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Fungal corneal ulcer is one of the leading causes of corneal blindness in developing countries. Corneal scars such as leukoplakia are formed due to inflammation, oxidative stress and non-directed repair, which seriously affect the patients' subsequent visual and life quality. In this study, drawing inspiration from the oriented structure of collagen fibers within the corneal stroma, we first proposed the directional arrangement of CuTA-CMHT hydrogel system at micro and macro scales based on the 3D printing extrusion method combined with secondary patterning. It played an antifungal role and induced oriented repair in therapy of fungal corneal ulcer. The results showed that it effectively inhibited Candida albicans, Aspergillus Niger, Fusarium sapropelum, which mainly affects TNF, NF-kappa B, and HIF-1 signaling pathways, achieving effective antifungal functions. More importantly, the fibroblasts interacted with extracellular matrix (ECM) of corneal stroma through formation of focal adhesions, promoted the proliferation and directional migration of cells in vitro, induced the directional alignment of collagen fibers and corneal stromal orthogonally oriented repair in vivo. This process is mainly associated with MYLK, MYL9, and ITGA3 molecules. Furthermore, the downregulation the growth factors TGF-ß and PDGF-ß inhibits myofibroblast development and reduces scar-type ECM production, thereby reducing corneal leukoplakia. It also activates the PI3K-AKT signaling pathway, promoting corneal healing. In conclusion, the oriented CuTA-CMHT hydrogel system mimics the orthogonal arrangement of collagen fibers, inhibits inflammation, eliminates reactive oxygen species, and reduces corneal leukoplakia, which is of great significance in the treatment of fungal corneal ulcer and is expected to write a new chapter in corneal tissue engineering.
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BACKGROUND: The unique size, physical and chemical properties, and ultra-high stability of nanozymes have attracted extensive attentions in sensing, but improvement of catalytic activity of the nanozymes is still an urgent issue. Given the ultra-high simulated enzyme activity of metal nanoparticles and the advantage of multi-enzyme catalysis, an Au-decorated MoS2 nanosheets (MoS2/Au NS) integrating the double peroxidase-like (POD) activity is developed. RESULTS: By optimizing and adjusting the density of AuNPs, as well as its morphology and other parameters, a monodisperse and high-density distribution of AuNPs on MoS2 nanosheets was obtained, which can greatly improve the POD-like activity of MoS2/Au NS. Nafion solution was applied to assist the modification of MoS2/Au NS on the electrode surface so as to improved its stability. An electrochemical H2O2 detection platform was constructed by modifying MoS2/Au NS nanozyme on the SPCE using the conductive Nafion solution. And the negatively charged sulfonic acid group can eliminate negatively charged electroactive substances to improve the specificity. Then ascorbic acid was used to stimulate tumor cells to produce H2O2 as therapeutic model, an ultrasensitive chronocoulometry detection for H2O2 in cell lysate was established. The logarithmically of ΔQ and the logarithmically of H2O2 concentration showed a good linear relationship between 1 µM and 500 mM, with a LOD value of 0.3 µM. SIGNIFICANCE: The developed H2O2 sensor has excellent stability, reproducibility (RSD = 2.3 %, n = 6) and selectivity, realized the quantitative detection of H2O2 in cell lysate. Compared with commercial fluorescence detection kits for H2O2 in cell lysate, it is worth mentioning that the electrochemical H2O2 sensor developed in this study is simpler and faster, with higher sensitivity and lower cost. This provides a potential substitute for disease diagnosis and treatment evaluation based on accurate detection of H2O2.
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Antineoplásicos , Dissulfetos , Técnicas Eletroquímicas , Ouro , Peróxido de Hidrogênio , Nanopartículas Metálicas , Molibdênio , Ouro/química , Molibdênio/química , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/química , Dissulfetos/química , Nanopartículas Metálicas/química , Técnicas Eletroquímicas/métodos , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/análise , Nanoestruturas/química , Limite de Detecção , Peroxidase/química , Peroxidase/metabolismo , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
BACKGROUND: This study investigates the potential of novel meniscal parameters as predictive factors for incident radiographic knee osteoarthritis (ROA) over a span of four years, as part of the Osteoarthritis Initiative (OAI) study. OBJECTIVES: Quantitative measurements of meniscal parameters alteration could serve as predictors of OA's occurrence and progression. METHODS AND MATERIALS: A nested matched case-control study design was used to select participants from OAI study. Case knees (n = 178) were defined as those with incident ROA (Kellgren Lawrence Grade (KLG) 0 or 1 at baseline (BL), evolving into KLG 2 or above by year 4). Control knees were matched one-to-one by sex, age and radiographic status with case knees. The mean distance from medial-to-lateral meniscal lesions [Mean(MLD)], mean value of tibial plateau width [Mean(TPW)] and the mean of the relative percentage of the medial-to-lateral meniscal lesions distance [Mean(RMLD)] were evaluated through coronal T2-weighted turbo spin echo (TSE) MRI at P-0 (visit when incident ROA was found on radiograph), P-1(one year prior to P-0) and baseline, respectively. Using the imaging data of one patient, the mechanism was investigated by finite element analysis. RESULTS: Participants were on average 60.22 years old, predominantly female (66.7%) and overweight (mean BMI: 28.15). Mean(MLD) and Mean(RMLD) were significantly greater for incident knees compared to no incident knees at baseline, P-1 and P-0. [Mean(MLD), Mean(RMLD); (42.56-49.73) mean ± (7.70-9.52) mm SD vs. (38.14-40.78) mean ± (5.51-7.05)mm SD; (58.61-68.95) mean ± (8.52-11.40) mm SD vs. (52.52-56.35) mean ± (6.53-7.85)mm SD, respectively]. Baseline Mean(MLD) and Mean(RMLD), [Adjusted OR, 95%CI: 1.11(1.07 to 1.16) and 1.13(1.09 to 1.17), respectively], were associated with incident ROA during 4 years, However, Mean(TPW) [Adjusted OR, 95%CI: 0.98(0.94 to 1.02)] was not associated with incident ROA during 4 years. While Mean(TPW) at P-1 and P-0 was not associated with the risk of incident ROA, Mean(MLD) and Mean(RMLD) at P-1 and P-0 were significantly positively associated with the risk of incident ROA. CONCLUSIONS: The meniscal parameters alteration could be an important imaging biomarker to predict the occurrence of ROA.
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Imageamento por Ressonância Magnética , Meniscos Tibiais , Osteoartrite do Joelho , Radiografia , Humanos , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estudos de Casos e Controles , Meniscos Tibiais/diagnóstico por imagem , Meniscos Tibiais/patologia , Valor Preditivo dos Testes , Incidência , Progressão da Doença , Lesões do Menisco Tibial/diagnóstico por imagem , Lesões do Menisco Tibial/epidemiologiaRESUMO
Background: The objective of this study was to explore the genetic etiology and propose a genetic diagnosis and counseling strategy for children with retinoblastoma (RB) and global developmental delay (GDD). Case presentation: We report on a 2 years and 4 months old boy with binocular retinoblastoma and global developmental delay (included intellectual disability, language development delay, motor development delay, etc.). Genomic DNA was extracted from peripheral blood mononuclear cells isolated from the proband and his parents. Whole exome sequencing (WES) was carried out for the proband and his parents to identify genetic etiology, which was subsequently verified by quantitative polymerase chain reaction (qPCR).The WES revealed a gross heterozygous deletion in the RB transcriptional corepressor 1 (RB1, OMIM:614041) gene, including exon 7-8, in the affected proband but not in his parents. Additionally, two pathogenic copy number variations (CNVs) were identified: a duplication at 7q11.23 and a microdeletion at 16p11.2-p12.2, respectively. Furthermore, the genomic qPCR analysis demonstrated a 50% reduction in the copy numbers of exon 7 and exon 8 in the RB1 gene of the proband, as compared to those detected in his parents. Simultaneous variants in the RB1 gene and two pathogenic CNVs can precisely explain the genetic etiology of the proband. Conclusion: The present study firstly reports a novel gross deletion variant of the RB1 gene coexisting with two pathogenic CNVs in a pediatric patient with retinoblastoma and comorbid global developmental delay in China. Additionally, our findings strongly support the use of WES in pediatric patients with RB comorbid GDD, and WES is recommended as the first-tier test.
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OBJECTIVES: Hemoperfusion (HP) is used to treat various diseases, including sepsis and acute respiratory distress syndrome. However, few studies have explored the efficiency of HP in dermatomyositis-associated acute exacerbation of interstitial lung disease. METHODS: We conducted a retrospective study. Two hundred and sixteen patients with dermatomyositis-associated acute exacerbation of interstitial lung disease were included. Patients were divided into the HP group (treatment group) and the control group. Changes in oxygenation, hemodynamic parameters, lung ultrasound scores, and inflammatory cytokine levels were evaluated before and after HP in the treatment group. The length of intensive care unit (ICU) stays, duration of ventilator therapy, mortality rate, and incidence of complications were compared between the treatment and control groups. RESULTS: Hemodynamic and oxygenation variables in the treatment group significantly improved after treatment. However, the levels of the inflammatory factors significantly decreased after treatment. The length of ICU stay and the duration of ventilator therapy were significantly shorter in the treatment group than in the control group. The mortality rate of the treatment group was significantly lower than that of the control group. CONCLUSION: This study demonstrated that HP could improve treatment efficacy in patients with dermatomyositis-associated acute exacerbation of interstitial lung disease.
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Bacillus cereus is a well-known foodborne pathogen that can cause human diseases, including vomiting caused by emetic toxin, cereulide, requiring 105-108 cells per gram to cause the disease. The bacterial cells may be eliminated during processing, but cereulide can survive in most processing techniques due to its resistance to high temperatures, extreme pH and proteolytic enzymes. Herein, we reported dynamic processes of biofilm formation of four different types and cereulide production within the biofilm. Confocal laser scanning microscopy (CLSM) images revealed that biofilms of the four different types reach each stage at different time points. Among the extracellular polymeric substances (EPS) components of the four biofilms formed by the emetic B. cereus F4810/72 strain, proteins account for the majority. In addition, there are significant differences (p < 0.05) in the EPS components at the same stage among biofilms of different types. The time point at which cereulide was first detected in the four types of biofilms was 24 h. In the biofilm of B. cereus formed in ultra-high-temperature (UHT) milk, the first peak of cereulide appeared at 72 h. The cereulide content of the biofilms formed in BHI was mostly higher than that of the biofilms formed in UHT milk. This study contributes to a better understanding of food safety issues in the industry caused by biofilm and cereulide toxin produced by B. cereus.
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Bacillus cereus , Biofilmes , Depsipeptídeos , Microbiologia de Alimentos , Bacillus cereus/metabolismo , Bacillus cereus/fisiologia , Biofilmes/crescimento & desenvolvimento , Depsipeptídeos/metabolismo , Microscopia Confocal , Animais , Leite/microbiologia , Temperatura Alta , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Doenças Transmitidas por Alimentos/microbiologia , Manipulação de Alimentos/métodosRESUMO
This study aimed to develop a prognostic risk model based on immune-related long non-coding RNAs (lncRNAs). By analyzing the expression profiles of specific long non-coding RNAs, the objective was to construct a predictive model to accurately assess the survival prognosis of breast cancer (BC) patients. This effort seeks to provide personalized treatment strategies for patients and improve clinical outcomes. Based on the median risk value, 300 samples of triple-negative BC (TNBC) patients were rolled into a high-risk group (HR group, n = 140) and a low-risk group (LR group, n = 160). Multivariate Cox (MVC) analysis was performed by combining the patient risk score and clinical information to evaluate the prognostic value of the prognostic risk (PR) model. A total of 371 immune-related lncRNAs associated with the prognosis of TNBC were obtained from 300 TNBC samples. Nine associated with prognosis were obtained by univariate Cox (UVC) analysis, and 3 (AC090181.2, LINC01235, and LINC01943) were selected by MVC analysis for the construction of TNBC PR model. Survival analysis showed a great difference in TNBC patients in different groups (P < 0.001). The receiver operator characteristic (ROC) curve showed the model possessed a good area under ROC curve (AUC), which was 0.928. The patient RS jointing with clinical information as well as the MVC analysis revealed that RS was an independent risk factor (IRF) for prognosis of TNBC (P < 0.05, HR = 1.033286). Therefore, the lncRNAs associated with TNBC immunity can be screened by bioinformatics analysis, and the established PR model of TNBC could better predict the prognosis of patients with TNBC, exhibiting a high application value in clinic.
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RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Feminino , Prognóstico , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/imunologia , Regulação Neoplásica da Expressão Gênica , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/imunologia , Medição de Risco/métodos , Curva ROC , Perfilação da Expressão Gênica , Análise de Sobrevida , Fatores de RiscoRESUMO
The effect of circumference and displacement of the third fracture fragment on fracture healing after intramedullary nailing of femoral shaft fractures with a third fracture fragment was investigated. A retrospective cohort study was conducted to analyze the data of 142 patients who suffered femoral shaft fractures with a third fracture fragment and were admitted to the First People's Hospital of Lianyungang from February 2016 to December 2021. According to the circumference of the third fracture fragments, these were divided into three types of type 1: 71 cases; type 2: 52 cases; and type 3: 19 cases. On the basis of the diaphyseal diameter, the degree of displacement of the third fracture fragment was classified into three degrees of degree I: 95 cases; degree II: 31 cases; and degree III: 16 cases. Postoperative follow-up was performed to compare the fracture healing rate, healing time, and the modified Radiographic Union Scale for Tibia (mRUST) at 9th month after surgery in each group. All 142 patients were followed up after operation, with an average of (14.7 ± 4.1) months, and the overall healing rate was 73.4%. When the third fracture fragments were displaced in degree II and III, the mRUST score at 9th month in the type 1 group was higher than that in the type 2 and 3 groups (P = 0.017). Logistic regression analysis showed that greater displacement of third fracture fragments and greater circumference were associated with lower fracture healing rates (P < 0.05). After intramedullary nailing of femoral fractures, the degree of third fragment displacement and circumference affect fracture healing, and the former has a greater impact. When the third fracture fragment is displaced to degree II or III and its circumference is type 2 or type 3, it significantly affects the fracture healing. Intraoperative intervention to reduce the distance of third displacement of the fragment is required to reduce the incidence of non-union.
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Fraturas do Fêmur , Fixação Intramedular de Fraturas , Consolidação da Fratura , Humanos , Fixação Intramedular de Fraturas/métodos , Fixação Intramedular de Fraturas/efeitos adversos , Fraturas do Fêmur/cirurgia , Masculino , Feminino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Fêmur/cirurgia , Resultado do Tratamento , IdosoRESUMO
Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease. Currently, no specific treatment strategy has been established; therefore, finding new treatment methods is essential. Clinically, Shenqi Huatan Decoction (SQHT) is a traditional Chinese medicinal formula for COPD treatment; however, its mechanism of action in treatment needs to be clarified. Methods: The COPD rat model was replicated by cigarette smoking and tracheal injection using the LPS method. The control group and the SQHT groups were treated with dexamethasone and SQHT by gavage, respectively. After treatment, superoxide dismutase (SOD) serum levels, total antioxidant capacity (TAOC), lipid peroxidation, and malondialdehyde (MDA) were detected by enzyme-linked immunosorbent assay (ELISA). Activated protein kinase alpha (AMPK-α), forkhead transcription factor O3a (FOXO3a), manganese SOD (MnSOD), and peroxisome proliferator-activated receptor gamma (PPARγ) were detected using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and Western blot. Microribonucleic acid and protein expression levels were measured, and pathological changes in lung tissue were observed using hematoxylin and eosin staining. Results: The pathological findings suggested that SQHT substantially affects COPD treatment by enhancing alveolar fusion and reducing emphysema. ELISA results showed that SQHT could lower the blood levels of MDA and lipid peroxide and raise SOD and TAOC levels, suggesting that it could lessen oxidative stress. In the lung tissue of rats with COPD, large doses of SQHT intervention dramatically increased AMPK protein expression, AMPK-α, FOXO3a, MnSOD, and PPARγ, indicating that SQHT may reduce oxidative stress by activating the PPARγ-mediated AMPK/FOXO3a signaling pathway. Similar results were obtained using RT-qPCR. Conclusion: SQHT is effective for COPD treatment. The mechanism of action may be related to the activation of the PPARγ-mediated AMPK/FOXO3a signaling pathway to improve oxidative stress in lung tissue.
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Medicamentos de Ervas Chinesas , Estresse Oxidativo , PPAR gama , Doença Pulmonar Obstrutiva Crônica , Ratos Sprague-Dawley , Transdução de Sinais , Animais , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Ratos , PPAR gama/metabolismo , PPAR gama/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Masculino , Proteína Forkhead Box O3/metabolismo , Modelos Animais de Doenças , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Superóxido Dismutase/efeitos dos fármacosRESUMO
This study utilized a prospective, large-sample, multi-center, and registered key specialty approach of hospitals to monitor the application of Reduning Injection. A total of 100 249 adolescent patients aged 14 years and below who received Reduning Injection were monitored, resulting in 83 cases of adverse events, with 76 of them being classified as adverse drug reaction(ADR). The calculated incidence rate of ADR for Reduning Injection was 0.076%, indicating a very rare ADR. The main symptoms of ADR were pruritus, diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsion, and chills. All ADR cases were reported for the first time, including three new ADR cases and 73 known ADR cases. The categories of ADR was general ADR. All ADR was mild in severity. There were more males than females in ADR patients. One patient had a history of ADR, and the drug causing ADR was buprofen. The largest number of ADR cases occurred when the dosage of Reduning injection was 5-10 mL. The dropping speed was 30 drops or less per min, and the solvent type was 5% glucose injection. The most common manifestation of ADR patients was pruritus, followed by diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsions, and chills. 72 patients(94.74% of ADR patients) discontinued the drug, and three patients(3.95% of ADR patients) were given oxygen inhalation. 47 cases(61.84% of ADR patients) were treated with medication, of which dexamethasone was the most used(24 cases, 46.15% of ADR patients). 76 ADR patients were cured or improved. ADRs are more likely to occur when diagnosed with acute bronchitis by western medicine and cough by traditional Chinese medicine(TCM), TCM syndrome type is wind heat syndrome, and the combination medicine is ambroxol hydrochloride and bromhexine hydrochloride injection, ascorbic acid/vitamin C injection. This result provides an evidence-based safety basis for active pharmacovigilance of Reduning Injection in adolescents aged 14 years and below.
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Medicamentos de Ervas Chinesas , Humanos , Feminino , Masculino , Adolescente , Criança , Estudos Prospectivos , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Pré-Escolar , Lactente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Hospitais , InjeçõesRESUMO
Uncontrollable growth of Zn dendrites, irreversible dissolution of cathode material and solidification of aqueous electrolyte at low temperatures severely restrict the development of aqueous Zn-ion batteries. In this work, 2,2,2-trifluoroethanol (TFEA) with a volume fraction of 50% as a highly compatible polar-solvent is introduced to 1.3 M Zn(CF3SO3)2 aqueous electrolyte, achieving stable high-performance Zn-ion batteries. Massive theoretical calculations and characterization analysis demonstrate that TFEA weakens the tip effect of Zn anode and restrains the growth of Zn dendrites due to electrostatic adsorption and coordinate with H2O to disrupt the hydrogen bonding network in water. Furthermore, TFEA increases the wettability of the cathode and alleviates the dissolution of V2O5, thus improving the capacity of the full battery. Based on those positive effects of TFEA on Zn anode, V2O5 cathode, and aqueous electrolyte, the Zn//Zn symmetric cell delivers a long cycle-life of 782 h at 5 mA cm-2 and 2 mA h cm-2. The full battery still declares an initial capacity of 116.78 mA h g-1, and persists 87.73% capacity in 2000 cycles at -25 °C. This work presents an effective strategy for fully compatible co-solvent to promote the stability of Zn anode, V2O5 cathode and aqueous electrolyte for high-performance Zn-ion batteries.
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Infections and neurodegenerative diseases induce neuroinflammation, but affected individuals often show nonneural symptoms including muscle pain and muscle fatigue. The molecular pathways by which neuroinflammation causes pathologies outside the central nervous system (CNS) are poorly understood. We developed multiple models to investigate the impact of CNS stressors on motor function and found that Escherichia coli infections and SARS-CoV-2 protein expression caused reactive oxygen species (ROS) to accumulate in the brain. ROS induced expression of the cytokine Unpaired 3 (Upd3) in Drosophila and its ortholog, IL-6, in mice. CNS-derived Upd3/IL-6 activated the JAK-STAT pathway in skeletal muscle, which caused muscle mitochondrial dysfunction and impaired motor function. We observed similar phenotypes after expressing toxic amyloid-ß (Aß42) in the CNS. Infection and chronic disease therefore activate a systemic brain-muscle signaling axis in which CNS-derived cytokines bypass the connectome and directly regulate muscle physiology, highlighting IL-6 as a therapeutic target to treat disease-associated muscle dysfunction.
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Encéfalo , COVID-19 , Músculo Esquelético , Transdução de Sinais , Animais , Encéfalo/imunologia , Encéfalo/metabolismo , Transdução de Sinais/imunologia , Camundongos , Músculo Esquelético/imunologia , Músculo Esquelético/metabolismo , COVID-19/imunologia , Doença Crônica , Interleucina-6/metabolismo , Interleucina-6/imunologia , Infecções por Escherichia coli/imunologia , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/imunologia , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/imunologia , Proteínas de Drosophila/genética , SARS-CoV-2/imunologia , Drosophila melanogaster/imunologia , Peptídeos beta-Amiloides/metabolismo , Humanos , Camundongos Endogâmicos C57BLRESUMO
The main challenges faced by aqueous rechargeable nickel-zinc batteries are their comparatively low energy density and poor cycling stability. Moreover, the preparation procedures of these cathodes are complex and not easily scalable. Herein, we utilized MXene to improve the electrodeposition preparation of NiCo layered double hydroxides (LDH). Benefiting from the improved interfacial contact between nickel foam (NF) and platting solution and the enhanced ionic conductivity of platting product based on MXene additives, the resulting binder-free NiCo LDH electrode can achieve ultrahigh areal loading (~65 mg cm-2) with abundant active surface for redox reactions and maintained short transport pathway for ion diffusion and charge transfer. Furthermore, the as-fabricated alkaline NiCo LDH-based battery delivers high discharge capacity, up to 20.2 mAh cm-2 (311 mAh g-1), accompanied by remarkable rate performance (9.6 mAh cm-2 or 148 mAh g-1 at 120 mA cm-2). Due to the high structural and chemical stability of MXenes/LDH-based electrode, excellent cycling life can also be achieved with 88.6% capacity retention after 10000 cycles. In addition, ultrahigh areal energy density (31.2 mWh cm-2) and gravimetric energy density (465 Wh kg-1) can be simultaneously achieved. This work has inspired the design of advanced cathode materials to develop high-performance aqueous zinc batteries.
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α-Amanitin and ß-amanitin, two of the most toxic amatoxin compounds, typically coexist in the majority of Amanita mushrooms. The aim of this study was to use a newly developed ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method to determine the toxicokinetics and tissue distribution of α- and ß-amanitin following single or combined oral (po) administration in mice. α-Amanitin and ß-amanitin administered at 2 or 10 mg/kg doses showed similar toxicokinetic profiles, except for peak concentration (Cmax). The elimination half-life (t1/2) values of α-amanitin and ß-amanitin in mice were 2.4-2.8 h and 2.5-2.7 h, respectively. Both α- and ß-amanitin were rapidly absorbed into the body, with times to reach peak concentration (Tmax) between 1.0 and 1.5 h. Following single oral administration at 10 mg/kg, the Cmax was significantly lower for α-amanitin (91.1 µg/L) than for ß-amanitin (143.1 µg/L) (p < 0.05). The toxicokinetic parameters of α-amanitin, such as t1/2, mean residence time (MRT), and volume of distribution (Vz/F) and of ß-amanitin, such as Vz/F, were significantly different (p < 0.05) when combined administration was compared to single administration. Tissues collected at 24 h after po administration revealed decreasing tissue distributions for α- and ß-amanitin of intestine > stomach > kidney > lung > spleen > liver > heart. The substantial distribution of toxins in the kidney corresponds to the known target organs of amatoxin poisoning. The content in the stomach, liver, and kidney was significantly higher for of ß-amanitin than for α-amanitin at 24 h following oral administration of a 10 mg/kg dose. No significant difference was detected in the tissue distribution of either amatoxin following single or combined administration. After po administration, both amatoxins were primarily excreted through the feces. Our data suggest the possibility of differences in the toxicokinetics in patients poisoned by mushrooms containing both α- and ß-amanitin than containing a single amatoxin. Continuous monitoring of toxin concentrations in patients' blood and urine samples is necessary in clinical practice.
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Alfa-Amanitina , Amanitinas , Toxicocinética , Animais , Alfa-Amanitina/farmacocinética , Alfa-Amanitina/toxicidade , Amanitinas/farmacocinética , Amanitinas/toxicidade , Camundongos , Distribuição Tecidual , Administração Oral , Espectrometria de Massas em Tandem , Masculino , Meia-Vida , Cromatografia Líquida de Alta PressãoRESUMO
Antiphospholipid syndrome (APS) is an autoimmune disease with arteriovenous thrombosis and recurrent miscarriages as the main clinical manifestations. Due to the complexity of its mechanisms and the diversity of its manifestations, its diagnosis and treatment remain challenging issues. Antiphospholipid antibodies (aPL) not only serve as crucial "biomarkers" in diagnosing APS but also act as the "culprits" of the disease. Endothelial cells (ECs), as one of the core target cells of aPL, bridge the gap between the molecular level of these antibodies and the tissue and organ level of pathological changes. A more in-depth exploration of the relationship between ECs and the pathogenesis of APS holds the potential for significant advancements in the precise diagnosis, classification, and therapy of APS. Many researchers have highlighted the vital involvement of ECs in APS and the underlying mechanisms governing their functionality. Through extensive in vitro and in vivo experiments, they have identified multiple aPL receptors on the EC membrane and various intracellular pathways. This article furnishes a comprehensive overview and summary of these receptors and signaling pathways, offering prospective targets for APS therapy.
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Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Células Endoteliais , Síndrome Antifosfolipídica/imunologia , Humanos , Anticorpos Antifosfolipídeos/imunologia , Células Endoteliais/imunologia , Células Endoteliais/metabolismo , Animais , Transdução de Sinais , BiomarcadoresRESUMO
Due to the limited maximum output power of the pulsers based on avalanche transistors, high-power ultrawideband (UWB) radiation systems usually synthesize plenty of modules simultaneously to achieve a high peak effective potential (rEp). However, this would lead to an increased aperture size as well as a narrower beam, which would limit their applications in intentional electromagnetic interference fields. In this paper, a high-power UWB radiation system with beam broadening capacity is developed. To achieve beam broadening in the time domain, a power-law time delay distribution method is proposed and studied by simulation, and then the relative excitation time delays of the modules are optimized to achieve higher rEp and avoid beam splitting in the beam broadening mode. In order to avoid false triggering of the pulser elements when implementing the beam broadening, the mutual coupling effect in the system is analyzed and suppressed by employing onboard high-pass filters, since the mutual coupling effect is much more severe in the low-frequency range. Finally, a radiation system with 36 modules is developed. Measuring results indicate that in the high-rEp mode, the developed system could achieve a maximum effective potential rEp of 313.6 kV and a maximum pulse-repetition-rate of 20 kHz. In the beam broadening mode, its half-peak-power beam width in the H-plane is broadened from the original value of 3.9° to 7.9°, with a maximum rEp of 272.9 kV. The polarization direction of the system could be flexibly adjusted by a built-in motor.
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Flexible photodetectors have attracted escalating attention due to their pivotal role in next-generation wearable optoelectronic devices. This work presents high-performance photodetector devices based on CdTe/MoS2 heterojunctions, showcasing outstanding photodetecting and distinctive mechanical properties. The MoS2 film was exfoliated from bulk layered MoS2 and covered by a sputtered ultrathin CdTe film (â¼8.4 nm) to form a heterojunction. Benefitting from the photovoltaic effect induced by the built-in electrical field near the high-quality interface, the fabricated CdTe/MoS2 heterojunction photodetector can operate as a self-powered photodetector without any external bias voltage, especially showing a high photodetectivity of 5.84 × 1011 Jones, remarkable photoresponsivity of 270.3 mA W-1, fast photoresponse with a rise/fall time of â¼44.8/134.2 µs and excellent bending durability. These results demonstrate that the CdTe/MoS2 heterojunctions could have significant potential for future applications in optoelectronic devices.
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Development of luminescent segmented heterostructures featuring multiple spatial-responsive blocks is important to achieve miniaturized photonic barcodes toward anti-counterfeit applications. Unfortunately, dynamic manipulation of the spatial color at micro/nanoscale still remains a formidable challenge. Here, a straightforward strategy is proposed to construct spatially varied heterostructures through amplifying the conformation-driven response in flexible lanthanide-metal-organic frameworks (Ln-MOFs), where the thermally induced minor conformational changes in organic donors dramatically modulate the photoluminescence of Ln acceptors. Notably, compositionally and structurally distinct heterostructures (1D and 2D) are further constructed through epitaxial growth of multiple responsive MOF blocks benefiting from the isomorphous Ln-MOF structures. The thermally controlled emissive colors with distinguishable spectra carry the fingerprint information of a specific heterostructure, thus allowing for the effective construction of smart photonic barcodes with spatially responsive characteristics. The results will deepen the understanding of the conformation-driven responsive mechanism and also provide guidance to fabricate complex stimuli-responsive hierarchical microstructures for advanced optical recording and high-security labels.
RESUMO
Although titanium alloy is the most widely used endoplant material in orthopedics, the material is bioinert and good bone integration is difficult to achieve. Zoledronic acid (ZOL) has been shown to locally inhibit osteoclast formation and prevent osteoporosis, but excessive concentrations of ZOL exert an inhibitory effect on osteoblasts; therefore, stable and controlled local release of ZOL may reshape bone balance and promote bone regeneration. To promote the adhesion of osteoblasts to many polar groups, researchers have applied gelatine methacryloyl (Gelma) combined with polyacrylamide hydrogel (PAAM), which significantly increased the hydrogen bonding force between the samples and improved the stability of the coating and drug release. A series of experiments demonstrated that the Gelma/PAAM-ZOL bioactive coating on the surface of the titanium alloy was successfully prepared. The coating can induce osteoclast apoptosis, promote osteoblast proliferation and differentiation, achieve dual regulation of bone regeneration, successfully disrupt the balance of bone remodelling and promote bone tissue regeneration. Additionally, the coating improves the metal biological inertness on the surface of titanium alloys and improves the bone integration of the scaffold, offering a new strategy for bone tissue engineering to promote bone technology.
RESUMO
Endoscopy, enabling high-resolution imaging of deep tissues and internal organs, plays an important role in basic research and clinical practice. Recent advances in photoacoustic microscopy (PAM), demonstrating excellent capabilities in high-resolution functional imaging, have sparked significant interest in its integration into the field of endoscopy. However, there are challenges in achieving functional PAM in the endoscopic setting. This Perspective article discusses current progress in the development of endoscopic PAM and the challenges related to functional measurements. Then, it points out potential directions to advance endoscopic PAM for functional imaging by leveraging fiber optics, microfabrication, optical engineering, and computational approaches. Finally, it highlights emerging opportunities for functional endoscopic PAM in basic and translational biomedicine.