A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Xue Li - Top 30 Publications

Adropin preserves the blood-brain barrier through a Notch1/Hes1 pathway after intracerebral hemorrhage in mice.

Adropin is expressed in the central nervous system (CNS) and plays a crucial role in the development of stroke. However, little is currently known about the effects of adropin on the blood-brain barrier (BBB) function after intracerebral hemorrhage (ICH). In this study, the role of adropin in collagenase-induced ICH was investigated in mice. At 1-h post ICH, mice were administered with recombinant human adropin by intranasal. Brain water content, BBB permeability, and neurological function were measured at different time intervals. Proteins were quantified using Western blot analysis, and the localizations of adropin and Notch1 were visualized via immunofluorescence staining. It is shown that adropin reduced brain water content and improved neurological functions. Adropin preserved the functionality of BBB by increasing N-cadherin expression and reducing extravasation of albumin. Moreover, in vivo knockdown of Notch1 and Hes1 both abolished the protective effects of adropin. Taken together, our data demonstrate that adropin constitutes a potential treatment value for ICH by preserving BBB and improving functional outcomes through the Notch1 signaling pathway. This article is protected by copyright. All rights reserved.

Prognostic value of supraclavicular nodes and upper abdominal nodes metastasis after definitive chemoradiotherapy for patients with thoracic esophageal squamous cell carcinoma.

The purpose of this study is to assess the prognostic value of supraclavicular nodes, left gastric nodes, celiac nodes and common hepatic nodes metastasis in esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. A total of 293 ESCC patients treated with radiotherapy or chemoradiotherapy entered the study. The results showed that the presence of supraclavicular nodes (χ(2) = 0.075, P = 0.785) and left gastric nodes (χ(2) = 3.603, P = 0.058) metastasis had no significant influence on survival, while celiac nodes (χ(2) = 33.775, P < 0.001) and common hepatic nodes (χ(2) = 42.350, P < 0.001) metastasis were associated with significantly shorter survival, regardless of the sites of primary tumor. Multivariate analysis showed that celiac nodes (HR: 0.457, 95% CI: 0.256-0.816; P = 0.008) and common hepatic nodes (HR: 0.241, 95% CI: 0.092-0.630; P = 0.004) metastasis were independently adverse indicator of survival in upper ESCC. While in the middle and lower ESCC, only the common hepatic nodes (middle ESCC: HR: 0.345, 95% CI: 0.161-0.738, P = 0.006; lower ESCC: HR: 0.377, 95% CI: 0.160-0.890, P = 0.026) metastasis was an independently adverse indicator of survival. In conclusion, our study demonstrated that in ESCC treated with definitive radiotherapy, both of celiac nodes and common hepatic nodes metastasis were adverse indicator of survival in upper ESCC, and common hepatic nodes metastasis were adverse indicator of survival in middle and lower ESCC. Supraclavicular nodes an left gastric nodes metastasis is not associated with patients survival in ESCC.

Tsp1 promotes alveolar stem cell proliferation and its down-regulation relates to lung inflammation in intralobar pulmonary sequestration.

An aberrant systemic artery supply results in recurrent infections in the abnormal lung lobe of intralobar pulmonary sequestration (ILS). The mechanisms underlying such persistent inflammation are unknown. Here, we hypothesize that alteration of an endothelial cell niche for alveolar epithelial cells results in the impaired proliferation potential of alveolar progenitor cells, leading to the defective defense mechanism in intralobar pulmonary sequestration. Paraffin sections of lung tissues from patients with intralobar pulmonary sequestration or from healthy controls were collected for analysis of alveolar epithelial alterations in intralobar pulmonary sequestration by quantitative RT-PCR or immunofluorescent staining. Differential transcripts were identified between human pulmonary artery endothelial cells and human aortic endothelial cells by microarray. Validation of microarray data by quantitative PCR analysis indicated that thrombospondin-1 expression level is low in near-lesion part but high in lesion part of ILS lobe as compared to healthy controls. In vitro 3-D matrigel culture was adopted to evaluate the regulation of alveolar progenitor cells by thrombospondin-1 and CD36. We found that the proliferative potential of alveolar type 2 stem/progenitor cells was impaired in intralobar pulmonary sequestration. Mechanistically, we discovered that endothelial thrombospondin-1 promotes alveolar type 2 cell proliferation through the interaction with CD36. These data demonstrate that alveolar stem cells are impaired in the abnormal lobe from patients with intralobar pulmonary sequestration and imply that restoring epithelial integrity can be beneficial for the future treatments of recurrent infections in lung pathologies.

Long-Term Room Temperature Storage of Dry Ribonucleic Acid for Use in RNA-seq Analysis.

RNA is an essential biological material for research in genomics and translational medicine. As such, its storage for biobanking is an important field of study. Traditionally, long-term storage in the cold (generally freezers or liquid nitrogen) is used to maintain high-quality (in terms of quantity and integrity) RNA. Room temperature (RT) preservation provides an alternative to the cold, which is plagued by serious problems (mainly cost and safety), for RNA long-term storage. In this study, we evaluated the performance of several RT storage procedures, including the RNAshell(®) from Imagene, where the RNA is dried and kept protected from the atmosphere, and the vacuum drying of RNA with additives such as the Imagene stabilization solution and a home-made trehalose solution. This evaluation was performed through accelerated (equivalent to 10 years for RNAshell) aging and real-time studies (4 years). To check RNA quality and integrity, we used RNA integrity number values and RNA-seq. Our study shows that isolation from atmosphere offers a superior protective effect for RNA storage compared with vacuum drying alone, and demonstrates that RNAshell permits satisfactory RNA quality for long-term RT storage. Thus, the RNA quality could meet the demand of downstream applications such as RNA-seq.

The role of TGFβ‑HGF‑Smad4 axis in regulating the proliferation of mouse airway progenitor cells.

The interaction between airway epithelial progenitor cells and their microenvironment is critical for maintaining lung homeostasis. This microenvironment includes fibroblast cells, which support the growth of airway progenitor cells. However, the mechanism of this support is not fully understood. In the present study, the authors observed that inhibition of transforming growth factor (TGF)‑β signal with SB431542 promotes the expression of hepatocyte growth factor (HGF) in fibroblast cells. The HGF receptor, c‑Met, is expressed on airway progenitor cells; HGF promotes the colony‑forming ability of airway progenitor cells. The deletion of Smad4 in airway progenitor cells increases the colony‑forming ability, suggesting that Smad4 plays a negative role in the regulating the proliferation of airway progenitor cells. These data demonstrated that the regulation of airway progenitor cells by TGF‑β depends on TGF‑βR1/2 on stromal cells, rather than on epithelial progenitor cells. These data suggested a role for the TGF‑β‑TGF‑βR1/2‑HGF‑Smad4 axis in airway epithelial homeostasis and sheds new light on the interaction between airway progenitor cells and their microenvironment.

A novel acridine derivative, LS-1-10 inhibits autophagic degradation and triggers apoptosis in colon cancer cells.

Autophagy promotes cancer cell survival and drug resistance by degrading harmful cellular components and maintaining cellular energy levels. Disruption of autophagy may be a promising approach to sensitize cancer cells to anticancer drugs. The combination of autophagic inhibitors, such as chloroquine (CQ) and lucanthone with conventional cancer therapeutics has been investigated in clinical trials, but adverse drug-drug interactions are a high possibility. Here we designed and synthesized a novel, small-molecule library based on an acridine skeleton and the CQ structure with various modifications and substitutions and screened the compounds for effective autophagy inhibition. We found that 9-chloro-2-(3-(dimethylamino)propyl)pyrrolo[2,3,4-kl]acridin-1(2H)-one (LS-1-10) was the most effective from our library at inhibiting autophagic-mediated degradation and could decrease the viability of multiple colon cancer cells. In addition, LS-1-10 induced DNA damage and caspase 8-mediated apoptosis. Overall, this small molecule was more efficient at reducing the viability of cancer cells than other conventional chemotherapeutic agents, such as CQ and amsacrine. The anticancer and autophagy-inhibiting activities of LS-1-10 were confirmed in vivo in a xenograft mouse model. Collectively, this study has identified a new and efficient single compound with both autophagy-inhibiting and anticancer activity, which may provide a novel approach for cancer therapy.

Fasting blood soluble RAGE may be causally implicated in impaired glucose metabolism in Chinese patients with primary hypertension.

We prepared to investigate the association of four well-defined polymorphisms in the receptor for advanced glycation end-products (RAGE) gene with the changes of fasting blood soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) and the risk for impaired glucose metabolism (IGM) in 1704 patients with primary hypertension, aiming to infer possible causality between sRAGE/esRAGE and IGM. This was a hospital-based case-control study, including 848 patients coexisting with IGM (the case group) and 856 patients with normal glucose tolerance (the control group). Fasting blood sRAGE and esRAGE concentrations were measured in 300 cases and 300 controls. There were significant differences in the genotypes/alleles of T-429C (rs1800625) and T-374A (rs1800624) polymorphisms between the case and control groups after Bonferroni correction (P<0.05/8). Adjusted estimates of above two polymorphisms for IGM risk were remarkably significant, especially under the recessive model (odd ratio [OR], 95% confidence interval [CI], P: 3.57, 1.95-5.18, 0.002 for T-429C and 3.49, 1.42-8.58, 0.007 for T-374A). Mean sRAGE and esRAGE concentrations were significantly higher in controls than in cases (P<0.001). Participants with the rs1800625 -429CC and -429TC genotypes had significantly lower sRAGE (417.3 and 473.6 vs. 502.3pg/mL, P<0.01) and esRAGE (230.1 and 298.0 vs. 340.4pg/mL, P<0.05) concentrations than those with the -429TT genotype in primary hypertensive patients with IGM. Further Mendelian randomization analysis revealed that per 100pg/mL reduction in fasting blood sRAGE and esRAGE was causally associated with 2.40-fold (95% CI: 1.46-3.94) and 2.65-fold (95% CI: 1.24-5.13) increased IGM risk, respectively. Our findings collectively demonstrate that fasting blood sRAGE and esRAGE may be causally implicated in IGM in primary hypertensive patients.

Ultra-small paramagnetic iron oxide nanoprobe targeting EGFR for in vivo MR imaging of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common worldwide cancer that is rising rapidly in incidence. MRI is a powerful non-invasive imaging modality for HCC detection but lack of specific contrast agents limits visualization of small tumors. EGFR is frequently overexpressed in HCC and is a promising target. Peptides have fast binding kinetics, short circulatory half-life, low imaging background, high vascular permeability, and enhanced tissue diffusion for deep tumor penetration. We demonstrate a peptide specific for EGFR labeled with an ultra-small paramagnetic iron oxide (UPIO) nanoparticle with 3.5 nm dimensions to target HCC using T1-weighted MRI. We modified the hydrophobic core with a water dispersible oleic acid coating and capped with PEGylated phospholipids DSPE-PEG and DSPE-PEG-Mal. The EGFR peptide is attached via thioether-mediated conjugation of a GGGSC linker to the maleimide-terminated phospholipids. On in vivo MR images of HCC xenograft tumors, we observed peak nanoprobe uptake at 2 hours post-injection followed by a rapid return to baseline by 24 hours. We measured significantly greater MR signal in tumor with the targeted nanoprobe versus scrambled peptide, blocked peptide, and Gadoteridol. Segmented regions on MR images support rapid renal clearance. No significant difference in animal weight, necropsy, hematology, and chemistry was found between treatment and control groups at one month post-injection. Our nanoprobe based on an EGFR specific peptide labeled with UPIO designed for high stability and biocompatibility showed rapid tumor uptake and systemic clearance to demonstrate safety and promise for clinical translation to detect early HCC.

A comparative study of rank aggregation methods for partial and top ranked lists in genomic applications.

Rank aggregation (RA), the process of combining multiple ranked lists into a single ranking, has played an important role in integrating information from individual genomic studies that address the same biological question. In previous research, attention has been focused on aggregating full lists. However, partial and/or top ranked lists are prevalent because of the great heterogeneity of genomic studies and limited resources for follow-up investigation. To be able to handle such lists, some ad hoc adjustments have been suggested in the past, but how RA methods perform on them (after the adjustments) has never been fully evaluated. In this article, a systematic framework is proposed to define different situations that may occur based on the nature of individually ranked lists. A comprehensive simulation study is conducted to examine the performance characteristics of a collection of existing RA methods that are suitable for genomic applications under various settings simulated to mimic practical situations. A non-small cell lung cancer data example is provided for further comparison. Based on our numerical results, general guidelines about which methods perform the best/worst, and under what conditions, are provided. Also, we discuss key factors that substantially affect the performance of the different methods.

Comparison of perceptual eye positions among patients with different degrees of anisometropia.

The aim of this study is to compare the perceptual eye positions (PEPs) among patients with different degrees of anisometropia.A total of 157 patients were recruited into this retrospective study. A detailed ophthalmic examination was conducted on each patient. The degree of refractive errors in the presence of astigmatism was converted into the degree of spherical equivalent (SE). Patients were divided into 3 groups according to the interocular SE difference: severe anisometropia group with interocular SE difference ≥2.50D, mild anisometropia group with interocular SE difference ≥1.00D and <2.50D, and non-anisometropia group with interocular SE difference <1.00D. The vertical and horizontal PEP were measured by a computer-controlled perceptual examination evaluation system. The results obtained from the 3 groups were compared and analyzed.A total of 157 patients were enrolled including 32 patients in the severe anisometropia group, 37 patients in the mild anisometropia group, and 88 patients in the non-anisometropia group. The quartiles of vertical PEP pixels were as follows: 7.50 (5.00, 16.75) in the severe anisometropia group, 5.00 (2.00, 7.50) in the mild anisometropia group, and 5.00 (3.00, 9.00) in the non-anisometropia group, respectively. The vertical PEP pixel was much higher in the severe anisometropia group than that in the other two groups (P < .05). The quartiles of horizontal PEP pixels were as follows: 27.50 (10.75, 67.50) in the severe anisometropia group, 17.00 (7.00, 54.50) in the mild anisometropia group, and 21.50 (11.00, 60.75) in the non-anisometropia group. There were no statistically significant differences among the 3 groups (P > .05).There was an obvious deviation of vertical PEP in patients with anisometropia ≥2.50D, indicating that the instability of vertical PEP might be associated with the development of severe anisometropia.

Chinese Herbal Formula, Modified Danggui Buxue Tang, Attenuates Apoptosis of Hematopoietic Stem Cells in Immune-Mediated Aplastic Anemia Mouse Model.

A derivative formula, DGBX, which is composed of three herbs (Radix astragali, Radix Angelicae sinensis, and Coptis chinensis Franch), is derived from a famous Chinese herbal formula, Danggui Buxue Tang (DBT) (Radix astragali and Radix Angelicae sinensis). We aimed to investigate the effects of DGBX on the regulation of the balance between proliferation and apoptosis of hematopoietic stem cells (HSCs) due to the aberrant immune response in a mouse model of aplastic anemia (AA). Cyclosporine (CsA), an immunosuppressor, was used as the positive control. Our results indicated that DGBX could downregulate the production of IFNγ in bone marrow cells by interfering with the binding between SLAM and SAP and the expressions of Fyn and T-bet. This herbal formula can also inhibit the activation of Fas-mediated apoptosis, interferon regulatory factor-1-induced JAK/Stat, and eukaryotic initiation factor 2 signaling pathways and thereby induce proliferation and attenuate apoptosis of HSCs. In conclusion, DGBX can relieve the immune-mediated destruction of HSCs, repair hematopoietic failure, and recover the hematopoietic function of HSCs in hematogenesis. Therefore, DGBX can be used in traditional medicine against AA as a complementary and alternative immunosuppressive therapeutic formula.

The role of methionine on metabolism, oxidative stress, and diseases.

Methionine is an aliphatic, sulfur-containing, essential amino acid, and a precursor of succinyl-CoA, homocysteine, cysteine, creatine, and carnitine. Recent research has demonstrated that methionine can regulate metabolic processes, the innate immune system, and digestive functioning in mammals. It also intervenes in lipid metabolism, activation of endogenous antioxidant enzymes such as methionine sulfoxide reductase A, and the biosynthesis of glutathione to counteract oxidative stress. In addition, methionine restriction prevents altered methionine/transmethylation metabolism, thereby decreasing DNA damage and carcinogenic processes and possibly preventing arterial, neuropsychiatric, and neurodegenerative diseases. This review focuses on the role of methionine in metabolism, oxidative stress, and related diseases.

Exosomes derived from bone marrow stromal cells decrease the sensitivity of leukemic cells to etoposide.

The aim of the study was to investigate the effect of exosomes derived from bone marrow stromal cells (BM-SCs) on the chemoresistant characteristics of nalm-6 cells treated with etoposide (VP16). The present study isolated exosomes from BM-SC-conditioned medium by using standard differential centrifugation steps and detected the expression of 70 kilodalton heat shock proteins (HSP70) and lysosomal-associated membrane protein 3 (CD63) in exosomes by western blot analysis. Nalm-6 cells were co-cultured with exosomes in the presence of VP16. Cell viability and apoptosis were then detected using the Cell Counting Kit-8 method and Annexin-V/propidium iodide, respectively. Finally, protein levels of B-cell lymphoma 2 (BCL-2), BCL-2-like protein 4 (BAX), caspase-3, and poly ADP-ribose polymerase (PARP) were examined by western blot analysis. Exosomes were successfully isolated from the conditioned medium and confirmed by the expression of HSP70 and CD63. BM-SC-derived exosomes increased the viability of nalm-6 cells in the presence of VP16 and inhibited the apoptosis induced by VP16. Western blot analysis results showed that exosomes can block the significant reduction of BCL-2, full-length caspase-3 and full-length PARP, while preventing the increase of BAX, cleaved caspase-3 and cleaved PARP induced by VP16. Exosomes derived from BM-SCs can protect nalm-6 cells from VP16-induced apoptosis to maintain their survival and induce resistance to VP16. In addition, BCL-2/BAX, caspase-3, and PARP may be involved in the mechanism of exosome-induced drug resistance.

Glycoprotein A repetitions predominant (GARP) positively regulates transforming growth factor (TGF) β3 and is essential for mouse palatogenesis.

Glycoprotein A repetitions predominant (GARP) (encoded by the Lrrc32 gene) plays important roles in cell-surface docking and activation of TGF-beta. However, GARP role in organ development in mammalian system is unclear. To determine the function of GARP in vivo, we generated a GARP-KO mouse model. Unexpectedly, the GARP-KO mice died within 24 hours after birth and exhibited defective palatogenesis without apparent abnormalities in other major organs. Furthermore, we observed decreased apoptosis and SMAD2 phosphorylation in the medial edge epithelial (MEE) cells of the palatal shelf of GARP-KO embryos at day 14.5 (E14.5), indicating a defect in the TGF-beta signaling pathway in the GARP-null developing palates. Of note, the failure to develop the secondary palate and concurrent reduction of SMAD phosphorylation without other defects in the GARP-KO mice phenocopied TGF-beta 3-KO mice, although GARP has not been previously suggested to interact with TGF-beta 3. We found that GARP and TGF-beta 3 co-localize in MEE cells at E14.5. In vitro studies confirmed that GARP and TGF-beta 3 directly interact and that GARP is indispensable for the surface expression of membrane-associated latent TGF-beta 3. Our findings indicate that GARP is essential for normal morphogenesis of the palate and demonstrate that GARP plays a crucial role in regulating TGF-beta 3 signaling during embryogenesis. In conclusion, we have uncovered a novel function of GARP in positively regulating TGF-beta 3 activation and function.

Metabolomics differences between silkworms (Bombyx mori) reared on fresh mulberry (Morus) leaves or artificial diets.

Silkworms (Bombyx mori) reared on artificial diets have great potential applications in sericulture. However, the mechanisms underlying the enhancement of metabolic utilization by altering silkworm nutrition are unclear. The aim of this study was to investigate the mechanisms responsible for the poor development and low silk protein synthesis efficiency of silkworms fed artificial diets. After multi-generational selection of the ingestive behavior of silkworms to artificial diets, we obtained two strains, one of which developed well and another in which almost all its larvae starved to death on the artificial diets. Subsequently, we analyzed the metabolomics of larval hemolymph by gas chromatography/liquid chromatography-mass spectrometry, and the results showed that vitamins were in critically short supply, whereas the nitrogen metabolic end product of urea and uric acid were enriched substantially, in the hemolymph of the silkworms reared on the artificial diets. Meanwhile, amino acid metabolic disorders, as well as downregulation of carbohydrate metabolism, energy metabolism, and lipid metabolism, co-occurred. Furthermore, 10 male-dominant metabolites and 27 diet-related metabolites that differed between male and female silkworms were identified. These findings provide important insights into the regulation of silkworm metabolism and silk protein synthesis when silkworms adapt to an artificial diet.

Hemoglobin level, a prognostic factor for nasal extranodal natural killer/T-cell lymphoma patients from stage I to IV: A validated prognostic nomogram.

Although nasal extranodal natural killer/T-cell lymphoma (nasal ENKL) shares some prognostic factors with other lymphomas, seldom studies had explored the prognostic value of hemoglobin. The ENKL cases in stage I-IV during 2000 to 2015 were collected from two medical centers (group A, n = 192), and were randomly divided into the group B (n = 155) and C (n = 37). Although the significant factors identified by the univariate analysis differed between the group A and B, the multivariate Cox regression indicated the same factors. C-index of the model was slightly better than Yang's, but its integrated Brier score (IBS) was obviously lower than Yang's both in the group A and B. Additionally, minimal depth of random survival forest (RSF) classifier confirmed that the prognostic ability of hemoglobin was better than age both in the group A and B. In the calibration of the nomogram, the predicted 3-year or 5-year OS of our nomogram well agreed with the corresponding actual OS. In conclusion, Hemoglobin is a prognostic factor for nasal ENKL patients in stage I - IV, and integrating it into a validated prognostic nomogram, whose generalization error is the smallest among the evaluated models, can be used to predict the patients' outcome.

Effects of Cyclin D1 Gene Silencing on cell Proliferation, cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells.

This study aims to investigate the effects of Cyclin D1 silencing on cell cycle, cell proliferation and apoptosis of hepatocellular carcinoma cells (HCC). Cells were divided into the blank group, negative control group (HCC cells transfected with control shRNA), Cyclin D1 shRNA group (HCC cells transfected with Cyclin D1 shRNA) and the normal group (human normal liver L-02 cells). Expressions of Cyclin D1, Caspase-3, Bcl-2 and C-myc were detected by RT-qPCR and Western blotting. Cell proliferation was detected by Cell Counting Kit-8. Cell cycle and apoptosis were detected by flow cytometry. Tumor xenograft in nude mice was performed to detect in vivo tumorigenesis. HCC tissues and HCC cells exhibited elevated expression levels of Cyclin D1. Cyclin D1 expression levels was found to be correlated with tumor size and tumor staging.Compared with the normal group, the blank group showed enhanced cell proliferation, a reduction in the amount of cells in G0/G1 phase, increased number cells in S and G2/M phase, reduced apoptosis, elevated expressions of Cyclin D1, Bcl-2 and C-myc, decreased Caspase-3 activity and significant tumorigenicity. In comparison with the blank group, the Cyclin D1 shRNA group revealed weakened cell proliferation, reduced cells in S and G2/M phase, increased cells in G0/G1 phase, increased Annexin V positive cell ratio, decreased expression of Cyclin D1, Bcl-2 and C-myc, elevated Caspase-3 activity and inhibited tumorigenicity. In conclusion, Cyclin D1 gene silencing suppresses cell proliferation and inhibits cell apoptosis, which may be a new target approach in the treatment and management for HCC.This article is protected by copyright. All rights reserved.

Interleukin-24 Concentrations Not Related with Age, but Affect Pro- and Anti-Inflammatory Cytokines Differently in Healthy Donors.

Interleukin 24 (IL-24) is expressed at different levels in a variety of tumor tissues and matched normal tissues and is regarded as a potential tumor biomarker as its expression levels in tumor tissues are associated with tumor patient prognosis. At present, the expression level of IL-24 in healthy human peripheral blood is unknown.

Wip1 Deficiency Promotes Neutrophil Recruitment to the Infection Site and Improves Sepsis Outcome.

Sepsis is defined as an uncontrolled host response to infection, and no specific therapy or drugs have been used in clinical trials currently. Discovering new therapeutic targets for sepsis treatment has always been a central problem in the field of sepsis research. Neutrophils stand at the first line in controlling infection and have been identified to be dysregulated with impaired migration and antimicrobial function during sepsis. Based on our previous results on demonstrating wild-type p53-induced phosphatase 1 in controlling neutrophil development, we explored the possible relationship among Wip1, neutrophils, and sepsis in the present study. Wip1-deficient mice exhibited improved outcomes in cecal ligation and puncture (CLP)-induced sepsis model with enhanced bacterial clearance and less multi-organ damage. The protection seen in Wip1 KO mice was mainly due to an increased accumulation of neutrophils in the primary infectious locus mediated by the decreased internalization of CXCR2, as well as by an increased antimicrobial function. Additionally, we also identified a negative correlation between CXCR2 and Wip1 in human neutrophils during sepsis. Pharmacological inhibition of Wip1 with its inhibitor can also prevent the internalization of CXCR2 on human neutrophils treated with lipopolysaccharides in vitro and significantly improve the outcome in CLP-induced sepsis model. Taken together, our results demonstrate that Wip1 can negatively regulate neutrophil migration and antimicrobial immunity during sepsis and inhibition of Wip1 can be a potential therapeutic target for sepsis treatment.

The light cycle controls the hatching rhythm in Bombyx mori via negative feedback loop of the circadian oscillator.

Hatching behavior is a key target in silkworm (Bombyx mori) rearing, especially for the control of Lepidoptera pests. According to previous research, hatching rhythms appear to be controlled by a clock mechanism that restricts or "gates" hatching to a particular time. However, the underlying mechanism remains elusive. Under 12-h light:12-h dark photoperiod (LD) conditions, the transcriptional levels of the chitinase5 (Cht5) and hatching enzyme-like (Hel) genes, as well as the enzymatic activities of their gene products, oscillated in time with ambient light cycles, as did the transcriptional levels of the cryptochrome 1, cryptochrome 2, period (per), and timeless genes, which are key components of the negative feedback loop of the circadian rhythm. These changes were related to the expression profile of the ecdysteroid receptor gene and the hatching behavior of B. mori eggs. However, under continuous light or dark conditions, the hatching behavior, the expression levels of Cht5 and Hel, as well as the enzymatic activities of their gene products, were not synchronized unlike under LD conditions. In addition, immunohistochemistry experiments showed that light promoted the translocation of PER from the cytoplasm to the nucleus. In conclusion, LD cycles regulate the hatching rhythm of B. mori via negative feedback loop of the circadian oscillator.

Online monitoring of astragaloside II metabolism using a homemade cultural device coupled with microdialysis and ultra-performance liquid chromatography-mass spectrometry.

A new system was described for the online monitoring of astragaloside II (AII) metabolism in intestinal microbial community. The system was based on a homemade cultural device coupled with microdialysis (MD) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Main improvements include a simplified anaerobic incubator enabling the experiment to be conducted in ambient atmosphere, continuous sampling, and decreased matrix effect. Importantly, our method distinctly decreases the interference of small molecules by adding 20mgml(-1) of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) to the perfusion fluid. Using the developed method, the metabolism of AII in intestinal bacteria was successfully investigated. Results were then compared with those obtained by conventional incubation and sampling method. We found that the integrated experimental system maintained the proper fermentation environment for bacteria and enabled high chromatography performance. With the advantages of auto-sampling, online detection, non-requirement of expensive fermenting equipment, and negligible matrix interference, the method can greatly contribute to the investigation of the dynamic biotransformation of astragalosides in complicated matrix-based biological samples.

Mycobacterium tuberculosis Major Facilitator Superfamily Transporters.

The cell membrane or biofilm serve as permeable barrier for xenobiotics to maintain the homeostasis of cells or bacterial community. Transport systems are essential for the uptake of nutrients and substances necessary for biofilm formation, efflux of deleterious compounds, as well as communication between cells and environment. Major facilitator superfamily (MFS) represents the largest secondary transporter family and is responsible for the transport of a broad spectrum of substrates with diverse physiochemical properties by utilizing the energy stored in electrochemical gradient across the membrane. Importantly, multidrug efflux pumps belonging to the major facilitator superfamily are important contributing factors to drug resistance and biofilm formation in many clinical strains like Mycobacterium tuberculosis. This review summarized the structural properties and functions of M. tuberculosis MFS transporters, molecular mechanisms of substrates transfer, and efflux pump inhibitors for better control of biofilm-associated infections.

Performance and extracellular polymers substance analysis of a pilot scale anaerobic membrane bioreactor for treating tetrahydrofuran pharmaceutical wastewater at different HRTs.

Tetrahydrofuran (THF) is one of the most representative characteristics of pollutant in pharmaceutical industry usually has high biological toxicity, making it difficult to treat. In this study, a pilot scale anaerobic membrane bioreactor (AnMBR) was employed to treat THF pharmaceutical wastewater under different hydraulic retention time (HRT). During the 80-day operating time, chemical oxygen demand (COD) and THF removal efficiencies reached 95.3% and 98.5% when HRT was above 24h. Mixed liquid suspended solids (MLSS) and mixed liquor volatile suspended solids (MLVSS) in the attached sludge on membrane surface showed a trend of rising on first 28days (48h-36h) and then decreasing. Protein is the major component of extracellular polymeric substances (EPS) independent of changes in HRT. The study concludes that THF pharmaceutical wastewater can be effectively remedied in the AnMBR system at low HRT.

A Multiview Learning Framework With a Linear Computational Cost.

Learning features from multiple views has attracted much research attention in different machine learning tasks, such as multiclass and multilabel classification problems. In this paper, we propose a multiclass multilabel multiview learning framework with a linear computational cost where an example is associated with at least one label and represented by multiple information sources. We simultaneously analyze all features by learning an integrated projection matrix. We can also automatically select more important views for subsequent classifier to predict each class. As the proposed objective function is nonsmooth and difficult to solve, we apply a novel optimization method that converts the multiview learning problem to a set of linear single-view learning problems by bridging our problem to an easily solvable approach. Compared to the conventional methods which learn the entire projection matrix, our algorithm independently optimizes each column of the projection matrix for each class, which can be easily parallelized. In each column optimization, the most computationally intensive step is pure and simple matrix-by-vector multiplication. As a result, our algorithm is much more applicable to large-scale problems than the multiview learning methods with a nonlinear computational cost. Moreover, rigorous convergence proof of the proposed algorithm is also provided. To evaluate the effectiveness of the proposed approach, experimental comparisons are made with state-of-the-art algorithms in multiclass and multilabel classification tasks on many multiview benchmarks. We also report the efficiency comparison results on different numbers of data samples. The experimental results demonstrate that our algorithm can achieve superior performance to all the compared algorithms.

Secreted frizzled-related protein 5 protects against oxidative stress-induced apoptosis in human aortic endothelial cells via downregulation of Bax.

This study was undertaken to determine the role of secreted frizzled-related protein 5 (SFRP5) in endothelial oxidative injury. Human aortic endothelial cells (HAECs) were exposed to different oxidative stimuli and examined for SFRP5 expression. The effects of SFRP5 overexpression and knockdown on cell viability, apoptosis, and reactive oxygen species production were measured. HAECs treated with angiotensin (Ang) II (1 μM) or oxidized low-density lipoprotein (oxLDL) (150 μg/mL) showed a significant increase in SFRP5 expression. Overexpression of SFRP5 significantly attenuated the viability suppression and apoptosis induction by Ang II and oxLDL, whereas the knockdown of SFRP5 exerted opposite effects. Overexpression of SFRP5 prevented ROS formation and β-catenin activation and reduced Bax expression. Co-expression of Bax significantly reversed the anti-apoptotic effect of SFRP5 overexpression, whereas knockdown of Bax restrained Ang II- and oxLDL-induced apoptosis in HAECs. Taken together, SFRP5 confers protection against oxidative stress-induced apoptosis through inhibition of β-catenin activation and downregulation of Bax.

Performance of HADDOCK and a simple contact-based protein-ligand binding affinity predictor in the D3R Grand Challenge 2.

We present the performance of HADDOCK, our information-driven docking software, in the second edition of the D3R Grand Challenge. In this blind experiment, participants were requested to predict the structures and binding affinities of complexes between the Farnesoid X nuclear receptor and 102 different ligands. The models obtained in Stage1 with HADDOCK and ligand-specific protocol show an average ligand RMSD of 5.1 Å from the crystal structure. Only 6/35 targets were within 2.5 Å RMSD from the reference, which prompted us to investigate the limiting factors and revise our protocol for Stage2. The choice of the receptor conformation appeared to have the strongest influence on the results. Our Stage2 models were of higher quality (13 out of 35 were within 2.5 Å), with an average RMSD of 4.1 Å. The docking protocol was applied to all 102 ligands to generate poses for binding affinity prediction. We developed a modified version of our contact-based binding affinity predictor PRODIGY, using the number of interatomic contacts classified by their type and the intermolecular electrostatic energy. This simple structure-based binding affinity predictor shows a Kendall's Tau correlation of 0.37 in ranking the ligands (7th best out of 77 methods, 5th/25 groups). Those results were obtained from the average prediction over the top10 poses, irrespective of their similarity/correctness, underscoring the robustness of our simple predictor. This results in an enrichment factor of 2.5 compared to a random predictor for ranking ligands within the top 25%, making it a promising approach to identify lead compounds in virtual screening.

Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection.

Severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-like coronavirus are a potential threat to global health. However, reviews of the long-term effects of clinical treatments in SARS patients are lacking. Here a total of 25 recovered SARS patients were recruited 12 years after infection. Clinical questionnaire responses and examination findings indicated that the patients had experienced various diseases, including lung susceptibility to infections, tumors, cardiovascular disorders, and abnormal glucose metabolism. As compared to healthy controls, metabolomic analyses identified significant differences in the serum metabolomes of SARS survivors. The most significant metabolic disruptions were the comprehensive increase of phosphatidylinositol and lysophospha tidylinositol levels in recovered SARS patients, which coincided with the effect of methylprednisolone administration investigated further in the steroid treated non-SARS patients with severe pneumonia. These results suggested that high-dose pulses of methylprednisolone might cause long-term systemic damage associated with serum metabolic alterations. The present study provided information for an improved understanding of coronavirus-associated pathologies, which might permit further optimization of clinical treatments.

Vitellogenin regulates antimicrobial responses in Chinese mitten crab, Eriocheir sinensis.

Vitellogenin (Vtg) is traditionally regarded as a key supplier of nutrients and energy during the early development of embryos and larvae, but accumulating evidence suggests that Vtg is also involved in innate immune defense. Whether Vtg is involved in innate immunity in Eriocheir sinensis, and its functions, remain largely unknown. In this study, a cDNA representing the vitellogenin1 gene from E. sinensis (Es-vtg1) was cloned. The full-length Es-vtg1 cDNA comprised 7939 nucleotides, encoding an open-reading frame of 2567 amino acid residues. Bioinformatic analysis showed that the domains of Es-Vtg1 have been conserved during evolution. Quantitative real-time PCR and western blotting showed that Es-vtg1 was highly expressed in ovary and hepatopancreas. Moreover, bacteria could induce the high-level expression of Es-Vtg1. Es-Vtg1 plays important roles in immunological defense, including binding to bacteria, inhibiting bacterial proliferation, and regulating the expression of antimicrobial peptides. Collectively, these results demonstrate that Es-Vtg1 plays critical roles in antimicrobial function.

Nature, Nurture, and Cancer Risks: Genetic and Nutritional Contributions to Cancer.

It is speculated that genetic variants are associated with differential responses to nutrients (known as gene-diet interactions) and that these variations may be linked to different cancer risks. In this review, we critically evaluate the evidence across 314 meta-analyses of observational studies and randomized controlled trials of dietary risk factors and the five most common cancers (breast, lung, prostate, colorectal, and stomach). We also critically evaluate the evidence across 13 meta-analyses of observational studies of gene-diet interactions for the same cancers. Convincing evidence for association was found only for the intake of alcohol and whole grains in relation to colorectal cancer risk. Three nutrient associations had highly suggestive evidence and another 15 associations had suggestive evidence. Among the examined gene-diet interactions, only one had moderately strong evidence.

Scallop genome provides insights into evolution of bilaterian karyotype and development.

Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology.