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High myopia is a leading cause of blindness worldwide, among which pathologic myopia, characterized by typical myopic macular degeneration, is the most detrimental. However, its pathogenesis remains largely unknown. Here, using a HuProt array, we first initiated a serological autoantibody profiling of high myopia and identified 18 potential autoantibodies, of which anti-LIMS1 autoantibody was validated by a customized focused microarray. Further subgroup analysis revealed its actual relevance to pathologic myopia, rather than simple high myopia without myopic macular degeneration. Mechanistically, anti-LIMS1 autoantibody predominantly belonged to IgG1/IgG2/IgG3 subclasses. Serum IgG obtained from patients with pathologic myopia could disrupt the barrier function of retinal pigment epithelial cells via cytoskeleton disorganization and tight junction component reduction, and also trigger a pro-inflammatory mediator cascade in retinal pigment epithelial cells, which were all attenuated by depletion of anti-LIMS1 autoantibody. Together, these data uncover a previously unrecognized autoimmune etiology of myopic macular degeneration in pathologic myopia.
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Autoanticuerpos , Autoinmunidad , Epitelio Pigmentado de la Retina , Humanos , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Epitelio Pigmentado de la Retina/patología , Epitelio Pigmentado de la Retina/metabolismo , Masculino , Femenino , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangre , Persona de Mediana Edad , Miopía Degenerativa/inmunología , Miopía/inmunología , AdultoRESUMEN
A composite nanoagent capable of phototriggered tumor microenvironment (TME) regulation is developed based on copper (II) metal-organic frameworks (MOFs) with encapsulation of blebbistatin (Bb) and surface modification of fibroblast activation protein-αtargeted peptide (Tp). Tp enables active targeting of the nanoagents to cancer-associated fibroblast (CAF) while near-infrared light triggers Cu2+ -to-Cu+ photoreduction in MOFs, which brings about the collapse of MOFs and the release of Bb and Cu+ . Bb mediates photogeneration of hydroxyl radicals (â¢OH) and therefore inhibits extracellular matrix production by inducing CAF apoptosis, which facilitates the penetration of nanoagent to deep tumor tissue. The dual-channel generation of â¢OH based on Bb and the Cu+ species, via distinct mechanisms, synergistically reinforces oxidative stress in TME capable of inducing immunogenic cell death, which activates the antitumor immune response and therefore reverses the immunosuppressive TME. The synergistic antitumor phototherapy efficacy of such a type of nanoagent based on the abovementioned TME remodeling is unequivocally verified in a cell-derived tumor xenograft model.
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Fibroblastos Asociados al Cáncer , Estructuras Metalorgánicas , Neoplasias , Humanos , Estructuras Metalorgánicas/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Microambiente Tumoral , Cobre/metabolismo , Neoplasias/metabolismo , Línea Celular TumoralRESUMEN
PURPOSE: To investigate the efficacy of combined application of B-scan ultrasonography (US) and ultrawide field imaging (UWFI) in detecting retinal tears before cataract surgery. METHODS: Of 1,277 cataract patients, 2,552 eyes were enrolled and received both B-scan US and UWFI examinations preoperatively. Three types of combination were applied: type 1 (union, B-scan US or centered UWFI), type 2 (intersection, B-scan US and centered UWFI), and type 3 (B-scan US and eye-steering UWFI). Sensitivity and specificity of detecting retinal tears by different methods were assessed. RESULTS: Totally 4.55% (116/2,552) of eyes were presented with retinal tears. The sensitivity of B-scan US and UWFI was 87.93% and 84.48%, and specificity was 95.16% and 99.79%, respectively. By applying type 1 and type 2 combination, the sensitivity was 98.28% and 74.14%, and specificity was 95.03% and 99.92%, respectively. By type 3 combination, the sensitivity increased to 95.69% and specificity to 99.88%, both of which were comparable to indirect ophthalmoscopy regardless of the number, type, and location of tears ( P > 0.05). In eyes with any cataract type or axial length, type 3 combination also gained comparable performance to indirect ophthalmoscopy. CONCLUSION: Combined application of B-scan US and eye-steering UWFI presented satisfactory performance in detecting retinal tears before cataract surgery.
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Extracción de Catarata , Perforaciones de la Retina , Ultrasonografía , Humanos , Masculino , Femenino , Anciano , Perforaciones de la Retina/diagnóstico por imagen , Perforaciones de la Retina/diagnóstico , Ultrasonografía/métodos , Persona de Mediana Edad , Anciano de 80 o más Años , Adulto , Catarata , Sensibilidad y Especificidad , Cuidados Preoperatorios/métodos , Estudios Retrospectivos , Reproducibilidad de los ResultadosRESUMEN
Acetamide- or formamide-assisted in situ strategy is designed to synthesize carbon atom self-doped g-C3 N4 (AHCNx ) or nitrogen vacancy-modified g-C3 N4 (FHCNx ). Different from the direct copolymerization route that suffers from the problem of mismatched physical properties of acetamide (or formamide) with urea, the synthesis of AHCNx (or FHCNx ) starts from a crucial preorganization step of acetamide (or formamide) with urea via freeze drying-hydrothermal treatment so that the chemical structures as well as C-doping level in AHCNx and N-vacancy concentration in FHCNx can be precisely regulated. By using various structural characterization methods, well-defined AHCNx and FHCNx structures are proposed. At the optimal C-doping level in AHCNx or N-vacancy concentration in FHCNx , both AHCNx and FHCNx exhibit remarkably improved visible-light photocatalytic performance in oxidation of emerging organic pollutants (acetaminophen and methylparaben) and reduction of proton to H2 in comparison of unmodified g-C3 N4 . Combination of the experimental results with theoretical calculations, it is confirmed that AHCNx and FHCNx show different charge separation and transfer mechanisms, while the enhanced visible-light harvesting capacity and the localized charge distributions on HOMO and LUMO are responsible for this excellent photocatalytic redox performance of AHCNx and FHCNx .
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Room temperature phosphorescence (RTP) materials are characterized with emission after removing the excitation source. Such long-lived emission feature possesses great potential in biological fluorescence imaging because it enables a way regarding temporal dimension for separating the interference of autofluorescence and common noises typically encountered in conventional fluorescence imaging. Herein, we constructed a new type of mesoporous silica nanoparticles (MSNs)-based composite nanoparticles (NPs) with dual-color long-lived emission, namely millisecond-level green phosphorescence and sub-millisecond-level delayed red fluorescence by encapsulating a typical RTP dye and Rhodamine dye in the cavities of the MSNs with the former acting as energy donor (D) while the latter as acceptor (A). Benefiting from the close D-A proximity, energy match between the donor and the acceptor and the optimized D/A ratio in the composite NPs, efficient triplet-to-singlet Förster resonance energy transfer (TS-FRET) in the NPs occurred upon exciting the donor, which enabled dual-color long-lived emission. The preliminary results of dual-color correlation imaging of live cells based on such emission feature unequivocally verified the unique ability of such NPs for distinguishing the false positive generated by common emitters with single-color emission feature.
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Transferencia Resonante de Energía de Fluorescencia , Nanopartículas , Transferencia Resonante de Energía de Fluorescencia/métodos , Rodaminas , Nanopartículas/químicaRESUMEN
PURPOSE: To evaluate the long-term progression pattern of myopic tractional maculopathy and the risk factors. METHODS: The prevalence and grade of myopic tractional maculopathy were assessed with optical coherence tomography at enrollment and at the 2-year follow-up. The severity of posterior staphyloma and the presence of dome-shaped macula were also evaluated. RESULTS: In total, 610 highly myopic eyes of 610 patients were analyzed. The prevalence of epiretinal membrane, myopic retinoschisis, and macular hole increased from 26.7%, 12.1%, and 4.4% at enrollment to 41.1%, 18.2%, and 9.5% at the 2-year follow-up, respectively. Epiretinal membrane progressed in 21.8% of eyes, but visual acuity did not decline significantly in these eyes. Myopic retinoschisis progressed in 6.8% of eyes, and macular hole progressed in 14.8% of eyes. Significantly greater best-corrected visual acuity reduction was detected in the eyes with myopic retinoschisis or macular hole progression than the rest ( P < 0.05). Multivariate analysis showed that longer axial length, more-severe posterior staphyloma, and absence of dome-shaped macula were associated with myopic tractional maculopathy progression. CONCLUSION: In highly myopic eyes, long-term visual acuity was relatively stable in those with epiretinal membrane, but was significantly affected by myopic retinoschisis or macular hole progression. Longer axial length, more-severe posterior staphyloma, and absence of dome-shaped macula were risk factors for myopic tractional maculopathy progression.
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Membrana Epirretinal , Degeneración Macular , Miopía Degenerativa , Perforaciones de la Retina , Retinosquisis , Enfermedades de la Esclerótica , Humanos , Retinosquisis/etiología , Retinosquisis/complicaciones , Membrana Epirretinal/diagnóstico , Membrana Epirretinal/epidemiología , Membrana Epirretinal/etiología , Perforaciones de la Retina/diagnóstico , Perforaciones de la Retina/epidemiología , Perforaciones de la Retina/etiología , Miopía Degenerativa/complicaciones , Miopía Degenerativa/diagnóstico , Enfermedades de la Esclerótica/complicaciones , Tomografía de Coherencia Óptica/métodos , Degeneración Macular/complicaciones , Factores de Riesgo , Estudios RetrospectivosRESUMEN
Hydrogen sulfide (H2S) typically plays biphasic biological roles in living organisms with subnormal H2S exerting cytoprotective effects such as participating in cardioprotective signaling pathways while H2S with higher-than-normal concentrations in localized tissues acting the opposite way such as inhibiting mitochondrial respiration. Such concentration-dependent biological and pathological roles of H2S with the wide involvement of mitochondria and the elusive feature of H2S definitely highlight the vital significance of fast and precise estimation of the physiological level of H2S in specific microenvironments, particularly within cellular mitochondria. In this work, we developed a new type of fluorescent probe (QcyCHO) featured with H2S-triggered off-to-on near-infrared (NIR) fluorescence conversion within ~ 10 min, limit of detection (LOD) down to 8.3 nM, and high recognition specificity over other similarly interfering species. The ideal mitochondrion-targeting ability, high recognition specificity over typical interfering substances and other physiologically relevant species, and the ability for mapping intracellular H2S in living cells of QcyCHO probe were also unequivocally confirmed, which imply its potential for shedding light on the biology of H2S and therapeutic development in H2S-associated diseases by identifying the specific physiological stimuli inducing H2S production and determining the levels of H2S at the location and time of stimulation.
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Colorantes Fluorescentes/química , Sulfuro de Hidrógeno/análisis , Mitocondrias/química , Células HeLa , Humanos , Microscopía Confocal , Microscopía Fluorescente , Mitocondrias/ultraestructura , Imagen ÓpticaRESUMEN
Previous studies show that mortalin, a HSP70 family member, contributes to the development and progression of ovarian cancer. However, details of the transcriptional regulation of mortalin remain unknown. We aimed to determine whether NF-κB p65 participates in the regulation of mortalin expression in ovarian cancer cells and to elucidate the underlying mechanism. Chromatin immunoprecipitation and luciferase reporter assay were used to identify mortalin gene sequences, to which NF-κB p65 binds. Results indicated that NF-κB p65 binds to the mortalin promoter at a site with the sequence 'CGGGGTTTCA'. Using lentiviral pLVX-NF-κB-puro and Lentivirus-delivered NF-κB short hairpin RNA (shRNA), we created ovarian cancer cell lines in which NF-κB p65 was stably up-regulated and down-regulated. Using these cells, we found that downregulation of NF-κB p65 inhibits the growth and migration of ovarian cancer cells. Further experimental evidence indicated that downregulation of NF-κB p65 reduced mortalin, and upregulation of mortalin rescued the proliferation and migration of ovarian cancer cells reduced by NF-κB p65 knockdown. In conclusion, NF-κB p65 binds to the mortalin promoter and promotes ovarian cancer cells proliferation and migration via regulating mortalin.
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Biomarcadores de Tumor/metabolismo , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas Mitocondriales/metabolismo , Neoplasias Ováricas/patología , Factor de Transcripción ReIA/metabolismo , Apoptosis , Biomarcadores de Tumor/genética , Femenino , Proteínas HSP70 de Choque Térmico/genética , Humanos , Proteínas Mitocondriales/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Regiones Promotoras Genéticas , Factor de Transcripción ReIA/genética , Activación Transcripcional , Células Tumorales CultivadasRESUMEN
Background: Non-small cell lung Cancer (NSCLC) persists as a lethal neoplastic manifestation, exhibiting a diminished 5-year survival rate, partially attributable to chemotherapeutic resistance. This investigative endeavor aimed to elucidate the synergistic antineoplastic effects and underlying mechanisms of the SMYD2 inhibitor BAY-598 and the chemotherapeutic agent doxorubicin (DOX) in NSCLC. Methods: The human non-small cell lung cancer cell lines A549 and H460 were subjected to treatment regimens involving BAY-598 and/or DOX. Cellular viability, apoptotic events, invasive capacity, and migratory potential were evaluated through the implementation of CCK-8 assays, flow cytometric analyses, and Transwell assays, respectively. Protein expression levels were quantified via Western blot analyses. An in vivo xenograft murine model was established to assess therapeutic efficacy. Results: BAY-598 and DOX synergistically suppressed the viability, invasiveness, and migratory capabilities of NSCLC cells. Co-treatment Promoting cell apoptosis and cell cycle arrest. Additionally, Furthermore, co-administration significantly inhibited cell migration and invasion. Mechanistic studies revealed coordinately inhibited JAK-STAT signaling upon combination treatment. In vivo study further validated the synergistic antitumor efficacy of BAY-598 and DOX against NSCLC xenografts. Conclusions: Our findings demonstrate that BAY-598 potentiates the anti-cancer effects of DOX in non-small cell lung cancer cells by modulating the JAK/STAT signaling pathway as a synergistic strategy. The combination holds promise as an emerging therapeutic strategy for NSCLC. Further optimization and validation are warranted to promote its translational potential.
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Background: High myopia is one of the major causes of visual impairment and has an ever-increasing prevalence, especially in East Asia. It is characterized by excessive axial elongation, leading to various blinding complications that extend beyond mere refractive errors and persist immovably after refractive surgery, presenting substantial public health challenge. Main text: High myopia-related complications include lens pathologies, atrophic and tractional maculopathy, choroidal neovascularization, peripheral retinal degenerations and retinal detachment, and glaucoma and heightened susceptibility to intraocular pressure (IOP) elevation. Pathological lens changes characteristic of high myopia include early cataractogenesis, overgrowth of lens, weakened zonules, and postoperative capsular contraction syndrome, possibly driven by inflammatory pathogenesis, etc. Dome-shaped macula and cilioretinal arteries are two newly identified protective factors for central vision of highly myopic patients. These patients also face risks of open-angle glaucoma and IOP spike following intraocular surgery. Morphologic alternations of optic nerve in high myopia can complicate early glaucoma detection, necessitating comprehensive examinations and close follow-up. Anatomically, thinner trabecular meshwork increases this risk; conversely lamina cribrosa defects may offer a fluid outlet, potentially mitigating the pressure. Notably, anxiety has emerged as the first recognized extra-ocular complication in high myopia, with an underlying inflammatory pathogenesis that connects visual stimulus, blood and brain. Conclusions: High myopia induces multiple ocular and potential mental health complications, underscoring the need to develop more effective strategies to improve both physical and emotional well-being of these patients, among which anti-inflammation might possibly represent a promising new target.
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Systemic lupus erythematosus (SLE) is an autoimmune inflammatory tissue disease. In view of the explosive growth in research on SLE, bibliometrics was performed to evaluate the 100 top-cited papers in this realm. We performed the search with terms "systemic lupus erythematosus" the Web of Science Core Collection database on May 3, 2023. Relevant literatures were screened. Data were extracted and analyzed by SPSS. The citations of 100 top-cited SLE studies spanned from 472 to 13,557. Most studies (60 out of 100) were conducted in the United States. Total citation times were positively associated with ACY, which was negatively correlated with the length of time since publication. Approximately half of the studies focused on the underlying mechanisms of SLE. New biologic therapies garnered attention and development. Our findings provide valuable insights into the developments in crucial areas of SLE and shed contributions to future studies.
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Bibliometría , Lupus Eritematoso Sistémico , HumanosRESUMEN
Purpose: To investigate the value of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and ApoA1/B ratio in pathogenic diagnosis of chronic obstructive pulmonary disease (COPD) complicated by acute lower respiratory tract infection, assisting comprehensive disease assessment. Patients and Methods: The study enrolled 171 COPD patients with acute lower respiratory tract infections, 35 COPD patients without acute lower respiratory tract infections, and 41 healthy controls. Correlation analysis and binary logistic regression were used to assess the roles of various factors in COPD with acute lower respiratory tract infections. Receiver operating characteristic (ROC) curves were plotted and area under curves (AUC) values were calculated to evaluate the predictive performance. Results: Infections were the cause of alterations in ApoA1, ApoB and ApoA1/B index. In correlation analysis for pathogenic diagnosis of COPD complicated by acute lower respiratory infections, age, ApoA1, ApoA1/B ratio, lymphocyte count (LYMPH), neutrophil count (NEUT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and endotoxin were significantly correlated. For predicting COPD complicated by acute lower respiratory tract bacterial infection, ApoA1 had the highest area under the ROC curve (AUC: 0.889), with sensitivity and specificity of 82.9% and 83.9%, respectively. The combination of NEUT and ApoA1 improved the prediction efficacy (AUC: 0.909; sensitivity/specificity: 85.1%/85.7%). Conclusion: ApoA1, ApoB, and ApoA1/B ratio are good indicators for predicting pathogens in COPD complicated by acute lower respiratory tract infection, especially ApoA1 which has high predictive value.
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Enfermedad Pulmonar Obstructiva Crónica , Infecciones del Sistema Respiratorio , Humanos , Apolipoproteína A-I , Apolipoproteínas B , Biomarcadores , Estudios Transversales , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Infecciones del Sistema Respiratorio/diagnósticoRESUMEN
AIMS: As a unique iron-dependent non-apoptotic cell death, Ferroptosis is involved in the pathogenesis and development of many human diseases and has become a research hotspot in recent years. However, the regulatory role of ferroptosis in the gut-liver-brain axis has not been elucidated. This paper summarizes the regulatory role of ferroptosis and provides theoretical basis for related research. MATERIALS AND METHODS: We searched PubMed, CNKI and Wed of Science databases on ferroptosis mediated gut-liver-brain axis diseases, summarized the regulatory role of ferroptosis on organ axis, and explained the adverse effects of related regulatory effects on various diseases. KEY FINDINGS: According to our summary, the main way in which ferroptosis mediates the gut-liver-brain axis is oxidative stress, and the key cross-talk of ferroptosis affecting signaling pathway network is Nrf2/HO-1. However, there were no specific marker between different organ axes mediate by ferroptosis. SIGNIFICANCE: Our study illustrates the main ways and key cross-talk of ferroptosis mediating the gut-liver-brain axis, providing a basis for future research.
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Encéfalo , Ferroptosis , Hígado , Estrés Oxidativo , Ferroptosis/fisiología , Humanos , Estrés Oxidativo/fisiología , Encéfalo/metabolismo , Hígado/metabolismo , Hígado/patología , Animales , Eje Cerebro-Intestino/fisiología , Transducción de Señal , Factor 2 Relacionado con NF-E2/metabolismoRESUMEN
BACKGROUND: Immune escape is an important feature of hepatocellular carcinoma (HCC). The overall response rate of immune checkpoint inhibitors (ICIs) in HCC is still limited. Revealing the immune regulation mechanisms and finding new immune targets are expected to further improve the efficacy of immunotherapy. Our study aims to use CRISPR screening mice models to identify potential targets that play a critical role in HCC immune evasion and further explore their value in improving immunotherapy. METHODS: We performed CRISPR screening in two mice models with different immune backgrounds (C57BL/6 and NPG mice) and identified the immunosuppressive gene Gsk3a as a candidate for further investigation. Flow cytometry was used to analyze the impact of Gsk3a on immune cell infiltration and T-cell function. RNA sequencing was used to identify the changes in neutrophil gene expression induced by Gsk3a and alterations in downstream molecules. The therapeutic value of the combination of Gsk3a inhibitors and anti-programmed cell death protein-1 (PD-1) antibody was also explored. RESULTS: Gsk3a, as an immune inhibitory target, significantly promoted tumor growth in immunocompetent mice rather than immune-deficient mice. Gsk3a inhibited cytotoxic T lymphocytes (CTLs) function by inducing neutrophil chemotaxis. Gsk3a promoted self-chemotaxis of neutrophil expression profiles and neutrophil extracellular traps (NETs) formation to block T-cell activity through leucine-rich α-2-glycoprotein 1 (LRG1). A significant synergistic effect was observed when Gsk3a inhibitor was in combination with anti-PD-1 antibody. CONCLUSIONS: We identified a potential HCC immune evasion target, Gsk3a, through CRISPR screening. Gsk3a induces neutrophil recruitment and NETs formation through the intermediate molecule LRG1, leading to the inhibition of CTLs function. Targeting Gsk3a can enhance CTLs function and improve the efficacy of ICIs.
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Carcinoma Hepatocelular , Inmunoterapia , Neoplasias Hepáticas , Animales , Humanos , Ratones , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/terapia , Línea Celular Tumoral , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3/metabolismo , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Evasión Inmune , Inmunoterapia/métodos , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Ratones Endogámicos C57BL , Escape del Tumor/efectos de los fármacosRESUMEN
Myopia is the leading cause of visual impairment in the world. With ever-increasing prevalence in these years, it creates an alarming global epidemic. In addition to the difficulty in seeing distant objects, myopia also increases the risk of cataract and advances its onset, greatly affecting the productivity of myopes of working age. Cataract management in myopic eyes, especially highly myopic eyes is originally more complicated than that in normal eyes, whereas the growing population of cataract with myopia, increasing popularity of corneal and lens based refractive surgery, and rising demand for spectacle independence after cataract surgery all further pose unprecedented challenges to ophthalmologists. Previous history of corneal refractive surgery and existence of implantable collamer lens will both affect the accuracy of biometry including measurement of corneal curvature and axial length before cataract surgery, which may result in larger intraocular lens (IOL) power prediction errors and a compromise in the surgical outcome especially in a refractive cataract surgery. A prudent choice of formula for cataract patients with different characteristics is essential in improving this condition. Besides, the characteristics of myopic eyes might affect the long-term stability of IOL, which is important for the maintenance of visual outcomes especially after the implantation of premium IOLs, thus a proper selection of IOL accordingly is crucial. In this mini-review, we provide an overview of the impact of myopia epidemic on treatment for cataract and to discuss new challenges that surgeons may encounter in the foreseeable future when planning refractive cataract surgery for myopic patients.
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For the purpose of searching for efficient photocatalysts to deal with recalcitrant organic micropollutants in wastewater, here an in-situ supramolecule self-assembly-thermal polymerization strategy is developed to prepare a series of porous cyclopentadiene (CPD) unit-incorporated g-C3N4 ultrathin nanosheets (CCPD-g-C3N4). The CCPD-g-C3N4 demonstrate CPD unit doping level-dependent and remarkably enhanced visible-light photocatalytic oxidation efficiency towards two organic micropollutants, acetaminophen and methylparaben, in which the optimized CCPD-g-C3N4-2 shows 6.1 and 3.5 times higher acetaminophen and methylparaben degradation rate than bulk g-C3N4; moreover, CCPD-g-C3N4-2 is still robust and efficient in the treatment of five mixed organic micropollutants in pharmaceutical wastewater, and the satisfactory micropollutant removal efficiency is obtained in a wide pH window and the presence of high concentrations of inorganic anions and cations as well as dissolved organic matters. Theoretical calculation combined with experimental test reveal that CCPD-g-C3N4 can significantly reduce ecological risk of the target pollutant after the photocatalytic degradation reaction. Such enhanced photocatalytic oxidation efficiency is dominated by the accelerated charge carrier separation dynamics and extended visible-light response region due to the incorporation of CPD units, which finally lead to the generation of abundant reactive oxygen species to degrade and mineralize target micropollutants efficiently.
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High-myopic cataract (HMC) is a complex cataract with earlier onset and more rapid progress than age-related cataract (ARC). Circular RNAs (circRNAs) have been implicated in many diseases. However, their involvement in HMC remain largely unexplored. To investigate the role of dysregulated circRNAs in HMC, lens epithelium samples from 24 HMC and 24 ARC patients were used for whole transcriptome sequencing. Compared with ARC, HMC had 3687 uniquely expressed circRNAs and 1163 significantly differentially expressed circRNAs (DEcRs) (|log2FC| > 1, p < 0.05). A putative circRNA-miRNA-mRNA network was constructed based on correlation analysis. We validated the differential expression of 3 DEcRs by quantitative polymerase chain reaction (qPCR) using different sets of samples. We further investigated the role of circAFF1 in cultured lens epithelial cells (LECs) and found that the overexpression of circAFF1 promoted cell proliferation, migration and inhibited apoptosis. We also showed that circAFF1 upregulated Tropomyosin 1 (TPM1) expression by sponging miR-760, which was consistent with the network prediction. Collectively, our study suggested the involvement of circRNAs in the pathogenesis of HMC and provide a resource for further study on this topic.
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The outcomes of toric intraocular lens (IOL) implantation in correcting asymmetric bowtie corneal astigmatism remain uncertain. The accurate measurement of corneal astigmatism is essential for surgical planning. In this prospective cohort study, patients with asymmetric or symmetric bowtie corneal astigmatism who underwent toric IOL implantation were recruited. Preoperative corneal astigmatism was measured with an IOLMaster and Pentacam (including the simulated keratometry (SimK), total corneal refractive power (TCRP), and wavefront aberration (WFA) modes). At 3 months after surgery, the refractive outcomes and residual astigmatic refractive errors were compared with patients with symmetric bowtie astigmatism. The prediction errors (the differences between the calculated actual corneal astigmatism and the measured corneal astigmatism) were compared among the different measurement modes in the asymmetric group. There were no differences in residual astigmatism between the asymmetric and symmetric groups. However, the mean absolute residual astigmatic refractive error was greater in the asymmetric group than in the symmetric group (0.72 ± 0.42 D vs. 0.53 ± 0.24 D, p = 0.043). In the asymmetric group, the mean absolute prediction errors for the IOLMaster, SimK, TCRP and WFA modes were 0.53 ± 0.40, 0.56 ± 0.47, 0.68 ± 0.52, and 0.43 ± 0.40 D, respectively. The Pentacam WFA mode was the most accurate mode (p < 0.05). The absolute prediction error of the WFA mode was positively correlated with the total corneal irregular astigmatism higher-order aberrations and coma (r = 0.416 and r = 0.473, respectively; both p < 0.05). Our study suggests toric IOL implantation effectively corrected asymmetric bowtie corneal astigmatism. The Pentacam WFA mode may be the most accurate measurement mode, although its accuracy decreased as asymmetry increased.
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High myopia is a leading cause of blindness worldwide. It may lead to emotional defects that rely closely on the link between visual sensation and the central nervous system. However, the extent of the defects and its underlying mechanism remain unknown. Here, we report that highly myopic patients exhibit greater anxiety, accompanied by higher CC chemokine ligand 2 (CCL2) and monocyte levels in the blood. Similar findings are found in the mouse model of high myopia. Mechanistic evaluations using GFP-positive bone marrow chimeric mice, parabiotic mouse model, enhanced magnetic resonance imaging, etc., show that highly myopic visual stimulation increases CCL2 expression in eyes, aggravates monocyte/macrophage infiltration into eyes and brains, and disrupts blood-ocular barrier and blood-brain barrier of mice. Conversely, Ccl2-deficient highly myopic mice exhibit attenuated ocular and brain infiltration of monocytes/macrophages, reduced disruption of the blood-ocular barrier and blood-brain barrier, and less anxiety. Substantial alleviation of high myopia-related anxiety can also be achieved with the administration of CCL2-neutralizing antibodies. Our results establish the association between high myopia and anxiety, and implicate the CCL2-mediated inflammatory pathogenesis as an underlying mechanism.
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The therapeutic efficacy of whole tumor cell vaccines (TCVs) is modest, which has delayed their translation into personalized immunotherapies in the clinic. Here, we develop a TCV platform based on photothermal nanoparticle-loaded tumor cells, which can be rationally applied to diverse tumor types to achieve on-demand boost of anti-tumor immune responses for inhibiting tumor growth. During the fabrication process, mild photothermal heating by near-infrared (NIR) laser irradiation induces the nanoparticle-bearing tumor cells to express heat shock proteins as endogenous adjuvants. After a single vaccination at the back of tumor-bearing mice, non-invasive NIR laser irradiation further induces mild hyperthermia at vaccination site, which promotes the recruitment, activation, and antigen presentation by dendritic cells. Using an indicator we term fluctuation of tumor growth rate, we determine appropriate irradiation regimens (including optimized irradiation intervals and times). This TCV platform enables on-demand NIR manipulation of immune responses, and we demonstrate potent therapeutic efficacy against six murine models that mimick a range of clinical scenarios, including a model based on humanized mice and patient-derived tumor xenografts.