Pyroptosis-mediator GSDMD promotes Parkinson's disease pathology via microglial activation and dopaminergic neuronal death.

GSDMD-mediated pyroptosis occurs in the nigrostriatal pathway in Parkinson's disease animals, yet the role of GSDMD in neuroinflammation and death of dopaminergic neurons in Parkinson's disease remains elusive. Here, our in vivo and in vitro studies demonstrated that GSDMD, as a pyroptosis executor, contributed to glial reaction and death of dopaminergic neurons across different Parkinson's disease models. The ablation of the Gsdmd attenuated Parkinson's disease damage by reducing dopaminergic neuronal death, microglial activation, and detrimental transformation. Disulfiram, an inhibitor blocking GSDMD pore formation, efficiently curtailed pyroptosis, thereby lessening the pathology of Parkinson's disease. Additionally, a modification in GSDMD was identified in the blood of Parkinson's disease patients in contrast to healthy subjects. Therefore, the detected alteration in GSDMD within the blood of Parkinson's disease patients and the protective impact of disulfiram could be promising for the diagnostic and therapeutic approaches against Parkinson's disease.

Challenges of mesenchymal stem cells in the clinical treatment of COVID-19.

The 2019 coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought an enormous public health burden to the global society. The duration of the epidemic, the number of infected people, and the widespread of the epidemic are extremely rare in modern society. In the initial stage of infection, people generally show fever, cough, and dyspnea, which can lead to pneumonia, acute respiratory syndrome, kidney failure, and even death in severe cases. The strong infectivity and pathogenicity of SARS-CoV-2 make it more urgent to find an effective treatment. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with the potential for self-renewal and multi-directional differentiation. They are widely used in clinical experiments because of their low immunogenicity and immunomodulatory function. Mesenchymal stem cell-derived exosomes (MSC-Exo) can play a physiological role similar to that of stem cells. Since the COVID-19 pandemic, a series of clinical trials based on MSC therapy have been carried out. The results show that MSCs are safe and can significantly improve patients' respiratory function and prognosis of COVID-19. Here, the effects of MSCs and MSC-Exo in the treatment of COVID-19 are reviewed, and the clinical challenges that may be faced in the future are clarified.

Hypoxia inducible factor-1α regulates microglial innate immune memory and the pathology of Parkinson's disease.

Neuroinflammation is one of the core pathological features of Parkinson's disease (PD). Innate immune cells play a crucial role in the progression of PD. Microglia, the major innate immune cells in the brain, exhibit innate immune memory effects and are recognized as key regulators of neuroinflammatory responses. Persistent modifications of microglia provoked by the first stimuli are pivotal for innate immune memory, resulting in an enhanced or suppressed immune response to second stimuli, which is known as innate immune training and innate immune tolerance, respectively. In this study, LPS was used to establish in vitro and in vivo models of innate immune memory. Microglia-specific Hif-1α knockout mice were further employed to elucidate the regulatory role of HIF-1α in innate immune memory and MPTP-induced PD pathology. Our results showed that different paradigms of LPS could induce innate immune training or tolerance in the nigrostriatal pathway of mice. We found that innate immune tolerance lasting for one month protected the dopaminergic system in PD mice, whereas the effect of innate immune training was limited. Deficiency of HIF-1α in microglia impeded the formation of innate immune memory and exerted protective effects in MPTP-intoxicated mice by suppressing neuroinflammation. Therefore, HIF-1α is essential for microglial innate immune memory and can promote neuroinflammation associated with PD.

MdNup62 involved in salt and osmotic stress tolerance in apple.

Abiotic stress of plants has serious consequences on the development of the apple industry. Nuclear pore complexes (NPCs) control nucleoplasmic transport and play an important role in the regulation of plant abiotic stress response. However, the effects of NPCs on apple salt and osmotic stress responses have not been reported yet. In this study, we analyzed the expression and function of NUCLEOPORIN 62 (MdNup62), a component of apple NPC. MdNup62 expression was significantly increased by salt and mannitol (simulated osmotic stress) treatment. The MdNup62-overexpressing (OE) Arabidopsis and tomato lines exhibited significantly reduced salt stress tolerance, and MdNup62-OE Arabidopsis lines exhibited reduced osmotic stress tolerance. We further studied the function of HEAT SHOCK FACTOR A1d (MdHSFA1d), the interacting protein of MdNup62, in salt and osmotic stress tolerance. In contrast to MdNup62, MdHSFA1d-OE Arabidopsis lines showed significantly enhanced tolerance to salt and osmotic stress. Our findings suggest a possible interaction of MdNup62 with MdHSFA1d in the mediation of nuclear and cytoplasmic transport and the regulation of apple salt and osmotic stress tolerance. These results contribute to the understanding of the salt and osmotic stress response mechanism in apple.

Design of polymetallic sulfide NiS2@Co4S3@FeS as bifunctional catalyst for high efficiency seawater splitting.

The shortage of freshwater resources in the world today has limited the development of water splitting, and our eyes have turned to the abundant seawater. The development of relatively low-toxicity and high-efficiency catalysts is the most important area in seawater electrolysis. In this paper, the preparation of NiS2@Co4S3@FeS via a hydrothermal method on nickel foam has been studied for the first time. In the process of vulcanization, Fe will first generate FeS by virtue of its high affinity for vulcanization. Once Fe is vulcanized, the residual sulfur will be used to generate NiS2, while the vulcanization of Co requires a higher sulfur concentration and reaction temperature; thus, Co4S3 will be generated last. NiS2@Co4S3@FeS is confirmed to have excellent hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) catalytic properties in alkaline seawater. Its unique structure allows it to expose more reaction centres, and the synergies between the multiple metals optimize the charge distribution of the material and accelerate the OER and HER kinetics. NiS2@Co4S3@FeS requires overpotentials of only 122 mV and 68 mV for the OER and HER when reaching 10 mA cm-2, which is superior to most catalysts reported to date for seawater electrolysis, and the material displays acceptable stability. In an electrolytic cell composed of both positive and negative electrodes, when the current density is 10 mA cm-2, the NiS2@Co4S3@FeS material displays a low overpotential of only 357 mV for seawater splitting. Density functional theory shows that the FeS electrode has the optimum Gibbs free energy of H to accelerate reaction kinetics, and the synergistic catalysis of the NiS2, Co4S3 and FeS materials promotes the hydrogen production activity of the NiS2@Co4S3@FeS electrode. This work proposes a novel idea for designing environmentally friendly seawater splitting catalysts.

TLR2 deficiency is beneficial at the late phase in MPTP-induced Parkinson' disease mice.

AIMS: Parkinson's disease (PD) is a progressive neurodegenerative disorder. The etiology of PD is still elusive but neuroinflammation is proved to be an important contributor. Toll-like receptor 2 (TLR2) involves in the release of several inflammatory cytokines. Whether TLR2 serves as a mediator contributing to the damage of DA system in PD remain unclear. MAIN METHODS: Tlr2 knockout (Tlr2-/-) and wild-type (WT) mice were treated with a subacute regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). At 3, 7 and 14 days after MPTP injection, the behavioral performance, including the Pole test, the Rotarod test, the Rearing test and the Wire hang test was evaluated. Moreover, the PD-like phenotypes, including dopaminergic degeneration, the activation of glial cells and the α-Syn expression were systematically analyzed in the nigrostriatal pathway. Finally, the composition of gut microbiota in the MPTP-treated groups were assessed. KEY FINDINGS: TLR2 deficiency had no obvious impact on the dopaminergic injury at 3 and 7 days following MPTP administration. On the contrary, at 14 days post injection, TLR2 deficiency not only significantly attenuated motor deficits in the Pole test and the Rotarod test, and the nigrostriatal dopaminergic degeneration, but also mitigated α-Syn abnormality, astrocyte activation and neuroinflammation through the suppressed TLR2/MyD88/TRAF6/NF-κB signaling pathways. Additionally, the alteration of gut microbiota was also detected in the mutant mice. SIGNIFICANCE: These findings highlight the neuroprotective effect of TLR2-pathways at the late phase in the MPTP-induced PD mouse model.

Discovery and identification of a novel canine coronavirus causing a diarrhea outbreak in Vulpes.

Cross-species transmission of viruses from wildlife animal reservoirs, such as bats, poses a threat to human and domestic animal health. Previous studies have shown that domestic animals have important roles as intermediate hosts, enabling the transmission of genetically diverse coronaviruses from natural hosts to humans. Here, we report the identification and characterization of a novel canine coronavirus (VuCCoV), which caused an epidemic of acute diarrhea in Vulpes (foxes) in Shenyang, China. The epidemic started on November 8, 2019, and caused more than 39,600 deaths by January 1, 2022. Full-length viral genomic sequences were obtained from 15 foxes with diarrhea at the early stage of this outbreak. The VuCCoV genome shared more than 90% nucleotide identity with canine coronavirus (CCoV) for three of the four structural genes, with the S gene showing a larger amount of divergence. In addition, 67% (10/15) of the VuCCoV genomes contained an open reading frame (ORF3) gene, which was previously only detected in CCoV-I genomes. Notably, VuCCoV had only two to three amino acid differences at the partial RNA-dependent RNA polymerase (RdRp) level to bat CoV, suggesting a close genetic relationship. Therefore, these novel VuCCoV genomes represent a previously unsampled lineage of CCoVs. We also show that the VuCCoV spike protein binds to canine and fox aminopeptidase N (APN), which may allow this protein to serve as an entry receptor. In addition, cell lines were identified that are sensitive to VuCCoV using a pseudovirus system. These data highlight the importance of identifying the diversity and distribution of coronaviruses in domestic animals, which could mitigate future outbreaks that could threaten livestock, public health, and economic growth.

Controlled synthesis of M doped NiVS (M = Co, Ce and Cr) as a robust electrocatalyst for urea electrolysis.

Urea electrolysis can be used to treat wastewater containing urea and alleviate the energy crisis, so it is one of the best ways to solve environmental and energy problems. This paper reports the synthesis of M doped NiVS (M = Co, Ce and Cr) composites by a simple hydrothermal process for the first time. What is noteworthy is that the Ce-NiVS material as a catalytic electrode requires only 141 mV overpotential for the hydrogen evolution reaction (HER) and 1.291 V potential for the urea oxidation reaction (UOR) at a current density of 10 mA cm-2 in 1.0 M KOH and 0.5 M urea mixed alkaline solution. Using Ce-NiVS/NF as both the anode and cathode for urea electrolysis, a current density of 10 mA cm-2 is driven by a voltage of only 1.55 V, which is better than most previous catalysts. Experimental results demonstrate that the excellent catalytic activity of Ce-NiVS materials is due to the formation of a large number of active sites and the improvement of conductivity due to doping with Ce. Density functional theory calculation shows that the VS4 material has a small Gibbs free energy of hydrogen adsorption, which plays a major role in the hydrogen production process, and Ce-NiS has a higher density of states (DOS) near the Fermi level, indicating that Ce-NiS has better electronic conductivity. The synergistic catalysis of VS4 and Ce-NiS promoted the hydrogen production performance of the Ce-NiVS material. This work provides guidance for the optimization and design of low-cost electrocatalysts to replace expensive precious metal-based electrocatalysts for overall urea electrolysis.

Controlled synthesis of ACo2O4 (A = Fe, Cu, Zn, Ni) as an environmentally friendly electrocatalyst for urea electrolysis.

Water electrolysis is relatively an environmentally friendly hydrogen production technology, but due to the slow transfer of four electrons in the anodic oxidation reaction, it needs a theoretical voltage of up to 1.23 V. Therefore, in this experiment, a series of transition metal oxides, ACo2O4 (A = Fe, Cu, Zn, Ni), was synthesized on Ni foam current collectors by a hydrothermal and calcination method, and the material was applied in urea electrolysis to produce hydrogen. What is noteworthy is that the CuCo2O4 electrode has a unique flower-like nanoneedle structure, and has a larger electrochemical active area, more reactive active sites, and a faster charge transfer rate. In 1.0 M KOH and 0.5 M urea solution, CuCo2O4 provides a potential of only 1.268 V at a current density of 10 mA cm-2 during the urea oxidation reaction (UOR), while in 1.0 M KOH solution, with the same current density, the oxygen evolution reaction (OER) is required to provide a potential of 1.53 V, indicating that the UOR can effectively replace the OER. Density functional theory calculations show that the CuCo2O4 material exhibits Gibbs free energy of the hydrogen closest to zero, thus promoting the electrochemistry performance of the electrode. In a cell composed of CuCo2O4//CuCo2O4, the current density of 10 mA cm-2 can be achieved by providing a potential of only 1.509 V. This work offers a novel scheme for reducing energy consumption of the OER and improving catalytic performance of the UOR.

HDAC6 Deficiency Has Moderate Effects on Behaviors and Parkinson's Disease Pathology in Mice.

Histone deacetylase 6 (HDAC6) is involved in the regulation of protein aggregation and neuroinflammation, but its role in Parkinson's disease (PD) remains controversial. In this study, Hdac6-/- mice were generated by CRISPR-Cas9 technology for exploring the effect of HDAC6 on the pathological progression of PD. We found that male Hdac6-/- mice exhibit hyperactivity and certain anxiety. In the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice, though motor injury was slightly alleviated by HDAC6 deficiency, dopamine (DA) depletion in the striatum, the decrease in the number of DA neurons in the substantia nigra (SN) and the reduction in DA neuronal terminals were not affected. In addition, activation of glial cells and the expression of α-synuclein, as well as the levels of apoptosis-related proteins in the nigrostriatal pathway, were not changed in MPTP-injected wild-type and Hdac6-/- mice. Therefore, HDAC6 deficiency leads to moderate alterations of behaviors and Parkinson's disease pathology in mice.

Autonomy support and prosocial impact facilitate meaningful work: A daily diary study.

This study pays attention to within-person fluctuations in meaningful work and its antecedents and consequences. Considering self- and other-oriented dimensions as crucial pathways to meaningful work, effects of daily perceived autonomy support and prosocial impact on one's meaningful work were examined. A daily diary study was conducted in which 86 nurses from varied hospitals reported their work experiences for 10 consecutive workdays (860 occasions). Results of multilevel modeling showed that both day-level perceived autonomy support and prosocial impact were positively related to day-level meaningful work, which served as the mediator between them and work engagement. Prosocial orientation strengthened the positive relationship between day-level perceived prosocial impact and day-level meaningful work. However, autonomy orientation negatively moderated the effect of day-level perceived autonomy support on day-level meaningful work, suggesting the necessity to distinguish between assisted and asserted autonomy orientation. Our findings illustrate the transient and dynamic nature of meaningful work and provide empirical evidences linking suggested managerial practices to employees' meaningful work.

The synthesis of W-Ni3S2/NiS nanosheets with heterostructure as a high-efficiency catalyst for urea oxidation.

The development of efficient and stable non-precious-metal-based electrocatalysts is essential for practical water splitting applications. The electrolysis of water for hydrogen production is a green and efficient method, while urea electrolysis can improve energy conversion efficiency. In this paper, W-Ni3S2/NiS catalysts with heterogeneous structures were synthesized via a one-step hydrothermal method using a W-doping-induced phase transition strategy. The doping of W modulates the morphology of the catalyst, which can form uniform nanorod arrays and improve the activity of the electrocatalyst. In an alkaline solution of 1 M KOH and 0.5 M urea, W-Ni3S2/NiS requires a potential of only 1.309 V to achieve a current density of 10 mA cm-2. An electrolyzer containing urea with W-Ni3S2/NiS as both the cathode and anode can drive a current density of 10 mA cm-2 with a potential of only 1.569 V and has relatively good stability after testing for 20 h. Experimental results show that the improvement in the catalytic activity is due to the rapid charge transfer, exposure of more active sites and better conductivity. Density functional theory calculations show that the W-Ni3S2 material exhibits higher urea adsorption energy, indicating that urea is preferentially adsorbed on its surface. The NiS material shows more state density near the Fermi level, indicating that the introduction of this material enhances the conductivity of the W-Ni3S2/NiS material. The synergistic catalysis of the two materials promoted the improvement of the catalytic activity. This work provides new ideas for the development of highly efficient and stable catalysts by means of doping and interface construction.

In situ construction of WNiM-WNi LDH (M = Se, S, or P) with heterostructure as highly efficient electrocatalyst for overall water splitting and urea oxidation reaction.

Electrochemical water splitting as an important means of obtaining high purity hydrogen fuel has attracted great interest. In this study, the structural engineering of complex WNiM-WNi LDH (M = Se, S, or P) was firstly developed by in situ growth on Ni foam for use in overall water splitting and the urea oxidation reaction. These WNiM-WNi LDH (M = Se, S, or P) catalysts exhibit outstanding electrocatalytic performance in the hydrogen evolution reaction (HER), oxygen evolution reaction (OER) and urea oxidation reaction (UOR), respectively. An overpotential of only 64 mV of OER is required for WNiS-WNi LDH and 126 mV of HER is required for WNiP-WNi LDH to achieve 10 mA cm-2. The WNiSe-WNi LDH materials display a particularly outstanding performance for UOR, requiring a potential of 1.25 V to drive 10 mA cm-2. Moreover, the optimized WNiS-WNi LDH as an anode and WNiP-WNi LDH as a cathode can achieve 10 mA cm-2 at a low cell voltage of 1.45 V in 1 M KOH solution for overall water splitting. The density functional theory calculations show that the introduction of the NiP2 and WP material greatly reduces the Gibbs free energy of the hydrogen adsorption of the material.

NOD-like receptor NLRC5 promotes neuroinflammation and inhibits neuronal survival in Parkinson's disease models.

Parkinson's disease (PD) is mainly characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and neuroinflammation mediated by overactivated microglia and astrocytes. NLRC5 (nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 5) has been reported to participate in various immune disorders, but its role in neurodegenerative diseases remains unclear. In the current study, we found that the expression of NLRC5 was increased in the nigrostriatal axis of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced PD, as well as in primary astrocytes, microglia and neurons exposed to different neurotoxic stimuli. In an acute MPTP-induced PD model, NLRC5 deficiency significantly reduced dopaminergic system degeneration and ameliorated motor deficits and striatal inflammation. Furthermore, we found that NLRC5 deficiency decreased the expression of the proinflammatory genes IL-1ß, IL-6, TNF-α and COX2 in primary microglia and primary astrocytes treated with neuroinflammatory stimuli and reduced the inflammatory response in mixed glial cells in response to LPS treatment. Moreover, NLRC5 deficiency suppressed activation of the NF-κB and MAPK signaling pathways and enhanced the activation of AKT-GSK-3ß and AMPK signaling in mixed glial cells. Furthermore, NLRC5 deficiency increased the survival of primary neurons treated with MPP+ or conditioned medium from LPS-stimulated mixed glial cells and promoted activation of the NF-κB and AKT signaling pathways. Moreover, the mRNA expression of NLRC5 was decreased in the blood of PD patients compared to healthy subjects. Therefore, we suggest that NLRC5 promotes neuroinflammation and dopaminergic degeneration in PD and may serve as a marker of glial activation.

Advances in mesenchymal stromal cells and nanomaterials for diabetic wound healing.

The delayed healing of diabetic wounds (DBW) will not only afflict patients, but also lead to amputation and even death in serious cases, which will create many negative effects on society and the country. Mesenchymal stromal cells (MSCs) have attracted extensive attention for their applications in chronic wound healing due to their excellent cytokine secretion ability and regulation of inflammation. Mesenchymal stromal cells can be used alone or wrapped with carrier/matrix and applied to enhance healing in the wound area. In this review, the etiology of the slow healing of DBW and the mechanism by which MSCs promote the healing of DBW were explored. In addition, we summarised the current research progress on the use of stromal cell-loaded biomaterials for wound healing in diabetic animal models. At the end of the article, we pointed out the challenges and improvement strategies for stromal cell therapy applied to DBW in future clinical practice.

Controlled synthesis of Crx-FeCo2P nanoarrays on nickel foam for overall urea splitting.

Urea splitting is a highly promising technology for hydrogen production to cope with the fossil energy crisis, which requires the development of catalysts with high electrocatalytic activity. In this article, Crx-FeCo2P/NF catalysts were synthesized by hydrothermal and low-temperature phosphorylation and used in the overall urea splitting process. Cr0.15-FeCo2P/NF and Cr0.1-FeCo2P/NF exhibited excellent urea oxidation reaction (UOR) activity (potential of 1.355 V at 100 mA cm-2) and hydrogen evolution reaction (HER) activity (overpotential of 173 mV at 10 mA cm-2) in 0.5 M urea solution containing 1 M KOH. In the assembled Cr0.15-FeCo2P/NF//Cr0.1-FeCo2P/NF electrolytic cell, only a small voltage of 1.50 V is needed to reach 10 mA cm-2. Density functional theory (DFT) calculation results demonstrate that an appropriate amount of Cr doping accelerates the kinetic performance of hydrogen production as well as improving the metallic properties of the electrode.

Ni3S2/MxSy-NiCo LDH (M = Cu, Fe, V, Ce, Bi) heterostructure nanosheet arrays on Ni foam as high-efficiency electrocatalyst for electrocatalytic overall water splitting and urea splitting.

Here, we synthesized a series of Ni3S2/MxSy-NiCo LDH materials (M = Cu, Fe, V, Ce, and Bi) by a two-step hydrothermal method for the first time, which display excellent oxygen evolution reaction (OER) and urea oxidation reaction (UOR) properties. M (M = Cu, Fe, V, Ce, and Bi) ions were firstly doped into NiCo LDH to change the original electronic structure and enhance the activity of the LDH. Then, Ni3S2 and MxSy were introduced by sulfurization of the Ni support and doping cations, and the combination of Ni3S2, MxSy and NiCo-LDH improved the electron transfer rate and activity of the original material. With Ni3S2/Bi2S3-NiCo LDH/NF as anode and Ni3S2/CuS-NiCo LDH as cathode, an electrolytic cell can reach 10 mA cm-2 at 1.622 V with outstanding durability for overall water splitting. In addition, with Ni3S2/Bi2S3-NiCo LDH/NF as both electrodes, it can reach 10 mA cm-2 at 1.56 V with outstanding durability for overall urea splitting, which is better than that of the overall water splitting. Density functional theory (DFT) calculation shows that the superior electrocatalytic activity can be explained by the water adsorption energy being optimized and enhanced conductivity. This study provides a new idea for improving the catalytic activity and stability of non-noble metals instead of noble metals.

NRSF regulates age-dependently cognitive ability and its conditional knockout in APP/PS1 mice moderately alters AD-like pathology.

NRSF/REST (neuron-restrictive silencer element, also known as repressor element 1-silencing transcription factor), plays a key role in neuronal homeostasis as a transcriptional repressor of neuronal genes. NRSF/REST relates to cognitive preservation and longevity of humans, but its specific functions in age-dependent and Alzheimer's disease (AD)-related memory deficits remain unclear. Here, we show that conditional NRSF/REST knockout either in the dorsal telencephalon or specially in neurons induced an age-dependently diminished retrieval performance in spatial or fear conditioning memory tasks and altered hippocampal synaptic transmission and activity-dependent synaptic plasticity. The NRSF/REST deficient mice were also characterized by an increase of activated glial cells, complement C3 protein and the transcription factor C/EBPß in the cortex and hippocampus. Reduction of NRSF/REST by conditional depletion upregulated the activation of astrocytes in APP/PS1 mice, and increased the C3-positive glial cells, but did not alter the Aß loads and memory retrieval performances of 6- and 12-month-old APP/PS1 mice. Simultaneously, overexpression of NRSF/REST improved cognitive abilities of aged wild type, but not in AD mice. These findings demonstrated that NRSF/REST is essential for the preservation of memory performance and activity-dependent synaptic plasticity during aging and takes potential roles in the onset of age-related memory impairments. However, while altering the glial activation, NRSF/REST deficiency does not interfere with the Aß deposits and the electrophysiological and cognitive AD-like pathologies.

Induction of autophagy via the PI3K/Akt/mTOR signaling pathway by Pueraria flavonoids improves non-alcoholic fatty liver disease in obese mice.

Non-alcoholic fatty liver disease (NAFLD) is the most common among lipid metabolism disorders. Autophagy plays an important role in lipid metabolism in NAFLD. Pueraria flavonoids, the main active ingredients of Pueraria lobata, exert antioxidant and anti-inflammatory effects. Herein, we report the potential lipid-lowering and anti-inflammatory effects of Pueraria flavonoids on NAFLD induced by a high-fat diet. In vivo and in vitro experiments showed that Pueraria flavonoids reduced intracellular lipid deposition by inhibiting lipid synthesis and the release of pro-inflammatory cytokines. We analyzed the autophagy flux by mRFP-GFP-LC3 plasmid transfection to assess the role of autophagy in intracellular scavenging. After treating mice fed on high fat and HepG2 cells with Pueraria flavonoids, the number of autophagosomes increased significantly, along with the level of autophagy. The autophagy loss after siRNA transfection aggravated lipid deposition and the release of inflammatory cytokines. Mechanistically, Pueraria flavonoids trigger autophagy through PI3K/Akt/mTOR signaling pathway to reduce lipid deposition and inflammation. In summary, our results showed that Pueraria flavonoids stimulated autophagy by inhibiting the PI3K/Akt/mTOR signaling pathway, thereby reducing intracellular lipid accumulation and inflammation levels and alleviating NAFLD.

Controlled synthesis of M doped Co3O4 (M = Ce, Ni and Fe) on Ni foam as robust electrocatalyst for oxygen evolution reaction and urea oxidation reaction.

Electrocatalytic water splitting has become one of the most promising and effective ways to solve energy crises and environmental pollution.In this work, a series of M-doped Co3O4 materials with foreign ions (M = Ce, Ni and Fe) were grown on a Ni foam substrate through classical hydrothermal and calcination methods.It is worth noting that not all doping of foreign ions can promote the electrocatalytic performance of intrinsic materials.The Ce-doped Co3O4 material shows excellent oxidation properties of water (overpotential of 320 mV at 50 mA cm-2) and urea (potential of 1.39 V at 50 mA cm-2).However, the doping of Ni reduces the water oxidation performance of the intrinsic material (overpotential of 410 mV@ 50 mA cm-2), and the doping of Fe reduces the urea oxidation performance of the inherent material (potential of 1.45 V@ 50 mA cm-2).A series of experimental results indicate that the improved activity of the Ce-Co3O4 electrode is attributed to faster electron transport capacity, higher exposure to active sites, and improved conductivity due to doping of Ce. It is noteworthy that the doping of these ions does alter the rate-determination step for the water oxidation reaction. The stability test demonstrated that the current density of water oxidation and urea oxidation of the catalyst had no significant attenuation after a long electrocatalytic activity test. This work provides a new idea for improving the electrocatalytic activity of catalysts by a doping strategy.