The role of ferroptosis in osteoarthritis: Progress and prospects.

Osteoarthritis (OA) is the most prevalent degenerative joint disease, marked by cartilage degeneration, synovitis, and subchondral bone changes. The absence of effective drugs and treatments to decelerate OA's progression highlights a significant gap in clinical practice. Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, has emerged as a research focus in osteoarthritic chondrocytes. This form of cell death is characterized by imbalances in iron and increased lipid peroxidation within osteoarthritic chondrocytes. Key antioxidant mechanisms, such as Glutathione Peroxidase 4 (GPX4) and the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) pathway, are vital in countering ferroptosis in osteoarthritic chondrocytes. This review collates recent findings on ferroptosis in osteoarthritic chondrocytes, emphasizing iron regulation, lipid peroxidation, and antioxidative responses. It also explores emerging therapeutics aimed at mitigating OA by targeting ferroptosis in chondrocytes.

Selection and Characterization of DNA Aptamers for Cytidine and Uridine.

Cytidine and uridine are two essential pyrimidine ribonucleotides, and accurate detection of these nucleosides holds significant biological importance. While many aptamers were reported to bind purines, little success was achieved for pyrimidine binding. This study employs the library-immobilization capture-SELEX technique to isolate aptamers capable of selectively binding to cytidine and uridine. First, a selection was performed using a mixture of cytidine and uridine as the target. This selection led to the isolation of a highly selective aptamer for cytidine with a dissociation constant (Kd ) of 0.9 µM as determined by isothermal titration calorimetry (ITC). In addition, a dual-recognition aptamer was also discovered, which exhibited selective binding to both cytidine and uridine. Subsequently, a separate selection was carried out using uridine as the sole target, and the resulting uridine aptamer displayed a Kd of 4 µM based on a thioflavin T fluorescence assay and a Kd of 102 µM based on ITC. These aptamers do not have a strict requirement of metal ions for binding, and they showed excellent selectivity since no binding was observed with their nucleobases or nucleotides. This study has resulted three aptamers for pyrimidines, which can be employed in biosensors and DNA switches.

Tilavonemab in early Alzheimer's disease: results from a phase 2, randomized, double-blind study.

Tau accumulation in patients with Alzheimer's disease tracks closely with cognitive decline and plays a role in the later stages of disease progression. This phase 2 study evaluated the safety and efficacy of tilavonemab, an anti-tau monoclonal antibody, in patients with early Alzheimer's disease. In this 96-week, randomized, double-blind, placebo-controlled study (NCT02880956), patients aged 55-85 years meeting clinical criteria for early Alzheimer's disease with a Clinical Dementia Rating-Global Score of 0.5, a Mini-Mental State Examination score of 22 to 30, a Repeatable Battery for the Assessment of Neuropsychological Status-Delayed Memory Index score of ≤85, and a positive amyloid PET scan were randomized 1:1:1:1 to receive one of three doses of tilavonemab (300 mg, 1000 mg, or 2000 mg) or placebo via intravenous infusion every 4 weeks. The primary end point was the change from baseline up to Week 96 in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. Safety evaluations included adverse event monitoring and MRI assessments. A total of 453 patients were randomized, of whom 337 were treated with tilavonemab (300 mg, n = 108; 1000 mg, n = 116; 2000 mg, n = 113) and 116 received placebo. Baseline demographics and disease characteristics were comparable across groups. The mean age was 71.3 (SD 7.0) years, 51.7% were female, and 96.5% were White. At baseline, the mean CDR-SB score was 3.0 (1.2), which worsened through Week 96 for all treatment groups. The least squares mean change from baseline at Week 96 in the CDR-SB score with tilavonemab was not significantly different compared with placebo [300 mg (n = 85): -0.07 (95% confidence interval, CI: -0.83 to 0.69); 1000 mg (n = 91): -0.06 (95% CI: -0.81 to 0.68); 2000 mg (n = 81): 0.16 (95% CI: -0.60 to 0.93); all P ≥ 0.05]. The incidence of any adverse event and MRI findings were generally comparable across groups. Tilavonemab was generally well tolerated but did not demonstrate efficacy in treating patients with early Alzheimer's disease. Further investigations of tilavonemab in early Alzheimer's disease are not warranted.

A Novel Curcumin-Loaded Nanoplatform Alleviates Osteoarthritis by Inhibiting Chondrocyte Ferroptosis.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of articular cartilage. Recent studies have demonstrated that chondrocyte ferroptosis plays a crucial role in the progression of OA. Consequently, developing nanomedicines that suppress chondrocyte ferroptosis is a promising strategy for OA treatment. However, there are few reports on nanomedicines specifically targeting chondrocyte ferroptosis for OA therapy. In this study, Curcumin-loaded nanoparticles (Cur-NPs) are fabricated to suppress chondrocyte ferroptosis by regulating reactive oxygen species (ROS), ferrous ion (Fe2⁺), and Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) levels of chondrocyte. This is achieved by combining the functions of curcumin and an amphiphilic block copolymer with ROS scavenging and iron-chelating properties. The in vitro anti-ferroptotic effects of Cur-NPs are thoroughly investigated. The findings indicate that Cur-NPs decrease the expression of ferroptosis markers such as ROS, Fe2⁺, and ACSL4, while protecting the mitochondrial membrane potential of chondrocytes. Additionally, Cur-NPs attenuated lipid peroxidation in chondrocytes. Furthermore, Cur-NPs significantly reduced the expression of the catabolic factor Matrix Metallopeptidase 13 (MMP13) and increased the expression of the anabolic factor Collagen type II (Col II) in vitro. This study demonstrates that Cur-NPs exhibit enhanced chondroprotective effects through anti-ferroptotic actions, presenting a promising approach for inhibiting chondrocyte ferroptosis using bioactive nanomaterials in OA treatment.

Hollow-Carbon Confinement Annealing: A New Synthetic Approach to Make High-Entropy Solid-Solution and Intermetallic Nanoparticles.

High-entropy alloy (HEA) nanoparticles (NPs) have been emerging with superior compositional tunability and multielemental synergy, presenting a unique platform for material discovery and performance optimization. Here we report a synthetic approach utilizing hollow-carbon confinement in the ordinary furnace annealing to achieve the nonequilibrium HEA-NPs such as Pt0.45Fe0.18Co0.12Ni0.15Mn0.10 with uniform size ∼5.9 nm. The facile temperature control allows us not only to reveal the detailed reaction pathway through ex situ characterization but also to tailor the HEA-NP structure from the crystalline solid solution to intermetallic. The preconfinement of metal precursors is the key to ensure the uniform distribution of metal nanoparticles with confined volume, which is essential to prevent the thermodynamically favored phase separation even during the ordinary furnace annealing. Besides, the synthesized HEA-NPs exhibit remarkable activity and stability in oxygen reduction catalysis. The demonstrated synthetic approach may significantly expand the scope of HEA-NPs with uncharted composition and performance.

Livestock grazing modifies soil nematode body size structure in mosaic grassland habitats.

Body size is closely related to the trophic level and abundance of soil fauna, particularly nematodes. Therefore, size-based analyses are increasingly prominent in unveiling soil food web structure and its responses to anthropogenic disturbances, such as livestock grazing. Yet, little is known about the effects of different livestock on the body size structure of soil nematodes, especially in grasslands characterized by local habitat heterogeneity. A four-year field grazing experiment from 2017 to 2020 was conducted in a meadow steppe characterized by typical mosaics of degraded hypersaline patches and undegraded hyposaline patches to assess the impacts of cattle and sheep grazing on the body size structure of soil nematodes within and across trophic groups. Without grazing, the hypersaline patches harbored higher abundance of large-bodied nematodes in the community compared to the hyposaline patches. Livestock grazing decreased large-bodied nematodes within and across trophic groups mainly by reducing soil microbial biomass in the hypersaline patches, with sheep grazing resulting in more substantial reductions compared to cattle grazing. The reduction in large-bodied nematode individuals correspondingly resulted in decreases in nematode community-weighted mean (CWM) body size, nematode biomass, and size spectra slopes. However, both cattle and sheep grazing had minimal impacts on the CWM body size and size spectra of total nematodes in the hyposaline patches. Our findings suggest that livestock grazing, especially sheep grazing, has the potential to simplify soil food webs by reducing large-bodied nematodes in degraded habitats, which may aggravate soil degradation by weakening the bioturbation activities of soil fauna. In light of the widespread land use of grasslands by herbivores of various species and the ongoing global grassland degradation of mosaic patches, the recognition of the trends revealed by our findings is critical for developing appropriate strategies for grassland grazing management.

Analysis of risk indicators for implant failure in patients with chronic periodontitis.

Dental implant restoration shows an effective method for the rehabilitation of missing teeth. The failure rate of periodontal implants in patients with chronic periodontitis is associated with periodontal flora, inflammation, and long-term periodontal bone resorption caused by chronic periodontitis. However, the therapeutic effects of dental implant restoration on inflammation in patients with chronic periodontitis have not addressed. The purpose of this study is to evaluate the risk indicators for inflammation, bone loss and implant failure in patients with chronic periodontitis. A total of 284 patients with dental implant restoration were recruited and divided into periodontally healthy patients (n = 128) and chronic periodontitis patients (n = 156). Periodontal indices including probing depth (PD), sulcus bleeding index (SBI), plaque index (PLI), gingival bleeding (GIL) and bleeding on probing (BOP) were compared in two groups. Inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 (IL-1), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) levels at baseline, 6 and 12 months after surgery, and the implant survival rate at 12 months after surgery, as well as the risk factors associated with failure of dental implant were also assessed. Outcomes demonstrated that patients in the chronic periodontitis group had higher values of periodontal indices than those in the periodontally healthy group. All inflammatory parameters in the chronic periodontitis group were higher than those in the periodontally healthy group and negatively associated with the chronic periodontal index (CPI) in chronic periodontitis patients. Chronic periodontitis patients had higher the prevalence of mucositis and peri-implantitis than patients with healthy periodontium. Implant diameter, length and design was associated with the risk of implant failure for chronic periodontitis patients receiving dental implant. The cumulative implant failure rate and incidence of implant fractures for chronic periodontitis patients at 12 months after surgery were 12.10% and 7.23% (p < 0.05), respectively, while were lower in the heathy periodontitis patients. Location, diameter, implant design, immediate loading and bone defect were risk indicators for bone loss for dental implant patients. The risk factors associated with failure of dental implant was higher in chronic periodontitis patients than patients in the periodontally healthy group (14.25% vs. 4.92%, p < 0.05). In conclusion, data in the current study indicate that inflammation is a risk indicator bone loss, implant fracture and implant failure in patients with chronic periodontitis.

Selective Hemin Binding by a Non-G-quadruplex Aptamer with Higher Affinity and Better Peroxidase-like Activity.

Previous aptamers for porphyrins and metalloporphyrins were all guanine-rich sequences that can fold in G-quadruplex structures. Due to stacking-based binding, these aptamers can hardly tell different porphyrins apart, and they can also bind other planar molecules, hindering their practical applications. In this work, we used the capture selection method to obtain aptamers for hemin and protoporphyrin IX (PPIX). The hemin aptamer (Hem1) features two highly conserved repeating binding loops, and it cannot form a G-quadruplex, which was supported by its Mg2+ -dependent but K+ -independent hemin binding and CD spectroscopy. Isothermal titration calorimetry revealed much higher enthalpy change for the new aptamer, and the best aptamer showed a Kd of 43 nM hemin. Hem1 can also enhance the peroxidase-like activity of hemin. This work demonstrates that aptamers have alternative ways to bind porphyrins allowing selective recognition of different porphyrins.

Ligand-Hybridization Activates Lattice-Hydroxyl-Groups of NiCo(OH)x Nanowires for Efficient Electrosynthesis.

Electrochemical dehydrogenation of hydroxides plays a crucial role in the formation of high-valence metal active sites toward 5-hydroxymethylfurfural oxidation reaction (HMFOR) to produce the value-added chemical of 2,5-furandicarboxylic (FDCA). Herein, we construct benzoic acid ligand-hybridized NiCo(OH)x nanowires (BZ-NiCo(OH)x) with ample electron-deficient Ni/Co sites for HMFOR. The robust electron-withdrawing capability of benzoic acid ligands in BZ-NiCo(OH)x speeds up the electrochemical activation and dehydrogenation of lattice-hydroxyl-groups (M2+-O-H⇌M3+-O), boosting the formation of abundant electron-deficient and high-valence Ni/Co sites. DFT calculation reveals that the deintercalation proton is prone to establishing a hydrogen bridge with the carbonyl group in benzoic acid, facilitating the proton transfer. Coupled with the synergistic oxidation of Ni/Co sites on hydroxyl and aldehyde groups, BZ-NiCo(OH)x delivers a remarkable current density of 111.20 mA cm-2 at 1.4 V for HMFOR, exceeding that of NiCo(OH)x by approximately fourfold. And the FDCA yield and Faraday efficiency are as high as 95.24 % and 95.39 %, respectively. The ligand-hybridized strategy in this work introduces a novel perspective for designing high-performance transition metal-based electrocatalysts for biomass conversion.

Stabilizing Diluted Active Sites of Ultrasmall High-Entropy Intermetallics for Efficient Formic Acid Electrooxidation.

The poisoning of undesired intermediates or impurities greatly hinders the catalytic performances of noble metal-based catalysts. Herein, high-entropy intermetallics i-(PtPdIrRu)2FeCu (HEI) are constructed to inhibit the strongly adsorbed carbon monoxide intermediates (CO*) during the formic acid oxidation reaction. As probed by multiple-scaled structural characterizations, HEI nanoparticles are featured with partially negative Pt oxidation states, diluted Pt/Pd/Ir/Ru atomic sites and ultrasmall average size less than 2 nm. Benefiting from the optimized structures, HEI nanoparticles deliver more than 10 times promotion in intrinsic activity than that of pure Pt, and well-enhanced mass activity/durability than that of ternary i-Pt2FeCu intermetallics counterpart. In situ infrared spectroscopy manifests that both bridge and top CO* are favored on pure Pt but limited on HEI. Further theoretical elaboration indicates that HEI displayed a much weaker binding of CO* on Pt sites and sluggish diffusion of CO* among different sites, in contrast to pure Pt that CO* bound more strongly and was easy to diffuse on larger Pt atomic ensembles. This work verifies that HEIs are promising catalysts via integrating the merits of intermetallics and high-entropy alloys.

Improving Alkaline Hydrogen Oxidation through Dynamic Lattice Hydrogen Migration in Pd@Pt Core-Shell Electrocatalysts.

Tracking the trajectory of hydrogen intermediates during hydrogen electro-catalysis is beneficial for designing synergetic multi-component catalysts with division of chemical labor. Herein, we demonstrate a novel dynamic lattice hydrogen (LH) migration mechanism that leads to two orders of magnitude increase in the alkaline hydrogen oxidation reaction (HOR) activity on Pd@Pt over pure Pd, even ≈31.8 times mass activity enhancement than commercial Pt. Specifically, the polarization-driven electrochemical hydrogenation process from Pd@Pt to PdHx @Pt by incorporating LH allows more surface vacancy Pt sites to increase the surface H coverage. The inverse dehydrogenation process makes PdHx as an H reservoir, providing LH migrates to the surface of Pt and participates in the HOR. Meanwhile, the formation of PdHx induces electronic effect, lowering the energy barrier of rate-determining Volmer step, thus resulting in the HOR kinetics on Pd@Pt being proportional to the LH concentration in the in situ formed PdHx @Pt. Moreover, this dynamic catalysis mechanism would open up the catalysts scope for hydrogen electro-catalysis.

Pseudo-Pt Monolayer for Robust Hydrogen Oxidation.

Heteroepitaxial core-shell structure is conducive to combining the advantages of the epilayer and the substrate, creating a novel multifunctionality for catalysis application. Herein, we report a pseudomorphic-Pt atomic layer (PmPt) epitaxially growing on an IrPd-core matrix (PmPt@IrPd/C) as an efficient and stable catalyst for alkaline hydrogen oxidation reaction that exhibits ∼29.2 times more mass activity enhancement than that of benchmark Pt/C. The PmPt@IrPd/C catalyst also gives rise to ∼25.0 times more enhancement than Pt/C during a 50,000-cycle accelerated stability test. This robust stability originates from the resistance to carbon corrosion owing to the stronger H2O interaction instead of carbon oxide (COx) poison species, and the modulated hydroxyl (OH*) adsorption could inhibit the OH* species from shuffling the surface Pt atoms away from the substrate. Moreover, the anion-exchange membrane fuel cells assembled by PmPt@IrPd/C with an ultralow Pt loading of 0.009 mgPt cm-2 in the anode can deliver a power density of 1.27 W cm-2.

Bimetallic Phosphide Heterostructure Coupled with Ultrathin Carbon Layer Boosting Overall Alkaline Water and Seawater Splitting.

Seawater electrolysis is promising for green hydrogen production but hindered by the sluggish reaction kinetics of both cathode and anode, as well as the detrimental chlorine chemistry environment. Herein, a self-supported bimetallic phosphide heterostructure electrode strongly coupled with an ultrathin carbon layer on Fe foam (C@CoP-FeP/FF) is constructed. When used as an electrode for the hydrogen and oxygen evolution reactions (HER/OER) in simulated seawater, the C@CoP-FeP/FF electrode shows overpotentials of 192 mV and 297 mV at 100 mA cm-2 , respectively. Moreover, the C@CoP-FeP/FF electrode enables the overall simulated seawater splitting at the cell voltage of 1.73 V to achieve 100 mA cm-2 , and operate stably during 100 h. The superior overall water and seawater splitting properties can be ascribed to the integrated architecture of CoP-FeP heterostructure, strongly coupled carbon protective layer, and self-supported porous current collector. The unique composites can not only provide enriched active sites, ensure prominent intrinsic activity, but also accelerate the electron transfer and mass diffusion. This work confirms the feasibility of an integration strategy for the manufacturing of a promising bifunctional electrode for water and seawater splitting.

Parasites as ecosystem modulators: foliar pathogens suppress top-down effects of large herbivores.

Parasites can catalyze or inhibit interactions between their hosts and other species, but the ecosystem-level effects of such interaction modifications are poorly understood. We conducted a large-scale field experiment in temperate grasslands of China to understand how foliar fungal pathogens influenced top-down effects of cattle on plant diversity and productivity. When foliar pathogens were suppressed, cattle grazing strongly reduced biomass of the dominant grass, Leymus chinensis, generating competitive release that significantly increased community-level species richness and evenness. In the absence of grazing, pathogen attack on L. chinensis had no measurable effect on host biomass. However, pathogens disrupted top-down effects of herbivory by inhibiting grazing effects on plant biomass and species richness. Mechanistically, fungal pathogens were linked to increased alkaloid and reduced nitrogen levels in leaf tissue, which appeared to deter cattle grazing on L. chinensis. In conclusion, foliar pathogens can suppress top-down effects of large herbivores on grassland community composition and ecosystem function by modifying the strength of their host's interactions with dominant consumers. Parasites may act as modulators of ecosystem function when their direct effects on host abundance are overshadowed by powerful influences on host traits that modify their interactions with competitors, herbivores, or predators.

Capture-SELEX of DNA Aptamers for Sulforhodamine B and Fluorescein.

While many dye binding aptamers have been reported, most of them were for light-up aptamers that can significantly enhance the quantum yield of fluorophores. Sulforhodamine B (SRhB) was used as a target previously to select both DNA and RNA aptamers, and the DNA aptamer was a G-quadruplex that can bind to a number of rhodamine analogs. In addition, the previous selections were performed by immobilizing the target molecules. In this work, the library immobilization method was used to respectively select aptamers for SRhB and fluorescein. The SRhB aptamer has a non-G-quadruplex structure with a Kd of 1.0 µM measured from isothermal titration calorimetry. Upon titration of the aptamer, the fluorescence of SRhB increased 2.5-fold, and this aptamer does not require Mg2+ for binding. Rhodamine B has even tighter binding suggesting binding through the xanthene moiety of the dyes. No binding was detected for fluorescein. For the fluorescein selection, a dominant aptamer sequence with a Kd of 147 µM was obtained. This study provides two new aptamers for two important fluorophores that can be used to study aptamer-based separation, dye detection and catalysis. Comparison of these aptamers also provides insights into the effect of functional groups on aptamer binding.

Patient characteristics and procedural variables are associated with length of stay and hospital cost among unilateral primary total hip arthroplasty patients: a single-center retrospective cohort study.

BACKGROUND: Total hip arthroplasty (THA) is a successful treatment for many hip diseases. Length of stay (LOS) and hospital cost are crucial parameters to quantify the medical efficacy and quality of unilateral primary THA patients. Clinical variables associated with LOS and hospital costs haven't been investigated thoroughly. METHODS: The present study retrospectively explored the contributors of LOS and hospital costs among a total of 452 unilateral primary THA patients from January 2019 to January 2020. All patients received conventional in-house rehabilitation services within our institute prior to discharge. Outcome parameters included LOS and hospital cost while clinical variables included patient characteristics and procedural variables. Multivariable linear regression analysis was performed to assess the association between outcome parameters and clinical variables by controlling confounding factors. Moreover, we analyzed patients in two groups according to their diagnosis with femur neck fracture (FNF) (confine THA) or non-FNF (elective THA) separately. RESULTS: Among all 452 eligible participants (266 females and 186 males; age 57.05 ± 15.99 year-old), 145 (32.08%) patients diagnosed with FNF and 307 (67.92%) diagnosed with non-FNF were analyzed separately. Multivariable linear regression analysis revealed that clinical variables including surgery duration, transfusion, and comorbidity (stroke) among the elective THA patients while the approach and comorbidities (stoke, diabetes mellitus, coronary heart disease) among the confine THA patients were associated with a prolonged LOS (P < 0.05). Variables including the American Society of Anesthesiologists classification (ASA), duration, blood loss, and transfusion among the elective THA while the approach, duration, blood loss, transfusion, catheter, and comorbidities (stoke and coronary heart disease) among the confine THA were associated with higher hospital cost (P < 0.05). The results revealed that variables were associated with LOS and hospital cost at different degrees among both elective and confine THA. CONCLUSIONS: Specific clinical variables of the patient characteristics and procedural variables are associated the LOS and hospital cost, which may be different between the elective and confine THA patients. The findings may indicate that evaluation and identification of detailed perioperative factors are beneficial in managing perioperative preparation, adjusting patients' anticipation, decreasing LOS, and reducing hospital cost.

Advances in the research of osteosarcoma stem cells and its related genes.

Osteosarcoma is a malignant tumor that often occurs in adolescents. There is an urgent need for new treatment options for osteosarcoma due to its poor prognosis after metastasis. Cancer stem cell (CSC) theory states that CSCs represent a small proportion of cancer cells. These CSC have self-renewal ability and are closely associated with cancer growth and metastasis as well as chemotherapy resistance. Similarly, osteosarcoma stem cells (OSCs) play an important role in the growth, metastasis, and chemotherapy resistance of osteosarcoma cells. Targeting OSCs may represent a future treatment of osteosarcoma. Furthermore, some genes have been shown to regulate the growth, metastasis, and chemotherapy resistance of osteosarcoma cells by altering the stemness of OSCs. Targeting these genes may help in the treatment of osteosarcoma. This review mainly discusses recent advances in the research of OSCs and their related genes.

Diversifying livestock promotes multidiversity and multifunctionality in managed grasslands.

Increasing plant diversity can increase ecosystem functioning, stability, and services in both natural and managed grasslands, but the effects of herbivore diversity, and especially of livestock diversity, remain underexplored. Given that managed grazing is the most extensive land use worldwide, and that land managers can readily change livestock diversity, we experimentally tested how livestock diversification (sheep, cattle, or both) influenced multidiversity (the diversity of plants, insects, soil microbes, and nematodes) and ecosystem multifunctionality (including plant biomass production, plant leaf N and P, above-ground insect abundance, nutrient cycling, soil C stocks, water regulation, and plant-microbe symbiosis) in the world's largest remaining grassland. We also considered the potential dependence of ecosystem multifunctionality on multidiversity. We found that livestock diversification substantially increased ecosystem multifunctionality by increasing multidiversity. The link between multidiversity and ecosystem multifunctionality was always stronger than the link between single diversity components and functions. Our work provides insights into the importance of multitrophic diversity to maintain multifunctionality in managed ecosystems and suggests that diversifying livestock could promote both multidiversity and ecosystem multifunctionality in an increasingly managed world.

Controlling the Valence-Electron Arrangement of Nickel Active Centers for Efficient Hydrogen Oxidation Electrocatalysis.

The valence-electron arrangement of heterogeneous catalysts can significantly affect the binding behavior of absorbates. However, it remains a challenge to understand the role of the valence-electron arrangement in electrocatalysis, which limits its utilization as a tool to design efficient electrocatalysts. Here, we describe experiments in which the valence-electron arrangement of Ni active centers for hydrogen oxidation is controlled precisely by using Ni-vacancy-enriched Ni3 N as a platform. These Ni vacancies can promote the valence-electron delocalization of OH-adsorption centers to enhance the Ni ds-O 2p valence-electron-orbital interaction with elevated OH adsorption. Meanwhile, the deficit of valence-electrons of H-adsorption centers at Ni vacancies can lower Ni ds-H 1s interaction with weakened H binding. Relative to Ni3 N poor in vacancies, the Ni-vacancy-enriched Ni3 N showed a mass activity enhanced by 15-fold. This strategy paves a rational way to design efficient catalysts by finely tuning the valence-electron arrangement.

Aucubin prevents steroid-induced osteoblast apoptosis by enhancing autophagy via AMPK activation.

Steroid-induced osteoblast apoptosis is a crucial pathological process in steroid-induced osteonecrosis of the femoral head (SONFH). Autophagy can resist apoptosis and AMPK plays an important role in autophagy regulation. Aucubin from the small tree Eucommia ulmoides Oliv., which has a long history of use in orthopaedics and traumatology in Asian medicine, can promote bone formation, but whether it can slow or prevent steroid-osteoblast apoptosis is unclear. Therefore, we investigated the pathogenesis of SONFH and how the osteoblast responds to aucubin under the dexamethasone stimulation. In human femoral head osteonecrosis specimens, we found that the autophage and apoptosis level were increased, and the AMPK signalling was crucial to autophagy. We observed that aucubin could prevent dexamethasone-induced apoptosis in osteoblasts by enhancing the level of autophagy. Further, we confirmed that the regulatory effect of aucubin on autophagy and apoptosis was achieved by activating AMPK signalling. We have demonstrated a mechanism of disease progression and shown that aucubin could enhance autophagy through AMPK signalling to prevent osteoblast apoptosis. These findings provide a basis for the further investigation of the potential therapeutic role of aucubin in the SONFH.