RESUMEN

Central vision loss (CVL) is a major form of low vision that remains inadequately managed worldwide. This study evaluated the clinical efficacy of a novel head-mounted device (HMD), Onyx, designed to enhance visual function and vision-related quality of life for CVL patients. It employs a projection system that enables patients to leverage their residual peripheral vision for environmental awareness. It also integrates artificial intelligence to augment the automatic recognition of text, faces, and objects. In this single-center, prospective cohort study, 41 binocularly low vision patients with CVL were instructed to use Onyx for 4 to 6 h daily over a one-month period. Various metrics were assessed, including near and distance visual acuity (VA), recognition abilities for faces and objects, and the low vision quality-of-life (LVQOL) questionnaire scores, at the start and end of the study. The results showed significant improvements in near VA for 60.98% of the participants, distance VA for 80.49%, and recognition ability for 90.24%. 68.29% of the participants showed significant improvements in the LVQOL scores. Improvement in recognition ability was negatively correlated with baseline recognition ability. Additionally, improvement in the LVQOL scores was correlated with age and the baseline LVQOL score. Overall, the study found that the novel HMD significantly improved visual function and vision-related quality of life for low vision patients with CVL, highlighting the potential benefits and the need for further evaluation of such devices.

Asunto(s)

Calidad de Vida , Baja Visión , Agudeza Visual , Humanos , Masculino , Femenino , Agudeza Visual/fisiología , Persona de Mediana Edad , Anciano , Baja Visión/fisiopatología , Baja Visión/terapia , Baja Visión/rehabilitación , Estudios Prospectivos , Adulto , Resultado del Tratamiento , Encuestas y Cuestionarios , Cabeza , Anciano de 80 o más Años

RESUMEN

BACKGROUND: Polypoidal choroidal vasculopathy (PCV) is a hemorrhagic fundus disease that can lead to permanent vision loss. Predicting the treatment response to anti-VEGF monotherapy in PCV is consistently challenging. We aimed to conduct a prospective multicenter study to explore and identify the imaging biomarkers for predicting the anti-VEGF treatment response in PCV patients, establish predictive model, and undergo multicenter validation. METHODS: This prospective multicenter study utilized clinical characteristics and images of treatment naïve PCV patients from 15 ophthalmic centers nationwide to screen biomarkers, develop model, and validate its performance. Patients from Peking Union Medical College Hospital were randomly divided into a training set and an internal validation set. A nomogram was established by univariate, LASSO regression, and multivariate regression analysis. Patients from the other 14 centers served as an external test set. Area under the curve (AUC), sensitivity, specificity, and accuracy were calculated. Decision curve analysis (DCA) and clinical impact curve (CIC) were utilized to evaluate the practical utility in clinical decision-making. FINDINGS: The eye distribution for the training set, internal validation set, and external test set were 66, 31, and 71, respectively. The 'Good responder' exhibited a thinner subfoveal choroidal thickness (SFCT) (230.67 ± 61.96 vs. 314.42 ± 88.00 µm, p < 0.001), lower choroidal vascularity index (CVI) (0.31 ± 0.08 vs. 0.36 ± 0.05, p = 0.006), fewer choroidal vascular hyperpermeability (CVH) (31.0 vs. 62.2%, p = 0.012), and more intraretinal fluid (IRF) (58.6 vs. 29.7%, p = 0.018). SFCT (OR 0.990; 95% CI 0.981-0.999; p = 0.033) and CVI (OR 0.844; 95% CI 0.732-0.971; p = 0.018) were ultimately included as the optimal predictive biomarkers and presented in the form of a nomogram. The model demonstrated AUC of 0.837 (95% CI 0.738-0.936), 0.891 (95% CI 0.765-1.000), and 0.901 (95% CI 0.824-0.978) for predicting 'Good responder' in the training set, internal validation set, and external test set, respectively, with excellent sensitivity, specificity, and practical utility. INTERPRETATION: Thinner SFCT and lower CVI can serve as imaging biomarkers for predicting good treatment response to anti-VEGF monotherapy in PCV patients. The nomogram based on these biomarkers exhibited satisfactory performances.

Asunto(s)

Inhibidores de la Angiogénesis , Biomarcadores , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular , Humanos , Masculino , Femenino , Estudios Prospectivos , Anciano , Persona de Mediana Edad , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Coroides/irrigación sanguínea , Coroides/diagnóstico por imagen , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/diagnóstico por imagen , Resultado del Tratamiento , Nomogramas , Pólipos/tratamiento farmacológico , Pólipos/diagnóstico por imagen , Pólipos/diagnóstico , Angiografía con Fluoresceína/métodos , Enfermedades de la Coroides/tratamiento farmacológico , Enfermedades de la Coroides/diagnóstico por imagen , Enfermedades de la Coroides/diagnóstico , Vasculopatía Coroidea Polipoidea

RESUMEN

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs and systems. Ocular involvement is estimated to manifest in one-third of individuals with SLE, of which lupus retinopathy and choroidopathy represent the severe subtype accompanied by vision impairment. Advancements in multimodal ophthalmic imaging have allowed ophthalmologists to reveal subclinical microvascular and structural changes in fundus of patients with SLE without ocular manifestations. Both ocular manifestations and subclinical fundus damage have been shown to correlate with SLE disease activity and, in some patients, even precede other systemic injuries as the first presentation of SLE. Moreover, ocular fundus might serve as a window into the state of systemic vasculitis in patients with SLE. Given the similarities of the anatomy, physiological and pathological processes shared among ocular fundus, and other vital organ damage in SLE, such as kidney and brain, it is assumed that ocular fundus involvement has implications in the diagnosis and evaluation of other systemic impairments. Therefore, evaluating the fundus characteristics of patients with SLE not only contributes to the early diagnosis and intervention of potential vision damage, but also holds considerate significance for the evaluation of SLE vasculitis state and prediction of other systemic injuries.

Asunto(s)

Fondo de Ojo , Lupus Eritematoso Sistémico , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Enfermedades de la Retina/etiología , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/patología , Enfermedades de la Coroides/etiología , Enfermedades de la Coroides/diagnóstico

RESUMEN

To explore the feasibility and safety of biomaterials for posterior scleral reinforcement (PSR) in rabbits. Decellularization and genipin crosslink were applied to the fresh bovine pericardium and porcine endocranium, and then mechanical properties, suture retention strength, and stability were tested. PSR operation was performed on 24 rabbit eyes using treated biological materials. Ophthalmic examination was performed regularly before and after PSR operation (1 week, 1 month, 3 months, 6 months). To evaluate the effectiveness, A ultrasound, diopter, and optical coherence tomography were conducted. General condition, fundus photograph, and pathological examination were recorded to evaluate the safety. Compared with genipin crosslinked bovine pericardium (Gen-BP) (21.29 ± 13.29 Mpa), genipin crosslinked porcine endocranium (Gen-PE) (34.85 ± 3.67 Mpa,P< 0.01) showed a closer elastic modulus to that of genipin crosslinked human sclera. There were no complications or toxic reactions directly related to the materials. Capillary hyperplasia, inflammatory cell infiltration, and collagen fiber deposition were observed, and the content of type I collagen fibers increased after PSR. Overall, the choroidal thickness of treated eyes was significantly thickened at different time points after PSR, which were 96.84 ± 21.08 µm, 96.72 ± 22.00 µm, 90.90 ± 16.57 µm, 97.28 ± 14.74 µm, respectively. The Gen-PE group showed changes that were almost consistent with the overall data. Gen-BP and Gen-PE are safe biological materials for PSR. The Gen-PE group demonstrated more significant advantages over the Gen-BP group in terms of material properties.

Asunto(s)

Materiales Biocompatibles , Estudios de Factibilidad , Iridoides , Ensayo de Materiales , Esclerótica , Animales , Conejos , Materiales Biocompatibles/química , Bovinos , Porcinos , Iridoides/química , Suturas , Pericardio , Tomografía de Coherencia Óptica , Humanos , Reactivos de Enlaces Cruzados/química , Módulo de Elasticidad

RESUMEN

The stratum corneum of the outermost skin is an important barrier impeding transdermal permeation, and permeation enhancers can reduce the barrier resistance of the stratum corneum and enhance the permeation of drugs in tissues. The optical imaging depth, signal intensity, and scattering coefficient variation rules of skin tissues in time dimension are obtained by using optical coherence tomography (OCT). The effect of optical clearing agents (OCAs) on OCT imaging is obtained by quantitatively analyzing the changes in the optical properties of tissues. D-fructose, one of the monosaccharides, and sucrose, one of the disaccharides, were selected for the ex vivo optical clearing experiments on pig skin tissues utilizing the dimethyl sulfoxide (DMSO) carrier effect. We find that DMSO synergized with sugars applied to skin tissue has a more significant increase in the optical imaging depth and signal intensity, and a reduction in the scattering coefficient with an increasing concentration of DMSO. DMSO with a high concentration and D-fructose with saturated concentration (10:1; v/v) effectively reduce light attenuation in OCT imaging and improve the image quality. This operation will also shorten the application time to minimize skin damage from hyperosmotic agents.

Asunto(s)

Azúcares , Tomografía de Coherencia Óptica , Animales , Porcinos , Dimetilsulfóxido/farmacología , Piel , Fructosa

RESUMEN

Intravitreal (IVT) injection of anti-vascular endothelial growth factor (anti-VEGF) has greatly improved the treatment of many retinal disorders, including wet age-related macular degeneration (wAMD), which is the third leading cause of blindness. However, frequent injections can be difficult for patients and may lead to various risks such as elevated intraocular pressure, infection, and retinal detachment. To address this issue, researchers have found that IVT injection of anti-VEGF proteins at their maximally viable concentration and dose can be an effective strategy. However, the intrinsic protein structure can limit the maximum concentration due to stability and solution viscosity. To overcome this challenge, we developed a novel anti-VEGF protein called nanoFc by fusing anti-VEGF nanobodies with a crystallizable fragment (Fc). NanoFc has demonstrated high binding affinity to VEGF165 through multivalency and potent bioactivity in various bioassays. Furthermore, nanoFc maintains satisfactory chemical and physical stability at 4°C over 1 month and is easily injectable at concentrations up to 200 mg/mL due to its unique architecture that yields a smaller shape factor. The design of nanoFc offers a bioengineering strategy to ensure both strong anti-VEGF binding affinity and high protein concentration, with the goal of reducing the frequency of IV injections.

RESUMEN

Human adenovirus (HAdV) infects the respiratory system, thus posing a threat to health. However, immunodiagnostic reagents for human adenovirus are limited. This study aimed to develop efficient diagnostic reagents based on monoclonal antibodies for diagnosing various human adenovirus infections. Evolutionary and homology analyses of various human adenoviral antigen genes revealed highly conserved antigenic fragments. The prokaryotic expression system was applied to recombinant penton, hexon, and IVa2 conserved fragments of adenovirus, which were injected into BALB/c mice to prepare human adenovirus-specific monoclonal antibodies. Enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and Western blotting were used to determine the immune specificity of the monoclonal antibodies. Indirect ELISA showed that monoclonal antibodies 1F10, 8D3, 4A1, and 9B2 were specifically bound to HAdV-3 and HAdV-55 and revealed high sensitivity and low detection limits for various human adenoviruses. Western blotting showed that 1F10 and 8D3 specifically recognized various human adenovirus types, including HAdV-1, HAdV-2, HAdV-3, HAdV-4, HAdV-5, HAdV-7, HAdV-21, and HAdV-55, and 4A1 specifically recognized HAdV-1, HAdV-2, HAdV-3, HAdV-5, HAdV-7, HAdV-21, and HAdV-55. IFAs showed that 1F10, 8D3, and 4A1 exhibited highly selective localization to A549 cells infected with HAdV-3 and HAdV-55. Finally, two antibody pairs that could detect hexon antigens HAdV-3 and HAdV-55 at low concentrations were developed. The monoclonal antibodies developed in this study show potential for detecting human adenoviruses. IMPORTANCE: In this study, we selected the three most conserved antigenic fragments of human adenovirus to prepare a murine monoclonal antibody for the first time, and human adenovirus antigenic fragments with heretofore unheard of degrees of conservatism were isolated. The three monoclonal antibodies with the ability to recognize human respiratory adenovirus over a broad spectrum were screened by hybridoma and monoclonal antibody preparation. Human adenovirus infections are serious; however, therapeutic drugs and diagnostic reagents are scarce. Thus, to reduce the serious consequences of human viral infections and adenovirus pneumonitis, early diagnosis of infection is required. The present study provides three monoclonal antibodies capable of recognizing a wide range of human adenoviruses, thereby offering guidance for subsequent research and development.

Asunto(s)

Infecciones por Adenovirus Humanos , Adenovirus Humanos , Humanos , Animales , Ratones , Anticuerpos Monoclonales , Anticuerpos Antivirales , Adenovirus Humanos/genética , Serogrupo , Proteínas de la Cápside/genética

RESUMEN

OBJECTIVE: To investigate the risk factors of lupus retinopathy (LR) in patients with systemic lupus erythematosus (SLE). METHODS: This is a retrospective, cross-sectional study. LR patients admitted at Peking Union Medical College Hospital from June 2013 to April 2023 were reviewed. Age- and gender-matched SLE patients without retinopathy were selected as controls. Medical records including clinical manifestations, laboratory data and ophthalmic examination were collected. Univariate and multivariate logistic regression analyses were conducted. RESULTS: One hundred and twelve LR patients (198 eyes) were included, with 12 cases (14 eyes) presenting with retinal macrovascular obstruction, and 100 cases (184 eyes) only exhibiting microvasculopathy. Multivariate analysis indicated the presence of haemolytic anaemia, decreased haemoglobin (HGB) and higher relative percentage of neutrophils were independent risk factors for LR (p < 0.05). The first two were also risk factors for retinal microvasculopathy, whereas secondary antiphospholipid syndrome (APS) was for macrovascular obstruction. In male group, LR had significant associations with decreased HGB, no matter which types of retinopathy (p < 0.05). In female group, LR was significantly associated with haemolytic anaemia, presence of antiphospholipid antibodies, decreased white blood cells and relative high percentage of neutrophils. Specifically, haemolytic anaemia (p = 0.002) was significantly associated with retinal microvasculopathy, and APS (p = 0.003) was significantly associated with macrovasculature obstruction. CONCLUSION: LR was related to haemolytic anaemia, decreased HGB levels and higher percentage of neutrophils. Retinal microvasculopathy accounted for most cases and macrovasculature obstructions were rare. Male and female patients have distinct risk factors. Early ophthalmic screening is recommended especially for those with risk factors of LR.

Asunto(s)

Lupus Eritematoso Sistémico , Enfermedades de la Retina , Humanos , Femenino , Masculino , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/sangre , Estudios Retrospectivos , Factores de Riesgo , Estudios Transversales , Adulto , Enfermedades de la Retina/etiología , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/epidemiología , Persona de Mediana Edad , China/epidemiología , Adulto Joven , Incidencia

RESUMEN

Purpose: To assess the retinal vasculature changes quantitatively using wide-field optical coherence tomography angiography (OCTA) in systemic lupus erythematosus (SLE), and explore its correlation with systemic clinical features. Design: Prospective, cross-sectional, observational study. Participants and controls: Patients with SLE who presented to the Ophthalmology Department of Peking Union Medical College Hospital from November 2022 to April 2023 were collected. The subjects were divided into retinopathy and without retinopathy groups. Age and gender-matched healthy subjects were selected as controls. Methods: Patients with SLE and control subjects were imaged with 24×20 mm OCTA scans centered on the fovea and 6×6 mm OCTA scans centered on the optic disc. The sub-layers of OCTA images were stratified by the built-in software of the device and then the retinal thickness and vessel density were measured automatically. The characteristics of retinal OCTA parameters of SLE and its correlation with systemic clinical indicators of patients without retinopathy were analyzed. Main outcome measures: OCTA parameters, visual acuity, intraocular pressure, and systemic clinical indicators of patients such as disease activity index, autoimmune antibodies, and inflammatory marker levels were collected. Results: A total of 102 SLE patients were included, 24 of which had retinopathy, and 78 had unaffected retina. Wide-field OCTA could effectively detect retinal vascular obstruction, non-perfusion area, and morphological abnormalities in patients with lupus retinopathy. SLE patients without retinopathy had significantly higher retinal superficial vessel density (SVD) in foveal (P=0.02), para-foveal temporal (P=0.01), nasal (P=0.01), peripheral foveal temporal (P=0.02), and inferior areas (P=0.02), as well as subregion temporal (P=0.01) and inferior areas (P=0.03) when compared with healthy controls (n=65 eyes from 65 participants). The area under curve (AUC) value of subregion inferior SVD combined parafoveal temporal SVD was up to 0.70. There was a significantly positive correlation between SVD and disease activity in SLE without retinopathy group. Patients with severe activity had the most significant increase in SVD. Conclusion: Wide-field OCTA can provide a relatively comprehensive assessment of the retinal vasculature in SLE. In the absence of pathological changes of the retina, the SVD was significantly increased and was positively correlated with the disease activity of SLE.

Asunto(s)

Retinopatía Diabética , Lupus Eritematoso Sistémico , Enfermedades de la Retina , Humanos , Tomografía de Coherencia Óptica/métodos , Angiografía con Fluoresceína/métodos , Estudios Transversales , Estudios Prospectivos , Retinopatía Diabética/patología , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Retina/diagnóstico por imagen , Enfermedades de la Retina/etiología , Enfermedades de la Retina/patología , Lupus Eritematoso Sistémico/patología

RESUMEN

AIM: To investigate the impacts of angiotensin II (Ang II) on retinal artery changes in apolipoprotein E deficient (apoE-/-) mice. METHODS: apoE-/- male mice were infused by minipumps with Ang II at 1000 ng/kg·min (Ang II group) or saline (control group) for 28d. They were underwent ophthalmic fundus examination on day 0, 14, and 28 of infusion. Histopathologic examination, ribonucleic acid (RNA) sequencing and local Ang II measurement of retinas were conducted. RESULTS: Ophthalmic fundus examination showed Ang II infusion promoted the formation of retinal arterial aneurysm-like lesions on day 28. Optical coherence tomography revealed the ganglion cell and inner plexiform layer (GCIPL) thickness in the control group was significantly thinner than that in Ang II group (P<0.001). Hematoxylin-eosin staining demonstrated diffused swelling of GCIPL layer and its disordered structure in Ang II group. Transmission electron microscopy showed Ang II infusion caused aggravation of atherosclerotic lesions, including increased swelling, roughness, disorganization of the retinal vasculature, and vacuoles formation. RNA-sequencing and gene ontology enrichment analysis demonstrated that the structure and function of cellular membrane might be disturbed and visual function might be compromised by Ang II. The local level of Ang II was higher in Ang II infusion group but did not show significant differences compared to the control group (P=0.086). CONCLUSION: Ang II infusion promotes the formation of retinal arterial aneurysm-like lesions in apoE-/- mice, causing aggravation of atherosclerotic lesions, more severe disorganization of the retinal vasculature and disturbance of the cellular membrane.

RESUMEN

PURPOSE: To investigate the distinct characteristics between young and elderly polypoidal choroidal vasculopathy (PCV) patients based on the pachy- or non-pachychoroid phenotypes. METHODS: PCV patients treated with intravitreal injections of Conbercept based on the 3 + PRN regimen from 27 centers of China PCV Research Alliance were included. Patients were categorized into the young and the elderly aged group based on the cut-off point determined using the Youden method according to the pachychoroid phenotypes. The characteristics of past medical history, lifestyle factors, fundus manifestations, and treatment response between the subgroups were analyzed. RESULTS: Three hundred eight eligible patients were included. Multivariate logistic regression showed a significant association between age and PCV subtype classification (OR = 0.921, P = 0.002). A cutoff age of 64.5 effectively distinguished between pachychoroid PCV and non-pachychoroid PCV (P < 0.001). Elderly PCV patients had a higher incidence of hypertension history (P = 0.044) but a lower incidence of diabetes history (P = 0.027). In terms of lifestyle, smoking history (P = 0.015) and staying up late (P = 0.004) were more significant in the young group of PCV patients. For clinical characteristics, the proportion of hemorrhagic PCV in the young group was significantly higher (P = 0.038), with a higher proportion of sharp-peaked PED (P = 0.049), thicker choroid (P < 0.001) but a lower portion of double-layer sign (P = 0.023) in OCT. Both groups showed significant anatomical changes compared to baseline in each follow-up period (P < 0.05), with the young group having a higher proportion of good anatomical response after the first injection (P = 0.009). CONCLUSION: PCV patients stratified by subtype exhibit distinct characteristics between the young and elderly groups.

Asunto(s)

Coroides , Angiografía con Fluoresceína , Fondo de Ojo , Inyecciones Intravítreas , Fenotipo , Pólipos , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Angiografía con Fluoresceína/métodos , Coroides/irrigación sanguínea , Pólipos/diagnóstico , Pólipos/tratamiento farmacológico , Tomografía de Coherencia Óptica/métodos , Estudios Retrospectivos , Estudios de Seguimiento , Neovascularización Coroidal/diagnóstico , Neovascularización Coroidal/tratamiento farmacológico , Enfermedades de la Coroides/diagnóstico , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Anciano de 80 o más Años , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Vasculopatía Coroidea Polipoidea

RESUMEN

OBJECTIVES: To develop a sensitive point-of-care testing (POCT) aqueous vascular endothelial growth factor (VEGF) detection system, and assess its role for predicting the response to anti-VEGF treatment in macular edema secondary to retinal vein occlusion (RVO-ME) patients. METHODS: An automatic point-of-care aqueous humor Magnetic Particle Chemiluminescence Enzyme Immuno-Assay (MPCLEIA) VEGF detection system was developed. The predictive values of aqueous cytokine levels, in combination with imaging parameters, on anatomical treatment response (ATR, the relative central macular thickness change [ΔCMT/bl-CMT]) were analyzed. RESULTS: The automatic MPCLEIA system was able to provide results in 45 min with only 20 µL sample. Among the 57 eyes with available pre- and post-treatment evaluation, ATR significantly correlated with levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and VEGF measured by Luminex xMAP platform, and VEGF measured by MPCLEIA. Optimal cut-off values for these biomarkers were 13.26 ng/L, 23.57 ng/L, 1,110.12 ng/L, 105.52 ng/L, and 85.39 ng/L, respectively. Univariate analysis showed significant associations between ATR category (good response if ATR≤-25 % or poor response otherwise) and IL-6, IL-8, MCP-1, VEGF-xMAP, and VEGF-MPCLEIA (p<0.05). Multivariate logistic regression revealed that ATR category was significantly associated with aqueous VEGF-MPCLEIA (p=0.006) and baseline(bl)-CMT (p=0.008). Receiver operating characteristics analysis yielded an AUC of 0.959 for the regression model combining VEGF-MPCLEIA and bl-CMT, for predicting ATR category. CONCLUSIONS: Our novel MPCLEIA-based automatic VEGF detection system enables accurate POCT of aqueous VEGF, which shows promise in predicting the treatment response of RVO-ME to anti-VEGF agents when combined with bl-CMT.

Asunto(s)

Edema Macular , Factor A de Crecimiento Endotelial Vascular , Humanos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Sistemas de Atención de Punto , Interleucina-8 , Edema Macular/diagnóstico , Edema Macular/metabolismo , Factores de Crecimiento Endotelial Vascular/metabolismo , Interleucina-6 , Humor Acuoso/metabolismo

RESUMEN

Sexual reproduction is crucial for population continuity in clonal plants. The effect of nutrient translocation between ramets on sexual reproduction of clonal plants under nitrogen addition remains unclear. In this study, we focused on clonal fragments of Leymus chinensis reproductive ramets with different number of vegetative ramets connected to tillering nodes. A series of pot experiments was conducted under nitrogen addition, including 13C and 15N bidirectional labelling of vegetative ramets and reproductive ramets at the milk-ripe stage, determination of the 13C and 15N amount translocated, and assessment of the quantitative characteristics, nitrogen and carbon concentrations of reproductive ramets and vegetative ramets. Nitrogen addition promoted the translocation of 13C while inhibiting 15N between vegetative ramets and reproductive ramets. With an increase in the number of connected vegetative ramets, the 13C translocated by reproductive ramets and the 15N translocated by reproductive and vegetative ramets gradually increased. The translocation of 13C and 15N between vegetative and reproductive ramets was bidirectional and unequal. The translocated amount of 13C and 15N from reproductive ramets to vegetative ramets was always higher than that from vegetative ramets to reproductive ramets. Nitrogen addition did not prominently affect the sexual reproductive performance of L. chinensis, whereas the number of connected vegetative ramets both positively and negatively affected sexual reproductive performance. Ramet biomass is an important driver of nutrient acquisition by L. chinensis ramets. We demonstrate for the first time that unequal nutrient translocation between ramets affects sexual reproductive performance in L. chinensis. The findings contribute to an enhanced understanding of the reproductive strategies of clonal plant populations in future environments.

Asunto(s)

Nitrógeno , Poaceae , Carbono , Biomasa , Reproducción

RESUMEN

INTRODUCTION: The aims of the study were to investigate whether first-dose efficacy can predict third-dose anatomical response and analyze the risk factors for first-dose response of polypoidal choroidal vasculopathy (PCV) patients. METHODS: We retrospectively reviewed patients' medical records from 27 centers of China PCV Research Alliance. PCV patients treated with intravitreal injections of conbercept (IVC) based on the 3+ pro re nata regimen (three initial monthly injections, followed by injections as needed) with complete 3-month injection data were included. Response correlations, risk factor associations, changes in central macular thickness (CMT) or best-corrected visual acuity (BCVA), and number of injections in the first year of follow-up were evaluated separately in the pachy-PCV and non-pachy-PCV phenotypes. RESULTS: Overall, 165 eligible patients were included. There was a significant correlation between first-dose and third-dose anatomical response in pachy-PCV or non-pachy-PCV patients (rs = 0.611, p < 0.001; rs = 0.638, p < 0.001). Multivariate analysis revealed associations of good first-dose anatomical response in pachy-PCV patients with baseline CMT with a predicted area under the curve (AUC) of 0.847, while a good response in non-pachy-PCV patients was associated with baseline BCVA, baseline CMT, pigment epithelial detachment (PED) height, higher proportion of intraretinal fluid, and lower PED minimum diameter with a predicted AUC of 0.940. CMT in the good first-dose response group was significantly decreased from baseline at all first-year follow-up visits in both groups (p < 0.001), and mean BCVA was improved in the good versus poor first-dose anatomical response group (5.4 vs. 1.6 ETDRS letters in pachy-PCV, 10.6 vs. 7.4 letters in non-pachy-PCV) after the third injection. No significant difference was observed in the number of injections in the first year of follow-up between different response groups. CONCLUSION: In PCV patients receiving IVC, the first- and third-dose responses are significantly correlated, and different factors influence the first-dose response in different subtypes of PCV.

Asunto(s)

Resinas Acrílicas , Hidrazinas , Pólipos , Desprendimiento de Retina , Humanos , Inhibidores de la Angiogénesis/uso terapéutico , Vasculopatía Coroidea Polipoidea , Estudios Retrospectivos , Resultado del Tratamiento , Desprendimiento de Retina/etiología , Factores de Riesgo , Inyecciones Intravítreas , Tomografía de Coherencia Óptica , Angiografía con Fluoresceína , Estudios de Seguimiento , Pólipos/diagnóstico , Pólipos/tratamiento farmacológico , Pólipos/complicaciones

RESUMEN

Klebsiella pneumoniae is a ubiquitous human pathogen, and its clinical treatment faces two major challenges: multidrug resistance and the pathogenesis of hypervirulent K. pneumoniae. The discovery and study of conditionally essential (CE) genes that can function as potential antimicrobial targets has always been a research concern due to their restriction in the development of novel antibiotics. However, the lack of essential functional genomic data has hampered the study of the mechanisms of essential genes related to antimicrobial susceptibility. In this study, we developed a pooled CE genes mobile clustered regularly interspaced short palindromic repeat (CRISPR) interference screening method (Mobile-CRISPRi-seq) for K. pneumoniae to identify genes that play critical roles in antimicrobial fitness in vitro and host immunity in vivo. Targeting 870 predicted CE genes in K. pneumoniae, Mobile-CRISPRi-seq uncovered the depletion of tetrahydrofolate synthesis pathway genes folB and folP under trimethoprim pressure. Our screening also identified genes waaE and fldA related to polymyxin and ß-lactam susceptibility by applying a screening strategy based on Mobile-CRISPRi-seq and comparative genomics. Furthermore, using a mouse infection model and Mobile-CRISPRi-seq, multiple virulence genes were identified, and among these genes, pal, yciS, and ribB were demonstrated to contribute to the pathogenesis of K. pneumoniae. This study provides a simple, rapid, and effective platform for screening potential antimicrobial targets and virulence genes in K. pneumoniae, and this broadly applicable system can be expanded for high-throughput functional gene study in multiple pathogenic bacteria, especially in gram-negative bacteria. IMPORTANCE The discovery and investigation of conditionally essential (CE) genes that can function as potential antimicrobial targets has always been a research concern because of the restriction of antimicrobial targets in the development of novel antibiotics. In this study, we developed a pooled CE gene-wide mobile clustered regularly interspaced short palindromic repeat (CRISPR) interference sequencing (Mobile-CRISPRi-seq) strategy in Klebsiella pneumoniae to identify genes that play critical roles in the fitness of antimicrobials in vitro and host immunity in vivo. The data suggest a robust tool to screen for loss-of-function phenotypes in a pooled gene knockdown library in K. pneumoniae, and Mobile-CRISPRi-seq may be expanded to multiple bacteria for screening and identification of genes with crucial roles in the fitness of antimicrobials and hosts.

Asunto(s)

Genes Esenciales , Klebsiella pneumoniae , Humanos , Klebsiella pneumoniae/genética , Virulencia/genética , Técnicas de Silenciamiento del Gen , Bacterias/genética , Antibacterianos/farmacología

RESUMEN

Polypoidal choroidal vasculopathy (PCV) is a disease characterized by subretinal pigment epithelium (RPE) orange-red polypoidal lesions and abnormal branching neovascular networks (BNNs). In recent years, various non-invasive imaging technologies have rapidly developed, especially the emergence of optical coherence tomography angiography (OCTA), multi-spectral imaging, and other technologies, which enable the observation of more features of PCV. In addition, these technologies are faster and less invasive compared to indocyanine green angiography (ICGA). Multi-modal imaging, which combined multiple imaging techniques, provides important references for the diagnosis and treatment of PCV with the assistance of regression models, deep learning, and other algorithms. In this study, we reviewed the non-invasive imaging techniques, multi-modal imaging diagnosis, and multi-scene therapeutic applications of PCV, with the aim of providing a reference for non-invasive multi-modal diagnosis and treatment of PCV.

RESUMEN

PURPOSE: To summarize the current evidence regarding the therapeutic effect of using autologous platelet concentrate (APC) in vitrectomy for macular hole (MH). METHODS: The PubMed, Web of Science, and Embase databases were searched according to the PROSPERO protocol (CRD42022366202). Controlled trials comparing whether APC was used in the vitrectomy of MH were included. The primary outcome was the closure rate of MH and postoperative best-corrected visual acuity, and the secondary outcome was the incidence of different types of complications. RESULTS: Seven studies that included 634 eyes were eligible. For the primary outcome, the usage of APC significantly improved the closure rate of MH in vitrectomy (odds ratio [OR] = 5.34, 95% confidence interval, 2.83-10.07, P < 0.001). Postoperative visual acuity did not significantly differ between the APC group and similar baseline controls (SMD = -0.07, 95% confidence interval, -0.35 to 0.22, P = 0.644). For the secondary outcome, using APC did not result in additional complications regarding postoperative retinal detachment or the recurrence of MH. CONCLUSION: The use of APC in vitrectomy was associated with a superior closure rate of the hole and no additional complications; therefore, it is effective and safe in MH surgery.

Asunto(s)

Desprendimiento de Retina , Perforaciones de la Retina , Humanos , Perforaciones de la Retina/etiología , Vitrectomía/métodos , Endotaponamiento/métodos , Desprendimiento de Retina/etiología , Ojo , Estudios Retrospectivos

RESUMEN

The gold standard for polypoidal choroidal vasculopathy (PCV) diagnosis is indocyanine green angiography (ICGA), but optical coherence tomography angiography (OCTA) has shown promise for PCV imaging in recent years. However, earlier generations of OCTA technology lacked the diagnostic efficacy to replace ICGA. Swept-source optical coherence tomography angiography (SS-OCTA), the latest generation of OCTA technology, has significantly improved penetrating ability, scanning speed, scanning range, and overall image quality compared with earlier generations of OCTA. SS-OCTA reveals a "tangled vasculature" pattern of polypoidal lesions (PLs), providing evidence that they are neovascular rather than aneurysmal structures. New choroidal biomarkers, such as the choriocapillaris flow void (FV), have been identified to explain the development of PCV lesions. Although no direct comparison between SS-OCTA and previous OCTA generations in terms of diagnostic capability has been performed, SS-OCTA has shown several advantages in differential diagnosis and monitoring early reactivation for PCV. These improvements make SS-OCTA a valuable tool for PCV diagnosis and follow-up, and it may become more important for this disease in the future. This review summarized recent advances in PCV morphology and structure, as well as the possible pathogenesis based on SS-OCTA findings. The value of SS-OCTA for PCV management is discussed, along with remaining issues, to provide an updated understanding of PCV and OCTA-guided management.

RESUMEN

The worldwide outbreak of the monkeypox virus (MPXV) has become a "Public Health Emergency of International Concern" (PHEIC). Severe monkeypox virus infection can be fatal, however, effective therapeutic methods are yet to be developed. Mice were immunized with A35R protein and A29L protein of MPXV, and the binding and neutralizing activities of the immune sera against poxvirus-associated antigens and viruses were identified. A29L protein and A35R protein-specific monoclonal antibodies (mAbs) were generated and their antiviral activities of these mAbs were characterized in vitro and in vivo. Immunization with the MPXV A29L protein and A35R protein induced neutralizing antibodies against the orthopoxvirus in mice. None of the mAbs screened in this study against A35R could effectively neutralize the vaccinia virus (VACV), while three mAbs against A29L protein, 9F8, 3A1 and 2D1 were confirmed to have strong broad binding and neutralizing activities against orthopoxvirus, among which 9F8 showed the best neutralizing activity. 9F8, 3A1, and 2D1 recognized different epitopes on MPXV A29L protein, showing synergistic antiviral activity in vitro against the VACV Tian Tan and WR strains; the best activity was observed when the three antibodies were combined. In the vivo antiviral prophylactic and therapeutic experiments, 9F8 showed complete protective activity, whereas 3A1 and 2D1 showed partial protective activity. Similarly, the three antibodies showed synergistic antiviral protective activity against the two VACVs. In conclusion, three mAbs recognized different epitopes on MPXV A29L protein were developed and showed synergistic effects against orthopoxvirus.

Asunto(s)

Enfermedades Transmisibles , Mpox , Orthopoxvirus , Animales , Ratones , Anticuerpos Neutralizantes , Orthopoxvirus/genética , Epítopos , Anticuerpos Antivirales , Proteínas Virales/genética , Virus Vaccinia , Monkeypox virus , Anticuerpos Monoclonales

RESUMEN

Predictive materials design of high-performance alloy electrocatalysts is a grand challenge in hydrogen production via water electrolysis. The vast combinatorial space of element substitutions in alloy electrocatalysts offers a wealth of candidate materials, but presents a significant challenge in terms of experimental and computational exploration of all possible options. Recent scientific and technological developments in machine learning (ML) have offered a new opportunity to accelerate such electrocatalyst materials design. Herein, by incorporating both the electronic and structural properties of alloys, we are able to construct accurate and efficient ML models and predict high-performance alloy catalysts for the hydrogen evolution reaction (HER). We have identified the light gradient boosting (LGB) algorithm as the best-performed method, with an excellent coefficient of determination (R2) value reaching 0.921 and the corresponding root-mean-square error (RMSE) being 0.224 eV. The average marginal contributions of alloy features towards ΔGH* values are estimated to determine the importance of various features during the prediction processes. Our results indicate that both the electronic properties of constituent elements and the structural adsorption site features play the most critical roles in the ΔGH* prediction. Furthermore, 84 potential alloys with |ΔGH*| values less than 0.1 eV are successfully screened out of 2290 candidates selected from the Material Project (MP) database. It is reasonable to expect that the ML models with structural and electronic feature engineering developed in this work would provide new insights in future electrocatalyst developments for the HER and other heterogeneous reactions.