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1.
Front Neurol ; 15: 1334786, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38385036

RESUMO

Stroke has long been a major threat to human health worldwide. Hemorrhagic stroke, including intracerebral hemorrhage and subarachnoid hemorrhage, exhibits a high incidence rate and a high mortality and disability rate, imposing a substantial burden on both public health and the economy and society. In recent years, the triggering receptor expressed on myeloid cells (TREM) family has garnered extensive attention in various pathological conditions, including hemorrhagic stroke. This review comprehensively summarizes the structure and function of TREM1/2, as well as their roles and potential mechanisms in hemorrhagic stroke, with the aim of providing guidance for the development of targeted therapeutic strategies in the future.

2.
Biochem Biophys Rep ; 37: 101646, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38333050

RESUMO

Adeno-associated virus (AAV) vectors have been widely used in therapy to treat hereditary retinal diseases. But its transduction efficiency by intravitreal injection still needs to be improved. In this study, we investigated the transduction efficiency of AAV-DJ (K137R)-GFP in different retinal cells of normal mice, as well as the therapy effection of AAV-DJ (K137R)-Rs1 on retinal function and structure in Rs1-KO mice. The intravitreal injection of AAV-DJ (K137R)-GFP demonstrated that this vector transduced cells in all layers of the retina, including the inner nuclear layer and photoreceptor layer. The intravitreal injection of AAV-DJ (K137R)-Rs1 found that 3 months post-injection of this vector improved retinal function and structure in Rs1-KO mice. Our conclusion is that AAV-DJ (K137R) vector can efficiently and safely penetrate the inner limiting membrane and transduce different layers of retinal cells in the long term, as well as being able to continuously and efficiently express target therapeutic proteins, making it a candidate therapeutic vector for X-linked retinoschisis (XLRS).

3.
Br J Anaesth ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38336518

RESUMO

BACKGROUND: Cigarette smoking is commonly reported among chronic pain patients in the clinic. Although chronic nicotine exposure is directly linked to nociceptive hypersensitivity in rodents, underlying neurobiological mechanisms remain unknown. METHODS: Multi-tetrode recordings in freely moving mice were used to test the activity of dopaminergic projections from the ventral tegmental area (VTA) to pyramidal neurones in the anterior cingulate cortex (ACC) in chronic nicotine-treated mice. The VTA→ACC dopaminergic pathway was inhibited by optogenetic manipulation to detect chronic nicotine-induced allodynia (pain attributable to a stimulus that does not normally provoke pain) assessed by von Frey monofilaments (force units in g). RESULTS: Allodynia developed concurrently with chronic (28-day) nicotine exposure in mice (0.36 g [0.0141] vs 0.05 g [0.0018], P<0.0001). Chronic nicotine activated dopaminergic projections from the VTA to pyramidal neurones in the ACC, and optogenetic inhibition of VTA dopaminergic terminals in the ACC alleviated chronic nicotine-induced allodynia in mice (0.06 g [0.0064] vs 0.28 g [0.0428], P<0.0001). Moreover, optogenetic inhibition of Drd2 dopamine receptor signalling in the ACC attenuated nicotine-induced allodynia (0.07 g [0.0082] vs 0.27 g [0.0211], P<0.0001). CONCLUSIONS: These findings implicate a role of Drd2-mediated dopaminergic VTA→ACC pathway signalling in chronic nicotine-elicited allodynia.

4.
J Nutr ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38340959

RESUMO

BACKGROUND: Weaning usually causes low feed intake and weight loss in piglets, which mobilizes lipid to energize. The microbe-derived antioxidants (MA) exhibit great potential in anti-oxidation, anti-inflammation and metabolic regulation. OBJECTIVE: To investigate the changes of lipid metabolism postweaning and effects of MA on growth performance and hepatic lipid metabolism in weanling piglets. METHODS: In the first experiment, piglets weaned at 21 days old were slaughtered on weaning day (d0), 4 (d4) and 14 (d14) days postweaning (6 piglets per day). In the second experiment, piglets were divided into two groups, receiving MA (MA) and saline gavage (CON), respectively. All piglets were weaned at 21 days old and 6 piglets from each group were slaughtered at 25 days old. RESULTS: In the experiment 1, the serum TG, TC and LDL-C on d4 and d14 declined significantly compared with d0 (P < 0.05). The serum leptin on d0 was higher than that on d4 and d14 (P < 0.05). The serum ghrelin kept increasing from d0 to d14 (P < 0.05). The hepatic HSL and ATGL firstly increased from d0 to d4 then decreased from d4 to d14 (P < 0.05). In the experiment 2, the ADG and ADFI from 21-25 days old increased in MA group compared with CON group (P < 0.05). The serum TC, hepatic TC and glucose of MA group showed a significant increase than that of CON group (P < 0.05). The expression of SCD1, ACAT2 and PPARγ were upregulated in MA group (P < 0.05). Contrary to the decreased expression of p-AMPKα (Thr172), the nuclear SREBP1c, FASN and PPARγ of MA group increased than that of CON group (P < 0.05). CONCLUSIONS: Weaning promoted hepatic lipolysis and MA could enhance lipid synthesis by regulating AMPKα-SREBP1c pathway, thus improving growth performance of weanling piglets.

5.
Tissue Cell ; 87: 102322, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38367324

RESUMO

Ribisin A has been shown to have neurotrophic activity. The aim of this study was to evaluate the neuroprotective effect of ribisin A on injured PC12 cells and elucidate its mechanism. In this project, PC12 cells were induced by H2O2 to establish an injury model. After treatment with ribisin A, the neuroprotective mechanism of ribisin A was investigated by methyl tetrazolium (MTT) assay, Enzyme-linked immunosorbent assay (ELISA), flow cytometric analysis, fluorescent probe analysis, and western blot. We found that ribisin A decreased the rate of lactate dehydrogenase (LDH) release, increased cellular superoxide dismutase (SOD) level, decreased the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), Ca2+ expression and reactive oxygen species (ROS). Moreover, ribisin A significantly increased mitochondrial membrane potential (MMP) and inhibited apoptosis of PC12 cells. Meanwhile, ribisin A activated the phosphorylation of ERK1/2 and its downstream molecule CREB by upregulating the expression of Trk A and Trk B, the upstream molecules of the ERK signaling pathway.

6.
Analyst ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38380690

RESUMO

Mesoporous Fe3O4-loaded silver nanocomposites (Fe3O4@Ag) were simply fabricated as bi-functional nanozymes for the catalysis-based detection and removal of Hg2+ ions. It was found that the as-prepared magnetic Fe3O4@Ag could display peroxidase-like catalysis activity that could be rationally enhanced in the presence of Hg2+ ions. To our surprise, the shell of the Ag element may decrease the catalysis of the Fe3O4 to some degree. However, the Ag particles could serve as the probes for specifically recognizing Hg2+ ions and trigger increased catalysis through the formation of Ag-Hg alloys, with a decreased signal background. A high-throughput colorimetric analytical method was thereby developed based on the Fe3O4@Ag catalysis for probing Hg2+ ions in the muscles of fish by using 96-well plates, at linear Hg2+ concentrations ranging from 0.010 to 2.5 mg kg-1. Moreover, the developed colorimetric analytical method was applied to evaluate Hg2+ levels in muscle samples of different kinds of fish. Unexpectedly, an obvious difference of Hg2+ levels in muscles of four kinds of fish was discovered, with the order of snakehead (Ophicephalus argus) > largemouth bass (Micropterus salmoides) > crucian carp (Carassius auratus) > silver carp (Hypophthalmichthys molitrix), where the carnivorous fish showed higher Hg2+ levels than the omnivorous or plant-based ones. Moreover, the as-fabricated Fe3O4@Ag adsorbents with their large specific surface area and high environmental robustness could exhibit efficient Hg2+ adsorption with capacities of up to 397.60 mg g-1. A removal efficiency of 99.40% can also be expected for Hg2+ ions from wastewater, with the magnet-aided recycling of Fe3O4@Ag adsorbents. Such an Fe3O4@Ag-based colorimetric analysis and removal strategy for Hg2+ ions should find wide applications in the fields of aquatic food safety, environmental monitoring, and clinical diagnostics of Hg-poisoning diseases.

7.
Cell Rep ; 43(2): 113804, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368612

RESUMO

Neural mechanisms underlying amputation-related secondary pain are unclear. Using in vivo two-photon imaging, three-dimensional reconstruction, and fiber photometry recording, we show that a microglial activation cascade from the primary somatosensory cortex of forelimb (S1FL) to the primary somatosensory cortex of hindlimb (S1HL) mediates the disinhibition and subsequent hyperexcitation of glutamatergic neurons in the S1HL (S1HLGlu), which then drives secondary mechanical hypersensitivity development in ipsilateral hindpaws of mice with forepaw amputation. Forepaw amputation induces rapid S1FL microglial activation that further activates S1HL microglia via the CCL2-CCR2 signaling pathway. Increased engulfment of GABAergic presynapses by activated microglia stimulates S1HLGlu neuronal activity, ultimately leading to secondary mechanical hypersensitivity of hindpaws. It is widely believed direct neuronal projection drives interactions between distinct brain regions to prime specific behaviors. Our study reveals microglial interactions spanning different subregions of the somatosensory cortex to drive a maladaptive neuronal response underlying secondary mechanical hypersensitivity at non-injured sites.

8.
J Org Chem ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363598

RESUMO

A tunable cascade reaction of ureidomalonates and alkenyl azlactones was disclosed, which gave rise to the construction of N-aroyl α-amino acid ester and imide-functionalized hydantoins in moderate to good yields and with excellent diastereoselectivities. The reaction pathway was precisely manipulated by organocatalysis and phase-transfer/sunlight relay catalysis, respectively, to realize the divergent synthesis. The successful gram-scale preparation of representative products exhibited the application potential of this protocol. Mechanistic studies indicated that the exchange and phase transfer of ethoxy anion played a key role in altering the reaction pathway, and sunlight might accelerate the oxidation process at the late stage of the reaction triggered by phase-transfer catalysis.

9.
Front Immunol ; 15: 1309509, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38352877

RESUMO

Immunotherapy of tumors plays a pivotal role in the current treatment of cancer. While interleukin 2 (IL-2) demonstrated its efficacy as an immunotherapeutic drug in the early days, its short blood circulation time poses challenges in maintaining effective therapeutic concentrations. Additionally, IL-2's activation of regulatory T cells can counteract its anti-cancer effects. Therefore, the primary goal of this study was to formulate IL-2-carrying nanoparticles via boron-nitrogen coordination between methoxy poly (ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide]phenylboronic acid (mPEG-b-PHEA-PBA, P-PBA) and poly (L-lysine) (PLL). These nanoparticles are intended to be used in combination with CDK4/6 inhibitors to address the short blood circulation time of IL-2, reduce its immunosuppressive effects, and enhance the overall immune response. The envisaged outcome is a sustained and potent therapeutic effect, offering a novel and promising combination therapy strategy for tumor immunotherapy.


Assuntos
Neoplasias do Colo , Nanopartículas , Piperazinas , Piridinas , Humanos , Interleucina-2/farmacologia , Interleucina-2/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Imunidade
10.
Microb Pathog ; : 106573, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38354989

RESUMO

The substantial increase of infections, caused by novel, sudden, and drug-resistant pathogens, poses a significant threat to human health. While numerous studies have demonstrated the antibacterial and antiviral effects of Traditional Chinese Medicine, the potential of a complex mixture of traditional Chinese Medicine with a broad-spectrum antimicrobial property remains underexplored. This study aimed to develop a complex mixture of Traditional Chinese Medicine (TCM), JY-1, and investigate its antimicrobial properties, along with its potential mechanism of action against pathogenic microorganisms. Antimicrobial activity was assessed using a zone of inhibition assay and the drop plate method. Hyphal induction of Candida albicans was conducted using RPMI1640 medium containing 10% FBS, followed by microscopic visualization. Quantitative real-time PCR (RT-qPCR) was employed to quantify the transcript levels of hyphal-specific genes such as HWP1 and ALS3. The impact of JY-1 on biofilm formation was evaluated using both the XTT reduction assay and scanning electron microscopy (SEM). Furthermore, the cell membrane integrity was assessed by protein and nucleic acid leakage assays. Our results clearly showed that JY-1 significantly inhibits the vegetative growth of Candidaspp. and Cryptococcusspp. In addition, this complex mixture is effectively against a wide range of pathogenic bacteria, including Staphylococcus aureus, Vancomycin-resistant enterococci, Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. More interestingly, JY-1 plays a direct anti-viral role against the mammalian viral pathogen vesicular stomatitis virus (VSV). Further mechanistic studies indicate that JY-1 acts to reduce the expression of hyphal specific genes HWP1 and ALS3, resulting in the suppression of the hyphal formation of C. albicans. The antimicrobial property of JY-1 could be attributed to its ability to reduce biofilm formation and disrupt the cell membrane permeability, a process resulting in microbial cell death and the release of cellular contents. Taken together, our work identified a potent broad-spectrum antimicrobial agent, a complex mixture of TCM which might be developed as a potential antimicrobial drug.

11.
Nat Chem Biol ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355722

RESUMO

The biosynthetic dogma of ribosomally synthesized and posttranslationally modified peptides (RiPP) involves enzymatic intermolecular modification of core peptide motifs in precursor peptides. The plant-specific BURP-domain protein family, named after their four founding members, includes autocatalytic peptide cyclases involved in the biosynthesis of side-chain-macrocyclic plant RiPPs. Here we show that AhyBURP, a representative of the founding Unknown Seed Protein-type BURP-domain subfamily, catalyzes intramolecular macrocyclizations of its core peptide during the sequential biosynthesis of monocyclic lyciumin I via glycine-tryptophan crosslinking and bicyclic legumenin via glutamine-tyrosine crosslinking. X-ray crystallography of AhyBURP reveals the BURP-domain fold with two type II copper centers derived from a conserved stapled-disulfide and His motif. We show the macrocyclization of lyciumin-C(sp3)-N-bond formation followed by legumenin-C(sp3)-O-bond formation requires dioxygen and radical involvement based on enzyme assays in anoxic conditions and isotopic labeling. Our study expands enzymatic intramolecular modifications beyond catalytic moiety and chromophore biogenesis to RiPP biosynthesis.

12.
Cell Discov ; 10(1): 13, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321019

RESUMO

Tumor cells are usually considered defective in mitochondrial respiration, but human non-small cell lung cancer (NSCLC) tumor tissues are shown to have enhanced glucose oxidation relative to adjacent benign lung. Here, we reported that oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) inhibited glycolysis and promoted oxidative metabolism in NSCLC cells. CIP2A bound to pyruvate kinase M2 (PKM2) and induced the formation of PKM2 tetramer, with serine 287 as a novel phosphorylation site essential for PKM2 dimer-tetramer switching. CIP2A redirected PKM2 to mitochondrion, leading to upregulation of Bcl2 via phosphorylating Bcl2 at threonine 69. Clinically, CIP2A level in tumor tissues was positively correlated with the level of phosphorylated PKM2 S287. CIP2A-targeting compounds synergized with glycolysis inhibitor in suppressing cell proliferation in vitro and in vivo. These results indicated that CIP2A facilitates oxidative phosphorylation by promoting tetrameric PKM2 formation, and targeting CIP2A and glycolysis exhibits therapeutic potentials in NSCLC.

13.
Heliyon ; 10(3): e24967, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38322910

RESUMO

Objectives: Postoperative delirium (POD) is considered to be a common complication of spine surgery. Although many studies have reported the risk factors associated with POD, the results remain unclear. Therefore, we performed a meta-analysis to identify risk factors for POD among patients following spinal surgery. Methods: We systematically searched the PubMed, Embase and the Cochrane Library for relevant articles published from 2006 to February 1, 2023 that reported risk factors associated with the incidence of POD among patients undergoing spinal surgery. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed, and random effects models were used to estimate pooled odds ratio (OR) estimates with 95 % confidence intervals (CIs) for each factor. The evidence from observational studies was classified according to Egger's P value, total sample size, and heterogeneity between studies. Results: Of 11,329 citations screened, 50 cohort studies involving 1,182,719 participants met the inclusion criteria. High-quality evidence indicated that POD was associated with hypertension, diabetes mellitus, cardiovascular disease, pulmonary disease, older age (>65 years), patients experiencing substance use disorder (take drug ≥1 month), cerebrovascular disease, kidney disease, neurological disorder, parkinsonism, cervical surgery, surgical site infection, postoperative fever, postoperative urinary tract infection, and admission to the intensive care unit (ICU). Moderate-quality evidence indicated that POD was associated with depression, American Society of Anesthesiologists (ASA) fitness grade (>II), blood transfusion, abnormal potassium, electrolyte disorder, length of stay, inability to ambulate and intravenous fluid volume. Conclusions: Conspicuous risk factors for POD were mainly patient- and surgery-related. These findings help clinicians identify high-risk patients with POD following spinal surgery and recognize the importance of early intervention.

14.
Front Bioeng Biotechnol ; 12: 1338029, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38357709

RESUMO

Repairing defects in alveolar bone is essential for regenerating periodontal tissue, but it is a formidable challenge. One promising therapeutic approach involves using a strategy that specifically recruits periodontal ligament cells (PDLCs) with high regenerative potential to achieve in situ regeneration of alveolar bone. In this study, we have created a new type of microsphere conjugated with an antibody to target p75 neurotrophin receptor (p75NTR), which is made of nano-hydroxyapatite (nHA) and chitosan (CS). The goal of this design is to attract p75NTR+hPDLCs selectively and promote osteogenesis. In vitro experiments demonstrated that the antibody-conjugated microspheres attracted significantly more PDLCs compared to non-conjugated microspheres. Incorporating nHA not only enhances cell adhesion and proliferation on the surface of the microsphere but also augments its osteoinductive properties. Microspheres effectively recruited p75NTR+ cells at bone defect sites in SD rats, as observed through immunofluorescent staining of p75NTR antibodies. This p75NTR antibody-conjugated nHA/CS microsphere presents a promising approach for selectively recruiting cells and repairing bone defects.

15.
J Colloid Interface Sci ; 662: 242-249, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38350347

RESUMO

As model catalysts, it is necessary to study the relationship between the structure and properties of ultra-small metal nanoclusters (MNCs) and to reduce their steric hindrance as much as possible, e.g. preparing ultrasmall MNCs protected by ultra-short ligands. However, it is challenging to attain various MNCs with the same cores but different surface stabilizing ligands. Additionally, shortening the chains of protecting ligands will lead to larger MNC cores. Here, four different Pd NCs (Pd6(SC4H9)12, Pd6(SC8H17)12, Pd6(SC6(C2)H17)12 and Pd6(SC6H13)12) were successfully synthesized by a slow synthesis process. All these clusters consist of six Pd atoms and are stabilized by 12 thiols with different chain lengths and steric hindrance. The catalytic properties of the as-prepared Pd6 NCs were evaluated using the catalytic reduction of p-nitroaniline to p-phenylenediamine as a model reaction. The outcomes indicated that shortening the chain length of the protecting thiols could enhance the catalytic activity of the Pd6 NCs. Notably, stable and active ultra-small Pd6 clusters stabilized by ultra-short ligands (HSC4H9) were successfully synthesized. Although the performance of Pd6(SC4H9)12 clusters protected by the ultra-short thiols is lower than that of commercial palladium on carbon (Pd/C), they display higher stability. Interestingly, the activity of Pd6 NCs protected by ethyl-branched alkane thiols is also better than that of Pd6 NCs protected by the alkane thiol ligands with the same chain length or the same number of carbon numbers. This work provides clear evidence that the catalytic activity of atomically precise MNCs can be controlled by regulating the surface stabilizing ligands.

16.
Small ; : e2310811, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38299466

RESUMO

Osmotic energy, as a renewable clean energy with huge energy density and stable yield, has received widespread attention over the past decades. Reverse electrodialysis (RED) based on ion-exchange membranes is an important method of obtaining osmotic energy from salinity gradients. The preparation of ion-exchange membranes with both high ion selectivity and ion permeability is in constant exploration. In this work, metal hydroxide-organic framework (MHOF) membranes are successfully prepared onto porous anodic aluminum oxide (AAO) membranes by a facile hydrothermal method to form Ni2 (OH)2 @AAO composite membranes, used for osmotic energy conversion. The surface is negatively charged with cation selectivity, and the asymmetric structure and extreme hydrophilicity enhance the ionic flux for effective capture of osmotic energy. The maximum output power density of 5.65 W m-2 at a 50-fold KCl concentration gradient is achieved, which exceeds the commercial benchmark of 5 W m-2 . Meanwhile, the composite membrane can also show good performance in different electrolyte solutions and acid-base environments. This work provides a new avenue for the construction and application of MHOF membranes in efficient osmotic energy conversion.

17.
Thromb Haemost ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38325399

RESUMO

Introduction Platelets bridge thrombosis and inflammation, but how platelets use the endogenous intraplatelet inflammatory machinery is less well understood. NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) is best known as the central component of the interleukin (IL)-1-producing inflammasome. Unveiling a cell type-specific mechanism of NLRP3 in platelets may improve our understanding of thrombotic diseases. Methods Ferric chloride-induced mesenteric arteriole thrombosis, tail bleeding models and microfluidic whole-blood perfusion were used to assess thrombosis and hemostasis. Additionally, we utilized aggregometry, flow cytometry, immunoprecipitation and western blot to investigate glycoprotein (GP) Ib-IX mediated platelet function and signaling. Results Our findings revealed that NLRP3-/- mice displayed severely impaired thrombosis and hemostasis, whereas apoptosis-associated speck-like protein containing a CARD (ASC)-/-, caspase-1-/-, or Nlrp3A350V/+CrePF4 mice did not exhibit such impairment. Subsequently, NLRP3-/- platelets exhibit reduced adhesion to injured vessel walls and collagen and impaired von Willebrand factor (vWF)-dependent translocation and rolling behavior. NLRP3 deficiency decreased botrocetin-induced aggregation and the phosphorylation of key signaling molecules in the GPIb-IX pathway. Mechanistically, diminished cAMP/PKA activity led to reduced phosphorylation of the Ser291 site on NLRP3, thereby enabling an NLRP3-filamin A interaction. This interaction accelerated the dissociation of filamin A from GPIbα, which allowed the 14-3-3ζ-dependent upregulation of GPIb-IX affinity to vWF. Finally, platelet NLRP3 largely regulated thrombotic disease models such as stroke and deep vein thrombosis. Conclusion NLRP3 promoted the function of the major platelet adhesion receptor GPIb-IX without involving NLRP3 inflammasome assembly or IL-1ß.

18.
Int Immunopharmacol ; 129: 111637, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38335653

RESUMO

The small intestine exhibits remarkable sensitivity to ionizing radiation (IR), which significantly hampers the effectiveness of radiotherapy in the treatment of abdominal and pelvic tumors. Unfortunately, no effective medications are available to treat radiation-induced intestinal damage (RIID). Fraxin (7-hydroxy-6-methoxycoumarin 8-glucoside), is a coumarin derivative extracted from the Chinese herb Cortex Fraxini. Several studies have underscored the anti-inflammatory, antibacterial, antioxidant, and immunomodulatory properties of fraxin. However, the efficacy of fraxin at preventing or mitigating RIID remains unclear. Thus, the present study aimed to investigate the protective effects of fraxin against RIID in vitro and in vivo and to elucidate the underlying mechanisms. The study findings revealed that fraxin markedly ameliorated intestinal injuries induced by 13 Gy whole abdominal irradiation (WAI), which was accompanied by a significant increase in the population of Lgr5+ intestinal stem cells (ISCs) and Ki67+ progeny. Furthermore, fraxin mitigated WAI-induced intestinal barrier damage, and reduced oxidative stress and intestinal inflammation in mice. Transcriptome sequencing of fraxin-treated mice revealed upregulation of IL-22, a pleiotropic cytokine involved in regulating the function of intestinal epithelial cells. Moreover, in both human intestinal epithelial cells and ex vivo cultured mouse intestinal organoids, fraxin effectively ameliorated IR-induced damage by promoting the expression of IL-22. The radioprotective effects of fraxin were partially negated in the presence of an IL-22-neutralizing antibody. In summary, fraxin is demonstrated to possess the ability to alleviate RIID and maintain intestinal homeostasis, suggesting that fraxin might serve as a strategy for mitigating accidental radiation exposure- or radiotherapy-induced RIID.

19.
Adv Sci (Weinh) ; 11(7): e2307780, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38168899

RESUMO

Batteries dissolving active materials in liquids possess safety and size advantages compared to solid-based batteries, yet the intrinsic liquid properties lead to material cross-over induced self-discharge both during cycling and idle when the electrolytes are in contact, thus highly efficient and cost-effective solutions to minimize cross-over are in high demand. An ultra-low self-discharge aqueous|organic membraneless battery using dichloromethane (CH2 Cl2 ) and tetrabutylammonium bromide (TBABr) added to a zinc bromide (ZnBr2 ) solution as the electrolyte is demonstrated. The polybromide is confined in the organic phase, and bromine (Br2 ) diffusion-induced self-discharge is minimized. At 90% state of charge (SOC), the membraneless ZnBr2 |TBABr (Z|T) battery shows an open circuit voltage (OCV) drop of only 42 mV after 120 days, 152 times longer than the ZnBr2  battery, and superior to 102 previous reports from all types of liquid active material batteries. The 120-day capacity retention of 95.5% is higher than commercial zinc-nickel (Zn-Ni) batteries and vanadium redox flow batteries (VRFB, electrolytes stored separately) and close to lithium-ion (Li-ion) batteries. Z|T achieves >500 cycles (2670 h, 0.5 m electrolyte, 250 folds of membraneless ZnBr2  battery) with ≈100% Coulombic efficiency (CE). The simple and cost-effective design of Z|T provides a conceptual inspiration to regulate material cross-over in liquid-based batteries to realize extended operation.

20.
Angew Chem Int Ed Engl ; 63(8): e202315841, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38179848

RESUMO

Inherent "soft" ionic lattice nature of halide perovskite quantum dots (QDs), triggered by the weak Pb-X (X=Cl, Br, I) bond, is recognized as the primary culprit for their serious instability. A promising way is to construct exceedingly strong ionic interaction inside the QDs and increase their crystal cohesive energy by substituting the interior X- with highly electronegative F- , however, which is challenging and hitherto remains unreported. Here, a "whole-body" fluorination strategy is proposed for strengthening the interior bonding architecture of QDs, wherein the F- are uniformly distributed throughout the whole nanocrystal encompassing both the interior lattice and surface, successfully stabilizing their "soft" crystal lattice and passivating surface defects. This approach effectively mitigates their intrinsic instability issues including light-induced phase segregation. As a result, light-emitting devices based on these QDs exhibit exceptional efficiency and remarkable stability.

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