Filamin C is Essential for mammalian myocardial integrity.

FLNC, encoding filamin C, is one of the most mutated genes in dilated and hypertrophic cardiomyopathy. However, the precise role of filamin C in mammalian heart remains unclear. In this study, we demonstrated Flnc global (FlncgKO) and cardiomyocyte-specific knockout (FlnccKO) mice died in utero from severely ruptured ventricular myocardium, indicating filamin C is required to maintain the structural integrity of myocardium in the mammalian heart. Contrary to the common belief that filamin C acts as an integrin inactivator, we observed attenuated activation of ß1 integrin specifically in the myocardium of FlncgKO mice. Although deleting ß1 integrin from cardiomyocytes did not recapitulate the heart rupture phenotype in Flnc knockout mice, deleting both ß1 integrin and filamin C from cardiomyocytes resulted in much more severe heart ruptures than deleting filamin C alone. Our results demonstrated that filamin C works in concert with ß1 integrin to maintain the structural integrity of myocardium during mammalian heart development.

Interaction of Filamin C With Actin Is Essential for Cardiac Development and Function.

BACKGROUND: FLNC (filamin C), a member of the filamin family predominantly expressed in striated muscles, plays a crucial role in bridging the cytoskeleton and ECM (extracellular matrix) in cardiomyocytes, thereby maintaining heart integrity and function. Although genetic variants within the N-terminal ABD (actin-binding domain) of FLNC have been identified in patients with cardiomyopathy, the precise contribution of the actin-binding capability to FLNC's function in mammalian hearts remains poorly understood. METHODS: We conducted in silico analysis of the 3-dimensional structure of mouse FLNC to identify key amino acid residues within the ABD that are essential for FLNC's actin-binding capacity. Subsequently, we performed coimmunoprecipitation and immunofluorescent assays to validate the in silico findings and assess the impact of these mutations on the interactions with other binding partners and the subcellular localization of FLNC. Additionally, we generated and analyzed knock-in mouse models in which the FLNC-actin interaction was completely disrupted by these mutations. RESULTS: Our findings revealed that F93A/L98E mutations completely disrupted FLNC-actin interaction while preserving FLNC's ability to interact with other binding partners ITGB1 (ß1 integrin) and γ-SAG (γ-sarcoglycan), as well as maintaining FLNC subcellular localization. Loss of FLNC-actin interaction in embryonic cardiomyocytes resulted in embryonic lethality and cardiac developmental defects, including ventricular wall malformation and reduced cardiomyocyte proliferation. Moreover, disruption of FLNC-actin interaction in adult cardiomyocytes led to severe dilated cardiomyopathy, enhanced lethality and dysregulation of key cytoskeleton components. CONCLUSIONS: Our data strongly support the crucial role of FLNC as a bridge between actin filaments and ECM through its interactions with actin, ITGB1, γ-SAG, and other associated proteins in cardiomyocytes. Disruption of FLN-actin interaction may result in detachment of actin filaments from the extracellular matrix, ultimately impairing normal cardiac development and function. These findings also provide insights into mechanisms underlying cardiomyopathy associated with genetic variants in FLNC ABD and other regions.

Correlation between remnant cholesterol and hyperuricemia in American adults.

BACKGROUND: Remnant cholesterol (RC) is an important marker for assessing the risk of metabolic syndrome. However, the correlation between RC and hyperuricemia (HUA) remains unclear. This study aimed to explore the correlation between RC and HUA in American adults. METHODS: A total of 9089 participants from the 2013-2020 National Health and Nutrition Examination Survey were investigated. The correlation between RC and the odds of HUA was evaluated using multivariate logistic regression analysis. The nonlinear correlation was described using fitted smoothed curves. The correlation in subgroups was analyzed based on race, gender, alcohol consumption, age, body mass index, waist circumference, diabetes and moderate physical activities. RESULTS: RC was correlated with uric acid (Spearman's correlation coefficient = 0.208 in males and 0.215 in females; all P < 0.001). Multiple logistic regression analysis indicated a positive correlation between RC and the risk of HUA (odds ratio = 1.022 in males and 1.031 in females; all P < 0.001). Subgroup analysis revealed that the correlation was stronger in females, participants aged < 50 years, and those without diabetes. Furthermore, the generalized smooth curve fitting demonstrated a linear correlation between RC and HUA, without threshold or saturation effects. CONCLUSION: Elevated RC significantly and positively correlated with HUA in American adults. This correlation was stronger among females, participants aged < 50 years, and those without diabetes.

IGF2 deficiency promotes liver aging through mitochondrial dysfunction and upregulated CEBPB signaling in D-galactose-induced aging mice.

BACKGROUND: Liver aging, marked by cellular senescence and low-grade inflammation, heightens susceptibility to chronic liver disease and worsens its prognosis. Insulin-like growth factor 2 (IGF2) has been implicated in numerous aging-related diseases. Nevertheless, its role and underlying molecular mechanisms in liver aging remain largely unexplored. METHODS: The expression of IGF2 was examined in the liver of young (2-4 months), middle-aged (9-12 months), and old (24-26 months) C57BL/6 mice. In vivo, we used transgenic IGF2f/f; Alb-Cre mice and D-galactose-induced aging model to explore the role of IGF2 in liver aging. In vitro, we used specific short hairpin RNA against IGF2 to knock down IGF2 in AML12 cells. D-galactose and hydrogen peroxide treatment were used to induce AML12 cell senescence. RESULTS: We observed a significant reduction of IGF2 levels in the livers of aged mice. Subsequently, we demonstrated that IGF2 deficiency promoted senescence phenotypes and senescence-associated secretory phenotypes (SASPs), both in vitro and in vivo aging models. Moreover, IGF2 deficiency impaired mitochondrial function, reducing mitochondrial respiratory capacity, mitochondrial membrane potential, and nicotinamide adenine dinucleotide (NAD)+/NADH ratio, increasing intracellular and mitochondrial reactive oxygen species levels, and disrupting mitochondrial membrane structure. Additionally, IGF2 deficiency markedly upregulated CCAAT/enhancer-binding protein beta (CEBPB). Notably, inhibiting CEBPB reversed the senescence phenotypes and reduced SASPs induced by IGF2 deficiency. CONCLUSIONS: In summary, our findings strongly suggest that IGF2 deficiency promotes liver aging through mitochondrial dysfunction and upregulated CEBPB signaling. These results provide compelling evidence for considering IGF2 as a potential target for interventions aimed at slowing down the process of liver aging.

Retrospective Study of Three Cases of Congenital Leukemia with Clinical Presentations and Particular Cytogenetic Abnormality.

BACKGROUND: The goal is to assess the prognosis of cytogenetic abnormality, because cytogenetic abnormality is rarely encountered in clinical practice. METHODS: We retrospectively report three cytogenetic abnormality cases with clinical, cytogenetic, and genetic characteristic. RESULTS: All cases occurred within one month of birth and had prominent hepatosplenomegaly, including acute myeloid leukemia (case 1, case 2) and acute leukemia (case 3). Moreover, case 1 appeared as leukemia cutis at birth, case 2 was born with respiratory distress, and both showed hyperleukocytosis. The R-banded karyotype detected cytogenetic abnormality in three cases, case 1 with 46,XY,t(8;12)(q21;p13), case 2 with 47,XX,+21 and case 3 with 46,XY,t(6;X)(q22:p12), respectively. Especially in case 1, reverse transcription-polymerase chain reaction analysis showed MLL-AF10 rearranged. CONCLUSIONS: In our studies, all cases had not received chemotherapy and survived about 1 - 2 months. It suggests that cytogenetic disorders are closely related to disease development and likely result in fatal outcome if untreated. Thus, we proposed that a proper treatment decision is urgently needed in congenital leukemia.

Circulating soluble receptor for advanced glycation end products and other factors in type 2 diabetes patients with colorectal cancer.

BACKGROUND: Recent study showed that individuals with type 2 diabetes have a high risk of developing colorectal cancer (CRC), in which Receptor for Advanced Glycation End Products (RAGE) plays a pivotal role. We conducted a cross-sectional study to examine the relationships of circulating sRAGE, CRC and other clinical factors in type2 diabetes patients. METHODS: A total of 150 type 2 diabetes patients aged 50 years and older were enrolled, including 50 patients with CRC and 100 patients without CRC. We measured Serum levels of sRAGE and interleukin-6(IL-6) using an enzyme-linked immunosorbent assay (ELISA). In addition, other clinical parameters were also measured during hospitalization. RESULTS: Type 2 diabetes patients with CRC had higher triglyceride, total cholesterol, IL-6, and circulating sRAGE levels and lower use of medicines than type 2 diabetes patients without CRC. Circulating sRAGE was associated with an increased risk for CRC (OR = 2.289 for each SD increase in sRAGE, 95% CI = 1.037-5.051; P = 0.04) among Type 2 diabetes patients after adjustment for confounders. Furthermore, circulating sRAGE levels among type 2 diabetes patients were positively correlated with triglyceride (r = 0.377, P < 0.001), total cholesterol (r = 0.491, P < 0.001), and low-density lipoprotein cholesterol (LDL-c)(r = 0.330, P < 0.001) levels; the homeostatic model assessment for insulin resistance(HOMA-IR)score (r = 0.194, P = 0.017); and fasting serum insulin (r = 0.167, P = 0.041) and IL-6 (r = 0.311, P < 0.001) concentrations. CONCLUSIONS: Our results suggested that circulating sRAGE is independently risk factor for CRC, and also closely related to inflammation, dyslipidemia in type 2 diabetes patients.

LncRNA PDIA3P interacts with c-Myc to regulate cell proliferation via induction of pentose phosphate pathway in multiple myeloma.

Multiple myeloma (MM), the second most common hematologic malignancy, is an incurable disease characterized by the accumulation of malignant plasma cells within the bone marrow. Though great progresses have been made in understanding the mechanisms of MM, metabolic plasticity and drug resistance remain largely unknown. In this study, we found lncRNA Protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P) is highly expressed in MM and is associated with the survival rate of MM patients. PDIA3P regulates MM growth and drug resistance through Glucose 6-phosphate dehydrogenase (G6PD) and the pentose phosphate pathway (PPP). Mechanistically, we revealed that PDIA3P interacts with c-Myc to enhance its transactivation activity and binding to G6PD promoter, stimulating G6PD expression and PPP flux. Our study identified PDIA3P as a novel c-Myc interacting lncRNA and elucidated crucial roles for PDIA3P in metabolic regulation of MM, providing a potential therapeutic target for MM patients.

PEG-PLA nanoparticles facilitate siRNA knockdown in adult zebrafish heart.

The remarkable regenerative capacity of the zebrafish has made it an important model organism for studying heart regeneration. However, current loss-of-function studies are limited by a lack of conditional-knockout and effective gene-knockdown methods for the adult heart. Here, we report a novel siRNA knockdown method facilitated by poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-PLA) nanoparticles. The siRNA-encapsulated nanoparticles successfully entered cells and resulted in remarkable gene-specific knockdown in the adult heart. This effect was demonstrated by down-regulation of the Aldh1a2 and Dusp6 proteins after intrapleural delivery of nanoparticle-encapsulated siRNAs. Furthermore, siRNA-mediated knockdown of Aldh1a2 was sufficient to inhibit myocardial proliferation and decrease the numbers of Gata4-positive cardiomyocytes after ventricular resection. Therefore, the results of this work demonstrate that nanoparticle-facilitated siRNA delivery provides an alternative tool for loss-of-function studies of genes in the adult heart in particular and other organs in general in the adult zebrafish.

Genetic interaction between pku300 and fbn2b controls endocardial cell proliferation and valve development in zebrafish.

Abnormal cardiac valve morphogenesis is a common cause of human congenital heart disease. The molecular mechanisms regulating endocardial cell proliferation and differentiation into cardiac valves remain largely unknown, although great progress has been made on the endocardial contribution to the atrioventricular cushion and valve formation. We found that scotch tape(te382) (sco(te382)) encodes a novel transmembrane protein that is crucial for endocardial cell proliferation and heart valve development. The zebrafish sco(te382) mutant showed diminished endocardial cell proliferation, lack of heart valve leaflets and abnormal common cardinal and caudal veins. Positional cloning revealed a C946T nonsense mutation of a novel gene pku300 in the sco(te382) locus, which encoded a 540-amino-acid protein on cell membranes with one putative transmembrane domain and three IgG domains. A known G3935T missense mutation of fbn2b was also found ∼570 kb away from pku300 in sco(te382) mutants. The genetic mutant sco(pku300), derived from sco(te382), only had the C946T mutation of pku300 and showed reduced numbers of atrial endocardial cells and an abnormal common cardinal vein. Morpholino knockdown of fbn2b led to fewer atrial endocardial cells and an abnormal caudal vein. Knockdown of both pku300 and fbn2b phenocopied these phenotypes in sco(te382) genetic mutants. pku300 transgenic expression in endocardial and endothelial cells, but not myocardial cells, partially rescued the atrial endocardial defects in sco(te382) mutants. Mechanistically, pku300 and fbn2b were required for endocardial cell proliferation, endocardial Notch signaling and the proper formation of endocardial cell adhesion and tight junctions, all of which are crucial for cardiac valve development. We conclude that pku300 and fbn2b represent the few genes capable of regulating endocardial cell proliferation and signaling in zebrafish cardiac valve development.

Association between serum uric acid-to-high-density lipoprotein cholesterol ratio and insulin resistance in an American population: A population-based analysis.

INTRODUCTION: Previous studies have demonstrated a correlation between the serum uric acid-to-high-density lipoprotein cholesterol ratio (UHR) and insulin resistance (IR) in individuals with type 2 diabetes mellitus. However, no existing studies have investigated the relationship between IR and UHR in the general population. Therefore, the primary objective of this study was to investigate the correlation between UHR and IR in the general American population. METHODS: A sample of 8,817 participants was selected from the 2013 to 2020 National Health and Nutrition Examination Survey (NHANES). Homeostatic model assessment of insulin resistance (HOMA-IR) was used to assess insulin resistance. Multiple logistic regression, generalized smooth curve fitting, and subgroup analysis were used to assess the association between IR and UHR. RESULTS: Multiple logistic regression analysis indicated a significant correlation between insulin resistance and UHR, with odds ratios (OR) of 1.07 (95% CI = 1.03-1.11) in males and 1.18 (95% CI = 1.13-1.25) in females. A non-linear relationship and saturation effect between IR risk and UHR were observed, characterized by an inverted L-shaped curve and a critical inflection point at 8.82. It was found that the area under the ROC curve (AUC) of UHR was significantly larger (AUC = 0.703 for males and 0.747 for females, all P < 0.01) compared with the use of UA or HDL-C alone. Subgroup analysis showed that this independent association remain consistent regardless of race, age, BMI, diabetes, moderate activities, education level, alcohol drinking, and gender. CONCLUSION: Elevated UHR demonstrates a significant correlation with insulin resistance, so it can be used as a potential indicator of insulin resistance within the American population.

N-methyl-2-pyrrolidonium methyl sulfonate acidic ionic liquid as a new dynamic coating for separation of basic proteins by capillary electrophoresis.

A simple and economical CE method has been developed for the analysis of four model basic proteins by employing N-methyl-2-pyrrolidonium methyl sulfonate ionic liquid (IL) as the dynamic coating material based on the interaction of both between electrostatic attraction and hydrogen bond, and between the organic cations of IL and the inner surface of bare fused-silica capillary. The N-methyl-2-pyrrolidonium-based IL modified capillary not only generated a stable suppressed electroosmotic flow, but also effectively eliminated the wall adsorption of proteins. Several important parameters such as the IL concentration, pH values, and concentrations of the background electrolyte were optimized to improve the separation of basic proteins. Consequently, under the optimum separation conditions, a satisfied separation of basic proteins including lysozyme, cytochrome c, ribonuclease A, and α-chymotrypsinogen A with theoretical plates ranging from 2.09 × 10(5) to 4.48 × 10(5) plates/m had been accomplished within 15 min. The proposed method first illustrated the effect of hydrogen bond between coating material and inner capillary surface on the coating, which should be a new strategy to design and select more effective coating materials to form more stable coatings in CE.

Electron Modulation and Morphology Engineering Jointly Accelerate Oxygen Reaction to Enhance Zn-Air Battery Performance.

Combining morphological control engineering and diatomic coupling strategies, heteronuclear FeCo bimetals are efficiently intercalated into nitrogen-doped carbon materials with star-like to simultaneously accelerate oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). The half-wave potential and kinetic current density of the ORR driven by FeCoNC/SL surpass the commercial Pt/C catalyst. The overpotential of OER is as low as 316 mV (η10 ), and the mass activity is at least 3.2 and 9.4 times that of mononuclear CoNC/SL and FeNC/SL, respectively. The power density and specific capacity of the Zn-air battery with FeCoNC/SL as air cathode are as high as 224.8 mW cm-2 and 803 mAh g-1 , respectively. Morphologically, FeCoNC/SL endows more reactive sites and accelerates the process of oxygen reaction. Density functional theory reveals the active site of the heteronuclear diatomic, and the formation of FeCoN5C configuration can effectively tune the d-band center and electronic structure. The redistribution of electrons provides conditions for fast electron exchange, and the change of the center of the d-band avoids the strong adsorption of intermediate species to simultaneously take into account both ORR and OER and thus achieve high-performance Zn-air batteries.

Atom-dispersed copper and nano-palladium in the boron-carbon-nitrogen matric cooperate to realize the efficient purification of nitrate wastewater and the electrochemical synthesis of ammonia.

Electrochemical nitrate reduction reaction (NIRR) driven by sustainable energy is not only expected to realize the green production of ammonia under ambient conditions, but also a promising way to purify nitrate wastewater. The ammonia yield rate and Faradaic efficiency of NIRR catalyzed by Pd10Cu/BCN constructed with structural constraints and pre-embedded reducing agent strategies were as high as 102,153 µg h-1 mgcat.-1 and 91.47%, respectively. Pd10Cu/BCN can remove nearly 100% of 50 mg L-1 NO3- without NO2- residue within 10 h, and the realization of this effect does not require the participation of any chloride. Control experiments and DFT calculations explain the efficient operation mechanism of NIRR on Pd10Cu/BCN, where the Pd and CuN4 sites play the role of synergistic catalysis. Compared with the reported literature, Pd10Cu/BCN with good biocompatibility has become an outstanding representative of NIRR catalyst, which provides an alternative way for the green production of ammonia and the purification of nitrate wastewater.

The Effects of the COVID-19 Pandemic on Mental Health Among Older Adults From Different Communities in Chengmai County, China: Cross-sectional Study.

BACKGROUND: Due to the strict measures employed to control the spread of SARS-CoV-2, the extent of COVID-19 goes beyond morbidity and mortality and affects individuals' mental health in the long term. OBJECTIVE: This cross-sectional study aimed to investigate the effects of the COVID-19 pandemic on mental health and its contributing factors among older people in Chengmai County, China. METHODS: A web-based survey was administered through WeChat between March and April 2020. Older people (ie, >50 years) from local and foreign community groups completed the survey, which included items on sociodemographic and clinical characteristics, the 7-item Generalized Anxiety Disorder scale (GAD-7), and the 9-item Patient Health Questionnaire (PHQ-9). Independent t tests and a multiple linear regression analysis were used to investigate differences between anxiety and depression and the factors associated with these symptoms across the 2 groups. RESULTS: Overall, 469 responses were received; 119 responses (25.4%) were from male participants and 202 (43.1%) were from those older than 65 years. Of the 469 responses, 245 (52.2%) were from the local community group and 224 (47.8%) from the foreign group. The mean GAD-7 (P=.003) scores were significantly higher in the local group. Anxiety was significantly more present in the local group (61/245, 24.9% compared to 35/224, 15.6% in the foreign group; P=.01). A total of 6 respondents presented severe anxiety and 2 presented severe depression. CONCLUSIONS: This study demonstrated that both community groups of older adults from the Chinese "Hometown of Longevity" presented anxiety or depressive disorders during the first months of the pandemic. Local community groups presented significantly more mental health disorders, which were associated with a history of previous psychological disorders.

Cu Nanoparticle-Decorated Boron-Carbon-Nitrogen Nanosheets for Electrochemical Determination of Chloramphenicol.

In the present work, irregular Cu nanoparticle-decorated boron-carbon-nitrogen (Cu-BCN) nanosheets were successfully synthesized. A Cu-BCN dispersion was deposited on a bare glassy carbon electrode (GCE) to prepare an electrochemical sensor (Cu-BCN/GCE) for the detection of chloramphenicol (CAP) in the environment. Cu-BCN was characterized using high-resolution scanning transmission electron microscopy (HRSTEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis, and X-ray photoelectron spectroscopy (XPS). The performance of the Cu-BCN/GCE was studied using electrochemical impedance spectroscopy (EIS), and its advantages were proven by electrode comparison. Differential pulse voltammetry (DPV) was used to optimize the experimental conditions, including the amount of Cu-BCN deposited, enrichment potential, deposition time, and pH of the electrolyte. A linear relationship between the CAP concentration and current response was obtained under the optimized experimental conditions, with a wide linear range and a limit of detection (LOD) of 2.41 nmol/L. Cu-BCN/GCE exhibited high stability, reproducibility, and repeatability. In the presence of various organic and inorganic species, the influence of the Cu-BCN-based sensor on the current response of CAP was less than 5%. Notably, the prepared sensor exhibited excellent performance in real-water samples, with satisfactory recovery.

Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction.

Dual-specificity phosphatase 6 (DUSP6) serves a specific and conserved function on the dephosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). We previously identified Dusp6 as a regenerative repressor during zebrafish heart regeneration, therefore we propose to investigate the role of this repressor in mammalian cardiac repair. Utilizing a rat strain harboring Dusp6 nonsense mutation, rat neutrophil-cardiomyocyte co-culture, bone marrow transplanted rats and neutrophil-specific Dusp6 knockout mice, we find that Dusp6 deficiency improves cardiac outcomes by predominantly attenuating neutrophil-mediated myocardial damage in acute inflammatory phase after myocardial infarction. Mechanistically, Dusp6 is transcriptionally activated by p38-C/EBPß signaling and acts as an effector for maintaining p-p38 activity by down-regulating pERK and p38-targeting phosphatases DUSP1/DUSP16. Our findings provide robust animal models and novel insights for neutrophil-mediated cardiac damage and demonstrate the potential of DUSP6 as a therapeutic target for post-MI cardiac remodeling and other relevant inflammatory diseases.

Cubic platinum nanoparticles capped with Cs2[closo-B12H12] as an effective oxidation catalyst for converting methane to ethanol.

Direct conversion of methane to alcohol remains a key challenge. Here, we report a novel aqueous catalyst, cubic platinum (Pt) nanoparticles capped with Cs2[closo-B12H12], capable of direct oxidation of methane to ethanol and methanol with H2O2 and O2 under facile conditions. The selective conversion to ethanol exceeded 97% with a yield reaching 148.41 mol·kgcat-1·h-1 at 50 °C. Experiments with 5,5'-dimethy1-1-pyrroline-N-oxide (DMPO) and electron paramagnetic resonance (EPR) tests revealed that methane oxidation occurred via free-radical chain reactions involving CH3, CH3CH2, and HO radicals. Theoretical analysis suggested that the {1 0 0} surface of the Pt nanoparticles was capped with Cs2[closo-B12H12] mediated by Pt-B bonds with a binding energy of -278.6 kcal/mol. This promoted the growth of particles along the direction of the (1 0 0) facets and finally formed a cubic structure. The EPR tests combined with theoretical calculations confirmed the hypothesis that methane-ethane-ethanol conversion was mediated by the catalyst by employing the features of nano-platinum and Cs2[closo-B12H12], on which only C1 and C2 products were generated, while no products with three or more carbon atoms were detected in the reaction systems described above.

P311 regulates distal lung development via its interaction with several binding proteins.

Little is known about the molecular mechanisms underlying alveolar development. P311, a putative neuronal protein originally identified for its high expression during neuronal development, has once been reported to play a potential role in distal lung generation. However, the function of this protein has been poorly understood so far. Hence, we carried out a yeast two-hybrid screen, combining with other protein-protein interaction experiments, to isolate several binding partners of P311 during lung development, which may help us explore its function. We report 7 proteins here, including Gal-1, Loxl-1 and SPARC, etc, that can interact with it. Most of them have similar spatio-temporal expression patterns to P311. In addition, it was also found that P311 could stimulate their expression indirectly in L929 mouse fibroblast. Besides, computational methods were applied to construct a P311 centered protein-protein interaction network during alveolarization, using the 7 binding partners and their protein interaction information provided by public data resources. By analyzing the structure and function of this network, the effects of P311 on lung development were further clarified and all of the bioinformatic predictions from the network could be validated by real experiments. We have found here that P311 can control lung redox events, extracellular matrix and cell cycle progression, which are all crucial to pulmonary morphogenesis. This gives us a novel thought to explore the mechanisms controlling alveolarization.

Bioinformatics analysis of the network of histone H3 lysine 9 trimethylation in acute myeloid leukaemia.

Changes in histone H3 lysine 9 trimethylation (H3K9me3) may be related to the development of drug­resistant acute myeloid leukaemia (AML); insights into the network of H3K9me3 may improve patient prognosis. Patient data were derived from the Gene Expression Omnibus (GEO) database and data from AML cells treated with chidamide, a novel benzamide chemical class of histone deacetylase inhibitor (HDACi), in vitro were derived from ChIP­seq. Patients and AML cell data were analysed using GEO2R, GOseq, KOBAS, the STRING database and Cytoscape 3.5.1. We identified several genes related to the upregulation or downregulation of H3K9me3 in AML patients; some of these genes were related to apoptosis, autophagy, and the pathway of cell longevity. AML cells treated with chidamide in vitro showed the same gene changes. The protein interactions in the network did not have significantly more interactions than expected, suggesting the need for more research to identify these interactions. One compelling result from the protein interaction study was that sirtuin 1 (SIRT1) may have an indirect interaction with lysine­specific demethylase 4A (KDM4A). These results help explain alterations of H3K9me3 in AML that may direct further studies aimed at improving patient prognosis. These results may also provide a basis for chidamide as a treatment strategy for AML patients in the future.

Efficient Ambient Electrocatalytic Ammonia Synthesis by Nanogold Triggered via Boron Clusters Combined with Carbon Nanotubes.

Currently, the development of stable electrochemical nitrogen reduction reaction (ENRR) catalysts with high N2 conversion activity and low cost to instead of the traditional Haber-Bosch ammonia production process of high-energy consumption remains a great challenge for researchers. Here, we have immobilized reductive closo-[B12H11]- boron clusters on a carbon nanotubes (CNT) surface and have successfully prepared a novel Au-CNT catalyst with extraordinary ENRR activity after adding HAuCl4 to the CNT-[B12H11]- precursor. The excellent properties of ammonia yield (57.7 µg h-1 cm-2) and Faradaic efficiency (11.97%) make it possible to achieve using this Au-CNT catalyst in large-scale industrial production of ammonia. Furthermore, its outstanding cyclic stability and long-term tolerability performance make it one of the most cost-effective catalysts to date. Here, by means of density functional theory we disclose the associative mechanism of N2-to-NH3 conversion on the Au(111) surface, providing visual theoretical support for the experimental results.