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1.
J Virol ; : e0112824, 2024 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-39480083

RESUMO

After the ejection of viral DNA into the host cytoplasm, the temperate bacteriophage (phage) lambda integrates a cascade of expressions from various regulatory genes, coupled with DNA replication, to commit to a decision between lysis and lysogeny. Higher multiplicity of infection (MOI) greatly shifts the decision toward the lysogenic pathway. However, how the phage separates the MOI from replicated viral DNA during lysis-lysogeny decision-making is unclear. To quantitatively understand the role of viral DNA replication, we constructed a reporter system facilitating the visualization of individual copies of phage DNA throughout the phage life cycle, along with the lysis-lysogeny reporters. We showed that intracellular viral DNA diverges between the lytic and lysogenic pathways from the early phase of the infection cycle, mostly due to the synchronization and success of DNA injection, as well as the competition for replication resources, rather than the replication rate. Strikingly, we observed two distinct replication patterns during lysogenization and surprisingly heterogeneous integration kinetics, which advances our understanding of temperate phage life cycles. We revealed that the weak repression function of Cro is critical for an optimal replication rate and plays a crucial role in establishing stable lysogens. IMPORTANCE: Temperate bacteriophages, such as lambda, incorporate environmental cues including host abundance and nutrient conditions to make optimal decisions between propagation and dormancy. A higher phage-to-host ratio or multiplicity of infection (MOI) during λ infection strongly biases toward lysogeny. However, a comprehensive understanding of this decision-making process and the impact of phage replication prior to the decision is yet to be achieved. Here, we used fluorescence microscopy to quantitatively track the spatiotemporal progression of viral DNA replication in individual cells with different cell fates. The implementation of this fluorescent reporter system and quantitative analysis workflow opens a new avenue for future studies to delve deeper into various types of virus-host interactions at a high resolution.

2.
Sci Total Environ ; 941: 173724, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38844218

RESUMO

The frost damage behavior of recycled aggregates concrete (RAC) in a cold region is inherently more complex due to the incorporation of recycled coarse aggregate (RCA). In real-world service environments, the combined effects of mechanical loading and environmental conditions further make RAC's damage mechanism more intricate. This study explores the impact of uniaxial compressive loading (at 0.1fc, 0.3fc, and 0.5fc, respectively), freeze-thaw cycles, and chloride penetration on the relative dynamic elastic modulus (RDEM), mass transport properties, and microstructure of RAC with varying RCA replacement ratios. The results indicate that specimens loaded at 0.3fc exhibit enhanced frost resistance, with reduced water absorption and chloride ion content. Additionally, a damage model is developed to quantify the effects of mechanical loading, freeze-thaw cycles, and chloride penetration on RDEM degradation. The investigation using X-ray computed tomography (X-CT), mercury intrusion porosimetry (MIP), and scanning electron microscopy (SEM) techniques reveals that as compressive stress levels increase, the microstructural density and porosity of RAC initially decrease before increasing. Moreover, the RDEM of RAC decreases with decreasing pore sphericity. Compared to the R100-S55 samples, the pore sphericity of R100-S55-0.5fc samples increased by 60.4 % in the range of 0.4-0.5, resulting in a decrease of approximately 17.72 % in the RDEM. Furthermore, the initial sorptivity of frost-damaged RAC exhibits a significant linear relationship with porosity. Overall, this study elucidates the evolving trends of mass transport properties and microstructure in RAC under loading and freeze-thaw conditions, laying a theoretical groundwork for the widespread application of RCA.

3.
Sci Adv ; 10(18): eadl4450, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701202

RESUMO

Caulobacter crescentus Tad (tight adherence) pili, part of the type IV pili family, are crucial for mechanosensing, surface adherence, bacteriophage (phage) adsorption, and cell-cycle regulation. Unlike other type IV pilins, Tad pilins lack the typical globular ß sheet domain responsible for pilus assembly and phage binding. The mechanisms of Tad pilus assembly and its interaction with phage ΦCb5 have been elusive. Using cryo-electron microscopy, we unveiled the Tad pilus assembly mechanism, featuring a unique network of hydrogen bonds at its core. We then identified the Tad pilus binding to the ΦCb5 maturation protein (Mat) through its ß region. Notably, the amino terminus of ΦCb5 Mat is exposed outside the capsid and phage/pilus interface, enabling the attachment of fluorescent and affinity tags. These engineered ΦCb5 virions can be efficiently assembled and purified in Escherichia coli, maintaining infectivity against C. crescentus, which presents promising applications, including RNA delivery and phage display.


Assuntos
Bacteriófagos , Caulobacter crescentus , Fímbrias Bacterianas , Caulobacter crescentus/citologia , Caulobacter crescentus/metabolismo , Caulobacter crescentus/virologia , Fímbrias Bacterianas/metabolismo , Fímbrias Bacterianas/ultraestrutura , Microscopia Crioeletrônica , Bacteriófagos/química , Bacteriófagos/metabolismo , Proteínas de Fímbrias , Escherichia coli , Proteínas Virais/química , Proteínas Virais/metabolismo
4.
Science ; 384(6691): eadl0635, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38574145

RESUMO

The retractile type IV pilus (T4P) is important for virulence of the opportunistic human pathogen Pseudomonas aeruginosa. The single-stranded RNA (ssRNA) phage PP7 binds to T4P and is brought to the cell surface through pilus retraction. Using fluorescence microscopy, we discovered that PP7 detaches T4P, which impairs cell motility and restricts the pathogen's virulence. Using cryo-electron microscopy, mutagenesis, optical trapping, and Langevin dynamics simulation, we resolved the structure of PP7, T4P, and the PP7/T4P complex and showed that T4P detachment is driven by the affinity between the phage maturation protein and its bound pilin, plus the pilus retraction force and speed, and pilus bending. Pilus detachment may be widespread among other ssRNA phages and their retractile pilus systems and offers new prospects for antibacterial prophylaxis and therapeutics.


Assuntos
Fímbrias Bacterianas , Fagos de Pseudomonas , Pseudomonas aeruginosa , Vírus de RNA , Internalização do Vírus , Humanos , Microscopia Crioeletrônica , Proteínas de Fímbrias/genética , Proteínas de Fímbrias/metabolismo , Fímbrias Bacterianas/virologia , Pseudomonas aeruginosa/patogenicidade , Pseudomonas aeruginosa/virologia , Vírus de RNA/química , Vírus de RNA/fisiologia , Fagos de Pseudomonas/química , Fagos de Pseudomonas/fisiologia , Proteínas Virais/metabolismo
5.
RSC Adv ; 14(15): 10255-10261, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38549794

RESUMO

Fluorescence imaging of organelles at the cellular level is important for studying biological processes. The development of a highly emissive fluorescent probe that operates under a suitable excitation light source is a key step in high-quality fluorescence imaging. For long-term, high-fidelity fluorescence imaging of mitochondria-related cellular processes using two-photon microscopy and stimulated emission depletion microscopy, we developed a new benzocoumarin-based cationic fluorescent probe (BS-CN) that is far-red emitting, water-soluble, photostable, and very bright in cells. BS-CN showed a remarkably high quantum yield of 0.35 and a large two-photon excited fluorescence action cross-section of 76 GM, enabling the long-term tracking of mitochondria in live cells. In addition, BS-CN exhibited a certain affinity for RNA and stained nucleoli in fixed cells. A comparative assessment of the photophysical properties and bioimaging performance of benzo[h]coumarin-pyridinium and the structurally similar styryl-pyridinium (BS-MN) clearly indicated the importance of structural rigidity for fluorescence efficiency.

6.
Nat Commun ; 15(1): 2746, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553443

RESUMO

Acinetobacters pose a significant threat to human health, especially those with weakened immune systems. Type IV pili of acinetobacters play crucial roles in virulence and antibiotic resistance. Single-stranded RNA bacteriophages target the bacterial retractile pili, including type IV. Our study delves into the interaction between Acinetobacter phage AP205 and type IV pili. Using cryo-electron microscopy, we solve structures of the AP205 virion with an asymmetric dimer of maturation proteins, the native Acinetobacter type IV pili bearing a distinct post-translational pilin cleavage, and the pili-bound AP205 showing its maturation proteins adapted to pilin modifications, allowing each phage to bind to one or two pili. Leveraging these results, we develop a 20-kilodalton AP205-derived protein scaffold targeting type IV pili in situ, with potential for research and diagnostics.


Assuntos
Acinetobacter , Bacteriófagos , Vírus de RNA , Humanos , Proteínas de Fímbrias/metabolismo , Acinetobacter/metabolismo , Microscopia Crioeletrônica , Fímbrias Bacterianas/metabolismo , Bacteriófagos/genética , Bacteriófagos/metabolismo
7.
Colloids Surf B Biointerfaces ; 236: 113772, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38394858

RESUMO

Peptides are recognized as highly effective and safe bioactive ingredients. However, t their practical application is limited and hampered by harsh conditions for practical drug delivery. Hence, a novel peptide nanocarrier of copper peptide (GHK-Cu) encapsulation developed by liposome technology combined with the classical Chinese concept of rigidity and flexibility. Different polyols were selected as modification ligands for phospholipid bilayers to construct a nano drug-carrying system with high loading rate, good stability and biocompatibility. In vitro, this complex not only significantly retarded the release ability of copper peptides, but also enabled copper peptides to be effectively resistant to enzymatic degradation. Furthermore, cellular experiments showed that this system mainly regulates Nrf2, SIRT1, and PEG2/COX-2-related signaling pathways, thus effectively counteracting cellular inflammation, senescence, and apoptosis from oxidative damage. Interestingly, a green, non-toxic, efficient and convenient antioxidant system was developed for the prevention and deceleration of skin aging.


Assuntos
Antioxidantes , Cobre , Antioxidantes/farmacologia , Pele , Peptídeos/farmacologia , Anti-Inflamatórios/farmacologia
8.
J Nanobiotechnology ; 21(1): 327, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37684667

RESUMO

BACKGROUND: Several common retinal diseases that cause blindness are characterised by pathological neovascularisation accompanied by inflammation and neurodegeneration, including retinopathy of prematurity (ROP), diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). The current treatment strategies for these diseases have limited benefits. Thus, safer and more effective alternative approaches are required. In this study, we loaded small extracellular vesicles (sEVs) derived from mesenchymal stem cell (MSC) with pigment epithelium-derived factor (PEDF), and tested the therapeutic effect of PEDF-loaded sEVs (PEDF-sEVs) using an oxygen induced retinopathy (OIR) mouse model, aiming to establish a new therapy strategy for the treatment of retinal pathological angiogenesis. RESULTS: We formulated PEDF-loaded sEVs (PEDF-sEVs) containing high concentrations of PEDF and evaluated their effects through in vivo and in vitro experiments. In OIR mice, PEDF-sEVs showed significantly better effects on retinal avascular areas, inflammation, and neuronal degeneration compared with the anti-vascular endothelial growth factor (VEGF) drug, which may indicate a possible advantage of PEDF-sEVs over anti-VEGF drugs in the treatment of pathological neovascularisation. In vitro, PEDF-sEVs greatly inhibited endothelial cell (EC) proliferation, migration, and tube formation by suppressing the VEGF-induced phosphorylation of extracellular signal-regulated kinase (ERK) and AKT (also known as Protein Kinase B). All experiments and analyses were performed in triplicate. PEDF-sEVs were more effective than PEDF or sEVs alone, both in vitro and in vivo. Furthermore, to determine the distribution of PEDF-sEVs, we used DiD-labelled sEVs and FITC-labelled PEDF to track the sEVs and PEDF, respectively. We found that PEDF-sEVs effectively reduced the degradation of PEDF. CONCLUSIONS: Loading PEDF on sEVs effectively enhanced the anti-angiogenic, anti-inflammatory, and neuroprotective effects of PEDF by increasing the stability and penetrability. These results suggest a potential role for PEDF-sEVs in retinal pathological neovascularisation.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Doenças Retinianas , Animais , Camundongos , Oxigênio , Inflamação , Neovascularização Patológica
9.
Int J Mol Sci ; 24(18)2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37762361

RESUMO

The flhDC operon of Escherichia coli encodes a transcription factor that initiates flagella synthesis, elevates flagella construction and enhances cell motility, which all are energetically costly and highly regulated processes. In this study, we found that overexpression of flhDC genes from a strong regulatable pN15E6 plasmid could inhibit the growth of E. coli host cells and even eventually cause death. We used transcriptome analysis to investigate the mechanism of flhDC overexpression lethal to host bacteria. The results showed that a total of 568 differentially expressed genes (DEGs), including 378 up-regulated genes and 190 down-regulated genes were detected when the flhDC genes were over-expressed. Functional enrichment analysis results showed that the DEGs are related to a series of crucial biomolecular processes, including flagella synthesis, oxidative phosphorylation and pentose phosphate pathways, etc. We then examined, using RT-qPCR, the expression of key genes of the oxidative phosphorylation pathway at different time points after induction. Results showed that their expression increased in the early stage and decreased afterward, which was suggested to be the result of feedback on the overproduction of ROS, a strong side effect product of the elevated oxidative phosphorylation process. To further verify the level of ROS output, flhDC over-expressed bacteria cells were stained with DCHF-DA and a fluorescence signal was detected using flow cytometry. Results showed that the level of ROS output was higher in cells with over-expressed flhDC than in normal controls. Besides, we found upregulation of other genes (recN and zwf) that respond to ROS damage. This leads to the conclusion that the bacterial death led by the overexpression of flhDC genes is caused by damage from ROS overproduction, which leaked from the oxidative phosphorylation pathway.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Transativadores/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Genes Reguladores , Perfilação da Expressão Gênica , Flagelos/metabolismo , Regulação Bacteriana da Expressão Gênica , Proteínas de Bactérias/metabolismo
10.
Pathogens ; 12(9)2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37764880

RESUMO

Hepatitis E virus (HEV) is a significant public health concern worldwide. Pregnant women are at high risk of severe HEV infection. Various adverse outcomes in pregnant women related to HEV infection have been well documented in low-income and middle-income countries with poor sanitation. However, previous studies have provided inconsistent conclusions regarding the effects of HEV infection on the health of pregnant women and their infants in developed countries and contemporary China. In China, previous studies on HEV in pregnant women mainly focused on anti-HEV IgM and/or anti-HEV IgG. In this study, 4244 pregnant women were retrospectively analyzed for HEV-related markers. The positive rates of HEV antigen, HEV RNA, anti-HEV IgM, and anti-HEV IgG were 0.28%, 0.54%, 0.35%, and 10.49%, respectively. Among the 467 pregnant women who tested positive for at least one HEV-related marker, 92.93% (434) were positive for anti-HEV IgG only and 0.21% (1) were positive for HEV antigen, anti-HEV IgM, and anti-HEV IgG. Although the prevalence of anti-HEV IgG significantly increased with age, the prevalence of anti-HEV IgM, HEV RNA, and HEV antigen did not differ among pregnant women of different ages. Thirty-three pregnant women were positive for at least one of anti-HEV IgM, HEV antigen, and HEV RNA, and these individuals were recently or currently infected with HEV. None of the 33 pregnant women exhibited obvious clinical symptoms. Of the 33 pregnant women, 39.39% (13) experienced adverse fetal outcomes, including preterm birth, fetal distress, and low birth weight, the incidence of which was significantly higher than in pregnant women who were not recently or currently infected with HEV. These findings suggest that maternal HEV infection may impact the health of fetuses; thus, these results may contribute to the development of appropriate public health interventions for this population.

11.
BMC Ophthalmol ; 23(1): 361, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37599349

RESUMO

BACKGROUND: To develop a deep learning (DL) model based on preoperative optical coherence tomography (OCT) training to automatically predict the 6-month postoperative visual outcomes in patients with idiopathic epiretinal membrane (iERM). METHODS: In this retrospective cohort study, a total of 442 eyes (5304 images in total) were enrolled for the development of the DL and multimodal deep fusion network (MDFN) models. All eyes were randomized into a training dataset with 265 eyes (60.0%), a validation dataset with 89 eyes (20.1%), and an internal testing dataset with the remaining 88 eyes (19.9%). The input variables for prediction consisted of macular OCT images and diverse clinical data. Inception-Resnet-v2 network was utilized to estimate the 6-month postoperative best-corrected visual acuity (BCVA). Concurrently, a regression model was developed using the clinical data and OCT parameters in the training data set for predicting postoperative BCVA. The reliability of the models was subsequently evaluated using the testing dataset. RESULTS: The prediction DL algorithm exhibited a mean absolute error (MAE) of 0.070 logMAR and root mean square error (RMSE) of 0.11 logMAR in the testing dataset. The DL model demonstrated a robust promising performance with R2 = 0.80, notably superior to R2 = 0.49 of the regression model. The percentages of BCVA prediction errors within ± 0.20 logMAR amounted to 94.32% in the testing dataset. CONCLUSIONS: The OCT-based DL model demonstrated sensitivity and accuracy in predicting postoperative BCVA in iERM patients. This innovative DL model exhibits substantial potential for integration into surgical planning protocols.


Assuntos
Aprendizado Profundo , Membrana Epirretiniana , Humanos , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/cirurgia , Olho , Reprodutibilidade dos Testes , Estudos Retrospectivos
12.
Front Immunol ; 14: 1183859, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37404820

RESUMO

Chronic hepatitis E virus (HEV) infection occurs mainly in immunosuppressed populations. We describe an investigation of chronic HEV infection of genotype 3a in an individual without evidence for immune deficiency who presented hepatitis with significant HEV viremia and viral shedding. We monitored HEV RNA in plasma and stools, and assessed anti-HEV specific immune responses. The patient was without apparent immunodeficiency based on quantified results of white blood cell, lymphocyte, neutrophilic granulocyte, CD3+ T cell, CD4+ T cell, and CD8+ T cell counts and CD4/CD8 ratio, as well as total serum IgG, IgM, and IgA, which were in the normal range. Despite HEV specific cellular response and strong humoral immunity being observed, viral shedding persisted up to 109 IU/mL. After treatment with ribavirin combined with interferon, the indicators of liver function in the patient returned to normal, accompanied by complete suppression and clearance of HEV. These results indicate that HEV chronicity can also occur in individuals without evidence of immunodeficiency.


Assuntos
Vírus da Hepatite E , Hepatite E , Síndromes de Imunodeficiência , Humanos , Hepatite E/diagnóstico , Hepatite E/tratamento farmacológico , Vírus da Hepatite E/genética , Linfócitos T CD8-Positivos , Relação CD4-CD8 , Linfócitos T CD4-Positivos , Síndromes de Imunodeficiência/complicações
13.
Front Endocrinol (Lausanne) ; 14: 1116136, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37139333

RESUMO

Retinal neovascular, neurodegenerative, and inflammatory diseases represented by diabetic retinopathy are the main types of blinding eye disorders that continually cause the increased burden worldwide. Pigment epithelium-derived factor (PEDF) is an endogenous factor with multiple effects including neurotrophic activity, anti-angiogenesis, anti-tumorigenesis, and anti-inflammatory activity. PEDF activity depends on the interaction with the proteins on the cell surface. At present, seven independent receptors, including adipose triglyceride lipase, laminin receptor, lipoprotein receptor-related protein, plexin domain-containing 1, plexin domain-containing 2, F1-ATP synthase, and vascular endothelial growth factor receptor 2, have been demonstrated and confirmed to be high affinity receptors for PEDF. Understanding the interactions between PEDF and PEDF receptors, their roles in normal cellular metabolism and the response the initiate in disease will be accommodating for elucidating the ways in which inflammation, angiogenesis, and neurodegeneration exacerbate disease pathology. In this review, we firstly introduce PEDF receptors comprehensively, focusing particularly on their expression pattern, ligands, related diseases, and signal transduction pathways, respectively. We also discuss the interactive ways of PEDF and receptors to expand the prospective understanding of PEDF receptors in the diagnosis and treatment of retinal diseases.


Assuntos
Doenças Retinianas , Serpinas , Humanos , Proteínas do Olho/metabolismo , Estudos Prospectivos , Doenças Retinianas/tratamento farmacológico , Serpinas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
14.
Materials (Basel) ; 16(10)2023 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-37241498

RESUMO

In order to investigate the seismic performance of a precast shear wall with a new bundled connection under a high axial compressive ratio, three full-scale precast short-limb shear walls and one full-scale cast-in-place short-limb shear wall were manufactured and loaded under cycling loading. The results show that the precast short-limb shear wall with a new bundled connection has a similar damage mode and crack evolution to the cast-in-place shear wall. Under the same axial compression ratio, the bearing capacity, ductility coefficient, stiffness, and energy dissipation capacity of the precast short-limb shear wall were better, and its seismic performance is related to the axial compression ratio, with the increase of the axial compression ratio. The embedded bellows can limit the cracking of the wall but have little effect on the bearing capacity and stiffness degradation performance. Furthermore, the bond between the vertical steel bars extending into the preformed holes and grouting materials was demonstrated to be reliable, thus ensuring the integrity of the precast specimens.

15.
Nucleic Acids Res ; 51(13): 6944-6965, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37246647

RESUMO

U-insertion/deletion (U-indel) RNA editing in trypanosome mitochondria is directed by guide RNAs (gRNAs). This editing may developmentally control respiration in bloodstream forms (BSF) and insect procyclic forms (PCF). Holo-editosomes include the accessory RNA Editing Substrate Binding Complex (RESC) and RNA Editing Helicase 2 Complex (REH2C), but the specific proteins controlling differential editing remain unknown. Also, RNA editing appears highly error prone because most U-indels do not match the canonical pattern. However, despite extensive non-canonical editing of unknown functions, accurate canonical editing is required for normal cell growth. In PCF, REH2C controls editing fidelity in RESC-bound mRNAs. Here, we report that KREH2, a REH2C-associated helicase, developmentally controls programmed non-canonical editing, including an abundant 3' element in ATPase subunit 6 (A6) mRNA. The 3' element sequence is directed by a proposed novel regulatory gRNA. In PCF, KREH2 RNAi-knockdown up-regulates the 3' element, which establishes a stable structure hindering element removal by canonical initiator-gRNA-directed editing. In BSF, KREH2-knockdown does not up-regulate the 3' element but reduces its high abundance. Thus, KREH2 differentially controls extensive non-canonical editing and associated RNA structure via a novel regulatory gRNA, potentially hijacking factors as a 'molecular sponge'. Furthermore, this gRNA is bifunctional, serving in canonical CR4 mRNA editing whilst installing a structural element in A6 mRNA.


Assuntos
Trypanosoma brucei brucei , Trypanosoma , RNA Mensageiro/metabolismo , RNA Helicases/genética , RNA Helicases/metabolismo , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/metabolismo , Trypanosoma/genética , RNA/genética , RNA de Protozoário/genética , RNA de Protozoário/metabolismo
16.
Front Endocrinol (Lausanne) ; 14: 1098638, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37206443

RESUMO

Objective: Our aim was to evaluate associations of different risk factors with odds of diabetic retinopathy (DR) diagnosis and retinal neurodegeneration represented by macular ganglion cell-inner plexiform layer (mGCIPL). Methods: This cross-sectional study analyzed data from individuals aged over 50 years examined between June 2020 and February 2022 in the community-based Beichen Eye Study on ocular diseases. Baseline characteristics included demographic data, cardiometabolic risk factors, laboratory findings, and medications at enrollment. Retinal thickness in both eyes of all participants was measured automatically via optical coherence tomography. Risk factors associated with DR status were investigated using multivariable logistic regression. Multivariable linear regression analysis was performed to explore associations of potential risk factors with mGCIPL thickness. Results: Among the 5037 included participants with a mean (standard deviation, SD) age of 62.6 (6.7) years (3258 women [64.6%]), 4018 (79.8%) were control individuals, 835 (16.6%) were diabetic individuals with no DR, and 184 (3.7%) were diabetic individuals with DR. The risk factors significantly associated with DR status were family history of diabetes (odds ratio [OR], 4.09 [95% CI, 2.44-6.85]), fasting plasma glucose (OR, 5.88 [95% CI, 4.66-7.43]), and statins (OR, 2.13 [95% CI, 1.03-4.43]) relative to the control individuals. Compared with the no DR, diabetes duration (OR, 1.17 [95% CI, 1.13-1.22]), hypertension (OR, 1.60 [95% CI, 1.26-2.45]), and glycated hemoglobin A1C (HbA1c) (OR, 1.27 [95% CI, 1.00-1.59]) were significantly correlated with DR status. Furthermore, age (adjusted ß = -0.19 [95% CI, -0.25 to -0.13] µm; P < 0.001), cardiovascular events (adjusted ß = -0.95 [95% CI, -1.78 to -0.12] µm; P = 0.03), and axial length (adjusted ß = -0.82 [95% CI, -1.29 to -0.35] µm; P = 0.001) were associated with mGCIPL thinning in diabetic individuals with no DR. Conclusion: Multiple risk factors were associated with higher odds of DR development and lower mGCIPL thickness in our study. Risk factors affecting DR status varied among the different study populations. Age, cardiovascular events, and axial length were identified as potential risk factors for consideration in relation to retinal neurodegeneration in diabetic patients.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Humanos , Feminino , Pessoa de Meia-Idade , Retinopatia Diabética/etiologia , Retinopatia Diabética/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Estudos Transversais , Retina , Fatores de Risco
17.
Int J Mol Sci ; 24(4)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36834980

RESUMO

Caffeic acid phenylethyl ester (CAPE) is an antioxidative agent originally derived from propolis. Oxidative stress is a significant pathogenic factor in most retinal diseases. Our previous study revealed that CAPE suppresses mitochondrial ROS production in ARPE-19 cells by regulating UCP2. The present study explores the ability of CAPE to provide longer-term protection to RPE cells and the underlying signal pathways involved. ARPE-19 cells were given CAPE pretreatment followed by t-BHP stimulation. We used in situ live cell staining with CellROX and MitoSOX to measure ROS accumulation; Annexin V-FITC/PI assay to evaluate cell apoptosis; ZO-1 immunostaining to observe tight junction integrity in the cells; RNA-seq to analyze changes in gene expression; q-PCR to validate the RNA-seq data; and Western Blot to examine MAPK signal pathway activation. CAPE significantly reduced both cellular and mitochondria ROS overproduction, restored the loss of ZO-1 expression, and inhibited apoptosis induced by t-BHP stimulation. We also demonstrated that CAPE reverses the overexpression of immediate early genes (IEGs) and activation of the p38-MAPK/CREB signal pathway. Either genetic or chemical deletion of UCP2 largely abolished the protective effects of CAPE. CAPE restrained ROS generation and preserved the tight junction structure of ARPE-19 cells against oxidative stress-induced apoptosis. These effects were mediated via UCP2 regulation of p38/MAPK-CREB-IEGs pathway.


Assuntos
Ácidos Cafeicos , Estresse Oxidativo , Álcool Feniletílico , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Ácidos Cafeicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Humanos
18.
Opt Express ; 31(2): 2846-2859, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36785289

RESUMO

We previously designed a dual-axis piezoelectric MEMS mirror with a low crosstalk gimbal structure, which is utilized as the key device for further research for laser beam scanning. This paper mainly focuses on studying the Lissajous scanning resolution of this MEMS mirror with frequency ratio and phase modulation. For accurately evaluating the scanning resolution, the center angular resolution of Lissajous scanning is redefined by theoretical calculation and verified with experimental measurement. Meanwhile, the scanning nonlinearity of MEMS mirror is studied carefully. Finally, the MEMS mirror works at the state of pseudo-resonance, and the center angular resolution better than 0.16° (H) × 0.03° (V) is achieved at a scanning Field of view (FoV) of 35.0° (H) × 16.5° (V). Moreover, a feasible route of resolution adjustable Lissajous scanning is provided by optimization of frequency ratio and phase modulation, which is helpful for high definition and high frame rate (HDHF) laser scanning imaging with the dual-axis mirror.

19.
Langmuir ; 39(5): 2063-2072, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36701637

RESUMO

In recent years, selective metallization on polymer surfaces has attracted considerable attention due to its excellent properties and wide applications. This paper reports that copper phosphate (Cu3(PO4)2) or nickel phosphate (Ni3(PO4)2) was selected as laser-active material to successfully fabricate metallic patterns on ordinary polymer substrates by laser direct activation and electroless plating. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) were utilized to characterize the interaction mechanism between a nanosecond-pulsed laser (355 and 1064 nm wavelengths) and Cu3(PO4)2 or Ni3(PO4)2. It was found that after 355 or 1064 nm laser activation with appropriate parameters, Cu+ was generated from Cu3(PO4)2, and NiO was generated from Ni3(PO4)2. At the same time, Cu+ or NiO adsorbed on the porous sponge-like microstructure of modified polycarbonate (PC), respectively, and acted as catalytic active centers to realize selective copper deposition in the laser-activated zone. Furthermore, the obtained copper layers were confirmed to possess good selectivity, electrical conductivity, and high adhesion strength (the highest grade of 5B). Moreover, from comparisons of Cu3(PO4)2 with Ni3(PO4)2 and of 355 nm laser activation with 1064 nm laser activation, the 1064 nm laser activation of Cu3(PO4)2 produced the most catalytic seeds (Cu+) and had the best catalytic effect.

20.
J Vis Exp ; (202)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38163268

RESUMO

Unilateral biportal endoscopy (UBE) is a minimally invasive spinal surgery technique increasingly employed in treating degenerative lumbar diseases, such as lumbar disc herniation, lumbar spinal stenosis, and spondylolisthesis. In UBE, two independent yet interconnected surgical channels are established-one for the endoscope and the other for surgical instruments-providing a broad and clear surgical field of view. UBE offers several advantages over traditional open surgery, including reduced tissue damage, shorter hospital stays, and faster recovery times. Additionally, it combines the benefits of microscopic surgery and interlaminar endoscopy, enhancing flexibility, accuracy, and reliability during the procedure. The learning curve for UBE is shorter than that for transforaminal endoscopy, as the surgical processes closely resemble those of conventional open surgery. Despite its favorable clinical outcomes, such as reduced blood loss and shorter hospitalization, UBE carries potential complications, including epidural hematoma, dural injury, and compression of the outlet nerve root. To mitigate these risks, it is crucial to ensure appropriate patient selection, apply the correct surgical technique, and engage in careful postoperative monitoring. This article provides a detailed summary of the step-by-step surgical techniques used in UBE for treating lumbar disc herniation. It serves as a comprehensive guide to enhance practitioners' understanding of UBE. The presentation also underscores the importance of rigorous training and expertise to ensure optimal patient outcomes.


Assuntos
Deslocamento do Disco Intervertebral , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Reprodutibilidade dos Testes , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Endoscopia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos , Endoscopia Gastrointestinal , Resultado do Tratamento , Estudos Retrospectivos
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