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1.
BMC Ophthalmol ; 24(1): 407, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39294597

RESUMO

PURPOSE: To evaluate retinal nerve fiber layer thickness (RNFLT) and radial peripapillary capillaries (RPC) density in adults with different degrees of myopia using optical coherence tomography angiography (OCTA) and explore their relationship with ocular factors, such as axial length (AL) and disc area. METHODS: A total of 188 subjects were included in this cross-sectional study. The eyes were divided into four groups according to AL. OCTA was used for the assessment of RNFLT, RPC density, and other optic disc measurements, such as disc area. One-way analysis of variance was performed to compare differences between four groups, and P value < 0.01 was considered significant. RESULTS: The RNFLT was significantly thinner in high myopia (HM) group at inferior nasal (IN) quadrant (P = 0.004) than low myopia (LM) group, but thicker at temporal inferior (TI) quadrant (P = 0.006). The RPC density of nasal superior (NS) quadrant, nasal inferior (NI) quadrant, and inferior nasal (IN) quadrant significantly decreased as AL increasing. By simple linear regression analysis, the inside disc RPC (iRPC) density tended to be correlated significantly with AL (0.3997%/mm, P < 0.0001). Peripapillary RPC (pRPC) density was in significant correlation with AL (-0.2791%/mm, P = 0.0045), and peripapillary RNFLT (pRNFLT) was in significant correlation with disc area (0.2774%/mm2, P = 0.0001). CONCLUSION: RNFLT and RPC density were closely associated with AL and disc area. They might be new indexes in assessing and detecting myopia development via OCTA.


Assuntos
Capilares , Angiofluoresceinografia , Miopia , Fibras Nervosas , Disco Óptico , Células Ganglionares da Retina , Vasos Retinianos , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Estudos Transversais , Masculino , Feminino , Adulto , Disco Óptico/irrigação sanguínea , Disco Óptico/diagnóstico por imagem , Disco Óptico/patologia , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologia , Capilares/patologia , Capilares/diagnóstico por imagem , Angiofluoresceinografia/métodos , Pessoa de Meia-Idade , Vasos Retinianos/patologia , Vasos Retinianos/diagnóstico por imagem , Adulto Jovem , Comprimento Axial do Olho/patologia , Comprimento Axial do Olho/diagnóstico por imagem
2.
Polymers (Basel) ; 16(14)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39065358

RESUMO

This study focused on effective methods of laser engraving treatment (LET), plasma spraying, and resin pre-coating (RPC) to manufacture the reinforced adhesive joints of titanium alloy and carbon fiber-reinforced polymer (TA-CFRP) composites. The combined treatments contributed to the creation of a better adhesive bonding condition and offer a vertical gap between circular protrusions to form epoxy pins and carbon nanotube (CNT)-reinforced epoxy pins. The bonding strength of the TA-CFRP composite was reinforced by 130.6% via treatments with a twice-engraving unit of 0.8 mm, plasma spraying, and RPC. The original debonding failure on the TA surface was changed into the cohesive failure of the epoxy adhesive and delamination-dominated failure of the CFRP panel. Overall, laser engraving has been confirmed as an effective and controllable treatment method to reinforce the bonding strength of the TA-CFRP joint combined with plasma spraying and RPC. It may be considered as an alternative in industry for manufacturing high-performance metal-CFRP composites.

3.
Sci Rep ; 14(1): 12327, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811693

RESUMO

Precast concrete structures have developed rapidly because they meet the requirements of green and low-carbon social development. In this paper, a precast post-tensioned high-performance concrete frame beam-column joint was proposed, and the low-cycle reversed load test was performed on the four proposed joints. The main differences between the four joints are the different prestress values applied by the joints and whether the beam-column joint is provided with L-shaped steel. The seismic performance indexes such as hysteresis curve, stiffness degradation, deformation capacity, energy dissipation capacity and residual deformation of each node were obtained through experiments. By comparing various seismic performance indicators, it could be found that the use of high-performance concrete could effectively avoid the phenomenon of local crushing of concrete due to excessive prestressing. At the same time, it was found that the setting of L-shaped steel plate at the beam-column junction could effectively avoid the early damage at the beam-column junction. On the basis of the test, the three-line restoring force model of the joint was established by the method of experimental regression analysis. The model could better reflect the stress situation of each stage of the joint. Based on the experimental and theoretical analysis, the finite element analysis model of the joint was established, and the model calculation results were in good agreement with the experimental results.

4.
Pharmaceutics ; 16(3)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38543193

RESUMO

In recent years, nuclear medicine has gained great interest, partly due to the success story of [177Lu]Lu-PSMA-617 (PluvictoTM). Still, in-depth preclinical characterization of radiopharmaceuticals mainly happens at centers that allow working with radioactive material. To support the development of novel radiopharmaceuticals, alternative non-radioactive characterization assays are highly desirable. The aim of this study was to demonstrate that inductively coupled plasma mass spectrometry (ICP-MS) associated with a chromatographic system can serve as a surrogate for the classical high-performance liquid chromatography (HPLC)-radiodetector combination for preclinical in vitro characterization of non-radioactive metal-labeled analogs of radiopharmaceuticals. In this proof-of-concept study, we demonstrate the applicability of HPLC-ICP-MS by assessing the stability of 175Lu- and natGa-labeled prostate-specific membrane antigen (PSMA)-targeting peptidomimetics, single domain antibody (sdAb) conjugates, and monoclonal antibody (mAb) conjugates. 175Lu-labeled DOTAGA-conjugated and natGa-labeled NODAGA-conjugated sdAbs and mAbs showed the highest stability with >90% still intact after 24 h. The peptidomime-tics [175Lu]Lu-PSMA-617 and [natGa]Ga-PSMA-11 showed identical in vitro serum stability as it was reported for their corresponding radioligands with >99% intact species after 24 h incubation in mouse serum, demonstrating the reliability of the method. Hence, the established HPLC-ICP-MS methods can support the development of novel radiopharmaceuticals in a classical pharmaceutical setting.

5.
J Ophthalmic Inflamm Infect ; 14(1): 2, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38177891

RESUMO

BACKGROUND: Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a rare inflammatory eye disorder that is characterized by the presence of multiple placoid lesions in the posterior pole of the eye. Relentless placoid chorioretinitis (RPC) is an inflammatory chorioretinopathy that combines clinical features of APMPPE and serpiginous chorioretinitis, which is a progressive condition with a high risk of visual disability. Patients with COVID-19 can develop various ocular manifestations, however, there have been limited reports of APMPPE and RPC associated with the infection. We report a case of a patient who developed APMPPE after a COVID-19 infection and subsequently progressed into RPC. CASE PRESENTATION: A 17-year-old male presented with a one-week history of painless gradual visual loss in both eyes. Two months prior to the visual symptoms, the patient had a SARS CoV-2 infection, confirmed by polymerase chain reaction test. Clinical findings with fundoscopy, optical coherence tomography and fluorescein angiography were consistent with APMPPE. Due to the severely affected vision in both eyes, the patient was started on 50 mg oral prednisolone daily, after which vision began to improve rapidly. Two months after symptom onset during steroid taper, the impression of continued inflammatory activity and new lesions in the retinal periphery of both eyes suggested RPC. Adalimumab 40 mg every other week was initiated with 12.5 mg prednisolone daily followed by slow tapering. Vision improved and five months after the start of the adalimumab treatment, the steroid was discontinued and there were no signs of active inflammation. The patient has been followed for a total of 21 months since presentation, had full visual recovery and good tolerance of the immunosuppressive treatment. CONCLUSION: COVID-19 might cause long-lasting activity of APMPPE. The scarcity of reports compared with the number of confirmed COVID-19 infections worldwide suggests a rare entity. The association of APMPPE with a variety of infections may suggest a common immunological aberrant response that might be triggered by various factors. Further examinations and case reports are needed to understand the role of biological therapy in the treatment of such cases.

6.
Materials (Basel) ; 16(24)2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38138761

RESUMO

This paper focuses on the development of thin-walled panels with specific properties for applications such as water-tight structures. The authors propose the use of textile-reinforced concrete (TRC) as a composite material and highlight its advantages, which include high tensile strength, improved crack resistance, and design flexibility. The study presents a novel approach which combines TRC with reactive powder concrete (RPC) as a matrix and a lightweight aggregate. RPC, known for its brittle behaviour, is reinforced with glass fibres and a textile fabric to increase its flexural strength. The research includes a comprehensive analysis of the physical and mechanical properties of both the unreinforced RPC matrix and the TRC composite. In particular, the lightweight aggregate RPC matrix has a porosity of 41%, and its mechanical properties, such as flexural and compressive strength, are discussed. The TRC composites, produced in thicknesses ranging from 1 mm to 4 mm, are subjected to flexural tests to evaluate their behaviour under load. The thicker elements show typical damage phases, while the thinner elements show greater flexibility and elasticity. SEM observations confirm good adhesion between the glass fibres and the RPC matrix. Water permeability tests show that the TRC composite, despite its highly porous structure, achieves a water permeability two orders of magnitude higher than that of a reference material, highlighting the roles of both the porous aggregate and the matrix hydration. The paper concludes with a proof of concept-a canoe called the PKanoe, which is constructed from the developed TRC composite. The design of the canoe is supported by numerical analysis to ensure its optimal shape and structural integrity under load. The research contributes to the exploration of innovative materials for sustainable civil engineering applications and addresses both structural and environmental considerations.

7.
AME Case Rep ; 7: 46, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37942044

RESUMO

Background: Acquired perforating dermatosis (APD) is a heterogeneous group of unfrequented diseases (2.5 cases for 100,000 habitants) associated with multiple pathologies like end-stage renal disease and other concomitant conditions such as diabetes mellitus (DM). Case Description: We described 3 cases of APD in patients on peritoneal dialysis (PD), one of them with a giant variant of reactive perforating collagenosis (RPC). The first case is a 28-year-old man with chronic kidney disease on PD and a lousy control of disturbances of calcium and phosphorus metabolism that develops an APD. The second case is a 44-year-old man with DM, chronic kidney disease (CKD) on PD, and poor control of disturbances of calcium and phosphorus metabolism that develops an RPC. The third case is a 58-year-old man with DM, rheumatoid arthritis, hypothyroidism, CKD and bad control of calcium and phosphorus metabolism that develops a giant variant of RPC with poor evolution. Conclusions: CKD and concomitant conditions such as DM present an increased risk of developing APD. Poor control of calcium and phosphorus metabolism is frequently found in patients with CKD and seems to be related to the development of APD in our cases. With the description of these cases, we want to emphasize the importance of knowing this rare disease, in order to promptly refer to Dermatology and start treatment.

8.
Front Neurol ; 14: 1254140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37915380

RESUMO

RNA polymerase III-related leukodystrophy (POLR3-related leukodystrophy) is a rare, genetically determined hypomyelinating disease arising from biallelic pathogenic variants in genes encoding subunits of RNA polymerase III (Pol III). Here, we describe the first reported case of POLR3-related leukodystrophy caused by biallelic pathogenic variants in POLR3D, encoding the RPC4 subunit of Pol III. The individual, a female, demonstrated delays in walking and expressive and receptive language as a child and later cognitively plateaued. Additional neurological features included cerebellar signs (e.g., dysarthria, ataxia, and intention tremor) and dysphagia, while non-neurological features included hypodontia, hypogonadotropic hypogonadism, and dysmorphic facial features. Her MRI was notable for diffuse hypomyelination with myelin preservation of early myelinating structures, characteristic of POLR3-related leukodystrophy. Exome sequencing revealed the biallelic variants in POLR3D, a missense variant (c.541C > T, p.P181S) and an intronic splice site variant (c.656-6G > A, p.?). Functional studies of the patient's fibroblasts demonstrated significantly decreased RNA-level expression of POLR3D, along with reduced expression of other Pol III subunit genes. Notably, Pol III transcription was also shown to be aberrant, with a significant decrease in 7SK RNA and several distinct tRNA genes analyzed. Affinity purification coupled to mass spectrometry of the POLR3D p.P181S variant showed normal assembly of Pol III subunits yet altered interaction of Pol III with the PAQosome chaperone complex, indicating the missense variant is likely to alter complex maturation. This work identifies biallelic pathogenic variants in POLR3D as a novel genetic cause of POLR3-related leukodystrophy, expanding the molecular spectrum associated with this disease, and proposes altered tRNA homeostasis as a factor in the underlying biology of this hypomyelinating disorder.

9.
Cancers (Basel) ; 15(20)2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37894362

RESUMO

RNA polymerase III (Pol III) subunit RPC7α, which is encoded by POLR3G in humans, has been linked to both tumor growth and metastasis. Accordantly, high POLR3G expression is a negative prognostic factor in multiple cancer subtypes. To date, the mechanisms underlying POLR3G upregulation have remained poorly defined. We performed a large-scale genomic survey of mRNA and chromatin signatures to predict drivers of POLR3G expression in cancer. Our survey uncovers positive determinants of POLR3G expression, including a gene-internal super-enhancer bound with multiple transcription factors (TFs) that promote POLR3G expression, as well as negative determinants that include gene-internal DNA methylation, retinoic-acid induced differentiation, and MXD4-mediated disruption of POLR3G expression. We show that novel TFs identified in our survey, including ZNF131 and ZNF207, functionally enhance POLR3G expression, whereas MXD4 likely obstructs MYC-driven expression of POLR3G and other growth-related genes. Integration of chromatin architecture and gene regulatory signatures identifies additional factors, including histone demethylase KDM5B, as likely influencers of POLR3G gene activity. Taken together, our findings support a model in which POLR3G expression is determined with multiple factors and dynamic regulatory programs, expanding our understanding of the circuitry underlying POLR3G upregulation and downstream consequences in cancer.

10.
Metabolites ; 13(10)2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37887405

RESUMO

For dairy cattle to perform well throughout and following lactations, precise dietary control during the periparturient phase is crucial. The primary issues experienced by periparturient dairy cows include issues like decreased dry matter intake (DMI), a negative energy balance, higher levels of non-esterified fatty acids (NEFA), and the ensuing inferior milk output. Dairy cattle have always been fed a diet high in crude protein (CP) to produce the most milk possible. Despite the vital function that dairy cows play in the conversion of dietary CP into milk, a sizeable percentage of nitrogen is inevitably expelled, which raises serious environmental concerns. To reduce nitrogen emissions and their production, lactating dairy cows must receive less CP supplementation. Supplementing dairy cattle with rumen-protected methionine (RPM) and choline (RPC) has proven to be a successful method for improving their ability to use nitrogen, regulate their metabolism, and produce milk. The detrimental effects of low dietary protein consumption on the milk yield, protein yield, and dry matter intake may be mitigated by these nutritional treatments. In metabolic activities like the synthesis of sulfur-containing amino acids and methylation reactions, RPM and RPC are crucial players. Methionine, a limiting amino acid, affects the production of milk protein and the success of lactation in general. According to the existing data in the literature, methionine supplementation has a favorable impact on the pathways that produce milk. Similarly, choline is essential for DNA methylation, cell membrane stability, and lipid metabolism. Furthermore, RPC supplementation during the transition phase improves dry matter intake, postpartum milk yield, and fat-corrected milk (FCM) production. This review provides comprehensive insights into the roles of RPM and RPC in optimizing nitrogen utilization, metabolism, and enhancing milk production performance in periparturient dairy cattle, offering valuable strategies for sustainable dairy farming practices.

11.
Materials (Basel) ; 16(19)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37834571

RESUMO

In pursuit of developing an eco-friendly and cost-effective reactive powder concrete (RPC), we utilized a multi-objective optimization technique. This approach pivoted on the incorporation of byproducts, with a spotlight on ground glass powder (GP) as a pivotal supplementary cementitious material (SCM). Our goal was twofold: engineering cost-efficient concrete while maintaining environmental integrity. The derived RPC showcased robust mechanical strength and impressive workability. Rigorous evaluations, containing attributes like compressive strength, resistance to chloride ion penetration, ultrasonic pulse speed, and drying shrinkage, highlighted its merits. Notably, the optimized RPC, despite an insignificant decrease in compressive strength at 90 days compared to its traditional counterpart, maintained steady strength augmentation over time. The refinement process culminated in a notable 29% reduction in ordinary Portland cement (OPC) usage and a significant 64% decrease in silica fume (SF), with the optimized mix composition being 590 for cement, 100 for SF, 335 for GP, and 257 kg/m3 for calcium carbonate. Additionally, the optimized RPC stood out due to the enhanced rheological behavior, influenced by the lubricative properties of calcium carbonate and the water conservation features of the glass powder. The reactive properties of SF, combined with GP, brought distinct performance variations, most evident at 28 days. Yet, both mixtures exhibited superior resistance to chloride, deeming them ideal for rigorous settings like coastal regions. Significantly, the RPC iteration, enriched with selective mineral admixtures, displayed a reduced tendency for drying-induced shrinkage, mitigating potential crack emergence.

12.
Rev. chil. infectol ; Rev. chil. infectol;40(5): 465-471, oct. 2023. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1521871

RESUMO

INTRODUCCIÓN: La diarrea aguda continúa siendo una de las principales causas de morbilidad en niños; sin embargo, el diagnóstico etiológico presenta limitaciones dada la baja sensibilidad de los métodos tradicionales. OBJETIVO: Describir los microorganismos identificados en niños que acudieron al Servicio de Urgencia (SU) de un hospital universitario en Santiago, Chile, por diarrea aguda y a los que se le solicitó panel molecular gastrointestinal. MÉTODOS: Se revisaron fichas clínicas y resultados de panel gastrointestinal realizados entre junio de 2017 y marzo de 2020. RESULTADOS: Se incluyeron 198 pacientes, edad promedio de 54,5 meses y 60,6% (120/198) de sexo masculino. La positividad del panel fue de 78,8% (156/198) con 35,3% (55/156) de las muestras polimicrobianas. Se identificaron 229 microorganismos, de los cuales 72,9% (167/229) corresponden a bacterias, 25,8% (59/229) a virus y 1,3% (3/229) a parásitos. Destacaron Campylobacter spp. y Escherichia coli enteropatógena (ECEP) como las bacterias más frecuentemente identificadas. Los pacientes con detección de Campylobacter spp. presentaron con mayor frecuencia fiebre (p = 0,00). ECEP se aisló principalmente (82,5%) en muestras polimicrobianas. DISCUSIÓN: Los resultados enfatizan el potencial que poseen los estudios moleculares para mejorar el diagnóstico etiológico de la diarrea, pero a la vez llevan a cuestionar el rol patogénico de algunos microorganismos identificados.


BACKGROUND: Acute diarrhea continues to be one of the main causes of morbidity in children, however the etiologica diagnosis presents limitations given the low sensitivity of traditional methods. AIM: To describe the microorganisms identified in children who attended the emergency department (ED) in Santiago, Chile, due to acute diarrhea and to whom a gastrointestinal panel was requested as part of their study. MATERIAL AND METHODS: Clinical records and results of the gastrointestinal panel carried out between June 2017 and March 2020 were reviewed. RESULTS: 198 patients were included, the average age was 54.5 months and 60.6% (120/198) were males. Positivity was 78.8% (156/198) with 35.3% (55/156) of the samples being polymicrobial. 229 microorganisms were identified, of which 72.9% (167/229) corresponded to bacteria, 25.8% (59/229) to viruses, and 1.3% (3/229) to parasites. Campylobacter spp. and enteropathogenic Escherichia coli (EPEC) were the most frequently identified bacteria. Patients with detection of Campylobacter spp. presented a higher frequency of fever (p = 0.00). EPEC was isolated in 82.5% of the cases in polymicrobial samples. DISCUSSION: The results emphasize the potential of molecular studies to improve the etiological diagnosis of diarrhea and at the same time lead to question the pathogenic role of some microorganisms.


Assuntos
Humanos , Masculino , Feminino , Diarreia/diagnóstico , Fezes/microbiologia , Parasitos/isolamento & purificação , Estações do Ano , Bactérias/isolamento & purificação , Vírus/isolamento & purificação , Chile , Estudos Retrospectivos , Diarreia/etiologia , Diarreia/epidemiologia , Serviço Hospitalar de Emergência , Fezes/parasitologia
13.
Materials (Basel) ; 16(15)2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37570013

RESUMO

Based on its characteristics of early strength, good toughness, and excellent mechanical and impact resistance, steel fiber-reinforced fast-hardening reactive powder concrete (RPC) is expected to become an alternative material used in the rapid repair of marine concrete structures. However, the steel fibers have also caused corrosion problems in coastal environments. To make doped fiber fast-hardening RPC more adaptable for use in ocean engineering, this study prepares fast-hardening RPC mixed with straw and studied the effects of straw content and curing age on its slump flow, setting time, and mechanical performance (flexural strength, compressive strength, and flexural toughness). The effects of straw addition on the compactness and hydration products of fast-hardening RPC were studied through macro- (ultrasonic analysis) and micro-scopic analysis (electron microscopy scanning and X-ray diffraction patterns). The straw content mentioned in this paper refers to the percentage of straw in relation to RPC volume. The results showed that straw reduced the fluidity of RPC slurry by 10.5-11.5% compared to concrete without straw, and it accelerated the initial setting of RPC slurry. When the straw content accounted for 1% of RPC volume, the setting rate was the fastest, with a increasing rate being 6-18%. Compared to concrete without straw, the flexural and compressive strength of fast-hardening RPC was enhanced by 3.7-30.5%. When the content was either 3% or 4%, the mechanical properties improved. Moreover, when the straw content accounted for 4% of RPC volume, the flexural toughness was the highest, with the increase rate being 21.4% compared to concrete without straw. Straw reduces the compactness of fast-hardening RPC.

14.
Materials (Basel) ; 16(16)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37629908

RESUMO

Secondary aluminum ash (SAA) is a type of common solid waste which leads to pollution without treatment. Due to its chemical reactivity, the application of SAA to reactive powder concrete (RPC) may help solidify this solid waste while increasing its performance. However, RPC is usually in active service when used with steel bars. NaCl can corrode the steel bars when reinforced RPC is used in a coastal environment. In this study, the corrosion resistance of reinforced RPC was investigated. The specimens were exposed to an environment of NaCl with freeze-thaw cycles (F-Cs) and dry-wet alternations (D-As). The corresponding mass loss rates (MRs), the electrochemical impedance spectroscopy (EIS) curves and the dynamic modulus of elasticity (DME) were measured. The results show that the MR and the DME of reinforced RPC decrease with increasing values of F-C and D-A. F-C and D-A increases lead to increased electrical resistance (R). The real part value corresponding to the extreme point of the EIS curve is increased by 0~213.7% when the SAA is added. The relationship between the imaginary part and the real part of the EIS fits the quadratic function. The equivalent circuit of the reinforced RPC is obtained from the EIS curves. The R of the rust is calculated by using the equivalent circuit. The rust's R decreases in the quadratic function with the mass ratio of the SAA. After 200 NaCl F-Cs, the MR, the DME and the R vary within the ranges of 23.4~113.6%, -2.93~-4.76% and 4.92~13.55%. When 20 NaCl D-As are finished, the MR, the DME and the R vary within the ranges of 34.7~202.8%, -13.21~-14.93% and 120.48~486.39%. The corrosion area rates are 2.3~68.7% and 28.7~125.6% higher after exposure to 200 NaCl F-Cs and 20 NaCl D-As. When the SAA is mixed, the MR is decreased by 0~13.12%, the DME increases by 0~3.11%, the R of the reinforced RPC increases by 26.01~152.43% and the corrosion area rates are decreased by 21.39~58.62%. This study will provide a novel method for solidifying SAA while improving the chlorine salt resistance of RPC.

15.
J Biol Chem ; 299(7): 104859, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37230389

RESUMO

The TFIIF-like Rpc53/Rpc37 heterodimer of RNA polymerase (pol) III is involved in various stages of transcription. The C-terminal region of Rpc53 dimerizes with Rpc37 to anchor on the lobe domain of the pol III cleft. However, structural and functional features of the Rpc53 N-terminal region had not been characterized previously. Here, we conducted site-directed alanine replacement mutagenesis on the Rpc53 N-terminus, generating yeast strains that exhibited a cold-sensitive growth defect and severely compromised pol III transcriptional activity. Circular dichroism and NMR spectroscopy revealed a highly disordered 57-amino acid polypeptide in the Rpc53 N-terminus. This polypeptide is a versatile protein-binding module displaying nanomolar-level binding affinities for Rpc37 and the Tfc4 subunit of the transcription initiation factor TFIIIC. Accordingly, we denote this Rpc53 N-terminus polypeptide as the TFIIIC-binding region or CBR. Alanine replacements in the CBR significantly reduced its binding affinity for Tfc4, highlighting its functional importance to cell growth and transcription in vitro. Our study reveals the functional basis for Rpc53's CBR in assembly of the pol III transcription initiation complex.


Assuntos
RNA Polimerase III , Fatores de Transcrição TFIII , RNA Polimerase III/metabolismo , Transcrição Gênica , Fatores de Transcrição TFIII/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Peptídeos/metabolismo
16.
Indian J Ophthalmol ; 71(5): 2324, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37203011

RESUMO

Background: Optic disc anomalies with abnormal tissue on the disc surface includes, myelinated nerve fiber, optic disc drusen, and Bergmeister papillae. Imaging the radial peripapillary capillary (RPC) network in optic disc anomalies with optical coherence tomography-angiography (OCTA) can give information on the RPC network in these conditions. Purpose: This video describes the OCTA of optic nerve head and RPC network using the angio disc mode in cases of optic disc anomalies with abnormal tissue on the disc surface. Synopsis: This video presents characteristic features of RPC network in one eye each of myelinated nerve fiber, optic disc drusen, and Bergmeister papillae. Highlights: OCTA in optic disc anomalies with abnormal tissue on the disc surface show a dense RPC microvascular network. OCTA is an effective imaging modality to study vascular plexus/RPC and their alteration in these disc anomalies. Video link: https://youtu.be/zlflgijy56c.


Assuntos
Anormalidades do Olho , Drusas do Disco Óptico , Disco Óptico , Vítreo Primário Hiperplásico Persistente , Humanos , Anormalidades do Olho/complicações , Anormalidades do Olho/diagnóstico , Angiofluoresceinografia/métodos , Microvasos , Disco Óptico/irrigação sanguínea , Vasos Retinianos , Tomografia de Coerência Óptica/métodos
17.
Ocul Immunol Inflamm ; : 1-7, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37134304

RESUMO

PURPOSE: To assess the efficacy of treatment on acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and relentless placoid chorioretinopathy (RPC). METHODS: Cases were identified from three UK uveitis centers. Retrospective analysis of visual acuity recovery; OCT structural outcomes; and retinal lesion quantification in observed and treated cases of APMPPE/RPC. RESULTS: There were nine APMPPE and three RPC cases. Out of 12 patients, six were female. Median age: 26.5 years (range, 20-57 years). Four cases (six eyes) were observed, and eight cases (15 eyes) received corticosteroids ± immunosuppression. 4/4 observed and 6/10 treated foveal involving eyes regained 0.00 LogMAR vision. Observed lesions achieved more favorable anatomical outcomes. New lesions post-presentation developed in 1/6 (16%) observed eye versus 10/15 (66%) treated eyes. In three cases, a delayed, rebound lesion occurrence was observed post-high-dose corticosteroids. CONCLUSIONS: While subject to potential treatment bias, in this small case series, natural history alone appears non-inferior to corticosteroid treatment.

18.
Polymers (Basel) ; 15(10)2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37242883

RESUMO

This study employed novel joint treatments to strengthen the carbon fiber reinforced polymer (CFRP) composites. Vertically aligned carbon nanotubes (VACNTs) were prepared in situ on the catalyst-treated CF surface via the chemical vapor deposition (CVD) method, intertwining into three-dimensional fiber-nets and fully surrounding CF to form an integrated structure. The resin pre-coating (RPC) technique was further used to guide diluted epoxy resin (without hardener) to flow into nanoscale and submicron spaces to eliminate void defects at the root of VACNTs. Three-point bending testing results showed the "growing CNTs and RPC"-treated CFRP composites yielded the best flexural strength, a 27.1% improvement over the specimens without treatment, while the failure modes indicated that the original delamination failure was changed into "flexural failure" with through-the-thickness crack propagation. In brief, growing VACNTs and RPC on the CF surface enabled toughening of the epoxy adhesive layer, reducing potential void defects and constructing the integrated quasi-Z-directional fiber bridging at the CF/epoxy interface for stronger CFRP composites. Therefore, the joint treatments of growing VACNTs in situ via the CVD method and RPC technique are very effective and have great potential in manufacturing high-strength CFRP composites for aerospace applications.

19.
Indian J Ophthalmol ; 71(3): 1058, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36872758

RESUMO

Background and Purpose: : "Congenital cavitary optic disk anomalies" is a term used to include optic disk pit (ODP), optic disk coloboma, and morning glory disk anomaly (MGDA). Imaging the radial peripapillary capillary (RPC) network in congenital optic disk anomalies with optical coherence tomography-angiography (OCTA) can shed light on its pathogenesis. This video describes the OCTA findings of optic nerve head and RPC network using the angio-disk mode in five cases of congenital cavitary optic disk anomalies. Synopsis: The video presents characteristic RPC network alterations in two eyes of ODP, one eye of optic disk coloboma, and two eyes of noncontractile MGDA. Highlights: OCTA in ODP and coloboma shows absence of RPC microvascular network and a region of capillary dropout. This finding is in contrast to MGDA, where the microvascular network is dense. OCTA is an effective imaging modality to study vascular plexus and RPC and their alteration in congenital disk anomalies, which could provide information about the structural differences among them. Video link: https://youtu.be/TyZOzpG4X4U.


Assuntos
Coloboma , Anormalidades do Olho , Disco Óptico , Humanos
20.
J Chromatogr A ; 1693: 463874, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36841023

RESUMO

The current study describes the development of a 2D-LC-MS-based strategy for assessing main peak purity in the analysis of pharmaceutical peptides. The focus is on 2D-LC using reversed-phase (RP) separations in both dimensions, and particularly peptide isomer selectivity, since compounds with the same mass to charge ratio are not readily differentiated by mass spectrometry and therefore must be separated chromatographically. Initially, 30 column / mobile phase combinations were evaluated for both general separation performance (i.e., selectivity and peak shape) and isomer selectivity using forcibly degraded peptide samples and mixtures of synthetic diastereomers. A ranking of more than 300 UV and MS chromatograms suggests that when developing a new method, screening a set of four columns and four volatile mobile phases with differing characteristics should be adequate to both cover the selectivity space, and yield good separation performance. When 2D-LC-MS is to be used to evaluate peak purity for a new method, our results show that a second-dimension separation comprising a C8/C18 column possessing no ionic functionality, and an acetic acid / ammonium acetate mobile phase buffered at pH 5, provides good selectivity at 25 °C for peptide isomers with a MW <10 kDa. Retention data for 29 diverse peptides (1 < MW < 14 kDa, 3.7 < pI < 12.5) measured in this study using a variety of column and mobile phase conditions (i.e., 30 in total) are consistent with the classification of these various chromatographic conditions using the previously reported Peptide RPC Column Characterisation Protocol. For the investigated peptides trifluoroacetic acid was found to reduce selectivity differences between columns of diverse properties, probably due to its potential to form ion-pairs with peptides. Trifluoroacetic acid often improves peak shape for very large peptides (i.e. MW > 10 kDa). In the current dataset which also contain smaller peptides it received the highest ranking for 40% of the column and mobile phase combinations due to better selectivity and/or peak shape. The reported work here constitutes part one of a series of two papers. The second paper focuses on the use of retention modelling for rapid and accurate selection of the shallow gradients (i.e., << 1% ACN/min) required to obtain sufficient peptide isomer retention and separation in the second dimension. The overall results presented in this series of papers provides the guidance needed to develop a 2D-LC-MS method from start to finish for the analysis of main peak purity of therapeutic peptides.


Assuntos
Cromatografia de Fase Reversa , Peptídeos , Cromatografia de Fase Reversa/métodos , Ácido Trifluoracético , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Peptídeos/análise , Preparações Farmacêuticas , Cromatografia Líquida de Alta Pressão/métodos
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