Search

Obesity is one of the most common metabolic diseases around the world, which is distinguished by the abnormal buildup of triglycerides within adipose cells. Recent research has revealed that autophagy regulates lipid mobilization to maintain energy balance. TIGAR (Trp53 induced glycolysis regulatory phosphatase) has been identified as a glycolysis inhibitor, whether it plays a role in the metabolism of lipids is unknown. Here, we found that TIGAR transgenic (TIGAR+/+) mice exhibited increased fat mass and trended to obesity phenotype. Non-target metabolomics showed that TIGAR caused the dysregulation of the metabolism profile. The quantitative transcriptome sequencing identified an increased levels of LRRK2 and RAB7B in the adipose tissue of TIGAR+/+ mice. It was confirmed in vitro that TIGAR overexpression increased the levels of LRRK2 by inhibiting polyubiquitination degradation, thereby suppressing macroautophagy and chaperone-mediated autophagy (CMA) while increasing lipid accumulation which were reversed by the LRRK2 inhibitor DNL201. Furthermore, TIGAR drove LRRK2 to interact with RAB7B for suppressing lysosomal degradation of lipid droplets, while the increased lipid droplets in adipocytes were blocked by the RAB7B inhibitor ML282. Additionally, fat-specific TIGAR knockdown of TIGAR+/+ mice alleviated the symptoms of obesity, and adipose tissues-targeting superiority DNL201 nano-emulsion counteracted the obesity phenotype in TIGAR+/+ mice. In summary, the current results indicated that TIGAR performed a vital function in the lipid metabolism through LRRK2-mediated negative regulation of macroautophagy and CMA in adipocyte. The findings suggest that TIGAR has the potential to serve as a viable therapeutic target for treating obesity and its associated metabolic dysfunction. [ABSTRACT FROM AUTHOR]

Premature ovarian insufficiency (POI) is one of the important causes of female infertility. Yet the aetiology for POI is still elusive. FBXW7 (F‐box with 7 tandem WD) is one of the important components of the Skp1‐Cullin1‐F‐box (SCF) E3 ubiquitin ligase. FBXW7 can regulate cell growth, survival and pluripotency through mediating ubiquitylation and degradation of target proteins via triggering the ubiquitin‐proteasome system, and is associated with tumorigenesis, haematopoiesis and testis development. However, evidence establishing the function of FBXW7 in ovary is still lacking. Here, we showed that FBXW7 protein level was significantly decreased in the ovaries of the cisplatin‐induced POI mouse model. We further showed that mice with oocyte‐specific deletion of Fbxw7 demonstrated POI, characterized with folliculogenic defects, early depletion of follicle reserve, disordered hormonal secretion, ovarian dysfunction and female infertility. Impaired oocyte‐GCs communication, manifested as down‐regulation of connexin 37, may contribute to follicular development failure in the Fbxw7‐mutant mice. Furthermore, single‐cell RNA sequencing and in situ hybridization results indicated an accumulation of Clu and Ccl2 transcripts, which may alter follicle microenvironment deleterious to oocyte development and accelerate POI. Our results establish the important role of Fbxw7 in folliculogenesis and ovarian function, and might provide valuable information for understanding POI and female infertility. [ABSTRACT FROM AUTHOR]

This work report the generation of high‐order Laguerre–Gaussian (LG) modes from a nanosecond, optical vortex pumped diamond Raman laser. This system is capable of generating first‐Stokes (λ1st = 1240 nm) LG modes with topological charge (ℓ) of up to 26 and second‐Stokes (λ2nd = 1485 nm) LG modes with topological charge of up to 22, when pumped using a first‐order vortex beam. The maximum first‐ and second‐Stokes LG mode energies are measured to be 0.5 and 1 mJ, respectively, when pumping with energy of 19.8 mJ. [ABSTRACT FROM AUTHOR]

In the field of civil aircraft maintenance, the formulation of special event tasks is always the focus of civil aircraft maintenance manual(AMM) development. Based on design experience and damage and special event analysis(DESA) of S3000L, the concept of effect rating is given through the detailed analysis and technical tailoring and supplement. The special events analysis theories and method are set up for domestic civil aircraft, and performed with case analysis. The results show that the theory and analysis method are reasonable and reliable, and can provide some references for compiling the Chapter 05 of AMM of domestic civil main aircraft manufacturer.

Vortex beams are unique in that they have annular spatial profiles and carry orbital angular momentum. This has led to their use in applications including laser processing, microparticle manipulation and signal transmission. Off-axis vortex beams, which may be considered a subset of vortex beams, display a broader spectrum of physical characteristics in comparison with their conventional (integer-order) counterparts. In this work, we derive the equations which describe the intensity distribution of off-axis vortex beams and use these to theoretically model their spatial profile. These models are supported by experimental generation of both integer and off-axis vortex beams, and the presence of orbital angular momentum is investigated through the use of the cylindrical lens transformation method. [ABSTRACT FROM AUTHOR]

Inequity between urban and rural education prevalently exists in China. A lack of qualified teachers is the main reason for disadvantaged education in rural areas. In order to solve this problem, Live Broadcast Classroom was adopted for use in grade 5 English classes. 90 students and 3 teachers of 3 classes from two primary schools in Yunnan Province were selected as participants. As for methodology, quantitative and qualitative methods were used. Results showed it was feasible to use Live Broadcast Classroom in solving the inequity problem in micro-level education (i.e., classroom): the gap between students' scores and attitudes towards English between urban and rural classes was narrowed. Challenges still exist and some suggestions are put forward in the end.

The purpose of this study is to investigate the use of SiO2 nanoparticles in assisting with surfactants and polymers for tertiary oil recovery, with the aim of enhancing oil recovery. The article characterizes the performance of SiO2 nanoparticles, including particle size, dispersion stability, and zeta potential, evaluates the synergistic effects of nanoparticles with alpha-olefin sulfonate sodium (AOS) surfactants and hydrolyzed polyacrylamide (HPAM) on reducing interfacial tension and altering wettability, and conducts core flooding experiments in rock cores with varying permeabilities. The findings demonstrate that the particle size decreased from 191 nm to 125 nm upon the addition of SiO2 nanoparticles to AOS surfactant, but increased to 389 nm upon the addition of SiO2 nanoparticles to HPAM. The dispersibility experiment showed that the SiO2 nanoparticle solution did not precipitate over 10 days. After adding 0.05% SiO2 nanoparticles to AOS surfactant, the zeta potential was −40.2 mV, while adding 0.05% SiO2 nanoparticles to 0.1% HPAM resulted in a decrease in the zeta potential to −25.03. The addition of SiO2 nanoparticles to AOS surfactant further reduced the IFT value to 0.19 mN/m, altering the rock wettability from oil-wet to strongly water-wet, with the contact angle decreasing from 110° to 18°. In low-permeability rock core oil displacement experiments, the use of AOS surfactants and HPAM for enhanced oil recovery increased the recovery rate by 24.5% over water flooding. The recovery rate increased by 21.6% over water flooding in low-permeability rock core experiments after SiO2 nanoparticles were added and surfactants and polymers were utilized for oil displacement. This is because the nanoparticles blocked small pore throats, resulting in increased resistance and hindered free fluid flow. The main causes of this plugging are mutual interference and mechanical entrapment, which cause the pressure differential to rise quickly. In high-permeability rock core oil displacement experiments, the use of AOS surfactants and HPAM for oil recovery increased the recovery rate by 34.6% over water flooding. Additionally, the recovery rate increased by 39.4% over water flooding with the addition of SiO2 nanoparticles and the use of AOS surfactants and HPAM for oil displacement. Because SiO2 nanoparticles create wedge-shaped structures inside highly permeable rock cores, they create structural separation pressure, which drives crude oil forward and aids in diffusion. This results in a comparatively small increase in pressure differential. Simultaneously, the nanoparticles change the rock surfaces' wettability, which lowers the amount of crude oil that adsorbs and improves oil recovery. [ABSTRACT FROM AUTHOR]

Ectopic lipid accumulation in renal tubules is closely related to the pathogenesis of diabetic kidney disease (DKD), and mitochondrial dysfunction is thought to play a key role in lipid accumulation. Therefore, maintaining mitochondrial homeostasis holds considerable promise as a therapeutic strategy for the treatment of DKD. Here, we report that the Meteorin-like (Metrnl) gene product mediates lipid accumulation in the kidney and has therapeutic potential for DKD. We confirmed the reduced expression of Metrnl in renal tubules, which was inversely correlated with DKD pathological changes in human patients and mouse models. Functionally, pharmacological administration of recombinant Metrnl (rMetrnl) or Metrnl overexpression could alleviate lipid accumulation and inhibit kidney failure. In vitro, rMetrnl or Metrnl overexpression attenuated palmitic acid–induced mitochondrial dysfunction and lipid accumulation in renal tubules accompanied by maintained mitochondrial homeostasis and enhanced lipid consumption. Conversely, shRNA-mediated Metrnl knockdown diminished the protective effect on the kidney. Mechanistically, these beneficial effects of Metrnl were mediated by the Sirt3-AMPK signaling axis to maintain mitochondrial homeostasis and through Sirt3-uncoupling protein-1 to promote thermogenesis, consequently alleviating lipid accumulation. In conclusion, our study demonstrates that Metrnl regulated lipid metabolism in the kidney by modulating mitochondrial function and is a stress-responsive regulator of kidney pathophysiology, which sheds light on novel strategies for treating DKD and associated kidney diseases. Article Highlights: Metrnl is expressed in renal tubules and is reduced under diabetic conditions. The concentration of Metrnl in the kidney is correlated with lipid accumulation and serum creatinine. Metrnl-specific overexpression in the kidney or recombinant Metrnl administration alleviates renal injuries in diabetic mice. Metrnl regulates renal tubules lipid metabolism through Sirt3-AMPK/UCP1 signaling axis–mediated mitochondrial homeostasis. [ABSTRACT FROM AUTHOR]