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1.
Sci Rep ; 14(1): 21268, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261626

RESUMEN

This paper systematically investigates the dynamic mechanical response and fragment characteristics of sandstone with asymmetrical conjugate fissures subjected to preexisting static stress based on the split Hopkinson pressure bar apparatus. The cross-fissured sandstone exhibits significant variations in mechanical behavior when exposed to higher dynamic strain rates under identical static pre-stress. The cross-fissured sandstone with a higher dynamic strain rate is characterized by a greater coupled strength under the same static pre-stress; for a given dynamic load, the highest coupled strength occurs under the static pre-stress of 60% UCS. The failure mode of the cross-fissured sandstone is predominantly governed by the dynamic strain rate, independent of static pre-stress variations considered in this investigation. At lower dynamic strain rates, the specimens typically exhibit a mixed tensile-shear failure mode, characterized by the dominance of larger fragments in the broken specimens. In contrast, under high dynamic impacts, the sandstone tends to fail in a shear-dominated manner, resulting in smaller fragments with a more uniform size distribution. Furthermore, the study explores how varying dynamic strain rates and static pre-stress influence the fragment characteristics of the cross-fissured sandstone. Higher dynamic strain rates and increased static pre-stress generally lead to smaller mean fragment sizes. This phenomenon is quantitatively described by fitting fragment size distributions using the Generalized Extreme Value (GEV) distribution, revealing a decrease in the location parameter (µ) and an increase in fractal dimension. These metrics indicate that higher dynamic strain rates and static pre-stress result in sandstone specimens breaking into smaller fragments with a more homogeneous size distribution. These findings contribute to a deeper understanding of rock dynamics, with potential implications for engineering applications involving similar geological configuration under dynamic loading conditions.

2.
Nano Lett ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39269785

RESUMEN

Bimetallic nanowires play important roles in the fields of electronics and mechanics. However, their structure types and morphological control methods are limited, especially for systems with low lattice mismatch. Herein, for a Cu-Ni bimetallic system with lattice mismatch ratio less than 2.5%, a novel preparation approach of various Cu-Ni nanowires dominated by Ni(II) reduction kinetics is presented. With the increase of Ni(II) reduction rate, the core-shell Cu@Ni straight nanowires, the asymmetric Cu-Ni nanocurves, and asymmetric Cu-Ni nanocoils can be prepared, respectively. The formation of Cu-Ni nanowires with different structures can be divided into the growth of Cu nanowires and the deposition of Ni. The regulatory effects were revealed by establishing a kinetic model for Ni(II) reduction. For the novel Cu-Ni asymmetrically distributed nanocurves and nanocoils, the formation mechanism was proposed by considering the Cu nanowire bending due to the rearrangement of surface ligand and bending-induced symmetry breaking of Ni(II) reduction.

3.
Sports Biomech ; : 1-12, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39295091

RESUMEN

This study aims to objectively evaluate the trunk posture of sweep rowers (bow-side rowers/stroke-side rowers) and compare the results with scull rowers and non-rowing controls. Sixty-four healthy individuals divided into four groups were assessed using a DIERS formetric III 4D device that is based on a method of moiré topography. There were seven parameters observed in an assessment of standing posture, and eight parameters were studied for an evaluation of posture during the gait cycle. In comparison with non-rowing controls and scull rowers, stroke-side rowers showed significantly greater rotational deviation of the trunk at the L3 vertebra level and a greater magnitude of scoliosis angle during walking throughout the single support phase on the left leg (p < 0.05). Stroke-side rowers also demonstrated greater magnitude of scoliosis angle than non-rowing controls in double support phase in the transition from the left to the right leg (p < 0.05). Moreover, as opposed to non-rowing controls, stroke-side rowers and scull rowers showed significantly greater values of coronal imbalance (p < 0.05). Bow-side rowers differed from non-rowing controls and scull rowers in a significantly greater magnitude of scoliosis angle throughout the single support phase on the left leg (p < 0.05). Trial registration number: clinicaltrials.gov (identifier: NCT05685563).

4.
BMC Bioinformatics ; 25(1): 266, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39143554

RESUMEN

BACKGROUND: Construction of co-occurrence networks in metagenomic data often employs correlation to infer pairwise relationships between microbes. However, biological systems are complex and often display qualities non-linear in nature. Therefore, the reliance on correlation alone may overlook important relationships and fail to capture the full breadth of intricacies presented in underlying interaction networks. It is of interest to incorporate metrics that are not only robust in detecting linear relationships, but non-linear ones as well. RESULTS: In this paper, we explore the use of various mutual information (MI) estimation approaches for quantifying pairwise relationships in biological data and compare their performances against two traditional measures-Pearson's correlation coefficient, r, and Spearman's rank correlation coefficient, ρ. Metrics are tested on both simulated data designed to mimic pairwise relationships that may be found in ecological systems and real data from a previous study on C. diff infection. The results demonstrate that, in the case of asymmetric relationships, mutual information estimators can provide better detection ability than Pearson's or Spearman's correlation coefficients. Specifically, we find that these estimators have elevated performances in the detection of exploitative relationships, demonstrating the potential benefit of including them in future metagenomic studies. CONCLUSIONS: Mutual information (MI) can uncover complex pairwise relationships in biological data that may be missed by traditional measures of association. The inclusion of such relationships when constructing co-occurrence networks can result in a more comprehensive analysis than the use of correlation alone.


Asunto(s)
Metagenómica , Metagenómica/métodos , Algoritmos , Metagenoma/genética
5.
J Anim Ecol ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39205404

RESUMEN

It is widely recognized that predators can influence prey through both direct consumption and by inducing costly antipredator behaviours, the latter of which can produce nonconsumptive effects that cascade through trophic systems. Yet, determining how particular prey manage risk in natural settings remains challenging as empirical studies disproportionately focus on single predator-prey dyads. Here, we contrast foraging strategies within the context of a primary and secondary prey to explore how antipredator behaviours emerge as a product of predation intensity as well as the setting in which an encounter takes place. We studied the effects of spotted owls (Strix occidentalis) on two species experiencing asymmetrical risk: dusky-footed woodrats (Neotoma fuscipes; primary prey) and deer mice (Peromyscus spp.; alternative prey). Woodrats are most abundant within young forests, but predominantly captured by owls foraging within mature forests; in contrast, deer mice occur in high densities across forest types and seral stages and are consumed at lower per-capita rates overall. We deployed experimental foraging patches within areas of high and low spotted owl activity, created artificial risky and safe refuge treatments, and monitored behaviour throughout the entirety of prey foraging bouts. Woodrats were more vigilant and foraged less within mature forests and at riskier patches, although the effect of refuge treatment was contingent upon forest type. In contrast, deer mice only demonstrated consistent behavioural responses to riskier refuge treatments; forest type had little effect on perceived risk or the relative importance of refuge treatment. Thus, habitat can interact with predator activity to structure antipredator responses differently for primary versus secondary prey. Our findings show that asymmetrical predation can modulate both the magnitude of perceived risk and the strategies used to manage it, thus highlighting an important and understudied contingency in risk effects research. Evaluating the direct and indirect effects of predation through the paradigm of primary and secondary prey may improve our understanding of how nonconsumptive effects can extend to population- and community-level responses.

6.
Angew Chem Int Ed Engl ; : e202413601, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39210675

RESUMEN

The control of enantioselectivity in radical cation reactions presents long-standing challenges, despite a few successful examples. We introduce a novel strategy of asymmetric counteranion-directed electrocatalysis to address enantioselectivity in radical cation chemistry. This concept has been successfully demonstrated in two reactions: an asymmetric dehydrogenative indole-phenol [3 + 2] coupling and an atroposelective C-H/N-H dehydrogenative coupling. These reactions have enabled the synthesis of benzofuroindolines and C-N axially chiral indoles with high yields and excellent enantiomeric excesses. Detailed mechanistic studies confirmed a radical-radical coupling mechanism. Moreover, density functional theory (DFT) calculations supported the indole radical cation as the pivotal intermediate, rather than a neutral indolyl radical, shedding new light on the underlying processes driving these reactions.

7.
Int Orthod ; 22(3): 100896, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38981305

RESUMEN

A satisfactory treatment of an 18-year-old lady was reported with right combination-type condylar hyperplasia (CH) in active phase. The chin severely deviated to the left, with the right gonial angle locating at a lower level. Intraorally, the lower centre line shifted to the left, the scale of which reached the width of one lower incisor. The right molar relation was mesial. Right maxillary second molar over-erupted without contact to lower teeth. There had been 2.5-mm anterior open bite (AOB) before surgery (T1) due to the tongue-spitting habit. After judging the benefits and disadvantages of all treatment alternatives, the decision was made to perform a right condylectomy and post-surgery orthodontics. Before orthodontics (T2) when the chin was positioned centred, an asymmetrical open bite occurred, caused by pre-contact between the right maxillary and mandibular second molars. Meanwhile, the AOB at T2 became 11.5mm. Orthodontic-related treatment included four premolars extraction and intrusion of bilateral maxillary molars using four miniscrews. Finally, this treatment achieved a clinically centred chin with two gonial angles at the same level. Post-condylectomy, the large AOB was resolved, together with a bilateral neutral molar relationship and alignment of the incisor midlines. Besides, the resected right condyle was covered by a continuous cortex bone and returned to the glenoid fossa. In sum, a high-challenging combined-type CH case was accomplished with impressive improvement in facial and occlusal symmetry, thanks to condylectomy and post-surgery miniscrew-assisted orthodontics.


Asunto(s)
Cefalometría , Hiperplasia , Cóndilo Mandibular , Mordida Abierta , Humanos , Femenino , Adolescente , Mordida Abierta/terapia , Mordida Abierta/cirugía , Cóndilo Mandibular/cirugía , Cóndilo Mandibular/patología , Ortodoncia Correctiva/métodos , Asimetría Facial/cirugía , Asimetría Facial/etiología , Planificación de Atención al Paciente , Procedimientos Quirúrgicos Ortognáticos/métodos
8.
Methods Mol Biol ; 2816: 175-191, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38977599

RESUMEN

The trabecular meshwork (TM) from primary open-angle glaucoma (POAG) cases has been found to contain decreased levels of intracellular plasmalogens. Plasmalogens are a subset of lipids involved in diverse cellular processes such as intracellular signaling, membrane asymmetry, and protein regulation. Proper plasmalogen biosynthesis is regulated by rate-limiting enzyme fatty acyl-CoA reductase (Far1). ATPase phospholipid transporting 8B2 (ATP8B2) is a type IV P-type ATPase responsible for the asymmetric distribution of plasmalogens between the intracellular and extracellular leaflets of the plasma membranes. Here we describe the methodology for extraction and culturing of TM cells from corneal tissue and subsequent downregulation of ATP8B2 using siRNA transfection. Further quantification and downstream effects of ATP8B2 gene knockdown will be analyzed utilizing immunoblotting techniques.


Asunto(s)
Glaucoma de Ángulo Abierto , Plasmalógenos , Malla Trabecular , Malla Trabecular/metabolismo , Malla Trabecular/citología , Humanos , Plasmalógenos/metabolismo , Glaucoma de Ángulo Abierto/metabolismo , Glaucoma de Ángulo Abierto/genética , Glaucoma de Ángulo Abierto/patología , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfatasas/genética , ARN Interferente Pequeño/genética , Regulación hacia Abajo , Células Cultivadas , Técnicas de Silenciamiento del Gen
9.
Methods Enzymol ; 701: 237-285, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39025573

RESUMEN

The Martini model is a popular force field for coarse-grained simulations. Membranes have always been at the center of its development, with the latest version, Martini 3, showing great promise in capturing more and more realistic behavior. In this chapter we provide a step-by-step tutorial on how to construct starting configurations, run initial simulations and perform dedicated analysis for membrane-based systems of increasing complexity, including leaflet asymmetry, curvature gradients and embedding of membrane proteins.


Asunto(s)
Membrana Dobles de Lípidos , Proteínas de la Membrana , Simulación de Dinámica Molecular , Membrana Dobles de Lípidos/química , Proteínas de la Membrana/química , Membrana Celular/química , Membrana Celular/metabolismo
10.
Adv Mater ; 36(33): e2404665, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38923612

RESUMEN

Double-atom catalysts (DACs) with asymmetric coordination are crucial for enhancing the benefits of electrochemical carbon dioxide reduction and advancing sustainable development, however, the rational design of DACs is still challenging. Herein, this work synthesizes atomically dispersed catalysts with novel sulfur-bridged Cu-S-Ni sites (named Cu-S-Ni/SNC), utilizing biomass wool keratin as precursor. The plentiful disulfide bonds in wool keratin overcome the limitations of traditional gas-phase S ligand etching process and enable the one-step formation of S-bridged sites. X-ray absorption spectroscopy (XAS) confirms the existence of bimetallic sites with N2Cu-S-NiN2 moiety. In H-cell, Cu-S-Ni/SNC shows high CO Faraday efficiency of 98.1% at -0.65 V versus RHE. Benefiting from the charge tuning effect between the metal site and bridged sulfur atoms, a large current density of 550 mA cm-2 can be achieved at -1.00 V in flow cell. Additionally, in situ XAS, attenuated total reflection surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS), and density functional theory (DFT) calculations show Cu as the main adsorption site is dual-regulated by Ni and S atoms, which enhances CO2 activation and accelerates the formation of *COOH intermediates. This kind of asymmetric bimetallic atom catalysts may open new pathways for precision preparation and performance regulation of atomic materials toward energy applications.

11.
Eur Spine J ; 33(8): 2935-2951, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38869649

RESUMEN

PURPOSE: To evaluate different patterns of coronal deformity secondary to ankylosing spondylitis (AS), to propose relevant treatment strategies, and to assess efficacy of asymmetrical pedicle subtraction osteotomy (APSO). METHODS: Coronal deformity was defined as coronal Cobb angle over 20º or coronal balance distance (CBD) more than 3 cm. 65 consecutive AS patients with concomitant coronal and sagittal deformity who underwent PSO were included. The average follow-up time was 40.4 months. Radiographic evaluation included coronal Cobb angle and CBD. Furthermore, sagittal parameters were used to assess magnitude and maintenance of kyphosis correction. RESULTS: Based on curve characteristics, coronal deformity caused by AS included four different radiologic patterns: Pattern I: lumbar scoliosis; Pattern II: C-shaped thoracolumbar curve; Pattern III: trunk shift without major curve; Pattern IV: proximal thoracic scoliosis. APSO was performed for patients in Pattern I to III while conventional PSO was applied for patients in Pattern IV. Significant improvement in all the sagittal parameters were noted in 65 patients without obvious correction loss at the last follow-up. Besides, significant and sustained correction of coronal mal-alignment was identified in 59 APSO-treated patients. Rod fracture occurred in four cases and revision surgery was performed for one case. CONCLUSION: According to radiologic manifestations, coronal deformity caused by AS could be categorized into four patterns. APSO proved to be a feasible and effective procedure for correction of Pattern I to III patients. Coronal deformity pattern, apex location, sagittal profile of lumbar spine and preoperative hip function should be considered for osteotomy level selection in APSO.


Asunto(s)
Cifosis , Vértebras Lumbares , Osteotomía , Espondilitis Anquilosante , Vértebras Torácicas , Humanos , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/cirugía , Espondilitis Anquilosante/diagnóstico por imagen , Cifosis/cirugía , Cifosis/diagnóstico por imagen , Masculino , Femenino , Adulto , Vértebras Lumbares/cirugía , Vértebras Lumbares/diagnóstico por imagen , Vértebras Torácicas/cirugía , Vértebras Torácicas/diagnóstico por imagen , Osteotomía/métodos , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven , Adolescente
12.
Nano Lett ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38856118

RESUMEN

Copper-based catalysts have been attracting increasing attention for CO2 electroreduction into value-added multicarbon chemicals. However, most Cu-based catalysts are designed for ethylene production, while ethanol production with high Faradaic efficiency at high current density still remains a great challenge. Herein, Cu clusters supported on single-atom Cu dispersed nitrogen-doped carbon (Cux/Cu-N/C) show ethanol Faradaic efficiency of ∼40% and partial current density of ∼350 mA cm-2. Quasi in situ X-ray photoelectron spectroscopy and operando X-ray absorption spectroscopy results suggest the generation of surface asymmetrical sites of Cu+ and Cu0 as well as Cu clusters by electrochemical reduction and reconstruction during the CO2 electroreduction process. Density functional theory calculations indicate that the interaction between Cu clusters and the Cu-N/C support enhances *CO adsorption, facilitates the C-C coupling step, and favors the hydrogenation rather than dehydroxylation of the critical intermediate *CHCOH toward ethanol in the bifurcation.

13.
Pharmaceuticals (Basel) ; 17(6)2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38931355

RESUMEN

For developing novel photosensitizers with therapeutic potential in non-malignant and malignant cutaneous disorders, the unsymmetrical porphyrin, 5-(2-hydroxy-3-methoxyphenyl)-10, 15, 20-tris-(4-carboxymethylphenyl) porphyrin, was evaluated in silico and in vitro. The cellular uptake of the investigated porphyrin and its ability to perform photodynamic therapy were investigated in terms of the viability, proliferation, and necrosis of human HaCaT keratinocytes and human Hs27 skin fibroblasts, in correlation with the predictions regarding diffusion through cell membranes, ADMET profile (absorption, distribution, metabolism, elimination, toxicity), and potential pharmacological mechanism. Molecular docking and 250 ns molecular dynamics simulations revealed that P5.2 has the potential to form a relatively stable complex with the carbonic anhydrase IX catalytic site, the lowest predicted free energy of binding (MM/PBSA) being -39.097 kcal/mol. The results of the in vitro study showed that P5.2 is incorporated within 24 h in the investigated cells, especially in HaCaT keratinocytes, indicating its photosensitizing ability. Nevertheless, P5.2 does not exert significant cytotoxicity in "dark" conditions. In turn, PDT induced a decrease in the number of metabolically active HaCaT keratinocytes within 24 h, accompanied by a 4-fold increase in lactate dehydrogenase release, indicating its ability to perform PDT in human skin cells. The experimental results suggest that the asymmetrical porphyrin is a promising candidate theranostics agent for skin disorders.

14.
Nurse Educ Today ; 139: 106261, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38796897

RESUMEN

BACKGROUND: Collaborative and innovative educational approaches are essential to building nurses' competencies in responding to healthcare challenges and to enhance high-quality nursing practice. Nurses are increasingly learning in various contexts, and thus, the understanding and organising of collaborative learning needs further exploration. AIM: To describe collaborative learning in nursing practice and education from the point of view of nurses, involved as students and teachers in master's education in nursing. DESIGN AND METHODS: Qualitative study using semi-structured focus groups involving 33 nurses as master's students and teachers from Estonia and Norway. The data were analysed using inductive content analysis. FINDINGS: The essence of collaborative learning in the context of nursing practice and education was identified as the aggregation of diverse learners' skills and reflections while working towards shared aims. This fostered the development of workplace competencies, professional attitudes, and personal growth. Organising collaborative learning requires careful planning and synchronisation between clinical and educational organisations. CONCLUSIONS: Collaborative learning is an inclusive method, aiding nurses at different phases of their career to gain knowledge and enhance their soft skills, and potentially reducing professional hierarchies. Further research is needed to develop methods for evaluating the outcomes of collaborative learning.


Asunto(s)
Conducta Cooperativa , Educación de Postgrado en Enfermería , Docentes de Enfermería , Grupos Focales , Investigación Cualitativa , Estudiantes de Enfermería , Humanos , Estudiantes de Enfermería/psicología , Estudiantes de Enfermería/estadística & datos numéricos , Educación de Postgrado en Enfermería/métodos , Docentes de Enfermería/psicología , Noruega , Estonia , Aprendizaje , Femenino , Adulto , Masculino , Competencia Clínica/normas , Entrevistas como Asunto/métodos
15.
Materials (Basel) ; 17(10)2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38793533

RESUMEN

In normal cold rolling, the elastic deformation of the strip is typically ignored because of the dominant plastic deformation. However, this neglect may introduce additional errors when the strip is very thin. The aim of this study is to investigate the characteristics of the deformation region and thickness reduction in the asymmetrical rolling of ultra-thin strips. Mathematical models were developed based on the slab method, with consideration of the elastic deformation of the strips, and employed in the simulation calculation. The percentage of the three zones and the thickness reduction were analyzed using the simulation results. An increase in the speed ratio results in an increase in the reduction ratio, which is influenced by parameters, such as front tension, back tension, friction coefficient, and entry thickness. The elastic deformation of the strip reduces the tension and the roll pressure and causes the reduction ratio to decrease. The findings and conclusions of this study may be helpful to the mill operating in the asymmetrical rolling process of ultra-thin strips.

16.
J Cardiovasc Echogr ; 34(1): 38-40, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38818313

RESUMEN

Overlapping of left ventricular noncompaction (LVNC) and hypertrophic cardiomyopathy in the same patient is rare and is associated with a more severe clinical course and unfavorable prognosis. The present report describes the case of a severely regurgitant bicuspid aortic valve in a 68-year-old man with overlapping LVNC and asymmetrical septal hypertrophy. Aortic valve replacement controlled the left ventricular dilatation that occurred secondary to the volume overload induced by the valvular disease. However, even 3 years postoperatively, severe systolic dysfunction persisted due to the preexisting myocardial disease, requiring close and lifelong follow-up with special attention to life-threatening arrhythmias and thromboembolism.

17.
Artículo en Inglés | MEDLINE | ID: mdl-38797372

RESUMEN

BACKGROUND AND OBJECTIVE: Sound localization plays a crucial role in our daily lives, enabling us to recognize voices, respond to alarming situations, avoid dangers, and navigate towards specific signals. However, this ability is compromised in patients with Single-Sided Deafness (SSD) and Asymmetric Hearing Loss (AHL), negatively impacting their daily functioning. The main objective of the study was to quantify the degree of sound source localization in patients with single-sided deafness or asymmetric hearing loss using a Cochlear Implant (CI) and to compare between the two subgroups. MATERIALS AND METHODS: This was a prospective, longitudinal, observational, single-center study involving adult patients diagnosed with profound unilateral or asymmetric sensorineural hearing loss who underwent cochlear implantation. Sound localization was assessed in a chamber equipped with seven speakers evenly distributed from -90º to 90º. Stimuli were presented at 1000 Hz and intensities of 65 dB, 70 dB, and 75 dB. Each stimulus was presented only once per speaker, totaling 21 presentations. The number of correct responses at different intensities was recorded, and angular error in degrees was calculated to determine the mean angular distance between the patient-indicated speaker and the speaker presenting the stimulus. Both assessments were conducted preoperatively without a cochlear implant and two years post-implantation. RESULTS: The total sample comprised 20 patients, with 9 assigned to the SSD group and 11 to the AHL group. The Preoperative Pure Tone Average (PTA) in free field was 31.7 dB in the SSD group and 41.8 dB in the AHL group. There was a statistically significant improvement in sound localization ability and angular error with the use of the cochlear implant at all intensities in both SSD and AHL subgroups. CONCLUSIONS: Cochlear implantation in patients with SSD and AHL enhances sound localization, reducing mean angular error and increasing the number of correct sound localization responses.

18.
ACS Biomater Sci Eng ; 10(6): 3994-4008, 2024 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-38736179

RESUMEN

Disruption of the symbiosis of extra/intratumoral metabolism is a good strategy for treating tumors that shuttle resources from the tumor microenvironment. Here, we report a precision treatment strategy for enhancing pyruvic acid and intratumoral acidosis to destroy tumoral metabolic symbiosis to eliminate tumors; this approach is based on PEGylated gold and lactate oxidase-modified aminated dendritic mesoporous silica with lonidamine and ferrous sulfide loading (PEG-Au@DMSNs/FeS/LND@LOX). In the tumor microenvironment, LOX oxidizes lactic acid to produce pyruvate, which represses tumor cell proliferation by inhibiting histone gene expression and induces ferroptosis by partial histone monoubiquitination. In acidic tumor conditions, the nanoparticles release H2S gas and Fe2+ ions, which can inhibit catalase activity to promote the Fenton reaction of Fe2+, resulting in massive ·OH production and ferroptosis via Fe3+. More interestingly, the combination of H2S and LND (a monocarboxylic acid transporter inhibitor) can cause intracellular acidosis by lactate, and protons overaccumulate in cells. Multiple intracellular acidosis is caused by lactate-pyruvate axis disorders. Moreover, H2S provides motive power to intensify the shuttling of nanoparticles in the tumor region. The findings confirm that this nanomedicine system can enable precise antitumor effects by disrupting extra/intratumoral metabolic symbiosis and inducing ferroptosis and represents a promising active drug delivery system candidate for tumor treatment.


Asunto(s)
Ferroptosis , Ácido Láctico , Ácido Pirúvico , Microambiente Tumoral , Ferroptosis/efectos de los fármacos , Humanos , Ácido Láctico/metabolismo , Animales , Ácido Pirúvico/metabolismo , Microambiente Tumoral/efectos de los fármacos , Nanopartículas/química , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/terapia , Línea Celular Tumoral , Ratones , Oro/química , Dióxido de Silicio/química , Femenino , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ratones Endogámicos BALB C , Proliferación Celular/efectos de los fármacos , Oxigenasas de Función Mixta , Indazoles
19.
Clin Exp Ophthalmol ; 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38803136

RESUMEN

BACKGROUND: To compare intraocular pressure (IOP) and anterior segment parameters between eyes with unilateral primary angle closure glaucoma (PACG) and their fellow eyes with primary angle closure (PAC) or primary angle closure suspect (PACS). METHODS: Subjects underwent anterior segment imaging using 360-degree swept-source optical coherence tomography (SS-OCT, CASIA Tomey, Nagoya, Japan) and ocular investigations including gonioscopy and IOP measurement. Each SS-OCT scan (divided into 8 frames, 22.5 degrees apart) was analysed and an average was obtained for the following anterior segment parameters: iridotrabecular contact (ITC), angle opening distance (AOD750), iris thickness and curvature, anterior chamber width, depth and area (ACW, ACD and ACA) and lens vault (LV). RESULTS: Among 132 unilateral PACG subjects (mean age: 62.91 ± 7.2 years; 59.1% male), eyes with PACG had significantly higher presenting IOP (24.81 ± 0.94 vs. 18.43 ± 0.57 mmHg, p < 0.001), smaller gonioscopic Shaffer grade (2.07 ± 0.07 vs. 2.31 ± 0.07, p < 0.001) and a greater extent of peripheral anterior synechiae (PAS, 1.21 ± 0.21 vs. 0.54 ± 0.16 clock hours, p = 0.001). PACG eyes also exhibited increased ITC, ITC area, greater LV and smaller AOD750, ACD and ACA (all p < 0.05). Using the forward stepwise regression model, an increase in 1 mmHg in presenting IOP before laser peripheral iridotomy (LPI) increases the odds of having PACG by 9% (95% confidence interval 5%-14%). CONCLUSIONS: PACG eyes have higher presenting IOP, smaller anterior segment parameters, greater extent of PAS, and larger LV compared to their fellow eyes with angle closure. Narrower anterior chamber dimensions and higher presenting IOP before LPI may increase risk of chronic elevated IOP and glaucomatous optic neuropathy after LPI.

20.
Cureus ; 16(3): e55371, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38562328

RESUMEN

Hypophyseal adenomas can present with or without minimal visual disturbances. We present a case of a 40-year-old male with a hypophyseal adenoma, highlighting bitemporal peripapillary retinal nerve fiber layer (NFL) thinning on optical coherence tomography (OCT) as a major sign of chiasmal damage despite minimal asymmetrical nonspecific changes detected on initial visual field testing. The bitemporal NFL thinning prompted further evaluation with MRI, which confirmed the presence of a macroadenoma of the hypophysis. Despite the large adenoma, treatment with cabergoline led to regression, and the patient's visual field improved. This case underscores the importance of OCT in detecting subtle structural changes associated with pituitary tumors, as it can facilitate early diagnosis and prompt intervention for optimal visual outcomes.

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