Accumulating evidences have suggested that extracellular vesicles (EVs) are crucial players in the pathogenesis of ischemic brain injury. This study was designed to explore the specific functions of ...M2 phenotype microglia-derived EVs in ischemic brain injury progression. The expression of microRNA-135a-5p (miR-135a-5p) in M2 microglia-derived EVs was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), followed by the identification of expression relationship among miR-135a-5p, thioredoxin-interacting protein (TXNIP), and nod-like receptor protein 3 (NLRP3) by dual luciferase reporter gene assay. After construction of an oxygen-glucose deprivation/reperfusion (OGD/R) cell model, the effects of miR-135a-5p on the biological characteristics of HT-22 cells were assessed by cell counting kit 8 (CCK-8) assay and flow cytometry. Finally, a mouse model of transient middle cerebral artery occlusion (tMCAO) was established and cerebral infarction volume was determined by triphenyltetrazolium chloride (TTC) staining and the expression of IL-18 and IL-1β in the brain tissue was determined by enzyme-linked immunosorbent assay (ELISA). We found that M2 microglia-derived EVs had high expression of miR-135a-5p, and that miR-135a-5p in M2 microglia-derived EVs negatively regulated the expression of NLRP3 via TXNIP. Overexpression of miR-135a-5p promoted the proliferation but inhibited the apoptosis of neuronal cells, and inhibited the expression of autophagy-related proteins. M2 microglia-derived EVs delivered miR-135a-5p into neuronal cells to inhibit TXNIP expression, which further inhibited the activation of NLRP3 inflammasome, thereby reducing neuronal autophagy and ischemic brain injury. Hence, M2 microglia-derived EVs are novel therapeutic targets for ischemic brain injury treatment.
M2 microglia-derived EVs inhibit neuronal autophagic activity. Mechanistically, M2 microglia-derived EVs deliver miR-135a-5p into neuronal cells to inhibit TXNIP expression, which further inhibits the activation of NLRP3 inflammasomes, thereby reducing neuronal autophagy and ischemic brain injury. Hence, M2 microglia-derived EVs can serve as novel therapeutic targets for ischemic brain injury.
The factors affecting the short-term and long-term prognosis of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) receiving transarterial chemoembolization (TACE) are ...still unclear.
To clarify the predictors correlated with the short-term and long-term survival of HCC patients with PVTT who underwent TACE.
The medical records of 181 HCC patients with PVTT who underwent TACE at the Second Affiliated Hospital of Chongqing Medical University from January 2015 to July 2019 were retrospectively analyzed. We explored the short-term and long-term prognostic factors by comparing the preoperative indicators of patients who died and survived within 3 mo and 12 mo after TACE. Multivariate analyses were conducted using logistic regression. The area under the receiver operating characteristic curve (area under curve) was used to evaluate the predictive ability of the factors related to the short-term and long-term prognosis.
The median survival time was 4.8 mo (range: 2.5-8.85 mo). The 3 mo, 6 mo, and 12 mo survival rates were 68.5%, 38.7%, and 15.5%, respectively. In multivariable analysis, total bilirubin, sex, and aspartate aminotransferase (AST) were closely linked to short-term survival. When AST ≥ 87 U/L and total bilirubin ≥ 16.15 µmol/L, the 3-mo survival rate after TACE was reduced significantly (
< 0.05). AST had the best predictive ability, followed by total bilirubin, while sex had the worst predictive ability for short-term survival area under curve: 0.763 (AST)
0.707 (total bilirubin)
0.554 (sex). The long-term survival outcome was significantly better in patients with a single lesion than in those with ≥ three lesions (
= 0.009). Patients with massive block HCC had a worse long-term survival than patients with nodular and diffuse HCC (
= 0.001).
AST, total bilirubin, and sex are independent factors associated with short-term survival. The number of tumors and the gross pathological type of tumor are related to the long-term outcome.
Abnormal epigenetic regulation has been implicated in oncogenesis. We report here the identification of somatic mutations by exome sequencing in acute monocytic leukemia, the M5 subtype of acute ...myeloid leukemia (AML-M5). We discovered mutations in DNMT3A (encoding DNA methyltransferase 3A) in 23 of 112 (20.5%) cases. The DNMT3A mutants showed reduced enzymatic activity or aberrant affinity to histone H3 in vitro. Notably, there were alterations of DNA methylation patterns and/or gene expression profiles (such as HOXB genes) in samples with DNMT3A mutations as compared with those without such changes. Leukemias with DNMT3A mutations constituted a group of poor prognosis with elderly disease onset and of promonocytic as well as monocytic predominance among AML-M5 individuals. Screening other leukemia subtypes showed Arg882 alterations in 13.6% of acute myelomonocytic leukemia (AML-M4) cases. Our work suggests a contribution of aberrant DNA methyltransferase activity to the pathogenesis of acute monocytic leukemia and provides a useful new biomarker for relevant cases.
For inorganic semiconductor nanostructure, excitons in the triplet states are known as the “dark exciton” with poor emitting properties, because of the spin-forbidden transition. Herein, we report a ...design principle to boost triplet excitons photoluminescence (PL) in all-inorganic lead-free double-perovskite nanocrystals (NCs). Our experimental data reveal that singlet self-trapped excitons (STEs) experience fast intersystem crossing (80 ps) to triplet states. These triplet STEs give bright green color emission with unity PL quantum yield (PLQY). Furthermore, efficient energy transfer from triplet STEs to dopants (Mn2+) can be achieved, which leads to white-light emitting with 87% PLQY in both colloidal and solid thin film NCs. These findings illustrate a fundamental principle to design efficient white-light emitting inorganic phosphors, propelling the development of illumination-related applications.
Sensitive and specific biomarkers for the early detection of esophageal squamous cell carcinoma (ESCC) are urgently needed to reduce the high morbidity and mortality of the disease. The discovery of ...serum microRNAs (miRNAs) and their unique concentration profiles in patients with various diseases makes them attractive, novel noninvasive biomarkers for tumor diagnosis. In this study, we investigated the serum miRNA profile in ESCC patients to develop a novel diagnostic ESCC biomarker.
Serum samples were taken from 290 ESCC patients and 140 age- and sex-matched controls. Solexa sequencing technology was used for an initial screen of miRNAs in serum samples from 141 patients and 40 controls. A hydrolysis probe-based stem-loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and verification phases to confirm the concentrations of selected miRNAs in serum samples from 149 patients and 100 controls.
The Solexa sequencing results demonstrated marked upregulation of 25 serum miRNAs in ESCC patients compared with controls. RT-qPCR analysis identified a profile of 7 serum miRNAs (miR-10a, miR-22, miR-100, miR-148b, miR-223, miR-133a, and miR-127-3p) as ESCC biomarkers. The area under the ROC curve for the selected miRNAs ranged from 0.817 to 0.949, significantly higher than for carcinoembryonic antigen (0.549; P < 0.0005). More importantly, this panel of 7 miRNAs clearly distinguished stage I/II ESCC patients from controls.
This panel of 7 serum miRNAs holds promise as a novel blood-based biomarker for the diagnosis of ESCC.
With the disruptive carbon cycle being blamed for global warming, the plausible electrocatalytic CO2 reduction reaction (CO2RR) to form valuable C2+ hydrocarbons and feedstock is becoming a hot ...topic. Cu-based electrocatalysts have been proven to be excellent CO2RR alternatives for high energy value-added products in this regard. However, the selectivity of CO2RR to form C2+ products via Cu-based catalysts suffers from a high overpotential, slow reaction kinetics, and low selectivity. This review attempts to discuss various cutting-edge strategies for understanding catalytic design such as Cu-based catalyst surface engineering, tuning Cu bandgap via alloying, nanocatalysis, and the effect of the electrolyte and pH on catalyst morphology. The most recent advances in in situ spectroscopy and computational techniques are summarized to fully comprehend reaction mechanisms, structural transformation/degradation mechanisms, and crystal facet loss with subsequent effects on catalyst activity. Furthermore, approaches for tuning Cu interactions are discussed from four key perspectives: single-atom catalysts, interfacial engineering, metal-organic frameworks, and polymer-incorporated materials, which provide new insights into the selectivity of C2+ products. Finally, major challenges are outlined, and potential prospects for the rational design of catalysts for robust CO2RR are proposed. The integration of catalytic design with mechanistic understanding is a step forward in the promising advancement of CO2RR technology for industrial applications.
A new fault-tolerant control method for Hall sensors in brushless DC motor driver of E-bicycle is presented. Contrary to the classical fault-tolerant control method that focused their attention on ...fault diagnosis, the proposed method uses pulse-width modulation input capture function to extract sensors' effective information and eliminate fault information, which helps to omit the process of fault diagnosis and improve the efficiency of fault-tolerant control. The effective information of Hall sensors includes edge jump information and velocity information, which are used to correct and estimate the rotor angle under field oriented control. The effectiveness and rapidity of the proposed fault-tolerant approach are illustrated through experimental results.
In Arabidopsis (Arabidopsis thaliana), the Shaker K⁺ channel AKT1 conducts K⁺ uptake in root cells, and its activity is regulated by CBL1/9-CIPK23 complexes as well as by the AtKC1 channel subunit. ...CIPK23 and AtKC1 are both involved in the AKT1-mediated low-K⁺ (LK) response; however, the relationship between them remains unclear. In this study, we screened suppressors of low-K⁺ sensitive lks1 (cipk23) and isolated the suppressor of lks1 (sls1) mutant, which suppressed the leaf chlorosis phenotype of lks1 under LK conditions. Map-based cloning revealed a point mutation in AtKC1 of sls1 that led to an amino acid substitution (G322D) in the S6 region of AtKC1. The G322D substitution generated a gain-of-function mutation, AtKC1D, that enhanced K⁺ uptake capacity and LK tolerance in Arabidopsis. Structural prediction suggested that glycine-322 is highly conserved in K⁺ channels and may function as the gating hinge of plant Shaker K⁺ channels. Electrophysiological analyses revealed that, compared with wild-type AtKC1, AtKC1D showed enhanced inhibition of AKT1 activity and strongly reduced K⁺ leakage through AKT1 under LK conditions. In addition, phenotype analysis revealed distinct phenotypes of lks1 and atkc1 mutants in different LK assays, but the lks1 atkc1 double mutant always showed a LK-sensitive phenotype similar to that of akt1. This study revealed a link between CIPK-mediated activation and AtKC1-mediated modification in AKT1 regulation. CIPK23 and AtKC1 exhibit distinct effects; however, they act synergistically and balance K⁺ uptake/leakage to modulate AKT1-mediated LK responses in Arabidopsis.
Linezolid has been reported to protect against chronic bone and joint infection. In this study, linezolid was loaded into the 3D printed poly (lactic-co-glycolic acid) (PLGA) scaffold with ...nano-hydroxyapatite (HA) to explore the effect of this composite scaffold on infected bone defect (IBD).
PLGA scaffolds were produced using the 3D printing method. Drug release of linezolid was analyzed by elution and high-performance liquid chromatography assay. PLGA, PLGA-HA, and linezolid-loaded PLGA-HA scaffolds, were implanted into the defect site of a rabbit radius defect model. Micro-CT, H&E, and Masson staining, and immunohistochemistry were performed to analyze bone infection and bone healing. Evaluation of viable bacteria was performed. The cytocompatibility of 3D-printed composite scaffolds in vitro was detected using human bone marrow mesenchymal stem cells (BMSCs). Long-term safety of the scaffolds in rabbits was evaluated.
The linezolid-loaded PLGA-HA scaffolds exhibited a sustained release of linezolid and showed significant antibacterial effects. In the IBD rabbit models implanted with the scaffolds, the linezolid-loaded PLGA-HA scaffolds promoted bone healing and attenuated bone infection. The PLGA-HA scaffolds carrying linezolid upregulated the expression of osteogenic genes including collagen I, runt-related transcription factor 2, and osteocalcin. The linezolid-loaded PLGA-HA scaffolds promoted the proliferation and osteogenesis of BMSCs in vitro via the PI3K/AKT pathway. Moreover, the rabbits implanted with the linezolid-loaded scaffolds showed normal biochemical profiles and normal histology, which suggested the safety of the linezolid-loaded scaffolds.
Overall, the linezolid-loaded PLGA-HA scaffolds fabricated by 3D printing exerts significant bone repair and anti-infection effects.
Display omitted
•Linezolid-loaded PLGA-HA scaffolds exhibited a sustained release of linezolid.•Linezolid-loaded PLGA-HA scaffolds promoted bone healing in rabbit radius defect model.•Linezolid-loaded PLGA-HA scaffolds prevented infection in vivo.•Linezolid-loaded PLGA-HA scaffolds exhibited good biocompatibility and promoted osteogenesis.
Metakaolin‐based Na/Ca‐geopolymers with a designed composition close to feldspar were used as precursors of Cs immobilization form materials. The sintering behaviors of geopolymers and their sintered ...materials' immobilization of Cs ions were investigated; the results indicated that the major phases of sintered geopolymers are plagioclase feldspars and feldspathoid. With the addition of Cs to the geopolymers, Cs‐leucite phase and caesium silicates were formed at 1150°C and 1170°C, respectively. It was found that Cs addition can slightly decrease the sintering temperature of geopolymers and make the grains finer. In addition, in order to reduce the volatilization of Cs ions during sintering, sintering temperatures of Cs‐geopolymer were further decreased to 850°C by introducing B2O3. After the geopolymer and Cs‐geopolymer were sintered using a low‐temperature liquid‐phase process, they remained structurally plagioclase feldspars and feldspathoid. Leaching on Product Consistency Test indicates that the leaching concentrations of Cs‐geopolymer samples sintered at higher temperatures are lower than those of samples sintered at lower temperatures. Thus, the increased volatilization of Cs ions at the higher temperatures and the formation of Cs‐leucite phase and caesium silicates can lead to the decrease of leaching concentrations in leachates. Therefore, low sintering temperatures and the fabrication of Cs crystalline ceramics are the key factors toward improving the immobilization of Cs ions.
Metakaolin‐based Na/Ca‐geopolymers were well sintered at 1200°C, whereas Cs addition to geopolymers caused the formation of Cs‐leucite phase by the solid‐state reaction between Cs ion and geopolymer precursors, and consequently decreased sintering temperatures. The increase in Cs content in compositions also created finer grain structure. The addition of B2O3 to geopolymers achieved a low‐temperature liquid phase during sintering; Consequently, Cs‐geopolymers could be sintered at as low as 850°C and keep aluminosilicate frame structures. For the as‐sintered Cs‐geoolymers' immobilization of Cs depends mainly on sintering temperature and mineral phases. Low sintering temperature and feldspathoid structures should be positive factors to achieve excellent immobilization on Cs ion.
PDF
