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Accumulation of senescent cells in organs and tissues is a hallmark of aging and known to contribute to age-related diseases. Although aging-associated immune dysfunction, or immunosenescence, is known to contribute to this process, the underlying mechanism remains elusive. Here, we report that type 2 cytokine signaling deficiency accelerated aging and, conversely, that the interleukin-4 (IL-4)-STAT6 pathway protected macrophages from senescence. Mechanistically, activated STAT6 promoted the expression of genes involved in DNA repair both via homologous recombination and Fanconi anemia pathways. Conversely, STAT6 deficiency induced release of nuclear DNA into the cytoplasm to promote tissue inflammation and organismal aging. Importantly, we demonstrate that IL-4 treatment prevented macrophage senescence and improved the health span of aged mice to an extent comparable to senolytic treatment, with further additive effects when combined. Together, our findings support that type 2 cytokine signaling protects macrophages from immunosenescence and thus hold therapeutic potential for improving healthy aging.
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Senescencia Celular , Interleucina-4 , Animales , Ratones , Interleucina-4/metabolismo , Envejecimiento/genética , Macrófagos , InflamaciónRESUMEN
BACKGROUND: Systemic allergic reactions (sARs) following coronavirus disease 2019 (COVID-19) mRNA vaccines were initially reported at a higher rate than after traditional vaccines. OBJECTIVE: We aimed to evaluate the safety of revaccination in these individuals and to interrogate mechanisms underlying these reactions. METHODS: In this randomized, double-blinded, phase 2 trial, participants aged 16 to 69 years who previously reported a convincing sAR to their first dose of COVID-19 mRNA vaccine were randomly assigned to receive a second dose of BNT162b2 (Comirnaty) vaccine and placebo on consecutive days in a blinded, 1:1 crossover fashion at the National Institutes of Health. An open-label BNT162b2 booster was offered 5 months later if the second dose did not result in severe sAR. None of the participants received the mRNA-1273 (Spikevax) vaccine during the study. The primary end point was recurrence of sAR following second dose and booster vaccination; exploratory end points included biomarker measurements. RESULTS: Of 111 screened participants, 18 were randomly assigned to receive study interventions. Eight received BNT162b2 second dose followed by placebo; 8 received placebo followed by BNT162b2 second dose; 2 withdrew before receiving any study intervention. All 16 participants received the booster dose. Following second dose and booster vaccination, sARs recurred in 2 participants (12.5%; 95% CI, 1.6 to 38.3). No sAR occurred after placebo. An anaphylaxis mimic, immunization stress-related response (ISRR), occurred more commonly than sARs following both vaccine and placebo and was associated with higher predose anxiety scores, paresthesias, and distinct vital sign and biomarker changes. CONCLUSIONS: Our findings support revaccination of individuals who report sARs to COVID-19 mRNA vaccines. Distinct clinical and laboratory features may distinguish sARs from ISRRs.
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Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , SARS-CoV-2 , Humanos , Persona de Mediana Edad , Masculino , Adulto , Femenino , Método Doble Ciego , COVID-19/prevención & control , COVID-19/inmunología , SARS-CoV-2/inmunología , Anciano , Adolescente , Adulto Joven , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Recurrencia , Vacunación , Vacuna nCoV-2019 mRNA-1273 , Estudios CruzadosRESUMEN
The clearance or transcriptional silencing of integrated HBV DNA is crucial for achieving a functional cure in patients with chronic hepatitis B and reducing the risk of hepatocellular carcinoma development. The PLC/PRF/5 cell line is commonly used as an in vitro model for studying HBV integration. In this study, we employed a range of multi-omics techniques to gain a panoramic understanding of the characteristics of HBV integration in PLC/PRF/5 cells and to reveal the transcriptional regulatory mechanisms of integrated HBV DNA. Transcriptome long-read sequencing (ONT) was conducted to analyze and characterize the transcriptional activity of different HBV DNA integration sites in PLC/PRF/5 cells. Additionally, we collected data related to epigenetic regulation, including whole-genome bisulfite sequencing (WGBS), histone chromatin immunoprecipitation sequencing (ChIP-seq), and assays for transposase-accessible chromatin using sequencing (ATAC-seq), to explore the potential mechanisms involved in the transcriptional regulation of integrated HBV DNA. Long-read RNA sequencing analysis revealed significant transcriptional differences at various integration sites in the PLC/PRF/5 cell line, with higher HBV DNA transcription levels at integration sites on chr11, chr13, and the chr13/chr5 fusion chromosome t (13:5). Combining long-read DNA and RNA sequencing results, we found that transcription of integrated HBV DNA generally starts downstream of the SP1, SP2, or XP promoters. ATAC-seq data confirmed that chromatin accessibility has limited influence on the transcription of integrated HBV DNA in the PLC/PRF/5 cell line. Analysis of WGBS data showed that the methylation intensity of integrated HBV DNA was highly negatively correlated with its transcription level (r = -0.8929, p = 0.0123). After AzaD treatment, the transcription level of integrated HBV DNA significantly increased, especially for the integration chr17, which had the highest level of methylation. Through ChIP-seq data, we observed the association between histone modification of H3K4me3 and H3K9me3 with the transcription of integrated HBV DNA. Our findings suggest that the SP1, SP2 and XP in integrated HBV DNA, methylation level of surrounding host chromosome, and histone modifications affect the transcription of integrated HBV DNA in PLC/PRF/5 cells. This provides important clues for future studies on the expression and regulatory mechanisms of integrated HBV.
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Epigénesis Genética , Virus de la Hepatitis B , Integración Viral , Humanos , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/fisiología , Integración Viral/genética , ADN Viral/genética , Transcripción Genética , Línea Celular , Metilación de ADN , Línea Celular Tumoral , Histonas/genética , Histonas/metabolismo , MultiómicaRESUMEN
We have successfully synthesized a series of bidentate ligands by utilizing 2-(trimethylsilyl)phenyl trifluorosulfonate as a precursor for the benzyl group. This method proceeded by inserting a polythiourea into the CâS π-bond, intramolecular ring proton migration, and ring opening. Salient features of this strategy are mild reaction conditions, a novel product structure, excellent stereochemistry, and a good functional group tolerance. Furthermore, a series of density functional theory calculations were performed to gain insights into the transfer mechanism.
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BACKGROUND: The objective is to analyze and review the clinical, laboratory, and neuroimaging characteristics of rheumatoid meningitis (RM) in six patients with known rheumatoid arthritis (RA). METHODS: We performed a retrospective review of patients diagnosed with RM from August 2012 to June 2023. To identify the cases, we used medical term search engines and the hospital´s radiology case database. Clinical information and laboratory findings were gathered from the medical records. A neuroradiologist with five years of experience reviewed and analyzed the RM to determine the characteristics findings of RM. RESULTS: Six patients with RM are included. Seizures along with headaches were among the clinical signs that were documented. All the patients had high levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptides (ACPA) in the peripheral blood. Biopsy in two cases confirmed typical rheumatoid nodules. Leptomeningeal enhancement was found bilaterally in all cases and was predominantly found in the frontoparietal region. "Mismatch DWI/FLAIR" was found in five patients. Bilateral subdural collections could be found in two patients. Brain PET scan revealed increased metabolism in two cases. CONCLUSION: Rheumatoid meningitis is a rare complication of rheumatoid arthritis (RA) with challenging clinical diagnosis due to non-specific symptoms. This study highlights the importance of MR in detecting characteristic neuroimaging patterns, including "mismatch DWI/FLAIR", to aid in early diagnosis. Increased awareness of this condition may facilitate timely intervention and improve prognosis. These results still need to be verified by large studies.
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Neutralizing antibodies to the SARS CoV-2 spike proteins have been issued Emergency Use Authorizations and are a likely mechanism of vaccines to prevent COVID-19. However, benefit of treatment with monoclonal antibodies has only been observed in clinical trials in outpatients with mild to moderate COVID-19 but not in patients who are hospitalized and/or have advanced disease. To address this observation, we evaluated the timing of anti SARS-CoV-2 antibody production in hospitalized patients with the use of a highly sensitive multiplexed bead-based immunoassay allowing for early detection of antibodies to SARS-CoV-2. We found significantly lower levels of antibodies to the SARS-CoV-2 spike protein in the first week after symptom onset in patients who expired as compared to patients who were discharged. We also developed a model to characterize the relationship between each patient's individual antibody level trajectory and eventual COVID 19 outcome which can be adapted into a prediction model with more data.
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Anticuerpos Antivirales/sangre , COVID-19/inmunología , COVID-19/mortalidad , SARS-CoV-2/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Especificidad de Anticuerpos , Antígenos Virales/inmunología , Femenino , Humanos , Inmunoglobulina G/sangre , Modelos Lineales , Masculino , Persona de Mediana Edad , Modelos Inmunológicos , Pandemias , Pronóstico , Glicoproteína de la Espiga del Coronavirus/inmunología , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
Orotate (OA) is a precursor of pyrimidine nucleotides and is widely used in food, pharmaceutical, and cosmetic industries. Although various microorganisms have been used for OA production, the production efficiency needs to be further improved for industrial application. In this study, we engineered Escherichia coli native metabolism for efficient OA production. The entire pathway was divided into the downstream OA synthesis, the midstream aspartate/glutamine supply, and the upstream glycolysis modules. First, the downstream module was optimized by disrupting pyrE to block OA consumption and release the feedback inhibition, and tuning expression of the biosynthetic genes. Second, the midstream pathway was enhanced by increasing the supply of the precursors and the cofactor nicotinamide adenine dinucleotide phosphate (NADPH). More importantly, we observed that pyrE disruption may lead to metabolic disorder as indicated by the accumulation of large amount of acetate. This problem was solved by reducing the flux of glycolysis. With these efforts, the final strain produced 80.3 g/L OA with a yield of 0.56 g/g glucose in fed-batch fermentation, which are the highest titer and yield reported so far. This work paves the way for industrial production of OA and represents as a good example of modulating cell metabolism for efficient chemical production.
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Escherichia coli , Glucólisis , Escherichia coli/genética , Escherichia coli/metabolismo , Fermentación , Ingeniería MetabólicaRESUMEN
PURPOSE: The aim of this study was to retrospectively review cases of intestinal anisakiasis diagnosed by CT over a 10-year period and to evaluate imaging findings associated with the disease. METHODS: This retrospective study included 71 patients with clinical suspicion of intestinal anisakiasis in whom an abdominopelvic computed tomography (CT) was performed at a single institution between June 2011 and December 2021. To identify the cases, we used medical term search engines and the hospital's radiology case database. Clinical information was gathered from the medical records. A radiologist with five years of experience reviewed and analyzed the CT images to determine the characteristic findings of intestinal anisakiasis. RESULTS: The study included 47 confirmed cases of intestinal anisakiasis. The mean age of the patients was 52 years (range 18-87 years), being more frequent in men than women (26:21). All patients reported ingestion of raw fish, most commonly anchovies in vinegar (30/47, 63,8%). Abdominal pain was the predominant symptom, accompanied by nausea, vomiting, and occasionally fever. The most common clinical suspicions were intestinal obstruction (14/47, 29,8%) and appendicitis (10/47, 21,3%), whereas intestinal anisakiasis was suspected in only 2 cases prior to imaging. CT showed thickening of the bowel wall with submucosal edema in all patients, predominantly involving the ileum (43/47, 91,5%), usually in a relatively long segment (mean of 17,5 cm, range 10-30 cm). Simultaneous involvement of multiple bowel segments was observed in 16 cases (34%). Intestinal obstruction with dilatation of proximal loops (33/47, 70,2%), ascites (45/47, 95,7%), and mesenteric fat striation (32/47, 68,1%) were also common findings. CONCLUSION: This study demonstrates the value of computed tomography in suggesting the diagnosis of intestinal anisakiasis, which often presents with nonspecific clinical manifestations. The characteristic CT findings that provide diagnostic clues are bowel wall thickening with submucosal edema, typically involving a long segment of the ileum, with signs of intestinal obstruction, ascites, and mesenteric fat striation. Simultaneous involvement of several intestinal segments (typically the gastric antrum and right colon) is an additional finding to be considered and may provide a diagnostic clue.
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Anisakiasis , Obstrucción Intestinal , Masculino , Animales , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Anisakiasis/diagnóstico por imagen , Anisakiasis/complicaciones , Estudios Retrospectivos , Ascitis/complicaciones , Tomografía Computarizada por Rayos X/métodos , Obstrucción Intestinal/diagnóstico por imagen , Peces , EdemaRESUMEN
In order to explore the mechanism responsible for the interactions in the surfactant-polymer composite flooding and broaden the application range of the binary system in heterogeneous oil reservoirs, in this paper, the influences of different surfactants on the viscosity of two polymers with similar molecular weights, partially hydrolyzed polyacrylamide (HPAM) and hydrophobically modified polyacrylamide (HMPAM), were studied at different reservoir environments. In addition, the relationship between the surfactant-polymer synergistic effects and oil displacement efficiency was also investigated. The experimental results show that for HPAM, surfactants mainly act as an electrolyte to reduce its viscosity. For HMPAM, SDBS and TX-100 will form aggregates with the hydrophobic blocks of polymer molecules, reducing the bulk viscosity. However, zwitterionic surfactant aralkyl substituted alkyl sulfobetaine BSB molecules can build "bridges" between different polymer molecules through hydrogen bonding and electrostatic interaction. After forming aggregates with HMPAM molecules, the viscosity will increase. The presence of two polymers all weakened the surfactant oil-water interfacial membrane strength to a certain extent, but had little effect on the interfacial tension. The synergistic effect of the "bridge" between HMPAM and BSB under macroscopic conditions also occurs in the microscopic pores of the core, which has a beneficial effect on improving oil recovery.
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Polímeros , Tensoactivos , Tensoactivos/química , Polímeros/química , Resinas Acrílicas/químicaRESUMEN
Micro visualization has become an important means of solving colloid and interface scientific problems in enhanced oil recovery. It can establish a relationship between a series of performance evaluations of an oil-water interface under macroscopic dimensions and the actual application effect in confined space, and more truly and reliably reflect the starting and migration behavior of crude oil or emulsion in rock pores. In this article, zwitterionic surfactant alkyl sulfobetaine (ASB) and anionic extended surfactant alkyl polyoxypropylene sulfate (A145) were employed as flooding surfactants. The macroscopic properties of the surfactant solutions, such as the oil-water interfacial tension (IFT), the interfacial dilational rheology and the viscosity of crude oil emulsions, have been measured. At the same time, we link these parameters with the oil displacement effect in several visual glass models and confirm the main factors affecting the migration ability of emulsions in micro-scale pores. The experimental results show that ASB reduces the IFT through mixed adsorption with crude oil fractions. The flat arrangement of the large hydrophilic group of ASB molecules enhances the interactions between the surfactant molecules on the oil-water interface. Compared with sulfate, betaine has higher interfacial membrane strength and emulsion viscosity. A145 has a strong ability to reduce the IFT against crude oil because of the larger size effect of the PO chains at the oil side of the interface. However, the membrane strength of A145 is moderate and the emulsion does not show a viscosity-increasing effect. During the displacement process, the deformation ability of the front emulsions or oil banks is the main controlling factor of the displacement efficiency, which is determined by the membrane strength and emulsion viscosity. The strong interfacial membrane strength and the high emulsion viscosity are not conducive to the migration of droplets in pore throats and may result in low displacement efficiency.
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Petróleo , Surfactantes Pulmonares , Emulsiones , Agua , Tensoactivos , Tensión SuperficialRESUMEN
Betaine is a new surfactant with good application prospects in high-temperature and high-salinity reservoirs. The interfacial properties of two kinds of betaine mixtures with a good synergistic effect were evaluated in this paper. On this basis, the effects of temperature-resistant, salt-resistant polymers with different contents of 2-acrylamide-2-methylpropanesulfonic acid (AMPS) on dynamic interfacial tensions (IFTs) against n-alkanes and crude oil were studied. The experimental results show that the IFTs between betaine ASB and n-alkanes can be reduced to ultra-low values by compounding with anionic surfactant petroleum sulfonate (PS) and extended anionic surfactant alkoxyethylene carboxylate (AEC), respectively. ASB@AEC is very oil-soluble with nmin value ≥14, and ASB@PS is relatively water-soluble with nmin value of 10. The water solubility of both ASB@PS and ASB@AEC is enhanced by the addition of water-soluble polymers. The HLB of the ASB@AEC solution becomes better against crude oil after the addition of polymers, and the IFT decreases to an ultra-low value as a result. On the contrary, the antagonistic effect in reducing the IFT can be observed for ASB@PS in the same case. In a word, polymers affect the IFTs of surfactant solutions by regulating the HLB.
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The anterior cingulate cortex (ACC) is located in the frontal part of the cingulate cortex, and plays important roles in pain perception and emotion. The thalamocortical pathway is the major sensory input to the ACC. Previous studies have show that several different thalamic nuclei receive projection fibers from spinothalamic tract, that in turn send efferents to the ACC by using neural tracers and optical imaging methods. Most of these studies were performed in monkeys, cats, and rats, few studies were reported systematically in adult mice. Adult mice, especially genetically modified mice, have provided molecular and synaptic mechanisms for cortical plasticity and modulation in the ACC. In the present study, we utilized rabies virus-based retrograde tracing system to map thalamic-anterior cingulate monosynaptic inputs in adult mice. We also combined with a new high-throughput VISoR imaging technique to generate a three-dimensional whole-brain reconstruction, especially the thalamus. We found that cortical neurons in the ACC received direct projections from different sub-nuclei in the thalamus, including the anterior, ventral, medial, lateral, midline, and intralaminar thalamic nuclei. These findings provide key anatomic evidences for the connection between the thalamus and ACC.
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Giro del Cíngulo , Tálamo , Animales , Giro del Cíngulo/metabolismo , Ratones , Vías Nerviosas , Neuronas , Ratas , Núcleos Talámicos/fisiologíaRESUMEN
Ferulic acid (FA) is a natural methylated phenolic acid which represents various bioactivities. Bioproduction of FA suffers from insufficient methyl donor supplement and inefficient hydroxylation. To overcome these hurdles, we first activate the S-adenosylmethionine (SAM) cycle in E. coli by using endogenous genes to supply sufficient methyl donor. Then, a small protein Fre is introduced into the pathway to efficiently regenerate FADH2 for the hydroxylation. Remarkably, regeneration of these two cofactors dramatically promotes FA synthesis. Together with decreasing the byproducts formation and boosting precursor supply, the titer of FA reaches 5.09 g/L under fed-batch conditions, indicating a 20-fold improvement compared with the original producing E. coli strain. This work not only establishes a promising microbial platform for industrial level production of FA and its derivatives, but also highlights a convenient and effective strategy to enhance the biosynthesis of chemicals requiring methylation and FADH2-dependent hydroxylation.
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Escherichia coli , Ingeniería Metabólica , Ácidos Cumáricos , Escherichia coli/genética , Escherichia coli/metabolismo , Hidroxilación , Metilación , RegeneraciónRESUMEN
Two pairs of enantiomerically pure hexanuclear and tetranuclear microporous molybdenum(V) d/l-tartrates, (H2trz)3[Mo6O6(µ2-O)3(µ2-S)3(d/l-Htart)3(Htrz)6]·8H2O (abbreviated as d-1 and l-1; H4tart = tartaric acid, Htrz = 1,2,4-triazole) and (H22-mim)8[Mo4O4(µ2-S)4(d/l-tart)2]2·4H2O (d-2/l-2; H2-mim = 2-methylimidazole), have been isolated in reduced media and well characterized. These enantiomers are observed to finish self-assemblies with single chiral configurations. Structural analyses indicate that tartrates adopt different coordination modes with α-carboxy and/or α-alkoxy groups in 1 and 2, which are further completed with nitrogen-containing ligands. There are two types of micropores that exist in 1 and 2, separately, which are all formed by the isolated molecules themselves. The significant roles of hydrogen bonding among lattice molecules, tartrates, and multi-azoles are suggested, where 1 and 2 exhibited interesting supramolecular networks only through intramolecular self-sorts. Adsorption tests show that 1 has good affinities toward CO2 and O2, while 2 is the most potential O2 adsorbent compared with other common gases CO2, H2, CH4, and N2 under different pressures. In addition, IR, UV-vis, CD (circular dichroism), and solid-state 13C NMR spectroscopies have demonstrated the special chemical properties of these novel molybdenum d/l-tartrates.
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Blunt injury to the abdominal aorta is a rare but potentially fatal event. Despite being much less common than thoracic aorta involvement, it carries high morbidity and mortality. Computed tomography (CT) has become the standard method for evaluating the trauma patient and can provide a rapid accurate diagnosis of aortic injury. Depending on the magnitude of the traumatic forces, aortic injuries may be present in blunt abdominal trauma and appear as a spectrum of disease ranging from small intraluminal defects to full-thickness circumferential ruptures. We classify lesions into four groups as it has been reported in the literature: intimal flap (grade I), intramural hematoma (grade II), pseudoaneurysm (grade III), and rupture (grade IV). Radiologists play a crucial role in the evaluation and care of these patients since imaging findings significantly affect clinical management. The purpose of this paper is to describe the different types of traumatic injury to the abdominal aorta, highlighting the key imaging findings on computed tomography (CT).
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Traumatismos Abdominales , Lesiones del Sistema Vascular , Heridas no Penetrantes , Traumatismos Abdominales/diagnóstico por imagen , Aorta Torácica/lesiones , Humanos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Lesiones del Sistema Vascular/diagnóstico por imagen , Heridas no Penetrantes/diagnóstico por imagenRESUMEN
Traumatic arterial injuries of the extremities are a rare but potentially fatal event. Computed tomography (CT) angiography of the extremities has become the technique of choice and can provide rapid accurate detection and characterization of vascular lesions. Vascular injuries can be classified in active hemorrhage, vasospasm, occlusion, post-traumatic arteriovenous fistula, pseudoaneurysm, and patterns of intimal injuries. The learning objectives of this pictorial essay are to review the normal arterial anatomy of the upper and lower limbs, describe the technique of CT angiography in vascular trauma of the extremities, describe and illustrate the CT-angiography findings of traumatic arterial injuries, and know the potential pitfalls when interpreting a CT-angiography of the extremities.
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Lesiones del Sistema Vascular , Angiografía , Arterias/lesiones , Humanos , Extremidad Inferior/diagnóstico por imagen , Radiólogos , Lesiones del Sistema Vascular/diagnóstico por imagenRESUMEN
Objective: To prepare supramolecular photosensitizer that can be retained at the site of tumors and that has high light conversion efficiency so as to improve the efficacy of tumor photodynamic therapy (PDT). Methods: A covalent organic framework material based on amino tetraphenyl porphyrin (Tapp), henceforth referred to as Tapp-COF, was synthesized. The spectral characteristics, energy gap characteristics and singlet oxygen generation ability of the material were characterized. Then, Tapp-COF was processed by thin film hydration method to derive T-C@PP, a nano micelle unstable in physiological environment. The same method was used to process Tapp in order to make T@PP micelles, which were used as the controls. The particle size, potential, surface morphology and stability were examined. B16F10 mouse melanoma cells were injected subcutaneously into C57 mice and T-C@PP or T@PP were injected intratumorally, followed by light exposure or no light exposure. We assessed the in vitro photodynamic killing efficiency of the nano micelles and the status of tumor cells co-cultured with the photosensitizer micelles and validated the tumor retention ability and killing efficiency of the micelles . Results: Compared with Tapp, Tapp-COF displayed higher photodynamic conversion efficiency, and could produce more ROS. The T-C@PP micelles were unstable in physiological environment, and adsorptive aggregation would occur after co-culturing with tumor cells for a period of time. T-C@PP showed low cytotoxicity when there was no light exposure, but could kill tumor cells at relatively low concentration under 660 nm laser irradiation. T-C@PP could be retained in tumor tissue, and had better in vivo killing efficiency that that of T@PP. Conclusion: In this study, highly efficient TPP-COF based T-C@PP micelles were prepared. Under physiological conditions, these micelles could achieve tumor retention through self-aggregation. Possessing sound safety, the nano micelles showed promise for potential application in tumor PDT.
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Fotoquimioterapia , Porfirinas , Animales , Línea Celular Tumoral , Ratones , Micelas , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/farmacologíaRESUMEN
Objective: To explore the influence of social capital on the local residents' choice of medical institutions and to provide a reference basis for promoting diagnosis and treatment services available at different tiers. Methods: A classification tree model was established using the exhaustive chi-square automatic interaction detection (Exhaustive CHAID) method to screen for factors influencing the residents' choice of medical institutions, and a logistic regression model was used to quantitatively analyze the interaction effect of the influencing factors. Results: The classification tree model showed that there were four layers and eight terminal nodes, identifying a total of six influencing factors, including individual social capital, self-reported physical health, education, community social capital, chronic disease prevalence, and self-reported mental health. Logistic regression analysis showed that education (odds ratio [OR]=0.660, 95% confidence interval [CI]: 0.502-0.869), community social capital (OR=0.746, 95% CI: 0.589-0.943), and individual social capital (OR=0.405, 95% CI: 0.287-0.572) (P<0.001) had an impact on residents' choice of medical institution. There was an interaction between individual social capital and self-reported physical health on residents' choice of medical institution (OR=1.872, 95% CI: 1.180-2.969, P<0.05). Conclusion: Interventions in terms of social capital factors should be considered in order to promote the rational use of medical resources.
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Capital Social , Humanos , Modelos Logísticos , Salud Mental , Oportunidad Relativa , Características de la ResidenciaRESUMEN
BACKGROUND: To investigate the effect of TriBAFF-CAR-T cells on hematological tumor cells. METHODS: TriBAFF-CAR-T and CD19-CAR-T cells were co-cultured with BAFFR-bearing B-cell malignancies at different effector/target ratios to evaluate the anti-tumor effects. In vivo, TriBAFF-CAR-T and CD19-CAR-T cells were intravenously injected into Raji-luciferase xenograft mice. CD19 antigens losing lymphoblasts was simulated by Raji knocking out CD19 (CD19KO) to investigate the effect of TriBAFF-CAR-T cells on CD19KO Raji. RESULTS: Both TriBAFF-CAR-T and CD19-CAR-T cells significantly induced the lysis of Raji, BALL-1, and Jeko-1. Moreover, when CD19-CAR-T cells specifically caused the lysis of K562 with overexpressed CD19, the lethal effect of TriBAFF-CAR-T cells was also specific for BAFFR-bearing K562 with increasing levels of interleukin-2 and INF-γ. The TriBAFF-CAR-T have the same effect with CD19-CAR-T cells in treating Raji xenofraft mice. TriBAFF-CAR-T cells also have great effect in CD19KO Raji cells. CONCLUSIONS: In this study, we successfully constructed novel TriBAFF-CAR-T cells to eliminate BAFFR-bearing and CD19 antigen loss in hematological tumor cells.
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Novel molybdenum(VI/V) POM-based self-constructed frameworks [MoVI 12 O24 (µ2 -O)12 (trz)6 (H2 O)6 ] â 6Hma â 18H2 O (1, Htrz=1H-1,2,3-triazole, ma=methylamine), [MoVI 7 O14 (µ2 -O)8 (trz)5 (H2 O)] â 7Hma â 5H2 O (2), Na3 [MoV 6 O6 (µ2 -O)9 (Htrz)3 (trz)3 ] â 7.5H2 O (3) and [MoV 8 O8 (µ2 -O)12 (Htrz)8 ] â 30H2 O (4) have been covalently decorated with tri-coordinated deprotonated/protonated 1,2,3-triazoles. Channels with an inner diameter of 7.5â Å were found in 1, whereas a tunnel composed of stacking molecules with an inner diameter of 4.1â Å along the b-axis exists in 2; it is occupied by free disordered methylamines, showing selective adsorption of O2 and CO2 at 25 °C. Obvious downfield shifts were observed by 13 C NMR spectroscopies for methylamines inside the confined channels in 1 and 2. There are diversified pores in 3 and 4, which are formed by the molecules themselves and intermolecular accumulations. Adsorption tests indicate that 3 and 4 are fine adsorption materials for CH4 and CO2 under low pressure that rely on the environments built by the POMs. Correspondingly, 1 and 2 display reversible photoresponsive thermochromism that is subtlety influenced by the channels. The polyoxometalate organic frameworks (POMOFs) with multiple functional adsorptions are easy to assemble. Their photo-/thermoresponse properties offer a new pathway for the self-constructions of one-off hybrid materials that possess the good properties of both POMs and MOFs.