychic and somatic anxiety factor scores, and response and remission rates based on total scores of HAM-A; (2) tolerability, assessed by discontinuation rate due to adverse events, the incidence of treatment emergent adverse events(TEAEs) and serious adverse events(SAEs). Review Manager 5.3 and Stata Version 12.0 software were used for all statistical analyses.The meta-analysis included 8 RCTs. Mean changes in the HADS anxiety subscale score [mean difference(MD) = 2.32, 95% confidence interval(CI) 1.77-2.88, P

We have created a new, fast-growing strain of common carp with higher unsaturated fatty acid content in muscle. To better understand the impacts of gene regulation in intestinal tissue on growth and unsaturated fatty acid content, we conducted a comparative RNA-Seq transcriptome analysis between intestine samples of Selected and Control groups (and corroborated selected results by PCR). After eight weeks of cage culture, weight gain of the Selected group was 20.84% higher. In muscles of the control group, monounsaturated fatty acids (FAs) were more abundant, whereas polyunsaturated FAs were more abundant in muscles of the Selected group. In total, we found 106 differentially expressed genes (DEGs) between the two groups. Only the endocytosis pathway was significantly enriched in DEGs, with two upregulated genes: il2rb and ehd1. The latter is involved in the growth hormone/insulin-like growth factor (Gh/Igf) axis, which plays a key role in the regulation of growth in animals. tll2, which is known to be associated with intestinal regeneration, was extremely highly upregulated in both transcriptomic (infinite) and qPCR (610.70) analyses. Two of the upregulated genes are associated with the fatty acid metabolism, several genes are likely to be indicators of heightened transcription levels, several are associated with metabolic and developmental roles, several with neuronal functions (including two with vision), several with the immune system, and two downregulated genes with the development of vasculature. The higher growth rate of the Selected group is likely to be at least partially attributed to increased endocytosis efficiency and genetically-driven behavioural differences (higher aggression levels). There are some indications that this new strain might have slightly impaired immune responses, and a higher propensity for inherited diseases leading to sight impairment, as well for neurodegenerative diseases in general, but these indications still need to be confirmed.

BACKGROUND:Previous results regarding the prevalence of Factor V Leiden (FVL) in patients with cerebral venous thrombosis (CVT) varied remarkably. Therefore, we performed a meta-analysis to evaluate the potential association between FVL and CVT. METHODS:The PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched for relevant case-control studies. The data were pooled for analysis of the association between FVL and CVT with a random-effects model. Subgroup and sensitivity analyses were performed to evaluate the robustness of the results. Publication bias was assessed by funnel plot and the Egger's test. RESULTS:A total of 39 case-control studies including 1807 cases of CVT and 7699 control cases were included. FVL was more common in patients with CVT (195/1822) than in controls(369/7795), [odds ratio(OR) = 2.70, 95% confidence interval(CI) 2.16-3.38, P < 0.00001]. Results of subgroup analyses indicated that the association between FVL and CVT varied according to geographic regions. The associations between FVL and CVT were significant in studies from Germany (OR = 2.42, 95%CI 1.70-3.45, P < 0.00001), Brazil(OR = 2.82, 95%CI 1.24-6.42, P = 0.01), France (OR = 5.44, 95%CI 1.35-21.92, P = 0.02), Iran (OR = 6.61, 95%CI 1.83-23.93, P = 0.004), and Tunisia (OR = 6.54, 95%CI 2.89-14.82, P < 0.00001), but not in those from Italy (OR = 1.49, 95%CI 0.59-3.78, P = 0.40) or the US (OR = 2.37, 95%CI 0.59-9.42, P = 0.22). CONCLUSION:FVL may be more common in patients with CVT. However, the association between FVL and CVT varied depending on the geographic origin of the studies.

Although efficacy of venlafaxine extended release (XR) for generalized anxiety disorder (GAD) has been reported in previous analyses in 2002 and 2004, the sample size was rather small and estimate of safety or tolerability was not clear. The present analysis had the advantage of large sample size and provided evidence for tolerability.Literature databases were searched, including Pubmed, Embase, Cochrane Central Register of Controlled Trials, Web of science and clinical trials. 10 eligible articles were finally selected and data was extracted and logged into the Review Manager 5.3 by two independent authors. The risk of bias was evaluated by the Cochrane Collaboration's Risk of Bias Tool and the stability of the results was assessed by sensitivity analysis. The publication bias was assessed by funnel plot and Egger's/Begg's test using Stata Version 12.0 software.In the current meta-analysis, 10 articles (14 studies) satisfying the inclusion criteria were analyzed. As efficacy outcomes, our findings indicated venlafaxine XR was significantly more effective than placebo according to mean change of the Hamilton Rating Scale for Anxiety total scores [mean difference = 3.31, 95% confidence interval(CI) 1.44-5.18, P = 0.0005], response [odds ratio(OR) = 1.83, 95%CI 1.58-2.12, P

Although several site-specific nucleases (SSNs), such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas, have emerged as powerful tools for targeted gene editing in many organisms, to date, gene targeting (GT) in plants remains a formidable challenge. In the present study, we attempted to substitute a single base in situ on the rice OsEPSPS gene by co-transformation of TALEN with chimeric RNA/DNA oligonucleotides (COs), including different strand composition such as RNA/DNA (C1) or DNA/RNA (C2) but contained the same target base to be substituted. In contrast to zero GT event obtained by the co-transformation of TALEN with homologous recombination plasmid (HRP), we obtained one mutant showing target base substitution although accompanied by undesired deletion of 12 bases downstream the target site from the co-transformation of TALEN and C1. In addition to this typical event, we also obtained 16 mutants with different length of base deletions around the target site among 105 calli lines derived from transformation of TALEN alone (4/19) as well as co-transformation of TELAN with either HRP (5/30) or C1 (2/25) or C2 (5/31). Further analysis demonstrated that the homozygous gene-edited mutants without foreign gene insertion could be obtained in one generation. The induced mutations in transgenic generation were also capable to pass to the next generation stably. However, the genotypes of mutants did not segregate normally in T1 population, probably due to lethal mutations. Phenotypic assessments in T1 generation showed that the heterozygous plants with either one or three bases deletion on target sequence, called d1 and d3, were more sensitive to glyphosate and the heterozygous d1 plants had significantly lower seed-setting rate than wild-type.

It remains unknown whether newly identified anti-inflammatory/immunosuppressive cytokine interleukin-35 (IL-35) is different from other anti-inflammatory cytokines such as IL-10 and transforming growth factor (TGF)-β in terms of inhibition of inflammation initiation and suppression of full-blown inflammation. Using experimental database mining and statistical analysis methods we developed, we examined the tissue expression profiles and regulatory mechanisms of IL-35 in comparison to other anti-inflammatory cytokines. Our results suggest that in contrast to TGF-β, IL-35 is not constitutively expressed in human tissues but it is inducible in response to inflammatory stimuli. We also provide structural evidence that AU-rich element (ARE) binding proteins and microRNAs target IL-35 subunit transcripts, by which IL-35 may achieve non-constitutive expression status. Furthermore, we propose a new system to categorize anti-inflammatory cytokines into two groups: (1) the house-keeping cytokines, such as TGF-β, inhibit the initiation of inflammation whereas (2) the responsive cytokines including IL-35 suppress inflammation in full-blown stage. Our in-depth analyses of molecular events that regulate the production of IL-35 as well as the new categorization system of anti-inflammatory cytokines are important for the design of new strategies of immune therapies.

In the title compound, C19H20Cl2O10, the hexopyranosyl ring adopts a chair conformation. The four substituents are in equatorial positions. The molecules arelinked via C—H...O contacts along the a axis.