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OBJECTIVES: Nasal, paranasal sinus and mucosal disorders are common symptoms in autoimmune rheumatic diseases. Soft tissue changes and fluid accumulation in the osteomeatal complexes and paranasal sinuses manifest as opaqueness on radiological images which can be assessed using visual scoring and computational methods on CT scans, but their results do not always correlate. Using MRI, we investigate the applicability of different image analysis methods in SLE. METHODS: We assessed paranasal sinus opaqueness on MRI from 51 SLE patients, using three visual scoring systems and expert-delineated computational volumes, and examined their association with markers of disease activity, inflammation, endothelial dysfunction and common small vessel disease (SVD) indicators, adjusting for age and sex-at-birth. RESULTS: The average paranasal sinus volume occupation was 4.55 (6.47%) [median (interquartile range) = 0.67 (0.25-2.65) ml], mainly in the maxillary and ethmoid sinuses. It was highly correlated with Lund-Mackay (LM) scores modified at 50% opaqueness cut-off (Spearman's ρ: 0.71 maxillary and 0.618 ethmoids, P < 0.001 in all), and with more granular variations of the LM system. The modified LM scores were associated with SVD scores (0: B = 5.078, s.e. = 1.69, P = 0.0026; 2: B = -0.066, s.e. = 0.023, P = 0.0045) and disease activity (anti-dsDNA: B = 4.59, s.e. = 2.22, P = 0.045; SLEDAI 3-7: 2.86 < B < 4.30; 1.38 < s.e. < 1.63; 0.0083 ≤ P ≤ 0.0375). Computationally derived percent opaqueness yielded similar results. CONCLUSION: In patients with SLE, MRI computational assessment of sinuses opaqueness and LM scores modified at a 50% cut-off may be useful tools in understanding the relationships among paranasal sinus occupancy, disease activity and SVD markers.
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Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Seios Paranasais , Sinusite , Humanos , Doença Crônica , Seios Paranasais/diagnóstico por imagem , Seios Paranasais/patologia , Imageamento por Ressonância Magnética , Doenças Autoimunes/patologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/patologiaRESUMO
Increasing evidence shows that smoking-obtained nicotine is indicated to improve cognition and mitigate certain symptoms of schizophrenia. In this study, we investigated whether chronic nicotine treatment alleviated MK-801-induced schizophrenia-like symptoms and cognitive impairment in mice. Mice were injected with MK-801 (0.2 mg/kg, i.p.), and the behavioral deficits were assessed using prepulse inhibition (PPI) and T-maze tests. We showed that MK-801 caused cognitive impairment accompanied by increased expression of PDZ and LIM domain 5 (Pdlim5), an adaptor protein that is critically associated with schizophrenia, in the prefrontal cortex (PFC). Pretreatment with nicotine (0.2 mg · kg-1 · d-1, s.c., for 2 weeks) significantly ameliorated MK-801-induced schizophrenia-like symptoms and cognitive impairment by reversing the increased Pdlim5 expression levels in the PFC. In addition, pretreatment with nicotine prevented the MK-801-induced decrease in CREB-regulated transcription coactivator 1 (CRTC1), a coactivator of CREB that plays an important role in cognition. Furthermore, MK-801 neither induced schizophrenia-like behaviors nor decreased CRTC1 levels in the PFC of Pdlim5-/- mice. Overexpression of Pdlim5 in the PFC through intra-PFC infusion of an adreno-associated virus AAV-Pdlim5 induced significant schizophrenia-like symptoms and cognitive impairment. In conclusion, chronic nicotine treatment alleviates schizophrenia-induced memory deficits in mice by regulating Pdlim5 and CRTC1 expression in the PFC.
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Disfunção Cognitiva , Maleato de Dizocilpina , Camundongos , Animais , Maleato de Dizocilpina/metabolismo , Maleato de Dizocilpina/farmacologia , Nicotina/farmacologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Córtex Pré-Frontal/metabolismo , Cognição , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: The prevalence of Restless legs syndrome (RLS) in End Stage Renal Disease (ESRD) patients is higher than that in the general population. However, the associations of RLS within the ESRD population are inconsistent and RLS is usually neglected in dialysis centers, although it impairs the life quality among ESRD patients. We aim to investigate the prevalence of RLS in patients with ESRD undergoing maintenance hemodialysis and evaluate the risk factors of developing RLS and the effect of RLS on quality of life among ESRD patients. METHODS: ESRD patients undergoing maintenance hemodialysis in Shanghai General Hospital dialysis unit from July 2016 to October 2016 were enrolled in the study. RLS was diagnosed according to the criteria of the International Restless Legs Syndrome Study Group (IRLSSG). IRLSSG Severity Scale was used to evaluate the severity of RLS. Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality, and Hospital Anxiety and Depression Scale (HADS) was used to estimate anxiety and depression. Serologic and historic variables were analyzed to determine predictors of RLS in the ESRD population. RESULTS: A total of 137 ESRD patients were enrolled. The prevalence of RLS among the ESRD patients was 20.44%. The risk of RLS was increased significantly in females (OR = 2.729, p = 0.032) and daily alcohol drinkers (OR = 4.716, p = 0.022). RLS increased the risks of sleep disorders (25/28, 89.3% vs 73/109, 67.0%, p = 0.02) and sedative hypnotics intake (7/28, 25.0% vs 10/109, 9.2%, p = 0.047) and impaired the sleep quality (7/109 vs 11/28, p = 0.001) according to PSQI sum scores. CONCLUSION: A high RLS prevalence among the ESRD patients undergoing hemodialysis was confirmed. ESRD patients who are women and drinking alcohol have a higher risk of RLS. The sleep quality was significantly impaired and sleeping medication use was more common among the ESRD patients with RLS.
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Falência Renal Crônica/terapia , Diálise Renal , Síndrome das Pernas Inquietas/epidemiologia , Adulto , Idoso , Ansiedade/epidemiologia , China , Depressão/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Qualidade de Vida , Fatores de Risco , Sono , Transtornos do Sono-Vigília/epidemiologiaRESUMO
BACKGROUND: Neurological disorders are an economic and public health burden which requires efficient and adequate medical resources. Currently, little is known about the status of the quality of neurological care services available in China. As neurological primary care is mostly provided at the county hospital level, investigation of this geographical level is required. The aim of this study is to evaluate currently available neurology care services in Yangtze River Delta Urban Agglomerations in east China. METHODS: A multi-site, county-level hospital-based observational survey was conducted in east China from January 2017 to December 2017. A questionnaire was made to assess hospital and the departmental patient care capabilities, human resources and technical capacity in neurology departments. RESULTS: Of 228 hospitals across the Yangtze River Delta Urban Agglomerations, 217 documents were returned. Of these, 22 were excluded due to invalid hospital information or duplicate submission. Overall, most hospitals have neurology departments (162, 83.1%) while less than half of the hospitals have a stroke center (80, 41.0%) and neurology emergency department (46, 23.6%). Among 162 hospitals with neurology department, 5 were excluded due to inadequate sharing, leaving 157 hospitals for analysis. About 84.1% of these neurology departments can administer intravenous thrombolysis while about one third of them has the ability to perform arterial thrombectomy (36.9%). In addition, 46.2% of hospitals can carry out computed tomography angiography (CTA) in emergency room. Tertiary care hospitals are much more equipped with modern medical resources compared to the secondary hospitals. In four administrative regions, the neurology services are better in more economically advanced regions. CONCLUSIONS: Neurological care services need to be enhanced at the county-level hospitals to improve health care delivery.
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Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Hospitais de Condado/estatística & dados numéricos , Neurologia/estatística & dados numéricos , China , Humanos , Neurologia/organização & administração , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: This study aimed to investigate the therapeutic potential of monoclonal antibody (mAb) against HBV as a novel treatment approach to chronic hepatitis B (CHB) in mouse models. METHODS: Therapeutic effects of mAbs against various epitopes on viral surface protein were evaluated in mice mimicking persistent HBV infection. The immunological mechanisms of mAb-mediated viral clearance were systematically investigated. RESULTS: Among 11 tested mAbs, a novel mAb E6F6 exhibited the most striking therapeutic effects in several HBV-persistent mice. Single-dose administration of E6F6 could profoundly suppress the levels of hepatitis B surface antigen (HBsAg) and HBV DNA for several weeks in HBV-transgenic mice. E6F6 regimen efficiently prevented initial HBV infection, and reduced viral dissemination from infected hepatocytes in human-liver-chimeric mice. E6F6-based immunotherapy facilitated the restoration of anti-HBV T-cell response in hydrodynamic injection (HDI)-based HBV carrier mice. Immunological analyses suggested that the Fcγ receptor-dependent phagocytosis plays a predominant role in E6F6-mediated viral suppression. Molecular analyses suggested that E6F6 recognises an evolutionarily conserved epitope (GPCK(R)TCT) and only forms a smaller antibody-viral particle immune complex with limited interparticle crosslinking when it binds to viral particles. This unique binding characteristic of E6F6 to HBV was possibly associated with its effective in vivo opsonophagocytosis for viral clearance. CONCLUSIONS: These results provided new insight into understanding the therapeutic role and mechanism of antibody against persistent viral infection. The E6F6-like mAbs may provide a novel immunotherapeutic agent against human chronic HBV infection.
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Anticorpos Monoclonais/farmacologia , Antígenos de Superfície da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Imunoterapia/métodos , Animais , DNA Viral/efeitos dos fármacos , Modelos Animais de Doenças , Epitopos , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatócitos/virologia , Camundongos , Camundongos Transgênicos , Fagocitose , Replicação Viral/efeitos dos fármacosRESUMO
The cAMP-responsive element binding protein (CREB)-regulated transcription coactivator, CRTC (also known as transducer of regulated CREB, TORC), is identified as a potent modulator of cAMP response element (CRE)-driven gene transcription. The CRTC family consists of three members (CRTC1-3), among which the CRTC1 shows the highest expression in the brain. Several studies have demonstrated that the CRTC1 plays critical roles in neuronal dendritic growth, long-term synaptic plasticity, memory consolidation and reconsolidation etc., whereas dysfunction of CRTC1 is mainly involved in neurodegenerative disorders. In light of these findings, we aim to review recent research reports that indicate the CRTC1 dysfunction and its underlying mechanisms in the neurodegenerative disorders.
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Doenças Neurodegenerativas/fisiopatologia , Fatores de Transcrição/fisiologia , Encéfalo/fisiologia , Dendritos/fisiologia , Humanos , Plasticidade NeuronalRESUMO
AIM: To analyze the spectrum of isolated pathogens and antibiotic resistance for ocular infections within 5y at two tertiary hospitals in east China. METHODS: Ocular specimen data were collected from January 2019 to October 2023. The pathogen spectrum and positive culture rate for different infection location, such as keratitis, endophthalmitis, and periocular infections, along with antibiotic resistance were analyzed. RESULTS: We included 2727 specimens, including 827 (30.33%) positive cultures. A total of 871 strains were isolated, 530 (60.85%) bacterial and 341 (39.15%) fungal strains were isolated. Gram-positive cocci (GPC) were the most common ocular pathogens. The most common bacterial isolates were Staphylococcus epidermidis (25.03%), Staphylococcus aureus (7.46%), Streptococcus pneumoniae (4.59%), Corynebacterium macginleyi (3.44%), and Pseudomonas aeruginosa (3.33%). The most common fungal genera were Fusarium spp. (12.74%), Aspergillus spp. (6.54%), and Scedosporium spp. (5.74%). Staphylococcus epidermidis strains showed more than 50% resistance to fluoroquinolones. Streptococcus pneumoniae and Corynebacterium macginleyi showed more than 90% resistance to erythromycin. The percentage of bacteria showing multidrug resistance (MDR) significantly decreased (χ 2=17.44, P=0.002). CONCLUSION: GPC are the most common ocular pathogens. Corynebacterium macginleyi, as the fourth common bacterium, may currently be the local microbiological feature of east China. Fusarium spp. is the most common fungus. More than 50% of the GPC are resistant to fluoroquinolones, penicillins, and macrolides. However, the proportion of MDR strains has been reduced over time.
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BACKGROUND: Growing interest surrounds perivascular spaces (PVS) as a clinical biomarker of brain dysfunction given their association with cerebrovascular risk factors and disease. Neuroimaging techniques allowing quick and reliable quantification are being developed, but, in practice, they require optimisation as their limits of validity are usually unspecified. NEW METHOD: We evaluate modifications and alternatives to a state-of-the-art (SOTA) PVS segmentation method that uses a vesselness filter to enhance PVS discrimination, followed by thresholding of its response, applied to brain magnetic resonance images (MRI) from patients with sporadic small vessel disease acquired at 3 T. RESULTS: The method is robust against inter-observer differences in threshold selection, but separate thresholds for each region of interest (i.e., basal ganglia, centrum semiovale, and midbrain) are required. Noise needs to be assessed prior to selecting these thresholds, as effect of noise and imaging artefacts can be mitigated with a careful optimisation of these thresholds. PVS segmentation from T1-weighted images alone, misses small PVS, therefore, underestimates PVS count, may overestimate individual PVS volume especially in the basal ganglia, and is susceptible to the inclusion of calcified vessels and mineral deposits. Visual analyses indicated the incomplete and fragmented detection of long and thin PVS as the primary cause of errors, with the Frangi filter coping better than the Jerman filter. COMPARISON WITH EXISTING METHODS: Limits of validity to a SOTA PVS segmentation method applied to 3 T MRI with confounding pathology are given. CONCLUSIONS: Evidence presented reinforces the STRIVE-2 recommendation of using T2-weighted images for PVS assessment wherever possible. The Frangi filter is recommended for PVS segmentation from MRI, offering robust output against variations in threshold selection and pathology presentation.
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Doenças de Pequenos Vasos Cerebrais , Humanos , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Neuroimagem , Gânglios da Base/diagnóstico por imagemRESUMO
The concept of L-fuzzy lattice is presented by means of an L-fuzzy partially ordered set. An L-fuzzy partially ordered set A is an L-fuzzy lattice if and only if one of A[a], A([a]), and A(a) is a lattice.
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Algoritmos , Lógica Fuzzy , Modelos Teóricos , Simulação por ComputadorRESUMO
OBJECTIVE: To survey the prevalence, operative status, surgical coverage rate and social burden rate of cataract blindness among older adults aged 50 years or above in 2 typical counties (district) of Jiangsu Province, China in 2010. METHODS: Cluster sampling was used in randomly selected 12 867 individuals aged 50 years or above in 58 clusters in Funing County of Northern Jiangsu and Binhu District of Southern Jiangsu. Among them, 12 053 individuals received visual acuity and eye examinations (response rate 93.8%). Lens and cataract operative status were evaluated by slit-lamp biomicroscope. Data bank was established by Epidata3.0 Software. Statistical analyses were performed with Stata/SE Statistical Software, version 10.0. Confidence intervals and P values (significant at P < 0.05) for prevalence of cataract, surgical coverage rate of cataract, social burden rate and surgical outcomes of cataract blindness were calculated with adjustment for clustering effects and stratification associated with the sampling design. RESULTS: Among 12 503 individuals, there were 2208 cases of cataract with a prevalence of 18.3%. The prevalence of cataract was higher in the aged, female and lower-income persons (P < 0.05). Among 2208 cataract patients, cataract surgery was performed in 263 cases (11.9%). The surgical coverage rate of cataract was 59.7% and the social burden rate of cataract blindness 1.93%. The social burden rate of cataract blindness was higher in the aged persons (P < 0.01). In 357 eyes with cataract surgery, the rate of intraocular lens implantation was 85.7%. At Binhu, 71.0% of eyes with cataract surgery underwent phacoemulsification. At Funing, 73.6% of eyes underwent modern extra-capsular surgery respectively. Post-operative presenting and best corrected visual acuity over 0.7 was 11.2% and 19.6% of operated eyes respectively. The main causes of post-operative eyes with worse visual acuity (< 0.3) were post-capsular opacity and retinal disorders. CONCLUSION: Cataract is the most common and important eye disease that may lead into blindness and severe visual impairment among older adults aged 50 years or above. The coverage rate of cataract surgery is higher in Jiangsu province than in other provinces. The visual outcomes of surgery is less than ideal. An important task in blindness prevention of Jiangsu province still is the elimination of cataract blindness and the improvement of visual outcomes for cataract surgery in the future.
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Extração de Catarata/estatística & dados numéricos , Catarata/epidemiologia , População Rural , Idoso , Idoso de 80 Anos ou mais , Catarata/diagnóstico por imagem , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , UltrassonografiaRESUMO
After meiosis, round spermatid develops into mature sperm through metamorphosis. During this stage, most cytoplasm in the germ cell is gradually lost. The histones associated with chromatin are replaced by transition proteins and eventually transformed into protamines. Thus, the spermatid chromatin is stringently packaged and highly concentrated. It was thought that the transcription activity of spermatid is lost and RNAs are absent in spermatid. Nevertheless, many types of transcripts are detected in recent years, including the transcripts needed during chromatin repackaged and some small RNAs, etc. Because histones in the nuclear are not replaced entirely, and there are some active sites on the chromatin, we conjectured that spermatid has some transcription activity, and this activity is regulated by hormone and epigenetic modification. These RNAs may be the residues in the spermatogenesis, or timely expressed during spermiogenesis. A deep study on gene transcription in spermiogenesis will help understand the genetic characteristics and provide the theoretic basis for reproductive control using male gamete. This article reviewed recent advances in spermiogenesis at gene transcription level and proposed the future research directions.
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Regulação da Expressão Gênica no Desenvolvimento , Espermatogênese , Espermatozoides/citologia , Transcrição Gênica , Animais , Humanos , Masculino , Espermátides/citologia , Espermátides/metabolismo , Espermatozoides/metabolismoRESUMO
Triacylglycerols (TAGs) are a major component of intramuscular fat. Diacylglycerol O-acyltransferase 2(DGAT2) expression determines the rate of TAG synthesis. The purpose of this study was to investigate the role of DGAT2 in the differentiation of Yanbian cattle preadipocytes and lipid metabolism-related signalling pathways. Bovine preadipocytes were infected with overexpression and interfering adenovirus vectors of DGAT2. The effects on the differentiation of Yanbian cattle preadipocytes were examined using molecular and transcriptomic techniques, including differentially expressed genes (DEGs) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. DGAT2 overexpression significantly increased (p < 0.05) intracellular TAG, adiponectin, and lipid droplet (LD) contents. Moreover, it upregulated (p < 0.05) peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α, and fatty acid binding protein 4 mRNA expression. In contrast, DGAT2 knockdown reduced intracellular TAG and LD content and downregulated (p < 0.05) C/EBPß, mannosyl (alpha-1,3-)-glycoproteinbeta-1,2-N-acetylglucosaminyltransferase, lipin 1,1-acylglycerol-3-phosphate O-acyltransferase 4, and acetyl-CoA carboxylase alpha mRNA expression. Between DGAT2-overexpressing preadipocytes and normal cells, 208 DEGs were identified, including 106 upregulated and 102 downregulated genes. KEGG pathway analysis revealed DEGs mainly enriched in PPAR signalling and AMP-activated protein kinase pathways, cholesterol metabolism, and fatty acid biosynthesis. These results demonstrated that DGAT2 regulated preadipocyte differentiation and LD and TAG accumulation by mediating the expression of adipose differentiation-, lipid metabolism-, and fatty acid synthesis-related genes.
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BACKGROUND: The paranasal sinus mucosal thickening, visible in magnetic resonance imaging (MRI), maybe a source of inflammation in microvessels, but its relationship with small vessel disease (SVD) is unclear. We reviewed the literature and analysed a sample of patients with sporadic SVD to identify any association between paranasal sinus opacification severity and SVD neuroimaging markers. METHODS: We systematically reviewed MEDLINE and EMBASE databases up to April 2020 for studies on paranasal sinus mucosal changes in patients with SVD, cerebrovascular disease (CVD), and age-related neurodegenerative diseases. We analysed clinical and MRI data from 100 participants in a prospective study, the Mild Stroke Study 3 (ISRCTN 12113543) at 1-3, 6 and 12 months following a minor stroke to test key outcomes from the literature review. We used multivariate linear regression to explore associations between modified Lund-Mackay (LM) scores and brain, white matter hyperintensities (WMH), enlarged perivascular spaces (PVS) volumes at each time point, adjusted for baseline age, sex, diabetes, hypercholesterolaemia, hypertension and smoking. RESULTS: The literature review, after screening 3652 publications, yielded 11 primary studies, for qualitative synthesis with contradictory results, as positive associations/higher risk from 5/7 CVD studies were contradicted by the two studies with largest samples, and data from dementia studies was equally split in their outcome. From the pilot sample of patients analysed (female N = 33, mean age 67.42 (9.70) years), total LM scores had a borderline negative association with PVS in the centrum semiovale at baseline and 6 months (B = -0.25, SE = 0.14, p = 0.06) but were not associated with average brain tissue, WMH or normal-appearing white matter volumes. CONCLUSION: The inconclusive results from the literature review and empirical study justify larger studies between PVS volume and paranasal sinuses opacification in patients with sporadic SVD.
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Doenças de Pequenos Vasos Cerebrais , Transtornos Cerebrovasculares , Seios Paranasais , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Masculino , Estudos Prospectivos , Doenças de Pequenos Vasos Cerebrais/patologia , Encéfalo/patologia , Acidente Vascular Cerebral/complicações , Transtornos Cerebrovasculares/complicações , Imageamento por Ressonância Magnética , Seios Paranasais/patologiaRESUMO
Cerebral small vessel disease (SVD) is a cause of stroke and dementia. Retinal capillary microvessels revealed by optical coherence tomography angiography (OCTA) are developmentally related to brain microvessels. We quantified retinal vessel density (VD) and branching complexity, investigating relationships with SVD lesions, white matter integrity on diffusion tensor imaging (DTI) and cerebrovascular reactivity (CVR) to CO2 in patients with minor stroke. We enrolled 123 patients (mean age 68.1 ± SD 9.9 years), 115 contributed retinal data. Right (R) and left (L) eyes are reported. After adjusting for age, eye disease, diabetes, blood pressure and image quality, lower VD remained associated with higher mean diffusivity (MD) (standardized ß; R -0.16 [95%CI -0.32 to -0.01]) and lower CVR (L 0.17 [0.03 to 0.31] and R 0.19 [0.02 to 0.36]) in normal appearing white matter (NAWM). Sparser branching remained associated with sub-visible white matter damage shown by higher MD (R -0.24 [-0.08 to -0.40]), lower fractional anisotropy (FA) (L 0.17 [0.01 to 0.33]), and lower CVR (R 0.20 [0.02 to 0.38]) in NAWM. OCTA-derived metrics provide evidence of microvessel abnormalities that may underpin SVD lesions in the brain.
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Doenças de Pequenos Vasos Cerebrais , Acidente Vascular Cerebral , Substância Branca , Humanos , Idoso , Imagem de Tensor de Difusão/métodos , Imageamento por Ressonância Magnética/métodos , Doenças de Pequenos Vasos Cerebrais/patologia , Substância Branca/patologia , Microvasos/patologia , Acidente Vascular Cerebral/patologiaRESUMO
PURPOSE: To explore the effect of doxycycline on vasculogenic mimicry (VM) formation and the potential mechanism in human pterygium fibroblasts in order to find novel targets for pterygium therapy. METHODS: First, we demonstrate the existence of VM in 73 pterygium specimens by CD31 and periodic acid Schiff (PAS) dual staining. Then we used cell counting kit-8, clone formation assay and flow cytometry to prove the inhibitory effect of doxycycline on cell proliferation and apoptosis. The VM formation was evaluated through wound healing assay, cell transwell assay and three-dimensional cell culture combined with PAS staining. Finally, we used Western blot to testify the correlation of the VM and the factors in protein level preliminarily. RESULTS: Our results showed that VM existed in human pterygium specimens exactly. Otherwise, in human pterygium fibroblasts, doxycycline induced a dose-dependent inhibitory effect on cell proliferation and apoptosis induction. Besides, doxycycline significantly suppressed vasculogenic mimicry tube formation, cell migration and invasion. Furthermore, doxycycline impaired the expression of MMP-9, MMP-2 and VEGF which may related to pterygium VM formation. CONCLUSIONS: Doxycycline decelerated pterygium progression might be through inhibiting VM formation according to the downregulation of MMP-9, MMP-2 and VEGF, which may provide the basis of further studies involving doxycycline for pterygium treatment.
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Metaloproteinase 2 da Matriz , Pterígio , Linhagem Celular Tumoral , Túnica Conjuntiva/anormalidades , Doxiciclina/farmacologia , Fibroblastos/metabolismo , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neovascularização Patológica/metabolismo , Ácido Periódico , Pterígio/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Intramuscular fat (IMF) is closely related to the tenderness, juiciness, and flavor of beef, and is an important indicator for beef quality assessment internationally. The main components of skeletal intramuscular fat (IMF) are phospholipids and triacylglycerols (TAG), and the final step of TAG biosynthesis is catalyzed by diacylglycerol acyltransferase 2 (DGAT2). To explore the effect of DGAT2 on the differentiation of bovine muscle satellite cells (BSCs) and its role in the signaling pathway related to lipid metabolism, the adenovirus overexpression and interference vector of the DGAT2 gene was constructed in this study, and the overexpression adenovirus Ad-DGAT2 and interfering adenovirus sh-DGAT2 were used to infect BSCs. Overexpression of DGAT2 resulted in a significant increase in the contents of TAG and ADP, and the mRNA and protein expression levels of PPARγ, C/EBPα, and SREBF1 (p < 0.05). Interfering with the expression of DGAT2 reduced the intracellular TAG content and lipid droplet accumulation. Furthermore, the mRNA and protein expression levels of PPARγ, C/EBPα, and SREBF1 (p < 0.05) were significantly downregulated. Transcriptome sequencing showed that a total of 598 differentially expressed genes (DEGs) were screened in BSCs infected with Ad-DGAT2, and these DEGs included 292 upregulated genes and 306 downregulated genes. A total of 49 DEGs were screened in BSCs infected with sh-DGAT2, and these DEGs included 25 upregulated and 24 downregulated genes. KEGG enrichment analysis showed that the DEGs, after overexpression of DGAT2, were mainly enriched in the PPAR signaling pathway, and the fat digestion and absorption, glycerophospholipid metabolism, fatty acid biosynthesis, and AMPK signaling pathways. The DEGs obtained after interfering with DGAT2 were mainly enriched in the metabolic pathways, such as the PPAR signaling pathway and PI3K/AKT signaling pathway. In summary, our study demonstrated that the lipid droplet formation, TAG accumulation, and adipogenic gene expression in BSCs overexpressing DGAT2 were higher than those in the control cells. These results highlight the important role of DGAT2 in regulating BSCs during adipogenic transdifferentiation and underscore the complexity of intramuscular adipogenesis.
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ABSTRACT: A quasi-dynamic food chain model (Chi-FDMT) was developed to predict the consequences of nuclear accidents on the food chain through the ingestion pathway in Chinese agricultural conditions. The Chi-FDMT structure is based on ECOSYS-87, with some revised calculation processes and the adoption of new parameters; herein, it was applied to two regions in China. The model was used to estimate the spatial and temporal patterns of crop plant activity and ingestion dose in the Chinese agricultural environment at the scale of the Fukushima nuclear disaster. A comparative study between Chi-FDMT and an equilibrium model demonstrated good agreement for depositions occurring during the growth season. The parameter sensitivity analysis of Chi-FDMT indicated that the parameters of food intake and processing factor are sensitive, and the sensitivity of the transfer factors within plant and soil-plant systems are dependent on the deposition scenario.
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Cadeia Alimentar , Acidente Nuclear de Fukushima , Agricultura , China , Solo/químicaRESUMO
[This corrects the article DOI: 10.7150/thno.20047.].
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Impulse control disorders (ICDs) in Parkinson's disease (PD) are aberrant behavior such as pathological gambling, hypersexuality, binge eating, and compulsive buying, which typically occur as a result of dopaminergic therapy. Numerous studies have focused on the broad spectrum of ICDs-related behaviors and their tremendous impact on patients and their family members. Recent advances have improved our understanding of ICDs. In this review, we discuss the epidemiology, pathogenesis and treatment of ICDs in the setting of PD.
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Wake-up stroke (WUS) is a subgroup of ischemic stroke in which patients show no abnormality before sleep while wake up with neurological deficits. In addition to the uncertain onset, WUS patients have difficulty to receive prompt and effective thrombolytic or reperfusion therapy, leading to relatively poor prognosis. A number of researches have indicated that CT or MRI based thrombolysis and endovascular therapy might have benefits for WUS patients. This review article narratively discusses the pathogenesis, risk factors, imaging-based diagnosis and recanalization treatments of WUS with the purpose of expanding current treatment options for this group of stroke patients and exploring better therapeutic methods. The result showed that multimodal MRI or CT scan might be the best methods for extending the time window of WUS and, therefore, a large proportion of WUS patients could have favorable prognosis.