Exosomes derived from human urine-derived stem cells ameliorate IL-1ß-induced intervertebral disk degeneration.

BACKGROUND: Human intervertebral disk degeneration (IVDD) is a sophisticated degenerative pathological process. A key cause of IVDD progression is nucleus pulposus cell (NPC) degeneration, which contributes to excessive endoplasmic reticulum stress in the intervertebral disk. However, the mechanisms underlying IVDD and NPC degeneration remain unclear. METHODS: We used interleukin (IL)-1ß stimulation to establish an NPC-degenerated IVDD model and investigated whether human urine-derived stem cell (USC) exosomes could prevent IL-1ß-induced NPC degeneration using western blotting, quantitative real-time polymerase chain reaction, flow cytometry, and transcriptome sequencing techniques. RESULTS: We successfully extracted and identified USCs and exosomes from human urine. IL-1ß substantially downregulated NPC viability and induced NPC degeneration while modulating the expression of SOX-9, collagen II, and aggrecan. Exosomes from USCs could rescue IL-1ß-induced NPC degeneration and restore the expression levels of SOX-9, collagen II, and aggrecan. CONCLUSIONS: USC-derived exosomes can prevent NPCs from degeneration following IL-1ß stimulation. This finding can aid the development of a potential treatment strategy for IVDD.

The RNA polymerase II subunit B (RPB2) functions as a growth regulator in human glioblastoma.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a poor prognosis. The growth of GBM cells depends on the core transcriptional apparatus, thus rendering RNA polymerase (RNA pol) complex as a candidate therapeutic target. The RNA pol II subunit B (POLR2B) gene encodes the second largest subunit of the RNA pol II (RPB2); however, its genomic status and function in GBM remain unclear. Certain GBM data sets in cBioPortal were used for investigating the genomic status and expression of POLR2B in GBM. The function of RPB2 was analyzed following knockdown of POLR2B expression by shRNA in GBM cells. The cell counting kit-8 assay and PI staining were used for cell proliferation and cell cycle analysis. A xenograft mouse model was established to analyze the function of RPB2 in vivo. RNA sequencing was performed to analyze the RPB2-regulated genes. GO and GSEA analyses were applied to investigate the RPB2-regulated gene function and associated pathways. In the present study, the genomic alteration and overexpression of the POLR2B gene was described in glioblastoma. The data indicated that knockdown of POLR2B expression suppressed tumor cell growth of glioblastoma in vitro and in vivo. The analysis further demonstrated the identification of the RPB2-regulated gene sets and highlighted the DNA damage-inducible transcript 4 gene as the downstream target of the POLR2B gene. The present study provides evidence indicating that RPB2 functions as a growth regulator in glioblastoma and could be used as a potential therapeutic target for the treatment of this disease.

Clinical Evaluation of Femoral Head Fractures: Which Classification Systems Have the Best Universality, Reliability, and Reproducibility?

BACKGROUND: Femoral head fractures are rare but potentially disabling injuries, and classifying them accurately and consistently can help surgeons make good choices about their treatment. However, there is no consensus as to which classification of these fractures is the most advantageous; parameters that might inform this choice include universality (the proportion of fractures that can be classified), as well as, of course, interobserver and intraobserver reproducibility. QUESTIONS/PURPOSES: (1) Which classification achieves the best universality (defined as the proportion of fractures that can be classified)? (2) Which classification delivers the highest intraobserver and interobserver reproducibility in the clinical CT assessment of femoral head fractures? (3) Based on the answers to those two questions, which classifications are the most applicable for clinical practice and research? METHODS: Between January 2011 and January 2023, 254 patients with femoral head fractures who had CT scans (CT is routine at our institution for patients who have experienced severe hip trauma) were potentially eligible for inclusion in this study, which was performed at a large Level I trauma center in China. Of those, 9% (23 patients) were excluded because of poor-quality CT images, unclosed physes, pathologic fractures, or acetabular dysplasia, leaving 91% (231 patients with 231 hips) for analysis here. Among those, 19% (45) were female. At the time of injury, the mean age was 40 ± 17 years. All fractures were independently classified by four observers according to the Pipkin, Brumback, AO/Orthopaedic Trauma Association (OTA), Chiron, and New classifications. Each observer repeated his classifications again 1 month later to allow us to ascertain intraobserver reliability. To evaluate the universality of classifications, we characterized the percentage of hips that could be classified using the definitions offered in each classification. The kappa (κ) value was calculated to determine interrater and intrarater agreement. We then compared the classifications based on the combination of universality and interobserver and intraobserver reproducibility to determine which classifications might be recommended for clinical and research use. RESULTS: The universalities of the classifications were 99% (228 of 231, Pipkin), 43% (99 of 231, Brumback), 94% (216 of 231, AO/OTA), 99% (228 of 231, Chiron), and 100% (231 of 231, New). The interrater agreement was judged as almost perfect (κ 0.81 [95% CI 0.78 to 0.84], Pipkin), moderate (κ 0.51 [95% CI 0.44 to 0.59], Brumback), fair (κ 0.28 [95% CI 0.18 to 0.38], AO/OTA), substantial (κ 0.79 [95% CI 0.76 to 0.82], Chiron), and substantial (κ 0.63 [95% CI 0.58 to 0.68], New). In addition, the intrarater agreement was judged as almost perfect (κ 0.89 [95% CI 0.83 to 0.96]), substantial (κ 0.72 [95% CI 0.69 to 0.75]), moderate (κ 0.51 [95% CI 0.43 to 0.58]), almost perfect (κ 0.87 [95% CI 0.82 to 0.91]), and substantial (κ 0.78 [95% CI 0.59 to 0.97]), respectively. Based on these findings, we determined that the Pipkin and Chiron classifications offer near-complete universality and sufficient interobserver and intraobserver reproducibility to recommend them for clinical and research use, but the other classifications (Brumback, AO/OTA, and New) do not. CONCLUSION: Based on our findings, clinicians and clinician-scientists can use either the Pipkin or Chiron classification systems to classify femoral head fractures based on CT images, with equal confidence. It seems unlikely that any new classifications will substantially outperform these, and the other available systems either lacked sufficient universality or reproducibility to recommend them for general use. LEVEL OF EVIDENCE: Level III, diagnostic study.

Physiological clearance of amyloid-beta by the kidney and its therapeutic potential for Alzheimer's disease.

Amyloid-ß (Aß) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer's disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aß produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aß clearance remain largely unknown. The kidney is thought to be responsible for Aß clearance, but direct evidence is lacking. In this study, we investigated the impact of unilateral nephrectomy on the dynamic changes in Aß in the blood and brain in both humans and animals and on behavioural deficits and AD pathologies in animals. Furthermore, the therapeutic effects of the diuretic furosemide on Aß clearance via the kidney were assessed. We detected Aß in the kidneys and urine of both humans and animals and found that the Aß level in the blood of the renal artery was higher than that in the blood of the renal vein. Unilateral nephrectomy increased brain Aß deposition; aggravated AD pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, and neuronal loss; and aggravated cognitive deficits in APP/PS1 mice. In addition, chronic furosemide treatment reduced blood and brain Aß levels and attenuated AD pathologies and cognitive deficits in APP/PS1 mice. Our findings demonstrate that the kidney physiologically clears Aß from the blood, suggesting that facilitation of Aß clearance via the kidney represents a novel potential therapeutic approach for AD.

Computational prediction of new magnetic materials.

The discovery of new magnetic materials is a big challenge in the field of modern materials science. We report the development of a new extension of the evolutionary algorithm USPEX, enabling the search for half-metals (materials that are metallic only in one spin channel) and hard magnetic materials. First, we enabled the simultaneous optimization of stoichiometries, crystal structures, and magnetic structures of stable phases. Second, we developed a new fitness function for half-metallic materials that can be used for predicting half-metals through an evolutionary algorithm. We used this extended technique to predict new, potentially hard magnets and rediscover known half-metals. In total, we report five promising hard magnets with high energy product (|BH|MAX), anisotropy field (Ha), and magnetic hardness (κ) and a few half-metal phases in the Cr-O system. A comparison of our predictions with experimental results, including the synthesis of a newly predicted antiferromagnetic material (WMnB2), shows the robustness of our technique.

[Regulation of ß-mercuryl alcohol metabolic flow in Saccharomyces cerevisiae cells].

In this study, citrate synthase gene(CIT2), and malate synthase gene(MLS1) were successfully knocked out in ß-amyrin-producing yeast cells by using CRISPR/CAS9. The promoter of phosphoglucose isomerase gene(PGI1) was replaced by that of cytochrome c oxidase subunit Ⅶa(Cox9)to weaken its expression, aiming to channel more carbon flux into the NADPH-producing pathway. The fermentation results showed that CIT2 deletion had no effect on the ß-amyrin production. Compared with the control strain, the production of ß-amyrin was increased by 1.85 times after deleting MLS1, reaching into 3.3 mg·L~(-1). By replacing the promoter of PGI1, the ß-amyrin yield was 3.75 times higher than that of the control strain, reaching up to 6.7 mg·L~(-1). This study successfully knocked out the CITT2 and MLS1 genes and weakened the PGI1 gene by using CRISPR/CAS9, which directly influenced the production of ß-amyrin and provided some reference for the the metabolic engineering of triterpernoid producing strain.

Mitochondrial pyruvate carrier 1 functions as a tumor suppressor and predicts the prognosis of human renal cell carcinoma.

Invasion and subsequent metastasis are major characteristics of malignant human renal cell carcinoma (RCC), though the mechanisms remain elusive. Mitochondrial pyruvate carrier (MPC), a key factor that controls pyruvate transportation in mitochondria, is frequently dysregulated in tumor cells and loss of MPC predicts poor prognosis in various types of cancer. However, the clinical relevance and functional significance of MPC in RCC remain to be elucidated. In this study, we investigated the expression of MPC1 and MPC2 in specimens from RCC patients and observed downregulation of MPC1, but not MPC2, in RCC tissues compared with adjacent non-cancerous tissue. Moreover, RCC patients with higher MPC1 expression exhibited longer overall survival rate than those with lower MPC1. Functionally, MPC1 suppressed the invasion of RCC cells in vitro and reduced the growth of RCC cells in vivo, possibly through inhibition of MMP7 and MMP9. Further studies revealed that loss of MPC1 was induced by hypoxia in RCC cells, and notably, MPC1 expression, was negatively correlated with HIF1α expression in RCC cells and patient samples. Taken together, our results identify anti-tumor function of MPC1 in RCC and revealed MPC1 as a novel prognostic biomarker to predict better patient survival.

Kawasaki disease OX40-OX40L axis acts as an upstream regulator of NFAT signaling pathway.

BACKGROUND: We investigated a costimulatory molecule OX40-OX40L acting as an upstream regulator to regulate the nuclear factor of activated T cell (NFAT) in the acute phase of Kawasaki disease (KD). METHODS: One hundred and one samples were collected and divided into six groups: coronary artery lesion (KD-CAL) before intravenous immunoglobulin (IVIG), KD-CAL after IVIG, KD without CAL (KD-nCAL) before IVIG, KD-nCAL after IVIG, fever of unknown (Fou), and Healthy. In vitro OX40-stimulating and OX40L-inhibiting tests were conducted in Healthy and KD groups, respectively. Both the messenger RNA (mRNA) and protein expression levels of OX40, OX40L, NFAT1, and NFAT2 were investigated using quantitative reverse transcription PCR and immunoblotting assay, respectively. RESULTS: The mRNA and protein expression levels of NFAT1, NFAT2, OX40, and OX40L were significantly increased in KD-CAL and KD-nCAL groups before IVIG compared with Fou and Healthy groups and decreased after IVIG. A positive correlation was found between them in KD. In vitro OX40-stimulating test demonstrated the significantly increased mRNA and protein expression levels of NFAT1 and NFAT2 in the peripheral blood mononuclear cells of the Healthy group. Meanwhile, OX40L-inhibiting test showed significantly decreased expression levels of NFAT1 and NFAT2 in the KD group. CONCLUSION: OX40-OX40L acts as an upstream regulator in the NFAT signaling pathway involved in KD.

[Study of heterologous efficient synthesis of ß-amyrin and high-density fermentation].

In this study, the synthetic pathway of ß-amyrin was constructed in the pre-constructed Saccharomyces cerevisiae chassis strain Y0 by introducing ß-amyrin synthase from Glycyrrhiza uralensis, resulting strain Y1-C20-6, which successfully produced ß-amyrin up to 5.97 mg·L~(-1). Then, the mevalonate pyrophosphate decarboxylase gene(ERG19), mevalonate kinase gene(ERG12), 3-hydroxy-3-methylglutaryl-CoA synthase gene(ERG13), phosphomevalonate kinase gene(ERG8) and IPP isomerase gene(IDI1)were overexpressed to promoted the metabolic fluxto the direction of ß-amyrin synthesis for further improving ß-amyrin production, resulting the strain Y2-C2-4 which produced ß-amyrin of 10.3 mg·L~(-1)under the shake flask fermentation condition. This is 100% higher than that of strain Y1-C20-6, illustrating the positive effect of the metabolic engineering strategy applied in this study. The titer of ß-amyrin was further improved up to 157.4 mg·L~(-1) in the fed-batch fermentation, which was almost 26 fold of that produced by strain Y1-C20-6. This study not only laid the foundation for the biosynthesis of ß-amyrin but also provided a favorable chassis strain for elucidation of cytochrome oxidases and glycosyltransferases of ß-amyrin-based triterpenoids.

Molecular mechanism of G1 arrest and cellular senescence induced by LEE011, a novel CDK4/CDK6 inhibitor, in leukemia cells.

BACKGROUND: Overexpression of cyclin D1 dependent kinases 4 and 6 (CDK4/6) is a common feature of many human cancers including leukemia. LEE011 is a novel inhibitor of both CDK4 and 6. To date, the molecular function of LEE011 in leukemia remains unclear. METHODS: Leukemia cell growth and apoptosis following LEE011 treatment was assessed through CCK-8 and annexin V/propidium iodide staining assays. Cell senescence was assessed by ß-galactosidase staining and p16INK4a expression analysis. Gene expression profiles of LEE011 treated HL-60 cells were investigated using an Arraystar Human LncRNA array. Gene ontology and KEGG pathway analysis were then used to analyze the differentially expressed genes from the cluster analysis. RESULTS: Our studies demonstrated that LEE011 inhibited proliferation of leukemia cells and could induce apoptosis. Hoechst 33,342 staining analysis showed DNA fragmentation and distortion of nuclear structures following LEE011 treatment. Cell cycle analysis showed LEE011 significantly induced cell cycle G1 arrest in seven of eight acute leukemia cells lines, the exception being THP-1 cells. ß-Galactosidase staining analysis and p16INK4a expression analysis showed that LEE011 treatment can induce cell senescence of leukemia cells. LncRNA microarray analysis showed 2083 differentially expressed mRNAs and 3224 differentially expressed lncRNAs in LEE011-treated HL-60 cells compared with controls. Molecular function analysis showed that LEE011 induced senescence in leukemia cells partially through downregulation of the transcriptional expression of MYBL2. CONCLUSIONS: We demonstrate for the first time that LEE011 treatment results in inhibition of cell proliferation and induction of G1 arrest and cellular senescence in leukemia cells. LncRNA microarray analysis showed differentially expressed mRNAs and lncRNAs in LEE011-treated HL-60 cells and we demonstrated that LEE011 induces cellular senescence partially through downregulation of the expression of MYBL2. These results may open new lines of investigation regarding the molecular mechanism of LEE011 induced cellular senescence.

Combined Theoretical and in Situ Scattering Strategies for Optimized Discovery and Recovery of High-Pressure Phases: A Case Study of the GaN-Nb2O5 System.

The application of pressure in solid-state synthesis provides a route for the creation of new and exciting materials. However, the onerous nature of high-pressure techniques limits their utility in materials discovery. The systematic search for novel oxynitrides-semiconductors for photocatalytic overall water splitting-is a representative case where quench high-pressure synthesis is useful and necessary in order to obtain target compounds. We utilize state of the art crystal structure prediction theory (USPEX) and in situ synchrotron-based X-ray scattering to speed up the discovery and optimization of novel compounds using high-pressure synthesis. Using this approach, two novel oxynitride phases were discovered in the GaN-Nb2O5 system. The (Nb2O5)0.84:(NbO2)0.32:(GaN)0.82 rutile structured phase was formed at 1 GPa and 900 °C and gradually transformed to a α-PbO2-related structure above 2.8 GPa and 1000 °C. The low-pressure rutile type phase was found to have a direct optical band gap of 0.84 eV and an indirect gap of 0.51 eV.

High sensitivity optical waveguide accelerometer based on Fano resonance.

An optical waveguide accelerometer based on tunable asymmetrical Fano resonance in a ring-resonator-coupled Mach-Zehnder interferometer (MZI) is proposed and analyzed. A Fano resonance accelerometer has a relatively large workspace of coupling coefficients with high sensitivity, which has potential application in inertial navigation, missile guidance, and attitude control of satellites. Due to the interference between a high-Q resonance pathway and a coherent background pathway, a steep asymmetric line shape is generated, which greatly improves the sensitivity of this accelerometer. The sensitivity of the accelerometer is about 111.75 mW/g. A 393-fold increase in sensitivity is achieved compared with a conventional MZI accelerometer and is approximately equal to the single ring structure.

Laboratory monitoring of rivaroxaban and assessment of its bleeding risk.

BACKGROUND: The aims of this study were to investigate the effects of rivaroxaban on routine coagulation assays using our local, widely available, reagents and to study the relationship between sensitive coagulation assays and bleeding risk caused by rivaroxaban. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT) and anti-factor Xa (FXa) chromogenic assays (Biophen DiXaI) and inhibition of FXa activity were performed in normal pooled plasma (NPP) spiked with rivaroxaban and plasma samples from patients treated with rivaroxaban. RESULTS: In vitro, the linear correlation coefficient of measured concentrations of rivaroxaban, by Biophen DiXaI, and spiked concentrations of rivaroxaban was 0.99. PT and APTT showed good linear correlation with rivaroxaban concentrations, while other assays showed poor correlation. In vivo, PT showed a moderate linear correlation with rivaroxaban concentrations while APTT had a weak correlation with rivaroxaban concentrations. In vitro and in vivo, the rivaroxaban concentrations, measured by Biophen DiXaI, always showed good correlation with the inhibition of FXa activity, and PT values showed moderate correlation with the inhibition of FXa activity. CONCLUSIONS: Biophen DiXaI can be considered as a quantitative method to monitor the anticoagulation activity of rivaroxaban, and could be used to evaluate bleeding risk caused by rivaroxaban. The PT reagent (Thrombosis S) could be considered as a rough method to monitor the anticoagulation activity of rivaroxaban and evaluate bleeding risk caused by rivaroxaban.

A novel phase of beryllium fluoride at high pressure.

A previously unknown thermodynamically stable high-pressure phase of BeF2 has been predicted using the evolutionary algorithm USPEX. This phase occurs in the pressure range 18-27 GPa. Its structure has C2/c space group symmetry and contains 18 atoms in the primitive unit cell. Given the analogy between BeF2 and SiO2, silica phases have been investigated as well, but the new phase has not been observed to be thermodynamically stable for this system. However, it is found to be metastable and to have comparable energy to the known metastable phases of SiO2, suggesting a possibility of its synthesis.

Nocardiopsis mangrovei sp. nov., isolated from mangrove sediment.

Two Gram-positive actinobacterial strains, designated HA11166(T) and HA12420, were isolated from mangrove sediments in Hainan, China. The bacterial cells grew with 0-9 % (w/v) NaCl, at 15-40 °C and pH 5.0-10.0, with the optimum growth at 1 % NaCl, 30-37 °C and pH 7.0. The organisms had a range of chemical and morphological properties consistent with their classification in the genus Nocardiopsis. Phylogenetic analysis of the 16S rRNA gene sequences indicated that strains HA11166(T) and HA12420 can be affiliated to the genus Nocardiopsis and most closely related to Nocardiopsis trehalosi VKM Ac-942(T) (with the similarity of 97.2 and 97.5 %, respectively). The value of DNA-DNA relatedness between type strain HA11166(T), selected as the representative strain, and N. trehalosi VKM Ac-942(T) was 38.8 %. The DNA G+C content of strain HA11166(T) was 73.7 %. On the basis of these phenotypic and genotypic data, strains HA11166(T) and HA12420 are proposed to represent a novel species of the genus Nocardiopsis, for which the name Nocardiopsis mangrovei sp. nov. is proposed. The type strain is HA11166(T) (=CGMCC 4.7119(T)=DSM 46665(T)).

Pseudonocardia nematodicida sp. nov., isolated from mangrove sediment in Hainan, China.

Two aerobic, Gram-stain positive actinobacterial strains with nematicidal activity, designated HA11164(T) and HA12591, were isolated from mangrove sediments in Hainan, China. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strains HA11164(T) and HA12591 belong to the genus Pseudonocardia and are closely related to Pseudonocardia carboxydivorans (with the similarities of 98.30 and 98.24 %, respectively), Pseudonocardia alni (98.23 and 98.16 %, respectively) and Pseudonocardia antimicrobica (98.10 and 98.03 %, respectively). The major polar lipids of the strain HA11164(T), as a representative strain of the two strains, were found to consist of phosphatidylmethylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, phosphatidylinositol, five unidentified glycolipids and four unidentified polar lipids. The predominant menaquinone of strain HA11164(T) was identified as MK-8 (H4), and the major fatty acids were identified as iso-C16:0, C17:1 ω10, C16:0 and C16:1 ω9. The G+C content of strain HA11164(T) was determined to be 74.9 mol%. The DNA-DNA relatedness values between strains HA11164(T) and P. alni, Pseudonocardia tropica, Pseudonocardia antarctica, P. carboxydivorans and Pseudonocardia parietis were 58.3, 56.2, 50.0, 57.1 and 46.0 %, respectively. Based on the results of this polyphasic study, strains HA11164(T) and HA12591 are considered to represent a novel species of the genus Pseudonocardia, for which the name Pseudonocardia nematodicida sp. nov. is proposed. The type strain is HA11164(T) (=CGMCC 4.7118(T) = DSM 45940(T)).

Wafer-Scale Periodic Poling of Thin-Film Lithium Niobate.

Periodically poled lithium niobate on insulator (PPLNOI) offers an admirably promising platform for the advancement of nonlinear photonic integrated circuits (PICs). In this context, domain inversion engineering emerges as a key process to achieve efficient nonlinear conversion. However, periodic poling processing of thin-film lithium niobate has only been realized on the chip level, which significantly limits its applications in large-scale nonlinear photonic systems that necessitate the integration of multiple nonlinear components on a single chip with uniform performances. Here, we demonstrate a wafer-scale periodic poling technique on a 4-inch LNOI wafer with high fidelity. The reversal lengths span from 0.5 to 10.17 mm, encompassing an area of ~1 cm2 with periods ranging from 4.38 to 5.51 µm. Efficient poling was achieved with a single manipulation, benefiting from the targeted grouped electrode pads and adaptable comb line widths in our experiment. As a result, domain inversion is ultimately implemented across the entire wafer with a 100% success rate and 98% high-quality rate on average, showcasing high throughput and stability, which is fundamentally scalable and highly cost-effective in contrast to traditional size-restricted chiplet-level poling. Our study holds significant promise to dramatically promote ultra-high performance to a broad spectrum of applications, including optical communications, photonic neural networks, and quantum photonics.

Ubiquitin ligase MDM2 mediates endothelial inflammation in Kawasaki disease vasculitis development.

Background: Kawasaki disease (KD) often complicates coronary artery lesions (CALs). Despite the established significance of STAT3 signaling during the acute phase of KD and signal transducer and activator of transcription 3 (STAT3) signaling being closely related to CALs, it remains unknown whether and how STAT3 was regulated by ubiquitination during KD pathogenesis. Methods: Bioinformatics and immunoprecipitation assays were conducted, and an E3 ligase, murine double minute 2 (MDM2) was identified as the ubiquitin ligase of STAT3. The blood samples from KD patients before and after intravenous immunoglobulin (IVIG) treatment were utilized to analyze the expression level of MDM2. Human coronary artery endothelial cells (HCAECs) and a mouse model were used to study the mechanisms of MDM2-STAT3 signaling during KD pathogenesis. Results: The MDM2 expression level decreased while the STAT3 level and vascular endothelial growth factor A (VEGFA) level increased in KD patients with CALs and the KD mouse model. Mechanistically, MDM2 colocalized with STAT3 in HCAECs and the coronary vessels of the KD mouse model. Knocking down MDM2 caused an increased level of STAT3 protein in HCAECs, whereas MDM2 overexpression upregulated the ubiquitination level of STAT3 protein, hence leading to significantly decreased turnover of STAT3 and VEGFA. Conclusions: MDM2 functions as a negative regulator of STAT3 signaling by promoting its ubiquitination during KD pathogenesis, thus providing a potential intervention target for KD therapy.

High-harmonic and single attosecond pulse generation using plasmonic field enhancement in ordered arrays of gold nanoparticles with chirped laser pulses.

Coherent XUV sources, which may operate at MHz repetition rate, could find applications in high-precision spectroscopy and for spatio-time-resolved measurements of collective electron dynamics on nanostructured surfaces. We theoretically investigate utilizing the enhanced plasmonic fields in an ordered array of gold nanoparticles for the generation of high-harmonic, extreme-ultraviolet (XUV) radiation. By optimization of the chirp of ultrashort laser pulses incident on the array, our simulations indicate a potential route towards the temporal shaping of the plasmonic near-field and, in turn, the generation of single attosecond pulses. The inherent effects of inhomogeneity of the local fields on the high-harmonic generation are analyzed and discussed. While taking the inhomogeneity into account does not affect the optimal chirp for the generation of a single attosecond pulse, the cut-off energy of the high-harmonic spectrum is enhanced by about a factor of two.

Pressure-induced stabilization and insulator-superconductor transition of BH.

Diborane (B(2)H(6)), a high energy density material, was believed to be stable in a wide P, T interval. A systematic investigation of the B-H system using the ab initio variable-composition evolutionary simulations shows that boron monohydride (BH) is thermodynamically stable and can coexist with solid B, H(2), and B(2)H(6) in a wide pressure range above 50 GPa. B(2)H(6) becomes unstable and decomposes into the Ibam phase of BH and H(2) (C2/c) at 153 GPa. The semiconducting layered Ibam structure of BH at 168 GPa transforms into a metallic phase with space group P6/mmm and a 3D topology with strong B-B and B-H covalent bonds. The Ibam-P6/mmm transformation pathway suggests the possibility of obtaining the metastable Pbcm phase on cold decompression of the P6/mmm phase. The electron-phonon coupling calculations indicate that P6/mmm-BH is a phonon-mediated superconductor with a critical temperature of superconductivity (T(c)) of 14.1-21.4 K at 175 GPa.