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1.
Brain Topogr ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35006499

RESUMO

To study the associations between RDH12 gene mutations, fundus types, and clinical manifestations. In total, 46 patients with inherited eye diseases caused by RDH12 gene mutations were included in this study. High-throughput chip capture sequencing, Sanger sequencing, and gene panel detection were used to determine that RDH12 was the pathogenic gene. All patients underwent the following detailed ophthalmic examinations: visual acuity, visual field, intraocular pressure, fundus photography, electroretinography, and optical coherence tomography (OCT). Statistical analysis was used to evaluate the clinical phenotype. A total of 32 mutations were identified in 46 patients. The most common mutations were c.437T > A, c.184C > T, and c.524C > T; the corresponding amino acid changes were p.Val146Asp, p.Arg62Ter, and p.Ser175Leu. Of the 46 patients, retinitis pigmentosa (RP) was found in 31 (68.9%); leber congenital amaurosis (LVA) was found in 11 (24.4%); early onset of severe retinal dystrophy (EOSRD) was found in one (2.2%); cone rod dystrophy (CORD) was found in one (2.2%); and Stargardt disease was found in one (2.2%). There was a significant difference in best-corrected visual acuity among patients based on fundus type (p = 0.0124). Linear trend analysis showed that best-corrected visual acuity gradually decreased as the fundus type increased in severity. In addition, there was a significant difference in the incidence of night blindness among patients with different fundus types (p = 0.0429): types I and IV fundi were associated with the highest incidences of night blindness. RDH12 gene mutation can cause serious inherited retinal diseases, which primarily include RP and LCA. Combined with clinical symptoms and fundus types, the progression of the disease can be characterized and used to guide genetic diagnosis and gene therapy.

2.
Support Care Cancer ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022886

RESUMO

BACKGROUND: Hospice care (HC) is specialized medical care for terminal patients who are nearing the end of life. Interdisciplinary collaborative hospice care (ICHC) is where experts from different disciplines and patients/caregivers form a treatment team to establish shared patient care goals. However, the ICHC efficacy has not been frequently studied in the terminal geriatric cancer patient (TGCP) population. This study aimed to gain insight into ICHC provided to TGCPs by an ICHC team and identify factors to ameliorate multidimensional HC. METHODS: 166 TGCPs were randomized by a computer-generated random number table using an allocation ratio of 1:1. The patients were divided into the ICHC group and life-sustaining treatment (LST) group. The scores of these questionnaires, such as EORTC, QLQ-C30, Hamilton anxiety scale, the median survival time (MST), symptoms improvement, the median average daily cost of drugs (MADDC), the median total cost of drugs (MTDC) in the last 2 days, and medical care satisfaction were observed in both groups. RESULTS: After treatment, the improvement of emotional function and symptoms in the ICHC group were statistically higher than those in the LST group (P < 0.05). The MADDC and the MTDC in the last 2 days were statistically lower in the ICHC group than those in the LSTs group (P < 0.01). In addition, the overall satisfaction situation and the cooperation ability in the ICHC group were statistically higher than those in the LST group (P < 0.01). CONCLUSION: The ICHC could provide TGCPs with coordinated, comfortable, high-quality, and humanistic care.

3.
Neural Regen Res ; 17(7): 1588-1595, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34916445

RESUMO

Cellular senescence and proliferation are essential for wound healing and tissue remodeling. However, senescence-proliferation cell fate after peripheral nerve injury has not been clearly revealed. Here, post-injury gene expression patterns in rat sciatic nerve stumps (SRP113121) and L4-5 dorsal root ganglia (SRP200823) obtained from the National Center for Biotechnology Information were analyzed to decipher cellular senescence and proliferation-associated genetic changes. We first constructed a rat sciatic nerve crush model. Then, ß-galactosidase activities were determined to indicate the existence of cellular senescence in the injured sciatic nerve. Ki67 and EdU immunostaining was performed to indicate cellular proliferation in the injured sciatic nerve. Both cellular senescence and proliferation were less vigorous in the dorsal root ganglia than in sciatic nerve stumps. These results reveal the dynamic changes of injury-induced cellular senescence and proliferation from both genetic and morphological aspects, and thus extend our understanding of the biological processes following peripheral nerve injury. The study was approved by the Animal Ethics Committee of Nantong University, China (approval No. 20190226-001) on February 26, 2019.

4.
Spectrochim Acta A Mol Biomol Spectrosc ; 269: 120694, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34922288

RESUMO

Wheat from different producing areas has different flavor and properties, and thus the identification of producing area of wheat is significant to assure the quality of wheat. The traditional method of producing area of wheat determination is time-consuming, complex and needs a lot of pretreatment. The purpose of this research is to develop a new method for the determination of wheat producing areas by terahertz time domain spectroscopy in combination with chemometrics. Firstly, a total of 240 wheat samples from Shandong Province, Shaanxi Province, Henan Province, Hebei Province and Anhui Province of China were collected to analyze and obtain the time-domain spectral signals, frequency-domain spectral signals, and absorption coefficient spectral signals of the samples were obtained. Then, four different preprocessing methods of Savitzky-Golay (S-G), multiplicative scatter correction (MSC), mean centering, and standard normal variate (SNV) were applied to preprocess the absorption coefficient spectral signals, and the uninformative variable elimination (UVE) was used for variable selection of THz spectra data, for developing an effective prediction model. Finally, chemometrics methods, including the partial least squares discriminant analysis (PLS-DA), back propagation neural network (BPNN) and least squares support vector machines (LS-SVM) qualitative models were used for model building and discrimination results obtained through such models were compared. According to the test results, the comprehensive discrimination accuracy of wheat from different origins by the SNV-LS-SVM model reached 96.76%, Furthermore, these results demonstrated that an accurate qualitative analysis of producing area of wheat samples could be achieved by terahertz time-domain spectroscopy combined with chemometrics, which can provide a fast and accurate solution for grain security detection and origin tracing.

5.
Proc Natl Acad Sci U S A ; 118(51)2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34921112

RESUMO

We uncovered a transcription factor (TF) network that regulates cortical regional patterning in radial glial stem cells. Screening the expression of hundreds of TFs in the developing mouse cortex identified 38 TFs that are expressed in gradients in the ventricular zone (VZ). We tested whether their cortical expression was altered in mutant mice with known patterning defects (Emx2, Nr2f1, and Pax6), which enabled us to define a cortical regionalization TF network (CRTFN). To identify genomic programming underlying this network, we performed TF ChIP-seq and chromatin-looping conformation to identify enhancer-gene interactions. To map enhancers involved in regional patterning of cortical progenitors, we performed assays for epigenomic marks and DNA accessibility in VZ cells purified from wild-type and patterning mutant mice. This integrated approach has identified a CRTFN and VZ enhancers involved in cortical regional patterning in the mouse.


Assuntos
Córtex Cerebral/embriologia , Redes Reguladoras de Genes , Elementos Reguladores de Transcrição , Fatores de Transcrição/metabolismo , Animais , Fator I de Transcrição COUP/metabolismo , Córtex Cerebral/metabolismo , Epigenoma , Proteínas de Homeodomínio/metabolismo , Proteínas com Homeodomínio LIM/metabolismo , Camundongos , Fator de Transcrição PAX6/metabolismo , Fator de Transcrição 1 de Leucemia de Células Pré-B/metabolismo , Fatores de Transcrição/genética
6.
Nature ; 598(7879): 129-136, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34616068

RESUMO

The mammalian cerebrum performs high-level sensory perception, motor control and cognitive functions through highly specialized cortical and subcortical structures1. Recent surveys of mouse and human brains with single-cell transcriptomics2-6 and high-throughput imaging technologies7,8 have uncovered hundreds of neural cell types distributed in different brain regions, but the transcriptional regulatory programs that are responsible for the unique identity and function of each cell type remain unknown. Here we probe the accessible chromatin in more than 800,000 individual nuclei from 45 regions that span the adult mouse isocortex, olfactory bulb, hippocampus and cerebral nuclei, and use the resulting data to map the state of 491,818 candidate cis-regulatory DNA elements in 160 distinct cell types. We find high specificity of spatial distribution for not only excitatory neurons, but also most classes of inhibitory neurons and a subset of glial cell types. We characterize the gene regulatory sequences associated with the regional specificity within these cell types. We further link a considerable fraction of the cis-regulatory elements to putative target genes expressed in diverse cerebral cell types and predict transcriptional regulators that are involved in a broad spectrum of molecular and cellular pathways in different neuronal and glial cell populations. Our results provide a foundation for comprehensive analysis of gene regulatory programs of the mammalian brain and assist in the interpretation of noncoding risk variants associated with various neurological diseases and traits in humans.


Assuntos
Cérebro/citologia , Cérebro/metabolismo , Sequências Reguladoras de Ácido Nucleico/genética , Animais , Atlas como Assunto , Cromatina/química , Cromatina/genética , Cromatina/metabolismo , Montagem e Desmontagem da Cromatina , Regulação da Expressão Gênica , Predisposição Genética para Doença/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doenças do Sistema Nervoso/genética , Neuroglia/classificação , Neuroglia/metabolismo , Neurônios/classificação , Neurônios/metabolismo , Análise de Sequência de DNA , Análise de Célula Única
7.
Curr Issues Mol Biol ; 43(2): 1156-1170, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34563051

RESUMO

HiChIP and PLAC-Seq are emerging technologies for studying genome-wide long-range chromatin interactions mediated by the protein of interest, enabling more sensitive and cost-efficient interrogation of protein-centric chromatin conformation. However, due to the unbalanced read distribution introduced by protein immunoprecipitation, existing reproducibility measures developed for Hi-C data are not appropriate for the analysis of HiChIP and PLAC-Seq data. Here, we present HPRep, a stratified and weighted correlation metric derived from normalized contact counts, to quantify reproducibility in HiChIP and PLAC-Seq data. We applied HPRep to multiple real datasets and demonstrate that HPRep outperforms existing reproducibility measures developed for Hi-C data. Specifically, we applied HPRep to H3K4me3 PLAC-Seq data from mouse embryonic stem cells and mouse brain tissues as well as H3K27ac HiChIP data from human lymphoblastoid cell line GM12878 and leukemia cell line K562, showing that HPRep can more clearly separate among pseudo-replicates, real replicates, and non-replicates. Furthermore, in an H3K4me3 PLAC-Seq dataset consisting of 11 samples from four human brain cell types, HPRep demonstrated the expected clustering of data that could not be achieved by existing methods developed for Hi-C data, highlighting the need for a reproducibility metric tailored to HiChIP and PLAC-Seq data.

9.
J Vis Exp ; (174)2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34487114

RESUMO

A combined regional homogeneity (ReHo) and functional connectivity (FC) method, a type of noninvasive functional magnetic resonance imaging (fMRI) method, has been used to evaluate synchronous neuronal activity changes in retinitis pigmentosa (RP). The purpose of this study is to describe our method for analysis of intra- and interregional synchronizations of changes in neuronal activity in RP patients. The advantages of the combined ReHo and FC method are that it is both noninvasive and sufficiently sensitive to investigate changes in cerebral synchronous neuronal activity changes in vivo. Here, 16 RP patients and 14 healthy controls closely matched in age, sex, and education underwent resting-state fMRI scans. Two sample t-tests were conducted to compare ReHo and FC across groups. Our results showed that visual network disconnection and reorganization of the retino-thalamocortical pathway and dorsal visual stream occurred in the RP patients. Here, we describe the details of this method, its use, and the impact of its key parameters in a step-by-step manner.


Assuntos
Imageamento por Ressonância Magnética , Córtex Visual , Encéfalo , Mapeamento Encefálico , Humanos , Córtex Visual/diagnóstico por imagem
10.
Anal Methods ; 13(36): 4120-4130, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34554150

RESUMO

The detection of the wheat moisture content plays a key role in grain storage and classification. Harvested wheat grains were taken as samples in the current research. A total of 240 reaped wheat samples with different moisture contents were tested by applying terahertz (THz) spectroscopy. The frequency domain spectra and absorption coefficient spectra of wheat were obtained in the band of 0.1-1.2 THz, and the spectra were pretreated by mean centering, Savitzky-Golay (S-G), Multiplicative Scatter Correction (MSC) and Stand Normal Variate (SNV), respectively. Then a special algorithm of Tabu Search (TS) was used to find out the effective variables and remove the useless variables from the terahertz spectrum of the sample. Finally, the partial least squares (PLS) of chemometrics were used for quantitative model building and prediction. The correlation coefficient of calibration (Rc) is 0.9522. The root mean square error of calibration (RMSEC) is 0.4730. The correlation coefficient of prediction (Rp) is 0.9531. The root mean square error of prediction (RMSEP) is 0.5396. The results demonstrated that an accurate quantitative analysis of moisture in wheat samples could be achieved by terahertz time-domain spectroscopy combined with the TS algorithm. In addition, the results show that the model S-G + MSC + TS + PLS can effectively predict wheat moisture, and provide a rapid quantitative detection and analysis method for the detection of wheat moisture.


Assuntos
Espectroscopia Terahertz , Algoritmos , Calibragem , Análise dos Mínimos Quadrados , Triticum
11.
Exp Eye Res ; 210: 108728, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34390734

RESUMO

PURPOSE: Activation of bone morphogenetic protein (BMP) 4 signaling promotes the survival of retinal ganglion cell (RGC) after acute injury. Chordin-like 1 (CHRDL1) is an endogenous BMP antagonist. In this study, we researched whether CHRDL1 was involved in BMP4 signaling and regulation of RGC degeneration in a mouse model of glaucoma. METHODS: Magnetic microbeads were intracameral injected to induce experimental glaucoma in a mouse model. A recombinant adeno-associated virus (rAAV) system was designed for overexpression of BMP4 or CHRDL1 in mouse retina. Immunohistochemistry and hematoxylin-eosin (HE) stains were performed to identify changes in retinal morphology. Electroretinogram (ERG) recordings were used to assess changes in visual function. RESULTS: The mRNA expression levels of Bmp4 and its downstream BMPRIa, small mothers against decapentaplegic 1 (Smad1), were significantly upregulated in retinas with glaucoma. RGC survival was significantly enhanced in the beads + AAV-BMP4 group and significantly reduced in the beads + AAV-CHRDL1 group, compared with the beads + AAV-EGFP group. Similar results were observed in retinal explant culture in vitro. Consistent with these findings, the photopic negative response (PhNR)responses in ERG, which indicate RGC function, were restored in mice overexpressing BMP4, whereas a-wave and b-wave responses were not. Activation of CHRLD1 inhibited Smad1/5/8 phosphorylation and exacerbated RGC damage. The expression of Glial fibrillary acidic protein (GFAP) was decreased significantly in beads + AAV-BMP4 group. CONCLUSIONS: BMP4 promoted RGC survival and visual function in an experimental glaucoma model. Activation of CHRDL1 exaggerated RGC degeneration by inhibiting the BMP4/Smad1/5/8 pathway. The mechanism of BMP4/Smad1/5/8 pathway may be related to the inhibition of glial cell activation. Our studies suggested that BMP4 and CHRLD1 might serve as therapeutic targets in glaucoma.


Assuntos
Proteína Morfogenética Óssea 4/genética , Modelos Animais de Doenças , Proteínas do Olho/metabolismo , Regulação da Expressão Gênica/fisiologia , Glaucoma/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Células Ganglionares da Retina/fisiologia , Animais , Proteína Morfogenética Óssea 4/antagonistas & inibidores , Sobrevivência Celular , Dependovirus/genética , Eletrorretinografia , Vetores Genéticos , Glaucoma/fisiopatologia , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Pressão Intraocular/fisiologia , Injeções Intravítreas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Retina/fisiopatologia
12.
Front Pharmacol ; 12: 694741, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34385918

RESUMO

Purpose: Chinese herbal medicine (CHM) is an important complementary and alternative therapy for the management of irritable bowel syndrome (IBS). Previous meta-analyses suggested that CHM is effective for IBS; nonetheless, its effectiveness is inconclusive owing to repeated significance testing. We aimed to examine the efficacy and safety of CHM for IBS through a meta-analysis and trial sequential analysis (TSA). Methods: We searched OVID Medline, Embase, Cochrane Central Register of Controlled Trials, and Web of Science from January 1, 1980, to September 20, 2020. The primary outcome was adequate relief of global IBS symptoms. The secondary outcomes included relief of abdominal pain and treatment-related adverse events. The relative ratio (RR) and required information size (RIS) were calculated for each outcome. Results: Ten trials recruiting 2,501 participants were included. Seven (70%) trials were at low risk of bias (RoB). Compared with placebo, CHM was associated with a significantly higher proportion of adequate relief of global IBS symptoms [RR 1.76 (95% confidence interval (95%CI), 1.33-2.33); I 2 = 81.1%; p < 0.001]. The RIS was 1,083 for the primary outcome, and the accrued information size was 1,716. The analysis of the relief of abdominal pain (three trials with 916 participants) showed similar results compared with placebo [RR 1.85 (95%CI, 1.59-2.14); I 2 = 0%; p < 0.001; RIS = 197 participants]. CHM was associated with a higher proportion of adverse events compared with placebo [RR 1.51 (95%CI, 1.14-2); I 2 = 0%; p = 0.004]. Conclusion: CHM was effective in relieving IBS symptoms but caused a higher adverse event rate than placebo. TSA analysis confirmed the findings with sufficient information size.

14.
Vascular ; : 17085381211040991, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34459287

RESUMO

PURPOSE: To assess the clinical efficiency and imaging outcome of applying covered stent grafts for the treatment of complex carotid artery lesions. METHOD: A total of 39 consecutive patients with carotid artery lesions treated with covered stent grafts at our institution from December 2016 to December 2019 were reviewed. Two kinds of stent including self-expandable covered stent (Viabahn; W. L. Gore & Associates) and balloon-expandable covered stent (Willis; Microport) were applied. The angiograms immediately after the procedure, perioperative complications, and follow-up outcomes were recorded. RESULT: Based on imaging features, 11 patients exhibited pseudoaneurysms, 23 patients had blood blister-like aneurysms (BBAs), and five patients were carotid cavernous fistulas. A total of 40 stent implantations were performed, including nine Viabahn stents and 31 Willis stents. Two patients received double implants of Willis stents. Stent failed to perform for one patient due to tortuous parent artery. The angiography reports immediately after the procedure showed that the lesions in 36 patients were completely occluded, whereas two patients had minimal endoleaks. With respect to the occurrence of procedural complications, an aneurysm ruptured during the procedure in one case, which resulted in CCF, and acute in-stent thrombosis occurred in another case. Clinical and angiographic follow-up (11.2±2.4 months) sessions were conducted for 38 patients and a complete lesion exclusion was achieved in 36 patients. The minimal endoleak persisted in one patient and another patient experienced recurrence with stent migration, leading to ipsilateral blepharoptosis. However, none of the patients developed hemorrhage or ischemia and in-stent stenosis was not observed. CONCLUSION: Covered stent grafts appear to be a safe and feasible for the treatment of complex carotid artery lesions. Despite the potential for stent delivery failure as well as endoleak and procedure-related complications, covered stent grafts should be considered when selecting the optimal treatment strategy.

15.
Diabetes Metab Syndr Obes ; 14: 3209-3219, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285528

RESUMO

Objective: The purpose of the study was to find the differences in intrinsic functional connectivity (FC) patterns of the primary visual area (V1) among diabetic retinopathy (DR), diabetes mellitus (DM), and healthy controls (HCs) applying resting-state functional magnetic resonance imaging (rs-fMRI). Patients and Methods: Thirty-five subjects with DR (18 males and 17 females), 22 DM (10 males and 12 females) and 38 HCs (16 males and 22 females) matched for sex, age, and education underwent rs-fMRI scanning. Seed-based FC analysis was performed to find the alterations in the intrinsic FC patterns of V1 in DR compared with DM and HCs. Results: The study found that DR patients had a significant lower FC between the bilateral calcarine (CAL)/left lingual gyrus (LING) (BA 17/18) and the left V1, and between the bilateral CAL/left LING (BA 17/18) and the right V1 compared with the HCs. Meanwhile, patients with DR exhibited higher FC strength between the left V1 and the bilateral Caudate/Olfactory/Orbital superior frontal gyrus (OSFG), and between the bilateral Caudate/Olfactory/OSFG (BA 3/4/6) and the right V1. Compared with DM group, patients with DR showed increased FC strength between the right CAL (BA 17/18) and the right V1. DM group exhibited lower FC strength between the left fusiform and the left V1, and between the bilateral CAL and the right V1 when compared with HCs. Moreover, DM group was observed to have higher FC strength between the left superior frontal gyrus and the left V1. Conclusion: Our findings indicated that DR patients exhibited FC disruptions between V1 and higher visual regions at rest, which may reflect the aberrant information communication in the V1 area of DR individuals. The findings offer important insights into the neuromechanism of vision disorder in DR patients.

17.
Ann Surg Oncol ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264409

RESUMO

INTRODUCTION: Breast cancer-related lymphedema occurs in up to 30% of women following axillary lymph node dissection (ALND) and less commonly following sentinel lymph node biopsy. To quantify disability in these patients, patient-reported outcome measures (PROMs) have proven useful; however, given the overlap of symptoms between ALND and lymphedema, examination of their accuracy, sensitivity, and specificity in detecting lymphedema in breast cancer patients undergoing ALND is needed. METHODS: The Lymphedema Life Impact Scale (LLIS) and the Upper Limb Lymphedema 27 scale (ULL27) were administered to patients who had undergone ALND at least 2 years prior and either did or did not develop lymphedema. Survey responses and the degree of disability were compared to generate receiver operator characteristic (ROC) curves, and the sensitivity and specificity of PROMs to diagnose lymphedema were analyzed. RESULTS: Both PROMs were highly accurate, sensitive, and specific for detecting lymphedema. The LLIS had an accuracy of 97%, sensitivity of 100%, and specificity of 84.8% at a cutoff of ≥ 5.88 overall percent impairment score (higher scores indicate worse disability). The ULL27 had an accuracy of 93%, sensitivity of 88.6%, and specificity of 90.9% at a cutoff of ≤ 83.3 global score (lower scores indicate worse disability). CONCLUSIONS: The LLIS and the ULL27 appear to be highly specific for lymphedema and capable of differentiating it from symptoms resulting from ALND alone. Our findings suggest that use of these questionnaires with a threshold may be effective for diagnosing lymphedema, potentially reducing the need for frequent clinic visits and time-consuming measurements.

18.
Nat Biomed Eng ; 5(6): 533-545, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34131321

RESUMO

Regular screening for the early detection of common chronic diseases might benefit from the use of deep-learning approaches, particularly in resource-poor or remote settings. Here we show that deep-learning models can be used to identify chronic kidney disease and type 2 diabetes solely from fundus images or in combination with clinical metadata (age, sex, height, weight, body-mass index and blood pressure) with areas under the receiver operating characteristic curve of 0.85-0.93. The models were trained and validated with a total of 115,344 retinal fundus photographs from 57,672 patients and can also be used to predict estimated glomerulal filtration rates and blood-glucose levels, with mean absolute errors of 11.1-13.4 ml min-1 per 1.73 m2 and 0.65-1.1 mmol l-1, and to stratify patients according to disease-progression risk. We evaluated the generalizability of the models for the identification of chronic kidney disease and type 2 diabetes with population-based external validation cohorts and via a prospective study with fundus images captured with smartphones, and assessed the feasibility of predicting disease progression in a longitudinal cohort.


Assuntos
Aprendizado Profundo , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/estatística & dados numéricos , Fotografação/estatística & dados numéricos , Insuficiência Renal Crônica/diagnóstico por imagem , Retina/diagnóstico por imagem , Área Sob a Curva , Glicemia/metabolismo , Estatura , Índice de Massa Corporal , Peso Corporal , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Progressão da Doença , Feminino , Fundo de Olho , Taxa de Filtração Glomerular , Humanos , Masculino , Metadados/estatística & dados numéricos , Pessoa de Meia-Idade , Redes Neurais de Computação , Fotografação/métodos , Estudos Prospectivos , Curva ROC , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Retina/metabolismo , Retina/patologia
19.
Chemosphere ; 284: 131298, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34175514

RESUMO

Bisulfite is used as an oxygen scavenger in waters used for oil production to prevent oxygen-mediated pipeline corrosion. Analysis of nitrate-containing water injected with ammonium bisulfite indicated increased concentrations of ammonium, sulfate and nitrite. To understand the microbial process causing these changes, water samples were used in enrichments with bisulfite and nitrate. Oxidation of bisulfite, reduction of nitrate, change in microbial community composition and corrosivity of bisulfite were determined. The results indicated that the microbial community was dominated by Sulfuricurvum, a sulfite-oxidizing nitrate-reducing bacterium (StONRB). Plating of the enriched StONRB culture yielded the bacterial isolate Sulfuricurvum sp. TK005, which coupled bisulfite oxidation with nitrate reduction to form sulfate and nitrite. Bisulfite also induced chemical corrosion of carbon steel at a rate of 0.28 ± 0.18 mm yr-1. Bisulfite and the generated sulfate could serve as electron acceptors for sulfate-reducing microorganisms (SRM), which reduce sulfate and bisulfite to sulfide. Nitrate is frequently injected to injection waters to contain the activity of SRM in oil reservoirs. This study suggests an alternative bisulfite injection procedure: Injection of nitrate after the chemical reaction of bisulfite with oxygen is completed. This could maintain the oxygen scavenger function of bisulfite and SRM inhibitory activity of nitrate.


Assuntos
Nitratos , Sulfatos , Oxirredução , Sulfitos , Água
20.
Elife ; 102021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061021

RESUMO

Genetic mutation of the human BEST1 gene, which encodes a Ca2+-activated Cl- channel (BEST1) predominantly expressed in retinal pigment epithelium (RPE), causes a spectrum of retinal degenerative disorders commonly known as bestrophinopathies. Previously, we showed that BEST1 plays an indispensable role in generating Ca2+-dependent Cl- currents in human RPE cells, and the deficiency of BEST1 function in patient-derived RPE is rescuable by gene augmentation (Li et al., 2017). Here, we report that BEST1 patient-derived loss-of-function and gain-of-function mutations require different mutant to wild-type (WT) molecule ratios for phenotypic manifestation, underlying their distinct epigenetic requirements in bestrophinopathy development, and suggesting that some of the previously classified autosomal dominant mutations actually behave in a dominant-negative manner. Importantly, the strong dominant effect of BEST1 gain-of-function mutations prohibits the restoration of BEST1-dependent Cl- currents in RPE cells by gene augmentation, in contrast to the efficient rescue of loss-of-function mutations via the same approach. Moreover, we demonstrate that gain-of-function mutations are rescuable by a combination of gene augmentation with CRISPR/Cas9-mediated knockdown of endogenous BEST1 expression, providing a universal treatment strategy for all bestrophinopathy patients regardless of their mutation types.


Assuntos
Bestrofinas/genética , Mutação com Ganho de Função , Mutação com Perda de Função , Degeneração Retiniana/genética , Bestrofinas/metabolismo , Sistemas CRISPR-Cas , Cloretos/metabolismo , Predisposição Genética para Doença , Terapia Genética , Células HEK293 , Humanos , Potenciais da Membrana , Fenótipo , Degeneração Retiniana/diagnóstico , Degeneração Retiniana/metabolismo , Degeneração Retiniana/terapia , Epitélio Pigmentado da Retina/metabolismo
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