Decline in the ovarian hormones with menopause may influence somatosensory, cognitive, and affective processing. The present study investigated whether hormonal depletion alters the nociceptive, ...depressive-like and learning behaviors in experimental rats after ovariectomy (OVX), a common method to deplete animals of their gonadal hormones. OVX rats developed thermal hyperalgesia in proximal and distal tail that was established 2 weeks after OVX and lasted the 7 weeks of the experiment. A robust mechanical allodynia was also occurred at 5 weeks after OVX. In the 5th week after OVX, dilute formalin (5%)-induced nociceptive responses (such as elevating and licking or biting) during the second phase were significantly increased as compared to intact and sham-OVX females. However, chronic constriction injury (CCI) of the sciatic nerve-induced mechanical allodynia did not differ as hormonal status (e.g. OVX and ovarian intact). Using formalin-induced conditioned place avoidance (F-CPA), which is believed to reflect the pain-related negative emotion, we further found that OVX significantly attenuated F-CPA scores but did not alter electric foot-shock-induced CPA (S-CPA). In the open field and forced swimming test, there was an increase in depressive-like behaviors in OVX rats. There was no detectable impairment of spatial performance by Morris water maze task in OVX rats up to 5 weeks after surgery. Estrogen replacement retrieved OVX-induced nociceptive hypersensitivity and depressive-like behaviors. This is the first study to investigate the impacts of ovarian removal on nociceptive perception, negative emotion, depressive-like behaviors and spatial learning in adult female rats in a uniform and standard way.
Silver screen: The AgNO3‐catalyzed carbon phosphorylation of alkenes occurs by an alkene addition/cyclization cascade. Ag+ reacts with Ph2P(O)H to form the crucial active intermediate 1, which ...promotes the reaction. This method requires a cheap, nontoxic silver salt as the catalyst and substrates for the transformation are simple and readily accessible.
Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; ...however, robust evidence in patients with ischemic stroke is lacking.
To assess the efficacy of RIC for acute moderate ischemic stroke.
This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021.
Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971).
The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set.
Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean SD age, 65 10.3 years; 606 women 34.1%), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% 95% CI, 1.0%-9.9%; odds ratio, 1.27 95% CI, 1.05-1.54; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group.
Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention.
ClinicalTrials.gov Identifier: NCT03740971.
Rational utilization of biomass waste into usable energy is of great significance. In this work, a facile method was proposed to prepare porous carbon as supercapacitor electrode by using biomass ...waste-kapok flower as a precursor. The obtained porous carbon exhibited hierarchical pores rich in microporous and mesoporous, containing oxygen from kapok flowers. The optimal porous carbon ACF-4.5, which was achieved with a mass ratio of KOH to the precursor obtained from kapok flower was 4.5:1, showed a remarkable electrochemical performance with a capacitance as high as 286.8 F/g at 1 A/g current density. It was worth noting that the capacitance retention rate can still reach 97.4% after 5000 cycles, which indicated that the ACF-4.5 supercapacitor electrode has excellent cyclic stability. Therefore, a strategy that not only utilizes biomass waste, but also produces high-performance supercapacitor electrode in industry effectively was realized.
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•Facile method of preparing porous carbon from biomass waste-kapok flower is proposed.•The oxygen-rich porous structure can be controlled by adjusting KOH/precursor ratio.•A high specific capacitance of 286.8 F/g at 1 A/g for ACF-4.5 was achieved.•The ACF-4.5 electrode shows a capacitance retention rate of 97.4% after 5000 cycles.
Diabetes mellitus (DM) patients are at a higher risk of developing brain injury characterized by neuronal death. Melatonin, a hormone produced by the pineal gland, exerts neuroprotective effects ...against brain damage. However, the effect of melatonin on diabetes‐induced brain injury has not been elucidated. This study was to evaluate the role of melatonin against neuronal death in DM and to elucidate the underlying mechanisms. Herein, we found that melatonin administration significantly alleviated the neuronal death in both streptozotocin (STZ)‐induced diabetic mice and high glucose (HG)‐treated neuronal cells. Melatonin inhibited neuronal pyroptosis and excessive autophagy, as evidenced by decreased levels of NLRP3, cleaved caspase‐1, GSDMD‐N, IL‐1β, LC3, Beclin1, and ATG12 both in vivo and in vitro. MicroRNA‐214‐3p (miR‐214‐3p) was decreased in DM mice and HG‐treated cells, and such a downregulation was corrected by melatonin, which was accompanied by repression of caspase‐1 and ATG12. Furthermore, downregulation of miR‐214‐3p abrogated the anti‐pyroptotic and anti‐autophagic actions of melatonin in vitro. Our results indicate that melatonin exhibits a neuroprotective effect by inhibiting neuronal pyroptosis and excessive autophagy through modulating the miR‐214‐3p/caspase‐1 and miR‐214‐3p/ATG12 axes, respectively, and it might be a potential agent for the treatment of brain damage in the setting of DM.
Abstract
Background
The Makorin ring finger protein 1 (
MKRN1
) gene, also called RNF61, is located on the long arm of chromosome 7 and is a member of the RING finger protein family. The E3 ubiquitin ...ligase MKRN1 is closely linked to tumour development, but the exact mechanism needs to be elucidated. In this study, we aimed to investigate the specific mechanism and role of
MKRN1
in colorectal cancer (CRC) development.
Methods
MKRN1
expression in CRC was analysed using the Cancer Cell Line Encyclopaedia and the Cancer Genome Atlas (TCGA) databases. Rectal tumour tissues were frozen to explore the MKRN1 expression in CRC and its clinical significance. The impact of
MKRN1
on CRC cell proliferation and migration was observed using CCK8, colony formation, wound healing, and transwell assays. A combination of MKRN1 quantitative proteomics, ubiquitination modification omics analysis, and a string of in vitro and in vivo experiments revealed the potential mechanisms by which
MKRN1
regulates CRC metastasis.
Results
MKRN1
expression was significantly elevated in CRC tissues compared to paracancerous tissues and was positively linked with prognosis (
P
< 0.01).
MKRN1
downregulation inhibits CRC cell proliferation, migration, and invasion. Conversely,
MKRN1
overexpression promotes the proliferation, migration, and invasion of CRC cells. Mechanistically,
MKRN1
induces epithelial-mesenchymal transition (EMT) in CRC cells via ubiquitination and degradation of Smad nuclear-interacting protein 1 (SNIP1). Furthermore, SNIP1 inhibits transforming growth factor-β (TGF-β) signalling, and
MKRN1
promotes TGF-β signalling by degrading SNIP1 to induce EMT in CRC cells. Finally, using conditional knockout mice, intestinal lesions and metastatic liver microlesions were greatly reduced in the intestinal knockout
MKRN1
group compared to that in the control group.
Conclusions
High
MKRN1
levels promote TGF-β signalling through ubiquitination and degradation of SNIP1, thereby facilitating CRC metastasis, and supporting
MKRN1
as a CRC pro-cancer factor. The MKRN1/SNIP1/TGF-β axis may be a potential therapeutic target in CRC.
Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic encephalopathy,many neonatal patients die or suffer from severe neurological dysfunction.Erythropoietin is considered one ...of the most promising neuroprotective agents.We hypothesized that erythropoietin combined with hypothermia will improve efficacy of neonatal hypoxic-ischemic encephalopathy treatment.In this study,41 neonates with moderate/severe hypoxic-ischemic encephalopathy were randomly divided into a control group（hypothermia alone for 72 hours,n = 20） and erythropoietin group（hypothermia ＋ erythropoietin 200 IU/kg for 10 days,n = 21）.Our results show that compared with the control group,serum tau protein levels were lower and neonatal behavioral neurological assessment scores higher in the erythropoietin group at 8 and 12 days.However,neurodevelopmental outcome was similar between the two groups at 9 months of age.These findings suggest that erythropoietin combined with hypothermia reduces serum tau protein levels and improves neonatal behavioral neurology outcome but does not affect long-term neurodevelopmental outcome.
Conspectus CO2 conversion to valuable chemicals is effective at reducing CO2 emissions. We previously proposed valorization strategies and developed efficient catalysts to address thermodynamic ...stability and kinetic inertness issues related to CO2 conversion. Earlier, we developed molecular capture reagents and catalysts to integrate CO2 capture and conversion, i.e., in situ transformation. Based on the mechanistic understanding of CO2 capture, activation, and transformation at a molecular level, we set out to develop heterogeneous catalysts by incorporating catalytic units into nanomaterials via the immobilization of active molecular catalysts onto nanomaterials and designing nanomaterials with intrinsic catalytic sites. In thermocatalytic CO2 conversion, carbonaceous and metal–organic framework (MOF)-based catalysts were developed for nonreductive and reductive CO2 conversion. Novel Cu- and Zn-based MOFs and carbon-supported Cu catalysts were prepared and successfully applied to the cycloaddition, carboxylation, and carboxylative cyclization reactions with CO2, generating cyclic carbonates, carboxyl acids, and oxazolidinones as respective target products. Reductive conversion of CO2, especially reductive functionalization with CO2, is a promising transformation strategy to produce valuable chemicals, alleviating chemical production that relies on petrochemistry. We explored the hierarchical reductive functionalization of CO2 using organocatalysts and proposed strategies to regulate the CO2 reduction level, triggering heterogeneous catalyst investigation. Introducing multiple active sites into nanomaterials opens possibilities to develop novel CO2 transformation strategies. CO2 capture and in situ conversion were realized with an N-doped carbon-supported Zn complex and MOF materials as CO2 adsorbents and catalysts. These nanomaterial-based catalysts feature high stability and excellent efficiency and act as shape-selective catalysts in some cases due to their unique pore structure. Nanomaterial-based catalysts are also appealing candidates for photocatalytic CO2 reduction (PCO2RR) and electrocatalytic CO2 reduction (ECO2RR), so we developed a series of hybrid photo-/electrocatalysts by incorporating active metal complexes into different matrixes such as porous organic polymers (POPs), metal–organic layers (MOLs), micelles, and conducting polymers. By introducing Re-bipyridine and Fe-porphyrin complexes into POPs and regulating the structure of the polymer chain, catalyst stability and efficiency increased in PCO2RR. PCO2RR in aqueous solution was realized by designing the Re-bipyridine-containing amphiphilic polymer to form micelles in aqueous solution and act as nanoreactors. We prepared MOLs with two different metallic centers, i.e., the Ni-bipyridine site and Ni-O node, to improve the efficiency for PCO2RR due to the synergistic effect of these metal centers. Sulfylphenoxy-decorated cobalt phthalocyanine (CoPc) cross-linked polypyrrole was prepared and used as a cathode, achieving the electrocatalytic transformation of diluted CO2 benefiting from the CO2 adsorption capability of polypyrrole. We fabricated immobilized 4-(t-butyl)-phenoxy cobalt phthalocyanine and Bi-MOF as cathodes to promote the paired electrolysis of CO2 and 5-hydroxymethylfurfural (HMF) and obtained CO2 reductive products and 2,5-furandicarboxylic acid (FDCA) efficiently.
Abstract Extracting uranium from real water samples remains a great challenge due to low uranium concentration, concentrated competing ions and volumes of water. The design and preparation of uranium ...adsorbents with high efficiency and affinity are still difficult. Herein, we presented a facile one‐pot strategy to obtain a novel metal organic framework (denoted as Mn‐NDISA) for stable and efficient trapping of low concentration uranium. Mn‐NDISA with a built‐in hydrophobic cavity can boost the absorption affinity to 1.99 × 10 6 mL g −1 through the cooperative capture composed of electrostatic interaction, coordination force and hydrogen binding. Owing to the coordination‐available oxygen sites in flexible framework, a rapid kinetic equilibrium was achieved in just 25 min. Moreover, these exceptional adsorption features enabled Mn‐NDISA to successfully capture the naturally occurring uranium traces (~ppb) in wastewater samples, making it one of the most influential absorbents toward UO 2 2+ ever reported. The experimental and theoretical studies revealed that the electrostatic attraction came from the surface negatively charged Mn‐NDISA and the positively charged UO 2 2+ . The coordination originated from Lewis basic hydroxyl, carbonyl groups, and Lewis acid UO 2 2+ , while hydrogen bonds further reinforced the as‐formed uranium binding complex. This research offered a promising cooperative capture strategy to improve the uranium affinity of the pristine MOF for trace contaminants removal in environmental remediation fields.
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