Multiwavelength Excitation in Ho3+-Doped All-Inorganic Double Perovskites Achieved by Codoping Mn2+ for Warm-White LEDs and Plant Growth.

Doping lanthanide ions is an efficient method to modify the optical properties of lead-free double-perovskite halides. However, most lanthanide-doped double perovskites show a low luminescence efficiency and require a high excitation energy. Here, we have successfully prepared a series of Ho3+-doped Cs2NaBiCl6 microcrystals through a simple hydrothermal method and obtained strong characteristic emissions of Ho3+ at 492 and 657 nm under low-energy excitation (449 nm). After codoping Mn2+, apart from the characteristic emissions from Ho3+ under 450 nm wavelength excitation, the orangish-red luminescence consisting of the emission band centered at 591 nm from Mn2+ and a sharp emission peak at 657 nm from Ho3+ is obtained under 355 nm UV light excitation. Photoluminescence (PL) emission and excitation spectra, along with the PL decay curves, confirm the existence of an energy-transfer channel from Cs2NaBiCl6 to Mn2+ and then from Mn2+ to Ho3+. The enhanced absorption efficiency (10.5 → 70.7%) suggests that the codoping of Mn2+ overcomes the low absorption efficiency caused by f-f forbidden transitions of Ho3+. Finally, the diverse luminescent performance within the Cs2NaBiCl6:Ho3+, Mn2+ phosphor is realized by altering the excitation wavelength, thereby enabling its application in warm-white-light-emitting diodes and plant growth in this work.

Identifying the genetic association between common rheumatic diseases and vitiligo.

BACKGROUND: Although observational studies have suggested a correlation between vitiligo and rheumatic diseases, conclusive evidence supporting a causal relationship is still lacking. Therefore, this study aims to explore the potential causal relationship between vitiligo and rheumatic diseases. METHODS: Using genome-wide association studies, we performed a two-sample Mendelian randomization (MR) analysis. In our analysis, the random-effects inverse variance weighted (IVW) method was predominantly employed, followed by several sensitivity analyses, which include heterogeneity, horizontal pleiotropy, outliers, and "leave-one-out" analyses. RESULTS: The genetically predicted vitiligo was associated with an increased risk of rheumatoid arthritis (RA) (OR, 1.47; 95% confidence interval [CI], 1.29-1.68; p < 0.001), and systemic lupus erythematosus (SLE) (OR, 1.22; 95% CI, 1.06-1.39; p = 0.005). The causal associations were supported by sensitivity analyses. In Sjögren's syndrome and ankylosing spondylitis, no causal relationship with vitiligo was found in the study. CONCLUSION: Our MR results support the causal effect that vitiligo leads to a higher risk of RA and SLE. Individuals with vitiligo should be vigilant for the potential development of RA and SLE. Managing and addressing this potential requires regular monitoring.

LncRNA SNHG5/miR-26a/SOX2 signal axis enhances proliferation of chondrocyte in osteoarthritis.

Chondrocyte is involved in the destruction of joints in osteoarthritis (OA) patients. The aim of this study was to explore the expression level of small nucleolar RNA host gene 5 (SNHG5) and evaluate its function in chondrocyte. In our current study, the expression levels of SNHG5, miR-26a, and SOX2 in 17 pairs of articular cartilage tissues and in the non-OA group were assessed by real-time quantitative reverse-transcription polymerase chain reaction. Results showed that the levels of SNHG5 and SOX2 were significantly downregulated in OA tissues, while the level of miR-26a was upregulated. MTT, colony formation and cell transwell assays were performed to assess the function of SNHG5 on the cell viability, growth ability, and migration capacity in CHON-001 cells. It was found that SNHG5 could promote chondrocyte cell proliferation and migration. The relationship between SNHG5 and miR-26a was confirmed by RIP and the luciferase reporter assays. SOX2 was identified as a target gene of miR-26a by the luciferase reporter assay. Rescue assay was applied to verify the relationship among SNHG5, miR-26a, and SOX2. Our current study demonstrated that SNHG5 is involved in the mechanism of OA through functioning as a ceRNA to competitively sponge miR-26a, therefore, regulating the expression of SOX2.

Mechanical Properties and Microstructure of Hot-Pressed Silica Matrix Composites.

Silica is one of the most widely used ceramics due to its excellent chemical stability and dielectric property. However, its destructive brittle nature inhabits it from wider application as a functional ceramic. An improvement in toughness is a challenging topic for silica ceramic, as well as other ceramics. In the paper, silica ceramic with different types of boron nitride powders and alumina platelets was fabricated by hot-pressing. Introduction of the additives had great influence on the composites' mechanical properties and microstructure. The silica matrix composite containing micro-sized boron nitride powders possessed the best mechanical properties, including the bending strength (134.5 MPa) and the fracture toughness (1.85 Mpa·m1/2). Meanwhile, the introduction of alumina platelets combined with boron nitride nanosheets achieved an effective enhancement of fracture toughness while maintaining the bending strength. Compared with the monolithic silica, the composite with simultaneous addition of alumina platelets and boron nitride nanosheets had a fracture toughness of 2.23 Mpa·m1/2, increased by approximately 27% (1.75 Mpa·m1/2). The crack deflection and platelet pullout were contributing to enhancement of the fracture toughness. The improved mechanical properties, combined with the intrinsic excellent dielectric and chemical properties, make the silica matrix composites promising wave transparent and thermal protection materials.

Influence of Additives on Microstructure and Mechanical Properties of Alumina Ceramics.

Alumina is one of the most commonly used and researched structural ceramic because of its excellent properties. However, its intrinsic brittleness is the fatal drawback, which hinders it from wider applications. How to improve its fracture toughness as well as the bending strength is always challenging for material researchers. In this paper, alumina matrix composites were fabricated by hot-pressing, in which some additives, including zirconia, alumina platelets, and MXene, were incorporated. The influence of the introduced additives on their microstructure and mechanical properties was investigated. Compare with the monolithic alumina, both bending strength and fracture toughness of all samples were improved greatly. Incorporation of zirconia was beneficial to the mechanical properties due to the phase-transformation strengthening and toughening mechanism. While alumina platelets resulted in high fracture toughness because of the self-toughening of elongated grains. The synergistic effect of alumina platelets and MXene enormously improved the fracture toughness from 2.9 ± 0.3 MPa·m1/2 for monolithic alumina to 7.5 ± 0.4 MPa·m1/2 for the composite, which was increased by 159%. This work will provide useful references for the fabrication of high-strength and high-toughness alumina ceramics by introducing additives properly.

Molecular cloning of amphioxus uncoupling protein and assessment of its uncoupling activity using a yeast heterologous expression system.

The present study describes the molecular cloning of a novel cDNA fragment from amphioxus (Branchiostoma belcheri) encoding a 343-amino acid protein that is highly homologous to human uncoupling proteins (UCP), this protein is therefore named amphioxus UCP. This amphioxus UCP shares more homology with and is phylogenetically more related to mammalian UCP2 as compared with UCP1. To further assess the functional similarity of amphioxus UCP to mammalian UCP1 and -2, the amphioxus UCP, rat UCP1, and human UCP2 were separately expressed in Saccharomyces cerevisiae, and the recombinant yeast mitochondria were isolated and assayed for the state 4 respiration rate and proton leak, using pYES2 empty vector as the control. UCP1 increased the state 4 respiration rate by 2.8-fold, and the uncoupling activity was strongly inhibited by GDP, while UCP2 and amphioxus UCP only increased the state 4 respiration rate by 1.5-fold and 1.7-fold in a GDP-insensitive manner, moreover, the proton leak kinetics of amphioxus UCP was very similar to UCP2, but much different from UCP1. In conclusion, the amphioxus UCP has a mild, unregulated uncoupling activity in the yeast system, which resembles mammalian UCP2, but not UCP1.

Polymorphisms in MAPK9 (rs4147385) and CSF1R (rs17725712) are associated with the development of inhibitors in patients with haemophilia A in North China.

INTRODUCTION: The formation of neutralizing antibodies (FVIII inhibitors) in haemophilia A patients is an immune response to the deficient factor. This process is multifactorial and includes environmental and genetic factors. Some genetic markers that play a decisive role in the immune response have been identified as risk factors for inhibitor development. OBJECTIVE: Our aim was to investigate the association between polymorphisms in several genes involved in the regulation of the immune response and inhibitor development in patients with haemophilia A in North China. METHODS: We analysed eight SNPs (MAPK9 rs4147385, CSF1R rs17725712, CD44 rs927335, STAT4 rs7574865, IKZF1 rs4917014, ETS1 rs6590330, BANK1 rs17266594 and rs10516487) by Snapshot SNP genotyping assays in 100 haemophilia A patients, including 29 with inhibitors and 71 without inhibitors. RESULTS: Our results demonstrated that the rs17725712 A allele and the AA homozygous genotype of CSF1R were more frequent in patients with inhibitors. The rs4147385 G allele in MAPK9 was also more frequent in the inhibitor cohort. CONCLUSION: We confirmed an association of CSF1R rs17725712 and MAPK9 rs4147385 with inhibitor development in haemophilia A patients in North China.

A phase II study of arsenic trioxide in patients with relapsed or refractory malignant lymphoma.

Limited data have been reported regarding the use of arsenic trioxide (ATO) in the treatment of patients with relapsed or refractory malignant lymphoma; therefore, the present phase II study evaluated the efficacy and toxicity of ATO in such patients. A total of 35 patients were treated with ATO (0.25 mg/kg) infused for 1 h daily, 5 days a week, for a 6-week cycle. Patients were evaluated for the efficacy and toxicity of this regimen. The primary outcome evaluated was the overall response rate (ORR), including the complete and partial response rates. The secondary outcomes evaluated were the overall survival (OS), progression-free survival (PFS), and toxicity. Tumor response data were obtained from all 35 enrolled patients. The ORR was 43%, including complete responses in four patients (11%) and partial responses in 11 patients (31%). The median duration of response was 16 weeks (range 11-23 weeks). The median OS was 79 weeks (range 14-171 weeks), and the median PFS was 55 weeks (range 14-135 weeks). Grade I or II hematological toxicities were the most commonly reported adverse events. The results of this study appear promising for the treatment of relapsed or refractory malignant lymphoma, with well-tolerated ATO toxicity.

Identification of antigens by monoclonal antibody PD4 and its expression in Escherichia coli.

AIM: To clone and express the antigen of monoclonal antibody (MAb) PD4 for further investigation of its function. METHODS: MGC803 cDNA expression library was constructed and screened with PD4 as probes to clone the antigen. After failed in the library screening, immunoprecipitation and SDS-polyacrylamide gel electrophoresis were applied to purify the antigen for sequence analysis. The antigen coming from Mycoplasma hyorhinis (M. hyorhinis) was further confirmed with Western blot analysis by infecting M. hyorhinis -free HeLa cells and eliminating the M. hyorhinis from MGC803 cells. The full p37 gene was cloned by PCR and expressed successfully in Escherichia coli after site-directed mutations. Immunofluorescence assay was used to demonstrate if p37 protein could directly bind to gastric tumor cell AGS. RESULTS: The cDNA library constructed with MGC803 cells was screened by MAb PD4 as probes. Unfortunately, the positive clones identified with MAb PD4 were also reacted with unrelated antibodies. Then, immunoprecipitation was performed and the purified antigen was identified to be a membrane protein of Mycoplasma hyorhinis (M. hyorhinis) by sequencing of N-terminal amino acid residues. The membrane protein was intensively verified with Western blot by eliminating M. hyorhinis from MGC803 cells and by infecting M. hyorhinis-free HeLa cells. The full p37 gene was cloned and expressed successfully in Escherichia coli after site-directed mutations. Immunofluorescence demonstrated that p37 protein could directly bind to gastric tumor cell AGS. CONCLUSION: The antigen recognized by MAb PD4 is from M. hyorhinis, which suggests the actions involved in MAb PD4 is possibly mediated by p37 protein or M. hyorhinis. As p37 protein can bind directly to tumor cells, the pathogenic role of p37 involved in tumorigenesis justifies further investigation.

Molecular cloning of lamprey uncoupling protein and assessment of its uncoupling activity using a yeast heterologous expression system.

We report the molecular cloning of a novel cDNA fragment from lamprey encoding a 313-amino acid protein that is highly homologous to human uncoupling proteins (UCP). We therefore named the protein lamprey UCP. This lamprey UCP, rat UCP1, human UCP2, and human mitochondrial oxoglutarate carrier were individually expressed in Saccharomyces cerevisiae and the recombinant yeast mitochondria were isolated and assayed for the state 4 respiration rate and proton leak. Only UCP1 showed a strong (3.6-fold increase of the ratio of mitochondrial state 4 respiration rate to FCCP-stimulated fully uncoupled respiration rate) and GDP-inhibitable uncoupling activity, while the uncoupling activities of both UCP2 and lamprey UCP were relatively weak (1.5-fold and 1.4-fold, respectively) and GDP-insensitive. The oxoglutarate carrier had no effect on the studied parameters. In conclusion, the lamprey UCP has a mild, unregulated uncoupling activity in the yeast system, which resembles UCP2, but not UCP1.

17beta-estradiol inhibits oleic acid-induced rat VSMC proliferation and migration by restoring PGC-1alpha expression.

Estrogen shows a vasoprotective role through inhibiting the proliferation and migration of vascular smooth muscle cells (VSMCs). The mechanism underlying the effect of estrogen, however, is not completely understood. Here, we explored the role of peroxisome proliferator-activated receptor-gamma (PPARgamma) coactivator-1alpha (PGC-1alpha) in estrogen-mediated vasoprotection. Firstly, we showed that oleic acid (OA) decreased PGC-1alpha expression while stimulating VSMC proliferation and migration. In contrast, administration of VSMCs with 17beta-estradiol (E(2), 1 or 10nM) significantly restored OA-decreased PGC-1alpha expression, treatment with 10nM E(2) almost completely abolished OA-induced VSMC proliferation and migration. Secondly, by using PGC-1alpha siRNA, the inhibitory effect of E(2) on VSMC growth is strongly reduced via suppressing PGC-1alpha expression, indicating that E(2) may exert its role through restoring PGC-1alpha. Finally, E(2) (10nM) treatment inhibits OA-induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, however, suppression of PGC-1alpha expression abolishes this inhibitory effect of E(2). Our findings demonstrate for the first time that in OA-stimulated rat VSMCs, treatment with E(2) (1 or 10nM) diminishes VSMC proliferation and migration via restoring OA-decreased PGC-1alpha expression. This observation offers a novel molecular basis of the vasoprotective effect of estrogen.

PGC-1alpha is a key regulator of glucose-induced proliferation and migration in vascular smooth muscle cells.

BACKGROUND: Atherosclerosis is a complex pathological condition caused by a number of mechanisms including the accelerated proliferation of vascular smooth muscle cells (VSMCs). Diabetes is likely to be an important risk factor for atherosclerosis, as hyperglycemia induces vascular smooth muscle cell (VSMC) proliferation and migration and may thus contribute to the formation of atherosclerotic lesions. This study was performed to investigate whether PGC-1alpha, a PPARgamma coactivator and metabolic master regulator, plays a role in regulating VSMC proliferation and migration induced by high glucose. METHODOLOGY/PRINCIPAL FINDINGS: PGC-1alpha mRNA levels are decreased in blood vessel media of STZ-treated diabetic rats. In cultured rat VSMCs, high glucose dose-dependently inhibits PGC-1alpha mRNA expression. Overexpression of PGC-1alpha either by infection with adenovirus, or by stimulation with palmitic acid, significantly reduces high glucose-induced VSMC proliferation and migration. In contrast, suppression of PGC-1alpha by siRNA mimics the effects of glucose on VSMCs. Finally, mechanistic studies suggest that PGC-1alpha-mediated inhibition of VSMC proliferation and migration is regulated through preventing ERK1/2 phosphorylation. CONCLUSIONS/SIGNIFICANCE: These results indicate that PGC-1alpha is a key regulator of high glucose-induced proliferation and migration in VSMCs, and suggest that elevation of PGC-1alpha in VSMC could be a useful strategy in preventing the development of diabetic atherosclerosis.

Identification and characterization of novel amphioxus microRNAs by Solexa sequencing.

BACKGROUND: microRNAs (miRNAs) are endogenous small non-coding RNAs that regulate gene expression at the post-transcriptional level. While the number of known human and murine miRNAs is continuously increasing, information regarding miRNAs from other species such as amphioxus remains limited. RESULTS: We combined Solexa sequencing with computational techniques to identify novel miRNAs in the amphioxus species B. belcheri (Gray). This approach allowed us to identify 113 amphioxus miRNA genes. Among them, 55 were conserved across species and encoded 45 non-redundant mature miRNAs, whereas 58 were amphioxus-specific and encoded 53 mature miRNAs. Validation of our results with microarray and stem-loop quantitative RT-PCR revealed that Solexa sequencing is a powerful tool for miRNA discovery. Analyzing the evolutionary history of amphioxus miRNAs, we found that amphioxus possesses many miRNAs unique to chordates and vertebrates, and these may thus represent key steps in the evolutionary progression from cephalochordates to vertebrates. We also found that amphioxus is more similar to vertebrates than are tunicates with respect to their miRNA phylogenetic histories. CONCLUSIONS: Taken together, our results indicate that Solexa sequencing allows the successful discovery of novel miRNAs from amphioxus with high accuracy and efficiency. More importantly, our study provides an opportunity to decipher how the elaboration of the miRNA repertoire that occurred during chordate evolution contributed to the evolution of the vertebrate body plan.

PGC-1alpha induces apoptosis in human epithelial ovarian cancer cells through a PPARgamma-dependent pathway.

Peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 alpha (PGC-1alpha) coactivates multiple transcription factors and regulates several metabolic processes. The current study investigated the role of PGC-1alpha in the induction of apoptosis in human epithelial ovarian cancer cells. The PGC-1alpha mRNA level between human ovaries and human ovarian epithelial tumors was examined by quantitative RT-PCR. Less PGC-1alpha expression was found in the surface epithelium of malignant tumors compared with normal ovaries. Overexpression of PGC-1alpha in human epithelial ovarian cancer cell line Ho-8910 induced cell apoptosis through the coordinated regulation of Bcl-2 and Bax expression. Microarray analyses confirmed that PGC-1alpha dramatically affected the apoptosis-related genes in Ho-8910 cells. Mitochondrial functional assay showed that the induction of apoptosis was through the terminal stage by the release of cytochrome c. Furthermore, PGC-1alpha-induced apoptosis was partially, but not completely, blocked by PPARgamma antagonist (GW9662), and suppression of PPARgamma expression by siRNA also inhibited PGC-1alpha-induced apoptosis in Ho-8910 cells. These data suggested that PGC-1alpha exerted its effect through a PPARgamma-dependent pathway. Our findings indicated that PGC-1alpha was involved in the apoptotic signal transduction pathways and downregulation of PGC-1alpha may be a key point in promoting epithelial ovarian cancer growth and progression.