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1.
Int J Biol Macromol ; 273(Pt 1): 133012, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866296

RESUMO

The process of dissolving cellulose is a pivotal step in transforming it into functional, value-added materials, necessitating a thorough comprehension of the underlying mechanisms to refine its advanced processing. This article reviews cellulose dissolution using various solvent systems, along with an in-depth exploration of the associated dissolution mechanisms. The efficacy of different solvents, including aqueous solvents, organic solvents, ionic liquids, hybrid ionic liquid/cosolvent systems, and deep eutectic solvents, in dissolving cellulose is scrutinized, and their limitations and advantages are highlighted. In addition, this review methodically outlines the mechanisms at play within these various solvent systems and the factors influencing cellulose solubility. Conclusions drawn highlight the integral roles of the degree of polymerization, crystallinity, particle size, the type and sizes of cations and anions, alkyl chain length, ionic liquid/cosolvent ratio, viscosity, solvent acidity, basicity, and hydrophobic interactions in the dissolution process. This comprehensive review aims to provide valuable insights for researchers investigating biopolymer dissolution in a broader context, thereby paving the way for broader applications and innovations of these solvent systems.

2.
Biosens Bioelectron ; 261: 116522, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38924815

RESUMO

Molecular detection of nucleic acid plays an important role in early diagnosis and therapy of disease. Herein, a novel and enhanced electrochemical biosensor was exploited based on target-activated CRISPR/Cas12a system coupling with nanoparticle-labeled covalent organic frameworks (COFs) as signal reporters. Hollow spherical COFs (HCOFs) not only served as the nanocarriers of silver nanoparticles (AgNPs)-DNA conjugates for enhanced signal output but also acted as three-dimensional tracks of CRISPR/Cas12a system to improve the cleavage accessibility and efficiency. The presence of target DNA triggered the trans-cleavage activity of the CRISPR/Cas12a system, which rapidly cleaved the AgNPs-DNA conjugates on HCOFs, resulting in a remarkable decrease of the electrochemical signal. As a proof of concept, the fabricated biosensing platform realized highly sensitive and selective detection of human papillomavirus type 16 (HPV-16) DNA ranging from 100 fM to 1 nM with the detection limit of 57.2 fM. Furthermore, the proposed strategy provided a versatile and high-performance biosensor for the detection of different targets by simple modification of the crRNA protospacer, holding promising applications in disease diagnosis.


Assuntos
Técnicas Biossensoriais , Sistemas CRISPR-Cas , DNA Viral , Técnicas Eletroquímicas , Papillomavirus Humano 16 , Nanopartículas Metálicas , Estruturas Metalorgânicas , Prata , Técnicas Biossensoriais/métodos , Humanos , Nanopartículas Metálicas/química , Técnicas Eletroquímicas/métodos , Prata/química , Estruturas Metalorgânicas/química , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , DNA Viral/análise , DNA Viral/genética , Limite de Detecção
3.
Vet Res ; 55(1): 83, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943190

RESUMO

Migratory birds are important vectors for virus transmission, how migratory birds recognize viruses and viruses are sustained in birds is still enigmatic. As an animal model for waterfowl among migratory birds, studying and dissecting the antiviral immunity and viral evasion in duck cells may pave a path to deciphering these puzzles. Here, we studied the mechanism of antiviral autophagy mediated by duck STING in DEF cells. The results collaborated that duck STING could significantly enhance LC3B-II/I turnover, LC3B-EGFP puncta formation, and mCherry/EGFP ratio, indicating that duck STING could induce autophagy. The autophagy induced by duck STING is not affected by shRNA knockdown of ATG5 expression, deletion of the C-terminal tail of STING, or TBK1 inhibitor BX795 treatment, indicating that duck STING activated non-classical selective autophagy is independent of interaction with TBK1, TBK1 phosphorylation, and interferon (IFN) signaling. The STING R235A mutant and Sar1A/B kinase mutant abolished duck STING induced autophagy, suggesting binding with cGAMP and COPII complex mediated transport are the critical prerequisite. Duck STING interacted with LC3B through LIR motifs to induce autophagy, the LIR 4/7 motif mutants of duck STING abolished the interaction with LC3B, and neither activated autophagy nor IFN expression, indicating that duck STING associates with LC3B directed autophagy and dictated innate immunity activation. Finally, we found that duck STING mediated autophagy significantly inhibited duck plague virus (DPV) infection via ubiquitously degraded viral proteins. Our study may shed light on one scenario about the control and evasion of diseases transmitted by migratory birds.


Assuntos
Autofagia , Patos , Transdução de Sinais , Animais , Mardivirus/fisiologia , Interferons/metabolismo , Alphaherpesvirinae/fisiologia , Imunidade Inata , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Infecções por Poxviridae/veterinária , Infecções por Poxviridae/imunologia , Infecções por Poxviridae/virologia
4.
Technol Cancer Res Treat ; 23: 15330338241261615, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887096

RESUMO

This study aimed to investigate the role of miR-558 in tumor angiogenesis by targeting heparinase (HPSE) in tongue squamous cell carcinoma (TSCC)-derived exosomes. In the present study, the role of exosome miR-558 in angiogenesis in vitro and in vivo was investigated by cell proliferation, migration, tube formation, subcutaneous tumor formation in mice, and in vivo Matrigel plug assay. The target genes of miR-558 were detected by means of dual luciferase assay. It was found that TSCC cells secrete miR-558 into the extracellular environment, with exosome as the carrier. Human umbilical vein endothelial cells (HUVEC) ingested exosomes, which not only increased the expression level of miR-558, but also enhanced their proliferation, migration, and tube formation functions. In vivo Matrigel plug assay demonstrated that TSCC cell-derived exosome miR-558 promoted neovascularization in vivo. Compared with negative control cells, TSCC cells overexpressing miR-558 formed subcutaneous tumors in nude mice, with larger volume, heavier mass, and more vascularization. Dual luciferase assay confirmed that HPSE was the direct target gene regulated by miR-558. HPSE promoted the proliferation, migration, and tube formation of HUVECs, and the knockout of HPSE could downregulate the pro-angiogenic effect of miR-558. In summary, miR-558 in TSCC exosomes promotes the proliferation, migration, and tube formation of HUVECs by targeting HPSE, and enhancing tumor angiogenesis.


Assuntos
Movimento Celular , Proliferação de Células , Exossomos , Regulação Neoplásica da Expressão Gênica , Heparina Liase , MicroRNAs , Neovascularização Patológica , Neoplasias da Língua , Humanos , Animais , MicroRNAs/genética , Exossomos/metabolismo , Exossomos/genética , Neoplasias da Língua/patologia , Neoplasias da Língua/genética , Neoplasias da Língua/metabolismo , Camundongos , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Movimento Celular/genética , Linhagem Celular Tumoral , Heparina Liase/metabolismo , Heparina Liase/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Células Endoteliais da Veia Umbilical Humana , Modelos Animais de Doenças , Ensaios Antitumorais Modelo de Xenoenxerto , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Angiogênese
5.
Ultrason Sonochem ; 108: 106958, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38889569

RESUMO

Fermented skim milk is an ideal food for consumers such as diabetic and obese patients, but its low-fat content affects its texture and viscosity. In this study, we developed an effective pretreatment method for fermented skim milk using low-frequency ultrasound (US), and investigated the molecular mechanism of the corresponding quality improvement. The skim milk samples were treated by optimal ultrasonication conditions (336 W power for 7 min at 3 °C), which improved the viscosity, water-holding capacity, sensory attributes, texture, and microstructure of fermented skim milk (P < 0.05). Further mechanistic analyses revealed that the US treatment enhanced the exposure of fluorescent amino acids within proteins, facilitating the cross-linking between casein and whey. The increased surface hydrophobicity of fermented milk indicates that the US treatment led to the exposure of hydrophobic amino acid residues inside proteins, contributing to the formation of a denser gel network; the average particle size of milk protein was reduced from 24.85 to 18.06 µm, which also contributed to the development of a softer curd texture. This work is the first attempt to explain the effect of a low-frequency ultrasound treatment on the quality of fermented skim milk and discuss the molecular mechanism of its improvement.

6.
Neurosurgery ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860769

RESUMO

BACKGROUND AND OBJECTIVES: This study aimed to investigate the clinical, radiological, pathological features, treatment options, and outcomes of isocitrate dehydrogenase (IDH)-mutant brainstem gliomas (BSG-IDHmut). METHODS: A retrospective analysis of 22 patients diagnosed with BSG-IDHmut and treated at our institution from January 2011 to January 2017 was performed. Their clinical, radiological data, and long-term outcomes were collected and analyzed. RESULTS: The median age of patients was 38.5 years, with a male predominance (63.6%). All patients had IDH1 and TP53 mutations, with noncanonical IDH mutations in 59.1% of cases, 06-methylguanine-DNA methyltransferase promoter methylation in 55.6%, and alpha-thalassemia mental retardation X-linked loss in 63.2%, respectively. Tumors were primarily located in the pontine-medullary oblongata (54.5%) and frequently involved the pontine brachium (50%). Most tumors exhibited ill-defined boundaries (68.2%), no T2-FLAIR mismatch (100%), and no contrast enhancement (86.3%). Two radiological growth patterns were also identified: focal and extensively infiltrative, which were associated with the treatment strategy when tumor recurred. Seven patients (31.8%) received surgery only and 15 (68.2%) surgery plus other therapy. The median overall survival was 124.8 months, with 1-year, 2-year, 5-year, and 10-year survival rates of 81.8%, 68.2%, 54.5%, and 13.6%, respectively. Six patients experienced tumor recurrence, and all retained their radiological growth patterns, with 2 transformed into central nervous system World Health Organization grade 4. CONCLUSION: BSG-IDHmut represents a unique subgroup of brainstem gliomas with distinctive features and more favorable prognosis compared with other brainstem gliomas. Further research is required to better understand the molecular mechanisms and optimize treatment strategies for this rare and complex disease.

7.
Eur J Med Res ; 29(1): 323, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867262

RESUMO

BACKGROUND: Abdominal aortic aneurysm (AAA) is a highly lethal cardiovascular disease. The aim of this research is to identify new biomarkers and therapeutic targets for the treatment of such deadly diseases. METHODS: Single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithms were used to identify distinct immune cell infiltration types between AAA and normal abdominal aortas. Single-cell RNA sequencing data were used to analyse the hallmark genes of AAA-associated macrophage cell subsets. Six macrophage-related hub genes were identified through weighted gene co-expression network analysis (WGCNA) and validated for expression in clinical samples and AAA mouse models. We screened potential therapeutic drugs for AAA through online Connectivity Map databases (CMap). A network-based approach was used to explore the relationships between the candidate genes and transcription factors (TFs), lncRNAs, and miRNAs. Additionally, we also identified hub genes that can effectively identify AAA and atherosclerosis (AS) through a variety of machine learning algorithms. RESULTS: We obtained six macrophage hub genes (IL-1B, CXCL1, SOCS3, SLC2A3, G0S2, and CCL3) that can effectively diagnose abdominal aortic aneurysm. The ROC curves and decision curve analysis (DCA) were combined to further confirm the good diagnostic efficacy of the hub genes. Further analysis revealed that the expression of the six hub genes mentioned above was significantly increased in AAA patients and mice. We also constructed TF regulatory networks and competing endogenous RNA networks (ceRNA) to reveal potential mechanisms of disease occurrence. We also obtained two key genes (ZNF652 and UBR5) through a variety of machine learning algorithms, which can effectively distinguish abdominal aortic aneurysm and atherosclerosis. CONCLUSION: Our findings depict the molecular pharmaceutical network in AAA, providing new ideas for effective diagnosis and treatment of diseases.


Assuntos
Aneurisma da Aorta Abdominal , Perfilação da Expressão Gênica , Macrófagos , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/diagnóstico , Humanos , Animais , Macrófagos/metabolismo , Camundongos , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Modelos Animais de Doenças , Transcriptoma , Biomarcadores/metabolismo
8.
ACS Appl Mater Interfaces ; 16(24): 31567-31575, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38836291

RESUMO

Solar energy is widely used in photovoltaic power generation as a kind of clean energy. However, the liquid film, frosting, and icing on the photovoltaic module seriously limit the efficiency of photovoltaic power generation. We developed a composite coating (Y6-NanoSH) by combining an in situ photothermal and transparent Y6 organic film with a nanosuperhydrophobic material. The Y6-NanoSH coated glass exhibited excellent optical clarity both indoors and outdoors, indicating that the coating holds great promise in anti-icing applications for photovoltaic panels. The Y6-NanoSH coating absorbs very little visible light but instead absorbs in the near-infrared region, thereby emitting heat. When exposed to sunlight, the Y6-NanoSH coated photovoltaic panel raises its surface temperature, inhibiting the growth and accumulation of ice and frost on its surface. This is achieved through a combination of photothermal emission and superhydrophobic repellency, which promotes the evaporation and rolling away of water droplets. This validates our success in developing a photothermal, transparent, and superhydrophobic coating with excellent anti-icing capabilities, suitable for use on photovoltaic panels, as well as potential applications in car windscreens, transmission lines, curtain walls, and weather radomes.

9.
Food Microbiol ; 122: 104563, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38839237

RESUMO

Thermosonication (UT) prestress treatments combining with varied fermentation patterns has been revealed as an effective method to regulate post-acidification as exerted by Lactobacillus delbrueckii subsp. bulgaricus (L. delbrueckii), but sono-biochemical controlling mechanisms remain elusive. This study employed physiological and transcriptomic analysis to explore the response mechanism of L. delbrueckii to UT-induced microstress (600 W, 33 kHz, 10 min). UT stress-induced inhibition of acidification of L. delbrueckii during (post)-fermentation was first confirmed, relying on the UT process parameters such as stress exposure duration and UT power. The significantly enhanced membrane permeability in cells treated by 600 W for 10 min than the microbes stressed by 420 W for 20 min suggested the higher dependence of UT-derived stresses on the treatment durations, relative to the ultrasonic powers. In addition, ultrasonication treatment-induced changes in cell membrane integrity enhanced and/or disrupted permeability of L. delbrueckii, resulting in an imbalance in intracellular conditions associated with corresponding alterations in metabolic behaviors and fermentation efficiencies. UT-prestressed inoculum exhibited a 21.46% decrease in the membrane potential during the lag phase compared to untreated samples, with an intracellular pH of 5.68 ± 0.12, attributed to the lower activities of H+-ATPase and lactate dehydrogenase due to UT stress pretreatments. Comparative transcriptomic analysis revealed that UT prestress influenced the genes related to glycolysis, pyruvate metabolism, fatty acid synthesis, and ABC transport. The genes encoding 3-oxoacyl-[acyl-carrier-protein] reductases I, II, and III, CoA carboxylase, lactate dehydrogenase, pyruvate oxidase, glucose-6-phosphate isomerase, and glycerol-3-phosphate dehydrogenase were downregulated, thus identifying the relevance of the UT microstresses-downregulated absorption and utilization of carbohydrates with the attenuated fatty acid production and energy metabolisms. These findings could contribute to provide a better understanding of the inactivated effects on the post-acidification of L. delbrueckii by ultrasonic pretreatments, thus providing theoretical basis for the targeted optimization of acidification inhibition efficiencies for yogurt products during chilled preservation processes.


Assuntos
Fermentação , Perfilação da Expressão Gênica , Lactobacillus delbrueckii , Lactobacillus delbrueckii/metabolismo , Lactobacillus delbrueckii/genética , Concentração de Íons de Hidrogênio , Transcriptoma , Sonicação , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética
10.
Environ Sci Technol ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940696

RESUMO

While partial nitrification (PN) has the potential to reduce energy for aeration, it has proven to be unstable when treating low-strength wastewater. This study introduces an innovative combined strategy incorporating a low rate of oxygen supply, pH control, and sulfide addition to selectively inhibit nitrite-oxidizing bacteria (NOB). This strategy led to a stable PN in a laboratory-scale membrane aerated biofilm reactor (MABR). Over a period of 260 days, the nitrite accumulation ratio exceeded 60% when treating synthetic sewage containing 50 mg NH4+-N/L. Through in situ activity testing and high-throughput sequencing, the combined strategy led to low levels of nitrite-oxidation activity (<5.5 mg N/m2 h), Nitrospira species (relative abundance <1%), and transcription of nitrite-oxidation genes (undetectable). The addition of sulfide led to simultaneous PN and autotrophic denitrification in the single-stage MABR, resulting in over 60% total inorganic nitrogen removal. Sulfur-based autotrophic denitrification consumed nitrite and inhibited NOB conversion of nitrite to nitrate. The combined strategy has potential to be applied in large-scale sewage treatment and deserves further exploration.

11.
Int J Biol Macromol ; 271(Pt 1): 132397, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38821787

RESUMO

The thickening and gelling mechanism of high-methoxyl pectins (HMPs) with different degree of esterification (DE) values (60.6 %, 66.1 %, and 72.4 %) synergistically affected by calcium ion (Ca2+) and sucrose was investigated using several technical methods. Rheological measurements, including steady-shear flow, thixotropy and dynamic viscoelasticity tests, texture analysis, water-holding capacity (WHC), thermal analyses (TG), and microstructure observation (TEM), were all systemically conducted. The results showed that the main thickening and gelling mechanism of Ca2+ on different HMPs was complex and the presence of sucrose had a synergistic effect on structure formation in HMP systems. Ca2+ was not always conducive to structure formation, and excessive Ca2+ addition may hinder structure formation. HMP systems with lower DE values had higher gel strengths due to the presence of more binding domains. The results of the texture properties, WHC, and thermal characteristics coincided with those obtained from the rheological measurements, which reflect the variations in HMPs affected by Ca2+ and DE. All of these results showed that Ca2+ addition at an appropriate concentration in the presence of sucrose favors HMP gelation even in the absence of acid. The results obtained here are expected to broaden the application of HMPs in acid-free gel food products.


Assuntos
Cálcio , Malus , Pectinas , Reologia , Sacarose , Pectinas/química , Malus/química , Sacarose/química , Cálcio/química , Viscosidade , Géis/química , Esterificação , Água/química
12.
Acta Crystallogr F Struct Biol Commun ; 80(Pt 5): 92-97, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38699970

RESUMO

The Rib domain, which is often found as tandem-repeat structural modules in surface proteins of Gram-positive bacteria, plays important roles in mediating interactions of bacteria with their environments and hosts. A comprehensive structural analysis of various Rib domains is essential to fully understand their impact on the structure and functionality of these bacterial adhesins. To date, structural information has been limited for this expansive group of domains. In this study, the high-resolution crystal structure of the second member of the long Rib domain, a unique subclass within the Rib-domain family, derived from Limosilactobacillus reuteri is presented. The data not only demonstrate a highly conserved structure within the long Rib domain, but also highlight an evolutionary convergence in structural architecture with other modular domains found in cell-adhesion molecules.


Assuntos
Limosilactobacillus reuteri , Modelos Moleculares , Domínios Proteicos , Limosilactobacillus reuteri/química , Limosilactobacillus reuteri/metabolismo , Limosilactobacillus reuteri/genética , Cristalografia por Raios X , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Adesinas Bacterianas/química , Adesinas Bacterianas/genética , Adesinas Bacterianas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
13.
Vet Res ; 55(1): 63, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760810

RESUMO

The maintenance of viral protein homeostasis depends on the interaction between host cell proteins and viral proteins. As a molecular chaperone, heat shock protein 70 (HSP70) has been shown to play an important role in viral infection. Our results showed that HSP70 can affect translation, replication, assembly, and release during the life cycle of duck hepatitis A virus type 1 (DHAV-1). We demonstrated that HSP70 can regulate viral translation by interacting with the DHAV-1 internal ribosome entry site (IRES). In addition, HSP70 interacts with the viral capsid proteins VP1 and VP3 and promotes their stability by inhibiting proteasomal degradation, thereby facilitating the assembly of DHAV-1 virions. This study demonstrates the specific role of HSP70 in regulating DHAV-1 replication, which are helpful for understanding the pathogenesis of DHAV-1 infection and provide additional information about the role of HSP70 in infection by different kinds of picornaviruses, as well as the interaction between picornaviruses and host cells.


Assuntos
Proteínas de Choque Térmico HSP70 , Vírus da Hepatite do Pato , Sítios Internos de Entrada Ribossomal , Replicação Viral , Vírus da Hepatite do Pato/fisiologia , Vírus da Hepatite do Pato/genética , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP70/genética , Animais , Proteínas Estruturais Virais/metabolismo , Proteínas Estruturais Virais/genética , Patos , Doenças das Aves Domésticas/virologia , Infecções por Picornaviridae/veterinária , Infecções por Picornaviridae/virologia , Infecções por Picornaviridae/metabolismo , Proteínas do Capsídeo/metabolismo , Proteínas do Capsídeo/genética , Hepatite Viral Animal/virologia , Hepatite Viral Animal/metabolismo , Biossíntese de Proteínas
14.
Int J Biol Macromol ; 268(Pt 2): 131936, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38692533

RESUMO

With the increasing environmental and ecological problems caused by petroleum-based packaging materials, the focus has gradually shifted to natural resources for the preparation of functional food packaging materials. In addition to biodegradable properties, nanocellulose (NC) mechanical properties, and rich surface chemistry are also fascinating and desired to be one of the most probable green packaging materials. In this review, we firstly introduce the recent progress of novel applications of NC in food packaging, including intelligent packaging, nano(bio)sensors, and nano-paper; secondly, we focus on the modification techniques of NC to summarize the properties (antimicrobial, mechanical, hydrophobic, antioxidant, and so on) that are required for food packaging, to expand the new synthetic methods and application areas. After presenting all the latest advances related to material design and sustainable applications, an overview summarizing the safety of NC is presented to promote a continuous and healthy movement of NC toward the field of truly sustainable packaging.


Assuntos
Celulose , Embalagem de Alimentos , Embalagem de Alimentos/métodos , Celulose/química , Nanoestruturas/química , Antioxidantes/química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Interações Hidrofóbicas e Hidrofílicas
15.
Anal Chim Acta ; 1311: 342743, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38816160

RESUMO

BACKGROUND: MicroRNA (miRNA) emerges as important cancer biomarker, accurate detection of miRNA plays an essential role in clinical sample analysis and disease diagnosis. However, it remains challenging to realize highly sensitive detection of low-abundance miRNA. Traditional detection methods including northern blot and real-time PCR have realized quantitative miRNA detection. However, these detection methods are involved in sophisticated operation and expensive instruments. Therefore, the development of novel sensing platform with high sensitivity and specificity for miRNA detection is urgently demanded for disease diagnosis. RESULTS: In this work, a novel electrochemical biosensor was constructed for miRNA detection based on target-driven cascade amplified assembly of electroactive covalent organic frameworks (COFs) on tetrahedral DNA nanostructure with multiplex recognition domains (m-TDN). COFs were employed as nanocarriers of electroactive prussian blue (PB) molecules by the "freeze-drying-reduction" method without the use of DNA as gatekeeper, which was simple, mild and efficient. The target-triggered catalytic hairpin assembly (CHA) and glutathione reduction could convert low-abundance miRNA into a large amount of Mn2+. Without the addition of exogenous Mn2+, the dynamically-generated Mn2+-powered DNAzyme cleavage process induced abundant PB-COFs probe assembled on the four recognition domains of m-TDN, resulting in significantly signal output. Using miRNA-182-5p as the model target, the proposed electrochemical biosensor achieved ultrasensitive detection of miRNA-182-5p in the range of 10 fM-100 nM with a detection limit of 2.5 fM. SIGNIFICANCE AND NOVELTY: Taking advantages of PB-COFs probe as the enhanced signal labels, the integration of CHA, Mn2+-powered DNAzyme and m-TDN amplification strategy significantly improved the sensitivity and specificity of the biosensor. The designed sensing platform was capable of miRNA detection in complex samples, which provided a new idea for biomarker detection, holding promising potential in clinical diagnosis and disease screening.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , DNA , Técnicas Eletroquímicas , Estruturas Metalorgânicas , MicroRNAs , Nanoestruturas , MicroRNAs/análise , Estruturas Metalorgânicas/química , Técnicas Biossensoriais/métodos , Nanoestruturas/química , DNA/química , Humanos , DNA Catalítico/química , DNA Catalítico/metabolismo , Limite de Detecção , Ferrocianetos/química
16.
Oncologist ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38821519

RESUMO

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is a liposome-encapsulated form of doxorubicin with equivalent efficacy and less cardiotoxicity. This phase 2 study evaluated the efficacy and safety of the PLD-containing CHOP regimen in newly diagnosed patients with aggressive peripheral T-cell lymphomas (PTCL). METHODS: Patients received PLD, cyclophosphamide, vincristine/vindesine, plus prednisone every 3 weeks for up to 6 cycles. The primary endpoint was the objective response rate at the end of treatment (EOT). RESULTS: From September 2015 to January 2017, 40 patients were treated. At the EOT, objective response was achieved by 82.5% of patients, with 62.5% complete response. As of the cutoff date (September 26, 2023), median progression-free survival (mPFS) and overall survival (mOS) were not reached (NR). The 2-year, 5-year, and 8-year PFS rates were 55.1%, 52.0%, and 52.0%. OS rate was 80.0% at 2 years, 62.5% at 5 years, and 54.3% at 8 years. Patients with progression of disease within 24 months (POD24) had worse prognosis than those without POD24, regarding mOS (41.2 months vs NR), 5-year OS (33.3% vs 94.4%), and 8-year OS (13.3% vs 94.4%). Common grade 3-4 adverse events were neutropenia (87.5%), leukopenia (80.0%), anemia (17.5%), and pneumonitis (17.5%). CONCLUSION: This combination had long-term benefits and manageable tolerability, particularly with less cardiotoxicity, for aggressive PTCL, which might provide a favorable benefit-risk balance. CLINICALTRIALS.GOV IDENTIFIER: Chinese Clinical Trial Registry, ChiCTR2100054588; IRB Approved: Ethics committee of Fudan University Shanghai Cancer Center (Date 2015.8.31/No. 1508151-13.

18.
Virology ; 595: 110084, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38692132

RESUMO

Duck Tembusu virus (DTMUV) belongs to the Flaviviridae family and mainly infects ducks. The genome of DTMUV is translated into a polyprotein, which is further cleaved into several protein by viral NS2B3 protease and host proteases. Crucially, the cleavage of the NS2A/2B precursor during this process is essential for the formation of replication complexes and viral packaging. Previous research has demonstrated that alanine mutations in NS2A/2B (P1P1' (AA)) result in an attenuated strain (rDTMUV-NS2A/2B-P1P1' (AA)) by disrupting NS2A/2B cleavage. In this study, we investigate the effects of the P1P1' (AA) mutation on the viral life cycle and explore compensatory mutations in rDTMUV-NS2A/2B-P1P1' (AA). Infected ducklings exhibit similar body weight gain and viral tissue loads to DTMUV-WT. Compensatory mutations E-M349E and P1(T) emerge, restoring proliferation levels to those of rDTMUV-WT. Specifically, E-M349E enhances viral packaging, while P1(T) reinstates NS2A/2B proteolysis in vitro. Thus, our findings reveal novel compensatory sites capable of restoring the attenuated DTMUV during polyprotein cleavage and packaging.


Assuntos
Patos , Flavivirus , Doenças das Aves Domésticas , Proteínas não Estruturais Virais , Montagem de Vírus , Replicação Viral , Animais , Patos/virologia , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Flavivirus/genética , Flavivirus/fisiologia , Doenças das Aves Domésticas/virologia , Infecções por Flavivirus/virologia , Mutação
19.
J Phys Condens Matter ; 36(32)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38701826

RESUMO

Er3+doped barium yttrium fluoride (BaY2F8) crystal has gained long-term attention due to its great potential in laser and medical device applications. However, the local structures of Er3+doped BaY2F8system (Er:BYF) remain uncertain, and the effect of doping concentration on structures and properties is unknown. Therefore, in this study, the first-principles study of the structural evolution of ErxBaY2-xF8(x= 0.125, 0.25) crystals was carried out. By means of density functional theory and particle swarm optimization algorithm, the stable structures of Er:BYF crystals with two different concentrations are shown as standard monoclinic structures withP2 symmetry for the first time. The impurity Er3+ions successfully enter the main lattice, replacing the Y3+ions, and forming a [ErF8]5-polyhedron withC2point group symmetry. By calculating the electronic properties, the band gap values of the two structures are significantly reduced compared with that of pure BaY2F8crystal. However, the conduction band does not break through the Fermi level, and the crystals still maintain the insulation characteristic. According to the calculation of the electron local density function, we conclude that Er-F and Y-F in Er:BYF are connected by ionic bonds. These results fill a theoretical gap in the study of Er:BYF crystals and provide inspiration for structural evolution and material design at different doping concentrations.

20.
Int J Biol Macromol ; 269(Pt 1): 132055, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38704073

RESUMO

Pretreatment is the key step to convert lignocelluloses to sustainable biofuels, biochemicals or biomaterials. In this study, a green pretreatment method based on choline chloride-lactic acid deep eutectic solvent (ChCl-LA) and niobium-based single-atom catalyst (Nb/CN) was developed for the fractionation of corn straw and further enzymatic hydrolysis of cellulose. With this strategy, significant lignin removal of 96.5 % could be achieved when corn straw was pretreated by ChCl-LA (1:2) DES over Nb/CN under 120 °C for 6 h. Enzymatic hydrolysis of the cellulose-enriched fraction (CEF) presented high glucose yield of 92.7 % and xylose yield of 67.5 %. In-depth investigations verified that the high yields of fractions and monosaccharides was attributed to the preliminary fractionation by DES and the deep fractionation by Nb/CN. Significantly, compared to other reported soluble catalysts, the synthesized single-atom catalyst displayed excellent reusability by simple filtration and enzymatic hydrolysis. The recyclability experiments showed that the combination of ChCl-LA DES and Nb/CN could be repeated at least three times for corn straw fractionation, moreover, the combination displayed remarkable feedstock adaptability.


Assuntos
Colina , Solventes Eutéticos Profundos , Ácido Láctico , Lignina , Nióbio , Lignina/química , Nióbio/química , Catálise , Colina/química , Hidrólise , Solventes Eutéticos Profundos/química , Ácido Láctico/química , Zea mays/química , Fracionamento Químico/métodos
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