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1.
Am J Cancer Res ; 14(4): 1712-1729, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726277

RESUMO

Melanoma is the most aggressive type of skin cancer and has a high mortality rate once metastasis occurs. Hypoxia is a universal characteristic of the microenvironment of cancer and a driver of melanoma progression. In recent years, long noncoding RNAs (lncRNAs) have attracted widespread attention in oncology research. In this study, screening was performed and revealed seven hypoxia-related lncRNAs AC008687.3, AC009495.1, AC245128.3, AL512363.1, LINC00518, LINC02416 and MCCC1-AS1 as predictive biomarkers. A predictive risk model was constructed via univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Patients were grouped according to the model risk score, and Kaplan-Meier analysis was performed to compare survival between groups. Functional and pathway enrichment analyses were performed to compare gene set enrichment between groups. Moreover, a nomogram was constructed with the risk score as a variable. In both the training and validation sets, patients in the low-risk group had better overall survival than did those in the high-risk group (P<0.001). The 3-, 5- and 10-year area under the curve (AUC) values for the nomogram model were 0.821, 0.795 and 0.820, respectively. Analyses of immune checkpoints, immunotherapy response, drug sensitivity, and mutation landscape were also performed. The results suggested that the low-risk group had a better response to immunotherapeutic. In addition, the nomogram can effectively predict the prognosis and immunotherapy response of melanoma patients. The signature of seven hypoxia-related lncRNAs showed great potential value as an immunotherapy response biomarker, and these lncRNAs might be treatment targets for melanoma patients.

2.
BMC Genomics ; 25(1): 373, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627659

RESUMO

The common dolphin (Delphinus delphis) is widely distributed worldwide and well adapted to various habitats. Animal genomes store clues about their pasts, and can reveal the genes underlying their evolutionary success. Here, we report the first high-quality chromosome-level genome of D. delphis. The assembled genome size was 2.56 Gb with a contig N50 of 63.85 Mb. Phylogenetically, D. delphis was close to Tursiops truncatus and T. aduncus. The genome of D. delphis exhibited 428 expanded and 1,885 contracted gene families, and 120 genes were identified as positively selected. The expansion of the HSP70 gene family suggested that D. delphis has a powerful system for buffering stress, which might be associated with its broad adaptability, longevity, and detoxification capacity. The expanded IFN-α and IFN-ω gene families, as well as the positively selected genes encoding tripartite motif-containing protein 25, peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, and p38 MAP kinase, were all involved in pathways for antiviral, anti-inflammatory, and antineoplastic mechanisms. The genome data also revealed dramatic fluctuations in the effective population size during the Pleistocene. Overall, the high-quality genome assembly and annotation represent significant molecular resources for ecological and evolutionary studies of Delphinus and help support their sustainable treatment and conservation.


Assuntos
Golfinhos Comuns , Animais , Evolução Biológica , Cromossomos/genética , Imunidade Inata/genética , Filogenia
3.
Artigo em Inglês | MEDLINE | ID: mdl-38662093

RESUMO

Ketamine has demonstrated rapid and sustained antidepressant effects, marking its emergence as an innovative treatment of depression. Despite the growing number of preclinical and clinical studies exploring the antidepressant effects of ketamine and its enantiomers, a comprehensive bibliometric analysis in this field has yet to be conducted. This study employs bibliometric methods and visualization tools to examine the literature and identify key topics related to the antidepressant effects of ketamine and its enantiomers. We sourced publications on the antidepressant effects of ketamine and its enantiomers from the Web of Science Core Collection (WOSCC) database, covering the period from 2000 to 2023. Tools such as VOSviewer, CiteSpace and the R package "bibliometrix" were utilized for visual analysis. The study included 4,274 publications, with a notable increase in publications peaking in 2022. Co-occurrence analysis highlighted two primary research focal points: the efficacy and safety of ketamine and its enantiomers in treating depression, and the mechanisms behind their antidepressant effects. In conclusion, this analysis revealed a significant increase in research on the antidepressant effects of ketamine and its enantiomers over the past two decades, leading to the approval of esketamine nasal spray for treatment-resistant depression. The rapid antidepressant effects of ketamine have spurred further studies into its mechanisms of action and the search for new antidepressants with fewer side effects.

4.
Adv Mater ; : e2403078, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38583072

RESUMO

Composite polymer solid electrolytes (CPEs), possessing good rigid flexible, are expected to be used in solid-state lithium-metal batteries. The integration of fillers into polymer matrices emerges as a dominant strategy to improve Li+ transport and form a Li+-conducting electrode-electrolyte interface. However, challenges arise as traditional fillers: 1) inorganic fillers, characterized by high interfacial energy, induce agglomeration; 2) organic fillers, with elevated crystallinity, impede intrinsic ionic conductivity, both severely hindering Li+ migration. Here, a concept of super-ionic conductor soft filler, utilizing a Li+ conductivity nanocellulose (Li-NC) as a model, is introduced which exhibits super-ionic conductivity. Li-NC anchors anions, and enhances Li+ transport speed, and assists in the integration of cathode-electrolyte electrodes for room temperature solid-state batteries. The tough dual-channel Li+ transport electrolyte (TDCT) with Li-NC and polyvinylidene fluoride (PVDF) demonstrates a high Li+ transfer number (0.79) due to the synergistic coordination mechanism in Li+ transport. Integrated electrodes' design enables stable performance in LiNi0.5Co0.2Mn0.3O2|Li cells, with 720 cycles at 0.5 C, and 88.8% capacity retention. Furthermore, the lifespan of Li|TDCT|Li cells over 4000 h and Li-rich Li1.2Ni0.13Co0.13Mn0.54O2|Li cells exhibits excellent performance, proving the practical application potential of soft filler for high energy density solid-state lithium-metal batteries at room temperature.

5.
Eur J Drug Metab Pharmacokinet ; 49(3): 317-330, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38393637

RESUMO

BACKGROUND AND OBJECTIVE: HY-088 injection is an ultrasmall superparamagnetic iron oxide nanoparticle (USPIOs) composed of iron oxide crystals coated with polyacrylic acid (PAA) on the surface. The purpose of this study was to investigate the pharmacokinetics, tissue distribution, and mass balance of HY-088 injection. METHODS: The pharmacokinetics of [55Fe]-HY-088 and [14C]-HY-088 were investigated in 48 SD rats by intravenous injection of 8.5 (low-dose group), 25.5 (medium-dose group), and 85 (high-dose group) mg/100 µCi/kg. Tissue distribution was studied by intravenous injection of 35 mg/100 µCi/kg in 48 SD rats, and its tissue distribution in vivo was obtained by ex vivo tissue assay. At the same time, [14C]-HY-088 was injected intravenously at a dose of 25.5 mg/100 µCi/kg into 16 SD rats, and its tissue distribution in vivo was studied by quantitative whole-body autoradiography. [14C]-HY-088 and [55Fe]-HY-088 were injected intravenously into 24 SD rats at a dose of 35 mg/100 µCi/kg, and their metabolism was observed. RESULTS: In the pharmacokinetic study, [55Fe]-HY-088 reached the maximum observed concentration (Cmax) at 0.08 h in the low- and medium-dose groups of SD rats. [14C]-HY-088 reached Cmax at 0.08 h in the three groups of SD rats. The area under the concentration-time curve (AUC) of [55Fe]-HY-088 and [14C]-HY-088 increased with increasing dose. In the tissue distribution study, [55Fe]-HY-088 and [14C]-HY-088 were primarily distributed in the liver, spleen, and lymph nodes of both female and male rats. In the mass balance study conducted over 57 days, the radioactive content of 55Fe from [55Fe]-HY-088 was primarily found in the carcass, accounting for 86.42 ± 4.18% in females and 95.46 ± 6.42% in males. The radioactive recovery rates of [14C]-HY-088 in the urine of female and male rats were 52.99 ± 5.48% and 60.66 ± 2.23%, respectively. CONCLUSIONS: Following single intravenous administration of [55Fe]-HY-088 and [14C]-HY-088 in SD rats, rapid absorption was observed. Both [55Fe]-HY-088 and [14C]-HY-088 were primarily distributed in the liver, spleen, and lymph nodes. During metabolism, the radioactivity of [55Fe]-HY-088 is mainly present in the carcass, whereas the 14C-labeled [14C]-HY-088 shell PAA is eliminated from the body mainly through the urine.


Assuntos
Nanopartículas Magnéticas de Óxido de Ferro , Ratos Sprague-Dawley , Animais , Distribuição Tecidual , Masculino , Ratos , Feminino , Nanopartículas Magnéticas de Óxido de Ferro/química , Injeções Intravenosas , Nanopartículas de Magnetita/química , Dextranos/farmacocinética , Resinas Acrílicas/química , Resinas Acrílicas/farmacocinética
6.
Toxicol Appl Pharmacol ; 484: 116840, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38307258

RESUMO

Isoprenaline hydrochloride (IH) is a ß-adrenergic receptor agonist commonly used in the treatment of hypotension, shock, asthma, and other diseases. However, IH-induced cardiotoxicity limits its application. A large number of studies have shown that long noncoding RNA (lncRNA) regulates the occurrence and development of cardiovascular diseases. This study aimed to investigate whether abnormal lncRNA expression is involved in IH-mediated cardiotoxicity. First, the Sprague-Dawley (SD) rat myocardial injury model was established. Circulating exosomes were extracted from the plasma of rats and identified. In total, 108 differentially expressed (DE) lncRNAs and 150 DE mRNAs were identified by sequencing. These results indicate that these lncRNAs and mRNAs are substantially involved in chemical cardiotoxicity. Further signaling pathway and functional studies indicated that lncRNAs and mRNAs regulate several biological processes, such as selective mRNA splicing through spliceosomes, participate in sphingolipid metabolic pathways, and play a certain role in the circulatory system. Finally, we obtained 3 upregulated lncRNAs through reverse transcription-quantitative PCR (RT-qPCR) verification and selected target lncRNA-mRNA pairs according to the regulatory relationship of lncRNA/mRNA, some of which were associated with myocardial injury. This study provides valuable insights into the role of lncRNAs as novel biomarkers of chemical-induced cardiotoxicity.


Assuntos
Exossomos , RNA Longo não Codificante , Ratos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Isoproterenol/toxicidade , Redes Reguladoras de Genes , Ratos Sprague-Dawley , Cardiotoxicidade , Exossomos/genética , Exossomos/metabolismo , RNA Mensageiro/metabolismo
7.
Small ; : e2310825, 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38342581

RESUMO

Bifunctional electrocatalysts with excellent activity and durability are highly desirable for alkaline overall water splitting, yet remain a significant challenge. In this contribution, palm-like Mo5 N6 /Ni3 S2 heterojunction arrays anchored in conductive Ni foam (denoted as Mo5 N6 -Ni3 S2 HNPs/NF) are developed. Benefiting from the optimized electronic structure configuration, hierarchical branched structure and abundant heterogeneous interfaces, the as-synthesized Mo5 N6 -Ni3 S2 HNPs/NF electrode exhibits remarkably stable bifunctional electrocatalytic activity in 1 m KOH solution. It only requires ultralow overpotentials of 59 and 190 mV to deliver a current density of 10 mA cm-2 for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in 1 m KOH solution, respectively. Importantly, the overall water splitting electrolyzer assembled by Mo5 N6 -Ni3 S2 HNPs/NF exhibits an exceptionally low cell voltage (1.48 V@10 mA cm-2 ) and outstanding durability, surpassing most of the reported Ni-based bifunctional materials. Density functional theory (DFT) further confirms the heterostructure can optimize the Gibbs free energies of H and O-containing intermediates (OH, O, OOH) during HER and OER processes, thereby accelerating the catalytic kinetics of electrochemical water splitting. The findings provide a new design strategy toward low-cost and excellent catalysts for overall water splitting.

8.
Animals (Basel) ; 14(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38396609

RESUMO

Microplastics (MPs) pollution is of global concern, which poses serious threats to various marine organisms, including many threatened apex predators. In this study, MPs were investigated from nine cetaceans of four different species, comprising one common dolphin (Delphinus delphis), two pygmy sperm whales (Kogia breviceps), one ginkgo-toothed beaked whale (Mesoplodon ginkgodens), and five Indo-Pacific humpback dolphins (Sousa chinensis) stranded along the western coast of the Taiwan Strait from the East China Sea based on Fourier transform infrared (FTIR) spectroscopy analysis. Mean abundances of 778 identified MPs items were 86.44 ± 12.22 items individual-1 and 0.43 ± 0.19 items g-1 wet weight of intestine contents, which were found predominantly to be transparent, fiber-shaped polyethylene terephthalate (PET) items usually between 0.5 and 5 mm. The abundance of MPs was found at a slightly higher level and significantly correlated with intestine contents mass (p = 0.0004*). The MPs source was mainly likely from synthetic fibers-laden sewage discharged from intense textile industries. Our report represents the first study of MPs in pelagic and deep-diving cetaceans in China, which not only adds baseline data on MPs for cetaceans in Asian waters but also highlights the further risk assessment of MPs consumption in these threatened species.

9.
Poult Sci ; 103(2): 103286, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38100949

RESUMO

In this study, we evaluated the enrichment efficiency of lutein in eggs and its function in preventing fatty liver hemorrhagic syndrome (FLHS) in aged laying hens. Five groups of laying hens (65 wk old) were fed basal diets supplemented with 0, 30, 60, 90, or 120 mg/kg of lutein. The supplementation period lasted 12 wk followed by 2 wk of lutein depletion in feed. The results revealed that lutein efficiently enriched the egg yolks and improved their color with a significant increase in relative redness (P < 0.001). Lutein accumulation increased in the egg yolk until day 10, then depletion reached a minimum level after 14 d. Overall, zeaxanthin content in all the groups was similar throughout the experimental period. However, triglycerides and total cholesterol were significantly decreased in the liver (P < 0.05) but not significantly different in the serum (P > 0.05). In the serum, the lipid metabolism enzyme acetyl-CoA synthetase was significantly reduced (P < 0.05), whereas dipeptidyl-peptidase 4 was not significantly different (P > 0.05), and there was no statistical difference of either enzyme in the liver (P > 0.05). Regarding oxidation and inflammation-related indexes, malondialdehyde, tumor necrosis factors alpha, interleukin-6, and interleukin-1 beta were decreased, whereas superoxide dismutase and total antioxidant capacity increased in the liver (P < 0.001). The function of lutein for the same indexes in serum was limited. It was concluded that lutein efficiently enriched the egg yolk of old laying hens to improve their color and reached the highest level on day 10 without being subject to a significant conversion into zeaxanthin. At the same time, lutein prevented liver steatosis in aged laying hens by exerting strong antioxidant and anti-inflammatory functions, but also through the modulation of lipid metabolism, which may contribute to reducing the incidence of FLHS in poultry.


Assuntos
Anormalidades Múltiplas , Anormalidades Craniofaciais , Fígado Gorduroso , Transtornos do Crescimento , Comunicação Interventricular , Luteína , Feminino , Animais , Luteína/metabolismo , Antioxidantes/metabolismo , Galinhas/metabolismo , Zeaxantinas/metabolismo , Suplementos Nutricionais/análise , Dieta/veterinária , Gema de Ovo/metabolismo , Fígado Gorduroso/prevenção & controle , Fígado Gorduroso/veterinária , Ração Animal/análise
10.
Exp Ther Med ; 27(1): 32, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38125338

RESUMO

Endoscopic retrograde cholangiopancreatography (ERCP) has become a common treatment method for common bile duct stones. However, ERCP is also associated with a high risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). Identification of risk factors is essential for reducing the incidence of PEP. The present study aimed to summarize the risk factors for PEP by performing a meta-analysis. Therefore, studies published between 2000 and 2022 were screened in PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Digital Periodicals and the Weipu Database, with no language restrictions. Newcastle-Ottawa Scale was used to assess the quality of the included studies. Stata 17.0 software was utilized for the meta-analysis of 14 possible risk factors. Overall, 15 high-quality studies were included into the present meta-analysis. The results showed that female [odds ratio (OR), 1.42; 95% CI, 1.23-1.64), age <60 years (OR, 1.53; 95% CI, 1.06-2.21), difficult intubation (OR, 4.87; 95% CI, 2.73-8.68), ≥3 cannulation attempts (OR, 9.64; 95% CI, 4.16-22.35), cannulation time ≥10 min (OR, 2.37; 95% CI, 1.67-3.35), history of pancreatitis (OR, 2.95; 95% CI, 1.06-5.51), pancreatic duct visualization (OR, 3.63; 95% CI, 2.47-5.34) and sphincter of Oddi dysfunction (OR, 5.72; 95% CI, 1.80-18.24) are potential risk factors for PEP (P<0.05). In conclusion, the present meta-analysis suggests that PEP can be affected by several risk factors, particularly the technique-related factors such as the frequency and time of cannulation. Therefore, effective precautions should be taken as early as possible to reduce the incidence of PEP.

11.
Front Vet Sci ; 10: 1292401, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38076566

RESUMO

Introduction: The emergence of multidrug-resistant (MDR) strains of Salmonella, which is a genus of important zoonotic pathogens, has aroused great public health concern worldwide. Methods: In this study, 167 strains of Salmonella were isolated from 947 samples from broiler farms, slaughterhouses, and markets in Shandong Province. Antibiotic sensitivity testing was performed, and 70 strains of Salmonella were screened out by whole-genome sequencing (WGS) to evaluate serotypes, antimicrobial resistance genes (ARGs), the prevalence of class 1 integrons, the plasmid carriage rate, and phylogenetic characteristics and for multilocus sequence typing (MLST). Results: The results showed that the 167 isolates showed the highest resistance to ampicillin (AMP, 87.4%), sulfamethoxazole (SF, 87.4%), compound sulfamethoxazole (SXT, 81.4%), nalidixic acid (NAL, 80.2%), and amoxicillin/clavulanic acid (A/C, 77.8%). All the strains were sensitive to meropenem (MEM), and 91.0% of the isolates were MDR strains. We screened a total of 45 ARGs, with the highest detection rate observed for the tetracycline (TET) resistance gene tet (A) (81.4%). A total of 21 types of plasmid replicons were detected in Salmonella, of which IncX1 was the most common (74.3%), and 62.9% of the isolates carried a class 1 integron. In addition, a total of 11 different serotypes were detected, with S. enteritidis as the predominant serovar., followed by S. infantis and S. Newport. Twelve different sequence types (STs) were detected, among which ST11 was the main type. There was a strong correspondence between serotypes and STs. We also found that S. Indiana and S. Kentucky had extremely high rates of resistance to ciprofloxacin (CIP) and third-generation cephalosporins. System-wide genome analysis showed the occurrence of long-distance transmission across fields. Conclusion: In conclusion, the detection of multidrug resistance and isolates carrying multidrug resistance genes is the main problem, and emergency strategies should be implemented to address this issue.

12.
Macromol Rapid Commun ; 44(23): e2300412, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37713720

RESUMO

Polydiacetylenes, as a class of conjugated polymers with alternating conjugated C═C and C≡C bonds, have emerged as a promising probe material for biomedical Raman imaging, given their ultrastrong Raman scattering intensity. However, the relationship between the structure, especially the molecular length of polydiacetylenes, and their Raman scattering intensity remains unclear. In this work, a series of water-soluble polydiacetylenes, namely poly(deca-4,6-diynedioic acid) (PDDA) with different molecular weights (MWs), is prepared through controlled polymerization and degradation. The ultraviolet-visible (UV-vis) absorption spectroscopic and Raman spectroscopic studies on these polymers reveal that the Raman scattering intensity of PDDA increases nonlinearly with the MW. The MW-Raman scattering intensity relationship in the polymerization process is completely different from that in the degradation process. In contrast, the Raman scattering intensity increases more linearly with the maximal absorbance of the polymer, and the relationship between the Raman scattering intensity and the maximal absorbance of PDDA in the polymerization process is consistent with that in the degradation process. The Raman scattering intensity of PDDA hence exhibits a better dependence on the effective conjugation length of the polymer, which should guide the future design of conjugated polymers for Raman imaging applications.


Assuntos
Polímeros , Análise Espectral Raman , Polímeros/química , Análise Espectral Raman/métodos , Polímero Poliacetilênico/química , Peso Molecular
13.
Sci Total Environ ; 904: 166742, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37659521

RESUMO

Forest swamp ecosystems plays crucial role in the global carbon cycle. However, the effects of forest swamp succession on soil organic matter (SOM) and microbial community structure remain unclear. To determine the drivers of SOM change and soil microbial communities in forest swamp succession, a 'space instead of time' approach was used. Soil samples from 0 to 40 cm were collected along forest swamp (early stage), dried-up forest swamp (middle stage), and forest (late stage) ecosystems. Our findings reveal that as succession progresses, the relative content of aromatics decreases and SOM undergoes a transition towards a more readily degradable form. These changes affect soil carbon sequestration and nutrient availability. Bacterial diversity was significantly influenced by succession and changes in soil depth, with fungi exhibiting higher resilience. Soil properties and environmental conditions exert influence over the structure and function of microorganisms. As succession occurred, microbial interactions shifted from cooperation to competition, with bacteria displaying a deterministic distribution pattern and fungi exhibiting a random distribution pattern. SOM quality plays a key role in shaping microbial communities and influencing their growth strategies. Microorganisms are the major drivers of soil respiration, with K-strategist dominated communities in early succession exhibiting slower degradation rates, whereas r-strategists dominated in later stages, leading to faster decomposition.


Assuntos
Microbiota , Solo , Solo/química , Áreas Alagadas , Carbono , Florestas , Bactérias , Fungos , Microbiologia do Solo
14.
Microb Pathog ; 180: 106149, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37169314

RESUMO

The abundance of specific gut microorganisms is strongly associated with the concentrations of microbially modified bile acids. This study aimed to investigate the composition of intestinal microbiota in rats subjected to bile duct ligation or biliary drainage. Extrahepatic bile duct ligation was conducted to induce bile duct obstruction in rats. The bile was drained via a percutaneous biliary drainage catheter to cause bile deficiency. The total DNA extracted from fecal samples was sequenced with 16S DNA sequencing. Taxonomic classifications were conducted using the Mothur algorithm and SILVA138 database and were presented along with the abundance presented using a heatmap. The inter- and intra-group differences in the intestinal microbiome composition were analyzed by ANOSIM test. The biomarker microorganisms were screened using the Linear discriminant analysis Effect size method. The possible functional pathways were predicted using the Tax4Fun package. A total of 3277 operational taxonomic units (OTUs) were examined, with 2410 in the Kongbai group, 2236 in the Gengzu group, and 1763 in the Yinliu group. The composition of microorganisms at the levels of phylum, class, order, family, and genus was altered in rats with bile duct obstruction. This composition was then restored by biliary drainage. The top 10 predominant microorganisms were identified that led to the inter-group differences. Functional annotation revealed that the potential functions of the microorganisms with significant differences were enriched in metabolism, cellular processes, and genetic and environmental information processing. The intestinal microbial community was significantly changed in rats with bile duct obstruction. The changes in the abundance of intestinal microbiota Prevotellaceae and Enterobacteriaceae were statistically significant after biliary drainage treatment.


Assuntos
Colestase , Microbioma Gastrointestinal , Ratos , Animais , Drenagem/métodos , Bile , Ácidos e Sais Biliares
15.
Adv Mater ; 35(17): e2210879, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36786375

RESUMO

Efficient therapeutic strategies that concurrently target both Aß aggregation and oxidative stress in the Alzheimer's disease (AD) microenvironment emerge as a cutting-edge tool to combat the intricate pathogenesis of AD. Here, a multivalent nanobody conjugate with rigid, reactive oxygen species (ROS) scavenging scaffold is developed to achieve simultaneous Aß amyloidogenesis mitigation, ROS elimination, and Aß plaque clearance. Grafting Aß segment (33-GLMVGGVVIA-42) into the third complementary-determining region of a parent nanobody generates an engineered nanobody NB that can recognize Aß and inhibit its aggregation through homotypic interactions. NB is further genetically modified with a fragment of human interleukin-1ß (163-VQGEESNDK-171), so that the obtained fusion nanobody NBIL can also facilitate the Aß clearance by microglia. Linking NBIL covalently onto a rigid, ROS scavenging scaffold poly(deca-4,6-diynedioic acid) (PDDA) creates the multivalent nanobody conjugate PNBIL, which not only boosts the binding affinity between NBIL and Aß aggregates for nearly 100 times but also possesses a long-term capability of oxidative stress alleviation, inflammation reduction, and neuron protection. PNBIL has significantly attenuated symptoms on two AD mouse models through amyloidogenesis inhibition and AD microenvironment modulation, validating that the multivalent nanobody conjugate design based on combinatory nanobody and molecular engineering is a promising approach of multi-target therapeutic strategies.


Assuntos
Doença de Alzheimer , Animais , Camundongos , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Peptídeos beta-Amiloides/metabolismo , Estresse Oxidativo
16.
ACS Nano ; 17(4): 3873-3888, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36791326

RESUMO

Accurate diagnosis and timely therapeutic intervention of inflammatory bowel disease (IBD) is essential in preventing the progression of the disease, although it still represents an insurmountable challenge. Here we report the design of bacterial-flagella-inspired polydiiododiacetylene (PIDA) nanofibers and its performance in targeted computed tomography (CT) imaging and on-demand therapeutic intervention of IBD. With a morphology mimicking bacterial flagella, PIDA nanofibers attach on the mucus layer of the gastrointestinal (GI) tract after oral administration, evenly distributing on the GI surface to portray the GI lining under CT scan within 2 h. PIDA can retain for a longer time in the damaged mucosa at the inflamed lesions than in normal GI tissues to enable the targeted CT visualization of IBD. PIDA also scavenges reactive oxygen species and ameliorates gut dysbiosis attributed to its iodine-substituted polydiacetylene structure, so that the enriched PIDA nanofibers at the targeted IBD lesions can alleviate the inflammation while maintaining the gut microbiota homeostasis, thus promoting the rebalance of GI microenvironment and the mucosal healing.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Nanofibras , Humanos , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inflamação , Tomografia Computadorizada por Raios X
17.
Environ Res ; 216(Pt 4): 114800, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36379233

RESUMO

Fe as an important redox-active transition metal plays a key role in the carbon cycle of ecosystems. To date, the mechanisms by which Fe affects organic carbon (soil respiration rate [Rs] and dissolved organic carbon [DOC] structure) remain unclear, because most studies only focused on the effect of Fe on soil organic carbon content. To understand these effects, a 30-day laboratory incubation experiment was conducted using forest swamp soils from northeastern China amended with different concentrations of exogenous Fe (no exogenous Fe added [L0], add exogenous Fe at 1 time the soil background value [L1], add exogenous Fe at 2 times the soil background value [L2]). Our results showed that exogenous Fe addition reduced the soil respiration rate by 54.8% during the incubation time. The DOC concentration decreased by 40.5% with exogenous Fe addition during the incubation time. The dissolved organic matter (DOM) characteristic parameters showed apparent variations (p < 0.05), including significant increases in the fluorescence and biological index and significant decreases in the humification index, which indicate that exogenous Fe addition reduced humification, which may lead to the increased fixation of dissolved organic carbon. In addition significant increases in tryptophan-like DOM was observed when exogenous Fe addition resulted in a soil Fe concentration of twice the background value (p < 0.05). These findings indicate that exogenous Fe addition promotes the production of endogenous soil DOC by microorganisms. Overall, Our study uses three-dimensional fluorescence spectroscopy techniques combined with the parallel factor analysis (PARAFAC) to characterize the dissolved organic matter components in soil samples under exogenous Fe addition conditions, with a view to exploring the differences in the effects of Fe on the DOC concentration and structure of wetland soils, providing a theoretical basis for the mechanisms of soil carbon fixation and soil organic matter transformation in wetland soils.


Assuntos
Solo , Áreas Alagadas , Solo/química , Carbono , Matéria Orgânica Dissolvida , Ecossistema , Taxa Respiratória , Florestas , China
18.
Front Immunol ; 14: 1307588, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38235137

RESUMO

Background: Cancer-associated fibroblasts (CAFs) contribute to the progression and treatment of breast cancer (BRCA); however, risk signatures and molecular targets based on CAFs are limited. This study aims to identify novel CAF-related biomarkers to develop a risk signature for predicting the prognosis and therapeutic response of patients with BRCA. Methods: CAF-related genes (CAFRGs) and a risk signature based on these genes were comprehensively analyzed using publicly available bulk and single-cell transcriptomic datasets. Modular genes identified from bulk sequencing data were intersected with CAF marker genes identified from single-cell analysis to obtain reliable CAFRGs. Signature CAFRGs were screened via Cox regression and least absolute shrinkage and selection operator (LASSO) analyses. Multiple patient cohorts were used to validate the prognosis and therapeutic responsiveness of high-risk patients stratified based on the CAFRG-based signature. In addition, the relationship between the CAFRG-based signature and clinicopathological factors, tumor immune landscape, functional pathways, chemotherapy sensitivity and immunotherapy sensitivity was examined. External datasets were used and sample experiments were performed to examine the expression pattern of MFAP4, a key CAFRG, in BRCA. Results: Integrated analyses of single-cell and bulk transcriptomic data as well as prognostic screening revealed a total of 43 prognostic CAFRGs; of which, 14 genes (TLN2, SGCE, SDC1, SAV1, RUNX1, PDLIM4, OSMR, NT5E, MFAP4, IGFBP6, CTSO, COL12A1, CCDC8 and C1S) were identified as signature CAFRGs. The CAFRG-based risk signature exhibited favorable efficiency and accuracy in predicting survival outcomes and clinicopathological progression in multiple BRCA cohorts. Functional enrichment analysis suggested the involvement of the immune system, and the immune infiltration landscape significantly differed between the risk groups. Patients with high CAF-related risk scores (CAFRSs) exhibited tumor immunosuppression, enhanced cancer hallmarks and hyposensitivity to chemotherapy and immunotherapy. Five compounds were identified as promising therapeutic agents for high-CAFRS BRCA. External datasets and sample experiments validated the downregulation of MFAP4 and its strong correlation with CAFs in BRCA. Conclusions: A novel CAF-derived gene signature with favorable predictive performance was developed in this study. This signature may be used to assess prognosis and guide individualized treatment for patients with BRCA.


Assuntos
Neoplasias da Mama , Fibroblastos Associados a Câncer , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Prognóstico , Biomarcadores , Perfilação da Expressão Gênica , Proteínas de Transporte , Glicoproteínas , Proteínas da Matriz Extracelular
19.
Biosensors (Basel) ; 12(11)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36354468

RESUMO

Nanotechnology has attracted much attention, and may become the key to a whole new world in the fields of food, agriculture, building materials, machinery, medicine, and electrical engineering, because of its unique physical and chemical properties, including high surface area and outstanding electrical and optical properties. The bottom-up approach in nanofabrication involves the growth of particles, and we were inspired to propose a novel nanoplasmonic method to detect the formation of nanoparticles in real time. This innovative idea may contribute to the promotion of nanotechnology development. An increase in nanometer particle size leads to optical extinction or density (OD)-value changes in our nanosensor chip at a specific wavelength measured in a generic microplate reader. Moreover, in applying this method, an ultrasensitive nanoplasmonic immunoturbidimetry assay (NanoPITA) was carried out for the high-throughput quantification of hypersensitive C-reactive protein (CRP), a well-known biomarker of cardiovascular, inflammatory, and tumor diseases. The one-step detection of the CRP concentration was completed in 10 min with high fidelity, using the endpoint analysis method. The new NanoPITA method not only produced a linear range from 1 ng/mL to 500 ng/mL CRP with the detection limit reduced to 0.54 ng/mL, which was an improvement of over 1000 times, with respect to regular immunoturbidity measurement, but was also effective in blood detection. This attractive method, combined with surface plasmon resonance and immunoturbidimetry, may become a new technology platform in the application of biological detection.


Assuntos
Técnicas Biossensoriais , Proteína C-Reativa , Proteína C-Reativa/análise , Imunoturbidimetria , Ressonância de Plasmônio de Superfície/métodos , Nanotecnologia/métodos , Biomarcadores , Técnicas Biossensoriais/métodos
20.
Food Chem X ; 15: 100396, 2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36211727

RESUMO

This study revealed the interaction mechanism between silver carp myofibrillar protein (MP) and key off-odors by combining fluorescence spectroscopy with molecular dynamics (MD) simulation. Spectroscopic results exhibited a dynamic quenching mechanism between MP and off-odors. Thermodynamic analysis indicated that the MP/off-odors interaction was spontaneous (ΔG° < 0) and dominated by hydrophobic interactions (ΔH° > 0, ΔS° > 0). Meanwhile, the binding affinity was in the order of nonanal (n = 1.38) > hexanal (n = 0.89) > 1-octen-3-ol (n = 0.65), which was further verified by the MD results. Among off-odors, nonanal had the highest binding energy with myosin (8105.66 kJ/mol) and formed more hydrophobic binding sites to Trp residues in myosin head (e.g., Trp820 and Trp822), thereby changing myosin conformations via both physical and chemical interactions. Additionally, higher binding energies of myosin/off-odors were observed at oral temperature (37 °C) than at cold storage temperature (4 °C), implying that less off-odors were released at 37 °C.

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