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1.
J Asthma ; : 1-14, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38478043

RESUMO

Objective: In a previous study we have shown that, in the presence of interleukin (IL)-33, repeated, per-nasal challenge of murine airways with Streptococcus pneumoniae (S. pneumoniae) organisms induces human asthma-like airways inflammation. It is not clear, however, whether this effect is unique or manifest in response to other common respiratory pathogens.Methods: To explore this, airways of BALB/c mice were repeatedly challenged per-nasally with formaldehyde-inactivated bacterial bodies in the presence or absence of murine recombinant IL-33. Serum concentrations of S.pneumoniae, Moraxella catarrhalis (M.catarrhalis) and Haemophilus influenzae (H.influenzae) lysates-specific IgE were measured in patients with asthma and control subjects.Results: We showed that in the presence of IL-33, repeated, per-nasal airways exposure to the bodies of these bacteria induced airways hyperresponsiveness (AHR) in the experimental mice. This was accompanied by cellular infiltration into bronchoalveolar lavage fluid (BALF), eosinophilic infiltration and mucous hypertrophy of the lung tissue, with elevated local expression of some type 2 cytokines and elevated, specific IgG and IgE in the serum. The precise characteristics of the inflammation evoked by exposure to each bacterial species were distinguishable.Conclusions: These results suggest that in the certain circumstances, inhaled or commensal bacterial body antigens of both Gram-positive (S. pneumoniae) and Gram-negative (M. catarrhalis and H. influenzae) respiratory tract bacteria may initiate type 2 inflammation typical of asthma in the airways. In addition, we demonstrated that human asthmatic patients manifest elevated serum concentrations of M.catarrhalis- and H.influenzae-specific IgE.

2.
J Mol Cell Biol ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38444183

RESUMO

Fusion pore opening is a transient intermediate state of synaptic vesicle exocytosis, which is highly dynamic and precisely regulated by the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex and synaptotagmin-1 (Syt1). Yet, the regulatory mechanism is not fully understood. In this work, using single-channel membrane fusion electrophysiology, we determined that SNAREpins are important for driving fusion pore opening and dilation but incapable of regulating the dynamics. When Syt1 was added, the closing frequency of fusion pores significantly increased, while the radius of fusion pores mildly decreased. In response to Ca2+, SNARE/Syt1 greatly increased the radius of fusion pores and reduced their closing frequency. Moreover, the residue F349 in the C2B domain of Syt1, which mediates Syt1 oligomerization, was required for clamping fusion pore opening in the absence of Ca2+, probably by extending the distance between the two membranes. Finally, in Ca2+-triggered fusion, the primary interface between SNARE and Syt1 plays a critical role in stabilizing and dilating the fusion pore, while the polybasic region of Syt1 C2B domain has a mild effect on increasing the radius of the fusion pore. In summary, our results suggest that Syt1, SNARE, and the anionic membrane synergically orchestrate the dynamics of fusion pore opening in synaptic vesicle exocytosis.

3.
J Hazard Mater ; 465: 133222, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38101014

RESUMO

Constructed wetlands (CWs) are reservoirs of microplastics (MPs) in the environment. However, knowledge about the impact of MPs on antibiotic removal and the fate of antibiotic resistance genes (ARGs) is limited. We focused on sulfamethoxazole (SMX) as a representative compound to examine the effects of MPs on SMX removal and the proliferation and dissemination of two SMX-related ARGs (sul1 and sul2) in vertical subsurface-flow CW (VFCW) microcosm. The presence of MPs in the substrate was found to enhance the proliferation of microorganisms owing to the large specific surface area of the MPs and the release of dissolved organic carbon (DOC) on MP surfaces, which resulted in a high SMX removal ranging from 97.80 % to 99.80 %. However, the presence of MPs promoted microbial interactions and the horizontal gene transfer (HGT) of ARGs, which led to a significant increase in the abundances of sul1 and sul2 of 68.47 % and 17.20 %, respectively. It is thus imperative to implement rigorous monitoring strategies for MPs to mitigate their potential ecological hazards.


Assuntos
Antibacterianos , Sulfametoxazol , Microplásticos , Plásticos , Águas Residuárias , Eliminação de Resíduos Líquidos/métodos , Áreas Alagadas , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos
4.
Cell Immunol ; 391-392: 104759, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37689011

RESUMO

BACKGROUND: Asthma is a common chronic respiratory disease characterized by airways inflammation, hyperresponsiveness and remodeling. IL-37, an anti-inflammatory cytokine, consists of five splice isoforms, that is, a-e. Although it has been previously shown that recombinant human IL-37b is able to inhibit airway inflammation and hyperresponsiveness in animal models of asthma, the effects and difference of other IL-37 isoforms, such as IL-37a on features of asthma are unknown. METHODS: Animal models of chronic asthma were established using IL-37a and IL-37b transgenic mice with C57BL/6J background and wild-type (WT) mice sensitized and nasally challenged with ovalbumin (OVA). Airway hyperresponsiveness was measured using FlexiVent apparatus, while histological and immunohistological stainings were employed to measure airways inflammation and remodeling indexes, including goblet cell metaplasia, mucus production, deposition of collagen, hypertrophy of airway smooth muscles and pulmonary angiogenesis. RESULTS: Compared to WT mice, both IL-37a and IL-37b transgenic mice had significant reduced airway hyperresponsiveness and the declined total numbers of inflammatory cells, predominant eosinophils into airways and lung tissues. Furthermore, all features of airways remodeling, including degrees of mucus expression, collagen deposition, hypertrophy of smooth muscles, thickness of airways and neovascularization markedly decreased in IL-37 transgenic mice compared with OVA-treated WT mice. CONCLUSION: Our data suggest that both IL-37a and IL-37b isoforms are able to not only ameliorate airways inflammation and airways hyperresponsiveness, but also greatly reduce airways structural changes of animal models of chronic asthma.


Assuntos
Asma , Hipersensibilidade Respiratória , Camundongos , Humanos , Animais , Ovalbumina , Camundongos Transgênicos , Camundongos Endogâmicos C57BL , Asma/metabolismo , Pulmão/metabolismo , Inflamação/patologia , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/patologia , Colágeno/efeitos adversos , Colágeno/metabolismo , Hipertrofia/metabolismo , Hipertrofia/patologia , Isoformas de Proteínas , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Líquido da Lavagem Broncoalveolar
5.
J Cataract Refract Surg ; 49(11): 1098-1105, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37531392

RESUMO

PURPOSE: To establish a numerical spectral-domain optical coherence tomography (SD-OCT)-based keratoconus (KC) staging system and compare it with existing KC staging systems. SETTING: Eye Hospital of Wenzhou Medical University, Wenzhou, China. DESIGNS: Retrospective case-control study. METHODS: Scheimpflug tomography, air-puff tonometry, and SD-OCT were performed on 236 normal and 331 KC eyes. All SD-OCT-derived parameters of the corneal epithelium and stroma were evaluated based on their receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, and specificity to discriminate between normal and KC eyes. The best performing parameters were subsequently used to create an OCT-based staging system, which was compared with existing tomographic and biomechanical staging systems. RESULTS: 236 eyes from 236 normal patients and 331 eyes from 331 KC patients of different stages were included. The highest ranked AUC ROC SD-OCT parameters, derived from stroma and epithelium, were stroma overall minimum thickness (ST: AUC 0.836, sensitivity 90%, specificity 67%) and epithelium overall SD (EP: AUC 0.835, sensitivity 75%, specificity 78%). A numerical SD-OCT staging system called STEP including 2 parameters-"ST" and "EP"-with 5 stages was proposed. CONCLUSIONS: The new SD-OCT-based KC staging system is the first to take the epithelium with its sublayer stroma information into account, showing a strong agreement to the existing staging systems. This system could be incorporated into daily practice, potentially leading to an overall improvement in KC treatment and follow-up management.


Assuntos
Epitélio Corneano , Ceratocone , Humanos , Ceratocone/diagnóstico , Estudos de Casos e Controles , Estudos Retrospectivos , Tomografia de Coerência Óptica , Curva ROC , Topografia da Córnea , Córnea
6.
Adv Sci (Weinh) ; 10(28): e2301478, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37590389

RESUMO

The receptor-binding domain (RBD) of spike recognizing the receptor angiotensin-converting enzyme 2 (ACE2) initiates membrane fusion between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and cell membrane. Although the structure of the RBD_ACE2 complex has been well studied, its functional mechanism in membrane fusion is still not fully understood. Here, using an in vitro cell-vesicle content-mixing assay, it is found that the cleavage at the S2' site by thrombin (Thr) protease strongly accelerates membrane fusion, compared to that of cleavage at the S1/S2 site by PreScission (3C) protease. Moreover, mutations at the RBD_ACE2 interface resulted in a positive correlation between binding affinity and fusion probability. In both the cell-vesicle and cell-cell fusion assays, by crosslinking two membranes via the neutravidin (NTV)_biotin interaction or complementary DNA strands, it is found that spike drives membrane fusion in the absence of ACE2, and a suitable distance between two membranes is critical for spike-mediated membrane fusion. Finally, unsuitable membrane crosslinkers significantly inhibited the fusion probability in the presence of ACE2. Taken together, the results suggest that the RBD_ACE2 complex may act as a crosslinker to bridge the viral and cell membranes at a suitable distance, which is critical, but also substitutable for spike-mediated SARS-CoV-2 entry.

7.
Eye (Lond) ; 37(18): 3743-3750, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37270614

RESUMO

OBJECTIVE: To investigate relationship of the retinal capillary plexus (RCP) and ganglion cell complex (GCC) with mild cognitive impairment (MCI) and dementia in a community-based study1. METHODS: This cross-sectional study incorporated the participants of the Jidong Eye Cohort Study. Optical coherence tomography angiography was performed to obtain RCP vessel density and GCC thickness with detailed segments. The Mini-mental State Examination and Montreal Cognitive Assessment were used to assess cognitive status by professional neuropsychologists. Participants were thus divided into three groups: normal, mild cognitive impairment, and dementia. Multivariable analysis was used to measure relationship of ocular parameters with cognitive impairment. RESULTS: Of the 2678 participants, the mean age was 44.1 ± 11.7 years. MCI and dementia occurred in 197 (7.4%) and 80 (3%) participants, respectively. Compared to the normal group, the adjusted odds ratio (OR) with the 95% confidence interval was 0.76 (0.65-0.90) for the correlation of lower deep RCP with MCI. We found the following items significantly associated with dementia compared with the normal group: a superficial (OR, 0.68 [0.54-0.86]) and deep (OR, 0.75 [0.57-0.99]) RCP, as well as the GCC (OR, 0.68 [0.54-0.85]). Compared to the MCI group, those with dementia had decreased GCC (OR, 0.75 [0.58-0.97]). CONCLUSIONS: Decreased deep RCP density was associated with MCI. Decreased superficial and deep RCP and the thin GCC were correlated with dementia. These implied that the retinal microvasculature may develop into a promising non-invasive imaging marker to predict severity of cognitive impairment.


Assuntos
Disfunção Cognitiva , Demência , Humanos , Adulto , Pessoa de Meia-Idade , Estudos de Coortes , Estudos Transversais , Retina , Disfunção Cognitiva/diagnóstico , Vasos Retinianos , Tomografia de Coerência Óptica/métodos
8.
Cont Lens Anterior Eye ; 46(3): 101840, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37055334

RESUMO

PURPOSE: To determine whether combinations of devices with different measuring principles, supported by artificial intelligence (AI), can improve the diagnosis of keratoconus (KC). METHODS: Scheimpflug tomography, spectral-domain optical coherence tomography (SD-OCT), and air-puff tonometry were performed in all eyes. The most relevant machine-derived parameters to diagnose KC were determined using feature selection. The normal and forme fruste KC (FFKC) eyes were divided into training and validation datasets. The selected features from a single device or different combinations of devices were used to develop models based on random forest (RF) or neural networks (NN) trained to distinguish FFKC from normal eyes. The accuracy was determined using receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, and specificity. RESULTS: 271 normal eyes, 84 FFKC eyes, 85 early KC eyes, and 159 advanced KC eyes were included. A total of 14 models were built. Air-puff tonometry had the highest AUC for detecting FFKC using a single device (AUC = 0.801). Among all two-device combinations, the highest AUC was accomplished using RF applied to selected features from SD-OCT and air-puff tonometry (AUC = 0.902), followed by the three-device combination with RF (AUC = 0.871) with the best accuracy. CONCLUSION: Existing parameters can precisely diagnose early and advanced KC, but their diagnostic ability for FFKC could be optimized. Applying an AI algorithm to a combination of air-puff tonometry with Scheimpflug tomography or SD-OCT could improve FFKC diagnostic ability. The improvement in diagnostic ability by combining three devices is modest.


Assuntos
Ceratocone , Humanos , Ceratocone/diagnóstico , Córnea/diagnóstico por imagem , Topografia da Córnea/métodos , Inteligência Artificial , Curva ROC , Tomografia de Coerência Óptica/métodos , Manometria
9.
Exp Gerontol ; 175: 112160, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37019047

RESUMO

Elderly asthmatics have higher morbidity and mortality compared with those of youngers. It has been shown that there are also some differences in clinic phenomena between young and elderly asthmatics, however, there is lack of the kinetic comparisons of the changes in the development of asthma between two populations. To better understand the specific pathophysiological manifestations in older patients with asthma, we dynamically and parallelly compared pathophysiological changes in the airways and lung tissues between young and old murine asthma surrogates based on sensitization and challenge with house dust mite (HDM). Murine models were established in young (6-8-week-old) and old (16-17-month-old) female wild-type C57BL/6 mice. Our data showed that repetitive HDM exposure induced relatively low type 2 immune responses (airway hyperresponsiveness, eosinophils recruitment, expression of type 2 cytokines, mucus secretion, serum HDM specific immunoglobulin E (IgE) and IgG) in old mice. However, the type 3 immune responses (neutrophils infiltration and IL-17A expression) were enhanced in old HDM exposed mice, which sustained longer and higher than that of young mice. Notably, the relatively weakened allergic inflammation characteristics might be associated with lower numbers of CD20+ B cells and IgE+ cells in the iBALTs in old mice compared with those in young mice. Our data suggest that aging might compromise the ability to induce type 2 immune responses, but enhance type 3 immune responses upon repetitive HDM challenge, which might cause relevant phenomena in old experimental mice and might even be applicable to elderly patients with asthma in the clinic.


Assuntos
Asma , Pyroglyphidae , Feminino , Animais , Camundongos , Pyroglyphidae/metabolismo , Camundongos Endogâmicos C57BL , Asma/metabolismo , Pulmão , Inflamação/metabolismo , Citocinas/metabolismo , Imunoglobulina E/metabolismo , Tecido Linfoide , Modelos Animais de Doenças
10.
Acta Ophthalmol ; 101(2): e185-e196, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36794626

RESUMO

PURPOSE: The purpose of this study is to assess the effect of various fluence levels on prophylactic corneal cross-linking (CXL) combined with femtosecond laser in situ keratomileusis (FS-LASIK-Xtra) or transepithelial photorefractive keratectomy (TransPRK-Xtra) on biomechanics, demarcation line (DL), and stromal haze. METHODS: Prospective analysis where two prophylactic CXL protocols (lower/higher fluence [LF/HF]: 30 mw/cm2 , 60/80 s, 1.8/2.4 J/cm2 ) were performed as part of either an FS-LASIK-Xtra or TransPRK-Xtra procedure. Data were collected preoperatively and at 1 week and 1, 3, and 6 months postoperatively. Main outcome measures were (1) dynamic corneal response parameters and the stress-strain index (SSI) from Corvis, (2) actual DL depth (ADL), and (3) stromal haze on OCT images analysed by a machine learning algorithm. RESULTS: Eighty-six eyes from 86 patients underwent FS-LASIK-Xtra-HF (21 eyes), FS-LASIK-Xtra-LF (21 eyes), TransPRK-Xtra-HF (23 eyes), and TransPRK-Xtra-LF (21 eyes). SSI increased similarly by around 15% in all groups 6 months postoperatively (p = 0.155). All other corneal biomechanical parameters were statistically significant worsening postoperatively, but the change was similar in all groups. At 1 month postoperatively, there was no statistical difference in mean ADL among four groups (p = 0.613), mean stromal haze was similar between the two FS-LASIK-Xtra groups, but higher in the TransPRK-Xtra-HF group compared with the TransPRK-Xtra-LF group. CONCLUSIONS: FS-LASIK-Xtra and TransPRK-Xtra lead to a similar ADL and improve SSI equally. Lower fluence prophylactic CXL might be recommended as it achieves similar mean ADL with potentially less induced stromal haze, especially in TransPRK. The clinical relevance and applicability of such protocols remains to be assessed.


Assuntos
Ceratomileuse Assistida por Excimer Laser In Situ , Ceratectomia Fotorrefrativa , Humanos , Ceratectomia Fotorrefrativa/métodos , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Crosslinking Corneano , Acuidade Visual , Lasers de Excimer/uso terapêutico , Córnea/cirurgia
11.
Water Res ; 230: 119577, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36638735

RESUMO

Progress in heterogeneous advanced oxidation processes (AOPs) is hampered by several issues including mass transfer limitation, limited diffusion of short-lived reactive oxygen species (ROS), aggregation of nanocatalysts, and loss of nanocatalysts to treated water. These issues have been addressed in recent studies by executing the heterogeneous AOPs in confinement, especially in the nanopores of catalytic membranes. Under nanoconfinement (preferably at the length of less than 25 nm), the oxidant-nanocatalyst interaction, ROS-micropollutant interaction and diffusion of ROS have been observed to significantly improve, which results in enhanced ROS yield and mass transfer, improved reaction kinetics and reduced matrix effect as compared to conventional heterogenous AOP configuration. Given the significance of nanoconfinement effect, this study presents a critical review of the current status of membrane-based nanoconfined heterogeneous catalysis system for the first time. A succinct overview of the nanoconfinement concept in the context of membrane-based nanofluidic platforms is provided to elucidate the theoretical and experimental findings related to reaction kinetics, reaction mechanisms and molecule transport in membrane-based nanoconfined AOPs vs. conventional AOPs. In addition, strategies to construct membrane-based nanoconfined catalytic systems are explained along with conflicting arguments/opinions, which provides critical information on the viability of these strategies and future research directions. To show the desirability and applicability of membrane-based nanoconfined catalysis systems, performance governing factors including operating conditions and water matrix effect are particularly focused. Finally, this review presents a systematic account of the opportunities and technological constraints in the development of membrane-based nanoconfined catalytic platform to realize effective micropollutant elimination in water treatment.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Espécies Reativas de Oxigênio , Purificação da Água/métodos , Oxirredução , Catálise
12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-974809

RESUMO

@#Whooping cough(pertussis)is a highly contagious respiratory disease,which mainly affects infants and young children.Vaccination is an effective measure to prevent pertussis infection.Due to the fewer side effects,acellular pertussis vaccines(aPVs)have replaced whole-cell pertussis vaccine(wPVs)in many countries.Despite vaccination coverage is high,the short immunity induced by aPVs is considered to be significant reason for the re-emergence of pertussis.For improving pertussis vaccine,genetically detoxified vaccine and live attenuated vaccine have showed obvious clinical results and other strategies including using novel adjuvants in aPVs,increasing antigen or packaging aPVs with nanoparticles also have good prospects.This paper reviews the antigen composition and protective effects of aPVs,vaccination programs in different countries,potential candidate components of pertussis vaccine and new strategies for prevention of pertussis.

13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-974741

RESUMO

@#Whooping cough(pertussis)is a highly contagious respiratory disease,which mainly affects infants and young children.Vaccination is an effective measure to prevent pertussis infection.Due to the fewer side effects,acellular pertussis vaccines(aPVs)have replaced whole-cell pertussis vaccine(wPVs)in many countries.Despite vaccination coverage is high,the short immunity induced by aPVs is considered to be significant reason for the re-emergence of pertussis.For improving pertussis vaccine,genetically detoxified vaccine and live attenuated vaccine have showed obvious clinical results and other strategies including using novel adjuvants in aPVs,increasing antigen or packaging aPVs with nanoparticles also have good prospects.This paper reviews the antigen composition and protective effects of aPVs,vaccination programs in different countries,potential candidate components of pertussis vaccine and new strategies for prevention of pertussis.

14.
Front Microbiol ; 13: 1052917, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36504808

RESUMO

Background: Chronic hepatitis B (CHB) remains a significant global health problem, leading to recurrent inflammation and liver-damaging diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Currently, although diagnostic markers for CHB are well established, the indicators for predicting liver injury caused by hepatitis B virus (HBV) infection still need to be further explored. Thus, the identification of credible infectious indicators is urgently needed to facilitate timely clinical intervention and avoid the progression of disease malignancy. Methods: The Gene Expression Omnibus (GEO) database GSE83148 data set was used to explore the hub genes for HBV infection. The quantitative real-time polymerase chain reaction (qPCR) was used to identify the impact of HBV infection on the expression of hub gene at the cell level. At the same time, serum samples and clinical information were collected from healthy, HBV-free and CHB patients. The enzyme-linked immunosorbent assay (ELISA) was used to verify the results of cell experiments and Pearson correlation analysis was used to clarify hub genes correlation with HBV infection indicators and liver injury-related indicators. Finally, the Gene Expression Profiling Interactive Analysis (GEPIA) database was used to analyze the differences in the expression of hub gene in liver injury diseases. Results: Chemokine (C-X-C motif) ligand (CXCL)8, CXCL9, CXCL10, and CXCL11 were identified as hub genes in HBV infection. After HBV infection, the expression of the four chemokines was significantly increased and the concentrations secreted into serum were also increased. Moreover, the four chemokines were significantly correlated with HBV infection-related indicators and liver injury-related indicators, which were positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatitis B e antigen (HBeAg), and negatively correlated with AST/ALT ratio and hepatitis B core antibody (HBcAb). In addition, the expression of CXCL9, CXCL10, and CXCL11 in HCC tissues was significantly higher than in normal tissues. Conclusion: Using a combination of bioinformatics, cell experiments, and clinical correlation analysis, this study showed that CXCL8, CXCL9, CXCL10, and CXCL11 can be used as serum biomarkers to forecast liver injury caused by HBV infection.

15.
Mol Biomed ; 3(1): 29, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36129576

RESUMO

Intracellular vesicle trafficking is the fundamental process to maintain the homeostasis of membrane-enclosed organelles in eukaryotic cells. These organelles transport cargo from the donor membrane to the target membrane through the cargo containing vesicles. Vesicle trafficking pathway includes vesicle formation from the donor membrane, vesicle transport, and vesicle fusion with the target membrane. Coat protein mediated vesicle formation is a delicate membrane budding process for cargo molecules selection and package into vesicle carriers. Vesicle transport is a dynamic and specific process for the cargo containing vesicles translocation from the donor membrane to the target membrane. This process requires a group of conserved proteins such as Rab GTPases, motor adaptors, and motor proteins to ensure vesicle transport along cytoskeletal track. Soluble N-ethyl-maleimide-sensitive factor (NSF) attachment protein receptors (SNARE)-mediated vesicle fusion is the final process for vesicle unloading the cargo molecules at the target membrane. To ensure vesicle fusion occurring at a defined position and time pattern in eukaryotic cell, multiple fusogenic proteins, such as synaptotagmin (Syt), complexin (Cpx), Munc13, Munc18 and other tethering factors, cooperate together to precisely regulate the process of vesicle fusion. Dysfunctions of the fusogenic proteins in SNARE-mediated vesicle fusion are closely related to many diseases. Recent studies have suggested that stimulated membrane fusion can be manipulated pharmacologically via disruption the interface between the SNARE complex and Ca2+ sensor protein. Here, we summarize recent insights into the molecular mechanisms of vesicle trafficking, and implications for the development of new therapeutics based on the manipulation of vesicle fusion.

16.
Eye Vis (Lond) ; 9(1): 38, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36180939

RESUMO

BACKGROUND: To assess age- and sex-related changes in the superficial retinal capillary plexus (SCP) and deep retinal capillary plexus (DCP) in healthy Chinese adults. METHODS: In this cross-sectional study, all data were derived from the community-based Jidong Eye Cohort Study. Participants underwent optical coherence tomography angiography (OCTA) and other ocular and systemic examinations. The vessel densities of the whole measured area, parafovea, and four quadrants in the SCP and DCP were measured. RESULTS: We recruited 1036 eyes of 1036 healthy participants; the mean age was 40.4 ± 9.8 years, and 449 (43.3%) participants were males. The SCP and DCP vessel densities in all regions, except for temporal and nasal regions in the SCP, non-linearly decreased with age. The DCP vessel densities began to decrease at approximately 35 years of age, while the SCP vessel densities began to decrease at approximately 40 years of age. The DCP vessel densities decreased more rapidly than the SCP vessel densities at 35-50 years of age. The DCP vessel densities remained stable or slightly decreased after the age of 50 years in females, while those decreased linearly in most regions in males. CONCLUSIONS: The retinal vessel density decreased earlier and more rapidly in the DCP than in the SCP, and the effect of aging on the DCP vessel density was sex-dependent. Our findings suggest that age and sex should be considered when interpreting clinical quantitative OCTA data.

17.
Front Physiol ; 13: 917808, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35991162

RESUMO

Purpose: Self-reported snoring has been reported to influence nerves and vessels. However, there are few direct evidences of snoring related to nerves and microvessels defects. Therefore, we evaluated the association of self-reported snoring with retinal structure and microcirculation. Methods: A total of 2,622 participants were recruited from the Jidong eye cohort study (JECS). Physical examinations, laboratory tests, and questionnaires were recorded. We also used optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) to assess the retinal structure and microvascular network. Snoring was defined as "never," "occasionally," and "frequently or more severe" according to self-reported frequency. Results: The prevalence of snoring were 84.6% (n = 983) and 45.0% (n = 657) in males and females, respectively. Compared with never snoring group, the retinal thickness increased in "occasionally" (p < 0.001) and "frequently or more severe" groups (p = 0.001), while no difference was found between snoring groups (p = 0.14). Superficial retinal capillary plexus (RCP) vessel density was lower in "frequently or more severe" group than in "never" (p < 0.001) and "occasionally" snoring groups (p < 0.001). After adjusting for confounders, "frequently or more severe" snoring was significantly associated with thinner total retinal thickness [ß = -2.79 (95% CI: -5.27, -0.30)] and lower superficial RCP vessel density [ß = -0.71 (95% CI: -1.19, -0.23)]. Conclusion: Our research showed self-reported snoring was associated with thinner retinal thickness and lower superficial RCP vessel density. The findings of our study emphasize the need for self-reported snoring assessments in determining retinal structure and microcirculation impairment.

18.
Nat Commun ; 13(1): 4010, 2022 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-35817796

RESUMO

The freshwater scarcity and inadequate access to clean water globally have rallied tremendous efforts in developing robust technologies for water purification and decontamination, and heterogeneous catalysis is a highly-promising solution. Sub-nanometer-confined reaction is the ultimate frontier of catalytic chemistry, yet it is challenging to form the angstrom channels with distributed atomic catalytic centers within, and to match the internal mass transfer and the reactive species' lifetimes. Here, we resolve these issues by applying the concept of the angstrom-confined catalytic water contaminant degradation to achieve unprecedented reaction rates within 4.6 Å channels of two-dimensional laminate membrane assembled from monolayer cobalt-doped titanium oxide nanosheets. The demonstrated degradation rate constant of the target pollutant ranitidine (1.06 ms-1) is 5-7 orders of magnitude faster compared with the state-of-the-art, achieving the 100% degradation over 100 h continuous operation. This approach is also ~100% effective against diverse water contaminates with a retention time of <30 ms, and the strategy developed can be also extended to other two-dimensional material-assembled membranes. This work paves the way towards the generic angstrom-confined catalysis and unravels the importance of utilizing angstrom-confinement strategy in the design of efficient catalysts for water purification.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Catálise , Água , Poluentes Químicos da Água/análise , Purificação da Água/métodos
19.
J Refract Surg ; 38(6): 374-380, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35686708

RESUMO

PURPOSE: To investigate the diagnostic capacity of spectral-domain optical coherence tomography (SD-OCT) combined with air-puff tonometry using artificial intelligence (AI) in differentiating between normal and keratoconic eyes. METHODS: Patients who had either undergone uneventful laser vision correction with at least 3 years of stable follow-up or those who had forme fruste keratoconus (FFKC), early keratoconus (EKC), or advanced keratoconus (AKC) were included. SD-OCT and biomechanical information from air-puff tonometry was divided into training and validation sets. AI models based on random forest or neural networks were trained to distinguish eyes with FFKC from normal eyes. Model accuracy was independently tested in eyes with FFKC and normal eyes. Receiver operating characteristic (ROC) curves were generated to determine area under the curve (AUC), sensitivity, and specificity values. RESULTS: A total of 223 normal eyes from 223 patients, 69 FFKC eyes from 69 patients, 72 EKC eyes from 72 patients, and 258 AKC eyes from 258 patients were included. The top AUC ROC values (normal eyes compared with AKC and EKC) were Pentacam Random Forest Index (AUC = 0.985 and 0.958), Tomographic and Biomechanical Index (AUC = 0.983 and 0.925), and Belin-Ambrósio Enhanced Ectasia Total Deviation Index (AUC = 0.981 and 0.922). When SD-OCT and air-puff tonometry data were combined, the random forest AI model provided the highest accuracy with 99% AUC for FFKC (75% sensitivity; 94.74% specificity). CONCLUSIONS: Currently, AI parameters accurately diagnose AKC and EKC, but have a limited ability to diagnose FFKC. AI-assisted diagnostic technology that uses both SD-OCT and air-puff tonometry may overcome this limitation, leading to improved treatment of patients with keratoconus. [J Refract Surg. 2022;38(6):374-380.].


Assuntos
Ceratocone , Inteligência Artificial , Córnea , Paquimetria Corneana , Topografia da Córnea/métodos , Humanos , Ceratocone/diagnóstico , Manometria , Curva ROC , Estudos Retrospectivos , Tomografia de Coerência Óptica
20.
Front Endocrinol (Lausanne) ; 13: 855430, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35498412

RESUMO

Background: To determine the association between serum uric acid (SUA) and the retinal capillary plexus (RCP) using optical coherence tomography angiography (OCTA). Methods: This cross-sectional study evaluated data from August 2019 to January 2020 from participants recruited from the Jidong community (Tangshan, Hebei, China). All participants completed detailed anthropometrical measurements, laboratory tests and comprehensive ophthalmic examinations. We assessed the vessel density in RCP using OCTA. We used multivariable analysis to evaluate the sex-specific association between SUA and RCP after adjusting for confounders. Results: A total of 2730 participants were included in this study. The mean age of the participants was 44.0 ± 11.6 years, and 1463 (53.6%) were women. The multivariable ßs and 95% confidence intervals (CIs) of superficial RCP vessel density in the second through fourth SUA quartiles compared with the lowest SUA quartiles were -0.27 (-0.56 - 0.03), -0.30 (-0.60 - 0.01), and -0.46 (-0.78 - -0.14) (P for trend = 0.007) in men. Conclusions: Higher SUA levels were significantly associated with lower RCP vessel density in men. Our findings provide evidence for the detrimental effect of high SUA levels on the retinal microvasculature and imply the importance of modulating SUA to prevent the microvascular alternation especially for men.


Assuntos
Retina , Ácido Úrico , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Microvasos , Pessoa de Meia-Idade , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica
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