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1.
World J Gastrointest Surg ; 16(7): 2337-2342, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39087118

RESUMEN

BACKGROUND: Severe bleeding as a result of a major vascular injury is a potentially fatal event commonly observed in the emergency department. Bowel necrosis and gastric ulcers secondary to ischemia are rare due to their rich blood supply. In this case, we present the case of a patient who was treated successfully following rupture of his femoral artery resulting in bowel necrosis and an unusually large gastric ulcer. CASE SUMMARY: A 28-year-old male patient sustained a knife stab wound to the right thigh, causing rupture of his femoral artery and leading to massive bleeding. He underwent cardiopulmonary resuscitation and received a large blood transfusion. Abdominal surgeries confirmed bowel necrosis, and jejunostomy was performed. The necrotic intestine was removed, the remaining intestine was anastomosed, and the right thigh was amputated. After three surgeries, the patient's overall condition gradually improved, and the patient was discharged from the hospital. However, one day after discharge, the patient was admitted again due to dizziness and melena, and a gastroduodenoscopy revealed a giant banded ulcer. After 2 weeks of treatment, the ulcer had decreased in size without bleeding. Six months after the last surgery, enterostomy and reintroduction surgery were completed. The patient was fitted with a right lower limb prosthesis one year after surgery. After 3 years of follow-up, the patient did not complain of discomfort. CONCLUSION: Trauma department physicians need to be aware of the possible serious complications involving the abdomen of trauma patients with massive bleeding.

3.
bioRxiv ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-39026723

RESUMEN

F luorogenic ap tamers (FAPs) have become an increasingly important tool in cellular sensing and pathogen diagnostics. However, fine-tuning FAPs for enhanced performance remains challenging even with the structural details provided by X-ray crystallography. Here we present a novel approach to optimize a DNA-based FAP (D-FAP), Lettuce, on repurposed Illumina next-generation sequencing (NGS) chips. When substituting its cognate chromophore, DFHBI-1T, with TO1-biotin, Lettuce not only shows a red-shifted emission peak by 53 nm (from 505 to 558 nm), but also a 4-fold bulk fluorescence enhancement. After screening 8,821 Lettuce variants complexed with TO1-biotin, the C14T mutation is found to exhibit an improved apparent dissociated constant ( vs. 0.82 µM), an increased quantum yield (QY: 0.62 vs. 0.59) and an elongated fluorescence lifetime (τ: 6.00 vs. 5.77 ns), giving 45% more ensemble fluorescence than the canonical Lettuce/TO1-biotin complex. Molecular dynamic simulations further indicate that the π-π stacking interaction is key to determining the coordination structure of TO1-biotin in Lettuce. Our screening-and-simulation pipeline can effectively optimize FAPs without any prior structural knowledge of the canonical FAP/chromophore complexes, providing not only improved molecular probes for fluorescence sensing but also insights into aptamer-chromophore interactions.

4.
Biochim Biophys Acta Bioenerg ; 1865(4): 149492, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38960080

RESUMEN

Mitochondrial DNA (mtDNA) mutations, including the m.3243A>G mutation that causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), are associated with secondary coenzyme Q10 (CoQ10) deficiency. We previously demonstrated that PPARGC1A knockdown repressed the expression of PDSS2 and several COQ genes. In the present study, we compared the mitochondrial function, CoQ10 status, and levels of PDSS and COQ proteins and genes between mutant cybrids harboring the m.3243A>G mutation and wild-type cybrids. Decreased mitochondrial energy production, defective respiratory function, and reduced CoQ10 levels were observed in the mutant cybrids. The ubiquinol-10:ubiquinone-10 ratio was lower in the mutant cybrids, indicating blockage of the electron transfer upstream of CoQ, as evident from the reduced ratio upon rotenone treatment and increased ratio upon antimycin A treatment in 143B cells. The mutant cybrids exhibited downregulation of PDSS2 and several COQ genes and upregulation of COQ8A. In these cybrids, the levels of PDSS2, COQ3-a isoform, COQ4, and COQ9 were reduced, whereas those of COQ3-b and COQ8A were elevated. The mutant cybrids had repressed PPARGC1A expression, elevated ATP5A levels, and reduced levels of mtDNA-encoded proteins, nuclear DNA-encoded subunits of respiratory enzyme complexes, MNRR1, cytochrome c, and DHODH, but no change in TFAM, TOM20, and VDAC1 levels. Alterations in the CoQ10 level in MELAS may be associated with mitochondrial energy deficiency and abnormal gene regulation. The finding of a reduction in the ubiquinol-10:ubiquinone-10 ratio in the MELAS mutant cybrids differs from our previous discovery that cybrids harboring the m.8344A>G mutation exhibit a high ubiquinol-10:ubiquinone-10 ratio.

5.
Health Aff Sch ; 2(7): qxae088, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39081720

RESUMEN

Dementia specialists-neurologists, geriatricians, and geriatric psychiatrists-serve a critical clinical function in diagnosing early-stage Alzheimer's disease and determining eligibility for treatment with disease-modifying therapies. However, the availability of dementia specialists is limited and varies across the United States. Using data from the Area Health Resources Files, we found that the median density of dementia specialists across hospital referral regions in United States is 28.8 per 100 000 population aged 65 years and older (interquartile range 19.3-43.6). We derived thresholds of 33-45 dementia specialists per 100 000 population aged 65 years and older as the provider density necessary to care for older adults with mild cognitive impairment and dementia. Based on these thresholds, we estimated that 34%-59% of the population aged 65 years and older resided in areas with potential dementia specialist shortfalls. The extent of potential shortfalls varied by state and rurality. A better understanding of potential gaps in the availability of dementia specialists will inform policies and practices to ensure access to services for people with cognitive impairment and dementia.

6.
Breast Cancer ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39085679

RESUMEN

BACKGROUND: Insufficient data available for older patients with breast cancer complicates decision-making regarding optimal treatment. A systematic review that uses real-world data is required for assessing the effectiveness and potential adverse effects of various therapies for this age group of patients. METHODS: Databases of PubMed, Embase, and Cochrane Library were searched. We included clinical studies that evaluated various treatments for geriatric breast cancer, including adjuvant radiation therapy, hypofractionated radiation therapy (hypo-RT) and accelerated and partial breast irradiation (APBI), endocrine therapy, chemotherapy, and targeted therapy. RESULTS: A total of 71 studies were retrieved. Adjuvant radiation therapy significantly improved overall survival (OS) compared with no radiation [hazard ratio (HR) = 0.60, 95% confidence interval (CI) 0.54-0.67]. The pooled estimates of OS for hypo-RT and APBI demonstrated no inferiority compared with conventional radiation. Both endocrine treatment (HR = 0.63, 95% CI 0.43-0.92) and chemotherapy (HR = 0.76, 95% CI 0.65-0.88) significantly increased OS compared with no treatment. Trastuzumab monotherapy significantly enhanced OS compared with no trastuzumab use (HR = 0.23, 95% CI 0.07-0.73). CONCLUSION: Despite concerns about potential complications during treatment in older patients, proactive therapies significantly increase their survival rates. For patients who are frailer, hypo-RT and APBI offer survival rates comparable to traditional modalities. Additionally, targeted therapy as a monotherapy holds promise as a viable option for patients with HER2-positive breast cancer who cannot undergo chemotherapy. Therefore, by conducting thorough general assessments and clinical evaluations, the side effects of postoperative treatments can be effectively managed.

7.
Am J Manag Care ; 30(7): e203-e209, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38995824

RESUMEN

OBJECTIVES: To identify factors associated with clinicians' likelihood and intensity of applying fluoride varnish (FV) overall and for visits paid by Medicaid and private insurers. STUDY DESIGN: Observational study using claims data. METHODS: Using the Massachusetts All-Payer Claims Database (2016-2018), we conducted a repeated cross-sectional study of 2911 clinicians (7277 clinician-year observations) providing well-child visits to children aged 1 to 5 years. Zero-inflated negative binomial models estimated the probability of a clinician applying FV and the number of visits with FV applications, overall and separately for visits paid by Medicaid and private insurers. RESULTS: A total of 30.9% of clinician-years applied FV at least once, and overall, an average of 8.4% of a clinician's well-child visits included FV annually. Controlling for all covariates, having a higher percentage of patients insured by Medicaid was associated with applying FV (OR, 1.35; 95% CI, 1.23-1.45) and a higher expected number of applications (OR, 1.05; 95% CI, 1.02-1.09). Additionally, having a higher percentage of patients aged 1 to 5 years was associated with applying FV (OR, 1.20; 95% CI, 1.01-1.43), but not the number of applications. Similar associations were observed among visits paid by private insurers. CONCLUSIONS: Despite clinical recommendations and mandated insurance reimbursements, the likelihood and intensity of FV applications was low for most pediatric primary care clinicians. Clinician behavior was associated with patient-panel characteristics, suggesting the need for interventions that account for these differences.


Asunto(s)
Fluoruros Tópicos , Medicaid , Humanos , Preescolar , Lactante , Estados Unidos , Medicaid/estadística & datos numéricos , Estudios Transversales , Femenino , Masculino , Fluoruros Tópicos/uso terapéutico , Fluoruros Tópicos/administración & dosificación , Massachusetts , Pautas de la Práctica en Medicina/estadística & datos numéricos , Revisión de Utilización de Seguros , Seguro de Salud/estadística & datos numéricos
8.
Anal Chim Acta ; 1318: 342941, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39067920

RESUMEN

BACKGROUND: Hydroxylamine (HA) is vital industrial raw material and pharmaceutical intermediate. In addition, HA is an important cellular metabolite, which is intermediate in the formation of nitric oxide and nitroxide. However, excessive amounts of HA are toxic to both animals and plants. Conventional methods for the detection of HA are cumbersome and complicated. The detection of HA with fluorescent probes is convenient and sensitive. There are few probes available for the detection of hydroxylamine. Therefore, a fluorescent probe for the sensitive and selective detection of HA was developed in this work. RESULTS: A coumarin derivative SWJT-22 was synthesized as a colorimetric fluorescent probe to detect hydroxylamine (HA), with high sensitivity and selectivity. The detection limit of the probe to HA was 0.15 µM, which was lower than most probes of HA. Upon the addition of HA to aqueous solution containing SWJT-22, the color of the solution changed from orange to yellow, and the fluorescence color also changed from orange to green. The reaction mechanism of SWJT-22 to HA was confirmed by 1H NMR titrations, mass spectrometry and round bottom flask experiments. Moreover, SWJT-22 had been fabricated into portable test strips for the detection of HA. SWJT-22 had been successfully used in cellular imaging and could detect both endogenous and exogenous HA in HeLa cells and RAW 264.7 cells. SIGNIFICANCE: Due to the physiological role of hydroxylamine in organisms, it is crucial to detect hydroxylamine selectively and sensitively. This work provided a convenient tool for the detection of hydroxylamine, not only to detect endogenous and exogenous HA in cells, but also made into portable test strips. The HA fluorescent probe SWJT-22 is expected to promote the study of HA in physiological processes.


Asunto(s)
Colorimetría , Cumarinas , Colorantes Fluorescentes , Hidroxilamina , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Hidroxilamina/química , Colorimetría/métodos , Ratones , Animales , Células RAW 264.7 , Cumarinas/química , Cumarinas/síntesis química , Humanos , Límite de Detección , Imagen Óptica , Células HeLa , Estructura Molecular
9.
Biomed Opt Express ; 15(5): 3094-3111, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38855698

RESUMEN

Two-photon excited fluorescence (TPEF) is a powerful technique that enables the examination of intrinsic retinal fluorophores involved in cellular metabolism and the visual cycle. Although previous intensity-based TPEF studies in non-human primates have successfully imaged several classes of retinal cells and elucidated aspects of both rod and cone photoreceptor function, fluorescence lifetime imaging (FLIM) of the retinal cells under light-dark visual cycle has yet to be fully exploited. Here we demonstrate a FLIM assay of photoreceptors and retinal pigment epithelium (RPE) that reveals key insights into retinal physiology and adaptation. We found that photoreceptor fluorescence lifetimes increase and decrease in sync with light and dark exposure, respectively. This is likely due to changes in all-trans-retinol and all-trans-retinal levels in the outer segments, mediated by phototransduction and visual cycle activity. During light exposure, RPE fluorescence lifetime was observed to increase steadily over time, as a result of all-trans-retinol accumulation during the visual cycle and decreasing metabolism caused by the lack of normal perfusion of the sample. Our system can measure the fluorescence lifetime of intrinsic retinal fluorophores on a cellular scale, revealing differences in lifetime between retinal cell classes under different conditions of light and dark exposure.

10.
Environ Pollut ; 356: 124253, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38851378

RESUMEN

Bioaugmentation techniques still show drawbacks in the cleanup of total petroleum hydrocarbons (TPHs) from petroleum-contaminated site soil. Herein, this study explored high-performance immobilized bacterial pellets (IBPs) embed Microbacterium oxydans with a high degrading capacity, and developed a controlled-release oxygen composite (CROC) that allows the efficient, long-term release of oxygen. Tests with four different microcosm incubations were performed to assess the effects of IBPs and CROC on the removal of TPHs from petroleum-contaminated site soil. The results showed that the addition of IBPs and/or CROC could significantly promote the remediation of TPHs in soil. A CROC only played a significant role in the degradation of TPHs in deep soil. The combined application of IBPs and CROC had the best effect on the remediation of deep soil, and the removal rate of TPHs reached 70%, which was much higher than that of nature attenuation (13.2%) and IBPs (43.0%) or CROC (31.9%) alone. In particular, the CROC could better promote the degradation of heavy distillate hydrocarbons (HFAs) in deep soil, and the degradation rates of HFAs increased from 6.6% to 33.2%-21.0% and 67.9%, respectively. In addition, the IBPs and CROC significantly enhanced the activity of dehydrogenase, catalase, and lipase in soil. Results of the enzyme activity were the same as that of TPH degradation. The combined application of IBPs and CROC not only increased the microbial abundance and diversity of soil, but also significantly enhanced the enrichment of potential TPH-biodegrading bacteria. M. oxydans was dominant in AP (bioaugmentation with addition of IBPs) and APO (bioaugmentation with the addition of IBPs and CROC) microcosms that added IBPs. Overall, the IBPs and CROC developed in this study provide a novel option for the combination of bioaugmentation and biostimulation for remediating organic pollutants in soil.

12.
Int Immunopharmacol ; 136: 112369, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38824903

RESUMEN

Estrogen and related receptors have been shown to have a significant impact on human development, reproduction, metabolism and immune regulation and to play a critical role in tumor development and treatment. Traditionally, the nuclear estrogen receptors (nERs) ERα and ERß have been thought to be involved in mediating the estrogenic effects. However, our group and others have previously demonstrated that the G protein-coupled estrogen receptor (GPER) is the third independent ER, and estrogen signaling mediated by GPER is known to play an important role in normal physiology and a variety of abnormal diseases. Interestingly, recent studies have progressively revealed GPER involvement in the maintenance of the normal immune system, abnormal immune diseases, and inflammatory lesions, which may be of significant clinical value primarily in the immunotherapy of tumors. In this article, we review current advances in GPER-related immunomodulators and provide a theoretical basis and potential clinical targets to ameliorate immune-related diseases and immunotherapy for tumors.


Asunto(s)
Neoplasias , Receptores de Estrógenos , Receptores Acoplados a Proteínas G , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/inmunología , Receptores de Estrógenos/metabolismo , Animales , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/metabolismo , Inmunoterapia/métodos , Transducción de Señal , Estrógenos/metabolismo
13.
BMC Cancer ; 24(1): 754, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38907215

RESUMEN

PURPOSE: Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG. METHODS: A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m2/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis. RESULTS: The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction. CONCLUSIONS: Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas , Glioma , Piridinas , Temozolomida , Humanos , Temozolomida/administración & dosificación , Temozolomida/uso terapéutico , Temozolomida/efectos adversos , Femenino , Masculino , Adulto , Piridinas/administración & dosificación , Piridinas/efectos adversos , Piridinas/uso terapéutico , Glioma/tratamiento farmacológico , Glioma/patología , Adolescente , Estudios Retrospectivos , Niño , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Preescolar , Persona de Mediana Edad , Resultado del Tratamiento
14.
J Am Heart Assoc ; 13(13): e034816, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38904247

RESUMEN

BACKGROUND: ELMSAN1 (ELM2-SANT domain-containing scaffolding protein 1) is a newly identified scaffolding protein of the MiDAC (mitotic deacetylase complex), playing a pivotal role in early embryonic development. Studies on Elmsan1 knockout mice showed that its absence results in embryo lethality and heart malformation. However, the precise function of ELMSAN1 in heart development and formation remains elusive. To study its potential role in cardiac lineage, we employed human-induced pluripotent stem cells (hiPSCs) to model early cardiogenesis and investigated the function of ELMSAN1. METHODS AND RESULTS: We generated ELMSAN1-deficient hiPSCs through knockdown and knockout techniques. During cardiac differentiation, ELMSAN1 depletion inhibited pluripotency deactivation, decreased the expression of cardiac-specific markers, and reduced differentiation efficiency. The impaired expression of genes associated with contractile sarcomere structure, calcium handling, and ion channels was also noted in ELMSAN1-deficient cardiomyocytes derived from hiPSCs. Additionally, through a series of structural and functional assessments, we found that ELMSAN1-null hiPSC cardiomyocytes are immature, exhibiting incomplete sarcomere Z-line structure, decreased calcium handling, and impaired electrophysiological properties. Of note, we found that the cardiac-specific role of ELMSAN1 is likely associated with histone H3K27 acetylation level. The transcriptome analysis provided additional insights, indicating maturation reduction with the energy metabolism switch and restored cell proliferation in ELMSAN1 knockout cardiomyocytes. CONCLUSIONS: In this study, we address the significance of the direct involvement of ELMSAN1 in the differentiation and maturation of hiPSC cardiomyocytes. We first report the impact of ELMSAN1 on multiple aspects of hiPSC cardiomyocyte generation, including cardiac differentiation, sarcomere formation, calcium handling, electrophysiological maturation, and proliferation.


Asunto(s)
Diferenciación Celular , Células Madre Pluripotentes Inducidas , Miocitos Cardíacos , Humanos , Acetilación , Señalización del Calcio , Células Cultivadas , Histonas/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Miocitos Cardíacos/metabolismo , Sarcómeros/metabolismo
15.
Angew Chem Int Ed Engl ; : e202405520, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38896428

RESUMEN

Functionalization of Si-bound methyl group provides an efficient access to diverse organosilanes. However, the asymmetric construction of silicon-stereogenic architectures by functionalization of Si-bound methyl group has not yet been described despite recent significant progress in producing chiral silicon. Herein, we disclosed the enantioselective silylmethyl functionalization involving the aryl to alkyl 1,5-palladium migration to access diverse naphthalenes possessing an enantioenriched stereogenic silicon center, which are inaccessible before. It is worthy to note that the realization of asymmetric induction at the step of metal migration itself remains challenging. Our study constitutes the first enantioselective aryl to alkyl 1,5-palladium migration reaction. The key to the success is the discovery and fine-tuning of the different substituents of α,α,α,α-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL)-based phosphoramidites, which ensure the enantioselectivity and desired reactivity.

16.
Artículo en Inglés | MEDLINE | ID: mdl-38787664

RESUMEN

The advent of single-cell RNA sequencing (scRNA-seq) has brought forth fresh perspectives on intricate biological processes, revealing the nuances and divergences present among distinct cells. Accurate single-cell analysis is a crucial prerequisite for in-depth investigation into the underlying mechanisms of heterogeneity. Due to various technical noises, like the impact of dropout values, scRNA-seq data remains challenging to interpret. In this work, we propose an unsupervised learning framework for scRNA-seq data analysis (aka Sc-GNNMF). Based on the non-negativity and sparsity of scRNA-seq data, we propose employing graph-regularized non-negative matrix factorization (GNNMF) algorithm for the analysis of scRNA-seq data, which involves estimating cell-cell similarity and gene-gene similarity through Laplacian kernels and p-nearest neighbor graphs ( p-NNG). By assuming intrinsic geometric local invariance, we use a weighted p-nearest known neighbors ( p-NKN) of cell-cell interactions to guide the matrix decomposition process, promoting the closeness of cells with similar types in cell-gene data space and determining a more suitable embedding space for clustering. Sc-GNNMF demonstrates superior performance compared to other methods and maintains satisfactory compatibility and robustness, as evidenced by experiments on 11 real scRNA-seq datasets. Furthermore, Sc-GNNMF yields excellent results in clustering tasks, extracting useful gene markers, and pseudo-temporal analysis.

17.
Mol Immunol ; 171: 47-55, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38795684

RESUMEN

Myopia is regarded as a worldwide epidemic ocular disease, has been proved related to inflammation. CD55, also known as decay-accelerating factor (DAF) can modulate the activation of complement through inhibiting the formation of complement 3 convertase and its dysregulation is involved in various inflammatory diseases. To investigate the association between CD55 and myopia, and to test whether CD55 can inhibit myopia development by suppressing inflammation in the eye, we use three different animal models including monocular form-deprivation myopia, myopia induced by TNF-α administration and allergic conjunctivitis animal model to reveal the CD55 in myopia development. The tears of thirty-eight participants with different spherical equivalents were collected and CD55 in the tears were also analyzed. Complement 3 and complement 5 levels increased while CD55 levels decreased in allergic conjunctivitis and myopic eyes. After anti-inflammatory drugs administration, CD55 expression was increased in monocular form-deprivation myopia model. We also found inflammatory cytokines TGF-ß, IL-6, TNF-α, and IL-1ß may enhance complement 3 and complement 5 activation while CD55 level was suppressed contrary. Moreover, lower CD55 levels were found in the tears of patients with myopia with decreased diopter values. Finally, CD55-Fc administration on the eyelids can inhibit the elongation of axial length and change of refractive error. CD55-Fc application also suppress myopia development subsequent to complement 3 and complement 5 reduction and can lower myopia-specific (MMP-2 and TGF-ß) cytokine expression in TNF-α induced myopia animal model. This suggests that CD55 can inhibit myopia development by suppression of complement activation and eventual down-regulation of inflammation.


Asunto(s)
Antígenos CD55 , Modelos Animales de Enfermedad , Inflamación , Miopía , Adolescente , Animales , Femenino , Humanos , Masculino , Adulto Joven , Antígenos CD55/metabolismo , Activación de Complemento/efectos de los fármacos , Complemento C3/metabolismo , Conjuntivitis Alérgica/inmunología , Conjuntivitis Alérgica/metabolismo , Citocinas/metabolismo , Miopía/metabolismo , Lágrimas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Complemento C5/metabolismo
18.
Vet Microbiol ; 294: 110131, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38805917

RESUMEN

Outer membrane vesicles (OMVs) are membranous structures frequently observed in Gram-negative bacteria that contain bioactive substances. These vesicles are rich in bacterial antigens that can activate the host's immune system, making them a promising candidate vaccine to prevent and manage bacterial infections. The aim of this study was to assess the immunogenicity and protective efficacy of OMVs derived from Salmonella enterica serovar Typhimurium and S. Choleraesuis, while also focusing on enhancing OMV production. Initial experiments showed that OMVs from wild-type strains did not provide complete protection against homologous Salmonella challenge, possible due to the presence of flagella in the purified OMVs samples, which may elicit an unnecessary immune response. To address this, flagellin-deficient mutants of S. Typhimurium and S. Choleraesuis were constructed, designated rSC0196 and rSC0199, respectively. These mutants exhibited reduced cell motility and their OMVs were found to be flagellin-free. Immunization with non-flagellin OMVs derived from rSC0196 induced robust antibody responses and improved survival rates in mice, as compared to the OMVs derived from the wild-type UK-1. In order to enhance OMV production, deletions of ompA or tolR were introduced into rSC0196. The deletion of tolR not only increase the yield of OMVs, but also conferred complete protection against homologous S. Typhimurium challenge in mice. Collectively, these findings indicate that the flagellin-deficient OMVs with a tolR mutation have the potential to serve as a versatile vaccine platform, capable of inducing broad-spectrum protection against significant pathogens.


Asunto(s)
Proteínas de la Membrana Bacteriana Externa , Ratones Endogámicos BALB C , Vacunas contra la Salmonella , Salmonella typhimurium , Animales , Salmonella typhimurium/inmunología , Salmonella typhimurium/genética , Ratones , Vacunas contra la Salmonella/inmunología , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas de la Membrana Bacteriana Externa/genética , Femenino , Flagelina/inmunología , Flagelina/genética , Salmonelosis Animal/prevención & control , Salmonelosis Animal/microbiología , Salmonelosis Animal/inmunología , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Membrana Externa Bacteriana/inmunología , Salmonella/inmunología , Salmonella/genética , Inmunogenicidad Vacunal , Antígenos Bacterianos/inmunología
19.
Nat Commun ; 15(1): 4470, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38796520

RESUMEN

Molecular ferroelectrics are attracting great interest due to their light weight, mechanical flexibility, low cost, ease of processing and environmental friendliness. These advantages make molecular ferroelectrics viable alternatives or supplements to inorganic ceramics and polymer ferroelectrics. It is expected that molecular ferroelectrics with good performance can be fabricated, which in turns calls for effective chemical design strategies in crystal engineering. To achieve so, we propose a hydrogen bond modification method by introducing the hydroxyl group, and successfully boost the phase transition temperature (Tc) by at least 336 K. As a result, the molecular ferroelectric 1-hydroxy-3-adamantanammonium tetrafluoroborate [(HaaOH)BF4] can maintain ferroelectricity until 528 K, a Tc value much larger than that of BTO (390 K). Meanwhile, micro-domain patterns, in stable state for 2 years, can be directly written on the film of (HaaOH)BF4. In this respect, hydrogen bond modification is a feasible and effective strategy for designing molecular ferroelectrics with high Tc and stable ferroelectric domains. Such an organic molecule with varied modification sites and the precise crystal engineering can provide an efficient route to enrich high-Tc ferroelectrics with various physical properties.

20.
J Phys Chem Lett ; 15(22): 5923-5934, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38809779

RESUMEN

The implementation of energy-saving policies has stimulated intensive interest in exploring self-powered optoelectronic devices. The 2D p-n homojunction exhibits effective generation and separation of carriers excited by light, realizing lower power consumption and higher performance photodetectors. Here, a self-powered photodetector with high performance is fabricated based on an F4-TCNQ localized molecular-doped lateral InSe homojunction. Compared with the intrinsic InSe photodetector, the switching light ratio (Ilight/Idark) of the p-n homojunction device can be enhanced by 2.2 × 104, and the temporal response is also dramatically improved to 24/30 µs. Benefiting from the built-in electric field, due to the formation of an InSe p-n homojunction after partial doping of F4-TCNQ on InSe, the device possesses a high responsivity (R) of 93.21 mA/W, with a specific detectivity (D*) of 1.14 × 1011 Jones. These results suggest a promising approach to get a lateral InSe p-n homojunction and reveal the potential application of the device for next generation low-consumption photodetectors.

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