ABSTRACT
Cathodic CO2 adsorption and activation is essential for high-temperature CO2 electrolysis in solid oxide electrolysis cells (SOECs). However, the component of oxygen ionic conductor in the cathode displays limited electrocatalytic activity. Herein, stable single Ruthenium (Ru) atoms are anchored on the surface of oxygen ionic conductor (Ce0.8 Sm0.2 O2-δ , SDC) via the strong covalent metal-support interaction, which evidently modifies the electronic structure of SDC surface for favorable oxygen vacancy formation and enhanced CO2 adsorption and activation, finally evoking the electrocatalytic activity of SDC for high-temperature CO2 electrolysis. Experimentally, SOEC with the Ru1 /SDC-La0.6 Sr0.4 Co0.2 Fe0.8 O3-δ cathode exhibits a current density as high as 2.39â A cm-2 at 1.6â V and 800 °C. This work expands the application of single atom catalyst to the high-temperature electrocatalytic reaction in SOEC and provides an efficient strategy to tailor the electronic structure and electrocatalytic activity of SOEC cathode at the atomic scale.
ABSTRACT
PURPOSE: Previous work identified rare variants in DSTYK associated with human congenital anomalies of the kidney and urinary tract (CAKUT). Here, we present a series of mouse and human studies to clarify the association, penetrance, and expressivity of DSTYK variants. METHODS: We phenotypically characterized Dstyk knockout mice of 3 separate inbred backgrounds and re-analyzed the original family segregating the DSTYK c.654+1G>A splice-site variant (referred to as "SSV" below). DSTYK loss of function (LOF) and SSVs were annotated in individuals with CAKUT, epilepsy, or amyotrophic lateral sclerosis vs controls. A phenome-wide association study analysis was also performed using United Kingdom Biobank (UKBB) data. RESULTS: Results demonstrate â¼20% to 25% penetrance of obstructive uropathy, at least, in C57BL/6J and FVB/NJ Dstyk-/- mice. Phenotypic penetrance increased to â¼40% in C3H/HeJ mutants, with mild-to-moderate severity. Re-analysis of the original family segregating the rare SSV showed low penetrance (43.8%) and no alternative genetic causes for CAKUT. LOF DSTYK variants burden showed significant excess for CAKUT and epilepsy vs controls and an exploratory phenome-wide association study supported association with neurological disorders. CONCLUSION: These data support causality for DSTYK LOF variants and highlights the need for large-scale sequencing studies (here >200,000 cases) to accurately assess causality for genes and variants to lowly penetrant traits with common population prevalence.
Subject(s)
Epilepsy , Urinary Tract , Urogenital Abnormalities , Animals , Mice , Humans , Penetrance , Mice, Inbred C3H , Mice, Inbred C57BL , Urogenital Abnormalities/genetics , Kidney/abnormalities , Risk Factors , Epilepsy/genetics , Receptor-Interacting Protein Serine-Threonine Kinases/geneticsABSTRACT
Perovskites exhibit excellent high-temperature oxygen evolution reaction (OER) activities as the anodes of solid oxide electrolysis cells (SOECs). However, the relationship between ion ordering and OER performances is rarely investigated. Herein, a series of PrBaCo2-x Fex O5+δ perovskites with tailored ion orderings are constructed. Physicochemical characterizations and density functional theory calculations confirm that the oxygen bulk migration and surface transport capacities as well as the OER activities are promoted by the A-site cation ordering, but weakened by the oxygen vacancy ordering. Hence, SOEC with the A-site-ordered and oxygen-vacancy-disordered PrBaCo2 O5+δ anode exhibits the highest performance of 3.40â A cm-2 at 800 °C and 2.0â V. This work sheds light on the critical role of ion orderings in the high-temperature OER performance and paves a new way for screening novel anode materials of SOECs.
ABSTRACT
Hepatic stellate cells (HSCs) play an important role in the initiation and development of liver fibrogenesis, and abnormal glucose metabolism is increasingly being considered a crucial factor controlling phenotypic transformation in HSCs. However, the role of the factors affecting glycolysis in HSCs in the experimental models of liver fibrosis has not been completely elucidated. In this study, we showed that glycolysis was significantly enhanced, while the expression of brain and muscle arnt-like protein-1 (Bmal1) was downregulated in fibrotic liver tissues of mice, primary HSCs, and transforming growth factor-ß1 (TGF-ß1)-induced LX2 cells. Overexpression of Bmal1 in TGF-ß1-induced LX2 cells blocked glycolysis and inhibited the proliferation and phenotypic transformation of activated HSCs. We further confirmed the protective effect of Bmal1 in liver fibrosis by overexpressing Bmal1 from hepatic adeno-associated virus 8 in mice. In addition, we also showed that the regulation of glycolysis by Bmal1 is mediated by the isocitrate dehydrogenase 1/α-ketoglutarate (IDH1/α-KG) pathway. Collectively, our results indicated that a novel Bmal1-IDH1/α-KG axis may be involved in regulating glycolysis of activated HSCs and might hence be used as a therapeutic target for alleviating liver fibrosis.
Subject(s)
ARNTL Transcription Factors/metabolism , Glycolysis , Hepatic Stellate Cells/metabolism , Isocitrate Dehydrogenase/metabolism , Liver Cirrhosis/metabolism , ARNTL Transcription Factors/physiology , Animals , Blotting, Western , Chromatography, High Pressure Liquid , Flow Cytometry , Hepatic Stellate Cells/pathology , Liver Cirrhosis/physiopathology , Male , Mass Spectrometry , Mice , Mice, Inbred C57BLABSTRACT
A novel facultatively aerobic bacterium designated SY8 was isolated from a peanut rhizosphere soil sample collected in Jiangsu Province, China. Cells are Gram-stain-positive, rod-shaped, and agar colonies are creamy, opaque, and usually rhizoidal. Strain growth occurs at 30 - 45 °C (optimum 30 °C), pH 4.0 - 10.0 (optimum pH 6.0) and 0 - 4% (w/v) NaCl (optimum 2%) in Luria-Bertani medium. Phylogenetic analysis of the 16S rRNA gene sequences indicated that strain SY8 forms a distinct lineage in the clade of genus Bacillus and is related to Bacillus pseudomycoides DSM 12442 T (99.9%). Phylogenetic analysis of the concatenated gene sequences of 16S rRNA, gryB and rpoD also indicated that strain SY8 forms a distinct lineage in Bacillus. Calculation of the average nucleotide identities and the digital DNA-DNA hybridization values between strain SY8 and the related type Bacillus strains further revealed that strain SY8 represents a distinct species. The predominant cellular fatty acids are iso C15:0 (28.7%) and summed feature 3 (C16:1ω7c and/or C16:1ω6c) (10.3%). The major polar lipids consisted of diphosphatidyl glycerol, phosphatidyl glycerol, phosphatidyl ethanolamine, phosphatidylinositol, and three unidentified phospholipids. The major menaquinone of SY8 was MK-7. Based on phenotypic, phylogenetic, chemotaxonomic, and genomic features, strain SY8 represents a novel species of the genus Bacillus. The name Bacillus arachidis sp. nov. is proposed with strain SY8T (= CCTCC AB 2021100 T=LMG 32409 T) designated as the type strain.
Subject(s)
Bacillus , Fabaceae , Arachis , Bacterial Typing Techniques , Base Composition , DNA, Bacterial/genetics , Fabaceae/genetics , Fatty Acids , Phosphatidylglycerols , Phylogeny , RNA, Ribosomal, 16S/genetics , Rhizosphere , Sequence Analysis, DNA , Soil , Soil MicrobiologyABSTRACT
Renal agenesis and hypodysplasia (RHD) are major causes of pediatric chronic kidney disease and are highly genetically heterogeneous. We conducted whole-exome sequencing in 202 case subjects with RHD and identified diagnostic mutations in genes known to be associated with RHD in 7/202 case subjects. In an additional affected individual with RHD and a congenital heart defect, we found a homozygous loss-of-function (LOF) variant in SLIT3, recapitulating phenotypes reported with Slit3 inactivation in the mouse. To identify genes associated with RHD, we performed an exome-wide association study with 195 unresolved case subjects and 6,905 control subjects. The top signal resided in GREB1L, a gene implicated previously in Hoxb1 and Shha signaling in zebrafish. The significance of the association, which was p = 2.0 × 10-5 for novel LOF, increased to p = 4.1 × 10-6 for LOF and deleterious missense variants combined, and augmented further after accounting for segregation and de novo inheritance of rare variants (joint p = 2.3 × 10-7). Finally, CRISPR/Cas9 disruption or knockdown of greb1l in zebrafish caused specific pronephric defects, which were rescued by wild-type human GREB1L mRNA, but not mRNA containing alleles identified in case subjects. Together, our study provides insight into the genetic landscape of kidney malformations in humans, presents multiple candidates, and identifies SLIT3 and GREB1L as genes implicated in the pathogenesis of RHD.
Subject(s)
Congenital Abnormalities/genetics , Exome/genetics , Kidney Diseases/congenital , Kidney/abnormalities , Mutation/genetics , Neoplasm Proteins/genetics , Alleles , Animals , Case-Control Studies , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , Female , Genetic Heterogeneity , Genome-Wide Association Study/methods , Genotype , Heredity/genetics , Homozygote , Humans , Kidney Diseases/genetics , Male , Membrane Proteins/genetics , Mice , Phenotype , RNA, Long Noncoding/genetics , Urinary Tract/abnormalities , Urogenital Abnormalities/genetics , ZebrafishABSTRACT
BACKGROUND: The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. METHODS: We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. RESULTS: We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10-14). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. CONCLUSIONS: We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.).
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Chromosome Deletion , DiGeorge Syndrome/genetics , Haploinsufficiency , Kidney/abnormalities , Nuclear Proteins/genetics , Urinary Tract/abnormalities , Adolescent , Animals , Child , Chromosomes, Human, Pair 22 , Exome , Female , Heterozygote , Humans , Infant , Infant, Newborn , Male , Mice , Models, Animal , Sequence Analysis, DNA , Young Adult , ZebrafishABSTRACT
The tumor suppressor protein p53 is a central governor of various cellular signals. It is well accepted that ubiquitination as well as ubiquitin-like (UBL) modifications of p53 protein is critical in the control of its activity. Interferon-stimulated gene 15 (ISG15) is a well-known UBL protein with pleiotropic functions, serving both as a free intracellular molecule and as a modifier by conjugating to target proteins. Initially, attentions have historically focused on the antiviral effects of ISG15 pathway. Remarkably, a significant role in the processes of autophagy, DNA repair, and protein translation provided considerable insight into the new functions of ISG15 pathway. Despite the deterministic revelation of the relation between ISG15 and p53, the functional consequence of p53 ISGylation appears somewhat confused. More important, more recent studies have hinted p53 ubiquitination or other UBL modifications that might interconnect with its ISGylation. Here, we aim to summarize the current knowledge of p53 ISGylation and the differences in other significant modifications, which would be beneficial for the development of p53-based cancer therapy.
Subject(s)
Cytokines/metabolism , Neoplasms/metabolism , Tumor Suppressor Protein p53/metabolism , Ubiquitination , Ubiquitins/metabolism , Animals , Antineoplastic Agents/therapeutic use , Humans , Molecular Targeted Therapy , Mutation , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/pathology , Protein Stability , Proteolysis , Sumoylation , Tumor Suppressor Protein p53/genetics , Ubiquitination/drug effectsABSTRACT
Oxidative dehydrogenation of ethane (ODE) is limited by the facile deep oxidation and potential safety hazards. Now, electrochemical ODE reaction is incorporated into the anode of a solid oxide electrolysis cell, utilizing the oxygen species generated at anode to catalytically convert ethane. By infiltrating γ-Al2 O3 onto the surface of La0.6 Sr0.4 Co0.2 Fe0.8 O3-δ -Sm0.2 Ce0.8 O2-δ (LSCF-SDC) anode, the ethylene selectivity reaches as high as 92.5 %, while the highest ethane conversion is up to 29.1 % at 600 °C with optimized current and ethane flow rate. Density functional theory calculations and inâ situ X-ray photoelectron spectroscopy characterizations reveal that the Al2 O3 /LSCF interfaces effectively reduce the amount of adsorbed oxygen species, leading to improved ethylene selectivity and stability, and that the formation of Al-O-Fe alters the electronic structure of interfacial Fe center with increased density of state around Fermi level and downshift of the empty band, which enhances ethane adsorption and conversion.
ABSTRACT
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic polyarticular pain, and its main pathological features include inflammatory cell infiltration, synovial fibroblast proliferation, and cartilage erosion. Immune cells, synovial cells and neuroendocrine factors play pivotal roles in the pathophysiological mechanism underlying rheumatoid arthritis. Biological clock genes regulate immune cell functions, which is linked to rhythmic changes in arthritis pathology. Additionally, the interaction between biological clock genes and neuroendocrine factors is also involved in rhythmic changes in rheumatoid arthritis. This review provides an overview of the contributions of circadian rhythm genes to RA pathology, including their interaction with the immune system and their involvement in regulating the secretion and function of neuroendocrine factors. A molecular understanding of the role of the circadian rhythm in RA may offer insights for effective disease management.
ABSTRACT
Solid oxide electrolysis cells provide a practical solution for the direct conversion of CO2 to other chemicals (i.e. CO), however, an in-depth mechanistic understanding of the dynamic reconstruction of active sites for perovskite cathodes during CO2 electrolysis remains a great challenge. Herein, we identify that iridium-doped Sr2Fe1.45Ir0.05Mo0.5O6-δ (SFIrM) perovskite displays a dynamic electrochemical reconstruction feature during CO2 electrolysis with abundant exsolution of highly dispersed IrFe alloy nanoparticles on the SFIrM surface. The in situ reconstructed IrFe@SFIrM interfaces deliver a current density of 1.46 A cm-2 while maintaining over 99% CO Faradaic efficiency, representing a 25.8% improvement compared with the Sr2Fe1.5Mo0.5O6-δ counterpart. In situ electrochemical spectroscopy measurements and density functional theory calculations suggest that the improved CO2 electrolysis activity originates from the facilitated formation of carbonate intermediates at the IrFe@SFIrM interfaces. Our work may open the possibility of using an in situ electrochemical poling method for CO2 electrolysis in practice.
ABSTRACT
Black Americans have a significantly higher risk of developing chronic kidney disease (CKD), especially focal segmental glomerulosclerosis (FSGS), than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of Black Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of the APOL1 high-risk alleles. These findings have important implications for our understanding of the mechanisms of APOL1 -associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele.
ABSTRACT
African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of the APOL1 high-risk alleles. These findings have important implications for our understanding of the mechanisms of APOL1-associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele.
Subject(s)
Glomerulosclerosis, Focal Segmental , Humans , Glomerulosclerosis, Focal Segmental/genetics , Apolipoprotein L1/genetics , Genetic Predisposition to Disease , Risk Factors , Genotype , Apolipoproteins/geneticsABSTRACT
Herein, we report a facile approach for rapid and maskless production of subwavelength structured antireflective surfaces with high and broadband transmittance-direct laser interference ablation. The interfered laser beams were introduced into the surface of a bare optical substrate, where structured surfaces consisting of a micropillar array were produced by two-step laser irradiation in the time frame of seconds. A multiple exposure of the two-beam interference approach was proposed instead of multiple-beam interference to simply realize planar patterns of a high aspect ratio. Tall sinusoidal pillars were created and shaped by pulse shot number control. As an example of the application, zinc sulfide substrates were processed with the technology, from which high transmission at an infrared wavelength, over 92%, at normal incidence was experimentally achieved.
Subject(s)
Biomimetics/instrumentation , Lasers , Optical Phenomena , Absorption , Sulfides/chemistry , Surface Properties , Time Factors , Zinc Compounds/chemistryABSTRACT
BACKGROUND AND AIMS: Alcoholic fatty liver (AFL) is a liver disease caused by long-term excessive drinking and is characterized by hepatic steatosis. Understanding the regulatory mechanism of steatosis is essential for the treatment of AFL. Rev-erbα is a member of the Rev-erbs family of nuclear receptors, playing an important role in regulating lipid metabolism. However, its functional role in AFL and its underlying mechanism remains unclear. RESULTS: Rev-erbα was upregulated in the liver of EtOH-fed mice and EtOH-treated L-02 cells. Further, Rev-erbα activation exacerbates steatosis in L-02 cells. Inhibition/downexpression of Rev-erbα improved steatosis. Mechanistically, autophagy activity was inhibited in vivo and vitro. Interestingly, inhibition/downexpression of Rev-erbα enhanced autophagy. Furthermore, silencing of Rev-erbα up-regulated the nuclear expression of Bmal1. Autophagy activity was inhibited and steatosis was deteriorated after EtOH-treated L-02 cells were cotransfected with Rev-erbα shRNA and Bmal1 siRNA. CONCLUSIONS: Rev-erbα induces liver steatosis, which promotes the progression of AFL. Our study reveals a novel steatosis regulatory mechanism in AFL and suggest that Rev-erbα might be a potential therapeutic target for AFL.
ABSTRACT
To understand the degradation and environmental fate of pyrethroids, the process of their photodegradation under simulated natural conditions was investigated. The results showed that the degradation process follows first-order kinetics. The degradation intermediates were identified with gas chromatography-mass spectrometry. A plausible mechanism was discussed to explain the process. Several influences on degradation process were investigated and reported such as the effects of initial concentration of pyrethroids, total time of light irradiation, solvents, and light source, as well as the effect of a few substances that exist in the environment. This study could be a good reference for the degradation of pyrethroids in practical circumstances.
Subject(s)
Nitriles/chemistry , Photolysis , Pyrethrins/chemistry , Refuse Disposal/methodsABSTRACT
CO2 electroreduction by solid oxide electrolysis cells (SOECs) can not only attenuate the greenhouse effect, but also convert surplus electrical energy into chemical energy. The adsorption and activation of CO2 on the cathode play an important role in the SOEC performance. La0.6 Sr0.4 Co0.2 Fe0.8 O3-δ -Ce0.8 Sm0.2 O2-δ (LSCF-SDC; SDC=samarium-doped ceria) is a promising SOEC cathode. However, its electrocatalytic activity still needs to be improved. In this study, Pt/SDC interfaces are constructed by decorating Pt nanoparticles onto the SDC surface. Electrochemical measurements indicate that the polarization resistance of the SOEC is decreased from 0.308 to 0.120â Ω cm2 , and the current density is improved from 0.913 to 1.420â A cm-2 at 1.6â V and 800 °C. Physicochemical characterizations suggest that construction of the Pt/SDC interfaces increases the oxygen vacancy concentration on the cathode and boosts CO2 adsorption and dissociation, which leads to enhanced CO2 electroreduction performance in SOECs.
ABSTRACT
A method for the determination of trace Te in the complex geological samples by hydride generation atomic fluorescence spectrometry using MIBK as extraction reagent was developed. The extraction ability of Te (IV) in the HCl-NaBr-MIBK system and the anti-extraction behavior of Te (IV) in the HCl-KMnO4-MIBK system were studied. Under the optimum extraction condition of 3.6 mol x L(-1) HCl-100 g x L(-1) NaBr, Te (IV) was extracted completely by MIBK, Te (IV) in the MIBK phase was oxidized to Te (VI) with HCl-KMnO4, Te (VI) in the MIBK phase was anti-extracted using water, then the interference elements such as Au, Ag, Pt, Pd, Cu, Pb, Co, Ni, Cd, As, Sb, Bi, Hg, Tl and Se for the determination of Te by hydride generation atomic fluorescence spectrometry were eliminated successfully. The detection limit of Te was 1.14 x 10(-4) microg(-1), and the relative standard deviations of Te was 6.84%. The method was applied to complicated geological samples.