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CX3CR1high myeloid cells in the small intestine mediate the induction of oral tolerance by driving regulatory T (Treg) cells. Bacterial metabolites, e.g. pyruvate and lactate, induce a dendrite extension of CX3CR1high myeloid cells into the intestinal lumen via GPR31. However, it remains unclear whether the pyruvate–GPR31 axis is involved in the induction of oral tolerance. Here, we show that pyruvate enhances oral tolerance in a GPR31-dependent manner. In ovalbumin (OVA)-fed Gpr31-deficient mice, an OVA-induced delayed-type hypersensitivity response was substantially induced, demonstrating the defective induction of oral tolerance in Gpr31-deficient mice. The percentage of RORγt+ Treg cells in the small intestine was reduced in Gpr31-deficient mice. In pyruvate-treated wild-type mice, a low dose of OVA efficiently induced oral tolerance. IL-10 production from intestinal CX3CR1high myeloid cells was increased by OVA ingestion in wild-type mice, but not in Gpr31-deficient mice. CX3CR1high myeloid cell-specific IL-10-deficient mice showed a defective induction of oral tolerance to OVA and a decreased accumulation of OVA-specific Treg cells in the small intestine. These findings demonstrate that pyruvate enhances oral tolerance through a GPR31-dependent effect on intestinal CX3CR1high myeloid cells.

Background Anastomotic leakage (AL) is one of the commonest and most serious complications after rectal cancer surgery. The previous analyses on predictors for AL included small-scale patients, and their prediction models performed unsatisfactorily. Methods Clinical data of 5,220 patients who underwent anterior resection for rectal cancer were scrutinized to create a prediction model via random forest classifier. Additionally, data of 836 patients served as the test dataset. Patients diagnosed with AL within 6 months' follow-up were recorded. A total of 20 candidate factors were included. Receiver operating characteristic (ROC) curve was conducted to determine the clinical efficacy of our model, and compare the predictive performance of different models. Results The incidence of AL was 6.2% (326/5,220). A multivariate logistic regression analysis and the random forest classifier indicated that sex, distance of tumor from the anal verge, bowel stenosis or obstruction, preoperative hemoglobin, surgeon volume, diabetes, neoadjuvant chemoradiotherapy, and surgical approach were significantly associated with AL. After propensity score matching, the temporary stoma was not identified as a protective factor for AL (P=0.58). Contrastingly, the first year of performing laparoscopic surgery was a predictor (P=0.009). We created a predictive random forest classifier based on the above predictors that demonstrated satisfactory prediction efficacy. The area under the curve (AUC) showed that the random forest had higher efficiency (AUC =0.87) than the nomogram (AUC =0.724). Conclusions Our findings suggest that eight factors may affect the incidence of AL. Our random forest classifier is an innovative and practical model to effectively predict AL, and could provide rational advice on whether to perform a temporary stoma, which might reduce the rate of stoma and avoid the ensuing complications.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves rapidly under the pressure of host immunity, as evidenced by waves of emerging variants despite effective vaccinations, highlighting the need for complementing antivirals. We report that targeting a pyrimidine synthesis enzyme restores inflammatory response and depletes the nucleotide pool to impede SARS-CoV-2 infection. SARS-CoV-2 deploys Nsp9 to activate carbamoyl-phosphate synthetase, aspartate transcarbamoylase, and dihydroorotase (CAD) that catalyzes the rate-limiting steps of the de novo pyrimidine synthesis. Activated CAD not only fuels de novo nucleotide synthesis but also deamidates RelA. While RelA deamidation shuts down NF-κB activation and subsequent inflammatory response, it up-regulates key glycolytic enzymes to promote aerobic glycolysis that provides metabolites for de novo nucleotide synthesis. A newly synthesized small-molecule inhibitor of CAD restores antiviral inflammatory response and depletes the pyrimidine pool, thus effectively impeding SARS-CoV-2 replication. Targeting an essential cellular metabolic enzyme thus offers an antiviral strategy that would be more refractory to SARS-CoV-2 genetic changes.

Background MicroRNAs (miRNAs) play an important regulatory role in carcinogenesis and cancer progression. MiR-95-3p has been reported to be an oncogene in hepatocellular carcinoma. However, the role of miR-95-3p in colorectal carcinoma (CRC) remains unclear. Methods miR-95-3p was validated in an independent validation sample cohort of 215 CRC tissues. Functional assays, Cell proliferation (MTT) assay colony formation, wound healing, transwell and animal xenograft assays were used to determine the oppressor role of miR-95-3p in human CRC progression. Furthermore, Bioinformatics analysis, western blotting and dual-luciferase reporter assay were used to determine the mechanism by which miR-95-3p suppresses progression of CRC cells. Results In this study, we found that miR-95-3p was downregulated in CRC tissues. The low level of miR-95-3p in CRC tumors was correlated with aggressive clinicopathological characteristics, and it predicted poor prognosis in CRC patients. The overexpression of miR-95-3p significantly inhibited CRC cell proliferation, colony formation and metastasis in vitro and in vivo. Bioinformatic analysis further identified hepatoma-derived growth factor (HDGF) as a novel target of miR-95-3p in CRC cells. These findings suggest that miR-95-3p regulates CRC cell survival, partially through the downregulation of HDGF. Conclusions Therefore, the miR-95-3p/HDGF axis might serve as a novel therapeutic target in patients with CRC.

Purpose: MicroRNAs (miRNAs) are key regulators of the growth and development of a wide range of cancer types such as colorectal cancer (CRC). A number of previously studies have observed that the levels of miR-365a-3p expression are dysregulated in many cancers, but the specific role of this miRNA in CRC and its association with patient prognosis remains unclear. Methods: The expression of miR-365a-3p in CRC tissues and cell lines was detected by Real-time Quantitative polymerase chain reaction (RT-qPCR), while the relationship between miR-365a-3p expression and clinicopathological characteristics was further analyzed. After increasing the expression of miR-365a-3p by plasmid transfection in CRC cells, we further investigated the cell proliferation, invasion and migration by cell counting kit-8 (CCK-8), and Transwell assays. Epithelial-mesenchymal transition (EMT) pathway was also measured by western blotting. In addition, the relationship among miR-365a-3p, ADAM10 and JAK in CRC, was explored by luciferase reporter assay. Results: In the present study, we determined that CRC cells and clinical samples exhibited decreased miR-365a-3p expression, and this was associated with larger tumor size, lymph node metastasis, and local invasion. Patients with lower expression of miR-365a-3p had significantly decreased recurrence-free survival (RFS) and overall survival (OS) relative to those with higher levels of this miRNA. In a multivariate analysis, we confirmed that reduced miR-365a-3p levels were independently predictive of poorer CRC patient outcomes. In a functional study, we determined that elevated miR-365a-3p expression inhibited the ability of CRC cells to proliferate and metastasize in vitro and in vivo. We further identified ADAM10 as a direct miR-365a-3p target, resulting in the suppression of ADAM10 expression in cells expressing this miRNA and ADAM10 levels were in turn closely linked to JAK/STAT signaling. Conclusion: Our study suggested the ability of miR-365a-3p to inhibit the progression of CRC at least in part via suppressing ADAM10 expression and associated JAK/STAT signaling, thus identifying this signaling axis as a possible prognostic and therapeutic target in CRC.

BackgroundAltered expression profile of microRNAs (miRNAs) was reported to be associated with colorectal cancer (CRC). The aims of this study are to identify the changed miRNAs in the plasma of CRC patients and explore the underlying mechanism of these miRNAs during tumorigenesis.MethodsPlasma miRNA expression profiles were compared between healthy people and CRC patients. MiRNA expression was measured using quantitative real-time PCR. Colony formation and MTT assays were used to test cell proliferation. Luciferase assay, immunohistochemistry and Western blotting were employed to explore the molecular mechanism.ResultsMiR-142-3p level was found as the most significantly repressed miRNA in CRC patients. Overexpression of miR-142-3p dramatically repressed colony formation and cell proliferation of both HT29 and HCT116 cells while inhibition of miR-142-3p promoted those of the cells. Interestingly, overexpression of miR-142-3p reduced the level and nuclear accumulation of β-catenin. We further observed that miR-142-3p remarkably inhibited the transcriptional activity of β-catenin gene (CTNNB1). However, mutations in the predicted binding sites blocked this inhibition, suggesting that miR-142-3p may directly bind to the mRNA of β-catenin.ConclusionIn conclusion, we identified miR-142-3p exerts its function as a tumor suppressor through blocking the activation of Wnt signaling by directly targeting to CTNNB1.

A protective loop ileostomy is recommended in ultra-low rectal cancer to reduce the complications associated with anastomotic leakage (AL), but there are few studies on the complications after AL. The purpose of this study was to outline our experience in the successful treatment of severe abdominal infection after AL in rectal cancer patients with the protective loop ileostomy.In this report, we describe three cases of AL after standard total mesorectal excision with the protective loop ileostomy. Severe abdominal infection occurred postoperatively. The patients were successfully treated by surgical reintervention and had an uneventful recovery. No recurrence was observed after 2 years.We consider that pelvic floor reconstruction and extending the extubation time should be performed in patients with a high risk of AL. Moreover, when severe abdominal infection and early infectious shock occur after AL, immediate reoperation should be performed to minimize the complication.Protective loop ileostomy can't decrease the re-operation rate for patients with AL. We should take preventive measures during and after the operation, as well as early detection and early treatment.

Highlights • The hemoclip device is effective and safe for endoscopic closure of the anastomotic leakage after low anterior resection. • Hemoclip device reduce costs as well as avoid an additional operation for the patient. • Strict criteria should be applied when identifying suitable patients., Introduction and importance Hemoclips have been used to protect leakage after endoscopic resection of large colorectal polyps or early-staged rectal cancer, or for perforation of the sigmoid colon during colonoscopy. However, endoscopic clips were seldom used to manage anastomotic leakage after low anterior resection of rectal cancer. Case presentation A patient with postoperative anastomotic leakage after low anterior resection for rectal cancer was successfully treated by endoscopic hemoclips under colonoscopic vision after failure of conservative treatment. Postoperative course was uncomplicated and the patient was discharged from the hospital seven days later. Clinical discussion and conclusion Endoscopic hemoclips should be considered as an alternative option for the treatment of an anastomotic leakage in cases where conservative treatment has failed. As they are safe and effective for closure, however good bowel preparation and strict inclusion criteria are required.

SQUAMOSA promoter-binding protein-like (SPL) transcription factors are very important for the plant growth and development. Here 15 RoSPLs were identified in Rubus occidentalis. The conserved domains and motifs, phylogenetic relationships, posttranscriptional regulation, and physiological function of the 92 SPL family genes in Fragaria vesca, Malus domestica, Prunus persica, R. occidentalis, and Pyrus pyrifolia were analyzed. Sequence alignment and phylogenetic analysis showed the SPL proteins had sequence conservation, some FvSPLs could be lost or developed, and there was a closer relationship between M. domestica and P. pyrifolia, F. vesca and R. occidentalis, respectively. Genes with similar motifs clustering together in the same group had their functional redundancy. Based on the function of SPLs in Arabidopsis thaliana, these SPLs could be involved in vegetative transition from juvenile to adult, morphological change in the reproductive phase, anthocyanin biosynthesis, and defense stress. Forty-eight SPLs had complementary sequences of miR156, of which nine PrpSPLs in P. persica and eight RoSPLs in R. occidentalis as the potential targets of miR156 were reported for the first time, suggesting the conservative regulatory effects of miR156 and indicating the roles of miR156-SPL modules in plant growth, development, and defense response. It provides a basic understanding of SPLs in Rosaceae plants.

BACKGROUND: Improved patient satisfaction in endoscopy is worthy of study as it is an invasive and potentially uncomfortable procedure. There is growing literature on patient satisfaction assessment in endoscopy as part of improving quality assurance. This study aimed to determine whether virtual reality (VR) technology can decrease patients' pain and nervousness during colonoscopies. METHODS: Patients enrolled without sedation were randomly categorised into groups that watched VR (VR group; n=58) and those that did not watch VR (control group; n=59). The primary outcomes were pain score and skin conductance. Secondary endpoints included heart rate, systolic and diastolic arterial pressures, overall patient satisfaction, willingness to repeat the procedure, the difficulty of the procedure, the procedure duration, and bowel preparation. RESULTS: The median (interquartile range (IQR)) pain scores were 7 (6–8) and 5 (4–6) in the control and VR groups, respectively (p

The State Council of China requires that all urban public hospitals must eliminate drug markups by September 2017, and that hospital drugs must be sold at the purchase price. Nanjing-one of the first provincial capital cities to implement the reform-is studied to evaluate the effects of the comprehensive reform on drug prices in public hospitals, and to explore differential compensation plans.Sixteen hospitals were selected, and financial data were collected over the 48-month period before the reform and for 12 months after the reform. An analysis was carried out using a simple linear interrupted time series model.The average difference ratio of drug surplus fell 13.39% after the reform, and the drug markups were basically eliminated. Revenue from medical services showed a net growth of 28.25%. The overall compensation received from government financial budget and medical service revenue growth was 103.69% for the loss from policy-permitted 15% markup sales, and 116.48% for the net loss. However, there were large differences in compensation levels at different hospitals, ranging from -21.92% to 413.74% by medical services revenue growth, causing the combined rate of both financial and service compensation to vary from 28.87-413.74%, There was a significant positive correlation between the services compensation rate and the proportion of medical service revenue (p .001), and the compensation rate increased by 8% for every 1% increase in the proportion of services revenue.Nanjing's pricing and compensation reform has basically achieved the policy targets of eliminating the drug markups, promoting the growth of medical services revenue, and adjusting the structure of medical revenue. However, the growth rate of service revenue of hospitals varied significantly from one another.Nanjing's reform represents successful pricing and compensation reform in Chinese urban public hospitals. It is recommended that a differentiated and dynamic compensation plan should be established in accordance with the revenue structure of different hospitals.

The purpose of this study was to evaluate the risk factors for anastomotic leakage (AL) after anterior resection for middle and low rectal cancer in order to help surgeons to decide which patients could benefit from a diverting stoma. Data on 319 patients having a middle and low rectal cancer resection with anastomosis between May 2011 and October 2015 from two hospitals were included in the study. The analysis included the following variables: patient-related variables (gender, age, diabetes mellitus, ASA score, preoperative radiochemotherapy, body mass index, blood hemoglobin, and serum albumin level), tumor-related variables (K-ras status, distance of tumor from the anal verge, histopathologic grade, pathological T stage, pathological N stage, pathological M stage, TNM stage, and tumor size), and surgery-related variables (laparoscopic or open surgery, blood loss, and operative time). Univariate and multivariate regression analysis were carried out to identify risk factors for AL. The AL rate was 11.91% (38/319). Male (OR 2.898, 95% CI 1.265–6.637, p = 0.012), diabetes mellitus (OR 2.482, 95% CI 1.004–6.134, p = 0.049), K-ras mutation (OR 2.544, 95% CI 1.210–5.348, p = 0.014), distance of tumor from the anal verge (OR 3.445, 95% CI 1.631–7.279, p = 0.001), and preoperative radiochemotherapy (OR 2.790, 95% CI 1.056–7.372, p = 0.039) were independent risk factors of AL. One (2.63%) in 38 patients with AL presented with no risk factor of AL, 6 (15.8%) in 38 patients with 1 risk factor, 16 (42.1%) in 38 patients with 2 risk factors, 9 (23.7%) in 38 patients with 3 risk factors, and 6 (15.7%) in 38 patients with 4 risk factors. No patient with 5 risk factors in our study. AL rate increased with the elevated number of risk factors clustering in individuals. K-ras mutation is first reported to be an independent risk factor for AL after sphincter-preserving surgery without diverting stoma. A diverting stoma should be performed in sphincter-preserving surgery for middle and low rectal cancer patients with 2 or more risk factors identified in this analysis.

Herpesviruses can be detected by pattern recognition receptors (PRRs), which then activate downstream adaptors, kinases and transcription factors (TFs) to induce the expression of interferons (IFNs) and inflammatory cytokines. IFNs further activate the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, inducing the expression of interferon-stimulated genes (ISGs). These signaling events constitute host innate immunity to defeat herpesvirus infection and replication. A hallmark of all herpesviruses is their ability to establish persistent infection in the presence of active immune response. To achieve this, herpesviruses have evolved multiple strategies to suppress or exploit host innate immune signaling pathways to facilitate their infection. This review summarizes the key host innate immune components and their regulation by herpesviruses during infection. Also we highlight unanswered questions and research gaps for future perspectives.

Welcome to G03: SiGe, Ge, and Related Compounds: Materials, Processing, and Devices 9! Take a moment to listen to welcome remarks from the lead organizer, Qizhi Liu.

Gene editing with CRISPR/Cas9 is a powerful tool to study the function of target genes. Although this technology has demonstrated wide efficiency in many species, including fertilized zebrafish and medaka fish embryos when microinjected, its application to achieve efficient gene editing in cultured fish cells have met some difficulty. Here, we report an efficient and reliable approach to edit genes in cultured medaka (Oryzias latipes) fish cells using pre-formed gRNA-Cas9 ribonucleoprotein (RNP) complex. Both medaka fish haploid and diploid cells were transfected with the RNP complex by electroporation. Efficient gene editing was demonstrated by polymerase chain reaction (PCR) amplification of the target gene from genomic DNA and heteroduplex mobility assay carried out with polyacrylamide gel electrophoresis (PAGE). The heteroduplex bands caused by RNP cleavage and non-homologous end joining could be readily detected by PAGE. DNA sequencing confirmed that these heteroduplex bands contains the mutated target gene sequence. The average gene editing efficiency in haploid cells reached 50%, enabling us to generate a clonal cell line with ntrk3b gene mutation for further study. This RNP transfection method also works efficiently in diploid medaka cells, with the highest mutation efficiency of 61.5%. The specificity of this synthetic RNP CRISPR/Cas9 approach was verified by candidate off-target gene sequencing. Our result indicated that transfection of pre-formed gRNA-Cas9 RNP into fish cells is efficient and reliable to edit target genes in cultured medaka fish cells. This method will be very useful for gene function studies using cultured fish cells., Summary: In this paper, we report an efficient genome editing method for cultured medaka fish cells using pre-formed CRISPR/Cas9 RNP. This method will be very useful for gene function studies using cultured fish cells.

C-type lectins (CTLs) are a large family of calcium-dependent carbohydrate-binding proteins. They function primarily in cell adhesion and immunity by recognizing various glycoconjugates. We identified 14 transcripts encoding proteins with one or two CTL domains from the transcriptome from Asian corn borer, Ostrinia furnacalis (Guenée; Lepidoptera: Pyralidae). Among them, five (OfCTL-S1 through S5) only contain one CTL domain, the remaining nine (OfIML-1 through 9) have two tandem CTL domains. Five CTL-Ss and six OfIMLs have a signal peptide are likely extracellular while another two OfIMLs might be cytoplasmic. Phylogenetic analysis indicated that OfCTL-Ss had 1:1 orthologs in Lepidoptera, Diptera, Coleoptera and Hymenoptera species, but OfIMLs only clustered with immulectins (IMLs) from Lepidopteran. Structural modeling revealed that the 22 CTL domains adopt a similar double-loop fold consisting of β-sheets and α-helices. The key residues for calcium-dependent or independent binding of specific carbohydrates by CTL domains were predicted with homology modeling. Expression profiles assay showed distinct expression pattern of 14 CTLs: the expression and induction were related to the developmental stages and infected microorganisms. Overall, our work including the gene identification, sequence alignment, phylogenetic analysis, structural modeling, and expression profile assay would provide a valuable basis for the further functional studies of O. furnacalis CTLs.

The true survival benefit of different curative strategies involving type of operative procedure and timing for patients with initial noncurative colorectal liver metastases remains uncertain. The goal of this study was to examine the effect of primary tumor resection on patients’ survival and to clarify the predictive factors related to overall survival (OS). This was a retrospective study that included 219 patients with initial noncurative colorectal liver metastases without extrahepatic disease. The clinicopathological characteristics of patients and their survival were examined. Survival analysis was performed using the Kaplan–Meier method. All variables associated with P

Insertional mutagenesis (IM) by retrovirus (RV) is a high-throughput approach for interrogating gene functions in model species. Haploid cell provides a unique system for genetic screening by IM and prosperous progress has been achieved in mammal cells. However, little was known in lower vertebrate cells. Here, we report development of retroviral vectors (rvSAchCVgfp, rvSAchCVpf and rvSAchSTpf) and establishment of IM library in medaka haploid cells. Each vector contains a modified gene trapping (GT) cassette, which could extend the mutated cell population including GT insertions not in-frame or in weakly expressed genes. Virus titration determined by flow cytometry showed that rvSAchSTpf possessed the highest supernatant virus titer (1.5×10(5)TU/ml) in medaka haploid cell, while rvSAchCVpf produced the lowest titer (2.8×10(4)TU/ml). However, quantification of proviral DNAs in transduced cells by droplet digital PCR (ddPCR) demonstrated that the "real titer" may be similar among the three vectors. Furthermore, an IM library was established by FACS of haploid cells transduced with rvSAchCVgfp at a MOI of 0.1. A single copy RV integration in the majority of cells was confirmed by ddPCR in the library. Notably, there was a significant decrease of haploid cell percentage after FACS, suggesting potential trapping for survival/growth essential genes. Our results demonstrated successful development of retroviral vectors for IM in medaka haploid cells, serving for haploid genetic screening of host factors for virus infection and genes underlying certain cellular processes in fish model.

Periostin (POSTN) expression in cancer cells and circulation has been related to poor prognosis of colorectal carcinoma (CRC). However, the role of POSTN expressed in intra-tumoral stroma on CRC progression remains largely unknown. This study enrolled 1098 CRC patients who received surgical treatment in Shanghai and Guangzhou, Mainland China. In Shanghai cohort, immunohistochemistry score of stromal POSTN expression increased consecutively from adjacent mucosa, primary CRC tissues, to metastatic CRC tissues (P < 0.001), while medium- and high-stromal POSTN expression, rather than epithelial POSTN expression, independently predicted unfavorable prognoses of CRC, adjusted for covariates including TNM stage and postoperative chemotherapy in multivariate Cox models. The results in Shanghai cohort were faithfully replicated in Guangzhou cohort. Stromal POSTN expression dose-dependently predicted an unfavorable prognosis of stage III CRC patients with postoperative chemotherapy in both cohorts. POSTN derived from colonic fibroblasts or recombinant POSTN significantly promoted proliferation, anchorage independent growth, invasion, and chemo-resistance of CRC cells; whereas these effects were counteracted via targeting to PI3K/Akt or Wnt/β-catenin signaling pathway. CRC cell RKO-derived factor(s) significantly induced POSTN production in colonic fibroblasts and autocrine POSTN promoted proliferation, migration, and anchorage independent growth of fibroblasts. Conclusively, stromal POSTN is prognostic and predictive for CRC via creating a niche to facilitate cancer progression. Targeting POSTN-induced signaling pathways may be therapeutic options for metastatic or chemoresistant CRC.

Background/Aims: Mitochondria (MT) and mitochondrial DNA (mtDNA) show maternal inheritance in most eukaryotic organisms; the sperm mtDNA is usually delivered to the egg during fertilization and then rapidly eliminated to avoid heteroplasmy, which can affect embryogenesis. In our previous study, fertilization-delivered sperm mtDNA exhibited late elimination and transcriptional quiescence in cyprinid fish embryos. However, the mechanisms underlying elimination and transcriptional quiescence of paternal mtDNA are unclear. Methods: Goldfish and zebrafish were used to investigate the fate of mtDNAs with different parental origins delivered by fertilization or microinjection in embryos. Goldfish MT from heart, liver and spermatozoa were microinjected into zebrafish zygotes, respectively. Specific PCR primers were designed so that the amplicons have different sizes to characterize goldfish and zebrafish cytb genes or their cDNAs. Results: The MT injection-delivered paternal mtDNA from sperm, as well as those from the heart and liver, was capable of persistence and transcription until birth, in contrast to the disappearance and transcriptional quiescence at the heartbeat stage of fertilization-delivered sperm mtDNA. In addition, the exogenous MT-injected zebrafish embryos have normal morphology during embryonic development. Conclusions: The fate of paternal mtDNA in fishes is dependent on the delivery strategy rather than the MT source, suggesting that the presence of sperm factor(s) is responsible for elimination and transcriptional quiescence of fertilization-delivered sperm mtDNA. These findings provide insights into the mechanisms underlying paternal mtDNA fate and heteroplasmy in cyprinid fishes.

Viral infection is a great challenge in healthcare and agriculture. The Singapore grouper iridovirus (SGIV) is highly infectious to numerous marine fishes and increasingly threatens mariculture and wildlife conservation. SGIV intervention is not available because little is known about key players and their precise roles in SGVI infection. Here we report the precise role of VP088 as a key player in SGIV infection. VP088 was verified as an envelope protein encoded by late gene orf088. We show that SGIV could be neutralized with an antibody against VP088. Depletion or deletion of VP088 significantly suppresses SGIV infection without altering viral gene expression and host responses. By precisely quantifying the genome copy numbers of host cells and virions, we reveal that VP088 deletion dramatically reduces SGIV infectivity through inhibiting virus entry without altering viral pathogenicity, genome stability and replication and progeny virus release. These results pinpoint that VP088 is a key player in SGIV entry and represents an ideal target for SGIV intervention.

Selectively-grown silicon deposited via reduced pressure chemical vapor deposition is a well-known epitaxial technique that is used in academia and industry. During a selective Si deposition process, epitaxial silicon is grown on single-crystal Si or poly Si seed layer while suppressing nucleation on dielectric surfaces. This technique is advantageous for BiCMOS development and cost reduction in SiGe manufacturing. GlobalFoundries has leadership in SiGe PA technologies for high-volume WiFi and cellular markets, and also in high performance SiGe technologies. For next generation SiGe PA, p+ selective silicon, or highly-boron-doped silicon, is one of the leading candidates to improve device performance to meet challenging customer demands. Optimizing this process, however, is a non-trivial task. The latest data for p+ selective silicon is discussed.

Sex is pivotal for reproduction, healthcare and evolution. In the fish medaka, the Y-chromosomal dmy (also dmrt1bY) serves the sex determiner, which activates dmrt1 for male sex maintenance. However, how dmy makes the male decision via initiating testicular differentiation has remained unknown. Here we report that autosomal gsdf serves a male sex initiator. Gene addition and deletion revealed that gsdf was necessary and sufficient for maleness via initiating testicular differentiation. We show that gsdf transcription is activated directly by dmy. These results establish the autosomal gsdf as the first male sex initiator. We propose that dmy determines maleness through activating gsdf and dmrt1 without its own participation in developmental processes of sex initiation and maintenance. gsdf may easily become a sex determiner or other autosomal genes can be recruited as new sex determiners to initiate gsdf expression. Our findings offer new insights into molecular mechanisms underlying sex development and evolution of sex-controlling genes in vertebrates.

A new anhydrous proton conducting material based on polyimide and phosphoric acid composite was prepared. The interaction between polyimide (PI) and phosphoric acid was investigated by FTIR. The results show that phosphoric acid interacts with polyimides mainly by hydrogen bonds rather than by protonation of PI at room temperature. Environmental scanning electron microscopy (ESEM) was employed to study the surface morphology of the membranes. The results show that the surface of PI–xH3PO4 membranes is very compact and homogeneous. Proton conductivity and methanol permeability of PI doped with phosphoric acid (PI–xH3PO4) were also studied. Proton conductivity of PI–xH3PO4 membranes increases with increasing concentration of phosphoric acid. Hydrogen bond seems to play an important role in the proton conductivity of this system. Effects of osmotic on the direct diffusion process of methanol in the membranes can be negligible due to the absence of micro-pore structure as already shown in ESEM results. Effects of methanol concentration and temperature on the methanol permeability of PI–xH3PO4 membranes were also discussed. Methanol permeability in PI–xH3PO4 membranes decreases with increasing methanol concentration, and increases with increasing temperature.

Polybenzimidazole (PBI)/polyimide (PI) and PBI/polyvinylpyrrolidone (PVP) blends were prepared. All of these polymers are suitable for acid doping as a matrix because of the existence of the N-heterocycle in the polymers, which can eventually be used as proton conductors. The miscibility of PBI/PVP blend is confirmed by Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM), while the miscibility of PBI/PI is already reported in references. Temperature dependence of proton conductivity of acid doped PBI/PI and PBI/PVP blends are studied. As the temperature increases, proton conductivity of H3PO4 doped PBI/PVP blends increases. Temperature dependence of proton conductivity of the blends can still be fitted by a simple Arrhenius relation. The proton transport of the blend is similar to that of PBI. The methanol permeability of PBI/PI blends is also studied. Methanol permeability in PBI/PI, PI, and PBI membranes decreases with increasing methanol concentration. POLYM. ENG. SCI., 45:1395–1400, 2005. © 2005 Society of Plastics Engineers

Silicon Germanium (SiGe) Heterojunction Bipolar Transistors (HBTs) in Bipolar Complementary Metal Oxide Semiconductor (BiCMOS) technologies have in recent years, emerged as a viable alternative to Gallium Arsenide (GaAs) [1] for commercial development of linear power amplifier (PA) modules for wireless communications. The explosion in WLAN applications at 2.4GHz has provided ample opportunity for SiGe BiCMOS to substantially penetrate the PA market [2]. SiGe HBTs offer several benefits compared to it’s GaAs HBT counterparts including the ability to provide high integration at a reduced cost [3]. The higher thermal conductivity associated with the silicon substrate enables reduced chip areas, smaller packages and provides improvements in chip robustness. Additionally, SiGe BiCMOS integration facilitates improved power densities, on-chip matching and bias chokes, temperature compensated power detector and a CMOS compatible interface [2]. SiGe HBT PA device design limits have traditionally been constrained by the performance tradeoff described by the Johnson limit, which states that the product of the current gain, fT and the DC open-base breakdown voltage, BVceo, should be relatively constant[3]. However, it is now generally accepted that DC emitter-open breakdown voltage, BVcbo is a more useful indicator of device ruggedness for PA applications. This arises since SiGe HBT operation in PA applications have been demonstrated at voltages significantly higher than BVceo, [1,4]. Furthermore, power-gain cut-off frequency, fMAX , has also been cited as relevant a device metric for PAs as fT , [1,3] and several authors have suggested that improvements in fMAX will enhance PA device performance. Typically, improvements in device fMAX are achieved by lateral scaling to accomplish a reduction in the base resistance and collector-base capacitance. Since SiGe HBT device physics do not demand rigid tradeoff between BVcbo and fMAX, , several potential device optimization opportunities exist for PA applications. Technology computer-aided design (TCAD) has been used to optimize the PA design performance relative to the base technology. The TCAD methodology was based on a detailed strategy which entailed developing a process and device model calibration for an existing 0.35um SiGe HBT device that features non-self-aligned emitter-base integration, with a carbon doped SiGe base layer and an implanted extrinsic base region [2]. The model calibration featured a close match of both process and electrical characteristics to the measured data. An important element to matching the electrical characteristics of the device, was simulating key artifacts of the process related to epitaxial growth of the SiGe base layer, which defined the final device topology. The calibration served as the baseline simulation for the optimization study and provided insight into the device performance limitations. The simulations demonstrated the device breakdown, BVcbo, occurs along the extrinsic region of the collector and the base, and is correspondingly set by the thickness of the collector n-epitaxial layer and the vertical diffusion of the extrinsic base into the collector. Several lateral scaling strategies were therefore investigated, which addressed optimization of collector-base capacitance, Ccb and base resistance, Rb for improvements in fMAX and BVcbo. Scaling the lateral dimension of the device resulted in improvements in the performance metrics peak fT , peak Ic and fMAX . Improvements in fT and Ic are explained by the reduced surface field effect, whereby a more uniform field distribution delays base push out effect in the transistor[5]. The AC and DC characteristcs will be reviewed. References [1] K. Nellis and P. Zampardi, "A Comparison of Linear Handset Power Amplifiers," IEEE JOURNAL OF SOLID-STATE CIRCUITS, vol. 39, no. 10, pp. 1746-1754, 2004. [2] A. Joseph et. al, "A 0.35um SiGe BiCMOS technology for Power Amplifier Applications," in IEEE Bipolar/BiCMOS Circuits and Technology Meeting, Boston, MA, 2007. [3] J. B. Johnson et. al, "Silicon-Germanium BiCMOS HBT Technology for Wireless Power Amplifier Applications," IEEE JOURNAL OF SOLID-STATE CIRCUITS,, vol. 39, no. 10, pp. 1605-1613, 2004. [4] T. Matsuno et. al, "RF power characteristics of SiGe heterojunction bipolar transistor with high breakdown voltage structures,”," in IEEE MTT-S Symp. Dig, 2002. [5] R. Heuting et.al, "A New Trench Bipolar Transistor for RF Applications," IEEE TRANSACTIONS ON ELECTRON DEVICES, vol. 51, no. 7, pp. 1108-1113, 2004.

Although the absolute number of positive lymph nodes (LNs) has been established as 1 of the most important prognostic factors in rectal cancers, many researchers have proposed that the lymph node ratio (LNR) may have better predicted outcomes. We conducted a retrospective study to compare the predictive ability of LNR and ypN category in rectal cancer. A total of 264 locally advanced rectal cancer (LARC) patients who underwent preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) between 2005 and 2012 were reviewed. All patients were categorized into 3 groups or patients with metastatic LNs were categorized into 2 groups according to the LNR. The prognostic effect on overall survival (OS) and disease-free survival (DFS) was evaluated. With a median follow-up of 45 months, the OS and DFS were 68.4% and 59.3% for the entire cohort, respectively. The respective 5-year OS and DFS rates for the 3 groups (LNR = 0, 0 < LNR ≤ 0.20, and 0.20 < LNR ≤ 1.0) were as follows: 83.2%, 72.6%, and 49.4% (P

Replant disease is a major limitation for strawberry production in greenhouse. Bio-control may be a good way to cope with the replant diseases. Here, we report identification and characterization of a bacterial strain TS06 that may be used as a bio-control agent against the replant diseases in strawberry. TS06 was identified as a new strain of Bacillus subtilis based on the homology of its 16S rRNA and gyrA sequences to the reference strains in Genbank. It has a 7 bp difference from the most homologous strain B. subtilis NRRL B-23978. TS06 formed a monophyletic group with species of the B. subtilis complex group in the 16S rDNA sequence analysis, and shared similarity values of 99.9% with the B. subtilis type strains in the sequence analysis of the gyrA genes. TS06 was demonstrated to be a potent inhibitor to Fusarium oxysporum and Verticillium dahliae . There were 89.6 and 84.5% growth inhibition of TS06 on F. oxysporum and V.dahliae respectively in the antagonism test of TS06 strain in vitro . The mycelia growth inhibition rate of TS06 for F. oxysporum and V.dahliae reached 65.96 and 68.45% respectively, in the 40% TS06 culture filtrate treatments. Strain TS06 reduced the average percentage of strawberry diseases ( Fusarium and Verticillium Wilts) by 88.94 and 79.94% respectively in greenhouse. In summary, B. subtilis strain TS06 has a broad antifungal spectrum and synchronously bio-control the two severe replant diseases (Fusarium and Verticilium Wilts), and TS06 can be developed as a biocontrol agent to be applied in strawberry production. Key words : Bacillus subtilis , strain TS06, biological control, strawberry Fusarium wilt , strawberry Verticillium wilt.