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Aims Hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs), a key component of the endosomal sorting complex required for transport (ESCRT), has been implicated in many essential biological processes. However, the physiological role of endogenous Hgs in the vascular system has not previously been explored. Here, we have generated brain endothelial cell (EC) specific Hgs knockout mice to uncover the function of Hgs in EC polarity and cerebrovascular stability. Methods and results Knockout of Hgs in brain ECs led to impaired endothelial apicobasal polarity and brain vessel collapse in mice. We determined that Hgs is essential for recycling of vascular endothelial (VE)-cadherin to the plasma membrane, since loss of Hgs blocked trafficking of endocytosed VE-cadherin from early endosomes to recycling endosomes, and impaired the motility of recycling endosomes. Supportively, overexpression of the motor kinesin family member 13A (KIF13A) restored endosomal recycling and rescued abrogated polarized trafficking and distribution of VE-cadherin in Hgs knockdown ECs. Conclusion These data uncover a novel physiological function of Hgs and support an essential role for the ESCRT machinery in the maintenance of EC polarity and cerebrovascular stability. [ABSTRACT FROM AUTHOR]

Abstract: In this study, a novel MgAl2O4 spinel whisker reinforced composite was synthesized in situ in an Al matrix by a powder metallurgy technique. In MgAl2O4/Al composite, the whisker content was varied from 3% to 15% in weight and each one was completely investigated. The as-produced MgAl2O4/Al composites were hot extruded and MgAl2O4/Al composites rods with high relative density were obtained. Both the hardness and the softening temperature of the composites increased with increasing content of MgAl2O4 whisker. The dilatometric measurements show that MgAl2O4 whisker reinforced Al composites exhibit better thermal stability and lower thermal expansion coefficient than aluminum alloys. Moreover, wear resistance is also enhanced due to the formation of the whisker-formed network structure which is capable of bearing and transferring abrasion effect. Thus, the enhanced properties of the composites could be obtained. [Copyright &y& Elsevier]

Short-chained perfluorobutane sulfonate (PFBS, four-carbon) and perfluorohexane sulfonate (PFHxS, six-carbon) are widely employed to substitute long-chained per- and poly-fluoroalkyl substances (PFASs). Recent studies showed the potential persistence of PFBS and PFHxS, and also reported their correlation with obesity. However, the long-term outcome and underlying mechanisms remained poorly understood. Presently, the effects of PFBS and PFHxS were studied on C. elegans with multi- and trans -generational experiments. The multi-generational effects were measured in continuous four generational exposure (i.e., F1 to F4). Results showed that PFBS did not stimulate the fat content in F1 but in F4 with continuous but different disturbances on the lipid metabolism and the insulin and insulin-like (IIS) pathway. PFHxS stimulated the fat content in F1 and F4 with similar disturbances on the lipid metabolism and IIS pathway. The trans -generational results showed that the effects of PFBS and PFHxS on the lipid metabolism and IIS pathway were not totally recovered in the offspring of F1 (i.e., T1-T3) and F4 (i.e., T1′-T3′) which were not continuously exposed. PFHxS showed a common pattern to up-regulate daf-7 in both multi- and trans -generational effects. The long-term consequences of the short-chained PFASs substitutes should be concerned and epigenetic regulations should be considered in future mechanism studies. [Display omitted] • PFBS stimulated the fat content not in F1 but in F4 generation. • PFBS disturbed lipid metabolism and IIS pathway differently from F1 to F4. • PFHS stimulated the fat content in F1 and F4 generation. • PFHS had similar disturbances on lipid metabolism and IIS pathway from F1 and F4. • PFHS commonly up-regulated daf-7 in both multi- and trans -generational effects. [ABSTRACT FROM AUTHOR]

These authors contributed equally: Pan Pan, Miaomiao Shen, Zhenyang Yu. The original version of this Article omitted the following from the Acknowledgements: Science & Technology Planning Project of Guangdong Province Office of Education (2018KCXTD007, 2021XK16), Special project for the prevention and control of new crown pneumonia in Guangdong colleges and universities (2020KZDZX1060). [Extracted from the article]

The 2219 aluminum alloy thin-walled complex components manufactured by spin forming are frequently applied to the bottom end of rocket fuel tanks. However, fracture and quality problems (large part-mold contact gap, low roundness, thickness accuracy) are prone to occur during their multi-pass spin forming. While the material anisotropy, complicated components geometry and the complex stress state evolution make it difficult to obtain the appropriate forming process parameters in spin forming. With the help of finite element methods, it is possible to solve this difficulty. Thus, based on the anisotropic Barlat89 yield function and the DF2016 fracture criterion, a spin forming finite element model considering material anisotropy and damage evolution is established first for the components. Then, a method by using multi-pass involute spinning track with variable diameter base circle to form the components is proposed, and also the spinning passes are determined. Finally, taking the non-fracture as the constraint condition and the forming quality indexes (part-mold contact gap, roundness, and thickness accuracy) as the optimization objectives, a multi-objective optimization model based on orthogonal experimental design and response surface model is established. The optimized process parameters are solved and determined by a combination of the Archive-Based Micro Genetic Algorithm, and the optimized results are verified by the experiments. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a kind of central nervous system (CNS) autoimmune disease, which mainly damages nerves, the brain, and the spinal cord. Recently, several clinical cases reported the relativity between Coronavirus Disease 2019 (COVID-19) and the development of MS, but the mechanism of how COVID-19 affects the occurrence of MS was still not clear. It is bioinformatics technology that we use to explore the potential association at the gene level. The genetic information related to the two diseases was collected from the DisGNET platform for functional protein network analysis and used STRING to identify the complete gene set. The protein–protein interaction (PPI) network was analyzed by STRING. Finally, in the GEO database, we selected peripheral blood mononuclear cell (PBMC) RNA sequencing data (GSE164805, GSE21942) from COVID-19 patients and MS patients to verify the potential cross mechanism between the two diseases. The similar gene set of immune or inflammation existed between the patients with COVID-19 and ones with MS, including L2RA, IFNG, IL1B, NLRP3, and TNF. Interaction network analysis among proteins revealed that IL1B, P2RX7, IFNB1, IFNB1, TNF, and CASP1 enhanced the network connectivity between the combined gene set of COVID-19 and MS associated with NOD-like receptor (NLR) signaling. The involvement of NLR signaling in both diseases was further confirmed by comparing peripheral blood monocyte samples from COVID-19 and MS patients. Activation of NLR signaling was found in both COVID-19 and MS. The PBMC samples analyses also indicated the involvement of the NLR signaling pathway. Taken together, our data analyses revealed that the NLR signaling pathway might play a critical role in the COVID-19-related MS. [ABSTRACT FROM AUTHOR]

• SMX provoked obesogenic effects on nematodes over 11 generations' exposure. • The obesogenic effects transferred from F10 to their non-exposed offspring T13. • The obesogenic effects were from greater fatty acid synthesis than its consumption. • Obesogenic mechanisms involved with regulations of PPAR and IIS pathways. • Epigenetic regulations via H3K4me3 were significant in F10 and T13. Increasing concerns are earned on the multigenerational hazards of antibiotics due to the connection between their mother-children transfer via cord blood and breast milk and obesity in the children. Currently, Caenorhabditis elegans was exposed to sulfamethoxazole (SMX) over 11 generations (F0–F10). Indicators of obesogenic effects and gene expressions were measured in each generation and also in T11 to T13 that were the offspring of F10. Biochemical analysis results showed that SMX stimulated fatty acids in most generations including T13. The stimulation was resulted from the balance between enzymes for fatty acid synthesis (e.g., fatty acid synthetase) and those for its consumption (e.g., fatty acid transport protein). Gene expression analysis demonstrated that the obesogenic effects of SMX involved peroxisome proliferator activated receptors (PPARs, e.g., nhr-49) and insulin/insulin-like signaling (IIS) pathways (e.g., ins-1 , daf-2 and daf-16). Further epigenetic analysis demonstrated that SMX caused 3-fold more H3K4me3 binding genes than the control in F10 and T13. In F10, the most significantly activated genes were in metabolic and biosynthetic processes of various lipids, nervous system and development. The different gene expressions in T13 from those in F10 involved development, growth, reproduction and responses to chemicals in addition to metabolic processes. [ABSTRACT FROM AUTHOR]

The reaction of N -arylpropynamides with (dichloroiodo)benzene (PhICl2) and diselenides/disulfides resulted in a divergent synthesis of chalcogenylated quinolinones and spiro[4.5]trienes through intramolecular electrophilic cyclization and chalcogenylation. The chalcogenyl functional group was introduced by an electrophilic reactive organosulfenyl chloride or selenenyl chloride species, generated in situ from the reaction of disulfides/diselenides and PhICl2. Notably, the divergent cyclization pathways were determined by the substituent type on the aniline ring in N -arylpropynamide substrates. Substrates bearing a fluoro, methoxy or trifluoromethoxy group at the para -position of the aniline underwent an alternative spiralization pathway to give the 3-chalcogenylated spiro[4,5]trienones. [ABSTRACT FROM AUTHOR]

The magnetic resonance sounding (MRS) method is a non-invasive, efficient and advanced geophysical method for groundwater detection. However, the MRS signal received by the coil sensor is extremely susceptible to electromagnetic noise interference. In MRS data processing, random noise suppression of noisy MRS data is an important research aspect. We propose an approach for intensive sampling sparse reconstruction (ISSR) and kernel regression estimation (KRE) to suppress random noise. The approach is based on variable frequency sampling, numerical integration and statistical signal processing combined with kernel regression estimation. In order to realize the approach, we proposed three specific sparse reconstructions, namely rectangular sparse reconstruction, trapezoidal sparse reconstruction and Simpson sparse reconstruction. To solve the distortion of peaks and valleys after sparse reconstruction, we introduced the KRE to deal with the processed data by the ISSR. Further, the simulation and field experiments demonstrate that the ISSR-KRE approach is a feasible and effective way to suppress random noise. Besides, we find that rectangular sparse reconstruction and trapezoidal sparse reconstruction are superior to Simpson sparse reconstruction in terms of noise suppression effect, and sampling frequency is positively correlated with signal-to-noise improvement ratio (SNIR). In one case of field experiment, the standard deviation of noisy MRS data was reduced from 1200.80 nV to 570.01 nV by the ISSR-KRE approach. The proposed approach provides theoretical support for random noise suppression and contributes to the development of MRS instrument with low power consumption and high efficiency. In the future, we will integrate the approach into MRS instrument and attempt to utilize them to eliminate harmonic noise from power line. [ABSTRACT FROM AUTHOR]

An anti-wear filler of molybdenum disulfide (MoS 2) coated chopped carbon fiber (SCF) was synthesized by hydrothermal method and blended with nano-SiO 2 to enhance the tribological properties of PEEK composites materials. The results show that the SCF-MoS 2 has stronger adhesion with the PEEK matrix, which is more conducive to the internal stress transfer of PEEK composites. Compared with pure PEEK, the elastic modulus and tensile strength of PEEK/SiO 2 /SCF-MoS 2 composites are increased by 62.04% and 26.49% respectively. The friction coefficient and wear rate of PEEK/SiO 2 /SCF-MoS 2 composites are reduced by 31.43% and 79.18% respectively. In addition, it also shows good tribological properties in the simulation coal mine environment. [ABSTRACT FROM AUTHOR]