ACS-20/FATP4 mediates the anti-ageing effect of dietary restriction in C. elegans.

Dietary restriction is an effective anti-ageing intervention across species. However, the molecular mechanisms from the metabolic aspects of view are still underexplored. Here we show ACS-20 as a key mediator of dietary restriction on healthy ageing from a genetic screen of the C. elegans acyl-CoA synthetase family. ACS-20 functions in the epidermis during development to regulate dietary restriction-induced longevity. Functional transcriptomics studies reveal that elevated expression of PTR-8/Patched is responsible for the proteostasis and lifespan defects of acs-20. Furthermore, the conserved NHR-23 nuclear receptor serves as a transcriptional repressor of ptr-8 and a key regulator of dietary restriction-induced longevity. Mechanistically, a specific region in the ptr-8 promoter plays a key role in mediating the transcription regulation and lifespan extension under dietary restriction. Altogether, these findings identify a highly conserved lipid metabolism enzyme as a key mediator of dietary restriction-induced lifespan and healthspan extension and reveal the downstream transcriptional regulation mechanisms.

Pregnane X receptor agonist nomilin extends lifespan and healthspan in preclinical models through detoxification functions.

Citrus fruit has long been considered a healthy food, but its role and detailed mechanism in lifespan extension are not clear. Here, by using the nematode C. elegans, we identified that nomilin, a bitter-taste limoloid that is enriched in citrus, significantly extended the animals' lifespan, healthspan, and toxin resistance. Further analyses indicate that this ageing inhibiting activity depended on the insulin-like pathway DAF-2/DAF-16 and nuclear hormone receptors NHR-8/DAF-12. Moreover, the human pregnane X receptor (hPXR) was identified as the mammalian counterpart of NHR-8/DAF-12 and X-ray crystallography showed that nomilin directly binds with hPXR. The hPXR mutations that prevented nomilin binding blocked the activity of nomilin both in mammalian cells and in C. elegans. Finally, dietary nomilin supplementation improved healthspan and lifespan in D-galactose- and doxorubicin-induced senescent mice as well as in male senescence accelerated mice prone 8 (SAMP8) mice, and induced a longevity gene signature similar to that of most longevity interventions in the liver of bile-duct-ligation male mice. Taken together, we identified that nomilin may extend lifespan and healthspan in animals via the activation of PXR mediated detoxification functions.

Phase Transition Engineering of Host Perovskite toward Optimal Exsolution-facilitated Catalysts for Carbon Dioxide Electrolysis.

The in situ exsolution technique of nanoparticles has brought new opportunities for the utilization of perovskite-based catalysts in solid oxide cells. However, the lack of control over the structural evolution of host perovskites during the promotion of exsolution has restricted the architectural exploitation of exsolution-facilitated perovskites. In this study, we strategically broke the long-standing trade-off phenomenon between promoted exsolution and suppressed phase transition via B-site supplement, thus broadening the scope of exsolution-facilitated perovskite materials. Using carbon dioxide electrolysis as an illustrative case study, we demonstrate that the catalytic activity and stability of perovskites with exsolved nanoparticles (P-eNs) can be selectively enhanced by regulating the explicit phase of host perovskites, accentuating the critical role of the architectures of perovskite scaffold in catalytic reactions occurring on P-eNs. The concept demonstrated could potentially pave the way for designing the advanced exsolution-facilitated P-eNs materials and unveiling a wide range of catalytic chemistry taking place on P-eNs.

Nanosecond Laser Confined Bismuth Moiety with Tunable Structures on Graphene for Carbon Dioxide Reduction.

Substrate-supported catalysts with atomically dispersed metal centers are promising for driving the carbon dioxide reduction reaction (CO2RR) to produce value-added chemicals; however, regulating the size of exposed catalysts and optimizing their coordination chemistry remain challenging. In this study, we have devised a simple and versatile high-energy pulsed laser method for the enrichment of a Bi "single atom" (SA) with a controlled first coordination sphere on a time scale of nanoseconds. We identify the mechanistic bifurcation routes over a Bi SA that selectively produce either formate or syngas when bound to C or N atoms, respectively. In particular, C-stabilized Bi (Bi-C) exhibits a maximum formate partial current density of -29.3 mA cm-2 alongside a TOF value of 2.64 s-1 at -1.05 V vs RHE, representing one of the best SA-based candidates for CO2-to-formate conversion. Our results demonstrate that the switchable selectivity arises from the different coupling states and metal-support interactions between the central Bi atom and adjacent atoms, which modify the hybridizations between the Bi center and *OCHO/*COOH intermediates, alter the energy barriers of the rate-determining steps, and ultimately trigger the branched reaction pathways after CO2 adsorption. This work demonstrates a practical and universal ultrafast laser approach to a wide range of metal-substrate materials for tailoring the fine structures and catalytic properties of the supported catalysts and provides atomic-level insights into the mechanisms of the CO2RR on ligand-modified Bi SAs, with potential applications in various fields.

Boosting the stability of perovskites with exsolved nanoparticles by B-site supplement mechanism.

Perovskites with exsolved nanoparticles (P-eNs) have immense potentials for carbon dioxide (CO2) reduction in solid oxide electrolysis cell. Despite the recent achievements in promoting the B-site cation exsolution for enhanced catalytic activities, the unsatisfactory stability of P-eNs at high voltages greatly impedes their practical applications and this issue has not been elucidated. In this study, we reveal that the formation of B-site vacancies in perovskite scaffold is the major contributor to the degradation of P-eNs; we then address this issue by fine-regulating the B-site supplement of the reduced Sr2Fe1.3Ni0.2Mo0.5O6-δ using foreign Fe sources, achieving a robust perovskite scaffold and prolonged stability performance. Furthermore, the degradation mechanism from the perspective of structure stability of perovskite has also been proposed to understand the origins of performance deterioration. The B-site supplement endows P-eNs with the capability to become appealing electrocatalysts for CO2 reduction and more broadly, for other energy storage and conversion systems.

A sphingolipid-mTORC1 nutrient-sensing pathway regulates animal development by an intestinal peroxisome relocation-based gut-brain crosstalk.

The mTOR-dependent nutrient-sensing and response machinery is the central hub for animals to regulate their cellular and developmental programs. However, equivalently pivotal nutrient and metabolite signals upstream of mTOR and developmental-regulatory signals downstream of mTOR are not clear, especially at the organism level. We previously showed glucosylceramide (GlcCer) acts as a critical nutrient and metabolite signal for overall amino acid levels to promote development by activating the intestinal mTORC1 signaling pathway. Here, through a large-scale genetic screen, we find that the intestinal peroxisome is critical for antagonizing the GlcCer-mTORC1-mediated nutrient signal. Mechanistically, GlcCer deficiency, inactive mTORC1, or prolonged starvation relocates intestinal peroxisomes closer to the apical region in a kinesin- and microtubule-dependent manner. Those apical accumulated peroxisomes further release peroxisomal-ß-oxidation-derived glycolipid hormones that target chemosensory neurons and downstream nuclear hormone receptor DAF-12 to arrest the animal development. Our data illustrate a sophisticated gut-brain axis that predominantly orchestrates nutrient-sensing-dependent development in animals.

Nanoalloy libraries from laser-induced thermionic emission reduction.

Nanoalloys, especially high-entropy nanoalloys (HENAs) that contain equal stoichiometric metallic elements in each nanoparticle, are widely used in vast applications. Currently, the synthesis of HENAs is challenged by slow reaction kinetics that leads to phase segregation, sophisticated pretreatment of precursors, and inert conditions that preclude scalable fabrication of HENAs. Here, we report direct conversion of metal salts to ultrafine HENAs on carbonaceous support by nanosecond pulsed laser under atmospheric conditions. Because of the unique laser-induced thermionic emission and etch on carbon, the reduced metal elements were gathered to ultrafine HENAs and stabilized by defective carbon support. This scalable, facile, and low-cost method overcomes the immiscible issue and can produce various HENAs uniformly with a size of 1 to 3 nanometers and metal elements up to 11 with productivity up to 7 grams per hour. One of the senary HENAs exhibited excellent catalytic performance in oxygen reduction reaction, manifesting great potential in practical applications.

MiR-181 Enhances Proliferative and Migratory Potentials of Retinal Endothelial Cells in Diabetic Retinopathy by Targeting KLF6.

PURPOSE: We aimed to uncover the role of microRNA-181 (miR-181) in the disease onset of diabetic retinopathy (DR) and its underlying mechanism. METHODS: MiR-181 levels in plasma and aqueous humor samples of non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR) and healthy subjects were analyzed by microarray and quantitative real-time polymerase chain reaction (qRT-PCR). Proliferative and migrative capacities of human retinal endothelial cells (hRECs) regulated by miR-181 were assessed. The binding between miR-181 and Kruppel-like factor 6 (KLF6) was verified by dual-luciferase reporter assay. RESULTS: MiR-181 was upregulated in plasma and aqueous humor samples of NPDR and PDR patients. Overexpression of miR-181 stimulated hRECs to proliferate and migrate. KLF6 was the downstream gene binding miR-181, which was involved in the regulation of hRECs by miR-181. CONCLUSIONS: MiR-181 is upregulated in plasma and aqueous humor of DR patients. It enhances proliferative and migratory potentials of retinal endothelial cells by targeting KLF6.

Tangeretin promotes lifespan associated with insulin/insulin-like growth factor-1 signaling pathway and heat resistance in Caenorhabditis elegans.

Tangeretin is a polymethoxylated flavonoid naturally occurred in citrus fruits with many pharmacological activities, such as anti-inflammatory, antiproliferative, and neuroprotective properties. A previous study reported that tangeretin-enriched orange extract could prolong the lifespan in Caenorhabditis elegans. However, the antiaging effect of tangeretin remains uncertain. In this study, we used the model organism C. elegans to conduct a lifespan test, observed the aging-related functional changes of nematodes, the fluorescence changes of stress-related proteins (DAF-16 and HSP-16.2) and its response to stress assay, and monitored the effect of tangeretin on the mRNA expression levels. The results showed that tangeretin supplementation (30 and 100 µM) extended the mean lifespan, slowed aging-related functional declines, and increased the resistance against heat-shock stress. Furthermore, tangeretin upregulated the mRNA expression of daf-16, hsp-16.2, and hsp-16.49, promoted the nuclear localization of DAF-16, and enhanced the fluorescence intensity of HSP-16.2, while it had no effect on the lifespan of daf-2, age-1, and daf-16 mutants. The current findings suggest that tangeretin can significantly extend the lifespan and enhance heat stress tolerance in an insulin/insulin-like growth factor signaling dependent manner.

Interface-Induced Electrocatalytic Enhancement of CO2 -to-Formate Conversion on Heterostructured Bismuth-Based Catalysts.

Electrochemical CO2 reduction reaction (CO2 RR) is a promising approach to convert CO2 to carbon-neutral fuels using external electric powers. Here, the Bi2 S3 -Bi2 O3 nanosheets possessing substantial interface being exposed between the connection of Bi2 S3 and Bi2 O3 are prepared and subsequently demonstrate to improve CO2 RR performance. The electrocatalyst shows formate Faradaic efficiency (FE) of over 90% in a wide potential window. A high partial current density of about 200 mA cm-2 at -1.1 V and an ultralow onset potential with formate FE of 90% are achieved in a flow cell. The excellent electrocatalytic activity is attributed to the fast-interfacial charge transfer induced by the electronic interaction at the interface, the increased number of active sites, and the improved CO2 adsorption ability. These collectively contribute to the faster reaction kinetics and improved selectivity and consequently, guarantee the superb CO2 RR performance. This study provides an appealing strategy for the rational design of electrocatalysts to enhance catalytic performance by improving the charge transfer ability through constructing a functional heterostructure, which enables interface engineering toward more efficient CO2 RR.

Monomethyl branched-chain fatty acid mediates amino acid sensing upstream of mTORC1.

Animals have developed various nutrient-sensing mechanisms for survival under fluctuating environmental conditions. Although extensive cell-culture-based analyses have identified diverse mediators of amino acid sensing upstream of mTOR, studies using animal models to examine intestine-initiated amino acid sensing mechanisms under specific physiological conditions are lacking. Here, we developed a Caenorhabditis elegans model to examine the impact of amino acid deficiency on development. We discovered a leucine-derived monomethyl branched-chain fatty acid and its downstream metabolite, glycosphingolipid, which critically mediates the overall amino acid sensing by intestinal and neuronal mTORC1, which in turn regulates postembryonic development at least partly by controlling protein translation and ribosomal biogenesis. Additional data suggest that a similar mechanism may operate in mammals. This study uncovers an amino-acid-sensing mechanism mediated by a lipid biosynthesis pathway.

Stripped Electrode Based Electrowetting-on-Dielectric Digital Microfluidics for Precise and Controllable Parallel Microdrop Generation.

Microdrop generation with excellent controllability and volume precision is of paramount significance for a large variety of microfluidic applications. In this work, we propose a new configuration comprising only stripped electrodes of rectangular shape for the closed electrowetting-on-dielectric digital microfluidic (EWOD DMF) system and investigate its parallel microdrop generation outcomes via a numerical approach. The microfluidic droplet motion is solved by a finite-volume scheme on a fixed computational domain. The numerical model is verified by an experimental study of microdrop production from an EWOD DMF device with three different electrode designs. After model verification, we examine the influences of the equilibrium contact angle and the spacing of the microchannel on stripped electrode based microdrop generation outcomes and discover five different regimes including the phenomena of satellite droplet formation and separation cessation. Despite the various generation outcomes, the daughter droplet size is found to vary linearly with a dimensionless EWOD parameter κ*. More importantly, for all successful generations, the deviation of the daughter droplet size from that of the stripped electrode is smaller than 3.5%, which even reaches zero in proper conditions. This new configuration can be utilized as a convenient alternative for electrowetting-induced parallel microdrop production with excellent precision and controllability.

Protective effects of carnosic acid on retinal ganglion cells in acute ocular hypertension rats.

OBJECTIVE: To observe the protective effects of carnosic acid on rat retinal ganglion cells (RGCs) among acute ocular hypertension rats. METHODS: Sixty male SPF (specific-pathogen-free) SD rats (10 weeks) were randomly assigned to untreated group, carnosic-acid-treated group and hypertensive group with 20 rats for each. The acute ocular hypertension animal model was induced by the perfusion of normal saline solution into anterior chamber of eyes to elevate the intraocular pressure (IOP) to 110 mmHg for 60 min in the rats of the carnosic-acid-treated group and hypertensive group. Then, the carnosic acid dissolving in dimethyl sulfoxide (DMSO) was intraperitoneally injected for consecutive 7 days in the carnosic-acid-treated group, and only DMSO was used in the same way in the hypertensive group. The rats were killed 2 weeks after experiment, and retinal sections were prepared for histopathological and apoptotic retinal ganglion cells (RGCs) examination by hemotoxylin and eosin staining and TUNEL staining. Use immunofluorescence employed to examine the survival of RGCs. This study protocol was approved by the Ethic Committee for Experimental Animal of Three Gorges University. RESULTS: The retinal morphology and structure were clear in the untreated group. The edema of retinal tissue, loosely arranged RGCs and swollen nucleus were seen in the hypertensive group. In the carnosic-acid-treated group, the retinal morphology and structure were regular. The retinal nerve fiber layer (RNFL) thickness was (32.96 ± 1.63), (58.96 ± 1.57) and (50.11 ± 2.37) µm, and the apoptotic cell number was (6.92 ± 2.96), (29.85 ± 6.40) and (14.69 ± 2.98)/field, and the survived cell number was (2363.17 ± 148.45), (1308.67 ± 106.02) and (1614.17 ± 96.39)/0.235 mm2 in the untreated group, hypertensive group and carnosic-acid-treated group, respectively, showing significant differences among groups (F = 339.284, 81.583, 122.68, all at P < 0.01). Compared with the untreated group, the RNFL thickness was thickened, the number of apoptotic RGCs was much more, and the number of survived RGCs was decreased in the hypertensive group. In the carnosic-acid-treated group, the RNFL thickness was thinner, the number of apoptotic RGCs was reduced, and the number of survived RGCs was increased in comparison with the untreated group (all at P < 0.01). CONCLUSIONS: Carnosic acid plays a protective effect on RGCs by inhibiting the cell apoptosis in acute ocular hypertension rats.

Inhibitive effect of TAK-242 on Tenon's capsule fibroblasts proliferation in rat eyes.

AIM: To study the inhibition effect of TAK-242 on the proliferation of rat eye Tenon's capsule fibroblasts via the toll-like receptor 4 (TLR4) signaling pathway. METHODS: SD rat Tenon's capsule fibroblasts were extracted and cultured, then the cells were divided into normal control group, lipopolysaccharide (LPS) group (10 g/mL LPS) and TAK-242 group (1 µmol/L TAK-242, and 10 µg/mL LPS after 30min). The expressions of TLR4, transforming growth factor-ß1 (TGF-ß1) and interleukin-6 (IL-6) in each group were detected by Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Cell proliferation was detected by cell counting kit-8 (CCK-8). RESULTS: Double immunofluorescent labeling in the extracted cells showed negative keratin staining and positive vimentin staining. Western blot showed that the LPS group had the highest expression of TLR4 and TGF-ß1 (P<0.01). Enzyme linked immunosorbent assay (ELISA) also showed that the secretion of IL-6 was the highest in LPS group (P<0.01). But there was no significant difference in TLR4 and TGF-1, as well as IL-6 expressions between the TAK-242 group and the normal control group (P>0.05). RT-PCR showed that the IL-6 mRNA expression in LPS group was the highest in the three groups (P<0.01). CONCLUSION: TAK-242 inhibits the proliferation of LPS-induced Tenon's capsule fibroblasts and the release of inflammatory factors by regulating the TLR4 signaling pathway, providing a new idea for reducing the scarring of the filter passage after glaucoma filtration surgery.

Uniform MnCo2O4 Porous Dumbbells for Lithium-Ion Batteries and Oxygen Evolution Reactions.

Three-dimensional (3D) binary oxides with hierarchical porous nanostructures are attracting increasing attentions as electrode materials in energy storage and conversion systems because of their structural superiority which not only create desired electronic and ion transport channels but also possess better structural mechanical stability. Herein, unusual 3D hierarchical MnCo2O4 porous dumbbells have been synthesized by a facile solvothermal method combined with a following heat treatment in air. The as-obtained MnCo2O4 dumbbells are composed of tightly stacked nanorods and show a large specific surface area of 41.30 m2 g-1 with a pore size distribution of 2-10 nm. As an anode material for lithium-ion batteries (LIBs), the MnCo2O4 dumbbell electrode exhibits high reversible capacity and good rate capability, where a stable reversible capacity of 955 mA h g-1 can be maintained after 180 cycles at 200 mA g-1. Even at a high current density of 2000 mA g-1, the electrode can still deliver a specific capacity of 423.3 mA h g-1, demonstrating superior electrochemical properties for LIBs. In addition, the obtained 3D hierarchical MnCo2O4 porous dumbbells also display good oxygen evolution reaction activity with an overpotential of 426 mV at a current density of 10 mA cm-2 and a Tafel slope of 93 mV dec-1.