Novel 3D Ni1−xCoxSe2 mesoporous nanosheet networks with tunable stoichiometry are successfully synthesized on Ni foam (Ni1−xCoxSe2 MNSN/NF with x ranging from 0 to 0.35). The collective effects of ...special morphological design and electronic structure engineering enable the integrated electrocatalyst to have very high activity for hydrogen evolution reaction (HER) and excellent stability in a wide pH range. Ni0.89Co0.11Se2 MNSN/NF is revealed to exhibit an overpotential (η10) of 85 mV at −10 mA cm−2 in alkaline medium (pH 14) and η10 of 52 mV in acidic solution (pH 0), which are the best among all selenide‐based electrocatalysts reported thus far. In particular, it is shown for the first time that the catalyst can work efficiently in neutral solution (pH 7) with a record η10 of 82 mV for all noble metal‐free electrocatalysts ever reported. Based on theoretical calculations, it is further verified that the advanced all‐pH HER activity of Ni0.89Co0.11Se2 is originated from the enhanced adsorption of both H+ and H2O induced by the substitutional doping of cobalt at an optimal level. It is believed that the present work provides a valuable route for the design and synthesis of inexpensive and efficient all‐pH HER electrocatalysts.
An integrated electrocatalyst comprising 3D mesoporous Ni0.89Co0.11Se2 nanosheet networks on Ni foam is synthesized, and it demonstrates very high activities and excellent stabilities for hydrogen evolution reaction (HER) in all‐pH conditions. Theoretical calculations verify that electronic structure engineering by optimal Co doping enhances the adsorption of H+ and H2O, leading to the advanced all‐pH HER activity of the catalyst.
Abstract
The oxidized platinum (Pt) can exhibit better electrocatalytic activity than metallic Pt
0
in the hydrogen evolution reaction (HER), which has aroused great interest in exploring the role of ...oxygen in Pt-based catalysts. Herein, we select two structurally well-defined polyoxometalates Na
5
H
3
Pt
(IV)
W
6
O
24
(PtW
6
O
24
) and Na
3
K
5
Pt
(II)
2
(W
5
O
18
)
2
(Pt
2
(W
5
O
18
)
2
) as the platinum oxide model to investigate the HER performance. Electrocatalytic experiments show the mass activities of PtW
6
O
24
/C and Pt
2
(W
5
O
18
)
2
/C are 20.175 A mg
−1
and 10.976 A mg
−1
at 77 mV, respectively, which are better than that of commercial 20% Pt/C (0.398 A mg
−1
). The in situ synchrotron radiation experiments and DFT calculations suggest that the elongated Pt-O bond acts as the active site during the HER process, which can accelerate the coupling of proton and electron and the rapid release of H
2
. This work complements the knowledge boundary of Pt-based electrocatalytic HER, and suggests another way to update the state-of-the-art electrocatalyst.
Skp2 is overexpressed in multiple cancers and plays a critical role in tumor development through ubiquitin/proteasome‐dependent degradation of its substrate proteins. Drugs targeting Skp2 have ...exhibited promising anticancer activity. Here, we identified a plant‐derived Skp2 inhibitor, betulinic acid (BA), via high‐throughput structure‐based virtual screening of a phytochemical library. BA significantly inhibited the proliferation and migration of non–small cell lung cancer (NSCLC) through targeting Skp2‐SCF E3 ligase both in vitro and in vivo. Mechanistically, BA binding to Skp2, especially forming H‐bonds with residue Lys145, decreases its stability by disrupting Skp1‐Skp2 interactions, thereby inhibiting the Skp2‐SCF E3 ligase and promoting the accumulation of its substrates; that is, E‐cadherin and p27. In both subcutaneous and orthotopic xenografts, BA significantly inhibited the proliferation and metastasis of NSCLC through targeting Skp2‐SCF E3 ligase and upregulating p27 and E‐cadherin protein levels. Taken together, BA can be considered a valuable therapeutic candidate to inhibit metastasis of NSCLC.
By screening a phytochemical library via high‐throughput molecular docking, we identified that betulinic acid is capable of binding to Skp2 at residue Lys145, leading to decreased protein stability of Skp2 and the accumulation of its substrate protein p27 and E‐cadherin. Betulinic acid significantly inhibited the proliferation and migration of NSCLC through downregulating Skp2 both in vitro and in vivo.
Ferrate (K2FeO4) is a powerful oxidant and up to 3 mol of electrons could be captured by 1 mol of ferrate in the theoretical conversion of Fe(VI)–Fe(V)–Fe(IV)–Fe(III). However, it is reported ...that the utilization efficiency of the ferrate oxidation capacity is quite low because of the rapid autodecomposition of intermediate iron species, which negatively influences the potential of ferrate on organic pollutants control. We accidentally found that for the ferrate oxidation of carbamazepine (CBZ), bisphenol S (BPS), diclofenac (DCF), and ciprofloxacin (CIP), the determined reaction rate constants were 1.7–2.4 times lower in phosphate buffer than those in borate buffer at pH 8.0. For the reaction of ferrate with 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) at pH 7.0, the determined reaction stoichiometries were 1:1.04 in 100 mM phosphate buffer, 1:1.18 in 10 mM phosphate buffer, and 1:1.93 in 10 mM borate buffer, respectively. The oxidation ability of ferrate seems depressed in phosphate buffer. A kinetic model involving the oxidation of ABTS by Fe(VI), Fe(V) and Fe(IV) species was developed and fitted the ABTS•+ formation kinetics well under different buffer conditions. The results showed that phosphate exhibited little influence on the oxidation ability of Fe(VI) and Fe(IV) species, but decreased the specific rate constants of ABTS with Fe(V) species by 1–2 orders of magnitude, resulting in the outcompeting of Fe(V) autodecomposition pathway. The complexation between phosphate anions and Fe(V) species may account for the inhibition effect of phosphate buffer. Considering that many studies regarding ferrate oxidation were carried out in phosphate buffer, the actual oxidation ability of ferrate may be underestimated.
Rutaceae plants are known for being a rich source of coumarins. Preliminary molecular docking showed that there was no significant difference for coumarins in Clausena and Murraya, both of which had ...high scoring values and showed good potential inhibitory activity to the MAO-B enzyme. Overall, 32 coumarins were isolated from Murraya exotica L., including a new coumarin 5-demethoxy-10′-ethoxyexotimarin F (1). Their structures were elucidated on the basis of a comprehensive analysis of 1D and 2D NMR and HRMS spectroscopic data, and the absolute configurations were assigned via a comparison of the specific rotations and the ECD exciton coupling method. The potential of new coumarin (1) as a selective inhibitor of MAO-B was initially evaluated through molecular docking and pharmacophore studies. Compound (1) showed selectivity for the MAO-B isoenzyme and inhibitory activity in the sub-micromolar range with an IC50 value of 153.25 ± 1.58 nM (MAO-B selectivity index > 172).
The prevalence and risk factors for subjective cognitive decline (SCD) and its correlation with objective cognition decline (OCD) among community-dwelling older adults is inconsistent.
Older adults ...underwent neuropsychological and clinical evaluations to reach a consensus on diagnoses.
This study included 7486 adults without mild cognitive impairment and dementia (mean age: 71.35 years standard deviation = 5.40). The sex-, age-, and residence-adjusted SCD prevalence was 58.33% overall (95% confidence interval: 58.29% to 58.37%), with higher rates of 61.25% and 59.87% in rural and female subgroups, respectively. SCD global and OCD language, SCD memory and OCD global, SCD and OCD memory, and SCD and OCD language were negatively correlated in fully adjusted models. Seven health and lifestyle factors were associated with an increased risk for SCD.
SCD affected 58.33% of older adults and may indicate concurrent OCD, which should prompt the initiation of preventative intervention for dementia.
SCD affects 58.33% of older adults in China. SCD may indicate concurrent objective cognitive decline. Difficulty finding words and memory impairments may indicate a risk for AD. The presence of SCD may prompt preventative treatment initiation of MCI or dementia. Social network factors may be initial targets for the early prevention of SCD.
A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single‐molecule platform for synergistic photodynamic, photothermal, ...and chemotherapy. The complexes have significant two‐photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA‐related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin‐resistant non‐small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two‐photon activatable metal complex may contribute to a new generation of single‐molecule‐based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.
A single‐molecule‐based integrated diagnosis and treatment platform for infrared two‐photon excitable synergistic photodynamic, photothermal, and chemotherapy has been constructed. The most potent Ru7 enters cells via macropinocytosis and regulates DNA‐related chemotherapeutic mechanisms intranuclearly and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy and safety in vivo for melanoma and cisplatin‐resistant non‐small cell lung cancer.
The mammalian target of rapamycin (mTOR) pathway plays critical roles in intrinsic chemoresistance by regulating Fanconi anaemia complementation group D2 (FANCD2) expression. However, the mechanisms ...by which mTOR regulates FANCD2 expression and related inhibitors are not clearly elucidated. Extracts of Centipeda minima (C. minima) showed promising chemosensitizing effects by inhibiting FANCD2 activity. Here, we have aimed to identify the bioactive chemosensitizer in C. minima extracts and elucidate its underlying mechanism.
The chemosensitizing effects of arnicolide C (ArC), a bioactive compound in C. minima, on non-small cell lung cancer (NSCLC) were investigated using immunoblotting, immunofluorescence, flow cytometry, the comet assay, small interfering RNA (siRNA) transfection and animal models. The online SynergyFinder software was used to determine the synergistic effects of ArC and chemotherapeutic drugs on NSCLC cells.
ArC had synergistic cytotoxic effects with DNA cross-linking drugs such as cisplatin and mitomycin C in NSCLC cells. ArC treatment markedly decreased FANCD2 expression in NSCLC cells, thus attenuating cisplatin-induced FANCD2 nuclear foci formation, leading to DNA damage and apoptosis. ArC inhibited the mTOR pathway and attenuated mTOR-mediated expression of E2F1, a critical transcription factor of FANCD2. Co-administration of ArC and cisplatin exerted synergistic anticancer effects in the A549 xenograft mouse model by suppressing mTOR/FANCD2 signalling in tumour tissues.
ArC suppressed DNA cross-linking drug-induced DNA damage response by inhibiting the mTOR/E2F1/FANCD2 signalling axis, serving as a chemosensitizing agent. This provides insight into the anticancer mechanisms of ArC and offers a potential combinatorial anticancer therapeutic strategy.
The present work revealed a potential to control the static recrystallization kinetics through regulating the feature of pre-existing Mg17Al12 particles in Mg-Al-Zn alloys. The AZ31 (Mg-3Al-1Zn) with ...rarely dispersoids exhibits the fastest recrystallization rate, while the AZ61 (Mg-6Al-1Zn) with only fine particles (∼100 nm) recrystallizes slower than AZ91 (Mg-9Al-1Zn) containing Mg17Al12 precipitates with scattered size distribution (ranging from less than 100 nm to above 0.6 μm). Especially, we found that coarse Mg17Al12 particles in AZ91 are easier to trigger particle stimulated nucleation (PSN) at 275 °C than 175 °C, which compensates the strong recrystallization inhibition of fine dispersoids, leading to the recrystallization dramatically transforms from retarded to accelerated.
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•The precipitate feature notably affects the kinetics of static recrystallization.•Recrystallization of alloys with mixed particle size is sensitive to temperature.•Coarse particles in Mg-9Al-1Zn accelerate recrystallization at high temperature.•The study shows an efficient route to control the static recrystallization process.
•Post-ablation LAAC is noninferior to OAC in stroke and MACE events prevention.•Post-ablation LAAC reduce major bleeding and all-cause death by comparing to OAC.•Patients could be OAC-free after AF ...ablation in the era of LAAC.
Left atrial appendage closure (LAAC) proved to be non-inferior to oral anticoagulation (OAC) in non-ablated patients with atrial fibrillation (AF). This study aimed to compare the efficacy and safety of LAAC with OAC therapy in patients after AF ablation. This study included patients who underwent catheter ablation (CA) of AF between January 2016 and December 2020. The cohort was divided into CA+LAAC and CA+OAC, where propensity score matching was used to select controls and each group contained 682 subjects. The enrolled patients’ mean age was 70.34±8.32 years, and 47.3% were female; their CHA2DS2-VASc score was 3.48±1.17. Baseline characteristics were similar between groups. After a 3-year mean follow-up, the incidence of thromboembolic events was 1.25, and 1.10 and that of major bleeding events was 0.65, and 1.72 per 100 patient-years in the CA+LAAC, and CA+OAC groups, respectively. The rate of thromboembolisms and major adverse cardiovascular events was similar between the two groups (hazard ratio HR, 1.162; 95% confidence interval CI, 0.665-2.030; P=0.598; HR, 0.711; 95% CI, 0.502–1.005; P=0.053); however, that of major bleeding and all-cause death was significantly reduced with LAAC (HR, 0.401; 95% CI, 0.216–0.746; P=0.004; HR, 0.528; 95% CI, 0.281–0.989; P=0.046). There was no significant difference in peri-procedural complications (P > 0.05) and the rate of AF recurrence (OAC vs. LAAC: 39.44% vs. 40.62%; P=0.658). LAAC is a reasonable and safer alternative to OAC therapy in high-risk patients after AF ablation.
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