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1.
J Pediatr Orthop ; 43(2): 83-90, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36607918

RESUMO

BACKGROUND: Irreducible atlantoaxial rotatory fixation (IAARF) often requires surgical treatment. Transoral unlocking the facet joints is a key measure for the treatment of IAARF. We investigate a novel method for treating pediatric IAARF by unlocking facet joint through transoral appraoch and fixed with slim-tarp plate in same stage with same approach. OBJECTIVE: The objective of this study is to investigate the method and efficacy of a unique transoral approach to unlock facet joints and fixation with slim-shaped transoral anterior reduction plate (slim-TARP) plate in the treatment of IAARF. METHODS: Fifteen patients diagnosed with AARF were transferred to our hospital. After 1 week of bidirectional cervical cranial traction, they were diagnosed with irreducible AARF that, and then underwent transoral release and fixation with slim-TARP plate procedures. Postoperative computed tomography and magnetic resonance were used to evaluate the reduction effect, bone fusion, and fusion time. Japanese orthopaedic association scores were used to compare the recovery of spinal cord function in patients before and after surgery. Complications such as wound infection, neurovascular injury, and loosening of internal fixation were evaluated too. RESULTS: All 15 patients underwent transoral unlocking facet joint and fixation with slim-TARP procedures smoothly. The operation time were 129.2±11.9 minutes, blood loose were 83±23 mL. There were no neurological injury, wound infections, verified or suspected vertebral artery injury, etc. All patients were followed up for a mean of 17.8±6.6 months (range: 12 to 36 mo). Bony fusion was achieved in all patients. Mean fusion time was 3.6±1.2 months (range: 3 to 6 mo). Complete correction of torticollis was achieved in all 15 cases. Preoperative symptoms of neck pain and limitation of neck movement were effectively alleviated at 3 months after surgery. The 3 patients with preoperative neurological deficits had significant relief after surgery, and their latest follow-up results showed that their Japanese orthopaedic association scores increased from 13.0±1.0 to 16.3±0.6. CONCLUSIONS: Transoral release and fixation with slim-TARP plate by transoral approach is a feasible and safe method for treating pediatric irreducible atlantoaxial rotatory fixation.


Assuntos
Articulação Atlantoaxial , Luxações Articulares , Fusão Vertebral , Articulação Zigapofisária , Humanos , Criança , Articulação Zigapofisária/cirurgia , Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoaxial/cirurgia , Descompressão Cirúrgica/métodos , Fusão Vertebral/métodos , Luxações Articulares/cirurgia , Luxações Articulares/etiologia , Resultado do Tratamento
2.
Expert Syst Appl ; 217: 119549, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36694806

RESUMO

The sudden outbreak of COVID-19 has dramatically altered the state of the global economy, and the stock market has become more volatile and even fallen sharply as a result of its negative impact, heightening investors' apprehension regarding the correlation between unexpected events and stock market volatility. Additionally, internal and external characteristics coexist in the stock market. Existing research has struggled to extract more effective stock market features during the COVID-19 outbreak using a single time-series neural network model. This paper presents a framework for multitasking learning-based stock market forecasting (COVID-19-MLSF), which can extract the internal and external features of the stock market and their relationships effectively during COVID-19.The innovation comprises three components: designing a new market sentiment index (NMSI) and COVID-19 index to represent the external characteristics of the stock market during the COVID-19 pandemic. Besides, it introduces a multi-task learning framework to extract global and local features of the stock market. Moreover, a temporal convolutional neural network with a multi-scale attention mechanism is designed (MA-TCN) alongside a Multi-View Convolutional-Bidirectional Recurrent Neural Network with Temporal Attention (MVCNN-BiLSTM-Att), adjusting the model to account for the changing status of COVID-19 and its impact on the stock market. Experiments indicate that our model achieves superior performance both in terms of predicting the accuracy of the China CSI 300 Index during the COVID-19 period and in terms of sing market trading.

3.
Chem Commun (Camb) ; 59(7): 904-907, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36594844

RESUMO

We report on the first example of a PdIV-containing polyoxopalladate(II). The discrete mixed-valent polyoxopalladate(IV/II), [PdIVPdII6O6((CH3)2AsO2)6]2-, comprising a central PdIV ion that is surrounded by a six-membered PdII-oxo ring capped by six dimethylarsinate groups, was synthesized and structurally characterized in the solid state, in solution and in the gas phase by multiple analytical techniques.

4.
Life Sci ; 316: 121378, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36623767

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP) is an environmental toxicant that is widely used in the whole world as a plasticizer that can enhance plastic properties. A number of reserarches have demonstrated that DEHP could cause varying degrees of damage to the normal function of nerve. The research aimed to investigate the mechanism of DEHP-induced cerebellar toxicity. In present study, we set DEHP-caused cerebellar injury models of quail and implied that DEHP induced cerebellar dysplasia by abnormity of Purkinje cell and reduction of cerebellar granule cell. Furthermore, the mitochondrial damage was confirmed by the swelling, cristae reduction, membrane rupture of mitochondria or even the occurrence of autophagic vacuole. To clarified DEHP-induced mitochondrial damage in cerebellum, we examined the relevant genes of mitochondrial biogenesis, mitochondrial dynamics, oxidative damage, the pathways related to Nrf2 and PINK1/Parkin in cerebellum. Based on data, it appeared that DEHP treatment had a damaging effect on the cerebellum and led to mitophagy as well as oxidative stress. In conclusion, the research indicated that DEHP-actuated mitochondrial injury has a directly relationship with mitophagy. DEHP-actuated reduced mitochondrial biogenesis and dysregulation of mitochondrial dynamics. The increase of oxidative stress damaged mitochondria, and the redundant ROS in damaged mitochondria that gave rise to cerebellar harm.

5.
Nature ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36634707

RESUMO

Despite the success of PD-1 blockade in melanoma and other cancers, effective treatment strategies to overcome resistance to cancer immunotherapy are lacking1,2. We identified the innate immune kinase TANK-binding kinase 1 (TBK1)3 as a candidate immune evasion gene in a pooled genetic screen4. Using a suite of genetic and pharmacologic tools across multiple experimental model systems, we confirm a role for TBK1 as an immune evasion gene. Targeting TBK1 enhances response to PD-1 blockade by lowering the cytotoxicity threshold to effector cytokines (TNFα/IFNγ). TBK1 inhibition in combination with PD-1 blockade also demonstrated efficacy using patient-derived tumour models, with concordant findings in matched patient-derived organotypic tumour spheroids (PDOTS) and matched patient-derived organoids (PDOs). Tumour cells lacking TBK1 are primed to undergo RIPK- and caspase-dependent cell death in response to TNFα/IFNγ in a JAK/STAT-dependent manner. Taken together, our results demonstrate that targeting TBK1 is a novel and effective strategy to overcome resistance to cancer immunotherapy.

6.
Life Sci ; 315: 121274, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36509195

RESUMO

AIMS: Oral squamous cell carcinoma (OSCC) is considered as the sixth most common cancer worldwide characterized by high invasiveness, high metastasis rate and high mortality. It is urgent to explore novel therapeutic strategies to overcome this feature. Metformin is currently a strong candidate anti-tumor drug in multiple cancers. However, whether metformin could inhibit cancer progression by regulating RNA alternative splicing remains largely unknown. MAIN METHODS: Cell proliferation and growth ability of CAL-27 and UM-SCC6 were analyzed by CCK8 and colony formation assays. Cell migration was judged by wound healing assay. Mechanistically, RNA-seq was applied to systematically identify genes that are regulated by metformin. The expression of metformin-regulated genes was determined by real-time quantitative PCR (RT-qPCR). Metformin-regulated alternative splicing events were confirmed by RT-PCR. KEY FINDINGS: We demonstrated that metformin could significantly inhibit the proliferation and migration of oral squamous cell carcinoma cells. Mechanistically, in addition to transcriptional regulation, metformin induces a wide range of alternative splicing alteration, including genes involved in centrosome, cellular response to DNA damage stimulus, GTPase binding, histone modification, catalytic activity, regulation of cell cycle process and ATPase complex. Notably, metformin specifically modulates the splicing of NUBP2, a component of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA). Briefly, metformin favors the production of NUBP2-L, the long splicing isoform of NUBP2, thereby inhibiting cancer cell proliferation. SIGNIFICANCE: Our findings provide mechanistic insights of metformin on RNA alternative splicing regulation, thus to offer a potential novel route for metformin to inhibit cancer progression.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Metformina , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , RNA/metabolismo , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Processamento Alternativo , Metformina/farmacologia , Metformina/uso terapêutico , Proliferação de Células , Neoplasias de Cabeça e Pescoço/genética , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica
8.
Front Oncol ; 12: 999873, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505800

RESUMO

Introduction: Cancer in patients of childbearing age continues to become increasingly common. The purpose of this study was to explore the impact of metastatic breast cancer (MBC) on overall survival (OS) and cancer-specifific survival (CSS) in patients of childbearing age and to construct prognostic nomograms to predict OS and CSS. Methods: Data from MBC patients of childbearing age were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015, and the patients were randomly assigned into the training and validation cohorts. Univariate and multivariate Cox analyses were used to search for independent prognostic factors impacting OS and CSS, and these data were used to construct nomograms. The concordance index (C-index), area under the curve (AUC), and calibration curves were used to determine the predictive accuracy and discriminative ability of the nomograms. Additional data were obtained from patients at the Yunnan Cancer Hospital to further verify the accuracy of the nomograms. Results: A total of 1,700 MBC patients of childbearing age were identifified from the SEER database, and an additional 92 eligible patients were enrolled at the Yunnan Cancer Hospital. Multivariate Cox analyses identifified 10 prognostic factors for OS and CSS that were used to construct the nomograms. The calibration curve for the probabilities of OS and CSS showed good agreement between nomogram prediction and clinical observations. The C-index of the nomogram for OS was 0.735 (95% CI = 0.725-0.744); the AUC at 3 years was 0.806 and 0.794 at 5 years.The nomogram predicted that the C-index of the CSS was 0.740 (95% CI = 0.730- 0.750); the AUC at 3 years was 0.811 and 0.789 at 5 years. The same results were observed in the validation cohort. Kaplan- Meier curves comparing the low-,medium-, and high-risk groups showed strong prediction results for the prognostic nomogram. Conclusion: We identifified several independent prognostic factors and constructed nomograms to predict the OS and CSS for MBC patients of childbearing age.These prognostic models should be considered in clinical practice to individualize treatments for this group of patients.

9.
EPMA J ; 13(4): 597-614, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36505894

RESUMO

Acute aortic dissection (AAD) is a severe aortic injury disease, which is often life-threatening at the onset. However, its early prevention remains a challenge. Therefore, in the context of predictive, preventive, and personalized medicine (PPPM), it is particularly important to identify novel and powerful biomarkers. This study aimed to identify the key markers that may contribute to the predictive early risk of AAD and analyze their role in immune infiltration. Three datasets, including a total of 23 AAD and 20 healthy control aortic samples, were retrieved from the Gene Expression Omnibus (GEO) database, and a total of 519 differentially expressed genes (DEGs) were screened in the training set. Using the least absolute shrinkage and selection operator (LASSO) regression model and the random forest (RF) algorithm, FERMT1 (AUC = 0.886) and SGCD (AUC = 0.876) were identified as key markers of AAD. A novel AAD risk prediction model was constructed using an artificial neural network (ANN), and in the validation set, the AUC = 0.920. Immune infiltration analysis indicated differential gene expression in regulatory T cells, monocytes, γδ T cells, quiescent NK cells, and mast cells in the patients with AAD and the healthy controls. Correlation and ssGSEA analysis showed that two key markers' expression in patients with AAD was correlated with many inflammatory mediators and pathways. In addition, the drug-gene interaction network identified motesanib and pyrazoloacridine as potential therapeutic agents for two key markers, which may provide personalized medical services for AAD patients. These findings highlight FERMT1 and SGCD as key biological targets for AAD and reveal the inflammation-related potential molecular mechanism of AAD, which is helpful for early risk prediction and targeted prevention of AAD. In conclusion, our study provides a new perspective for developing a PPPM method for managing AAD patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00302-4.

10.
JTCVS Tech ; 16: 139-148, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36510546

RESUMO

Objectives: Localization of pulmonary nodules is challenging. However, traditional localization methods have high radiation doses and a high risk of complications. We developed a noninvasive 3-dimensional printing navigational template for intraoperative localization. It can reduce puncture-related complications and simplify the localization process. This study will verify the feasibility of this method. Methods: Patients with peripheral pulmonary nodules were included in this study. The computed tomography scan sequences were obtained to design a digital template model, which was then imported into a 3-dimensional printer to produce a physical navigational template. Finally, the navigational template is placed into the patient's pleural cavity for intraoperative localization. The precision of the nodule localization and associated complications were evaluated. Results: Twelve patients were finally included in this study. Intraoperative navigational template localization was used in all patients. The success rate of intraoperative nodule localization was 100%, and the median time of localization was 19.5 minutes (range, 16-23.5 minutes). The deviation median of the navigational template was 2.1 mm (range, 1.1-2.7 mm). Among the included patients, no significant complications occurred during intraoperative localization. Conclusions: The 3-dimensional printing template for intraoperative localization is feasible, will cause no trauma to the patient, and has acceptable accuracy for application in nodules localization. This navigational template greatly simplifies the localization process and may potentially break the dependence of percutaneous localization on computed tomography scanning.

11.
ACS Omega ; 7(49): 45535-45544, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36530244

RESUMO

Microwave-assisted synthesis and spectral analysis of certain novel derivatives of 3,4-diaminothieno[2,3-b]thiophene-2,5-dicarbonitrile 1-7 were carried out. Compounds 1-7 were examined for cytotoxicity against MCF-7 and A549 cell lines using the quantitative MTT method, and gefitinib and erlotinib were used as reference standards. Compounds 1-7 were shown to be more active than erlotinib against the two cell lines tested. Compound 2 outperformed regular erlotinib by 4.42- and 4.12-fold in MCF-7 and A549 cells, respectively. The most cytotoxic compounds were subsequently studied for their suppression of kinase activity using the homogeneous time-resolved fluorescence assay versus epidermal growth factor receptor (EGFRWT) and EGFR790M. With IC50 values of 0.28 ± 0.03 and 5.02 ± 0.19, compound 2 was demonstrated to be the most effective against both forms of EGFR. Furthermore, compound 2 also had the best antioxidant property, decreasing the radical scavenging activity by 78%. Molecular docking research, on the other hand, was carried out for the analyzed candidates (1-7) to study their mechanism of action as EGFR inhibitors. In silico absorption, distribution, metabolism, excretion, and toxicity tests were also performed to explain the physicochemical features of the examined derivatives.

12.
Risk Manag Healthc Policy ; 15: 2311-2322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518997

RESUMO

Purpose: Students spend extended hours using electronic devices due to online teaching. Digital eye strain (DES) and dry eye disease (DED) symptoms are both associated with prolonged screen exposure time and may co-occur. This study aimed to evaluate the correlation between DES and DED symptoms and determine the prevalence of DED according to the severity of DES. Patients and Methods: This cross-sectional study was conducted among international students in Chinese universities. The survey was built using Wenjuan Mini Program and distributed using the WeChat platform. The questionnaire assessed participants' screen exposure, the 20-20-20 rule, ED practices, and DED awareness. Computer Vision Syndrome Questionnaire (CVS-Q) and Dry Eye Questionnaire (DEQ-5) were used to diagnose DES and DED symptoms, respectively. Results: 498 students completed the survey, but 452 were considered for the study. Predictors of DES and DED symptoms were conjunctivitis, eye allergy, glares, tired eye, neck pain, back pain, PhD students, and daily spending > 9h on screen (P < 0.05 for all). We observed that an increase in DES scores also exponentially increases DED scores. Among students diagnosed with DES symptoms, 26.5% had mild to moderate DED symptoms, and 8.2% had severe DED symptoms. In contrast, only 8.4% and 0.9% of those with asymptomatic DES had mild to moderate and severe DED symptoms, respectively (P < 0.000). A strong and significant positive correlation (r = 0.695, P < 0.000) between DES and DED scores was found. Conclusion: We found an extremely high prevalence of DES and DED symptoms compared to the previous studies with a similar population group. We believe that the prevalence of DED may be underestimated in the young population. Training about proper ED practices is mandatory to prevent these deleterious ocular surface conditions.

13.
Front Pharmacol ; 13: 1044375, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36569291

RESUMO

Background: Neuroinflammation plays a pivotal role in the pathogenesis of Central Nervous System (CNS) diseases. The phenolic glucoside gastrodin (GAS), has been known to treat CNS disorders by exerting anti-inflammatory activities. Our aim was to investigate the potential neuroprotective mechanisms of GAS on lipopolysaccharide (LPS)-induced mice. Methods: Male C57BL/6J mice were treated by LPS, before which GAS was adminisrated. The behavior tests such as forced swim test, tail suspension test, and elevated plus maze were performed to evaluate depressive-anxiety-like behaviors. A high-throughput sequencing (HTS) analysis was performed to screen out distinctive miRNAs which were validated using quantitative real-time PCR. Then, miRNA agomir or NC was injected stereotaxically into hippocampus of mice to explore the role of miRNA on GAS in response to LPS. Furthermore, Immunofluorescence and the hematoxylin and eosin (H&E) staining were employed to observe the cellular morphology. The protein levels of pro-inflammatory factors were evaluated by western blot. Finally, the target mRNA of miRNA was predicted using bioinformatics analysis. GO and KEGG enrichment analyses were conducted to clarify the potential function of target protein, which were visualized by bubble charts. Results: The behavioral data showed that mice in the LPS group had obvious depressive-anxiety-like behaviors, and 100 mg/kg GAS could improve these behavioral changes and alleviate the levels of pro-inflammatory cytokines in the hippocampus when mice were exposed to LPS for 6 h. Meanwhile, LPS-induced microglia and astrocyte activation in the CA1, CA2, CA3, and DG regions of the hippocampus were also reversed by GAS. Furthermore, miR-107-3p were screened out and verified for GAS in response to LPS. Importantly, miR-107-3p overexpression negatively abrogated the neuroprotective effects of GAS. Moreover, KPNA1 might be the target molecular of miR-107-3p. KPNA1 might regulate 12 neuroinflammation-related genes, which were mainly involved in cytokine-mediated signaling pathway. Conclusion: These results suggested that GAS might alleviate the LPS-induced neuroinflammation and depressive-anxiety-like behaviors in mice by downregulating miR-107-3p and upregulating the downstream target KPNA1. The indicates miR-107-3p may provide a new strategy for the treatment of CNS diseases.

14.
Sensors (Basel) ; 22(23)2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36502040

RESUMO

In this paper, an optimal-damage-effectiveness cooperative-control strategy based on a damage-efficiency model and a virtual-force method is proposed to solve the pursuit-evasion problem with multiple guided missiles. Firstly, different from the overly ideal assumption in the traditional pursuit-evasion problem, an optimization problem that maximizes the damage efficiency is established and solved, making the optimal-damage-effectiveness strategy more meaningful for practical applications. Secondly, a modified virtual-force method is proposed to obtain this optimal-damage-effectiveness control strategy, which solves the numerical solution challenges brought by the high-complexity damage function. Thirdly, adaptive gain is designed in this strategy based on guidance-integrated fuze technology to achieve robust maximum damage efficiency in unpredictable interception conditions. Finally, the effectiveness and robustness of the proposed strategy are verified by numerical simulations.

15.
Nat Commun ; 13(1): 7841, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36543785

RESUMO

The developments of pure organic room-temperature phosphorescence (RTP) materials with circularly polarized luminescence (CPL) have significantly facilitated the future integration and systemization of luminescent material in fundamental science and technological applications. Here, a type of photoinduced circularly polarized RTP materials are constructed by homogeneously dispersing phosphorescent chiral helical substituted polyacetylenes into a processable poly(methyl methacrylate) (PMMA) matrix. These substituted polyacetylenes play vital roles in the propagation of CPL and present prominently optical characteristics with high absorption and luminescent dissymmetric factors up to 0.029 (gabs) and 0.019 (glum). The oxygen consumption properties of the films under UV light irradiation endow materials with dynamic chiro-optical functionality, which can leverage of light to precisely control and manipulate the circularly polarized RTP properties with the remarkable advantages of being contactless, wireless and fatigue-resistant. Significantly, the distinct materials with dynamic properties can be used as anti-counterfeiting materials involving photoprogrammability.

16.
Brain Sci ; 12(12)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36552081

RESUMO

PURPOSE: Retinal pigment epithelial (RPE) cells are highly specialized neural cells with several functions essential for vision. Progressive deterioration of RPE cells in elderly individuals can result in visual impairment and, ultimately, blinding disease. While human embryonic stem cell-derived RPE cell (hESC-RPE) growth conditions are generally harsher than those of cell lines, the subretinal transplantation of hESC-RPE is being clinically explored as a strategy to recover the damaged retina and improve vision. The cell-adhesion ability of the support is required for RPE transplantation, where pre-polarized cells can maintain specific functions on the scaffold. This work examined four typical biodegradable hydrogels as supports for hESC-RPE growth. METHODS: Four biodegradable hydrogels were examined: gelatin methacryloyl (GelMA), hyaluronic acid methacryloyl (HAMA), alginate, and fibrin hydrogels. ARPE-19 and hESC-RPE cells were seeded onto the hydrogels separately, and the ability of these supports to facilitate adherence, proliferation, and homogeneous distribution of differentiated hESC-RPE cells was investigated. Furthermore, the hydrogel's subretinal bio-compatibility was assessed in vivo. RESULTS: We showed that ARPE-19 and hESC-RPE cells adhered and proliferated only on the fibrin support. The monolayer formed when cells reached confluency, demonstrating the polygonal semblance, and revealing actin filaments that moved along the cytoplasm. The expression of tight junction proteins at cell interfaces on the 14th day of seeding demonstrated the barrier function of epithelial cells on polymeric surfaces and the interaction between cells. Moreover, the expression of proteins crucial for retinal functions and matrix production was positively affected by fibrin, with an increment of PEDF. Our in vivo investigation with fibrin hydrogels revealed high short-term subretinal biocompatibility. CONCLUSIONS: The research of stem cell-based cell therapy for retinal degenerative diseases is more complicated than that of cell lines. Our results showed that fibrin is a suitable scaffold for hESC-RPE transplantation, which could be a new grafting material for tissue engineering RPE cells.

17.
Proc Natl Acad Sci U S A ; 119(48): e2208934119, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36409895

RESUMO

In ischemic retinopathy, overactivated retinal myeloid cells are a crucial driving force of pathological angiogenesis and inflammation. The cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) signaling are key regulators of inflammation. This study aims to investigate the association of cGAS-STING signaling with ischemic retinopathy and the regulation of its activation. We found that protein levels of cGAS and STING were markedly up-regulated in retinal myeloid cells isolated from mice with oxygen-induced retinopathy (OIR). Knockout of Sting and pharmacological inhibition of STING both alleviated retinal neovascularization (NV) and reduced retinal vascular leakage in OIR. Further, Sting knockout and STING inhibitor also alleviated leukocyte adhesion to retinal vasculature and infiltration into the retina as well as microglial activation in OIR. These results suggest that cGAS-STING signaling played a pathogenic role in retinal myeloid cell activation and NV in ischemic retinopathy. To identify the regulation of cGAS-STING signaling in OIR, we evaluated the role of transcription factor peroxisome proliferator-activated receptor α (PPARα). The results demonstrated that PPARα was down-regulated in OIR retinas, primarily in myeloid cells. Furthermore, Pparα knockout significantly up-regulated cGAS and STING levels in retinal CD11b+ cells, while PPARα agonist inhibited cGAS-STING signaling and cytosolic mitochondrial DNA (mtDNA) release, a causative feature for cGAS activation. Knockout of Sting ameliorated retinal NV, hyperpermeability, and leukostasis in Pparα-/- mice with OIR. These observations suggest that PPARα regulates cGAS-STING signaling, likely through mtDNA release, and thus, is a potential therapeutic target for ischemic retinopathy.


Assuntos
PPAR alfa , Doenças Retinianas , Animais , Camundongos , Modelos Animais de Doenças , DNA Mitocondrial , Inflamação , Isquemia/complicações , Proteínas de Membrana/metabolismo , Camundongos Knockout , Neovascularização Patológica , Nucleotidiltransferases/metabolismo , PPAR alfa/genética , Doenças Retinianas/genética
18.
World J Pediatr ; 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36409451

RESUMO

Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment,  and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.

19.
Neuroradiology ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36394613

RESUMO

PURPOSE: To describe vertebral artery (VA) variation in patients with or without osseous anomalies at congenital craniovertebral junction (CVJ). METHODS: In the present study, we retrospectively analyzed 258 patients with VA variation who underwent three-dimensional computed tomography angiography (3D CTA) in our hospital from March 2017 to October 2019. RESULTS: Among 258 patients, 180 were accompanied by skeleton structural malformation, including 105 cases of occipital ossification of the atlas, 8 cases of the bipartite atlas, 7 cases of hypoplasia of the posterior arch of the atlas, 45 cases of C2/3 congenital fusion, 2 cases of C2/3/4 congenital fusion, and 13 cases of congenital os odontoid. VA variation was divided into type A (VA variation in the CVJ area without osseous anomalies) and type B (VA variation in the CVJ area with osseous anomalies). There are totally 10 subtypes, including type A1 (atlas occipitalization with VA entrance approach close to middle line, 20.2%); type A2 (atlas occipitalization with VA entrance approach far from middle line, 30.2%); type A3 (first intersegmental VA in C1-C2, 1.9%); type A4 (fenestration of the VA, 2.3%); type A5 (VA bulging type, 6.6%); type A6 (VA exposures with the absence of the posterior atlas arch, 2.3%); type A7 (C2 inner wall type, 0.4%); type A8 (single vertebral artery, 2.3%); type B1 (posterior ponticuli, 2.7%); and type B2 (high-riding VA, 31.4%). CONCLUSION: This study is expected to take the lead in the most comprehensive classification of VA variation.

20.
Inorg Chem ; 61(46): 18524-18535, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36342975

RESUMO

A family of five host-guest assemblies comprising different metal ions inside a cuboid 12-palladium-oxo cage, [MO8Pd12L8]n- (MPd12L8, M = ScIII, CoII, CuII, L = AsO43-; M = CdII, HgII, L = PhAsO32-), was synthesized and structurally characterized in the solid state by single-crystal X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and thermogravimetric analysis, and their solution and gas-phase stability were validated by multinuclear NMR spectroscopy and electrospray-ionization mass spectrometry (ESI-MS). The polyoxopalladates (POPs) ScPd12As8, CoPd12As8, and CuPd12As8 represent the first three examples of the MPd12As8 archetype. The unique cubic ligand field of {MO8} allows for collecting the speciation profiles of the POPs in solution using 45Sc and 113Cd NMR techniques. Detailed magnetic and electron paramagnetic resonance (EPR) studies were performed on CuPd12As8. Catalytic studies on MPd12As8 (M = CuII and CoII) supported on SBA-15 unveiled a guest metal-dependent structure-function relationship, with CuPd12As8 being the more efficient precatalyst for the hydroconversion of o-xylene in a fixed-bed reactor.

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