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1.
Macromol Biosci ; : e2400051, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38663437

RESUMO

Bioactive scaffolds capable of simultaneously repairing osteochondral defects remain a big challenge due to the heterogeneity of bone and cartilage. Currently modular microgel-based bioassembly scaffolds are emerged as potential solution to this challenge. Here, microgels based on methacrylic anhydride and dopamine modified gelatin (GelMA-DA) were loaded with chondroitin sulfate (the obtained microgel named GC Ms) or bioactive glass (the obtained microgel named GB Ms), respectively. GC Ms and GB Ms showed good biocompatibility with BMSCs, which suggested by the adhesion and proliferation of BMSCs on their surfaces. Specially, GC Ms promoted chondrogenic differentiation of BMSCs, while GB Ms promoted osteogenic differentiation. Furthermore, the injectable GC Ms and GB Ms were assembled integrally by bottom-up in situ crosslinking to obtain modular microgel-based bioassembly scaffold (GC-GB/HM), which showed a distinct bilayer structure and good porous properties and swelling properties. Particularly, the results of in vivo and in vitro experiments showed that GC-GB/HM could simultaneously regulate the expression levels of chondrogenic- and osteogenesis-related genes and proteins. Therefore, modular microgel-based assembly scaffold in this work with the ability to promote bidirectional differentiation of BMSCs and has great potential for application in the minimally invasive treatment of osteochondral tissue defects. This article is protected by copyright. All rights reserved.

2.
J Immunother Cancer ; 12(4)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38642938

RESUMO

BACKGROUND: Colitis caused by checkpoint inhibitors (CPI) is frequent and is treated with empiric steroids, but CPI colitis mechanisms in steroid-experienced or refractory disease are unclear. METHODS: Using colon biopsies and blood from predominantly steroid-experienced CPI colitis patients, we performed multiplexed single-cell transcriptomics and proteomics to nominate contributing populations. RESULTS: CPI colitis biopsies showed enrichment of CD4+resident memory (RM) T cells in addition to CD8+ RM and cytotoxic CD8+ T cells. Matching T cell receptor (TCR) clonotypes suggested that both RMs are progenitors that yield cytotoxic effectors. Activated, CD38+ HLA-DR+ CD4+ RM and cytotoxic CD8+ T cells were enriched in steroid-experienced and a validation data set of steroid-naïve CPI colitis, underscoring their pathogenic potential across steroid exposure. Distinct from ulcerative colitis, CPI colitis exhibited perturbed stromal metabolism (NAD+, tryptophan) impacting epithelial survival and inflammation. Endothelial cells in CPI colitis after anti-TNF and anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) upregulated the integrin α4ß7 ligand molecular vascular addressin cell adhesion molecule 1 (MAdCAM-1), which may preferentially respond to vedolizumab (anti-α4ß7). CONCLUSIONS: These findings nominate CD4+ RM and MAdCAM-1+ endothelial cells for targeting in specific subsets of CPI colitis patients.


Assuntos
Linfócitos T CD8-Positivos , Colite , Humanos , Células Endoteliais , Inibidores do Fator de Necrose Tumoral , Colite/induzido quimicamente , Colite/tratamento farmacológico , Linfócitos T CD4-Positivos , Esteroides/farmacologia , Esteroides/uso terapêutico , Células Estromais
3.
Theranostics ; 14(6): 2544-2559, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646641

RESUMO

Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin (Ctsk)-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk+ PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk+ PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Diferenciação Celular , Condrócitos , Consolidação da Fratura , Osteogênese , Células-Tronco , Canais de Cátion TRPP , Animais , Consolidação da Fratura/fisiologia , Camundongos , Canais de Cátion TRPP/metabolismo , Canais de Cátion TRPP/genética , Condrócitos/metabolismo , Células-Tronco/metabolismo , Osteogênese/fisiologia , Camundongos Knockout , Condrogênese/fisiologia , Periósteo/metabolismo , Osteoblastos/metabolismo , Osteoblastos/fisiologia , Modelos Animais de Doenças , Masculino
4.
CNS Neurosci Ther ; 30(4): e14696, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38668740

RESUMO

AIMS: Excessive neuroinflammation mediated mainly by microglia plays a crucial role in ischemic stroke. AZD1390, an ataxia telangiectasia mutated (ATM) specific inhibitor, has been shown to promote radio-sensitization and survival in central nervous system malignancies, while the role of AZD1390 in ischemic stroke remains unknown. METHODS: Real-time PCR, western blot, immunofluorescence staining, flow cytometry and enzyme-linked immunosorbent assays were used to assess the activation of microglia and the release of inflammatory cytokines. Behavioral tests were performed to measure neurological deficits. 2,3,5-Triphenyltetrazolium chloride staining was conducted to assess the infarct volume. The activation of NF-κB signaling pathway was explored through immunofluorescence staining, western blot, co-immunoprecipitation and proximity ligation assay. RESULTS: The level of pro-inflammation cytokines and activation of NF-κB signaling pathway was suppressed by AZD1390 in vitro and in vivo. The behavior deficits and infarct size were partially restored with AZD1390 treatment in experimental stroke. AZD1390 restrict ubiquitylation and sumoylation of the essential regulatory subunit of NF-κB (NEMO) in an ATM-dependent and ATM-independent way respectively, which reduced the activation of the NF-κB pathway. CONCLUSION: AZD1390 suppressed NF-κB signaling pathway to alleviate ischemic brain injury in experimental stroke, and attenuated microglia activation and neuroinflammation, which indicated that AZD1390 might be an attractive agent for the treatment of ischemic stroke.


Assuntos
Microglia , Doenças Neuroinflamatórias , Piridinas , Quinolonas , Animais , Microglia/efeitos dos fármacos , Microglia/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Citocinas/metabolismo , Transdução de Sinais/efeitos dos fármacos
5.
Sci Transl Med ; 16(743): eadk5395, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630847

RESUMO

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.


Assuntos
Aprendizado Profundo , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Lesões Pré-Cancerosas , Humanos , Pessoa de Meia-Idade , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Estudos Prospectivos , Lesões Pré-Cancerosas/patologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-38608288

RESUMO

Osteoarthritis (OA), primarily characterized by the deterioration of articular cartilage, is a highly prevalent joint-disabling disease. The pathological onset and progression of OA are closely related to cartilage lubrication dysfunction and synovial inflammation. Synergistic options targeted at restorative lubrication and anti-inflammation are expected to be the most attractive candidates to treat OA and perhaps help prevent it. Herein, a bioinspired lubricant (HA/PA@Lipo) was fabricated by combining anionic hyaluronan-graft-poly(2-acrylamide-2-methylpropanesulfonic acid sodium salt) (HA/PA) with cationic liposomes (Lipo) via electrostatic interaction. HA/PA@Lipo mimicked the lubrication complex located on the outer cartilage surface and was endowed cartilage with excellent cartilage-lubricating performances. After the antioxidant gallic acid (GA) was loaded for dual functionality, HA/PA@Lipo-GA was prepared with added anti-inflammatory properties. HA/PA@Lipo-GA showed favorable biocompatibility with C28/I2 cells, inhibited the production of reactive oxygen, and regulated the expression levels of anabolic genes and proteins. The therapeutic effects of HA/PA@Lipo-GA were evaluated using a sodium iodoacetate-induced OA rat model, and the preventive effects of HA/PA@Lipo-GA were estimated in vivo. The results suggested the robust potential of HA/PA@Lipo-GA with dual functions as a candidate option for OA treatment and prevention.

7.
Cell Death Dis ; 15(4): 271, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632264

RESUMO

Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.


Assuntos
Complicações do Diabetes , Diabetes Mellitus , Exossomos , Células-Tronco Mesenquimais , Humanos , Exossomos/metabolismo , Complicações do Diabetes/metabolismo , Comunicação Celular , Células-Tronco Mesenquimais/metabolismo , Resultado do Tratamento , Diabetes Mellitus/metabolismo
8.
Cell Death Discov ; 10(1): 124, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461159

RESUMO

Pancreatic cancer is a malignant tumor of the digestive system. It is highly aggressive, easily metastasizes, and extremely difficult to treat. This study aimed to analyze the genes that might regulate pancreatic cancer migration to provide an essential basis for the prognostic assessment of pancreatic cancer and individualized treatment. A CRISPR knockout library directed against 915 murine genes was transfected into TB 32047 cell line to screen which gene loss promoted cell migration. Next-generation sequencing and PinAPL.py- analysis was performed to identify candidate genes. We then assessed the effect of serine/threonine kinase 11 (STK11) knockout on pancreatic cancer by wound-healing assay, chick agnosia (CAM) assay, and orthotopic mouse pancreatic cancer model. We performed RNA sequence and Western blotting for mechanistic studies to identify and verify the pathways. After accelerated Transwell migration screening, STK11 was identified as one of the top candidate genes. Further experiments showed that targeted knockout of STK11 promoted the cell migration and increased liver metastasis in mice. Mechanistic analyses revealed that STK11 knockout influences blood vessel morphogenesis and is closely associated with the enhanced expression of phosphodiesterases (PDEs), especially PDE4D, PDE4B, and PDE10A. PDE4 inhibitor Roflumilast inhibited STK11-KO cell migration and tumor size, further demonstrating that PDEs are essential for STK11-deficient cell migration. Our findings support the adoption of therapeutic strategies, including Roflumilast, for patients with STK11-mutated pancreatic cancer in order to improve treatment efficacy and ultimately prolong survival.

9.
Huan Jing Ke Xue ; 45(2): 1090-1097, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471946

RESUMO

A farmland area in Zhaotong City was taken as the research object, and the method of point-to-point collaborative sampling was used to collect farmland soil and vegetables in Zhaotong and test the content of six heavy metals, namely As, Pb, Cu, Zn, Cd, and Cr. The geo-accumulation index and potential ecological risk index were used to evaluate the heavy metal pollution of soil. The health risk model was used to evaluate the risk to the human body imposed by vegetables. The results showed that Cu, Zn, Pb, Cd, and Cr pollution existed in the research area. Compared with the risk screening value of farmland, the over-standard rates were 34.35%, 6.87%, 2.29%, 80.15%, and 6.11%, respectively; Pb, Cd, and Cr were found in vegetables. Compared with the pollutant limit in food, the over-standard rates were 6.87%, 15.27%, and 36.64%, respectively. According to the soil pollution evaluation, Cd in the soil showed a strong ecological risk, and other heavy metals in the soil showed a mild ecological risk. The human health risk evaluation model showed that both non-carcinogenic risk and carcinogenic risk were out of the acceptable range and had a greater influence on children. Correlation analysis showed that As in the soil had an antagonistic effect on Cu and Zn absorption by vegetables, whereas Cr in the soil could promote Cu and Zn absorption by vegetables.


Assuntos
Metais Pesados , Poluentes do Solo , Criança , Humanos , Solo , Fazendas , Verduras , Cádmio , Chumbo , Monitoramento Ambiental/métodos , Poluentes do Solo/análise , Metais Pesados/análise , Poluição Ambiental , Medição de Risco , China
10.
Surg Endosc ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38456946

RESUMO

BACKGROUND: Bile duct leaks (BDLs) are serious complications that occurs after hepatobiliary surgery and trauma, leading to rapid clinical deterioration. Endoscopic retrograde cholangiopancreatography (ERCP) is the first-line treatment for BDLs, but it is not clear which patients will respond to this therapy and which patients will require additional surgical intervention. The aim of our study was to explore the predictors of successful ERCP for BDLs. METHODS: A retrospective analysis was conducted using data from six centers' databases. All consecutive patients who were clinically confirmed as BDLs were included in the study. Collected data were demographics, disease severity, and ERCP procedure characteristics. Univariate and multivariate analysis were used to select independent predictive factors that affect the outcome of ERCP for BDLs, and a nomogram was established. Calibration and ROC curves were used to evaluate the models. RESULTS: Four hundred and forty-eight consecutive patients were clinically confirmed as BDLs and 347 were excluded. In the 101 patients included patients, clinical success was achieved in 78 patients (77.2%). In logistic multivariable regression, two independent factors were negatively associated with the success of ERCP: SIRS (OR, 0.183; 95% CI 0.039-0.864; P = 0.032) and high-grade leak (OR 0.073; 95% CI 0.010-0.539; P = 0.010). Two independent factors were positively associated with the success of ERCP: leak-bridging drainage (OR 4.792; 95% CI 1.08-21.21; P = 0.039) and cystic duct leak (OR 6.193; 95% CI 1.03-37.17; P = 0.046). The prediction model with these four factors was evaluated using a receiver-operating characteristic (ROC) curve, which demonstrated an area under the curve of 0.9351. The calibration curve showed that the model had good predictive accuracy. CONCLUSION: Leak-bridging drainage and cystic duct leak are positive predictors for the success of ERCP, while SIRS and high-grade leak are negative predictors. This prediction model with nomogram has good predictive ability and practical clinical value, and may be helpful in clinical decision-making and prognostication.

11.
Sci Rep ; 14(1): 7179, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531936

RESUMO

In order to improve the accuracy of transformer fault diagnosis and improve the influence of unbalanced samples on the low accuracy of model identification caused by insufficient model training, this paper proposes a transformer fault diagnosis method based on SMOTE and NGO-GBDT. Firstly, the Synthetic Minority Over-sampling Technique (SMOTE) was used to expand the minority samples. Secondly, the non-coding ratio method was used to construct multi-dimensional feature parameters, and the Light Gradient Boosting Machine (LightGBM) feature optimization strategy was introduced to screen the optimal feature subset. Finally, Northern Goshawk Optimization (NGO) algorithm was used to optimize the parameters of Gradient Boosting Decision Tree (GBDT), and then the transformer fault diagnosis was realized. The results show that the proposed method can reduce the misjudgment of minority samples. Compared with other integrated models, the proposed method has high fault identification accuracy, low misjudgment rate and stable performance.

12.
J Tradit Chin Med ; 44(2): 303-314, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38504536

RESUMO

OBJECTIVE: To investigate the impact of Yemazhui (Herba Eupatorii Lindleyani, HEL) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore its underlying mechanism in vivo. METHODS: The chemical constituents of HEL were analyzed by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry method. Then, HEL was found to suppress LPS-induced ALI in vivo. Six-week-old male Sprague-Dawley rats were randomly divided into 6 groups: control, LPS, Dexamethasone (Dex), HEL low dose 6 g/kg (HEL-L), HEL medium dose 18 g/kg (HEL-M) and HEL high dose 54 g/kg (HEL-H) groups. The model rats were intratracheally injected with 3 mg/kg LPS to establish an ALI model. Leukocyte counts, lung wet/dry weight ratio, as well as myeloperoxidase (MPO) activity were determined followed by the detection with hematoxylin and eosin staining, enzyme linked immunosorbent assay, quantitative real time polymerase chain reaction, western blotting, immunohistochemistry, and immunofluorescence. Besides, to explore the effect of HEL on ALI-mediated intestinal flora, we performed 16s rRNA sequencing analysis of intestinal contents. RESULTS: HEL attenuated LPS-induced inflammation in lung tissue and intestinal flora disturbance. Mechanism study indicated that HEL suppressed the lung coefficient and wet/dry weight ratio of LPS-induced ALI in rats, inhibited leukocytes exudation and MPO activity, and improved the pathological injury of lung tissue. In addition, HEL reduced the expression of tumor necrosis factor-alpha, interleukin-1beta (IL-1ß) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid and serum, and inhibited nuclear displacement of nuclear factor kappa-B p65 (NF-κBp65). And 18 g/kg HEL also reduced the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88, NF-κBp65, phosphorylated inhibitor kappa B alpha (phospho-IκBα), nod-like receptor family pyrin domain-containing 3 protein (NLRP3), IL-1ß, and interleukin-18 (IL-18) in lung tissue, and regulated intestinal flora disturbance. CONCLUSIONS: In summary, our findings revealed that HEL has a protective effect on LPS-induced ALI in rats, and its mechanism may be related to inhibiting TLR4/ NF-κB/NLRP3 signaling pathway and improving intestinal flora disturbance.


Assuntos
Lesão Pulmonar Aguda , Microbioma Gastrointestinal , Ratos , Masculino , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Lipopolissacarídeos/efeitos adversos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Domínio Pirina , RNA Ribossômico 16S , Ratos Sprague-Dawley , Transdução de Sinais , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/genética , Pulmão , Interleucina-6
13.
Adv Sci (Weinh) ; : e2308181, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459671

RESUMO

Developing synthetic molecular devices for controlling ion transmembrane transport is a promising research field in supramolecular chemistry. These artificial ion channels provide models to study ion channel diseases and have huge potential for therapeutic applications. Compared with self-assembled ion channels constructed by intermolecular weak interactions between smaller molecules or cyclic compounds, metallacage-based ion channels have well-defined structures and can exist as single components in the phospholipid bilayer. A naphthalene diimide-based artificial chloride ion channel is constructed through efficient subcomponent self-assembly and its selective ion transport activity in large unilamellar vesicles and the planar lipid bilayer membrane by fluorescence and ion-current measurements is investigated. Molecular dynamics simulations and density functional theory calculations show that the metallacage spans the entire phospholipid bilayer as an unimolecular ion transport channel. This channel transports chloride ions across the cell membrane, which disturbs the ion balance of cancer cells and inhibits the growth of cancer cells at low concentrations.

14.
Front Plant Sci ; 15: 1326917, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38516657

RESUMO

Introduction: Endophytes play a significant role in regulating plant root development and facilitating nutrient solubilization and transportation. This association could improve plant growth. The present study has uncovered a distinct phenotype, which we refer to as "white root", arising from the intricate interactions between endophytic fungi and bacteria with the roots in a sugarcane and bamboo fungus (Dictyophora indusiata) intercropping system. Methods: We investigated the mechanisms underlying the formation of this "white root" phenotype and its impact on sugarcane yield and metabolism by metabarcoding and metabolome analysis. Results and Discussion: Initial analysis revealed that intercropping with D. indusiata increased sugarcane yield by enhancing the number of viable tillers compared with bagasse and no input control. Metabarcoding based on second-generation and third-generation sequencing indicated that D. indusiate and Bacillus aryabhattai dominates the fungal and bacterial composition in the "white root" phenotype of sugarcane root. The coexistence of D. indusiata and B. aryabhattai as endophytes induced plant growth-promoting metabolites in the sugarcane root system, such as lysoPC 18:1 and dihydrobenzofuran, probably contributing to increased sugarcane yield. Furthermore, the association also enhanced the metabolism of compounds, such as naringenin-7-O-glucoside (Prunin), naringenin-7-O-neohesperidoside (Naringin)*, hesperetin-7-O-neohesperidoside (Neohesperidin), epicatechin, and aromadendrin (Dihydrokaempferol), involved in flavonoid metabolism during the formation of the endophytic phenotype in the sugarcane root system. These observations suggest that the "white root" phenotype promotes sugarcane growth by activating flavonoid metabolism. This study reports an interesting phenomenon where D. indusiata, coordinate with the specific bacteria invade, forms a "white root" phenotype with sugarcane root. The study also provides new insights into using D. indusiata as a soil inoculant for promoting sugarcane growth and proposes a new approach for improve sugarcane cultivation.

15.
Sci Adv ; 10(12): eadn3544, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517970

RESUMO

The formation of jets in black hole accretion systems is a long-standing problem. It has been proposed that a jet can be formed by extracting the rotation energy of the black hole ("BZ-jet") or the accretion flow ("disk-jet"). While both models can produce collimated relativistic outflows, neither has successfully explained the observed jet morphology. By using general relativistic magnetohydrodynamic simulations and considering nonthermal electrons accelerated by magnetic reconnection that is likely driven by magnetic eruption in the underlying accretion flow, we obtain images by radiative transfer calculations and compared them to millimeter observations of the jet in M87. We find that the BZ-jet originating from a magnetically arrested disk around a high-spin black hole can well reproduce the jet morphology, including its width and limb-brightening feature.

16.
Brain Res ; : 148882, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38521160

RESUMO

Ferroptosis is a newly identified form of non-apoptotic regulated cell death (RCD) andplaysanimportantrole in epileptogenesis. The p38 mitogen-activated protein kinase (p38 MAPK) pathway has been confirmed to be involved in ferroptosis. The mitochondria-targeting antioxidant Elamipretide (SS-31) can reduce the generation of lipid peroxidation and the buildup of reactive oxygen species (ROS). Collectively, our present study was to decipher whether SS-31 inhibits ferroptosis via the p38 MAPK signaling pathway in the rat epilepsy model induced by pilocarpine (PILO).Adult male Wistar rats were randomly divided into four groups: control group (CON group), epilepsy group (EP group), SS-31 treatment group (SS group), and p38 MAPK inhibitor (SB203580) treatment group (SB group). Our results demonstrated that the rat hippocampal neurons after epilepsy were followed by accumulated iron and malondialdehyde (MDA) content, upregulated phosphorylated p38 MAPK protein (P-p38) and nuclear factor erythroid 2-related factor 2 (Nrf2) levels, reduced glutathione peroxidase 4 (Gpx4) content, and depleted glutathione (GSH) activity. Morphologically, mitochondrial ultrastructural damage under electron microscopy was manifested by a partial increase in outer membrane density, disappearance of mitochondrial cristae, and mitochondrial shrinkage. SS-31 and SB203580 treatment blocked the initiation and progression of ferroptosis in the hippocampus of epileptic rats via reducing the severity of epileptic seizures, reversing the expression of Gpx4, P-p38 and Nrf2, decreasing the levels of iron and MDA, as well as increasing the activity of GSH. To summarize, our findings proved that ferroptosis was coupled with the pathology of epilepsy, and SS-31 can inhibit PILO-induced seizures by preventing ferroptosis, which may be connected to the inhibition of p38 MAPK phosphorylation, highlighting the potential therapeutic value for targeting ferroptosis process in individuals with seizure-related diseases.

17.
ACS Nano ; 18(11): 8496-8510, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38456818

RESUMO

Designing three-dimensional (3D) porous carbonaceous skeletons for K metal is one of the most promising strategies to inhibit dendrite growth and enhance the cycle life of potassium metal batteries. However, the nucleation and growth mechanism of K metal on 3D skeletons remains ambiguous, and the rational design of suitable K hosts still presents a significant challenge. In this study, the relationships between the binding energy of skeletons toward K and the nucleation and growth of K are systematically studied. It is found that a high binding energy can effectively decrease the nucleation barrier, reduce nucleation volume, and prevent dendrite growth, which is applied to guide the design of 3D current collectors. Density functional theory calculations show that P-doped carbon (P-carbon) exhibits the highest binding energy toward K compared to other elements (e.g., N, O). As a result, the K@P-PMCFs (P-binding porous multichannel carbon nanofibers) symmetric cell demonstrates an excellent cycle stability of 2100 h with an overpotential of 85 mV in carbonate electrolytes. Similarly, the perylene-3,4,9,10-tetracarboxylic dianhydride || K@P-PMCFs cell achieves ultralong cycle stability (85% capacity retention after 1000 cycles). This work provides a valuable reference for the rational design of 3D current collectors.

18.
J Colloid Interface Sci ; 662: 377-390, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359502

RESUMO

Developing highly efficient photocatalysts based on conjugated microporous polymers (CMPs) are often impeded by the intrinsically large exciton binding energy and sluggish charge transfer kinetics that result from their vulnerable driving force. Herein, a family of pyrene-based nitrogen-implanted CMPs were constructed, where the nitrogen gradient was regulated. Accordingly, the built-in electric field endowed by the nitrogen gradient dramatically accelerates the dissociation of exciton into free carriers, thereby enhancing charge separation efficiency. As a result, PyCMP-3N generated by polymerization of 1,3,6,8-tetrakis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrene and 2,4,6-tris(4-bromophenyl)-1,3,5-triazine featured an optimized built-in electric field and exhibited the highest photocatalytic removal efficiency of uranium (VI) (99.5 %). Our proposed strategy not only provides inspiration for constructing the built-in electric field by controlling nitrogen concentration gradients, but also offers an in-depth understanding the crucial role of built-in electric field in exciton dissociation and charge transfer, efficiently promoting CMPs photocatalysis.

19.
Virus Res ; 342: 199336, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342315

RESUMO

Enterovirus 71 (EV71) is the common causative agent of hand-foot-mouth disease (HFMD). Despite evidence in mice model suggested that the interferon (IFN) signaling pathways play a role in defending against this virus, knowledge on the IFN-mediated antiviral response is still limited. Here we identified an IFN-stimulated gene (ISG) called L3HYPDH, whose expression inhibits EV71 replication. Mapping assay indicated that amino acids 61-120 and 295-354 are critical for its optimal antiviral activity. Mechanismly, L3HYPDH specifically inhibits protein translation mediated by EV71 internal ribosome entry site (IRES). Our data thus uncovered a new mechanism utilized by the host cell to restrict EV71 replication.


Assuntos
Doença de Mão, Pé e Boca , Interferons , Animais , Camundongos , RNA , Aminoácidos , Antivirais
20.
Angew Chem Int Ed Engl ; 63(18): e202403149, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38421194

RESUMO

Expanded azahelicenes, as heteroanalogues of helically chiral helicenes, hold significant potential for chiroptical materials. Nevertheless, their investigation and research have remained largely unexplored. Herein, we present the facile synthesis of a series of expanded azahelicenes NHn (n=1-5) consisting of 11, 19, 27, 35, and 43 fused rings, mainly by Suzuki coupling followed by Bi(OTf)3-mediated cyclization of vinyl ethers. The structures of NH2, NH3 and NH4 were confirmed through X-ray crystallography analysis, and their (P)- and (M)- enantiomers were also isolated with chiral high performance liquid chromatography. The enantiomers exhibit large absorption (abs) and luminescence (lum) dissymmetry factors, with |gabs|max=0.044; |glum|max=0.003 for NH2, |gabs|max=0.048; |glum|=0.014 for NH3, and |gabs|max=0.043; |glum|max=0.021 for NH4, which are superior to their respective all-carbon analogues.

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