Single‐atom catalysts (SACs) have attracted tremendous interests due to their ultrahigh activity and selectivity. However, the rational control over coordination microenvironment of SACs remains a ...grand challenge. Herein, a post‐synthetic metal substitution (PSMS) strategy has been developed to fabricate single‐atom Ni catalysts with different N coordination numbers (denoted Ni‐Nx‐C) on pre‐designed N‐doped carbon derived from metal‐organic frameworks. When served for CO2 electroreduction, the obtained Ni‐N3‐C catalyst achieves CO Faradaic efficiency (FE) up to 95.6 %, much superior to that of Ni‐N4‐C. Theoretical calculations reveal that the lower Ni coordination number in Ni‐N3‐C can significantly enhance COOH* formation, thereby accelerating CO2 reduction. In addition, Ni‐N3‐C shows excellent performance in Zn–CO2 battery with ultrahigh CO FE and excellent stability. This work opens up a new and general avenue to coordination microenvironment modulation (MEM) of SACs for CO2 utilization.
A post‐synthetic metal substitution (PSMS) strategy has been developed to construct single‐atom Ni catalysts with different N coordination numbers (denoted as Ni‐Nx‐C) on defective carbon supports derived from metal‐organic frameworks. When served as an electrocatalyst, the Ni‐N3‐C catalyst, with lower N coordination number around Ni atoms, achieves superior catalytic performance for CO2 reduction.
Flavonoids are well known as antibacterial agents against a wide range of pathogenic microorganism. With increasing prevalence of untreatable infections induced by antibiotic resistance bacteria, ...flavonoids have attracted much interest because of the potential to be substitutes for antibiotics. In this review, the structure-relationship of flavonoids as antibacterial agents is summarized, and the recent advancements on the antibacterial mechanisms of flavonoids are also discussed. It is concluded that hydroxyls at special sites on the aromatic rings of flavonoids improve the activity. However, the methylation of the active hydroxyl groups generally decreases the activity. Besides, the lipopholicity of the ring A is vital for the activity of chalcones. The hydrophobic substituents such as prenyl groups, alkylamino chains, alkyl chains, and nitrogen or oxygen containing heterocyclic moieties usually enhance the activity for all the flavonoids. The proposed antibacterial mechanisms of flavonoids are as follows: inhibition of nucleic acid synthesis, inhibition of cytoplasmic membrane function, inhibition of energy metabolism, inhibition of the attachment and biofilm formation, inhibition of the porin on the cell membrane, alteration of the membrane permeability, and attenuation of the pathogenicity.
Abstract
Single-atom catalysts (SACs) have sparked broad interest recently while the low metal loading poses a big challenge for further applications. Herein, a dual protection strategy has been ...developed to give high-content SACs by nanocasting SiO
2
into porphyrinic metal–organic frameworks (MOFs). The pyrolysis of SiO
2
@MOF composite affords single-atom Fe implanted N-doped porous carbon (Fe
SA
–N–C) with high Fe loading (3.46 wt%). The spatial isolation of Fe atoms centered in porphyrin linkers of MOF sets the first protective barrier to inhibit the Fe agglomeration during pyrolysis. The SiO
2
in MOF provides additional protection by creating thermally stable FeN
4
/SiO
2
interfaces. Thanks to the high-density Fe
SA
sites, Fe
SA
–N–C demonstrates excellent oxygen reduction performance in both alkaline and acidic medias. Meanwhile, Fe
SA
–N–C also exhibits encouraging performance in proton exchange membrane fuel cell, demonstrating great potential for practical application. More far-reaching, this work grants a general synthetic methodology toward high-content SACs (such as Fe
SA
, Co
SA
, Ni
SA
).
Single‐atom catalysts (SACs) are of great interest because of their ultrahigh activity and selectivity. However, it is difficult to construct model SACs according to a general synthetic method, and ...therefore, discerning differences in activity of diverse single‐atom catalysts is not straightforward. Herein, a general strategy for synthesis of single‐atom metals implanted in N‐doped carbon (M1‐N‐C; M=Fe, Co, Ni and Cu) has been developed starting from multivariate metal–organic frameworks (MOFs). The M1‐N‐C catalysts, featuring identical chemical environments and supports, provided an ideal platform for differentiating the activity of single‐atom metal species. When employed in electrocatalytic CO2 reduction, Ni1‐N‐C exhibited a very high CO Faradaic efficiency (FE) up to 96.8 % that far surpassed Fe1‐, Co1‐ and Cu1‐N‐C. Remarkably, the best‐performer, Ni1‐N‐C, even demonstrated excellent CO FE at low CO2 pressures, thereby representing a promising opportunity for the direct use of dilute CO2 feedstock.
A series of porphyrinic multivariate metal–organic frameworks (MTV‐MOFs) were pyrolyzed to generate a range of single‐atom metals implanted in N‐doped carbon (M1‐N‐C; M=Fe, Co, Ni and Cu). The M1‐N‐C model catalysts, with an almost identical carbon support environment, demonstrated different activities toward CO2 electroreduction. The best performer, Ni1‐N‐C, achieved highly selective reduction of CO2 even at low pressures.
The chemical environment of metal nanoparticles (NPs) possesses significant influence on their catalytic performance yet is far from being well understood. Herein, tiny Pd NPs are encapsulated into ...the pore space of metal–organic frameworks (MOFs), UiO‐66‐X (X = H, OMe, NH2, 2OH, 2OH(Hf)), affording Pd@UiO‐66‐X composites. The surface microenvironment of the Pd NPs is readily modulated by pore wall engineering, via the functional group and metal substitution in the MOFs. Consequently, the catalytic activity of Pd@UiO‐66‐X follows the order of Pd@UiO‐66‐OH > Pd@UiO‐66‐2OH(Hf) > Pd@UiO‐66‐NH2 > Pd@UiO‐66‐OMe > Pd@UiO‐66‐H toward the hydrogenation of benzoic acid. It is found that the activity difference is not only ascribed to the distinct charge transfer between Pd and the MOF, but is also explained by the discriminated substrate adsorption energy of Pd@UiO‐66‐X (–OH < –2OH(Hf) < –NH2 < –OMe < –H), based on CO‐diffuse reflectance infrared Fourier transform spectra and density‐functional theory (DFT) calculations. The Pd@UiO‐66‐OH, featuring a high Pd electronic state and moderate adsorption energy, displays the highest activity. This work highlights the influence of the surface microenvironment of guest metal NPs, the catalytic activity of which is dominated by electron transfer and the adsorption energy, via the systematic substitution of metal and functional groups in host MOFs.
Pd nanoparticles (NPs) encapsulated into UiO‐66‐X (X = H, OMe, NH2, 2OH, 2OH(Hf)) show drastically different activities toward the hydrogenation of benzoic acid. This work highlights the influence of the surface microenvironment of guest metal NPs, the catalytic activity of which is dominated by electron transfer and the adsorption energy, via the systematic modification of host metal–organic frameworks (MOFs).
•Diamine modified mesoporous silica on MWCNTs was firstly synthesized.•The prepared adsorbent was characterized by various instrumental methods.•The adsorption process using Cu(II) as a model was ...thoroughly investigated.•This new adsorbent showed excellent adsorption efficiency for heavy metals.
An effective adsorbent of diamine functionalized mesoporous silica on multi-walled carbon nanotubes (NN-mSiO2@MWCNTs) has been prepared to remove heavy metals in aqueous solution. Structural characterization was conducted by Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), N2 adsorption–desorption measurement and X-ray diffraction (XRD), which confirmed the successful grafting of organic moiety on mSiO2@MWCNTs. Metals removal from aqueous solution was examined for Cu(II), Ni(II), Pb(II) and Zn(II). In addition, Cu(II) adsorption process was thoroughly studied from both kinetic and equilibrium points of view. Adsorption kinetics could be well described by pseudo-second-order kinetic equation and exhibited 3-stage intraparticle diffusion mode. Adsorption isotherms fitted well with Langmuir model, exhibiting high adsorption capacity at low concentration. The thermodynamic analysis revealed that the adsorption of Cu(II) onto NN-mSiO2@MWCNTs was endothermic and spontaneous. The prepared adsorbent is expected to be a new material for the removal and recovery of heavy metals from contaminated water.
Abstract
STUDY QUESTION
Does metformin inhibit excessive androgen-induced endoplasmic reticulum (ER) stress in mouse granulosa cells (GCs) in vivo and in vitro?
SUMMARY ANSWER
Metformin inhibits ...testosterone-induced ER stress and unfolded protein response (UPR) activation by suppressing p38 MAPK phosphorylation in ovarian GCs.
WHAT IS KNOWN ALREADY
Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism. Excessive testosterone induces ER stress and UPR activation in human cumulus cells, leading to cell apoptosis. Metformin has potential inhibitory effects on ER stress and UPR activation, as demonstrated in human pancreatic beta cells and obese mice.
STUDY DESIGN, SIZE, DURATION
Cumulus cells and follicular fluid were collected from 25 women with PCOS and 25 controls at our IVF centre. A dihydrotestosterone (DHT)-induced PCOS mouse model was constructed and treated with or without metformin. Primary mouse GCs and cumulus-oocyte complexes (COCs) were cultured with testosterone, metformin, a p38 MAPK inhibitor, or p38 MAPK small interfering RNA.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The levels of UPR sensor proteins and UPR-related genes were measured in cumulus cells from PCOS and control patients by real-time quantitative PCR (qPCR) and western blot. The ovaries, oocytes, GCs and COCs were collected from PCOS mice treated with metformin and controls. The expressions of ER stress markers and p38 MAPK phosphorylation were assessed by qPCR, western blot and immunofluorescence. A subsequent in vitro analysis with primary cultured GCs and COCs was used to confirm the influence of metformin on ER stress activation by qPCR and western blot. Finally, the effects of ER stress activation on GCs and COCs in relation to LH responsiveness were examined by qPCR and COC expansion.
MAIN RESULTS AND THE ROLE OF CHANCE
The expression of the ER stress markers GRP78, CHOP and XBP1s in the cumulus cells was higher in PCOS patients than in control patients, as were the levels of the UPR sensor proteins p-IRE1α, p-EIF2α and GRP78. Compared to those of control mice, the ovaries, GCs and COCs of DHT-treated PCOS mice showed increased levels of ER stress marker genes and proteins. Hyperandrogenism in PCOS mouse ovaries also induced p38 MAPK phosphorylation in COCs and GCs. Metformin inhibited ER stress activation was associated with decreased p-p38 MAPK levels. In vitro experiments, testosterone-induced ER stress was mitigated by metformin or p38 MAPK inhibition in primary cultured GCs and COCs. COCs expanded rapidly in the presence of testosterone during LH administration, and ovulation-related genes, namely, Areg, Ereg, Ptgs2, Sult1e1, Ptx3 and Tnfaip6, were strongly expressed in the COCs and GCs. These effects were reversed by treatment with metformin, an ER stress inhibitor or by knockdown of p38 MAPK.
LIMITATIONS, REASONS FOR CAUTION
The number of PCOS patients in this study was small.
WIDER IMPLICATIONS OF THE FINDINGS
This study provides further evidence for metformin as a PCOS treatment.
STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by the National Key Research and Developmental Program of China (2018YFC1004800), the Key Research and Development Program of Zhejiang Province (2017C03022), the Zhejiang Province Medical Science and Technology Plan Project (2017KY085, 2018KY457), the National Natural Science Foundation of China (31701260, 81401264, 81701514), and the Special Funds for Clinical Medical Research of the Chinese Medical Association (16020320648). The authors report no conflict of interest in this work and have nothing to disclose.
TRIAL REGISTRATION NUMBER
N/A.
Neuroinflammation-induced injury is intimately associated with poor prognosis in patients with cerebral venous sinus thrombosis (CVST). The cyclic GMP-AMP synthase-stimulator of interferon gene ...(cGAS-STING) axis is a cytoplasmic double-stranded DNA (dsDNA) sensing pathway has recently emerged as a crucial mediator of neuroinflammation in ischemic stroke. However, the role of the cGAS-STING pathway in modulating post-CVST inflammation and the underlying mechanisms involved remain unclear.
A CVST model was induced by ferric chloride in male C57BL/6J mice. The selective cGAS inhibitor RU.521, STING agonist 2'3'-cGAMP, and STING siRNA were delivered by intranasal administration or intraventricular injection. Post-CVST assessments included rotarod test, TUNEL staining, Fluoro-Jade C staining, dihydroethidium staining, western blotting, qPCR, immunofluorescence, immunohistochemistry, ELISA and flow cytometry.
cGAS, STING, NLRP3 and GSDMD were significantly upregulated after CVST and mostly in the microglia of the mouse brain. CVST triggered the release of dsDNA into the cytoplasm and elicited an inflammatory response via activating the cGAS-STING axis. RU.521 decreased the levels of 2'3'-cGAMP, STING and downstream inflammatory cytokines, and suppressed the expressions of NLRP3 inflammasome and pyroptosis-pertinent components containing cleaved caspase-1, GSDMD, GSDMD-C, pro- and cleaved IL-1β, and cleaved IL-1β/pro-IL-1β. Besides, RU.521 treatment also reduced oxidative stress, lessened the numbers of microglia and neutrophils, and ameliorated neuronal apoptosis, degeneration along with neurological deficits post-CVST. 2'3'-cGAMP delivery enhanced the expressions of STING and related inflammatory mediators, NLRP3 inflammasome and pyroptosis-relevant proteins, whereas these alterations were significantly abrogated by the silencing of STING by siRNA.
Our data demonstrate that repression of the cGAS-STING pathway diminishes the neuroinflammatory burden of CVST and highlight this approach as a potential therapeutic tactic in CVST-mediated pathologies.
Abstract
Background
The prognostic and therapeutic potential of microRNAs (miRNAs) in spinal cord injury (SCI) has aroused increasing concerns. This study aims to research the functions of ...miR-29a/199B in the neurological function recovery after SCI and the mechanical mechanism.
Methods
A rat model with SCI was induced with sham-operated ones as control. The locomotor function and coordination of rat hindlimbs were determined by a Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and a ladder-climbing test, respectively. Expression of a neurofilament protein NF-200 and synaptophysin in gray matter of rats was determined to evaluate neuronal recovery in a cellular perspective. Binding relationships between miR-29a/199B with RGMA were predicted and validated using luciferase assays. Altered expression of miR-29a/199B and RGMA was introduced to explore their functions in rat neurological functions. The protein level and phosphorylation of STAT3 in gray matter were measured by western blot analysis.
Results
miR-29a and miR-199B were poorly expressed, while RGMA was abundantly expressed in gray matter at injury sites. Either miR-29a or miR-199B could bind to RGMA. Overexpression of miR-29a/199B or silencing of RGMA led to an increase in BBB locomotor scores, hindlimb coordination ability, and the expression of NF-200 and synaptophysin in gray matter. Further inhibition in miR-29a/199B blocked the promoting roles of RGMA silencing in neurological recovery. Upregulation of miR-29a/199B or downregulation of RGMA suppressed the phosphorylation of STAT3.
Conclusion
This study evidenced that miR-29a and miR-199B negatively regulated RGMA to suppress STAT3 phosphorylation, therefore promoting the neurological function recovery in rats following SCI.
The inhibitory effects of flavonoids on acetylcholinesterase (AChE) have attracted great interest among researchers. However, few reports have focused on the structure-activity relationship for AChE ...inhibition of flavonoids. This work mainly concerns the structural aspects of inhibitory activities and binding affinities of flavonoids as AChE inhibitors. The results show that hydroxyl groups in the A ring of flavonoids are favorable for inhibiting AChE, and the hydroxylation increases the affinities for AChE. However, methoxylation may decrease or increase the activities depending on the class of flavonoids. The glycosylation decreases the AChE inhibitory activities of flavonoids and lowers the affinities for AChE by 1 to 5 times depending on the conjunction site and the type of sugar moiety. The hydrogenation of the C2-C3 double bond of apigenin decreases both the affinity for AChE and AChE inhibition. The molecular property-affinity relationship reveals that the hydrogen bond force plays an important role in binding flavonoids to AChE. The AChE inhibitions generally increase with the increasing affinities of flavonoids within the class, especially for flavones and flavonols.
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