Search

The simultaneous enhancement of lipophagy and mitochondrial biogenesis has emerged as a promising strategy for lipid lowering. The transcription factor EB (TFEB) exhibits a dual role, whereby it facilitates the degradation of lipid droplets (LDs) through the process of lipophagy while simultaneously stimulating mitochondrial biogenesis to support the utilization of lipophagy products. The purpose of this study was to explore the effect of astragaloside I (AS I) on hyperlipidemia and elucidate its underlying mechanism. AS I improved serum total cholesterol and triglyceride levels and reduced hepatic steatosis and lipid accumulation in db/db mice. AS I enhanced the fluorescence colocalization of LDs and autophagosomes and promoted the proteins and genes related to the autolysosome. Moreover, AS I increased the expression of mitochondrial biogenesis-related proteins and genes, indicating that AS I promoted lipophagy and mitochondrial biogenesis. Mechanistically, AS I inhibits the protein level of p-TFEB (ser211) expression and promotes TFEB nuclear translocation. The activation of TFEB by AS I was impeded upon the introduction of the mammalian target of rapamycin (mTOR) agonist MHY1485. The inhibition of p-mTOR by AS I and the activation of TFEB were no longer observed after administration of the Akt agonist SC-79, which indicated that AS I activated TFEB to promote lipophagy-dependent on the Akt/mTOR pathway and may be a potentially effective pharmaceutical and food additive for the treatment of hyperlipidemia.

Graphical abstract:

The effect of alternating magnetic field (AMF) on the microstructure evolution and mechanical properties during tempering of M50 bearing steel have been investigated for evaluating the application prospect of magnetic field in steels. Microstructural observation and EDS analysis shows that during solidification process, M2C carbides rich in molybdenum are easily formed on the matrix of M50 bearing steel. Microstructure characterization results show that the application of AMF promotes the dissolution and refinement of carbides. At medium tempering temperature (300 °C, 380 °C), Vickers hardness increased with the application of AMF. Furthermore, due to the occurrence of secondary hardening, the Vickers hardness increases at high tempering temperature of 540 °C and the application of AMF has little effect on the hardness change. In addition, tensile fracture morphology observation shows that the morphology is mainly quasi-cleavage fracture. At medium tempering temperature, the presence of large carbides and transgranular cracks on the matrix results in the low tensile strength. For the high tempering temperature, the AMF could significantly reduce the carbide size and increase the tensile strength. This provides a new idea for improving the mechanical properties of M50 bearing steel by using AMF during tempering process.

The fruit of Fructus Moriis food and medicine, which has been demonstrated to have a significant neuroprotective effect. However, the effective constituent remains unknown. We speculate that the glycopeptide in the extract of the fruit has similar activity. To address this hypothesis, we isolated a novel pectin-like glycopeptide (FMP-6-S4) with a molecular weight of 11.23 kDa from the fruit. It contains about 20% of peptide comprising 17 amino acids and 80% glycan consisting of L-rhamnose (L-Rha), D-galactose (D-Gal), D-galacturonic acid (D-GalA), L-arabinose (L-Ara) and d-glucose (D-Glc) in molar ratios of 7.25:4.62:77.66:5.62:4.85. The backbone of the glycan part consisted of 1,4-linked α-D-GalpA and 1, 2-linked α-L-Rhap, while the branches were composed of hexenuronic acid (HexA) substituted at the C-3 position of partial galacturonic acid, and traces of galactose, glucose, and arabinose were substituted at the C-4 position of rhamnose. The in vitroexperiments revealed that FMP-6-S4 might inhibit Aβ42(β-amyloid peptides 42) aggregation and decrease Aβ42production by modulating APP (amyloid precursor protein) processing.

Mars Surface Composition Detector (MarSCoDe) is one of the important payloads carried by the Zhurong rover, China's first Mars exploration mission Tianwen‐1. The laser‐induced breakdown spectroscopy (LIBS) instrument of MarSCoDe is mainly used to detect major and trace elements on the surface of Mars. The quantitative analysis of alkali trace elements, namely lithium (Li), strontium (Sr), and rubidium (Rb), holds significance in unraveling the geological evolution of the Zhurong landing site. This study focuses on establishing univariate calibration models using MarSCoDe LIBS spectra from 84 samples tested in the ground laboratory. The accuracy of these models, within a few parts per million (ppm), was subsequently validated through the analysis of 12 onboard MarSCoDe Calibration Targets (MCCTs). With these models, Li, Sr, and Rb concentrations in the surface targets during the initial 300 sols (Martian days) traverse were determined. These concentrations ranged from 6 to 18, 106–628, and 22–87 ppm, respectively. Our results suggest that Li, Sr, and Rb are mainly related to the igneous rock components in the rocks and soils at the Zhurong landing site. The major secondary minerals in MarSCoDe scientific targets are likely small amounts of sulfates, which appear to have formed from the acidic weathering of recent surface brine. Clay minerals are likely either absent or very sparse in the scientific targets. The surface igneous materials at the landing site likely have originated from the most recent lava flow during the Amazonian epoch. Mars Surface Composition Detector (MarSCoDe) is a crucial instrument carried by China's Zhurong rover on the Tianwen‐1 mission, the country's first Mars exploration mission. The primary function of the laser‐induced breakdown spectroscopy (LIBS) on MarSCoDe is to measure the composition of Martian surface materials. Studying lithium (Li), strontium (Sr), and rubidium (Rb) can help us understand the history of where Zhurong is located. This study has developed precise models using MarSCoDe LIBS data from 84 ground test samples to measure these elements. The high accuracy of these models was verified through the Martian results of 12 MarSCoDe Calibration Targets (MCCTs). Using these models, we determined Li, Sr, and Rb contents in the surface targets during the first 300 Martian days of Zhurong rover exploration. Our results indicate that elevated Li, Sr, and Rb contents are primarily related to the magmatic rocks in MarSCoDe Martian targets. These targets contain small amounts of sulfates, which possibly formed due to recent acidic erosion connected to surface salty water. Clay minerals are likely either absent or very few in these targets. The surface magmatic materials where Zhurong is located likely formed from the most recent lava flow. Lithium, strontium, and rubidium concentrations have been obtained by a Mars surface composition detector using univariate modelsLithium, strontium, and rubidium are primarily associated with the igneous rock components in the rocks and soils at the Zhurong landing siteThe surface igneous materials may originate from an Amazonian lava flow, possibly with minor acidic weathering from recent surface brine Lithium, strontium, and rubidium concentrations have been obtained by a Mars surface composition detector using univariate models Lithium, strontium, and rubidium are primarily associated with the igneous rock components in the rocks and soils at the Zhurong landing site The surface igneous materials may originate from an Amazonian lava flow, possibly with minor acidic weathering from recent surface brine

The unified power quality conditioner (UPQC) integrated with the battery energy storage system not only mitigates the power quality problems on the grid side and load side but also supplies active power to the load or the grid. The wide voltage variation of the battery and the high efficiency of the whole system can be achieved with the hybrid connected configuration, i.e., the battery is connected simultaneously to the series and shunt converters of the UPQC directly and indirectly through the dc–dc converter. However, the control and modulation strategies are the major challenges for this configuration. This study proposes a control scheme based on asymmetrical sinusoidal pulse width modulation (SPWM) to realize high-efficiency active power delivery, thereby addressing the issue above. The mechanism of the modulation scheme to regulate active power is revealed, and the voltage variation of the battery is considered. The modified SPWM strategy features easy implementation and a low computation burden. The effectiveness of the system with the proposed control and modulation schemes is verified by both simulation and experimental results.

Glucagon-like peptide 2 (GLP-2) is a peptide hormone derived from the proglucagon gene expressed in the intestines, pancreas and brain. Some previous studies showed that GLP-2 improved aging and Alzheimer’s disease related memory impairments. Parkinson’s disease (PD) is a progressive neurodegenerative disorder, and to date, there is no particular medicine reversed PD symptoms effectively. The aim of this study was to evaluate neuroprotective effects of a GLP-2 analogue in the 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) PD mouse model. In the present study, the protease resistant Gly(2)-GLP-2 (50 nmol/kg ip.) analogue has been tested for 14 days by behavioral assessment, transmission electron microscope, immunofluorescence histochemistry, enzyme-linked immunosorbent assay and western blot in an acute PD mouse model induced by MPTP. For comparison, the incretin receptor dual agonist DA5-CH was tested in a separate group. The GLP-2 analogue treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement imbalance of mice. Gly(2)-GLP-2 treatment also protected dopaminergic neurons and restored tyrosine hydroxylase expression levels in the substantia nigra. Gly(2)-GLP-2 furthermore reduced the inflammation response as seen in lower microglia activation, and decreased NLRP3 and interleukin-1βpro-inflammatory cytokine expression levels. In addition, the GLP-2 analogue improved MPTP-induced mitochondrial dysfunction in the substantia nigra. The protective effects were comparable to those of the dual agonist DA5-CH. The present results demonstrate that Gly(2)-GLP-2 can attenuate NLRP3 inflammasome-mediated inflammation and mitochondrial damage in the substantia nigra induced by MPTP, and Gly(2)-GLP-2 shows neuroprotective effects in this PD animal model.

Porous materials with selective wettability and permeability have significant importance in oil–water separation, but complex fabrication processes are typically required to obtain the desired structures with suitable surface chemistry. In this work, an industrial melt-blown strategy that utilized commercially available polypropylene (PP) was used for the large-scale fabrication of superhydrophobic/superoleophilic membranes with staggered fabric structures. These membranes could readily separate different oils including pump oil and crude oil from various aqueous solutions such as strongly acidic, alkaline, and saline media. In addition, the separation efficiencies of these membranes exceeded 99%, and they could remain functional even after exposure to corrosive media. We anticipate that this work will further the design of membranes and enhance their applicability in oil–water separation, and provide researchers and engineers with a more effective tool for performing challenging separations and mitigating pollution.

Materials with opposite affinities toward oil and water have been extensively used to coat porous substrates for oil–water separation, but the applications of these materials have been limited by the need for complex coating processes as well as the short-term adherence of these materials onto different substrates under extreme conditions. As reported herein, the robust porous polyurethane hydrogel has been theoretically and structurally designed with ultralow-oil-adhesion properties which is free stand without depending on additional substrates. The combination of superhydrophilic properties along with the underwater superoleophobic behavior of this porous hydrogel allows gravity driven separations of oil–water mixtures, and its antiadhesion performance toward oil prevents undesirable oily fouling. The underwater superoleophobic properties were also illustrated by molecular dynamics simulation to understand the resisting effect of hydrated layers. The as-prepared porous hydrogel shows ultrahigh oil–water separation efficiencies of 99.9% for various oil–water mixtures, ranging from those containing viscous oils (pump oil and peanut oil) to organic solvents (n-hexane, n-hexadecane, and toluene). In addition, this hydrogel is durable even with exposure to various harsh conditions including acidic and basic media (pH 0–14) as well as exposure to mechanical abrasion. We believe that the combination of facile preparation, substrate independence, gravity driven separation, antifouling properties, high durability, as well as the outstanding separation flux and efficiency of this robust porous hydrogel will help to advance the design and application of materials in oil–water separation fields.

ABSTRACTThe effects of axial static magnetic field (ASMF) on the columnar-to-equiaxed transition (CET) in directionally solidified low carbon steel including peritectic reactions were investigated. Experimental results show that the dendrite morphology of this peritectic steel can be modified under ASMF. The increases of the magnetic field intensity and temperature gradient and the decrease of the growth speed can promote the CET. The columnar dendrites become equiaxed dendrites at a low growth speed. According to numerical simulations, a thermoelectric magnetic convection in the melts and a thermoelectric magnetic force acting on the secondary dendrite neck are induced by the interaction between a thermoelectric current and ASMF. The influence of ASMF on the CET covers the formation of the thermoelectric magnetic convection, transport of the fragments in the melts and detachment of dendritic side arms. In addition, the application of ASMF can extend the process window of equiaxed grains formed.

The effects of axial static magnetic field (ASMF) on the columnar-to-equiaxed transition (CET) in directionally solidified low carbon steel including peritectic reactions were investigated. Experimental results show that the dendrite morphology of this peritectic steel can be modified under ASMF. The increases of the magnetic field intensity and temperature gradient and the decrease of the growth speed can promote the CET. The columnar dendrites become equiaxed dendrites at a low growth speed. According to numerical simulations, a thermoelectric magnetic convection in the melts and a thermoelectric magnetic force acting on the secondary dendrite neck are induced by the interaction between a thermoelectric current and ASMF. The influence of ASMF on the CET covers the formation of the thermoelectric magnetic convection, transport of the fragments in the melts and detachment of dendritic side arms. In addition, the application of ASMF can extend the process window of equiaxed grains formed.

Celastrol (Cel), extracted from Tripterygium wilfordiiHook, is a potential antiobesity drug, except for its adverse reactions in clinic. In the present study, we synthesized a promising celastrol–chitosan conjugate (Cel-CS1K) and evaluated its antiobesity effect and biological safety in diet-induced obese mice. Cel-CS1K showed higher drug loading (over 10 wt %), good solubility (18–19 mg/mL) in water, slower peak time (Tmax= 4 h), and clearance (T1/2= 8.97 h) in rats. Cel-CS1K effectively attenuated the cytotoxicity, celastrol-induced apoptosis, and fat accumulation of hepatocytes. Cel-CS1K reduced body weight and dietary amount same as the free Cel but with lower toxicity in blood, liver, and testis. Cel-CS1K improved the glucose homeostasis, HDL-C level, insulin sensitivity, and leptin sensitivity, while it significantly reduced the gene expression levels of LDL-C, TG, and TC in obese mice. Furthermore, the adipose-related gene expression levels provided evidence in support of a role for Cel-CS1K in losing weight by the multimode regulation. Overall, Cel-CS1K provides a translatable therapeutic strategy for the treatment of diet-induced obese humans.

Visible-light-driven chemical transformation has emerged as a powerful tool for the synthesis of γ-lactams. However, during this transformation, the α-bromoimides need to be pre-prepared. Herein, we report a photoreodox/copper-catalyzed one-pot three-component reaction of alkenes with primary amines for the construction of γ-lactams. In this transformation, the orthoquinones were generated via a photocatalytic pathway, followed by attack by Cu–amido complexes and intramolecular cyclization to give the γ-lactams. This method represents a simple synthetic route displaying broad functional group tolerance, including substrates bearing alcohols, ketones, heterocycles, esters, halides, alkynes, nitriles, ethers, etc.

Parkinson’s disease (PD) is a complex syndrome with many elements, such as chronic inflammation, oxidative stress, mitochondrial dysfunction, loss of dopaminergic neurons, build-up of alpha-synuclein (α-syn) in cells, and energy depletion in neurons, that drive the disease. We and others have shown that treatment with mimetics of the growth factor glucagon-like peptide 1 (GLP-1) can normalize energy utilization, neuronal survival, and dopamine levels and reduce inflammation. Liraglutide is a GLP-1 analogue that recently showed protective effects in phase 2 clinical trials in PD patients and in Alzheimer disease patients. We have developed a novel dual GLP-1/GIP receptor agonist that can cross the blood-brain barrier and showed good protective effects in animal models of PD. Here, we test liraglutide against the dual GLP-1/GIP agonist DA5-CH (KP405) in the A53T tg mouse model of PD which expresses a human-mutated gene of α-synuclein. Drug treatment reduced impairments in three different motor tests, reduced levels of α-syn in the substantia nigra, reduced the inflammation response and proinflammatory cytokine levels in the substantia nigra and striatum, and normalized biomarker levels of autophagy and mitochondrial activities in A53T mice. DA5-CH was superior in almost all parameters measured and therefore may be a better drug treatment for PD than liraglutide.

Insulin desensitization has been observed in the brains of patients with Parkinson’s disease (PD), which is a progressive neurodegenerative disorder for which there is no cure. Semaglutide is a novel long-actingglucagon-likepeptide-1 (GLP-1) receptor agonist that is on the market as a treatment for type 2 diabetes. It is in a phase II clinical trial in patients with PD. Two previous phase II trials in PD patients showed good effects with the older GLP-1 receptor agonists, exendin-4 and liraglutide. We have developed a dual GLP-1/GIP receptor agonist (DA5-CH) that can cross the blood-brain barrier (BBB) at a higher rate than semaglutide. We tested semaglutide and DA5-CH in the 6-OHDA-lesion rat model of PD. Treatment was semaglutide or DA5-CH (25 nmol/kg, i.p.) daily for 30 days postlesion. Both drugs reduced the apomorphine-induced rotational behavior and alleviated dopamine depletion and the inflammation response in the lesioned striatum as shown in reduced IL-1β and TNF-α levels, with DA5-CH being more effective. In addition, both drugs protected dopaminergic neurons and increased TH expression in the substantia nigra. Furthermore, the level of monomer and aggregated α-synuclein was reduced by the drugs, and insulin resistance as shown in reduced pIRS-1ser312 phosphorylation was also attenuated after drug treatment, with DA5-CH being more effective. Therefore, while semaglutide showed good effects in this PD model, DA5-CH was superior and may be a better therapeutic drug for neurodegenerative disorders such as PD than GLP-1 receptor agonists that do not easily cross the BBB.

Celastrol is a promising drug candidate for treating diet-induced obesity, but the cytotoxicity and poor water solubility limit its clinical application. We prepared a novel celastrol conjugate (Cel-CMCS) with excellent water solubility (33.94 mg/mL), and then investigated its anti-obesity and toxic activities in diet-induced obese mice. Just as the parent celastrol, Cel-CMCS reduced body weight and body fat mass in an equally effective manner, but with lower toxicity. Collectively, Cel-CMCS provides a possible solution for the treatment of obesity in humans. In addition, the present study provided a practical experience of the development of carboxymethyl chitosan-based delivery system for poorly water-soluble drugs.

A solid model of a high-speed train axle box bearing was built by using 3D modeling software. On the platform of ANSYS/LS-DYNA, the combined dynamic and finite element analysis method is used to apply the combined radial and axial loads to the high-speed rail bearing. In order to demonstrate the dynamic contact characteristics of the bearing during operation, two operating conditions were designed. One is running at a uniform speed in a straight line, the other is running at an assumed speed with a minimum turning radius. The results show that the stress distribution, velocity and acceleration of bearing components under two different working conditions are obviously different. The research can provide reference for the design, selection and optimization of domestic high-speed rail bearings.