ABSTRACT
BACKGROUND: Müllerian duct anomalies (MDAs) are congenital developmental disorders that present as a series of abnormalities within the reproductive tracts of females. Genetic factors are linked to MDAs and recent advancements in whole-exome sequencing (WES) provide innovative perspectives in this field. However, relevant mechanism has only been investigated in a restricted manner without clear elucidation of respective observations. METHODS: Our previous study reported that 2 of 12 patients with MDAs harbored the CHD1L variant c.348-1G>C. Subsequently, an additional 85 MDAs patients were recruited. Variants in CHD1L were screened through the in-house database of WES performed in the cohort and two cases were identified. One presented with partial septate uterus with left renal agenesis and the other with complete septate uterus, duplicated cervices and longitudinal vaginal septum. The pathogenicity of the discovered variants was further assessed by molecular dynamics simulation and various functional assays. RESULTS: Ultimately, two novel heterozygous CHD1L variants, including a missense variant c.956G>A (p.R319Q) and a nonsense variant c.1831C>T (p.R611*) were observed. The variants were absent in 100 controls. Altogether, the contribution yield of CHD1L to MDAs was calculated as 4.12% (4/97). All three variants were assessed as pathogenic through various functional analysis. The splice-site variant c.348-1G>C resulted in a 11 bp sequence skipping in exon 4 of CHD1L and led to nonsense mediated decay of its transcripts. Unlike WT CHD1L, the truncated R611* protein mislocalized to the cytoplasm, abolish the ability of CHD1L to promote cell migration and failed to interact with PARP1 owing to the loss of macro domain. The R319Q variant exhibited conformational disparities and showed abnormal protein recruitment behavior through laser microirradiation comparing with the WT CHD1L. All these variants impaired the CHD1L function in DNA damage repair, thus participating in MDAs. CONCLUSIONS: The current study not only expands the mutational spectrum of CHD1L in MDAs but determines three variants as pathogenic according to ACMG guidelines with reliable functional evidence. Additionally, the impairment in DNA damage repair is an underlying mechanism involved in MDAs.
Subject(s)
DNA Helicases , DNA-Binding Proteins , Mullerian Ducts , Female , Humans , DNA Helicases/genetics , DNA-Binding Proteins/genetics , Exome Sequencing , Mullerian Ducts/abnormalities , Mutation , Mutation, MissenseABSTRACT
Reclaimed water poses environmental and human health risks due to residual organic micropollutants and pathogens. Ozonation of reclaimed water to control pathogens and trace organics is an important step in advanced water treatment systems for potable reuse of reclaimed water. Ensuring efficient pathogen reduction while controlling disinfection byproducts remains a significant challenge to implementing ozonation in reclaimed water reuse applications. This study aimed to investigate ozonation conditions using a plug flow reactor (PFR) to achieve effective pathogen removal/inactivation while minimizing bromate and N-Nitrosodimethylamine (NDMA) formation. The pilot scale study was conducted using three doses of ozone (0.7, 1.0 and 1.4 ozone/total organic carbon (O3/TOC) ratio) to determine the disinfection performance using actual reclaimed water. The disinfection efficiency was assessed by measuring total coliforms, Escherichia coli (E. coli), Pepper Mild Mottle Virus (PMMoV), Tomato Brown Rugose Fruit Virus (ToBRFV) and Norovirus (HNoV). The ozone CT values ranged from 1.60 to 13.62 mg min L-1, resulting in significant reductions in pathogens and indicators. Specifically, ozone treatment led to concentration reductions of 2.46-2.89, 2.03-2.18, 0.46-1.63, 2.23-2.64 and > 4 log for total coliforms, E. coli, PMMoV, ToBRFV, and HNoV, respectively. After ozonation, concentrations of bromate and NDMA increased, reaching levels between 2.8 and 12.0 µg L-1, and 28-40.0 ng L-1, respectively, for average feed water bromide levels of 86.7 ± 1.8 µg L-1 and TOC levels of 7.2 ± 0.1 mg L-1. The increases in DBP formation were pronounced with higher ozone dosages, possibly requiring removal/control in subsequent treatment steps in some potable reuse applications.
Subject(s)
Disinfection , Ozone , Water Purification , Disinfection/methods , Water Purification/methods , Pilot Projects , Escherichia coli/drug effects , Disinfectants/analysis , Drinking Water/microbiology , Drinking Water/chemistry , Norovirus/drug effects , Water Microbiology , Bromates/analysisABSTRACT
PURPOSE: Non-small cell lung cancer (NSCLC) is a widespread and serious global malignancy. This study aimed to examine the clinical relevance of serum exosomal SNORD116 and SNORA21 as novel diagnostic biomarkers for NSCLC. METHODS: Serum exosomes from 226 healthy controls and 305 NSCLC patients were isolated by ultracentrifugation. Characterization of exosomes was conducted by qNano, transmission electron microscopy (TEM) and Western immunoblotting. RT-PCR revealed snoRNAs that were differentially expressed. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance. RESULTS: In NSCLC patients, the levels of serum exosomal SNORD116 and SNORA21 were significantly reduced compared to those in healthy controls (P < 0.0001 for both). ROC curves showed AUC values of 0.738 and 0.761. By combining SNORD116 and SNORA21 with traditional blood biomarkers CYFRA21-1 and carcinoembryonic antigen (CEA), the AUC increased to 0.917. Moreover, these two exosomal snoRNAs distinguished between patients with metastatic NSCLC (n = 132) and those with non-metastatic NSCLC (n = 173) significantly (P < 0.0001 for both). The ROC curves gave AUC values of 0.743 and 0.694, respectively. The combined analysis raised the AUC to 0.751. The diagnostic power of these two exosomal snoRNAs combined with CYFRA21-1 and CEA increased to 0.784. CONCLUSION: This study demonstrated that serum exosomal SNORD116 and SNORA21 can be used as potential promising non-invasive diagnostic biomarkers for NSCLC.
ABSTRACT
OBJECTIVE: To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells. METHODS: Breast cancer 4T1 cells were divided into 6 groups: control, brazilin 1/2 half maximal inhibitory concentration (IC50), IC50, 2×IC50, erastin (10 µg/mL) and capecitabine (10 µg/mL) groups. The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay, and the treatment dose of brazilin was screened. The effect of brazilin on the mitochondrial morphology of 4T1 cells, and the mitochondrial damage was evaluated under electron microscopy. The levels of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase 4 (GPX4) were estimated using various detection kits. The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay. The expressions levels of tumor protein p53, solute carrier family 7 member 11 (SLC7A11), GPX4 and acyl-CoA synthetase long-chain family member 4 (ACSL4) proteins were quantified by Western blot assay. RESULTS: Compared to the control group, the 10 (1/2 IC50), 20 (IC50) and 40 (2×IC50) µg/mL brazilin, erastin, and capecitabine groups showed a significant decrease in the cell survival rate, invasion and migration abilities, GSH, SLC7A11 and GPX4 protein expression levels, and mitochondrial volume and ridge (P<0.05), and a significant increase in the mitochondria membrane density, Fe2+, ROS and MDA levels, and p53 and ACSL4 protein expression levels (P<0.05). CONCLUSIONS: Brazilin actuated ferroptosis in breast cancer cells, and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.
Subject(s)
Amino Acid Transport System y+ , Breast Neoplasms , Ferroptosis , Phospholipid Hydroperoxide Glutathione Peroxidase , Signal Transduction , Tumor Suppressor Protein p53 , Ferroptosis/drug effects , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/drug therapy , Signal Transduction/drug effects , Female , Cell Line, Tumor , Tumor Suppressor Protein p53/metabolism , Amino Acid Transport System y+/metabolism , Humans , Reactive Oxygen Species/metabolism , Animals , Mice , Cell Proliferation/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Coenzyme A Ligases/metabolism , Cell Movement/drug effects , BenzopyransABSTRACT
BACKGROUND: tRF-RNA-a representative of non-coding RNA (ncRNA)-is a precursor or fragment of mature tRNA and plays a crucial regulatory role in the occurrence and development of cancer. There is currently little research on tRF-RNA as a diagnostic marker in cancer, especially for NSCLC from serum exosomes. METHOD: Serum exosomes were successfully extracted from serum; their physical morphology was captured by transmission electron microscopy (TEM); appropriate particle size detection was performed using qNano; surface labeling was verified through western blotting. Serum exosomes i-tRF-AspGTC and tRF-1-SerCGA were selected through gene microarray, and qPCR was used to validate their significance in 242 patients and 201 healthy individuals. The area under the curve (AUC) was used to evaluate the diagnostic indicators of non-small cell lung cancer (NSCLC). RESULT: Compared with 201 healthy individuals, i-tRF-AspGTC and tRF-1-SerCGA were significantly downregulated in 242 NSCLC patients and 95 early-stage patients. For tRF-AspGTC and tRF-1-SerCGA, the predictive diagnostic efficiency rates of AUC were 0.690 and 0.680, respectively, whereas the early diagnostic efficiency rates were 0.656 and 0.688, respectively. The result of combined diagnosis with CEA and CYFRA21-1 was 0.928, and the early diagnostic efficiency was 0.843, which is a very high biological predictive factor for NSCLC. CONCLUSION: The expression of serum exosomes i-tRF-AspGTC and tRF-1-SerCGA was significantly downregulated in NSCLC patients. These exosomes could be used as predictive indicators for diagnosis or early diagnosis of NSCLC.
Subject(s)
Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung , Exosomes , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/pathology , Exosomes/metabolism , Lung Neoplasms/blood , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Male , Female , Middle Aged , Biomarkers, Tumor/blood , Case-Control Studies , Aged , Adult , PrognosisABSTRACT
This research investigated the removal of contaminants of emerging concern (CECs) and characterized the microbial community across an advanced water treatment (AWT) train consisting of Coagulation/Flocculation/Clarification/Granular Media Filtration (CFCGMF), Ozone-Biological Activated Carbon Filtration (O3/BAC), Granular Activated Carbon filtration, Ultraviolet Disinfection, and Cartridge Filtration (GAC/UV/CF). The AWT train successfully met the goals of CECs and bulk organics removal. The microbial community at each treatment step of the AWT train was characterized using 16S rRNA sequencing on the Illumina MiSeq platform generated from DNA extracted from liquid and solid (treatment media) samples taken along the treatment train. Differences in the microbial community structure were observed. The dominant operational taxonomic units (OTU) decreased along the treatment train, but the treatment steps did impact the microbial community composition downstream of each unit process. These results provide insights into microbial ecology in advanced water treatment systems, which are influenced and shaped by each treatment step, the microbial community interactions, and their potential metabolic contribution to CECs degradation.
Subject(s)
Drinking Water , Ozone , Water Pollutants, Chemical , Water Purification , Charcoal/chemistry , RNA, Ribosomal, 16S , Water Pollutants, Chemical/chemistry , Water Purification/methods , Filtration/methods , Ozone/chemistryABSTRACT
OBJECTIVE: Second-generation catheters used in mechanical thrombectomy have different advantages and disadvantages. The objective of this study was to evaluate the effectiveness and safety of the combination of contact aspiration and stent retriever technique on the rate of reperfusion after mechanical thrombectomy for large vessel occlusion. METHODS: Patients who underwent contact aspiration alone (CAA cohort, n = 150), stent retriever alone (SRA cohort, n = 129), or combined contact aspiration and stent retriever (CSR cohort, n = 122) techniques following mechanical thrombectomy were included in the analysis. A balloon guide catheter was used for all thrombectomies. Digital subtraction angiography was used to identify thrombolysis in cerebral infarction. RESULTS: The number of patients with thrombolysis in cerebral infarction score of ≥ 2c (near complete or complete antegrade reperfusion) was significantly higher in the CSR cohort than those in the CAA cohort (101 [83%] vs. 90 [60%], p < 0.0001) and those of SRA cohort (101 [83%] vs. 77 [59%], p = 0.0001). Arterial perforation was higher in patients in the CSR cohort than in those in the CAA (p < 0.0001) and SRA (p = 0.015) cohorts. Intracerebral hemorrhage was lower in patients in the CSR cohort than in those in the CAA (p = 0.0001) and SRA (p = 0.0353) cohorts. All-cause mortality at 1 year was fewer in the CSR cohort than in the CAA cohort (p = 0.018). CONCLUSIONS: The combination of thrombo aspiration by large bore aspiration catheter and stent retriever is the most effective technique but has some related risks. LEVEL OF EVIDENCE: IV. TECHNICAL EFFICACY STAGE: 1.
Subject(s)
Ischemic Stroke , Humans , Cerebral Infarction , Angiography, Digital Subtraction , Stents , ThrombectomyABSTRACT
ABSTRACT Introduction: The quality of flexibility greatly impacts the performance of aerobics athletes. It is believed that stretching by proprioceptive neuromuscular facilitation (PNF) can contribute to this aspect by maximizing active joint range motion. Objective: Explore the influences of PNF stretching on the physical fitness of aerobics athletes. Methods: 24 professional aerobics athletes were selected, and randomly distributed into two groups with no statistical discrepancies in physical indices. PNF stretching exercise was performed on aerobics athletes in the experimental group, while no training intervention was performed in the control group. Physical fitness was assessed before and after the nine weeks of the intervention. Results: After PNF stretching training, the lower limb vertical score in the experimental group was from 6.58±0.19 to 8.20±0.47, and the transverse pronation score changed from 5.95±0.35 to 7.09±0.61. The vertical score in the control group was from 6.44±59.89 to 6.83±0.37 after the experiment; the transverse pronation penetration score was from 5.78±0.37 to 6.58±0.33. Conclusion: PNF stretching can effectively improve athletes' physical fitness, both statically and dynamically, generating gains in range of motion and providing favorable conditioning for overall competitive performance. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.
RESUMO Introdução: A qualidade da flexibilidade tem um grande impacto sobre o desempenho dos atletas de aeróbica, e acredita-se que o alongamento por facilitação neuromuscular proprioceptiva (PNF) possa contribuir neste quesito com a maximização da amplitude de movimento articular ativa. Objetivo: Explorar as influências do alongamento PNF sobre a aptidão física dos atletas de aeróbica. Métodos: Foram selecionadas 24 atletas profissionais de aeróbica, aleatoriamente distribuídas em dois grupos sem discrepâncias estatísticas nos índices físicos. Foi realizado o exercício de alongamento PNF em atletas de aeróbica no grupo experimental, enquanto nenhuma intervenção de treinamento foi realizada no grupo de controle. A aptidão física foi avaliada antes e após as nove semanas da intervenção. Resultados: Após o treinamento de alongamento PNF, a pontuação de membros inferiores vertical no grupo experimental foi de 6,58±0,19 para 8,20±0,47, e a pontuação da pronação transversal mudou de 5,95±0,35 para 7,09±0,61. A pontuação vertical no grupo de controle foi de 6,44±59,89 para 6,83±0,37 depois do experimento; a pontuação da penetração transversal de pronação foi de 5,78±0,37 para 6,58±0,33. Conclusão: O alongamento PNF pode efetivamente melhorar a aptidão física das atletas, tanto estática quanto dinâmica, gerando ganhos à amplitude de movimento proporcionando um condicionamento favorável ao desempenho competitivo geral. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.
RESUMEN Introducción: La calidad de la flexibilidad tiene un gran impacto en el rendimiento de los atletas de aeróbic, y se cree que el estiramiento por facilitación neuromuscular propioceptiva (PNF) puede contribuir en esta cuestión con la maximización de la amplitud articular activa de movimiento. Objetivo: Explorar las influencias del estiramiento PNF en la condición física de atletas de aeróbic. Métodos: Fueron seleccionados 24 atletas profesionales de aeróbic, distribuidos aleatoriamente en dos grupos sin discrepancias estadísticas en los índices físicos. Se realizaron ejercicios de estiramiento PNF en los atletas de aeróbic del grupo experimental, mientras que en el grupo de control no se realizó ninguna intervención de entrenamiento. Se evaluó la aptitud física antes y después de las nueve semanas de intervención. Resultados: Tras el entrenamiento de estiramiento PNF, la puntuación vertical de las extremidades inferiores en el grupo experimental fue de 6,58±0,19 a 8,20±0,47, y la puntuación de pronación transversal cambió de 5,95±0,35 a 7,09±0,61. La puntuación vertical en el grupo de control fue de 6,44±59,89 a 6,83±0,37 después del experimento; la puntuación de penetración de pronación transversal fue de 5,78±0,37 a 6,58±0,33. Conclusión: El estiramiento PNF puede mejorar eficazmente la condición física de los atletas, tanto estática como dinámica, generando ganancias en el rango de movimiento y proporcionando un acondicionamiento favorable para el rendimiento competitivo general. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.
ABSTRACT
ABSTRACT Introduction: The standardization of body movements is essential for aerobics gymnastic practitioners and motor coordination for the execution of consecutive movements of large amplitudes is strongly related to balance ability. Therefore, it is believed that balance training can positively impact motor coordination in aerobics students Objective: Explore the influences of balance training on motor coordination in aerobics students. Methods: 100 volunteers were selected as aerobics students, divided into an experimental and a control group for a 6-week experiment. The experimental group was given a balance training protocol, while the control group maintained the traditional teaching protocol. Data on functional exercises and fitness indices were collected before and after the experiment for comparison and analysis. Results: The difference in the exercise in the unipodal orthostatic position with eyes closed was 6.45, the difference in the balance test in the swallow position was 4.04, the difference in the later-forward Y balance exercise was 1.88, the later-posterior was 2.09, and posterior Y balance was 2.53. The difference between all items in the control group was small, especially the three items of frontal, lateral, posterior, and mid-posterior Y balance. Conclusion: Balance training positively affected the motor coordination of aerobics students, resulting in a statistically significant increase in all analyzed postural balance indexes. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.
RESUMO Introdução: A padronização dos movimentos corporais é essencial para os praticantes de ginástica aeróbica e a coordenação motora para a execução de movimentos consecutivos de grandes amplitudes está fortemente relacionada à capacidade de equilíbrio. Acredita-se, por isso, que o treino de equilíbrio possa impactar positivamente a coordenação motora dos estudantes de aeróbica Objetivo: Explorar as influências do treinamento de equilíbrio na coordenação motora dos estudantes de aeróbica. Métodos: Foram selecionados 100 voluntários estudantes de aeróbica, divididos em grupo experimental e controle para um experimento de 6 semanas. Ao grupo experimental foi incrementado um protocolo de treinamento de equilíbrio, enquanto o grupo de controle manteve o protocolo de ensino tradicional. Os dados pertinentes aos exercícios funcionais e índices de aptidão física foram coletados antes e após o experimento para comparação e análise. Resultados: A diferença do exercício em posição ortostática unipodal de olhos fechados foi 6,45, a diferença no teste de equilíbrio em posição de andorinha foi 4,04, a diferença do exercício de equilíbrio latero-dianteiro em Y foi 1,88, latero-posterior foi 2,09, e posterior em Y foi 2,53. A diferença de todos os itens do grupo de controle foi pequena, especialmente os três itens de equilíbrio frontal, lateral, posterior e médio-posterior em Y. Conclusão: O treinamento de equilíbrio afetou positivamente a coordenação motora dos estudantes de aeróbica, resultando num incremento estatisticamente expressivo em todos os índices de balanço postural analisados. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.
RESUMEN Introducción: La estandarización de los movimientos corporales es esencial para los practicantes de gimnastica aeróbic y la coordinación motora para la ejecución de movimientos consecutivos de gran amplitud está fuertemente relacionada con la capacidad de equilibrio. Por lo tanto, se cree que el entrenamiento del equilibrio puede influir positivamente en la coordinación motora de los estudiantes de aeróbic Objetivo: Explorar las influencias del entrenamiento del equilibrio en la coordinación motora de los estudiantes de aeróbic. Métodos: Se seleccionaron 100 voluntarios estudiantes de aeróbic, divididos en un grupo experimental y un grupo de control para un experimento de 6 semanas. Al grupo experimental se le incrementó un protocolo de entrenamiento del equilibrio, mientras que el grupo de control mantuvo el protocolo de enseñanza tradicional. Se recogieron datos relativos a ejercicios funcionales e índices de aptitud física antes y después del experimento para su comparación y análisis. Resultados: La diferencia en el ejercicio en posición ortostática unipodal con ojos cerrados fue de 6,45, la diferencia en la prueba de equilibrio en posición de deglución fue de 4,04, la diferencia en el ejercicio de equilibrio latero-direccional en Y fue de 1,88, latero-posterior fue de 2,09, y posterior en Y fue de 2,53. La diferencia de todos los ítems en el grupo de control fue pequeña, especialmente los tres ítems de equilibrio frontal, lateral, posterior y medio-posterior en Y. Conclusión: El entrenamiento en equilibrio afectó positivamente a la coordinación motora de los estudiantes de aeróbic, resultando en un incremento estadísticamente expresivo en todos los índices de equilibrio postural analizados. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.
ABSTRACT
Abstract Objective Second-generation catheters used in mechanical thrombectomy have different advantages and disadvantages. The objective of this study was to evaluate the effectiveness and safety of the combination of contact aspiration and stent retriever technique on the rate of reperfusion after mechanical thrombectomy for large vessel occlusion. Methods Patients who underwent contact aspiration alone (CAA cohort, n = 150), stent retriever alone (SRA cohort, n = 129), or combined contact aspiration and stent retriever (CSR cohort, n = 122) techniques following mechanical thrombectomy were included in the analysis. A balloon guide catheter was used for all thrombectomies. Digital subtraction angiography was used to identify thrombolysis in cerebral infarction. Results The number of patients with thrombolysis in cerebral infarction score of ≥ 2c (near complete or complete antegrade reperfusion) was significantly higher in the CSR cohort than those in the CAA cohort (101 [83%] vs. 90 [60%], p < 0.0001) and those of SRA cohort (101 [83%] vs. 77 [59%], p = 0.0001). Arterial perforation was higher in patients in the CSR cohort than in those in the CAA (p < 0.0001) and SRA (p = 0.015) cohorts. Intracerebral hemorrhage was lower in patients in the CSR cohort than in those in the CAA (p = 0.0001) and SRA (p = 0.0353) cohorts. All-cause mortality at 1 year was fewer in the CSR cohort than in the CAA cohort (p = 0.018). Conclusions The combination of thrombo aspiration by large bore aspiration catheter and stent retriever is the most effective technique but has some related risks. Level of evidence IV. Technical efficacy stage 1.
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Mineral fillers hinder cellulosic fiber bonding and thus limit the increase of filler content in paper. Herein, precipitated calcium carbonate (PCC)/cellulose nanofibrils (CNF) composites were fabricated by a facile and efficient strategy, i.e., co-refining process (CRP). During this process, CNF and PCC were activated by mechanochemical effect and formed encapsulation structure by calcium ion coordination and hydrogen bonding. The encapsulation structure and H-bond/ionic coordination interactions not only endowed the composite with excellent size stability but also enhanced interfacial interaction between composite fillers and cellulosic fibers. Compare with the paper filled with only PCC, PCC + CNF mixture, the tensile index of the cellulosic paper containing PCC/CNF composite was increased by 44.48% and 12.14%, respectively. These results not only provide a facile and scalable approach to increase interaction between cellulosic fiber and mineral filler but also create more possibilities for special paper-based materials with requiring high content of inorganic materials.
Subject(s)
Cellulose , Nanofibers , Calcium Carbonate/chemistry , Cellulose/chemistry , Ions , Minerals , Nanofibers/chemistryABSTRACT
OBJECTIVE: To determine changes in mitochondrial DNA (mtDNA) copy number in peripheral blood in Rett syndrome caused by methyl-CpG-binding protein-2 (MECP2) variants and explore the mechanism of mitochondrial dysfunction in Rett syndrome. STUDY DESIGN: Female patients who were diagnosed with Rett syndrome and had an MECP2 variant (n = 142) were recruited in this study, along with the same number of age- and sex-matched healthy controls. MtDNA copy number was quantified by real-time quantitative polymerase chain reaction with TaqMan probes. The differences in mtDNA copy number between the Rett syndrome group and the control group were analyzed using the independent-samples t test. Linear regression, biserial correlation analysis, and one-way ANOVA were applied for the correlations between mtDNA copy number and age, clinical severity, variant types, functional domains, and hot-spot variants. RESULTS: MtDNA copy number was found to be significantly increased in the patients with Rett syndrome with MECP2 gene variants compared with the control subjects. Age, clinical severity, variant types, functional domains, and hot-spot variants were not related to mtDNA copy number in patients with Rett syndrome. CONCLUSIONS: MtDNA copy number is increased significantly in patients with Rett syndrome, suggesting that changes in mitochondrial function in Rett syndrome trigger a compensatory increase in mtDNA copy number and providing new possibilities for treating Rett syndrome, such as mitochondria-targeted therapies.
Subject(s)
DNA Copy Number Variations , DNA, Mitochondrial , Methyl-CpG-Binding Protein 2/genetics , Mitochondria/genetics , Rett Syndrome/genetics , Adolescent , Adult , Case-Control Studies , Child , Child, Preschool , Cross-Sectional Studies , Female , Genetic Markers , Humans , Infant , Linear Models , Patient Acuity , Rett Syndrome/physiopathology , Young AdultABSTRACT
SUMMARY: The cutaneous wounds of trunk and tail healing scar-free or with scar were different in lizard species. Full- thickness cutaneous injuries of tail and body of Scincella tsinlingensis were examined by histomorphological and immunohistochemistrical methods. The results showed that all injuries healed without scarring. The process of the wound healing of S. tsinlingensis involved hemostasis, re-epithelialization, proliferation and remodelling, which also could be further subdivided into six stages. Stage I, 0-2 day post wound (dpw), the blood oozed gradually, no obvious wound contraction, minimal blood loss. Stage II, 2-10 dpw, the wound bed covered by the fibrin clot of blood, tissue fluid and tissue debris. Stage III, 7d-15 dpw, the wrinkled wound epitheliums was gradually stratified, and its surface was keratinized and exfoliated. Stage IV, 10-28 dpw, pigment cells were distributed at the boundary between epidermis and dermis, with few blood vessels and no granulation tissue formation. Stage V, 20-70 dpw, opaque scales covered the wound epithelium with randomly scattered melanophores in the base of the epidermis. Stage VI, 45-135 dpw, the epidermis and dermis restored to the thickness of the original skin. Regenerated scales were similar to scales of the uninjured dermis. The positive immunostaining of matrix metalloproteinases-9, cytokeratin 6, alpha smooth muscle actin, caspase 3 and transforming growth factor-β3 showed the specificity of healing period and different stages, which participated in skin wounds healing of S. tsinlingensis.
RESUMEN: En las diferentes especies de lagartos las heridas cutáneas del tronco y la cola sin cicatrices, o con algún tipo de cicatriz son diversas. En este estudio se examinaron las heridas cutáneas de espesor total de la cola y el cuerpo de Scincella tsinlingensis mediante métodos histomorfológicos e inmunohistoquímicos. Los resultados indicaron que todas las lesiones sanaron sin cicatrices visibles. El proceso de cicatrización de heridas de S. tsinlingensis implicó hemostasia, reepitelización, proliferación y remodelación, que también podrían subdividirse en seis etapas. Etapa I, 0-2 días después de la herida (dph), la sangre filtraba gradualmente, sin contracción evidente de la herida, con pérdida mínima de sangre. Etapa II, 2-10 dph, el lecho de la herida estaba cubierto por el coágulo de sangre, líquido tisular y restos tisulares de fibrina. Etapa III, 7-15 dph, los epitelios de la herida se estratificaron gradualmente y su superficie se queratiniza y exfolia. Etapa IV, 10-28 dph, las células pigmentarias se distribuyeron en el límite entre la epidermis y la dermis, con pocos vasos sanguíneos y sin formación de tejido de granulación. Etapa V, 20-70 dph, escamas opacas cubrieron el epitelio de la herida con melanóforos dispersos al azar en la base de la epidermis. Etapa VI, 45-135 dph, la epidermis y la dermis restauradas al grosor de la piel original. Las escamas regeneradas eran similares a las escamas de la dermis sin herida. La inmunotinción positiva de metaloproteinasas- 9 de matriz, citoqueratina 6, actina de músculo liso alfa, caspasa 3 y factor de crecimiento transformante-β3 mostró la especificidad del período de curación y las diferentes etapas, que participaron en la curación de heridas cutáneas de S. tsinlingensis.
Subject(s)
Animals , Skin Physiological Phenomena , Wound Healing/physiology , Lizards , ImmunohistochemistryABSTRACT
Energy and storage restrictions are relevant variables that software applications should be concerned about when running in low-power environments. In particular, computer vision (CV) applications exemplify well that concern, since conventional uniform image sensors typically capture large amounts of data to be further handled by the appropriate CV algorithms. Moreover, much of the acquired data are often redundant and outside of the application's interest, which leads to unnecessary processing and energy spending. In the literature, techniques for sensing and re-sampling images in non-uniform fashions have emerged to cope with these problems. In this study, we propose Application-Oriented Retinal Image Models that define a space-variant configuration of uniform images and contemplate requirements of energy consumption and storage footprints for CV applications. We hypothesize that our models might decrease energy consumption in CV tasks. Moreover, we show how to create the models and validate their use in a face detection/recognition application, evidencing the compromise between storage, energy, and accuracy.
ABSTRACT
OBJECTIVES: Anemia and changes in platelets (PLT) are common in inflammatory bowel disease (IBD). In our study, we aimed to verify whether PLT count can independently reflect the severity of IBD. METHODS: In our hospital, 137 Crohn's Disease (CD), 69 Ulcerative colitis (UC) patients, and 412 healthy controls were included to compare the differences in PLT count. In addition, the effect of anemia, C-reactive protein (CRP), age, CD activity index (CDAI) or Mayo on PLTs was also analyzed. If PLTs independently affected CD or UC, we used the receiver operating characteristic (ROC) curve to verify the diagnostic value and obtain the cut-off value of PLT. RESULTS: CD and UC patients had higher PLT than controls (p<0.001, p<0.001; respectively). In CD patients, the results showed that patients with anemia (P<0.01), Iron Deficiency Anemia (IDA) (p<0.001), CRP≥8 mg/L (p=0.046), and CDAI≥150 (p<0.001) had higher PLT, while in UC patients, those with anemia (p=0.018), CRP≥8 mg/L (p=0.045), and Mayo≥3 (p=0.029) had higher PLT. Univariate analysis showed that CDAI was positively correlated with PLT count (p<0.001), while hemoglobin (p=0.001) and age (p<0.001) were negatively correlated with PLT in CD. In UC patients, Mayo (p=0.001) and CRP (p<0.001) were positively correlated with PLT, while hemoglobin (p=0.002) was negatively correlated. Finally, by linear stepwise multivariate analysis, we clarified the positive relationship between PLT and CD (p<0.001) by eliminating the interference of hemoglobin, and determined the cut-off value of PLT as 298×109/L. For UC, we did not obtain similar results. CONCLUSIONS: PLT can be an indicator of disease severity in CD, while there is a lack of evidence regarding this finding in UC.
Subject(s)
Anemia , Colitis, Ulcerative , Crohn Disease , Adult , Biomarkers , Blood Platelets , C-Reactive Protein , Female , Humans , Male , Middle Aged , Severity of Illness IndexABSTRACT
Due to the great change in the morphology of squamate vomeronasal organ (VNO), the histomorphology characteristics of VNO in Scincella tsinlingensis were studied by light and electronic microscopy. The results indicated that the VNO of S. tsinlingensis was located at the base of nasal cavity and consisted of a mushroom body situated anteroventrally and a sensory epithelium (SE) situated dorsocaudally. SE was composed of supporting cells, receptor cells and basal cells, and the supporting cells contained secretory granules near the surface membrane. Most of receptor cells were irregular in shape with long cytoplasmic extensions and characterized by microtubules, vesicles, and mitochondria. The basal cells with long cytoplasmic extensions were also irregular in shape and appeared a greater electron density than others. The thick nerve bundles were found on the dorsomedial area of VNO, and the surface of mushroom body was non-sensory epithelium consisting of ciliated and basal cells, without goblet cells. Epithelial cells were arranged in irregular, with many cilia and microvilli distributed on its free surface. Cells on the basal layer were irregularly circular in shape and arranged sparsely. Taken together, the results indicated that the fine structure of VNO in S. tsinlingensis was similar to other species from scincomorphs.
Debido al gran cambio en la morfología del órgano vomeronasal (OVN), se estudiaron las características histomorfológicas en la Scincella tsinlingensis por microscopías de luz y electrónica. Los resultados indicaron que el OVN de S. tsinlingensis se localizaba en la base de la cavidad nasal y consistía en un cuerpo como hongo situado anteroventralmente y un epitelio sensorial (ES) situado dorso caudamente. El ES estaba compuesto de células de soporte, células receptoras y células basales, y las células de soporte contenían gránulos secretores cerca de la membrana superficial. En gran parte de la mayoría de las células receptoras se observó una forma irregular con largas extensiones citoplasmáticas, caracterizadas por microtúbulos, vesículas y mitocondrias. Las células basales con extensiones citoplasmáticas también tenían forma irregular y algunas parecían tener una mayor densidad de electrones. Los haces gruesos nerviosos se encontraron en el área dorsomedial del OVN, la superficie del cuerpo de estaba compuesto de epitelio no sensorial y consistía de células ciliadas y basales, sin células caliciformes. Las células epiteliales estaban dispuestas de manera irregular, con muchos cilios y microvellosidades distribuidas en su superficie libre. Las células en la capa basal eran escasas y de forma circular irregular. Tomados en conjunto, los resultados indicaron que la estructura fina del OVN en S. tsinlingensis era similar a otras especies de scincomorpha.