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Microplastics have emerged as a significant global concern, particularly in marine ecosystems. While extensive research has focused on the toxicological effects of microplastics on marine animals and/or their associated microorganisms as two separate entities, the holistic perspective of the adaptability and fitness of a marine animal metaorganism-comprising the animal host and its microbiome-remains largely unexplored. In this study, mussel metaorganisms subjected chronic PS-MPs exposure experienced acute mortality but rapidly adapted. We investigated the response of innate immunity, digestive enzymes and their associated microbiomes to chronic PS-MPs exposure. We found that PS-MPs directly and indirectly interacted with the host and microbe within the exposure system. The adaptation was a joint effort between the physiological adjustments of mussel host and genetic adaptation of its microbiome. The mussel hosts exhibited increased antioxidant activity, denser gill filaments and increased immune cells, enhancing their innate immunity. Concurrently, the gill microbiome and the digestive gland microbiome respective selectively enriched for plastic-degrading bacteria and particulate organic matter-utilizing bacteria, facilitating the microbiome's adaptation. The microbial adaptation to chronic PS-MPs exposure altered the ecological roles of mussel microbiome, as evidenced by alterations in microbial interactions and nutrient cycling functions. These findings provided new insights into the ecotoxicological impact of microplastics on marine organisms from a metaorganism perspective.
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Humans can estimate the number of visually presented items without counting. In most studies on numerosity perception, items are uniformly distributed across displays, with identical distributions in central and eccentric parts. However, the neural and perceptual representation of the human visual field differs between the fovea and the periphery. For example, in peripheral vision, there are strong asymmetries with regard to perceptual interferences between visual items. In particular, items arranged radially usually interfere more strongly with each other than items arranged tangentially (the radial-tangential anisotropy). This has been shown for crowding (the deleterious effect of clutter on target identification) and redundancy masking (the reduction of the number of perceived items in repeating patterns). In the present study, we tested how the radial-tangential anisotropy of peripheral vision impacts numerosity perception. In four experiments, we presented displays with varying numbers of discs that were predominantly arranged radially or tangentially, forming strong and weak interference conditions, respectively. Participants were asked to report the number of discs. We found that radial displays were reported as less numerous than tangential displays for all radial and tangential manipulations: weak (Experiment 1), strong (Experiment 2), and when using displays with mixed contrast polarity discs (Experiments 3 and 4). We propose that numerosity perception exhibits a significant radial-tangential anisotropy, resulting from local spatial interactions between items.
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Reconocimiento Visual de Modelos , Humanos , Anisotropía , Adulto , Masculino , Femenino , Adulto Joven , Reconocimiento Visual de Modelos/fisiología , Estimulación Luminosa/métodos , Campos Visuales/fisiología , Enmascaramiento Perceptual/fisiología , Percepción Visual/fisiologíaRESUMEN
Brain injury caused by stroke has a high rate of mortality and remains a major medical challenge worldwide. In recent years, there has been significant attention given to the use of human Umbilical cord-derived Mesenchymal Stem Cells (hUC-MSCs) for the treatment of stroke in different adult and neonate animal models of stroke. However, using hUC-MSCs by systemic administration to treat ischemic stroke has not been investigated sufficiently. In this study, we conducted various experiments to explore the neuroprotection of hUC-MSCs in rats. Our findings demonstrate that an intravenous injection of a high dose of hUC-MSCs at 2 × 10^7 cells/kg markedly ameliorated brain injury resulting from ischemic stroke. This improvement was observed one day after inducing transient middle cerebral artery occlusion (MCAO) and subsequent reperfusion in rats. Notably, the efficacy of this single administration of hUC-MSCs surpassed that of edaravone, even when the latter was used continuously over three days. Mechanistically, secretory factors derived from hUC-MSCs, such as HGF, BDNF, and TNFR1, ameliorated the levels of MDA and T-SOD to regulate oxidative stress. In particular, TNFR1 also improved the expression of NQO-1 and HO-1, important proteins associated with oxidative stress. More importantly, TNFR1 played a significant role in reducing inflammation by modulating IL-6 levels in the blood. Furthermore, TNFR1 was observed to influence the permeability of the blood-brain barrier (BBB) as demonstrated in the evan's blue experiment and protein expression of ZO-1. This study represented a breakthrough in traditional methods and provided a novel strategy for clinical medication and trials.
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Accidente Cerebrovascular Isquémico , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Estrés Oxidativo , Ratas Sprague-Dawley , Cordón Umbilical , Animales , Estrés Oxidativo/fisiología , Humanos , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/metabolismo , Cordón Umbilical/citología , Masculino , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/terapia , Ratas , Inflamación/metabolismo , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/terapia , Neuroprotección/fisiología , Infarto de la Arteria Cerebral Media/terapia , Infarto de la Arteria Cerebral Media/metabolismoRESUMEN
OBJECTIVE: The aim of this study is to demonstrate that the freeze-dried human rabies vaccine (Vero cell), administered in a four-dose schedule (2-1-1) to the 10-60 years old population, has immunogenicity that is not inferior to the approved five-dose schedule and similar vaccines with a four-dose schedule, and to evaluate its safety. METHOD: A total of 1800 individuals were enrolled and divided into three groups: four-dose test group, four-dose control group, and five-dose control group. The rabies virus neutralizing antibodies were measured using the Rapid Fluorescent Focus Inhibition Test to assess immunogenicity, and the incidence of adverse events and serious adverse events were statistically analyzed. RESULTS: The seroconversion rates 14 days after the first dose and 14 days after the complete course of vaccination were 100% in all three groups. The antibody GMC of the four-dose test group was higher than that of the five-dose control group, but slightly lower than the four-dose control group. Seven days after the first dose, both four-dose regimen groups showed higher seroconversion rates and antibody GMCs compared to the five-dose regimen group, proving that the immunogenic effect of the four-dose regimen seven days post-first vaccination is superior to the five-dose regimen. The overall incidence of adverse events showed no significant difference between the four-dose test group and the five-dose control group, but was significantly lower in the four-dose test group compared to the four-dose control group. CONCLUSION: The vaccine in the four-dose test group is equivalent in immunogenic effect to the four-dose control group vaccine and superior to the five-dose control group vaccine; the safety of the vaccine in the four-dose test group is equivalent to the five-dose control group vaccine and superior to the four-dose control group vaccine. CLINICALTRIALS: gov number: NCT05549908.
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Cucumber (Cucumis sativus L.) is an important horticultural crop in China. Consumer requirements for aesthetically pleasing appearances of horticultural crops are gradually increasing, and cucumbers having a good visual appearance, as well as flavor, are important for breeding and industry development. The gloss of cucumber fruit epidermis is an important component of its appeal, and the wax layer on the fruit surface plays important roles in plant growth and forms a powerful barrier against external biotic and abiotic stresses. The wax of the cucumber epidermis is mainly composed of alkanes, and the luster of cucumber fruit is mainly determined by the alkane and silicon contents of the epidermis. Several genes, transcription factors, and transporters affect the synthesis of ultra-long-chain fatty acids and change the silicon content, further altering the gloss of the epidermis. However, the specific regulatory mechanisms are not clear. Here, progress in research on the luster of cucumber fruit epidermis from physiological, biochemical, and molecular regulatory perspectives are reviewed. Additionally, future research avenues in the field are discussed.
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Cucumis sativus , Frutas , Regulación de la Expresión Génica de las Plantas , Cucumis sativus/genética , Cucumis sativus/metabolismo , Cucumis sativus/crecimiento & desarrollo , Frutas/genética , Frutas/metabolismo , Epidermis de la Planta/metabolismo , Epidermis de la Planta/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ceras/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Mre11 is one of important proteins that are involved in DNA repair and recombination by processing DNA ends to produce 3'-single stranded DNA, thus providing a platform for other DNA repair and recombination proteins. In this work, we characterized the Mre11 protein from the hyperthermophilic euryarchaeon Thermococcus barophilus Ch5 (Tba-Mre11) biochemically and dissected the roles of its four conserved residues, which is the first report on Mre11 proteins from Thermococcus. Tba-Mre11 possesses exonuclease activity for degrading ssDNA and dsDNA in the 5'-3' direction, which contrasts with other reported Mre11 homologs. Maximum degradation efficiency was observed with Mn2+ at 80 °C and at pH 7.5-9.5. In addition to possessing 5'-3' exonuclease activity, Tba-Mre11 has endonuclease activity that nicks plasmid DNA and circular ssDNA. Mutational data show that residues D10, D51 and N86 in Tba-Mre11 are essential for DNA degradation since almost no activity was observed for the D10A, D51A and N86A mutants. By comparison, residue D44 in Tba-Mre11 is not responsible for DNA degradation since the D44A mutant possessed the similar WT protein activity. Notably, the D44A mutant almost completely abolished the ability to bind DNA, suggesting that residue D44 is essential for binding DNA.
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Proteínas Arqueales , ADN de Cadena Simple , Thermococcus , Thermococcus/enzimología , Thermococcus/genética , Proteínas Arqueales/metabolismo , Proteínas Arqueales/química , Proteínas Arqueales/genética , ADN de Cadena Simple/metabolismo , Exodesoxirribonucleasas/metabolismo , Exodesoxirribonucleasas/genética , Exodesoxirribonucleasas/química , Secuencia de Aminoácidos , Endonucleasas/metabolismo , Endonucleasas/química , Endonucleasas/genética , Mutación , EndodesoxirribonucleasasRESUMEN
Glycyrrhiza inflata Bat. produces a lot of licorice waste after water extraction, which also retains abundant total flavonoids (TFs) and licochalcone A. However, licorice residue is often wasted due to the lack of good utilization of resources in practical applications. This study first screened the optimal membrane pore size and resin type and then explored the mechanism and conditions of the adsorption of TFs on the resin. Then, different combinations and sequences of membrane and macroporous resin (MR) methods were investigated. It was found that using the membrane method for initial purification, followed by the MR method for further purification, yielded the best purification results. Next, response surface methodology was utilized to investigate the resin's dynamic desorption conditions for TFs. Finally, the TF purity increased from 32.9% to 78.2% (2.38-fold) after purification by a combined membrane-MR process; the purity of licochalcone A increased from 11.63 mg·g-1 to 22.70 mg·g-1 (1.95-fold). This study verified the feasibility of enriching TFs and licochalcone A from licorice residue using a membrane-MR coupling method. In addition, a quality-control method was established using a fingerprinting method on the basis of ultrahigh-performance liquid chromatography (UPLC) to ensure the stability of the enrichment process.
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Chalconas , Flavonoides , Glycyrrhiza , Chalconas/química , Chalconas/aislamiento & purificación , Glycyrrhiza/química , Flavonoides/química , Control de Calidad , Porosidad , Cromatografía Líquida de Alta Presión , Adsorción , Extractos Vegetales/químicaRESUMEN
AIM: To investigate the metabolism and disposition characteristics of HSK7653 in healthy male Chinese participants. METHODS: A single oral dose of 80 µCi (25 mg) [14C]HSK7653 capsules was administered to six healthy participants, and blood, plasma, urine and faeces were collected. Quantitative and qualitative analysis was conducted to investigate the pharmacokinetics, blood-to-plasma ratio, mass balance and metabolism of HSK7653. RESULTS: The drug was well absorbed and reached a maximum concentration at 1.25 h. The drug-related components (HSK7653 and its metabolites) were eliminated slowly, with a half-life (t1/2) of 111 h. Unchanged HSK7653 contributed to more than 97% of the total radioactivity in all plasma samples. The blood-to-plasma ratio (0.573-0.845) indicated that HSK7653 did not tend to distribute into blood cells. At 504 h postdose, up to 95.9% of the dose was excreted, including 79.8% in urine and 16.1% in faeces. Most of the radioactivity (75.5% dose) in excreta was unchanged HSK7653. In addition, nine metabolites were detected in urine and faeces. The most abundant metabolite was M6-2, a dioxidation product of HSK7653, which accounted for 4.73% and 2.63% of the dose in urine and faeces, respectively. The main metabolic pathways of HSK7653 in vivo included oxidation, pyrrole ring opening and sulphonamide hydrolysation. CONCLUSION: HSK7653 was well absorbed, slightly metabolized and slowly excreted in humans. The high plasma exposure and long t1/2 of HSK7653 may contribute to its long-lasting efficacy as a long-acting dipeptidyl peptidase-4 inhibitor.
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Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Humanos , Masculino , Inhibidores de la Dipeptidil-Peptidasa IV/farmacocinética , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Adulto , Biotransformación , Semivida , Heces/química , Adulto Joven , Voluntarios Sanos , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/uso terapéutico , Administración OralRESUMEN
Archaeal NurA protein plays a key role in producing 3'-single stranded DNA used for homologous recombination repair, together with HerA, Mre11, and Rad50. Herein, we describe biochemical characteristics and roles of key amino acid residues of the NurA protein from the hyperthermophilic euryarchaeon Thermococcus barophilus Ch5 (Tba-NurA). Tba-NurA possesses 5'-3' exonuclease activity for degrading DNA, displaying maximum efficiency at 45 °C-65 °C and at pH 8.0 in the presence of Mn2+. The thermostable Tba-NurA also possesses endonuclease activity capable of nicking plasmid DNA and circular ssDNA. Mutational data demonstrate that residue D49 of Tba-NurA is essential for exonuclease activity and is involved in binding ssDNA since the D49A mutant lacked exonuclease activity and reduced ssDNA binding. The R96A and R129A mutants had no detectable dsDNA binding, suggesting that residues R96 and R129 are important for binding dsDNA. The abolished degradation activity and reduced dsDNA binding of the D120A mutant suggest that residue D120 is essential for degradation activity and dsDNA binding. Additionally, residues Y392 and H400 are important for exonuclease activity since these mutations resulted in exonuclease activity loss. To our knowledge, it is the first report on biochemical characterization and mutational analysis of the NurA protein from Thermococcus.
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Proteínas Arqueales , ADN de Cadena Simple , Thermococcus , Thermococcus/genética , Thermococcus/metabolismo , Thermococcus/enzimología , Proteínas Arqueales/genética , Proteínas Arqueales/metabolismo , Proteínas Arqueales/química , ADN de Cadena Simple/metabolismo , ADN de Cadena Simple/genética , Análisis Mutacional de ADN , Concentración de Iones de Hidrógeno , Exonucleasas/metabolismo , Exonucleasas/genética , Exonucleasas/química , Temperatura , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/química , Unión Proteica , ADN de Archaea/genética , ADN de Archaea/química , Endonucleasas/genética , Endonucleasas/metabolismo , Endonucleasas/químicaRESUMEN
Drug-resistant bacterial infection of cutaneous wounds causes great harm to the human body. These infections are characterized by a microenvironment with recalcitrant bacterial infections, persistent oxidative stress, imbalance of immune regulation, and suboptimal angiogenesis. Treatment strategies available to date are incapable of handling the healing dynamics of infected wounds. A Schiff base and borate ester cross-linked hydrogel, based on phenylboronic acid-grafted chitosan (CS-PBA), dibenzaldehyde-grafted poly(ethylene glycol), and tannic acid (TA), is fabricated in the present study. Customized phenylboronic acid-modified zinc oxide nanoparticles (ZnO) are embedded in the hydrogel prior to gelation. The CPP@ZnO-P-TA hydrogel effectively eliminates methicillin-resistant Staphylococcus aureus (MRSA) due to the pH-responsive release of Zn2+ and TA. Killing is achieved via membrane damage, adenosine triphosphate reduction, leakage of intracellular components, and hydrolysis of bacterial o-nitrophenyl-ß-d-galactopyranoside. The CPP@ZnO-P-TA hydrogel is capable of scavenging reactive oxygen and nitrogen species, alleviating oxidative stress, and stimulating M2 polarization of macrophages. The released Zn2+ and TA also induce neovascularization via the PI3K/Akt pathway. The CPP@ZnO-P-TA hydrogel improves tissue regeneration in vivo by alleviating inflammatory responses, stimulating angiogenesis, and facilitating collagen deposition. These findings suggest that this versatile hydrogel possesses therapeutic potential for the treatment of MRSA-infected cutaneous wounds.
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Quitosano , Hidrogeles , Staphylococcus aureus Resistente a Meticilina , Cicatrización de Heridas , Quitosano/química , Quitosano/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Hidrogeles/química , Hidrogeles/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones , Neovascularización Fisiológica/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/química , Óxido de Zinc/química , Óxido de Zinc/farmacología , Taninos/química , Taninos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Células RAW 264.7 , Bases de Schiff/química , Bases de Schiff/farmacología , Ácidos Borónicos/química , Ácidos Borónicos/farmacología , Humanos , Masculino , AngiogénesisRESUMEN
X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.
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Andrógenos , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Femenino , Andrógenos/genética , Riñón , Cromosomas Humanos X/genética , Elementos de Respuesta , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad , Tetraspaninas/genéticaRESUMEN
The remote region of the South China Sea (SCS), situated far from urban mainland areas, is commonly perceived to experience minimal pollution. However, this may evolve into a considerably polluted region owing to increasing anthropogenic pollutants. In this study, we employ a multidisciplinary approach to analyze the surface sediments collected from the offshore area of the southern SCS. Our aim is to explore potential anthropogenic pollutants, their interactions, and the related controlling factors. This research endeavors to enhance our understanding of the current pollution status in the SCS and help making relevant policy management decisions. Comparison with previous reports reveals that now, the area is more extensively and increasingly contaminated by petroleum hydrocarbons and heavy metals (Cd and As) than before. For the first time, we report the recognition of coprostanol and long-chain alkyl mid-chain ketones, unveiling the noticeable incorporation of sewage fecal matter and biomass burning into offshore sediments. Moreover, sedimentary multipollutants (except ketones) exhibit strong correlations with terrestrial elements and fine-sized particles, displaying a roughly high-west/low-east spatial variability in pollutant accumulation or enrichment. These signatures evidently demonstrate the major impact of river discharges (e.g., the Mekong River to the west and the Pearl and Red Rivers to the north) on the SCS. They have hydrodynamic effects on the subsequent basin-wide dispersal of pollutants, driven by monsoon-induced large- and regional-scale currents. The different behavior of burning-related ketones may be partly due to their aerosol form, leading to atmospheric transportation. Because anthropogenic multipollutants pose compounded threats, exacerbating oceanic warming and acidification to marine ecosystems such as the widespread coral reefs in the southern SCS, scientific management of urban emissions is required to mitigate ecosystem degradation in the Anthropocene era.
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This study provides a comprehensive overview of the preparation methods for polyhedral oligomeric silsesquioxane (POSS) monomers and polymer/POSS nanocomposites. It focuses on the latest advancements in using POSS to design polymer nanocomposites with reduced dielectric constants. The study emphasizes exploring the potential of POSS, either alone or in combination with other materials, to decrease the dielectric constant and dielectric loss of various polymers, including polyimides, bismaleimide resins, poly(aryl ether)s, polybenzoxazines, benzocyclobutene resins, polyolefins, cyanate ester resins, and epoxy resins. In addition, the research investigates the impact of incorporating POSS on improving the thermal properties, mechanical properties, surface properties, and other aspects of these polymers. The entire study is divided into two parts, discussing systematically the role of POSS in reducing dielectric constants during the preparation of POSS composites using both physical blending and chemical synthesis methods. The goal of this research is to provide valuable strategies for designing a new generation of low dielectric constant materials suitable for large-scale integrated circuits in the semiconductor materials domain.
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Nanocompuestos , Polímeros , Polímeros/química , Nanocompuestos/químicaRESUMEN
BACKGROUND: Glycine dehydrogenase (GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). METHODS: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B (CHB), and 35 healthy controls (HCs). The methylation status of GLDC promoter in peripheral mononuclear cells (PBMCs) was identified by methylation specific polymerase chain reaction (MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction (qPCR). RESULTS: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients (27.0%) compared to that in CHB patients (68.6%) and HCs (74.3%) (P < 0.001). The methylated group had lower alanine aminotransferase level (P = 0.035) and lower rates of tumor node metastasis (TNM) III/IV (P = 0.043) and T3/T4 (P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients (P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters (P = 0.003). The diagnostic accuracy of alpha-fetoprotein (AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone (AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients (P = 0.038). CONCLUSIONS: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/metabolismo , alfa-Fetoproteínas/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Glicina-Deshidrogenasa , Leucocitos Mononucleares/química , Leucocitos Mononucleares/metabolismo , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/genética , Metilación de ADN , Reacción en Cadena en Tiempo Real de la Polimerasa , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
The cell membrane serves as a barrier against the free entry of foreign substances into the cell. Limited by factors such as solubility and targeting, it is difficult for some drugs to pass through the cell membrane barrier and exert the expected therapeutic effect. Two-dimensional nanomaterial (2D NM) has the advantages of high drug loading capacity, flexible modification, and multimodal combination therapy, making them a novel drug delivery vehicle for drug membrane attachment and intracellular transport. By modulating the surface properties of nanocarriers, it is capable of carrying drugs to break through the cell membrane barrier and achieve precise treatment. In this review, we review the classification of various common 2D NMs, the primary parameters affecting their adhesion to cell membranes, and the uptake mechanisms of intracellular transport. Furthermore, we discuss the therapeutic potential of 2D NMs for several major disorders. We anticipate this review will deepen researchers' understanding of the interaction of 2D NM drug carriers with cell membrane barriers, and provide insights for the subsequent development of novel intelligent nanomaterials capable of intracellular transport.
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Nanopartículas , Nanoestructuras , Humanos , Nanoestructuras/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos , Transporte Biológico , Propiedades de Superficie , Nanopartículas/metabolismoRESUMEN
Objective To observe changes of thickness and elasticity of skeletal muscles in patients with type 2 diabetes mellitus(T2DM)and relative impact factors.Methods Totally 62 T2DM patients(T2DM group)and 60 healthy adults(HC group)were prospectively recruited.Shear wave elastography(SWE)technology was used to measure the maximum Young's modulus(Emax)of the rectus abdominis and gastrocnemius muscles under relaxed and contracted states in both groups.The thickness and elasticity modulus of the skeletal muscles under the two states were compared between groups.Multiple linear regression analysis was performed to screen impact factors of the elasticity modulus of the rectus abdominis and gastrocnemius muscles.Results No significant difference of muscle thicknesses of rectus abdominis,nor of gastrocnemius muscle was found between groups under relaxed and contracted states(all P>0.05).Under both relaxed and contracted states,the Emax of the rectus abdominis and gastrocnemius muscle in T2DM group were all lower than those in HC group(all P<0.05).Multiple linear regression analysis showed that in T2DM group,the elasticity modulus of the rectus abdominis and gastrocnemius muscle under both relaxed and contracted states decreased linearly with disease duration,fasting blood glucose(FBG)and glycosylated hemoglobin(HbA1c)(all P<0.05).Conclusion The elasticity modulus of skeletal muscle decreased in T2DM patients,and the reducing scales linearly related to disease duration,FBG and HbA1c.
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Objective To investigate the predictive value of new simplified insulin resistance(IR)assessment indexes in identifying subclinical left ventricular systolic function impairment in patients with type 2 diabetes mellitus(T2DM).Methods A total of 150 T2DM patients with preserved left ventricular ejection fraction(LVEF≥50%)who were admitted to Department of Endocrinology of the First Affiliated Hospital of Air Force Medical University from June 2021 to December 2021 were retrospectively analyzed.All patients underwent two-dimensional speckle tracking echocardiography to measure left ventricular global longitudinal strain(GLS).According to GLS value,the subjects were divided into the normal group(GLS≥18%group,n=80)and the impaired group(GLS<18%group,n=70).Some new simplified IR assessment indicators were calculated and compared between the two groups,including body mass index(BMI),TG/HDL-C ratio,triglyceride-glucose(TyG)index,TyG-BMI index,TyG-WHR and metabolic score for IR(METS-IR).Correlation between the GLS and the new simplified IR assessment indexes was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of different simplified IR assessment indexes,with the area under the curve(AUC)calculated.Furthermore,according to whether the subjects were complicated with hypertension,binary logistics regression analysis was performed to explore the independent correlation between the simplified IR assessment index and GLS<18%.Results Total 150 were included with aged(54.5±13.7)years with 96(64.0%)men and 54(36.0%)women.Compared with the GLS≥18%group,the TG/HDL-C ratio,TyG index,TyG-BMI,and METS-IR of subjects in the GLS<18%group were significantly increased(P<0.05).Pearson correlation analysis showed that TG/HDL-C ratio,TyG index,TyG-BMI,TyG-WHR,and METS-IR were negatively correlated with GLS(P<0.05).ROC analysis showed that TyG index had a certain predictive value for the evaluation of GLS<18%(AUC=0.678,95%CI 0.591-0.765,P<0.001).Stratification based on hypertension and further adjusting for confounding factors,TyG index remains significantly associated with GLS<18%(OR=3.249,95%CI 1.045-10.103,P=0.042).Conclusions The novel simplified insulin resistance evaluation indexes are closely associated with left ventricular subclinical systolic dysfunction in T2DM patients with preserved ejection fraction.TyG index is an effective index to identify left ventricular subclinical dysfunction in these populations.
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BACKGROUND:Knee osteoarthritis is a common disease in middle-aged and elderly people.It is a kind of disease that seriously affects the quality of life of patients and even has the risk of disability.Therefore,the pathogenesis and treatment of knee osteoarthritis have become the focus of research.In Chinese medicine,knee osteoarthritis is often treated as"biness,"which is closely related to"biness"caused by blood stasis and blood vessels blocking collaterals in the theory of"blood stasis"in traditional Chinese medicine.Iron overload is a kind of pathological state caused by iron metabolism disorder,which highly coincides with the pathogenic characteristics and clinical manifestations of the"blood stasis"theory of traditional Chinese medicine,and is a risk factor that promotes the development of knee osteoarthritis. OBJECTIVE:Based on the"blood stasis"theory,to summarize the effects of iron overload on cartilage metabolism and subchondral bone reconstruction,to lay a new theoretical foundation for the treatment of knee osteoarthritis with traditional Chinese medicine,and to explore the therapeutic effect of traditional Chinese medicine for promoting blood circulation after interfering with bone tissue. METHODS:CNKI,WanFang database,PubMed and Web of Science databases were searched for relevant literature.The Chinese search terms were"ferroptosis,iron,iron overload,osteoarthritis,blood stasis"and the English search terms were"ferroptosis,iron,iron overload,osteoarthritis,TCM."In the end,76 articles were included for further review. RESULTS AND CONCLUSION:First of all,we explored the potential of the"blood stasis"theory in treating knee osteoarthritis,and found that"blood stasis"is a crucial part in the progress of knee osteoarthritis,indicating that the"blood stasis"theory is the key to the treatment of knee osteoarthritis in traditional Chinese medicine.Secondly,"blood stasis"and iron overload have a high degree of similarity in pathogenic factors,clinical manifestations,and pathogenic characteristics,suggesting the possibility of"blood stasis"theory in treating iron overload.This finding reminds us that iron overload may be an important mechanistic basis for the"blood stasis"theory in the treatment of knee osteoarthritis.The extracts of blood-activating drugs can relieve iron overload and treat knee osteoarthritis,but the specific mechanism is still unclear.Therefore,we believe that the relationship between"blood stasis"theory and iron overload and related mechanisms are important research directions for knee osteoarthritis in the future.The related mechanism of"blood stasis"theory to alleviate iron overload and then treat knee osteoarthritis also provides a theoretical basis for the modernization of traditional Chinese medicine,such as the development of new drugs and innovative usage,and has certain guiding significance for clinical practice.