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The confused gene expressions and molecular mechanisms for mitochondrial dysfunction of traditional nanoenzymes is a challenge for tumor therapy. Herein, a nano-bacilliform-enzyme obtains the ability to inhibit p52-ZER6 signal pathway, regulate the genes related to mitochondrial metabolism, and possess the GOx/CAT/POD-like property. NBE acquires catalytic activity from the electronic energy transition. The tannin of NBE as a mitochondrial (Mito)-targeting guide overloads MitoROS, and then metabolic disorder and lipid peroxidation of Mito membrane occurs, thus leading to a novel death pathway called PAFerroptosis (pyroptosis, apoptosis, and Ferroptosis). Simultaneously, in order to refrain from mitophagy, hydroxychloroquine is mixed with NBE to form a combo with strength pyroptosis. As a result, NBE/combo improves the PAFerroptosis obviously by activation of CD8+T cells and inactivation of MDSC cells, up-regulating expression of caspase-3 signal pathway, intercepting DHODH pathway to arrive excellent antitumor effect (93%). Therefore, this study establishes a rational nanoenzyme for mitochondrial dysfunction without mitophagy for effective antitumor therapy.
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COP9 signalosome catalytic subunit CSN5 plays a key role in tumorigenesis and tumor immunity, showing potential as an anticancer target. Currently, only a few CSN5 inhibitors have been reported, at least partially, due to the challenges in establishing assays for CSN5 deubiquitinase activity. Here, we present the establishment and validation of a simple and reliable non-catalytic activity assay platform for identifying CSN5 inhibitors utilizing a new fluorescent probe, CFP-1, that exhibits enhanced fluorescence and fluorescence polarization features upon binding to CSN5. By using this platform, we identified 2-aminothiazole-4-carboxylic acids as new CSN5 inhibitors, which inhibited CSN5 but slightly downregulated PD-L1 in cancer cells. Furthermore, through the integration of deep learning-enabled virtual screening, we discovered that shikonins are nanomolar CSN5 inhibitors, which can upregulate PD-L1 in HCT116 cells. The binding modes of these structurally distinct inhibitors with CSN5 were explored by using microsecond-scale molecular dynamics simulations and tryptophan quenching assays.
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Complexo do Signalossomo COP9 , Humanos , Complexo do Signalossomo COP9/metabolismo , Complexo do Signalossomo COP9/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Simulação de Dinâmica Molecular , Corantes Fluorescentes/química , Células HCT116 , Antineoplásicos/farmacologia , Antineoplásicos/química , Descoberta de Drogas/métodos , Relação Estrutura-Atividade , Peptídeo Hidrolases , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
This study addresses the challenge of accurately diagnosing sepsis subtypes in elderly patients, particularly distinguishing between Escherichia coli (E. coli) and non-E. coli infections. Utilizing machine learning, we conducted a retrospective analysis of 119 elderly sepsis patients, employing a random forest model to evaluate clinical biomarkers and infection sites. The model demonstrated high diagnostic accuracy, with an overall accuracy of 87.5%, and impressive precision and recall rates of 93.3% and 87.5%, respectively. It identified infection sites, platelet distribution width, reduced platelet count, and procalcitonin levels as key predictors. The model achieved an F1 Score of 90.3% and an area under the receiver operating characteristic curve of 88.0%, effectively differentiating between sepsis subtypes. Similarly, logistic regression and least absolute shrinkage and selection operator analysis underscored the significance of infectious sites. This methodology shows promise for enhancing elderly sepsis diagnosis and contributing to the advancement of precision medicine in the field of infectious diseases.
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Biomarcadores , Infecções por Escherichia coli , Escherichia coli , Aprendizado de Máquina , Sepse , Humanos , Idoso , Sepse/diagnóstico , Sepse/microbiologia , Sepse/sangue , Biomarcadores/sangue , Masculino , Feminino , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/sangue , Idoso de 80 Anos ou mais , Escherichia coli/isolamento & purificação , Estudos Retrospectivos , Curva ROC , Pró-Calcitonina/sangue , Algoritmo Florestas AleatóriasRESUMO
BACKGROUND: The pathophysiology and the potential risks of placental transfusion (PT) differ substantially in preterm infants, necessitating specific studies in this population. This study aimed to evaluate the safety and efficacy of PT in preterm infants from the perspective of long-term neurodevelopmental outcomes. METHODS: We conducted a systematic literature search using placental transfusion, preterm infant, and its synonyms as search terms. Cochrane Central Register of Controlled Trials, Medline, and Embase were searched until March 07, 2023. Two reviewers independently identified, extracted relevant randomized controlled trials, and appraised the risk of bias. The extracted studies were included in the meta-analysis of long-term neurodevelopmental clinical outcomes using fixed-effects models. RESULTS: A total of 5612 articles were identified, and seven randomized controlled trials involving 2551 infants were included in our meta-analysis. Compared with immediate cord clamping (ICC), PT may not impact adverse neurodevelopment events. No clear evidence was found of a difference in the risk of neurodevelopmental impairment (risk ratio [RR]: 0.89, 95% confidence interval [CI]: 0.76 to 1.03, P = 0.13, I2 = 0). PT was not associated with the incidence of cerebral palsy (RR: 1.23, 95% CI: 0.59 to 2.57, P = 0.79, I2 = 0). Analyses showed no differences between the two interventions in cognitive, language, and motor domains of neurodevelopment. CONCLUSIONS: From the perspective of long-term neurodevelopment, PT at preterm birth may be as safe as ICC. Future studies should focus on standardized, high-quality clinical trials and individual participant data to optimize cord management strategies for preterm infants after birth.
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Recém-Nascido Prematuro , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Recém-Nascido Prematuro/fisiologia , Recém-Nascido , Gravidez , Feminino , Transtornos do Neurodesenvolvimento/etiologia , Placenta , Transfusão de Sangue IntrauterinaRESUMO
BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS: Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.
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Background: The disease burden of gastrointestinal disease (GD) in China is high, with significant variation across provinces. A comprehensive agreed set of indicators could guide rational resource allocation to support better GD outcomes. Methods: This study collected data from multiple sources, including national surveillance, surveys, registration systems, and scientific research. Literature reviews and Delphi methods were used to obtain monitoring indicators; the analytic hierarchy process was used to determine indicator weights. Findings: The China Gastrointestinal Health Index (GHI) system consisted of four dimensions and 46 indicators. The weight of the four dimensions from high to low included the prevalence of gastrointestinal non-neoplastic diseases and gastrointestinal neoplasms (GN) (0.3246), clinical treatment of GD (0.2884), prevention and control of risk factors (0.2606), and exposure to risk factors (0.1264). The highest indicator weight of GHI rank was the successful smoking cessation rate (0.1253), followed by the 5-year survival rate of GN (0.0905), and the examination rate of diagnostic oesophagogastroduodenoscopy (0.0661). The overall GHI for China in 2019 was 49.89, varying from 39.19 to 76.13 across all sub-regions. The top five sub-regions in the total GHI score were in the eastern region. Interpretation: GHI is the first system designed to monitor gastrointestinal health systematically. In the future, data from sub-regions of China should be used to test and improve the GHI system for its impact. Funding: This research was supported by the National Health Commission of China, the First Affiliated Hospital of Naval Medical University (2019YXK006), and the Science and Technology Commission of Shanghai Municipality (21Y31900100).
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A rod-shaped, Gram-negative staining strain, FBM22T, was isolated from a microbial fermentation bed substrate from a pig farm. Its colonies appeared yellow and were 0.5-1.2 mm in diameter. Cells were 0.3-0.5 µm wide, 0.5-0.83 µm long. Optimal growth occurred at 30 °C and pH 7.0-8.0; NaCl was not required for growth. The strain performed denitrification and nitrate reduction functions. And it could produce catalase. FBM22-1T utilized the following organic substrates for growth: tyrosine, glutamic acid, D-glucose, and galactose. The novel isolate could degrade 2-nitropropane as carbon and nitrogen source. The dominant respiratory quinone was Q-10. The major polar lipids were diphosphatidylglycerol, phosphatidylcholine and phosphatidylethanolamine. C18:1 ω7c, C16:1 ω7c and/ or C16:1 ω6c, and C14:0 2-OH were the major (≥ 8%) fatty acids. The G+C content was 56.8 mol%. FBM22T was found to be a member of the genus Sphingopyxis in the family Sphingomonadaceae of the class Alphaproteobacteria. It had the highest sequence similarity with the type strains Sphingopyxis terrae subsp. ummariensis UI2T (96.47%) and Sphingopyxis terrae subsp. terrae NBRC 15098T (96.40%). Furthermore, FBM22T had 18.7% and 18.4% relatedness (based on digital DNA-DNA hybridization) with its two relatives (S. terrae subsp. ummariensis UI2T and S. terrae subsp. terrae NBRC 15098T). The morphological, physiological, and genotypic differences identified in this study support the classification of FBM22T as a novel species within the genus Sphingopyxis, for which the name Sphingopyxis yananensis sp. nov. is proposed. The type strain is FBM22T (= KCTC 82290T = CCTC AB2020286T).
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Sphingomonadaceae , Animais , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Ácidos Graxos/análise , Fermentação , Nitroparafinas , Fosfolipídeos/química , Filogenia , Propano/análogos & derivados , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , SuínosRESUMO
AIMS: The aim of this study was to investigate the effectiveness, safety and pharmacokinetics of adamgammadex in surgical patients. METHODS: Forty-eight patients aged 18-64 years old were randomized to receive adamgammadex (2, 4, 6, and 8 mg.kg-1 ) or placebo at a ratio of 10:2 for reversal of 0.6 mg.kg-1 rocuronium-induced neuromuscular block. Neuromuscular function was monitored by TOF-Watch® SX. When the T2 of train-of-four (TOF) reappeared at the end of surgery, patients received an intravenous administration of adamgammadex or placebo. RESULTS: The recovery time of the TOF ratio to 0.9 decreased significantly from 39.3 [29.5, 50.2] minutes in the group that received placebo to 3.0 [2.3, 3.9] minutes, P < .0001; 2.1 [1.5, 3.0] minutes, P < .0001; 2.1 [1.8, 3.3] minutes, P < .0001; and 1.8 [1.5, 2.2] minutes, P < .0001 in the 2, 4, 6 and 8 mg.kg-1 adamgammadex groups, respectively. Then, adamgammadex also showed a shortened recovery time for the TOF ratio recovered to 0.8 and 0.7. Adamgammadex was well tolerated, and no cases of anaphylactic reactions, post-operative bleeding, recurarization, abnormal basic vital signs and prolonged QT intervals were observed. The pharmacokinetics of adamgammadex in plasma increased in dose-dependent manner. The 24-hour cumulative fraction of adamgammadex in urine was 65-83%, and that of rocuronium was increased after using adamgammadex from 15% to about 25-30%. CONCLUSION: Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block, and it was safe and well tolerated in patients.
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Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Adolescente , Adulto , Androstanóis/efeitos adversos , Humanos , Pessoa de Meia-Idade , Bloqueio Neuromuscular/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Rocurônio , Sugammadex/farmacologia , Adulto Jovem , gama-Ciclodextrinas/farmacologia , gama-Ciclodextrinas/uso terapêuticoRESUMO
PURPOSE: This study focused on the role and mechanism of IGF2BP1 in cell cisplatin resistance of oral squamous cell carcinoma. METHODS: Low-dose intermittent induction method was used to induce cisplatin-sensitive oral squamous cell carcinoma cell line HN30, and establish cisplatin-resistant cell line HN30/DDP. Western blot was used to detect the protein expression level of IGF2BP1 in parental and resistant cell line. Knockdown or overexpression of IGF2BP1 by RNAi and lentivirus transfection method was utilized to analyze the effect of decreased or increased the gene expression of IGF2BP1 on cisplatin resistance. MTT method was used to detect the change of IC50. Statistical analysis of data was performed using SPSS 17.0 software package. RESULTS: Cisplatin-resistant oral squamous cell carcinoma cell line was successfully established. The IC50 of the drug-resistant cells was significantly higher than that of the parental cells. Knocking down the expression level of IGF2BP1 in drug-resistant strains reduced cell resistance; on the contrary, after overexpression of IGF2BP1 in parental cells dramatically increased cisplatin resistance. Mechanically, activation of Akt signaling pathway was the key factor mediating IGF2BP1 to promote cisplatin resistance in oral squamous cell carcinoma. CONCLUSIONS: IGF2BP1 is significantly associated with cisplatin resistance in oral squamous cell carcinoma. IGF2BP1 can promote cisplatin resistance of oral squamous cells by activating downstream Akt signaling pathway.
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Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Preparações Farmacêuticas , Antineoplásicos/farmacologia , Apoptose , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
INTRODUCTION: The rapid rise in the prevalence of diabetes has a negative impact on patients' quality of life. Diabetes self-management group education is cost-effective and efficient for patients to control blood glucose. However, there are no consistent standards for self-management group education, and its long-term effects (≥12 months) are unclear. Although a few systematic reviews evaluated the long-term effects, they did not make clear provisions on the content of self-management, and the number and sample size of included studies were small, which may lead to misclassification bias and reporting bias. Therefore, we plan to conduct this systematic review to evaluate the long-term effects of self-management group education and determine the effects of different self-management characteristics on glycosylated haemoglobin (HbA1c). METHODS AND ANALYSIS: We will retrieve Chinese databases (Wanfang, Chinese Hospital Knowledge Warehouse) and English databases (PubMed, ScienceDirect, EMBASE, Web of Science, Bailian Platform, Cochrane Central Register of Controlled Trials, Google Scholar) for randomly controlled trials and cluster randomly controlled trials of which participants are adults with type 2 diabetes mellitus. We will manually search citation lists and trial registries, and consult authors to obtain relevant articles. The retrieval time range will be from the establishment of the database to July 2020 to avoid omitting relevant studies. The primary outcome will be HbA1c. The secondary outcomes will be fasting plasma glucose, postprandial blood glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, systolic blood pressure, diastolic blood pressure, body mass index, waist circumference and death event. Two reviewers will independently conduct article screening and assessment of risk of bias, with a third reviewer arbitrating if necessary. We will give priority to the use of meta-analysis to evaluate the pooled effects of all outcomes. For the outcomes of unrecognised sources of heterogeneity, missing data and less than three related studies, narrative synthesis approach will be used. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review. We plan to present the findings in a peer-reviewed scientific journal, relevant and responsible organisations, and training meetings. PROSPERO REGISTRATION NUMBER: CRD42020209011.
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Diabetes Mellitus Tipo 2 , Autogestão , Adulto , Glicemia , Diabetes Mellitus Tipo 2/terapia , Hemoglobinas Glicadas , Humanos , Metanálise como Assunto , Qualidade de Vida , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Alisol A 24-acetate (AA-24-a), one of the main active triterpenes isolated from the well-known medicinal plant Alisma orientale (Sam.) Juz., exhibits multiple biological activities including hypolipidemic activity. However, its effect on lipid metabolism in adipocytes remains unclear. The present study aimed to clarify the effect of AA-24-a on adipocyte lipolysis and to determine its potential mechanism of action using 3 T3-L1 cells. METHODS: We assayed the release of glycerol into culture medium of 3 T3-L1 cells under treatment with AA-24-a. Protein and mRNA expression and phosphorylation levels of the main lipases and kinases involved in lipolysis regulation were determined by quantitative polymerase chain reaction and western blotting. Specific inhibitors of protein kinase A (PKA; H89) and extracellular signal-regulated kinase (ERK; PD98059), which are key enzymes in relevant signaling pathways, were used to examine their roles in AA-24-a-stimulated lipolysis. RESULTS: AA-24-a significantly stimulated neutral lipolysis in fully differentiated adipocytes. To determine the underlying mechanism, we assessed the changes in mRNA and protein levels of key lipolysis-related genes in the presence or absence of H89 and PD98059. Both inhibitors reduced AA-24-a-induced lipolysis. Moreover, pretreatment with H89 attenuated AA-24-a-induced phosphorylation of hormone-sensitive lipase at Ser660, while pretreatment with PD98059 attenuated AA-24-a-induced downregulation of peroxisome proliferator-activated receptor-γ and perilipin A. CONCLUSIONS: Our results indicate that AA-24-a promoted neutral lipolysis in 3 T3-L1 adipocytes by activating PKA-mediated phosphorylation of hormone-sensitive lipase and ERK- mediated downregulation of expression of perilipin A.
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Alisma , Hipolipemiantes/farmacologia , Triterpenos/farmacologia , Adipócitos/efeitos dos fármacos , Animais , Lipólise/efeitos dos fármacos , Camundongos , FitoterapiaRESUMO
A nano-calcium peroxide (nCaO2) powder with a purity of 89.1% was prepared using an improved traditional method. Then, the as-prepared nCaO2 was used as the source of hydrogen peroxide (H2O2) for the Fenton-like degradation of diclofenac sodium (DCF). The results showed that nCaO2 performed better for DCF removal when compared to nCaO2 prepared by a conventional method and commercial calcium peroxide (CaO2). Further experimental results indicated that 97.5% of DCF could be removed in 180 min at a nCaO2/Fe2+-EDTA/DCF molar ratio of 16/8-8/1, which was more efficient than in the H2O2/EDTA-Fe2+/DCF and nCaO2/Fe2+/DCF systems. The best removal rate of DCF was at pH 6.0, unlike previous claims that stated that the lower the pH in the buffer system, the better the degradation of DCF. In addition, the influence of water quality parameters, such as Cl-, NO3-, SO42-, HCO3-, and humic acid (HA), on DCF removal were evaluated. A free radical masking experiment revealed the existence of hydroxyl radical (OH), superoxide radical (O2-) and singlet oxygen (1O2), and indicated that the degradation of DCF was mainly due to oxidation caused by OH. Electron paramagnetic resonance (EPR) studies for different systems and different active oxygen species were carried out, and it was further confirmed that OH radicals have high intensity in the Fenton-like system based on nCaO2. EPR results also showed that the addition of EDTA can promote the production of OH. According to the identification of the dominant reactive species and GC-MS, the possible theoretical DCF degradation pathways were proposed.
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Diclofenaco , Poluentes Químicos da Água , Peróxido de Hidrogênio , Oxirredução , Peróxidos , Tecnologia , Poluentes Químicos da Água/análiseRESUMO
Algal organic matter (AOM) and natural organic matter (NOM) from a typical eutrophic lake were comprehensively investigated in terms of their physico-chemical property, components and disinfection byproduct formation potentials (DBPFPs). The relationships between specific chemical properties of AOM and NOM with their corresponding DBPFPs were further evaluated during chlorination. Results indicated that AOM had lower specific UV absorbance (SUVA) but richer organic nitrogen contents than NOM. Fluorescence excitation emission matrix spectroscopy further demonstrated that AOM were chiefly composed of aromatic protein-like and soluble microbial byproduct-like matters, while NOM were mainly contributed from humic acid-like and soluble microbial byproduct-like substances. Although the molecular weight (MW) distribution of AOM and NOM showed no significant difference, size-exclusion chromatography with organic carbon as well as organic nitrogen detection (LC-OCD-OND) revealed that AOM were concentrated with the fraction of building blocks and NOM had higher concentrations of biopolymers and humics (HS). Moreover, AOM displayed higher DBPFPs than NOM, especially for nitrogenous DBPFP (N-DBPFP). MW < 1 kDa fractions both in AOM and NOM contributed the largest proportion to the formation of carbonaceous disinfection byproducts (C-DBPs). In addition, Pearson correlation analysis showed that bulk parameter SUVA was significantly relevant to the formation potentials of trihalomethane both in AOM and NOM, but was ineffective for carbonaceous DBPFP (C-DBPFP) prediction. Dissolved organic nitrogen contents in biopolymer and HS characterized by LC-OCD-OND had strong correlations with N-DBPFPs from AOM and NOM, indicating that LC-OCD-OND quantitative analysis could improve the prediction accuracy of the DBP formation than bulk parameters during NOM and AOM chlorination.
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Poluentes Químicos da Água , Purificação da Água , Desinfecção , Halogenação , Nitrogênio/análise , Trialometanos/análise , Poluentes Químicos da Água/análiseRESUMO
The internal source pollution of sediment is the main factor leading to the repetition of black-odorous river channels. In order to prevent this situation, a river channel in the Binhu District of Wuxi City was used as an experimental site. In-situ CaO2 combined with a biochar covering technology was used to repair the black odorous river sediment in this channel. The effects of this technology on the quality of mud water, sedimentary volatile sulfide (AVS) and phosphorus forms, microorganisms, and restoration of black odorous sediment were investigated. The results showed that CaO2 combined with biochar coverage could significantly increase the dissolved oxygen (DO) concentration and redox potential (ORP) of the muddy water system. The DO concentration and ORP in the overlying water were maintained above 2 mg·L-1 and 50 mV, respectively. The removal rates of interstitial water ammonia-nitrogen (NH4+-N), chemical oxygen demand (COD), and total phosphorus (TP) reached 43.40%, 41.18%, and 50.97%, respectively. The removal rate of AVS in the sediment reached 37.03%. The high-throughput sequencing showed that the relative abundance of anaerobic microorganisms in the sediment was significantly reduced, and that nitrogen and sulfur removal microorganisms appeared (e.g., Thermomonas, Dechloromonas, Proteus hauser, Desulfomicrobium, and Thiobacillus). Phosphorus in the sediment was converted into Fe/Al-P and Ca-P. Therefore, in-situ CaO2 combined with biochar coverage had a good repairing effect on black odorous sediment.
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Rios , Poluentes Químicos da Água , Carvão Vegetal , Sedimentos Geológicos , Nitrogênio/análise , Peróxidos , Fósforo , Poluentes Químicos da Água/análiseRESUMO
Adenosine triphosphate (ATP) biomolecules play critial roles in the biomineralization process during the formation of amorphous calcium phosphate composites (ACPC), and ACPC is an important drug carrier due to its significant advantages of biocompatibility and biodegradability. Hence, studying the behavior of ACPC nanodrug carriers is crucial to investigate the structural regulation of biomimetic minerals and calcium phosphate (CaP)-based drug delivery systems. However, it is difficult to probe these interactions using traditional characterization methods. In this paper, XANES analysis together with STXM successfully provided a method to reveal the interaction of ATP and drug molecules with individual mesoporous ACPC. We found that the adenosine and phosphate groups of ATP biomolecules coordinated with Ca2+ and played critical roles in the formation of ACPC; drug molecules with the -COOH groups were linked to Ca2+via carboxylic acid groups primarily by electrostatic interactions, and the N-containing ring structures within the drug molecules also coordinated with Ca2+.
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Trifosfato de Adenosina/química , Fosfatos de Cálcio/química , Doxorrubicina/química , Nanocompostos/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Hemoglobinas/química , Tamanho da Partícula , Porosidade , Propriedades de Superfície , Espectroscopia por Absorção de Raios XRESUMO
Pennisetum sinese is a good forage grass with high biomass production and crude proteins. However, little is known about the endophytic fungi diversity of P. sinese, which might play an important role in the plant's growth and biomass production. Here, we used high throughput sequencing of the Internal Transcribed Spacer (ITS) sequences based on primers ITS5-1737 and ITS2-2043R to investigate the endophytic fungi diversity of P. sinese roots at the maturity stage, as collected from four provinces (Shaanxi province, SX; Fujian province, FJ; the Xinjiang Uyghur autonomous prefecture, XJ and Inner Mongolia, including sand (NS) and saline-alkali land (NY), China). The ITS sequences were processed using QIIME and R software. A total of 374,875 effective tags were obtained, and 708 operational taxonomic units (OTUs) were yielded with 97% identity in the five samples. Ascomycota and Basidiomycota were the two dominant phyla in the five samples, and the genera Khuskia and Heydenia were the most abundant in the FJ and XJ samples, respectively, while the most abundant tags in the other three samples could not be annotated at the genus level. In addition, our study revealed that the FJ sample possessed the highest OTU numbers (242) and the NS sample had the lowest (86). Moreover, only 22 OTUs were present in all samples simultaneously. The beta diversity analysis suggested a division of two endophytic fungi groups: the FJ sample from the south of China and the other four samples from north or northwest China. Correlation analysis between the environmental factors and endophytic fungi at the class level revealed that Sordariomycetes and Pucciniomycetes had extremely significant positive correlations with the total carbon, annual average precipitation, and annual average temperature, while Leotiomycetes showed an extremely significant negative correlation with quick acting potassium. The results revealed significant differences in the root endophytic fungi diversity of P. sinese in different provinces and might be useful for growth promotion and biomass production in the future.
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One-dimensional hydroxyapatite (HA) particularly mimics the structure of mineralized collagen fibrils and displays superior mechanical properties such as toughness. Herein, we report Se-doped HA/chitosan (Se-HA/CS) biopapers constructed with self-assembled Se-doped HA nanowires and chitosan. The Se-HA/CS biopapers with high flexibility and manufacturability can not only be further processed into arbitrary shapes by folding or using scissors but also display high performances in in vitro/vivo anti-bone tumor studies. The Se-HA/CS biopapers are more inclined to inhibit the growth of tumor cells (HCS 2/8 and SJSA cells) than that of normal human bone marrow stromal cells (hBMSCs). The potential mechanisms of this meaningful anti-tumor effect were investigated, such as reactive oxygen species accumulation and the activation of apoptosis and the underlying signal pathway involved (including caspase family, Bcl-2 family and JNK/STAT3). The results demonstrate that Se-HA/CS biopapers may inhibit the growth of HCS 2/8 and SJSA cells by synchronously inducing JNK activation and STAT3 inhibition and consequently promote the apoptosis of these cells. Furthermore, the in vivo anti-tumor studies confirm that the Se-HA/CS biopapers obviously suppress the growth of patient-derived xenograft tumor models.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/patologia , Durapatita/química , Selênio/química , Selênio/farmacologia , Animais , Linhagem Celular Tumoral , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Nanofios/química , Papel , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Water movement over and through soil is largely driven by topography and soil management across landscapes. This research tested the hypothesis that the water movement determines the potential for P and Ca redistribution and pH variance across landscapes. This hypothesis was evaluated by using digital elevation model-derived terrain attributes in fields after 55 yr of broiler litter applications on pastures in Smith County, Mississippi. Results show that soils receiving broiler litter had mean Mehlich-3 P levels of 1221.8 mg kg at 0- to 15-cm depth and 618.6 mg kg at 15- to 30-cm depth, and Ca with mean values of 768.3 and 645.0 mg kg at 0- to 15-cm and 15- to 30-cm soil depths, respectively. Across fields, soils in areas of predicted convergent flow contained higher P, Ca, and lower pH values in the upper 0 to 15 cm, suggesting contributions via surface overland flow from areas with higher elevation and lower slope gradient. On the other hand, soils in areas with lesser slope and higher elevation also contained high levels of P, Ca, and pH for the subsurface soil depth, suggesting that vertical flow of water on this landscape is a mechanism for movement of P and Ca deeper in the profile. The incorporation of topographic characteristics across fields offers promising results that may be incorporated into improved P indices and management, making them more robust indicators of P mobilization to waterways.
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Fósforo , Solo , Animais , Cálcio , Galinhas , Concentração de Íons de Hidrogênio , Esterco , MississippiRESUMO
In vivo mineralization is a multistep process involving mineral-protein complexes and various metastable compounds in vertebrates. In this complex process, the minerals produced in the mitochondrial matrix play a critical role in initiating extracellular mineralization. However, the functional mechanisms of the mitochondrial minerals are still a mystery. Herein, an in vitro enzymatic reaction strategy is reported for the generation of biomimic amorphous calcium phosphate (EACP) nanominerals by an alkaline phosphatase (ALP)-catalyzed hydrolysis of adenosine triphosphate (ATP) in a weakly alkalescent aqueous condition (pH 8.0-8.5), which is partially similar to the mitochondrial environment. Significantly, the EACP nanomineral obviously promotes autophagy and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by activating an AMPK related pathway, and displays a high performance in promoting bone regeneration. These results provide in vitro evidence for the effect of ATP on the formation and stabilization of the mineral in the mineralization process, demonstrating a potential strategy for the preparation of the biomimic mineral for treating bone related diseases.
Assuntos
Biomimética/métodos , Fosfatase Alcalina/metabolismo , Autofagia/fisiologia , Fosfatos de Cálcio/química , Diferenciação Celular/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese/fisiologiaRESUMO
With the growing popularity of electrical communication equipment, high-performance electromagnetic interference (EMI) shielding materials are widely used to deal with radiation pollution. However, the large thickness and poor mechanical properties of many EMI shielding materials usually limit their applications. In this study, ultrathin and highly flexible Ti3C2T x (d-Ti3C2T x, MXene)/cellulose nanofiber (CNF) composite paper with a nacre-like lamellar structure is fabricated via a vacuum-filtration-induced self-assembly process. By the interaction between one-dimensional (1D) CNFs and two-dimensional (2D) d-Ti3C2T x MXene, the binary strengthening and toughening of the nacre-like d-Ti3C2T x/CNF composite paper has been successfully achieved, leading to high tensile strength (up to 135.4 MPa) and fracture strain (up to 16.7%), as well as excellent folding endurance (up to 14â¯260 times). Moreover, the d-Ti3C2T x/CNF composite paper exhibits high electrical conductivity (up to 739.4 S m-1) and excellent specific EMI shielding efficiency (up to 2647 dB cm2 g-1) at an ultrathin thickness (minimum thickness 47 µm). The nacre-inspired strategy in this study offers a promising approach for the design and preparation of the strong integrated and flexible MXene/CNF composite paper, which may be applied in various fields such as flexible wearable devices, weapon equipment, and robot joints.