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Dysregulation of the immune system is a cardinal feature of opioid addiction. Here, we characterize the landscape of peripheral immune cells from patients with opioid use disorder and from healthy controls. Opioid-associated blood exhibited an abnormal distribution of immune cells characterized by a significant expansion of fragile-like regulatory T cells (Tregs), which was positively correlated with the withdrawal score. Analogously, opioid-treated mice also showed enhanced Treg-derived interferon-γ (IFN-γ) expression. IFN-γ signaling reshaped synaptic morphology in nucleus accumbens (NAc) neurons, modulating subsequent withdrawal symptoms. We demonstrate that opioids increase the expression of neuron-derived C-C motif chemokine ligand 2 (Ccl2) and disrupted blood-brain barrier (BBB) integrity through the downregulation of astrocyte-derived fatty-acid-binding protein 7 (Fabp7), which both triggered peripheral Treg infiltration into NAc. Our study demonstrates that opioids drive the expansion of fragile-like Tregs and favor peripheral Treg diapedesis across the BBB, which leads to IFN-γ-mediated synaptic instability and subsequent withdrawal symptoms.
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Interferon gama , Transtornos Relacionados ao Uso de Opioides , Síndrome de Abstinência a Substâncias , Linfócitos T Reguladores , Animais , Camundongos , Analgésicos Opioides/administração & dosagem , Interferon gama/metabolismo , Transtornos Relacionados ao Uso de Opioides/metabolismo , Transtornos Relacionados ao Uso de Opioides/patologiaRESUMO
Three-dimensional (3D) chromatin organization is highly dynamic during development and seems to play a crucial role in regulating gene expression. Self-interacting domains, commonly called topologically associating domains (TADs) or compartment domains (CDs), have been proposed as the basic structural units of chromatin organization. Surprisingly, although these units have been found in several plant species, they escaped detection in Arabidopsis (Arabidopsis thaliana). Here, we show that the Arabidopsis genome is partitioned into contiguous CDs with different epigenetic features, which are required to maintain appropriate intra-CD and long-range interactions. Consistent with this notion, the histone-modifying Polycomb group machinery is involved in 3D chromatin organization. Yet, while it is clear that Polycomb repressive complex 2 (PRC2)-mediated trimethylation of histone H3 on lysine 27 (H3K27me3) helps establish local and long-range chromatin interactions in plants, the implications of PRC1-mediated histone H2A monoubiquitination on lysine 121 (H2AK121ub) are unclear. We found that PRC1, together with PRC2, maintains intra-CD interactions, but it also hinders the formation of H3K4me3-enriched local chromatin loops when acting independently of PRC2. Moreover, the loss of PRC1 or PRC2 activity differentially affects long-range chromatin interactions, and these 3D changes differentially affect gene expression. Our results suggest that H2AK121ub helps prevent the formation of transposable element/H3K27me1-rich long loops and serves as a docking point for H3K27me3 incorporation.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Histonas/genética , Histonas/metabolismo , Proteínas de Arabidopsis/metabolismo , Lisina/metabolismo , Proteínas do Grupo Polycomb/genética , Proteínas do Grupo Polycomb/metabolismo , Cromatina/genética , Cromatina/metabolismo , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismoRESUMO
We theoretically show the asymmetric spin wave transmission in a coupled waveguide-skyrmion structure, where the skyrmion acts as an effective nanocavity allowing the whispering gallery modes for magnons. The asymmetry originates from the chiral spin wave mode localized in the circular skyrmion wall. By inputting two-tone excitations and mixing them in the skyrmion wall, we observe a unidirectional output magnon frequency comb propagating in the waveguide with a record number of teeth (>50). This coupled waveguide-cavity structure turns out to be a universal paradigm for generating asymmetric magnon frequency combs, where the cavity can be generalized to other magnetic structures that support the whispering gallery mode of magnons. Our results advance the understanding of the nonlinear interaction between magnons and magnetic textures and open a new pathway to exploring the asymmetric spin wave transmission and to steering the magnon frequency comb.
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OBJECTIVE: To determine the association of nirmatrelvir/ritonavir (NMV/r) with hospitalization or death within 30 days as compared with untreated controls previously uninfected and nonhospitalized. METHODS: We used a matched cohort design using inverse probability of treatment weight (IPTW). Individuals prescribed NMV/r within 3 days of COVID-19 diagnosis were compared with IPTW-based untreated controls. Variables for IPTW included age, race, sex, body mass index, geographic location, vaccination status, and multiple comorbidities. Additional analyses were conducted on NMV/r-treated and propensity score-matched untreated controls. RESULTS: Among 7615 individuals prescribed NMV/r and 62 077 controls identified between 1 January 2022 and 25 February 2023, the risk of hospitalization/death was lower among NMV/r-treated persons vs untreated controls (243 vs 3468 events; absolute risk difference [ARD], -2.36 [95% CI, -2.57 to -2.14]). The difference was significant for those >60 and ≤60 years old (ARD, -3.86 [95% CI, -4.19 to -3.54] vs -0.27 [95% CI, -0.51 to -0.03]) and for persons asymptomatic and symptomatic (ARD, -7.09 [95% CI, -7.62 to -6.55] vs -1.46 [95% CI, -1.66 to -1.25]). Significant benefit was observed among individuals unvaccinated and vaccinated, with or without a booster dose. CONCLUSIONS: NMV/r is associated with a significant reduction in 30-day hospitalization or death among individuals previously uninfected and nonhospitalized.
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COVID-19 , Lactamas , Leucina , Nitrilas , Prolina , Humanos , Pessoa de Meia-Idade , Tratamento Farmacológico da COVID-19 , Teste para COVID-19 , Estudos de Coortes , Ritonavir/uso terapêutico , Hospitalização , Pontuação de Propensão , Antivirais/uso terapêuticoRESUMO
Functional fibers composed of textiles are considered a promising platform for constructing electronic skin (e-skin). However, developing robust electronic fibers with integrated multiple functions remains a formidable task especially when a complex service environment is concerned. In this work, a continuous and controllable strategy is demonstrated to prepare e-skin-oriented ceramic fibers via coaxial wet spinning followed by cold isostatic pressing. The resulting core-shell structured fiber with tightly compacted Al-doped ZnO nanoparticles in the core and highly ordered aramid nanofibers in the shell exhibit excellent tensile strength (316 MPa) with ultra-high elongation (33%). Benefiting from the susceptible contacts between conducting ceramic nanoparticles, the ceramic fiber shows both ultrahigh sensitivity (gauge factor = 2141) as a strain sensor and a broad working range up to 70 °C as a temperature sensor. Furthermore, the tunable core-shell structure of the fiber enables the optimization of impedance matching and attenuation of electromagnetic waves for the corresponding textile, resulting in a minimum reflection loss of -39.1 dB and an effective absorption bandwidth covering the whole X-band. Therefore, the versatile core-shell ceramic fiber-derived textile can serve as a stealth e-skin for monitoring the motion and temperature of robots under harsh conditions.
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Lithium-sulfur (Li-S) batteries are one of the most promising energy storage devices due to their environmental friendliness, low cost, and high specific capacity. However, the slow electrochemical kinetics and the "shuttle effect" have seriously hindered their commercialization. Herein, the nanoflower Bi2S3âMoS2 (BMS) heterostructure is synthesized by a two-step hydrothermal method, and then the Bi2S3âMoS2-Polypropylene (BMS-PP) interlayer is constructed. The heterostructure is rich in active sites, in which BMS has strong adsorption to lithium polysulfides (LiPSs) and can effectively anchor LiPSs while catalyzing LiPSs and promote the redox of Li2S at the same time, which can improve the utilization of active substances. More importantly, the d-band center can be tuned by the formation of Bi2S3âMoS2 heterostructure. Thus, Li-S batteries containing the BMS-PP interlayer show excellent rate performance (841.6 mAh g-1 at 5 C) and cycling performance (70.3% capacity retention after 500 cycles at 3 C). This work provides a new route for high-performance lithium-sulfur batteries.
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Orbital angular momentum flow can be used to develop a low-dissipation electronic information device by manipulating the orbital current. However, efficiently generating and fully harnessing orbital currents is a formidable challenge. In this study, an approach is presented that induces a colossal orbital current by gradient oxidation in Pt/Ta to enhance spin-orbit torque (SOT) and achieve high-efficiency magnetization switching. The maximum efficiency of the SOT before and after the gradient oxidation of Ta is improved relative to that of Pt by ≈600 and 1200%, respectively. The large SOT originates from the colossal orbital current because of the orbital Rashba-Edelstein effect induced by the gradient oxidation of Ta. In addition, a large spin-to-charge conversion efficiency is observed in yttrium iron garnet/Pt/TaOx because of the inverse orbital Rashba-Edelstein effect. Harnessing the orbital current can help effectively minimize the critical current density of the current-induced magnetization switching to 2.26-1.08 × 106 A cm-2, marking a 12-fold reduction compared to that using Pt. This findings provide a new path for research on low-dissipation spin-orbit devices and improve the tunability of orbital current generation.
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2D-3D tin-based perovskites are considered as promising candidates for achieving efficient lead-free perovskite solar cells (PSCs). However, the existence of multiple low-dimensional phases formed during the film preparation hinders the efficient transport of charge carriers. In addition, the non-homogeneous distribution of low-dimensional phases leads to lattice distortion and increases the defect density, which are undesirable for the stability of tin-based PSCs. Here, mixed spacer cations [diethylamine (DEA+) and phenethylamine (PEA+)] are introduced into tin perovskite films to modulate the distribution of the 2D phases. It is found that compared to the film with only PEA+, the combination of DEA+ and PEA+ favors the formation of homogeneous low-dimensional perovskite phases with three octahedral monolayers (n = 3), especially near the bottom interface between perovskite and hole transport layer. The homogenization of 2D phases help improve the film quality with reduced lattice distortion and released strain. With these merits, the tin PSC shows significantly improved stability with 94% of its initial efficiency retained after storing in a nitrogen atmosphere for over 4600 h, and over 80% efficiency maintained after continuous illumination for 400 h.
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Insect-induced plant volatile organic compounds (VOCs) may function as either direct defence molecules to deter insects or indirect defence signals to attract the natural enemies of the invading insects. Tea (Camellia sinensis L.), an important leaf-based beverage crop, is mainly infested by Ectropis obliqua which causes the most serious damage. Here, we report a mechanistic investigation of tea plant-derived VOCs in an indirect defence mechanism against E. obliqua. Parasitoid wasp Parapanteles hyposidrae, a natural enemy of E. obliqua, showed strong electrophysiological response and selection behaviour towards S-linalool and ß-ocimene, two monoterpenes with elevated emission from E. obliqua-damaged tea plants. Larvae frass of E. obliqua, which also released S-linalool and ß-ocimene, was found to attract both mated female or male Pa. hyposidrae according to gas chromatography-electroantennogram detection and Y-tube olfactometer assays. In a field setting, both S-linalool and ß-ocimene were effective in recruiting both female and male Pa. hyposidrae wasps. To understand the molecular mechanism of monoterpenes-mediated indirect defence in tea plants, two novel monoterpene synthase genes, CsLIS and CsOCS-SCZ, involved in the biosynthesis of S-linalool or ß-ocimene, respectively, were identified and biochemically characterised. When the expression of these two genes in tea plants was inhibited by antisense oligodeoxynucleotide, both volatile emission and attraction of wasps were reduced. Furthermore, gene expression analysis suggested that the expression of CsLIS and CsOCS-SCZ is regulated by the jasmonic acid signalling pathway in the tea plant.
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Monoterpenos Acíclicos , Alcenos , Camellia sinensis , Mariposas , Vespas , Animais , Monoterpenos , Camellia sinensis/genética , Sinais (Psicologia) , Mariposas/fisiologia , Insetos , CháRESUMO
Scedosporium apiospermum species complex are widely distributed fungi that can be found in a variety of polluted environments, including soil, sewage, and decaying vegetation. Those opportunistic pathogens with strong potential of invasion commonly affect immunosuppressed populations However, few cases of scedosporiosis are reported in immunocompetent individuals, who might be misdiagnosed, leading to a high mortality rate. Here, we reported an immunocompetent case of systemtic infection involved in lung, brain and spine, caused by S. apiospermum species complex (S. apiospermum and S. boydii). The patient was an elderly male with persistent fever and systemtic infection after near-drowning. In the two tertiary hospitals he visited, definite diagnosis was extremely difficult. After being admitted to our hospital, he was misdiagnosed as tuberculosis infection, before diagnosis of S. apiospermum species complex infection by the metagenomic next-generation sequencing. His symptoms were alleviated after voriconazole treatment. In the present case, the details associated with its course were reported and published studies on Scedosporium spp. infection were also reviewed, for a better understanding of this disease and reducing the misdiagnosis rate.
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Infecções Fúngicas Invasivas , Afogamento Iminente , Scedosporium , Humanos , Masculino , Idoso , Antifúngicos/uso terapêutico , Voriconazol/uso terapêutico , Pulmão/diagnóstico por imagem , Encéfalo/diagnóstico por imagemRESUMO
Microbial transformation of per- and polyfluoroalkyl substances (PFAS), including fluorotelomer-derived PFAS, by native microbial communities in the environment has been widely documented. However, few studies have identified the key microorganisms and their roles during the PFAS biotransformation processes. This study was undertaken to gain more insight into the structure and function of soil microbial communities that are relevant to PFAS biotransformation. We collected 16S rRNA gene sequencing data from 8:2 fluorotelomer alcohol and 6:2 fluorotelomer sulfonate biotransformation studies conducted in soil microcosms under various redox conditions. Through co-occurrence network analysis, several genera, including Variovorax, Rhodococcus, and Cupriavidus, were found to likely play important roles in the biotransformation of fluorotelomers. Additionally, a metagenomic prediction approach (PICRUSt2) identified functional genes, including 6-oxocyclohex-1-ene-carbonyl-CoA hydrolase, cyclohexa-1,5-dienecarbonyl-CoA hydratase, and a fluoride-proton antiporter gene, that may be involved in defluorination. This study pioneers the application of these bioinformatics tools in the analysis of PFAS biotransformation-related sequencing data. Our findings serve as a foundational reference for investigating enzymatic mechanisms of microbial defluorination that may facilitate the development of efficient microbial consortia and/or pure microbial strains for PFAS biotransformation.
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Biotransformação , Microbiologia do Solo , RNA Ribossômico 16S/genética , Solo/química , Poluentes do Solo/metabolismo , Fluorocarbonos/metabolismoRESUMO
The underlying adaptative mechanisms of anammox bacteria to salt stress are still unclear. The potential role of the anammoxosome in modulating material and energy metabolism in response to salinity stress was investigated in this study. The results showed that anammox bacteria increased membrane fluidity and decreased mechanical properties by shortening the ladderane fatty acid chain length of anammoxosome in response to salinity shock, which led to the breakdown of the proton motive force driving ATP synthesis and retarded energy metabolism activity. Afterward, the fatty acid chain length and membrane properties were recovered to enhance the energy metabolic activity. The relative transmission electron microscopy (TEM) area proportion of anammoxosome decreased from 55.9 to 38.9% under salinity stress. The 3D imaging of the anammox bacteria based on Synchrotron soft X-ray tomography showed that the reduction in the relative volume proportion of the anammoxosome and the concave surfaces was induced by salinity stress, which led to the lower energy expenditure of the material transportation and provided more binding sites for enzymes. Therefore, anammox bacteria can modulate nitrogen and energy metabolism by changing the membrane properties and morphology of the anammoxosome in response to salinity stress. This study broadens the response mechanism of anammox bacteria to salinity stress.
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Oxidação Anaeróbia da Amônia , Bactérias , Anaerobiose , Bactérias/metabolismo , Ácidos Graxos/metabolismo , Estresse Salino , Oxirredução , Salinidade , Nitrogênio/metabolismoRESUMO
Carbonaceous aerosols (CA) from anthropogenic emissions have been significantly reduced in urban China in recent years. However, the relative contributions of fossil and nonfossil sources to CA in rural and background regions of China remain unclear. In this study, the sources of different carbonaceous fractions in fine aerosols (PM2.5) from five background sites of the China Meteorological Administration Atmosphere Watch Network during the winter of 2019 and 2020 were quantified using radiocarbon (14C) and organic markers. The results showed that nonfossil sources contributed 44-69% to total carbon at these five background sites. Fossil fuel combustion was the predominant source of elemental carbon at all sites (73 ± 12%). Nonfossil sources dominated organic carbon (OC) in these background regions (61 ± 13%), with biomass burning or biogenic-derived secondary organic carbon (SOC) as the most important contributors. However, the relative fossil fuel source to OC in China (39 ± 13%) still exceeds those at other regional/background sites in Asia, Europe, and the USA. SOC dominated the fossil fuel-derived OC, highlighting the impact of regional transport from anthropogenic sources on background aerosol levels. It is therefore imperative to develop and implement aerosol reduction policies and technologies tailored to both the anthropogenic and biogenic emissions to mitigate the environmental and health risks of aerosol pollution across China.
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Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Material Particulado/análise , Fósseis , Monitoramento Ambiental/métodos , China , Carbono , Combustíveis Fósseis/análise , Aerossóis/análise , Estações do Ano , AtmosferaRESUMO
BACKGROUND: Missed early gastric cancer (MEGC) is prevalent during esophagogastroduodenoscopy (EGD), which is the first-line recommended strategy for detecting early gastric cancer (EGC). Hence, we explored the risk factors for MEGC and different types of MEGC, based on the endoscopic resected population. METHODS: This retrospective, case-control study was conducted at Nanjing Drum Tower Hospital (NJDTH). We included patients who were diagnosed with EGC during screening EGD, underwent endoscopic resection, and were confirmed by postoperative pathology at the NJDTH from January 2014 to December 2021, and classified them into different types according to the different root causes of misses. Univariable, multivariable, subgroup and propensity score analyses were used to explore the risk factors for MEGC and different types of MEGC. RESULTS: A total of 447 patients, comprising 345 with initially detected early gastric cancer (IDEGC) and 102 with MEGC, were included in this study. Larger size (≥ 1 cm) (OR 0.45, 95% CI 0.27-0.74, P = 0.002) and invasion depth of submucosa (OR 0.26, 95% CI 0.10-0.69, P = 0.007) were negatively associated with MEGC. Use of sedation (OR 0.32, 95% CI 0.20-0.52, P < 0.001) and longer observation time (OR 0.60, 95% CI 0.37-0.96, P = 0.034) exhibited protective effect on MEGC. CONCLUSIONS: Smaller and more superficial EGC lesions are more susceptible to misdiagnosis. The use of sedation and prolonged observation time during EGD could help reduce the occurrence of MEGC.
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Detecção Precoce de Câncer , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Fatores de Risco , Idoso , Detecção Precoce de Câncer/métodos , Diagnóstico Ausente/estatística & dados numéricos , Endoscopia do Sistema Digestório/métodos , Gastroscopia/métodosRESUMO
BACKGROUND AND AIMS: The atherogenic index of plasma (AIP) is associated with progression of atherosclerosis and used to describe how pro- or anti-atherogenic components are balanced. However, the association of AIP with asymptomatic intracranial arterial stenosis (aICAS) is uncertain. The purpose of this study is to investigate the association between AIP and aICAS in rural China. METHODS AND RESULTS: A total of 1990 participants aged ≥40 years free of stroke or transient ischemic attack were enrolled in this study. The presence of aICAS was examined by Transcranial Doppler ultrasound and confirmed by magnetic resonance angiography. The adjusted AIP (aAIP) was calculated according to the ratio of TG and HDL-C and further separated into 4 quartiles. Multiple logistic regression was used to investigate the association between aAIP and aICAS, and the dose-response relationship was explored by restricted cubic spline. After adjusting for conventional confounders, aAIP was significantly higher in the aICAS group than that in the non-aICAS group. Furthermore, the common odds ratios for aICAS risk increased with increasing aAIP quartiles. Multivariate logistic regression revealed that aAIP was independently associated with aICAS in female or middle-aged and elderly (age ≥50 years), and superior to other lipid profiles. Multiple-adjusted spline regression showed the dose-response association between aAIP levels and aICAS prevalence. CONCLUSIONS: AIP might be independently and positively associated with the prevalence of aICAS in middle-aged and elderly women, which might be superior to traditional and nontraditional lipid profiles in rural China.
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Aterosclerose , Acidente Vascular Cerebral , Idoso , Pessoa de Meia-Idade , Feminino , Humanos , Estudos Transversais , Constrição Patológica , Aterosclerose/diagnóstico por imagem , Aterosclerose/epidemiologia , China/epidemiologia , LipídeosRESUMO
BACKGROUND: VT (Ventricular Thrombus) is a serious complication of dilated cardiomyopathy (DCM). Our goal is to develop a nomogram for personalized prediction of incident VT in DCM patients. METHODS: 1267 patients (52.87 ± 11.75 years old, 73.8% male) were analyzed retrospectively from January 01, 2015, to December 31, 2020. A nomogram model for VT risk assessment was established using minimum absolute contraction and selection operator (LASSO) and multivariate logistic regression analysis, and its effectiveness was validated by internal guidance. The model was evaluated by the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). We compared the performance in predicting VT between nomogram and CHA2DS2, CHA2DS2- VASc or ATRIA by AUC, akaike information criterion (AIC), bayesian information criterion (BIC), net reclassification index (NRI), and integrated discrimination index (IDI). RESULTS: 89 patients (7.02%) experienced VT. Multivariate logistic regression analysis revealed that age, left ventricular ejection fraction (LVEF), uric acid (UA), N-terminal precursor B-type diuretic peptide (NT-proBNP), and D-dimer (DD) were important independent predictors of VT. The nomogram model correctly separates patients with and without VT, with an optimistic C score of 0.92 (95%CI: 0.90-0.94) and good calibration (Hosmer-Lemeshow χ2 = 11.51, P = 0.12). Our model showed improved prediction of VT compared to CHA2DS2, CHA2DS2-VASc or ATRIA (all P < 0.05). CONCLUSIONS: The novel nomogram demonstrated better than presenting scores and showed an improvement in predicting VT in DCM patients.
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Cardiomiopatia Dilatada , Cardiopatias , Trombose , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Teorema de Bayes , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/diagnóstico , Nomogramas , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda , Trombose/diagnóstico , Trombose/etiologiaRESUMO
PURPOSE: To our knowledge, we present the first case series investigating the relationship between adaptive optics (AO) imaging and intravenous fluorescein angiography (IVFA) parameters in patients with diabetic retinopathy. METHODS: Consecutive patients with diabetic retinopathy older than age 18 years presenting to a single center in Toronto, Canada, from 2020 to 2021 were recruited. Adaptive optics was performed with the RTX1 camera (Imagine Eyes, Orsay, France) at retinal eccentricities of 2° and 4°. Intravenous fluorescein angiography was assessed with the artificial intelligence-based RETICAD system to extract blood flow, perfusion, and blood-retinal-barrier (BRB) permeability at the same retinal locations. Correlations between AO and IVFA parameters were calculated using Pearson's correlation coefficient. RESULTS: Across nine cases, a significant positive correlation existed between photoreceptor spacing on AO and BRB permeability (r = 0.303, P = 0.027), as well as perfusion (r = 0.272, P = 0.049) on IVFA. When stratified by location, a significant positive correlation between photoreceptor dispersion and both BRB permeability and perfusion (r = 0.770, P = 0.043; r = 0.846, P = 0.034, respectively) was observed. Cone density was also negatively correlated with BRB permeability (r = -0.819, P = 0.046). CONCLUSION: Photoreceptor spacing on AO was significantly correlated with BRB permeability and perfusion on IVFA in patients with diabetic retinopathy. Future studies with larger sample sizes are needed to understand the relationship between AO and IVFA parameters in diverse patient populations.
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Diabetes Mellitus , Retinopatia Diabética , Humanos , Adolescente , Angiofluoresceinografia , Inteligência Artificial , Retina , Células Fotorreceptoras Retinianas Cones , Tomografia de Coerência Óptica/métodosRESUMO
PURPOSE: To investigate the correlation between diabetic retinopathy (DR) severity and microscopic retinal and vascular alterations using adaptive optics imaging. METHODS: In this single-center, prospective cohort study, adult participants with healthy eyes or DR underwent adaptive optics imaging. Participants were classified into control/mild nonproliferative DR, moderate/severe nonproliferative DR, and proliferative DR. Adaptive optics imaging using the RTX1 camera was obtained from 48 participants (87 eyes) for photoreceptor data and from 36 participants (62 eyes) for vascular data. RESULTS: Photoreceptor parameters significantly differed between DR groups at 2° and 4° of retinal eccentricity. Wall-to-lumen ratio varied significantly at 2° eccentricity, while other vascular parameters remained nonsignificant. Cone density and dispersion were the strongest predictors for DR severity ( P < 0.001) in multivariable generalized estimating equation modeling, while other vascular parameters remained nonsignificant between DR severity groups. All photoreceptor parameters showed significant correlations with visual acuity overall and across most DR severity groups. CONCLUSION: To date, this is one of the largest studies evaluating the use of adaptive optics imaging in DR. Adaptive optics imaging was demonstrated to differentiate between various levels of disease severity in DR. These results support the potential role in diagnostic and therapeutic microstructural evaluation in research and clinical practice.
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Retinopatia Diabética , Acuidade Visual , Humanos , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/fisiopatologia , Estudos Prospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Acuidade Visual/fisiologia , Adulto , Idoso , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologiaRESUMO
BACKGROUND: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in pediatric patients, leading to long-term physical, cognitive, and psychological impairments. Blood lactate and fibrinogen levels have emerged as potential biomarkers associated with tissue hypoperfusion and coagulation dysfunction, respectively. However, limited research has specifically focused on the significance of these biomarkers in pediatric TBI. This study aimed to investigate the clinical significance of blood lactate and fibrinogen levels upon admission in pediatric patients with traumatic brain injury. METHODS: The medical records of 80 children with a traumatic brain injury who were admitted from January 2017 to January 2021 were retrospectively analyzed. The two groups were compared according to whether the blood lactate in the admission arterial blood gas increased and the fibrinogen content in the coagulation function decreased. The clinical data of the children in the two groups were different, and then they were divided into a good prognosis group and a poor prognosis group according to the GOS prognostic score, and the differences in the clinical indicators of the two groups were compared. RESULTS: Among the 80 patients, 33 had elevated blood lactate levels, 34 had decreased fibrinogen levels, and 29 had an unfavorable outcome (GOS < 4). Compared to the normal blood lactate group, there were no statistically significant differences in age, sex ratio, or platelet count in the elevated blood lactate group (P > 0.05). However, the elevated blood lactate group had lower Glasgow Coma Scale (GCS) scores upon admission, higher blood lactate levels, lower fibrinogen levels, longer hospital stay, lower GOS scores, and a higher proportion of GOS < 4 (P < 0.05). Compared to the normal fibrinogen group, there were no statistically significant differences in age, sex ratio, or platelet count in the decreased fibrinogen group (P > 0.05). However, the decreased fibrinogen group had lower GCS scores upon admission, higher blood lactate levels, lower fibrinogen levels, longer hospital stays, lower GOS scores, and a higher proportion of GOS < 4 (P < 0.05). Compared to the favorable outcome group, there were no statistically significant differences in age, sex ratio, or platelet count in the unfavorable outcome group (P > 0.05). However, the unfavorable outcome group had lower GCS scores upon admission, higher blood lactate levels, lower fibrinogen levels, longer hospital stays, a higher incidence of pulmonary infection, a higher incidence of stress ulcers, and lower GOS scores (P < 0.05). CONCLUSION: The levels of blood lactate and fibrinogen may represent the severity of children with traumatic brain injury and may be risk factors for poor prognosis of children with traumatic brain injury.
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Lesões Encefálicas Traumáticas , Fibrinogênio , Humanos , Criança , Prognóstico , Estudos Retrospectivos , Lesões Encefálicas Traumáticas/complicações , Escala de Coma de Glasgow , Biomarcadores , LactatosRESUMO
OBJECTIVE: Our research aimed to investigate the therapeutic effects of Tubastatin-A, a glucocorticoid receptor (GR) mitochondrial translocation inhibitor, and mitoquinone (MitoQ), an antioxidant, on attenuating dexamethasone (DEX)-induced macrophage apoptosis. METHODS: We treated RAW264.7 macrophages with different combinations of DEX and either Tubastatin-A or MitoQ. Parameters such as mitochondrial GR translocation, mitochondrial reactive oxygen species levels, mitochondrial membrane potential, mitochondrial permeability transition pore opening, cytochrome C efflux to the cytosol, and apoptosis were subsequently evaluated in the different treatment groups via qRT-PCR, western blotting, and immunofluorescence assays. RESULTS: DEX intervention increased the translocation of GRs into the mitochondria, while reducing the expression of the mitochondrial gene MT-CO1 and the activity of mitochondrial respiratory chain complex IV in macrophages. In addition, DEX administration increased mtROS levels, mitochondrial permeability transition pore opening, and mitochondrial cytochrome C release in macrophages, which promoted their apoptosis. We found that Tubastatin-A inhibited mitochondrial GR translocation and reversed the DEX-induced increase in GR levels within the mitochondria. Furthermore, Tubastatin-A mitigated various mitochondrial changes induced by DEX, including reducing the efflux of mitochondrial cytochrome C and inhibiting macrophage apoptosis. Similarly, MitoQ exerted its effects on macrophage apoptosis by reducing mtROS levels through the mitochondrial pathway. CONCLUSIONS: The DEX-mediated translocation of GR into mitochondria disrupts the mitochondrial function of macrophages, which induces their apoptosis. By inhibiting mitochondrial translocation of GR and reducing mtROS levels, Tubastatin-A and MitoQ can effectively attenuate macrophage apoptosis, which has clinical implications for reducing the notable side effects associated with glucocorticoid use.