An iron-base oxygen-evolution electrode for high-temperature electrolyzers.

High-temperature molten-salt electrolyzers play a central role in metals, materials and chemicals production for their merit of favorable kinetics. However, a low-cost, long-lasting, and efficient high-temperature oxygen evolution reaction (HT-OER) electrode remains a big challenge. Here we report an iron-base electrode with an in situ formed lithium ferrite scale that provides enhanced stability and catalytic activity in both high-temperature molten carbonate and chloride salts. The finding is stemmed from a discovery of the ionic potential-stability relationship and a basicity modulation principle of oxide films in molten salt. Using the iron-base electrode, we build a kiloampere-scale molten carbonate electrolyzer to efficiently convert CO2 to carbon and oxygen. More broadly, the design principles lay the foundations for exploring cheap, Earth-abundant, and long-lasting HT-OER electrodes for electrochemical devices with molten carbonate and chloride electrolytes.

Effect of hydrogen sulphide on inflammatory factors of the mitochondria after limb ischaemia-reperfusion injury in rats.

The goal of this study was to evaluate the effect of hydrogen sulphide on inflammatory factors and the energy metabolism of mitochondria after limb reperfusion injury in rats. Sixty Wistar rats were divided into three groups: the sham operated group, the control group (the ischaemia-reperfusion injury [IRI] + normal saline group), and the experimental group (the IRI + H2 S group). An experimental rat model of limb IRI was established. Skeletal muscle samples were collected to observe the content of necrotic products (including myoglobin (MB), lysophosphatidylcholine (LPC), and lipid peroxidation (LPO)); blood samples were collected to observe changes in the contents of interleukin-1 (IL-1), Interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α); and the mitochondria of skeletal muscle cells were extracted for mitochondrial transmembrane potential measurement and adenosine triphosphate (ATP) content determination. The results underwent further statistical analysis. The contents of MB, LPC, and LPO in the limb skeletal muscle, liver, lung, and kidney tissues of rats in the control group were significantly increased (P < 0.05) after IRI, which was markedly attenuated by treatment with hydrogen sulphide (P < 0.05). Ischaemia/reperfusion of the lower extremities in rats triggered a significant increase in serum levels of IL-1, IL-6, and TNF-α, which was significantly inhibited by treatment with H2 S during ischaemia/reperfusion. In addition, the inhibitory effect tended to be time-dependent. After limb ischaemia/reperfusion, the mitochondrial transmembrane potential of skeletal muscle cells in the control group decreased significantly (P < 0.05), while the potential energy of the mitochondrial membrane in the experimental group was significantly higher than that in the control group (P < 0.05). The content of ATP in mitochondria of skeletal muscle cells of ischaemia-reperfusion rats in the control group was significantly lower than that in the sham operated group (P < 0.05), while the content of ATP of mitochondria in the experimental group after H2 S treatment was significantly higher than the control group (P < 0.05). Hydrogen sulphide can alleviate the injury of skeletal muscle and distal organs after limb ischaemia-reperfusion and reduce local inflammatory reaction, which is essential in alleviating mitochondrial transmembrane potential and energy metabolism disorder during reperfusion injury. The purpose of the study is to summarise the available information and provide theoretical support for the application of hydrogen sulphide in the treatment of limb IRI in skeletal muscle and distal organs.

IL-27 gene therapy induces depletion of Tregs and enhances the efficacy of cancer immunotherapy.

Tumor-induced expansion of Tregs is a significant obstacle to cancer immunotherapy. However, traditional approaches to deplete Tregs are often inefficient, provoking autoimmunity. We show here that administration of IL-27-expressing recombinant adeno-associated virus (AAV-IL-27) significantly inhibits tumor growth and enhances T cell responses in tumors. Strikingly, we found that AAV-IL-27 treatment causes rapid depletion of Tregs in peripheral blood, lymphoid organs, and - most pronouncedly - tumor microenvironment. AAV-IL-27-mediated Treg depletion is dependent on IL-27 receptor and Stat1 in Tregs and is a combined result of CD25 downregulation in Tregs and inhibition of IL-2 production by T cells. In combination with a GM-CSF vaccine, AAV-IL-27 treatment not only induced nearly complete tumor rejection, but also resulted in amplified neoantigen-specific T cell responses. AAV-IL-27 also dramatically increased the efficacy of anti-PD-1 therapy, presumably due to induction of PD-L1 in T cells and depletion of Tregs. Importantly, AAV-IL-27 therapy did not induce significant adverse events, partially due to its induction of IL-10. In a plasmacytoma mouse model, we found that IL-10 was required for AAV-IL-27-mediated tumor rejection. Thus, our study demonstrates the potential of AAV-IL-27 as an independent cancer therapeutic and as an efficient adjuvant for cancer immunotherapy.

MiR-29b reverses oxaliplatin-resistance in colorectal cancer by targeting SIRT1.

Oxaliplatin is a commonly used chemotherapeutic drug for the treatment of advanced colorectal cancer. However, acquired drug resistance against oxaliplatin remains a major obstacle for efficient use of it, and mechanisms underlying oxaliplatin resistance are still required to be explored. In the present study, we exposed colorectal cancer cell line SW480 to oxaliplatin for a long time to obtain oxaliplatin-resistant colorectal cancer cell model (OR-SW480). We found that intracellular expression of miR-29b was decreased when the SW480 cells became oxaliplatin-resistant. More importantly, overexpression of miR-29b resensitized OR-SW480 cells to oxaliplatin treatment. Mechanically, gene of SIRT1 was identified to be the target of miR-29b. Overexpression of miR-29b in oxaliplatin-treated OR-SW480 decreased the expression of SIRT1 to enhance the ROS production and JNK phosphorylation, and thus promoting apoptosis via activation of caspase 9, 7 and 3. On the other hand, expression plasmid of SIRT1, N-acetyl cysteine or SP600125 (JNK specific inhibitor) abolished the effect of miR-29b on oxaliplatin-treated OR-SW480. We therefore demonstrated that miR-29b reverses oxaliplatin-resistance in colorectal cancer by targeting SIRT1/ROS/JNK pathway.

Effect of icariin on fracture healing in an ovariectomized rat model of osteoporosis.

Osteoporosis is frequently asymptomatic, presenting a significant clinical and economic burden, particularly following an osteoporosis-associated fracture. Icariin has been reported to inhibit osteoporosis in vitro, and the present study investigated whether icariin also promoted bone fracture healing in ovariectomized osteoporotic (OVX) rats in vivo. A total of 30 female rats were randomly divided into three groups (n=10 per group): i) Sham surgery; ii) OVX; and iii) OVX with icariin (OVX + ICA) groups. At 3 months after the ovariectomy, a unilateral cross-tibia fracture was made at the proximal right tibia. Animals were then sacrificed after 5 weeks of oral treatment. X-rays were taken at 1 week, 3 weeks and 5 weeks of treatment, and dual energy X-ray absorptiometry was used to measure the bone mineral density (BMD). Changes to the osteocalcin (BGLAP), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and estradiol levels in blood were measured. Callus formation and bone union were observed, the BMD was significantly higher and the BGLAP, ALP and TRAP levels were reduced, but no significant increase was observed in the blood estradiol level in the OVX + ICA group compared with the OVX group. The present findings indicate that icariin has potential as a novel alternative therapeutic agent for fracture healing in postmenopausal osteoporosis.

SPDEF inhibits prostate carcinogenesis by disrupting a positive feedback loop in regulation of the Foxm1 oncogene.

SAM-pointed domain-containing ETS transcription factor (SPDEF) is expressed in normal prostate epithelium. While its expression changes during prostate carcinogenesis (PCa), the role of SPDEF in prostate cancer remains controversial due to the lack of genetic mouse models. In present study, we generated transgenic mice with the loss- or gain-of-function of SPDEF in prostate epithelium to demonstrate that SPDEF functions as tumor suppressor in prostate cancer. Loss of SPDEF increased cancer progression and tumor cell proliferation, whereas over-expression of SPDEF in prostate epithelium inhibited carcinogenesis and reduced tumor cell proliferation in vivo and in vitro. Transgenic over-expression of SPDEF inhibited mRNA and protein levels of Foxm1, a transcription factor critical for tumor cell proliferation, and reduced expression of Foxm1 target genes, including Cdc25b, Cyclin B1, Cyclin A2, Plk-1, AuroraB, CKS1 and Topo2alpha. Deletion of SPDEF in transgenic mice and cultures prostate tumor cells increased expression of Foxm1 and its target genes. Furthermore, an inverse correlation between SPDEF and Foxm1 levels was found in human prostate cancers. The two-gene signature of low SPDEF and high FoxM1 predicted poor survival in prostate cancer patients. Mechanistically, SPDEF bound to, and inhibited transcriptional activity of Foxm1 promoter by interfering with the ability of Foxm1 to activate its own promoter through auto-regulatory site located in the -745/-660 bp Foxm1 promoter region. Re-expression of Foxm1 restored cellular proliferation in the SPDEF-positive cancer cells and rescued progression of SPDEF-positive tumors in mouse prostates. Altogether, SPDEF inhibits prostate carcinogenesis by preventing Foxm1-regulated proliferation of prostate tumor cells. The present study identified novel crosstalk between SPDEF tumor suppressor and Foxm1 oncogene and demonstrated that this crosstalk is required for tumor cell proliferation during progression of prostate cancer in vivo.

Association between glutathione S-transferase M1 null genotype and risk of gallbladder cancer: a meta-analysis.

Glutathione S-transferases (GSTs) are a family of enzymes which are involved in the detoxification of potential carcinogens. Glutathione S-transferase M1 (GSTM1) null genotype can impair the enzyme activity of GSTs and is suspected to increase the susceptibility to gallbladder cancer. Previous studies investigating the association between GSTM1 null genotype and risk of gallbladder cancer reported inconsistent findings. To quantify the association between GSTM1 null genotype and risk of gallbladder cancer, we performed a meta-analysis of published studies. We searched PubMed, Embase, and Wanfang databases for all possible studies. We estimated the pooled odds ratio (OR) with its 95% confidence interval (95% CI) to assess the association. Meta-analysis of total included studies showed that GSTM1 null genotype was not associated with gallbladder cancer risk (OR = 1.13, 95% CI 0.88-1.46, P = 0.332). Subgroup analysis by ethnicity showed that there was no association between GSTM1 null genotype and risk of gallbladder cancer in both Caucasians and Asians. However, meta-analysis of studies with adjusted estimations showed that GSTM1 null genotype was associated with increased risk of gallbladder cancer (OR = 1.46, 95% CI 1.02-2.09, P = 0.038). Thus, this meta-analysis shows that GSTM1 null genotype is likely to be associated with risk of gallbladder cancer. More studies with well design and large sample size are needed to further validate the association between GSTM1 null genotype and gallbladder cancer.

Significant association between MTHFR C677T polymorphism and hepatocellular carcinoma risk: a meta-analysis.

Previous studies investigated the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and hepatocellular carcinoma risk, but the impact of MTHFR C677T polymorphism on hepatocellular carcinoma was still unclear, owing to the obvious inconsistence from those studies. This study aimed to quantify the strength of the association between MTHFR C677T polymorphism and hepatocellular carcinoma risk by performing a meta-analysis. We searched the PubMed and Wanfang databases for studies on the association between MTHFR C677T polymorphism and hepatocellular carcinoma risk. We estimated the pooled odds ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the association. Fifteen studies with 8,625 participants were finally included into the meta-analysis. Meta-analyses of total 15 studies suggested that MTHFR C677T polymorphism was significantly associated with an increased risk of hepatocellular carcinoma under two main genetic models (for TT versus CC, OR = 1.19, 95% CI 1.03-1.37, P = 0.016; for TT versus CT/CC, OR = 1.14, 95% CI 1.01-1.28, P = 0.032). Subgroup meta-analyses suggested that MTHFR C677T polymorphism was associated with an increased risk of hepatocellular carcinoma in Asians, but not in Caucasians. Thus, individuals with homozygote genotype TT of MTHFR C677T have obviously increased risk of hepatocellular carcinoma.

Transcriptional regulatory network and protein-protein interaction to reveal the mechanism of pancreatic cancer.

The development of pancreatic cancer (PC) may involve the over-expression of oncogenes, inactivation tumor suppressor genes or the deregulation of various signaling proteins. Thus identification and analysis of transcriptional regulatory relationship as well as protein-protein interaction (PPI) in PC to provide deep insights into the pathogenetic mechanism of pancreatic cancer. In this study, we downloaded the gene expression profile of PC from Gene Expression Omnibus and identified differentially expressed genes (DEGs) in PC patients compared with controls. To further understand how these DEGs act together to account for the initiation of pancreatic cancer, a transcriptional regulatory network was constructed to find the notes for GO function and KEGG pathways annotation, aiming to explore the clusters and pathways in PC. A total of 1,821 transcriptional regulatory relationships were identified. Then, a PPI network was constructed and noted by GO and KEGG, and some special modules, clusters and pathways were identified to involved in PC. Finally, we constructed the transcriptional regulatory network and PPI network of pancreatic cancer. Comparing the pathways involved in Transcriptional regulatory network and PPI network, pathway in cancer, PC, p53 signaling pathway, Hematopoietic cell lineage and graft-versus-host disease co-existed in these two network, so we predict these pathways may play key factors in development of cancer.

Reduction of polyhedrin mRNA and protein expression levels in Sf9 and Hi5 cell lines, but not in Sf21 cells, infected with Autographa californica multiple nucleopolyhedrovirus fp25k mutants.

During cell infection, the fp25k gene of baculoviruses frequently mutates, producing the few polyhedra (FP) per cell phenotype with reduced polyhedrin (polh) expression levels compared with wild-type baculoviruses. Here we report that the fp25k gene of the model baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), contains two hypermutable seven-adenine (A7) mononucleotide repeats (MNRs) that were mutated to A8 MNRs and a TTAA site that had host DNA insertions, producing fp25k mutants during Sf21 cell infection. The FP phenotype in Sf9 and Hi5 cells was more pronounced than in Sf21 cells. AcMNPV fp25k mutants produced similar levels of polyhedra or enhanced GFP, which were both under the control of the AcMNPV polh promoter for expression, in Sf21 cells but lower levels in Sf9 and Hi5 cells compared with AcMNPV with an intact fp25k gene. This correlated with the polh mRNA levels detected in each cell line. The majority of Sf21 cells infected with fp25 mutants showed high polh promoter-mediated GFP expression levels. Two cell lines subcloned from Sf21 cells that were infected with fp25k mutants showed different GFP expression levels. Furthermore, a small proportion of Hi5 cells infected with fp25k mutants showed higher production of polyhedra and GFP expression than the rest, and the latter was not correlated with increased m.o.i. Therefore, these data suggest that AcMNPV polh promoter-mediated gene expression activities differ in the three cell lines and are influenced by different cells within the cell line.

Cell-dependent production of polyhedra and virion occlusion of Autographa californica multiple nucleopolyhedrovirus fp25k mutants in vitro and in vivo.

Members of the family Baculoviridae are insect-specific dsDNA viruses that have been used for biological control of insect pests in agriculture and forestry, as well as in research and pharmaceutical protein expression in insect cells and larvae. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is the type species of the family Baculoviridae. During infection of AcMNPV in permissive cells, fp25k mutants are positively selected, leading to the formation of the few polyhedra (FP) phenotype with reduced yield of polyhedra and reduced virion occlusion efficiency, which leads to decreased oral infectivity for insects. Here we report that polyhedra of AcMNPV fp25k mutants produced from different insect cell lines and insects have differences in larval per os infectivity, and that these variations are due to different virion occlusion efficiencies in these cell lines and insects. Polyhedra of AcMNPV fp25k mutants produced from Sf cells (Sf21 and Sf9, derived from Spodoptera frugiperda) and S. frugiperda larvae had poorer virion occlusion efficiency than those from Hi5 cells (derived from Trichoplusia ni) and T. ni larvae, based on immunoblots, DNA isolation and larval oral infection analysis. AcMNPV fp25k mutants formed clusters of FP and many polyhedra (MP) in the fat body cells of both T. ni and S. frugiperda larvae. Transmission electron microscopy revealed that the nature of virion occlusion of AcMNPV fp25k mutants was dependent on the different cells of the T. ni fat body tissue. Taken together, these results indicate that the FP phenotype and virion occlusion efficiency of fp25k mutants are influenced by the host insect cells.

Short-term clinical outcomes of 42 cases of arthroscopic meniscectomy for discoid lateral meniscus tears.

Discoid lateral meniscus of the knee causes a high morbidity in China. Since the traditional treatment to open the capsule and resect the meniscus often results in arthritis, it is now believed that a discoid lateral meniscus should be treated with arthroscopy to preserve part of the meniscus. The current study aimed to investigate the short-term clinical outcomes of arthroscopic meniscectomy for the treatment of discoid lateral meniscus tears. In the present study, we diagnosed and treated 42 patients (47 knees) with discoid lateral meniscus tears using arthroscopy between February, 2007 and December, 2010. Thirty-seven knees received partial resection of the discoid meniscus, 8 received hypo-complete resection and 2 received complete resection. Thirty-nine of the patients were followed up for a mean of 21 months (ranging from 9 to 53 months). The Lysholm scoring system was used to assess the knee function prior to surgery and during the follow-up. The results were analyzed using a Student's t-test with SPSS 12.0. Our study showed that patients with treated knees returned to normal activities within 4-6 weeks, and knee functions were more improved at 9 months after operation than 3 months, as measured by the Lysholm score (P<0.05). Arthroscopic meniscectomy is an effective treatment for discoid menisci resulting in minimal invasion, quick recovery and early functional exercise. The use of arthroscopy during surgery aids to preserve the meniscus and to reduce stress, therefore, having a beneficial effect on short-term clinical outcomes.

AcMNPV enhances infection by ThorNPV in Sf21 cells and SeMNPV in Hi5 cells.

An expression cassette containing the DsRed2 gene, which encodes the red fluorescent protein (RFP), was inserted into the wide-host-range Autographa californica M nucleopolyhedrovirus (AcMNPV) at the polyhedrin locus (vAcDsRed2). An expression cassette containing the enhanced green fluorescent protein (EGFP) gene was inserted at the gp37 locus of the narrow-host-range Thysanoplusia orichalcea MNPV (ThorMNPV) and the p10 locus of Spodoptera exigua MNPV (SeMNPV) to produce vThGFP and vSeGFP, respectively. vThGFP and vSeGFP are poor at infecting Sf21 and Hi5 cells, respectively, whereas vAcDsRed2 is highly infectious to both cell lines. During co-infection, vAcDsRed2 enhanced vThGFP infection in Sf21 cells by approximately 20-fold, and it enhanced vSeGFP infection in Hi5 cells by more than 300-fold, as detected by fluorescence measurements. In contrast, vThGFP reduced vAcDsRed2 infection by 5.4-fold in Sf21 cells, while vSeGFP reduced vAcDsRed2 by 3.2-fold in Hi5 cells. Plaque assay data did not suggest viral recombination, but vThGFP plaques surrounded by vAcDsRed2 plaques were observed. A viral DNA replication assay performed by real-time quantitative PCR suggested that the detected fluorescence correlated with virus replication. Sf21 cells infected with vAcDsRed2 were resistant to superinfection by viruses of the same type expressing EGFP (vAcGFP). These results demonstrated that AcMNPV could enhance replication of ThorMNPV and SeMNPV in non-permissive cells without recombination.