Explore the vast range of titles available.

Objectives: Dimeric pyruvate kinase (PK) M2 (PKM2) plays an important role in promoting the accumulation of hypoxia-inducible factor (HIF)-1α, mediating aberrant glycolysis and inducing fibrosis in diabetic kidney disease (DKD). The aim of this work was to dissect a novel regulatory mechanism of Yin and Yang 1 (YY1) on lncRNA-ARAP1-AS2/ARAP1 to regulate EGFR/PKM2/HIF-1α pathway and glycolysis in DKD. Materials and methods: We used adeno-associated virus (AAV)-ARAP1 shRNA to knocked down ARAP1 in diabetic mice and overexpressed or knocked down YY1, ARAP1-AS2 and ARAP1 expression in human glomerular mesangial cells. Gene levels were assessed by Western blotting, RT-qPCR, immunofluorescence staining and immunohistochemistry. Molecular interactions were determined by RNA pull-down, co-immunoprecipitation, ubiquitination assay and dual-luciferase reporter analysis. Results: YY1, ARAP1-AS2, ARAP1, HIF-1α, glycolysis and fibrosis genes expressions were upregulated and ARAP1 knockdown could inhibit dimeric PKM2 expression and partly restore tetrameric PKM2 formation, while downregulate HIF-1α accumulation and aberrant glycolysis and fibrosis in in-vivo and in-vitro DKD models. ARAP1 knockdown attenuates renal injury and renal dysfunction in diabetic mice. ARAP1 maintains EGFR overactivation in-vivo and in-vitro DKD models. Mechanistically, YY1 transcriptionally upregulates ARAP1-AS2 and indirectly regulates ARAP1 and subsequently promotes EGFR activation, HIF-1α accumulation and aberrant glycolysis and fibrosis. Conclusion: Our results first highlight the role of the novel regulatory mechanism of YY1 on ARAP1-AS2 and ARAP1 in promoting aberrant glycolysis and fibrosis by EGFR/PKM2/HIF-1α pathway in DKD and provide potential therapeutic strategies for DKD treatments.

Impedance matching is important for achieving high-efficiency microwave absorbers. The high conductivity of dielectric loss materials such as pure metals and carbon nanomaterials generally results in poor absorption owing to the low impedance matching between the absorbers and air. Carbon nanostructures are very promising candidates for high-efficiency absorption because of their attractive features including low density, high surface area, and good stability. Herein, a new strategy is proposed to improve the impedance matching of dielectric loss materials using electrospun carbon nanofibers as an example. The carbon nanofibers are coated with specifically designed gradient multilayer nanofilms with gradually increasing electroconductibility synthesized by doping ZnO with different A1203 content （AZO） by atomic layer deposition. The gradient nanofilms are composed of five layers of dielectric films, namely, pure A1203, AZO （5：1, the pulse cycle ratio of ZnO to A1203）, pure ZnO, AZO （10：1）, and AZO （20：1）. The versatile gradient films serve as intermediate layers to tune the impedance matching between air and the carbon nanofiber surfaces. Therefore, the carbon nanofibers coated with gradient films of rationally selected thicknesses exhibit remarkably enhanced microwave absorption performance, and the optimal reflection loss reaches -58.5 dB at 16.2 GHz with a thickness of only 1.8 mm. This work can help further understand the contribution of impedance matching to microwave absorption. Our strategy is general and can be applied to improve the absorption properties of other dielectric loss materials and even for applications in other fields.

The multiphase reaction process of pressure leaching is mainly carried out in the liquid phase. Therefore, gas holdup is essential for the gas-liquid-solid phase reaction and the extraction rate of valuable metals. In this paper, a transparent quartz autoclave, a six blades disc turbine-type agitator, and a high-speed camera were used to investigate the gas holdup of the pressure leaching process. Furthermore,experiments determining the effects of agitation rate, temperature, and oxygen partial pressure on gas holdup were carried out. The results showed that when the agitation rate increased from 350 to 600 r/min, the gas holdup increased from 0.10% to 0.64%. When the temperature increased from 363 to 423 K, the gas holdup increased from 0.14% to 0.20%. When the oxygen partial pressure increased from 0.1 to 0.8 MPa, the gas holdup increased from 0.13% to 0.19%. A similar criteria relationship was established by Homogeneous Principle and Buckingham's theorem. Comprehensively, empirical equation of gas holdup was deduced on the basis of experimental data and the similarity theory, where the criterion equation was determined as 11 3.65 2.08 0.18 ε 4.54 10 n T Pg . It can be seen from the formula that agitation rate made the most important impact on gas holdup in the pressure leaching process using the mixed-flow agitator.

The multiphase reaction process of pressure leaching is mainly carried out in the liquid phase. Therefore, gas holdup is essential for the gas–liquid–solid phase reaction and the extraction rate of valuable metals. In this paper, a transparent quartz autoclave, a six blades disc turbine-type agitator, and a high-speed camera were used to investigate the gas holdup of the pressure leaching process. Furthermore, experiments determining the effects of agitation rate, temperature, and oxygen partial pressure on gas holdup were carried out. The results showed that when the agitation rate increased from 350 to 600 r/min, the gas holdup increased from 0.10% to 0.64%. When the temperature increased from 363 to 423 K, the gas holdup increased from 0.14% to 0.20%. When the oxygen partial pressure increased from 0.1 to 0.8 MPa, the gas holdup increased from 0.13% to 0.19%. A similar criteria relationship was established by Homogeneous Principle and Buckingham’s theorem. Comprehensively, empirical equation of gas holdup was deduced on the basis of experimental data and the similarity theory, where the criterion equation was determined as ε=4.54×10-11n3.65T2.08Pg0.18. It can be seen from the formula that agitation rate made the most important impact on gas holdup in the pressure leaching process using the mixed-flow agitator.

Antarctic tabular icebergs are important active components in the ice sheet-ice shelf-ocean system.Seafloor topography is the key factor that affects the drifting and grounding of icebergs,but it has not been fully investigated.This study analyzes the impact of seafloor topography on the drifting and grounding of Antarctic tabular icebergs using Bedmap-2 datasets and iceberg route tracking data from Brigham Young University.The results highlight the following points.（1） The quantitative distributions of iceberg grounding events and the tracking points of grounded icebergs are mainly affected by iceberg draft and reach their peak values in sea water with depths between 200 m and 300 m.The peak tracking point number and linear velocity of free-drifting icebergs are found in the Antarctic Slope Front（water depth of approximately 500 m）.（2） The area of possible grounding regions of small-scale icebergs calved from ice shelf fronts accounts for 28%of the sea area at water depths less than 2000 m outside the Antarctic coastline periphery（3.62 million km2）.Their spatial distribution is mainly around East Antarctica and the Antarctic Peninsula.The area of possible grounding regions of large tabular icebergs with long axes larger than 18.5 km（in water depths of less than 800 m） accounts for 74%of the sea area.（3） The iceberg drifting velocity is positively correlated with ocean depth in areas where the depth is less than 2000 m（R=0.85,P〈0.01）.This result confirms the effect of water depth variations induced by seafloor topography fluctuations on iceberg drifting velocity.

Antarctic tabular icebergs are important active components in the ice sheet-ice shelf-ocean system.Seafloor topography is the key factor that affects the drifting and grounding of icebergs,but it has not been fully investigated.This study analyzes the impact of seafloor topography on the drifting and grounding of Antarctic tabular icebergs using Bedmap-2 datasets and iceberg route tracking data from Brigham Young University.The results highlight the following points.(1) The quantitative distributions of iceberg grounding events and the tracking points of grounded icebergs are mainly affected by iceberg draft and reach their peak values in sea water with depths between 200 m and 300 m.The peak tracking point number and linear velocity of free-drifting icebergs are found in the Antarctic Slope Front(water depth of approximately 500 m).(2) The area of possible grounding regions of small-scale icebergs calved from ice shelf fronts accounts for 28%of the sea area at water depths less than 2000 m outside the Antarctic coastline periphery(3.62 million km2).Their spatial distribution is mainly around East Antarctica and the Antarctic Peninsula.The area of possible grounding regions of large tabular icebergs with long axes larger than 18.5 km(in water depths of less than 800 m) accounts for 74%of the sea area.(3) The iceberg drifting velocity is positively correlated with ocean depth in areas where the depth is less than 2000 m(R=0.85,P<0.01).This result confirms the effect of water depth variations induced by seafloor topography fluctuations on iceberg drifting velocity.

Endocardial fibroelastosis （EFE） refers to the thickening of the ventricular endocardium as a result of de novo deposition of subendocardial fibrous tissue layers during neonatal heart development. The origin of EFE fibroblasts is proposed to be postnatal endocardial cells that undergo an aberrant endothelial-to-mesenchymal transition （End- MT）. Genetic lineage tracing of endocardial cells with the inducible endocardial Cre line Npr3-CreER and the endo- thelial cell tracing line Cdh5-CreER on an EFE-like model did not reveal any contribution of neonatal endocardial cells to fibroblasts in the EFE-like tissues. Instead, lineage tracing of embryonic epicardium by Wtl-CreER suggested that epicardium-derived mesenchymal cells （MCs） served as the major source of EFE fibroblasts. By labeling MCs using Sox9-CreER, we confirmed that MCs of the embryonic heart expand and contribute to the majority of neonatal EFE fibroblasts. During this pathological process, TGFp signaling, the key mediator of fibroblasts activation, was highly upregulated in the EFE-like tissues. Targeting TGFp signaling by administration of its antagonist bone mor- phogenetic protein 7 effectively reduced fibroblast accumulation and tissue fibrosis in the EFE-like model. Our study provides genetic evidence that excessive fibroblasts in the EFE-like tissues mainly originate from the epicardium-de- rived MCs through epicardial to mesenchymal transition （EpiMT）. These EpiMT-derived fibroblasts within the EFE- like tissues could serve as a potential therapeutic target.

The importance of tacrolimus in the treatment of myasthenia gravis （MG） as a substitute for corticosteroid-dependent immunosuppressive therapy is increasing. Thus far, however, no population pharmacokinetic （PopPK） analysis of tacrolimus in treating MG patients has been published. This article aimed to construct a PopPK model of tacrolimus for Chinese MG patients with the goal of improving its performance in MG treatment. A total of 253 trough concentration records were obtained from 83 Chinese MG patients. The effects of demographics, lifestyle and health status, biochemical test data, disease progression and treatment-related information （including co-administered medications） as covariates on the various parameters were investigated. The covariate selection was based on biological plausibility, clinical significance, statistical significance and reduction in inter-individual variability （IIV）. Bootstrap and normalized prediction distribution error （NPDE） analysis were performed to validate the final model. A one-compartment PopPK model with first-order elimination and a fixed absorption phase was constructed. The estimated apparent oral clearance （CL/F） and apparent oral volume of distribution （V/F） were 3.6 L/h and 1700 L, respectively, in the MG patients. Hematocrit and blood urea nitrogen were identified as two covariates that significantly influenced the CL/F. Immunoglobulin treatment （PRO） also had the potential to influence V/F, which was consistent with the clinical observations and the high protein-binding property of tacrolimus. Other covariates including age, weight, gender and co-administered medications had no obvious influence on CL/F or V/F. The first PopPK model of tacrolimus in MG patients was established. The identified covariates were of biological plausibility and clinical importance to help individualize the dosing schedule in MG patients.

A method was proposed for removing zirconium （Zr） from hydrous titanium dioxide （HTD） by the NaF solution. The effects of main parameters, i.e. pH values, NaF dosage, temperature and retention time, on the removal of zirconium were stud- ied. The optimal conditions were found as the following： pH value, 〈5.5; molar ratio of NaF to TiQ, 0.6; retention time, 80 min and temperature, 80℃. The removal rate of Zr under the optimized conditions was above 87.7%. The adsorption energy of the preferential absorption of hydrofluoric acid for Zr（OH）2SOt（OH2） on the （001） crystal surface of HTD was determined by theo- retical calculation. The possible mechanism of the removal process was also discussed.