CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia.

Resistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-of-function experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GCresistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GCs against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL.

The Effect of Notch and Molecular Weight on the Impact Fracture Behavior of Polycarbonate.

The impact protection applications of polycarbonate (PC) products are gradually increasing. Due to the high sensitivity of PC to notches, research on notch impacts has become very important. In this paper, the impact performance of PC with two different molecular weights under different notch states was investigated. Three notch size factors, namely notch tip radius, notch angle, and notch center depth, were selected to design orthogonal experiments and research impact toughness. Subsequently, a single-factor study was conducted on the impact radius at the tip of the notch, which was the most important factor affecting the impact performance. Research shows that the brittle-ductile-transition tip radius of high-molecular-weight PC is 0.15 mm, and it has a higher impact toughness than low-molecular-weight PC during the brittle fracture process. The brittle-ductile-transition tip radius of lower molecular weight is 0.25 mm, while low-molecular-weight PC has a higher impact toughness during the ductile fracture process. The brittle and ductile fracture mechanisms of PC with different molecular weights were analyzed by observing the stress changes and cross-sectional morphology.

Comparison of industry payments to psychiatrists and psychiatric advanced practice clinicians in the USA, 2021: a cross-sectional study.

OBJECTIVES: To compare industry payment patterns among US psychiatrists and psychiatric advanced practice clinicians (APCs) and determine how scope of practice laws has influenced these patterns. DESIGN: Cross-sectional study. SETTING: This study used the publicly available US Centers for Medicare and Medicaid Services Sunshine Act Open Payment database and the National Plan and Provider Enumeration System (NPPES) database for the year 2021. PARTICIPANTS: All psychiatrists and psychiatric APCs (subdivided into nurse practitioners (NPs) and clinical nurse specialists (CNSs)) included in either database. PRIMARY AND SECONDARY OUTCOME MEASURES: Number and percentage of clinicians receiving industry payments and value of payments received. Total payments and number of transactions by type of payment, payment source and clinician type were also evaluated. RESULTS: A total of 85 053 psychiatric clinicians (61 011 psychiatrists (71.7%), 21 895 NPs (25.7%), 2147 CNSs (2.5%)) were reviewed; 16 240 (26.6%) psychiatrists received non-research payment from industry, compared with 10 802 (49.3%) NPs and 231 (10.7%) CNSs (p<0.001) for pairwise comparisons). Psychiatric NPs were significantly more likely to receive industry payments compared with psychiatrists (incidence rate ratio (IRR), 1.85 (95% CI 1.81 to 1.88); p<0.001)). Compared with psychiatrists, NPs were more likely to receive payments of > United States Dollars (US) $) 100 (33.9% vs 14.6%; IRR, 2.14 (2.08 to 2.20); p<0.001) and > US$ 1000 (5.3% vs 4.1%; IRR, 1.29 (1.20 to 1.38); p<0.001) but less likely to receive > US$ 10 000 (0.4% vs 1.0%; IRR, 0.39 (0.31 to 0.49); p<0.001). NPs in states with 'reduced' or 'restricted' scope of practice received more frequent payments (reduced: IRR, 1.22 (1.18 to 1.26); restricted: IRR, 1.26 (1.22 to 1.30), both p<0.001). CONCLUSIONS: Psychiatric NPs were nearly two times as likely to receive industry payments as psychiatrists, while psychiatric CNSs were less than half as likely to receive payment. Stricter scope of practice laws increases the likelihood of psychiatric NPs receiving payment, the opposite of what was found in a recent specialty agnostic study.

Co-production of pigment and high value-added bacterial nanocellulose from Suaeda salsa biomass with improved efficiency of enzymatic saccharification and fermentation.

This study evaluated the co-production of pigment and bacterial nanocellulose (BNC) from S. salsa biomass. The extraction of the beet red pigment reduced the salts and flavonoids contents by 82.7%-100%, promoting the efficiencies of enzymatic saccharification of the biomass and the fermentation of BNC from the hydrolysate. SEM analysis revealed that the extraction process disrupted the lignocellulosic fiber structure, and the chemical analysis revealed the lessened cellulase inhibitors, consequently facilitating enzymatic saccharification for 10.4 times. BNC producing strains were found to be hyper-sensitive to NaCl stress, produced up to 400.4% more BNC from the hydrolysate after the extraction. The fermentation results of BNC indicated that the LDU-A strain yielded 2.116 g/L and 0.539 g/L in ES-M and NES-M, respectively. In comparison to the control, the yield in ES-M increased by approximately 20.0%, while the enhancement in NES-M was more significant, reaching 292.6%. After conducting a comprehensive characterization of BNC derived from S. salsa through Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), and Thermogravimetric Analysis (TGA), the average fiber diameter distribution of these four BNC materials ranges from 22.23 to 33.03 nanometers, with a crystallinity range of 77%-90%. Additionally, they exhibit a consistent trend during the thermal degradation process, further emphasizing their stability in high-temperature environments and similar thermal properties. Our study found an efficient co-production approach of pigment and BNC from S. salsa biomass. Pigment extraction made biomass more physically and chemically digestible to cellulase, and significantly improved BNC productivity and quality.

Synchronous stabilization of Pb, Zn, Cd, and As in lead smelting slag by industrial solid waste.

In order to prevent heavy metal (HM) pollution from lead smelting slag (LSS) to the surrounding environment, this work investigated the feasibility, influencing factors, and mechanisms of using industrial solid waste such as fly ash (FA), oil sludge pyrolysis residue (PR), and steel slag (SS) as remediation amendments. The results demonstrated that the stabilization process was influenced by the material dosage, water content, and LSS particle size. Compared to single materials, the combination amendment PR2FA1 (with a mass ratio of PR to FA as 2:1) exhibited the best stabilization effect, simultaneously reducing the leaching concentrations of As, Zn, Cd, and Pb in LSS to 0.032, 0.034, 0.002, and 0.014 mg/L, respectively. The pH value of the leachate remained between 8 and 9, which met the requirements of surface water quality class IV (GB3838-2002). Through morphological analysis, microscopic characterization, and simulated solution adsorption experiments, it was determined that the stabilization process of HMs was controlled by various mechanisms, including electrostatic attraction, physical adsorption, ion exchange, and chemical precipitation. PR2FA1 had more active components, and its fine-porous structure provided more active sites, resulting in good stabilization performance for As, Zn, Cd, and Pb. Furthermore, cost analysis showed that PR2FA1, as an environmentally friendly material, could generate profits of 157.2 ¥/ton. In conclusion, the prepared PR2FA1 not only addressed the HMs pollution from lead smelting slag to the surrounding environment but also achieved the safe and resourceful disposal of hazardous waste-oil sludge. Its excellent performance in stabilizing HMs and cost-effectiveness suggested promising commercial applications.

Building Coarse to Fine Convex Hulls with Auxiliary Vertices for Palette-based Image Recoloring.

Constructing a convex hull for the pixel colors of an image by viewing them as 3D points can extract a set of palette colors for the image, then image recoloring can be achieved by modifying the palette colors. For better recoloring effect, the convex hull should contain more pixels (inclusive) and be more compact. Otherwise, reconstruction error would occur or the extracted palette color would be less representative, yielding wrong recoloring results or less effective edit. We observe that convex hulls constructed by prior methods can contain all the image pixels, but are far from compact. Efforts have been made to optimize the vertices of convex hull to increase the compactness but are still not perfect. In this paper, we propose a novel coarse to fine convex hull construction scheme with auxiliary vertices. We start by constructing a coarse convex hull whose vertices are directly image pixels which is thus the most compact but cannot contain all pixels. We then make a remedy by adding auxiliary vertices into the coarse convex hull to obtain a fine convex hull. More auxiliary vertices are added, more image pixels will be contained into the fine convex hull. The auxiliary vertices are image pixels too so that the compactness can still be maintained. During editing, the auxiliary vertices are not allowed to be edited for edit convenience, but deformed as-rigid-as-possible with the adjusting of other vertices. Our convex hull is both inclusive and compact. Extensive experiments validate the effectiveness of the proposed method.

Bonding and Acidity of the Formal Hydride in the Prototypical Au9 (PPh3 )8 H2+ Nanocluster.

The role of hydrogen atoms as surface ligands on metal nanoclusters is of profound importance but remains difficult to directly study. While hydrogen atoms often appear to be incorporated formally as hydrides, evidence suggests that they donate electrons to the cluster's delocalized superatomic orbitals and may consequently behave as acidic protons that play key roles in synthetic or catalytic mechanisms. Here we directly test this assertion for the prototypical Au9 (PPh3 )8 H2+ nanocluster, formed by addition of a hydride to the well-characterized Au9 (PPh3 )8 3+ . Using gas-phase infrared spectroscopy, we were able to unambiguously isolate Au9 (PPh3 )8 H2+ and Au9 (PPh3 )8 D2+ , revealing an Au-H stretching mode at 1528 cm-1 that shifts to 1038 cm-1 upon deuteration. This shift is greater than the maximum expected for a typical harmonic potential, suggesting a potential governing cluster-H bonding that has some square-well character consistent with the hydrogen nucleus behaving as a metal atom in the cluster core. Complexing this cluster with very weak bases reveals a redshift of 37 cm-1 in the Au-H vibration, consistent with those typically seen for moderately acidic groups in gas phase molecules and providing an estimate of the acidity of Au9 (PPh3 )8 H2+ , at least with regard to its surface reactivity.

The immunogenic involvement of miRNA-492 in mycoplasma pneumoniae infection in pediatric patients

Abstract Objective: This study aimed to evaluate the role of miRNA-492 in the progression of mycoplasma pneumoniae (MP) infection in pediatric patients. Methods: Forty-six children admitted to the present study's hospital and diagnosed with mycoplasma pneumonia were recruited as the study group from March 2018 to August 2019, and 40 healthy children were selected as the control group. Results: The expression levels of miRNA-492, TNF-α, IL-6 and IL-18 in the study group were significantly higher than those in the control group (p < 0.05). There was no significant correlation between miRNA-492 and most of the immune-correlated indicators in the study group, except for IL-6, IL-18 and HMGB1. Meanwhile, overexpression of miRNA-492 increased IL-6 secretion in PMA-activated monocytes (p < 0.01). Conclusion: The present study's results suggested that miRNA-492 might play a role in the pathogenesis of mycoplasma pneumoniae pneumonia in children by regulating the secretion of immune-inflammatory factors such as IL-6 and IL-18 in the mononuclear macrophages.

The immunogenic involvement of miRNA-492 in mycoplasma pneumoniae infection in pediatric patients.

OBJECTIVE: This study aimed to evaluate the role of miRNA-492 in the progression of mycoplasma pneumoniae (MP) infection in pediatric patients. METHODS: Forty-six children admitted to the present study's hospital and diagnosed with mycoplasma pneumonia were recruited as the study group from March 2018 to August 2019, and 40 healthy children were selected as the control group. RESULTS: The expression levels of miRNA-492, TNF-α, IL-6 and IL-18 in the study group were significantly higher than those in the control group (p < 0.05). There was no significant correlation between miRNA-492 and most of the immune-correlated indicators in the study group, except for IL-6, IL-18 and HMGB1. Meanwhile, overexpression of miRNA-492 increased IL-6 secretion in PMA-activated monocytes (p < 0.01). CONCLUSION: The present study's results suggested that miRNA-492 might play a role in the pathogenesis of mycoplasma pneumoniae pneumonia in children by regulating the secretion of immune-inflammatory factors such as IL-6 and IL-18 in the mononuclear macrophages.

Parametrization of the PM7 Semiempirical Quantum Mechanical Method for Silver Nanoclusters.

Semiempirical quantum mechanical methods (SEQMs) are widely used in computational chemistry because of their low computational cost, but their accuracy depends on the quality of the parameters. The neglect of diatomic differential overlap method PM7 is among the few SEQMs that contain parameters for Ag, but the experimental reference data was insufficient to obtain reliable parameters in the original parametrization. In this work, we reparametrize the PM7 parameters for Ag to accurately reproduce the ground-state potential energy surfaces of Ag clusters. Since little experimental data is available, we use reference data obtained from the ab initio method CCSD(T). The resulting parameters significantly reduce the errors in binding energies, energies required to displace clusters along their normal modes, and relative energies of isomers compared to the default PM7 Ag parameters.

Pharmacogenomic Profiling of Pediatric Acute Myeloid Leukemia to Identify Therapeutic Vulnerabilities and Inform Functional Precision Medicine.

Despite the expanding portfolio of targeted therapies for adults with acute myeloid leukemia (AML), direct implementation in children is challenging due to inherent differences in underlying genetics. Here we established the pharmacologic profile of pediatric AML by screening myeloblast sensitivity to approved and investigational agents, revealing candidates of immediate clinical relevance. Drug responses ex vivo correlated with patient characteristics, exhibited age-specific alterations, and concorded with activities in xenograft models. Integration with genomic data uncovered new gene-drug associations, suggesting actionable therapeutic vulnerabilities. Transcriptome profiling further identified gene-expression signatures associated with on- and off-target drug responses. We also demonstrated the feasibility of drug screening-guided treatment for children with high-risk AML, with two evaluable cases achieving remission. Collectively, this study offers a high-dimensional gene-drug clinical data set that could be leveraged to research the unique biology of pediatric AML and sets the stage for realizing functional precision medicine for the clinical management of the disease. SIGNIFICANCE: We conducted integrated drug and genomic profiling of patient biopsies to build the functional genomic landscape of pediatric AML. Age-specific differences in drug response and new gene-drug interactions were identified. The feasibility of functional precision medicine-guided management of children with high-risk AML was successfully demonstrated in two evaluable clinical cases. This article is highlighted in the In This Issue feature, p. 476.

Carbonaceous material prepared by pyrolysis of refinery oily sludge for removal of flotation collectors in wastewater.

The carbonaceous material (CM) prepared by refinery oily sludge was proposed to remove flotation collectors, butyl xanthate (BX), and diethyldithiocarbamate (DDTC) in synthetic wastewater. The effects of the CM on removal efficiency, adsorption kinetics, and isotherms were experimentally carried out. The surface structure and composition of CM were characterized by BET isotherm, XRD, and SEM-EDS, and the concentration of BX and DDTC was tested by UV-VIS spectrometer. The adsorption behavior and removal mechanism were investigated by zeta potential, ToF-SIMS, FTIR, etc. The removal efficiencies of BX and DDTC were both more than 99%, and the maximum adsorption capacity peaked when the pH of the solution was neutral. The two collectors were heterogeneous adsorption on the surface of CM. BX, DDTC, and related metal compounds were found on the surface of carbonaceous material, confirming the existence of both physical and chemical adsorption, and physical adsorption accounted for the main mechanism. It is proved that BX and DDTC can be removed by carbonaceous material and realize the high-effective utilization of refinery oily sludge.

AZI2 positively regulates the induction of type I interferon in influenza-trigger pediatric pneumonia.

5-azacytidine-induced protein 2 (AZI2) is known to have a crucial role in antiviral innate immunity. This study aims to explore the roles of AZI2 in influenza-trigger pediatric pneumonia and its molecular mechanism. qPCR and immunoblotting assays were used to determine the levels of target genes and proteins. The lung infection mouse model was established by using PR8 H1N1 virus in AZI2 germline knockout (AZI2-/-) and wild-type (WT) mice. In addition, HEK293T cell-based luciferase reporter assays were used to investigate the regulatory effects of AZI2 on type I interferon. Immune precipitation and immunofluorescence staining were used to evaluate the interactions between AZI2 and TANK binding kinase 1 (TBK1). We observed an elevation in the expressions of IFN-I and AZI2 in peripheral blood mononuclear cells from the pneumonia patients with mild symptoms. Interestingly, AZI2 deficiency deteriorated the influenza-induced pathological symptoms in the lung as well as reduced the survival rate. It was further showed that AZI2 positively regulated the expressions of type I interferon, inflammatory cytokines, and IFN production-related genes. The molecular mechanism data revealed that AZI2 regulated the interactions between TBK1 and TANK. In summary, AZI2 positively regulates type I interferon production in influenza-induced pediatric pneumonia by promoting the interactions between TBK1 and TANK.

Stem cell therapy for pulmonary arterial hypertension: An update.

Pulmonary arterial hypertension (PAH) remains a deadly disease, and there currently is no cure for this life-threating medical problem. The average lifespan is about 5 to 7 years after diagnosis of PAH. Therefore, a conceptual breakthrough to develop new therapeutic strategies for PAH is urgently needed. Growing evidence shows that stem cells are emerging as a novel effective treatment, but the understanding of its underlying mechanisms is still limited. This review highlights the mechanisms through which stem cells successfully reverse pulmonary vascular endothelial dysfunction, pulmonary artery smooth muscle cell over-proliferation, and mitochondrial dysfunction in PAH patients and common rodent models used in PAH research. They can modulate common underlying pathways involved in PAH, including the nitric oxide synthase, mitochondrial regulators, microRNAs and STAT3-BMPR signaling. Genetic modifications further enhance the therapeutic effects of stem cells on PAH. Clinical trials showed promising therapeutic potential of mesenchymal stem cells and endothelial progenitor cells for PAH. Potential limitations and challenges are also discussed. The current findings support the need for further investigation and validation of stem cell therapy for PAH.

Hydrothermal Synthesis of 1T-MoS2/Pelagic Clay Composite and Its Application in the Catalytic Reduction of 4-Nitrophenol.

Pelagic clay is an emerging marine resource with strong hydrophilicity, fine particles and a large specific surface area. In this work, a 1T-MoS2/pelagic clay composite was fabricated by hydrothermal synthesis. In the composite, 1T-MoS2 nanosheets are evenly dispersed on the surface of the clay minerals, significantly reducing the agglomeration of MoS2. Compared with pure 1T-MoS2, the 1T-MoS2 nanosheets generated on the surface of pelagic clay have significantly smaller lateral dimensions and thicknesses. Moreover, the specific surface area is much larger than that of the pure 1T-MoS2 nanosheets fabricated by the same method, indicating that the active sites of the MoS2 sheets are fully exposed. In addition, the composite exhibited excellent hydrophilicity, leading to a high dispersibility in aqueous solutions. In this work, the composite was used as a catalyst in the reduction of 4-nitrophenol (4-NP), and the conversion of 4-NP reached up to 96.7%. This result shows that the 1T-MoS2/pelagic clay composite is a promising catalyst in a variety of reactions.

Genome-wide survey and characterization of transcription factors in the silk gland of the silkworm, Bombyx mori.

Transcription factors (TFs) are key proteins that modulate gene transcription and thereby lead to changes in the gene expression profile and the subsequent alteration of cellular functions. In the silk gland (SG) of silkworm Bombyx mori, an important silk-producing insect, TFs are of vital importance in the regulation of silk protein synthesis in this organ. However, which TFs exist and express in the SG remains largely unknown. Here, we report the large-scale identification of TFs in the SG based on available full-length transcript sequences and the most recent version of silkworm genome data. In total, 348 candidate TFs were identified by strict filtration and were classified into 56 TF families. Chromosomal distribution, motif composition, and phylogenetic relationship analyses revealed the typical characteristics of these TFs. In addition, the expression patterns of 348 TFs in various tissues of B. mori, especially the SG of fourth-molt (4LM) and day-3 and day-4 fifth-instar (5L3D and 5L4D) larvae, were investigated based on public RNA-seq data and gene microarray data, followed by spatiotemporal verification of TF expression levels by quantitative real-time PCR (qRT-PCR). This report describes the first comprehensive analysis of TFs in the B. mori SG. The results can serve as a baseline for further studies of the roles of TFs in the B. mori SG.

Urban-rural differences in catastrophic health expenditure among households with chronic non-communicable disease patients: evidence from China family panel studies.

BACKGROUND: The prevalence of chronic non-communicable diseases (NCDs) challenges the Chinese health system reform. Little is known for the differences in catastrophic health expenditure (CHE) between urban and rural households with NCD patients. This study aims to measure the differences above and quantify the contribution of each variable in explaining the urban-rural differences. METHODS: Unbalanced panel data were obtained from the China Family Panel Studies (CFPS) conducted between 2012 and 2018. The techniques of Fairlie nonlinear decomposition and Blinder-Oaxaca decomposition were employed to measure the contribution of each independent variable to the urban-rural differences. RESULTS: The CHE incidence and intensity of households with NCD patients were significantly higher in rural areas than in urban areas. The urban-rural differences in CHE incidence increased from 8.07% in 2012 to 8.18% in 2018, while the urban-rural differences in CHE intensity decreased from 2.15% in 2012 to 2.05% in 2018. From 2012 to 2018, the disparity explained by household income and self-assessed health status of household head increased to some extent. During the same period, the contribution of education attainment to the urban-rural differences in CHE incidence decreased, while the contribution of education attainment to the urban-rural differences in CHE intensity increased slightly. CONCLUSIONS: Compared with urban households with NCD patients, rural households with NCD patients had higher risk of incurring CHE and heavier economic burden of diseases. There was no substantial change in urban-rural inequality in the incidence and intensity of CHE in 2018 compared to 2012. Policy interventions should give priority to improving the household income, education attainment and health awareness of rural patients with NCDs.

Electrochemical Fixation of Nitrogen by Promoting N2 Adsorption and N-N Triple Bond Cleavage on the CoS2/MoS2 Nanocomposite.

An electrochemical N2 reduction reaction (NRR), as an environmentally benign method to produce NH3, is a suitable alternative to substitute the energy-intensive Haber-Bosch technology. Unfortunately, to date, it is obstructed by the lack of efficient electrocatalysts. Here, a CoS2/MoS2 nanocomposite with CoS2 nanoparticles decorated on MoS2 nanosheets is fabricated and adapted as a catalyst for the NRR. As unveiled by experimental and theoretical results, the strong interaction between CoS2 and MoS2 modulates interfacial charge distribution with electrons transferring from CoS2 to MoS2. Consequently, a local electrophilic region is formed near the CoS2 side, which enables effective N2 absorption. On the other hand, the nucleophilic area formed near the MoS2 side is in favor of breaking stable N≡N, the potential-determining step (*N2 → *N2H) which brings about a much decreased energy barrier than that on pure MoS2. As a result, this catalyst exhibits an excellent NRR performance, NH3 yield and Faradaic efficiency of 54.7 µg·h-1·mg-1 and 20.8%, respectively, far better than most MoS2-based catalysts.

Symbiotic composite composed of MoS2 and pelagic clay with enhanced disinfection efficiency.

Molybdenum disulfide (MoS2) has attracted increasing attention as a promising photocatalyst. In addition to its application in photocatalytic hydrogen production and pollutant degradation, MoS2 is also used in water disinfection. However, its poor disinfection performance limits its practical utility. Herein, we prepared a symbiotic composite composed of MoS2 and pelagic clay (MoS2/PC) as a photocatalyst for water disinfection. The composite achieved a high disinfection rate of 99.95% to Escherichia coli (E. coli) under visible light illumination, which is significantly higher than that of bulk MoS2 (61.87%). Characterization shows that abundant hydroxyl groups in illite/montmorillonite (I/M) formed during hydrothermal synthesis of MoS2, which contributed to the enhanced disinfection activity. Those hydroxyl groups can attract photogenerated holes through electrostatic attraction, and facilitate the separation of photogenerated charge carriers, thereby enhancing the disinfection activity. Moreover, the good hydrophilicity of pelagic clay improves the dispersity of MoS2 in water, which is beneficial for its utility in aqueous solutions. In addition, the symbiotic structure restricts the growth and aggregation of MoS2 nanosheets and shortens the diffusion distance of charge carriers to the material surface, further reducing the recombination of electrons and holes. This study provides a way to improve the disinfection activity of MoS2 and also sheds light on high value-added utilization of pelagic clay.

Klotho Deficiency Causes Heart Aging via Impairing the Nrf2-GR Pathway.

RATIONALE: Cardiac aging is an important contributing factor for heart failure, which affects a large population but remains poorly understood. OBJECTIVE: The purpose of this study is to investigate whether Klotho plays a role in cardiac aging. METHODS AND RESULTS: Heart function declined in old mice (24 months), as evidenced by decreases in fractional shortening, ejection fraction, and cardiac output. Heart size and weight, cardiomyocyte size, and cardiac fibrosis were increased in old mice, indicating that aging causes cardiac hypertrophy and remodeling. Circulating Klotho levels were dramatically decreased in old mice, which prompted us to investigate whether the Klotho decline may cause heart aging. We found that Klotho gene mutation (KL-/-) largely decreased serum klotho levels and impaired heart function. Interestingly, supplement of exogenous secreted Klotho prevented heart failure, hypertrophy, and remodeling in both old mice and KL (-/-) mice. Secreted Klotho treatment inhibited excessive cardiac oxidative stress, senescence and apoptosis in old mice and KL (-/-) mice. Serum phosphate levels in KL (-/-) mice were kept in the normal range, suggesting that Klotho deficiency-induced heart aging is independent of phosphate metabolism. Mechanistically, Klotho deficiency suppressed GR (glutathione reductase) expression and activity in the heart via inhibition of transcription factor Nrf2 (nuclear factor-erythroid 2 p45-related factor 2). Furthermore, cardiac-specific overexpression of GR prevented excessive oxidative stress, apoptosis, and heart failure in both old and KL (-/-) mice. CONCLUSIONS: Klotho deficiency causes cardiac aging via impairing the Nrf2-GR pathway. Supplement of exogenous secreted Klotho represents a promising therapeutic strategy for aging-associated cardiomyopathy and heart failure.