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1.
J Autism Dev Disord ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34813034

RESUMO

Autism spectrum disorders (ASDs) are a group of neurodevelopmental-related disorders with a high genetic risk. Recently, chromatin remodeling factors have been found to be related to ASDs. SMARCA4 is such a catalytic subunit of the chromatin-remodeling complex. In this report, we identified seven novel missense variants in the SMARCA4 gene from eight pediatric patients. All eight patients had moderate to severe intellectual disability, and seven showed autistic/likely autistic features. Compared with the patients reported in the literature, our patients were less likely to show craniofacial or finger/toe anomalies. Our findings further supported that SMARCA4 is associated with ASDs. We suggest that individuals with the abovementioned phenotypes should consider genetic testing.

2.
BMC Cancer ; 21(1): 1276, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34823500

RESUMO

BACKGROUND: Cancer development is strictly correlated to composition and physical properties of the extracellular matrix. Particularly, a higher matrix stiffness has been demonstrated to promote tumor sustained growth. Our purpose was to explore the role of matrix stiffness in liver cancer development. METHODS: The matrix stiffness of tumor tissues was determined by atomic force microscopy (AFM) analysis. In vitro, we used a tunable Polyacrylamide (PA) hydrogels culture system for liver cancer cells culture. The expression level of integrin ß1, phosphorylated FAK, ERK1/2, and NF-κB in SMMC-7721 cells was measured by western blotting analysis. We performed MTT, colony formation and transwell assay to examine the tumorigenic and metastatic potential of SMMC-7721 cells cultured on the tunable PA hydrogels. SMMC-7721 cancer xenografts were established to explore the anticancer effects of integrin inhibitors. RESULTS: Our study provided evidence that liver tumor tissues from metastatic patients possessed a higher matrix stiffness, when compared to the non-metastatic group. Liver cancer cells cultured on high stiffness PA hydrogels displayed enhanced tumorigenic potential and migrative properties. Mechanistically, activation of integrin ß1/FAK/ ERK1/2/NF-κB signaling pathway was observed in SMMC-7721 cells cultured on high stiffness PA hydrogels. Inhibition of ERK1/2, FAK, and NF-κB signaling suppressed the pro-tumor effects induced by matrix stiffness. Combination of chemotherapy and integrin ß1 inhibitor suppressed the tumor growth and prolonged survival time in hepatocellular cancer xenografts. CONCLUSION: A higher matrix stiffness equipped tumor cells with enhanced stemness and proliferative characteristics, which was dependent on the activation of integrin ß1/FAK/ERK1/2/NF-κB signaling pathway. Blockade of integrin signals efficiently improved the outcome of chemotherapy, which described an innovative approach for liver cancer treatment.

3.
Transl Pediatr ; 10(10): 2521-2532, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34765476

RESUMO

Background: A low-phenylalanine (Phe) diet affects the metabolism and diversity of gut microbial communities in children with phenylketonuria (PKU). Our study examined gut microbiota characteristics and metabolic pathways, and their correlations with clinical phenotypes in a high-incidence population. Methods: We assessed clinical phenotypes and gut microbiota by 16S ribosomal RNA (rRNA) sequencing, and performed a correlation analysis between phenotype and gut microbiota in a PKU group (n=11) and a healthy group (n=11). Results: The PKU group had significantly lower microbiota diversity than the healthy group (Pshannon=0.014). Phylum-level composition differed significantly between the PKU and healthy groups (Firmicutes: 44.3% vs. 43.1%; Actinobacteria: 25.9% vs. 3.3%; Bacteroidetes: 16.6% vs. 53.2%; and Proteobacteria: 10.9% vs. 0.12%, respectively). Further, a significantly decreased level of genus Bacteroidetes (P<0.0001) in the PKU group was negatively correlated with blood Phe level (P=0.014). The microbial function prediction of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways exhibited a decreased ability of glycan degradation and glutamate metabolism in the PKU group. Conclusions: Our findings revealed that genus Bacteroide was not only in extremely low abundance in the PKU group, but was also negatively correlated with blood Phe level. The remarkable capability of genus Bacteroides to use complex recalcitrant glycans may be the main reason for the decreased ability of glycan degradation in the PKU group.

5.
Front Pediatr ; 9: 727301, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733806

RESUMO

Neonatal metabolic acidosis (NMA) is a common problem, particularly in critically ill patients in neonatal intensive care units (NICUs). Complex etiologies and atypical clinical signs make diagnosis difficult; thus, it is crucial to investigate the underlying causes of NMA rapidly and provide disorder-specific therapies. Our study aims to provide an overview of the genetic causes of NMA in patients from NICUs. We performed next-generation sequencing (NGS) on neonates with NMA from January 2016 to December 2019. Clinical features, genetic diagnoses, and their effects on clinical interventions were collected for analysis. In the 354 enrolled patients, 131 (37%) received genetic diagnoses; 95 (72.5%) of them were autosomal recessively inherited diseases. Two hundred and fifteen variants spanning 57 genes were classified as pathogenic (P) or likely pathogenic (LP) in 131 patients. The leading cause was metabolic disorders due to 35 genes found in 89 patients (68%). The other 42 NMA patients (32%) with 22 genes had malformations and renal, neuromuscular, and immune-hematological disorders. Seven genes (MMUT, MMACHC, CHD7, NPHS1, OTC, IVD, and PHOX2B) were noted in more than four patients, accounting for 48.9% (64/131) of the identified P/LP variants. Forty-six diagnosed patients with uncorrected NMA died or gave up. In conclusion, 37% of neonates with metabolic acidosis had genetic disorders. Next-generation sequencing should be considered when investigating the etiology of NMA in NICUs. Based on early molecular diagnoses, valuable treatment options can be provided for some genetic diseases to achieve better outcomes.

6.
ACS Omega ; 6(44): 30027-30039, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34778674

RESUMO

Poor osseointegration and infection are the main reasons leading to the failure of hard tissue implants; especially, in recent years, the failure rate has been increasing every year owing to the continuously increasing conditions such as injury, trauma, diseases, or infections. Therefore, the development of a biomimetic surface coating of bone tissues with antibacterial function is an effective means to improve bone healing and inhibit bacterial infection. Mimicking the natural bone, in this study, we have designed a silk fibroin (collagen-like structure)-based coating inlaid with nanohydroxyapatite (nHA) and silver nanoparticles (AgNPs) for promoting antibacterial ability and osteogenesis, especially focusing on the bone mimetic structure for enhancing bone health. Observing the morphology and size of the composite nanoparticles by transmission electron microscope (TEM), nHA provided nucleation sites for the formation of AgNPs, forming an nHA/AgNP complex with a size of about 100-200 nm. Characterization of the nHA/Ag-loaded silk fibroin biomimetic coating showed an increased surface roughness with good density and compact performances. The silk fibroin-based coating loaded with uniformly distributed AgNPs and nHA could effectively inhibit the adhesion of Staphylococcus aureus on the surface and, at the same time, quickly kill planktonic bacteria, indicating their good antibacterial ability. In vitro cell experiments revealed that the biomimetic silk fibroin-based coating was beneficial to the adhesion, spreading, and proliferation of osteoblasts (MC3T3-E1). In addition, by characterizing LDH and ROS, it was found that the nHA/Ag complex could significantly reduce the cytotoxicity of AgNPs, and the osteoblasts on the coating surface maintained the structure intact.

7.
J Pediatr ; 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34788679

RESUMO

OBJECTIVE: To explore the genetic spectrum of cerebral palsy (CP) in a Chinese paediatric cohort. STUDY DESIGN: This was a retrospective observational study of patients with CP from the Children's Hospital of Fudan University between June 2015 and December 2019. Their clinical data and exome sequencing data were collected and analysed. RESULTS: A total of 217 patients with CP were enrolled, and genetic variants were identified in 78 subjects (35.9%): 65 patients with single-nucleotide variants (SNVs), 12 patients with copy number variants (CNVs) and one patient with both an SNV and a CNV. The genetic diagnosis rates were significantly higher in patients without clinical risk factors than in patients with clinical risk factors (χ2=21.705, P = .000) and were significantly higher in patients with a family history than in those without a family history (χ2=4.493, P=0.034). Variants in genes related to neurologic disorders were the most commonly detected variants, affecting 41 patients (62.1%, 41/66). Among the patients with SNVs detected, the top 12 genes were found to cover 62.1% (41/66) of cases, and 39.4% (26/66) of patients with SNVs had medically actionable genetic findings. CONCLUSIONS: The overall genetic diagnostic rate in this study was 35.9%, and patients without any clinical risk factors or with a family history were more likely to have genetic risk factors. The top 12 genes detected in this study as well as genes related to neurologic disorders or other medically actionable disorders should be noted in the analysis of genetic testing results in patients with CP.

8.
Neonatology ; : 1-8, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34802008

RESUMO

OBJECTIVES: The genetic characteristics in neonates admitted to the NICU with recurrent hypernatremia remained unknown. We aimed to implement early genetic sequencing to identify possible genetic etiologies, optimize the treatment, and improve the outcome. METHODS: We prospectively performed exome sequencing or targeted panel sequencing on neonates diagnosed with recurrent hypernatremia (plasma sodium ≥150 mEq/L, ≥2 episodes) from January 1, 2016, to June 30, 2020. RESULTS: Among 22,375 neonates admitted to the NICU, approximately 0.33% (73/22,375) developed hypernatremia. The incidence of hypernatremia >14 days and ≤14 days was 0.03% and 0.3%, respectively. Among 38 neonates who had ≥2 hypernatremia episodes, parents of 28 patients consented for sequencing. Genetic diagnosis was achieved in 25% neonates (7/28). Precision medicine treatment was performed in 85.7% (6/7) of the patients, including hydrochlorothiazide and indomethacin for 57.1% (4/7) with arginine vasopressin receptor 2 (AVPR2) deficiency-associated congenital nephrogenic diabetes insipidus; a special diet of fructose formula for 1 patient with solute carrier family 5 member 1 deficiency-associated congenital glucose-galactose malabsorption (1/7, 14.3%); and kallikrein-inhibiting ointment for 1 patient with serine protease inhibitor of Kazal-type 5 deficiency-associated Netherton syndrome (1/7, 14.3%). Only hypernatremia onset age (adjusted odds ratio 1.32 [1.01-1.72], p = 0.040) independently predicted the underlying genetic etiology. The risk of a genetic etiology of hypernatremia was 9.0 times higher for neonates with a hypernatremia onset age ≥17.5 days (95% confidence interval, 1.1-73.2; p = 0.038). CONCLUSIONS: Single-gene disorders are common in neonates with recurrent hypernatremia, and >50% of cases are caused by AVPR2 deficiency-associated congenital nephrogenic diabetes insipidus. Early genetic testing can aid the diagnosis of unexplained recurrent neonatal hypernatremia and improve therapy and outcome.

9.
Phys Rev Lett ; 127(14): 147401, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34652196

RESUMO

Symmetries play a major role in identifying topological phases of matter and in establishing a direct connection between protected edge states and topological bulk invariants via the bulk-boundary correspondence. One-dimensional lattices are deemed to be protected by chiral symmetry, exhibiting quantized Zak phases and protected edge states, but not for all cases. Here, we experimentally realize an extended Su-Schrieffer-Heeger model with broken chiral symmetry by engineering one-dimensional zigzag photonic lattices, where the long-range hopping breaks chiral symmetry but ensures the existence of inversion symmetry. By the averaged mean displacement method, we detect topological invariants directly in the bulk through the continuous-time quantum walk of photons. Our results demonstrate that inversion symmetry protects the quantized Zak phase but edge states can disappear in the topological nontrivial phase, thus breaking the conventional bulk-boundary correspondence. Our photonic lattice provides a useful platform to study the interplay among topological phases, symmetries, and the bulk-boundary correspondence.

10.
BMC Genomics ; 22(1): 732, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627155

RESUMO

BACKGROUND: Enzyme-based host depletion significantly improves the sensitivity of clinical metagenomics. Recent studies found that real-time adaptive sequencing of DNA molecules was achieved using a nanopore sequencing machine, which enabled effective enrichment of microbial sequences. However, few studies have compared the enzyme-based host depletion and nanopore adaptive sequencing for microbial enrichment efficiency. RESULTS: To compare the host depletion and microbial enrichment efficiency of enzyme-based and adaptive sequencing methods, the present study collected clinical samples from eight children with respiratory tract infections. The same respiratory samples were subjected to standard methods, adaptive sequencing methods, enzyme-based host depletion methods, and the combination of adaptive sequencing and enzyme-based host depletion methods. We compared the host depletion efficiency, microbial enrichment efficiency, and pathogenic microorganisms detected between the four methods. We found that adaptive sequencing, enzyme-based host depletion and the combined methods significantly enriched the microbial sequences and significantly increased the diversity of microorganisms (p value < 0.001 for each method compared to standard). The highest microbial enrichment efficiency was achieved using the combined method. Compared to the standard method, the combined method increased the microbial reads by a median of 113.41-fold (interquartile range 23.32-327.72, maximum 1812), and the number of genera by a median of 70-fold (interquartile range 56.75-86.75, maximum 164). The combined method detected 6 pathogens in 4 samples with a median read of 547, compared to 5 pathogens in 4 samples with a median read of 4 using the standard method. CONCLUSION: The combined method is an effective, easy-to-run method for enriching microbial sequences in clinical metagenomics from sputum and bronchoalveolar lavage fluid samples and may improve the sensitivity of clinical metagenomics for other host-derived clinical samples.


Assuntos
Sequenciamento por Nanoporos , Nanoporos , Criança , DNA , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Metagenômica
11.
Clin Genet ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34671977

RESUMO

Emerging evidence demonstrates the clinical utility of genomic applications in newborn intensive care unit (NICU) patients with strong indications of Mendelian etiology. However, such applications' diagnostic yield and utility remain unclear for NICU cohorts with minimal phenotype selection. In this study, focused medical exome sequencing was used as a first-tier, singleton-focused diagnostic tool for 2303 unrelated sick neonates. Integrated analysis of single nucleotide variants (SNVs), small insertions and deletions (Indels), and large copy number variants (CNVs) was performed. The diagnostic rate in this NICU cohort is 12.3% (284/2303), with 190 probands with molecular diagnoses made from SNV/Indel analyses (66.9%), 93 patients with diagnostic aneuploidy/CNVs findings (32.8%), and 1 patient with both SNV and CNV (0.4%). In addition, 54 (2.3%) of patients had a reportable incidental finding. Multiple organ involvements, craniofacial abnormalities, and dermatologic abnormalities were the strongest positive predictors for a molecular diagnosis. Among the 190 cases with SNV/Indel defects, direct impacts on medical management were observed in 46.8% of patients after the results were reported. In this study, we demonstrate that focused medical exome sequencing is a powerful first-line diagnostic tool for NICU patients. Significant number of diagnosed NICU patients can benefit from more focused medical management and long-term care.

12.
Front Pediatr ; 9: 713458, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660482

RESUMO

MEGDEL syndrome and SATB2-associated syndrome (SAS) are both rare congenital disorders with poor prognoses caused by gene mutations. We present the case of a 2-day-old girl with an unexplained abnormal liver function, feeding problem, and dystonia. Using next-generation sequencing, we identified two novel mutations in SERAC1 and a mutation in SATB2. Now, she is 15 months old and has the characteristics of SAS, such as downslanting palpebral fissures and delayed primary dentition. Besides the typical phenotypes of MEGDEL syndrome, such as hypertonia, failure to thrive, deafness, and motor regression, she has progressive cholestasis and is prone to high serum lactate after rehabilitation training and hypoglycemia with low ketone under starving conditions. These phenotypes substantially differ from the transient liver function abnormalities and hypoglycemia reported in the literature.

13.
Front Pediatr ; 9: 711200, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671584

RESUMO

Background: The Chinese Neonatal Network (CHNN) is a nationwide neonatal network that aims to improve clinical neonatal care quality and short- and long-term health outcomes of infants. This study aims to assess the quality of the Chinese Neonatal Network database by conducting an internal audit of data extraction. Methods: A data audit was performed by independently replicating the data collection and entry process in all 58 tertiary neonatal intensive care units (NICU) participating in the CHNN. Eighty-eight data elements selected for re-abstraction were classified into three categories (critical, important, less important), and agreement rates for original and re-abstracted data were predefined. Three to five records were randomly selected at each site for re-abstraction, including one short- (0-7 days), two medium- (8-28 days), and two long-stay (more than 28 days) cases. Agreement rates for each data item were calculated for individual NICUs and across the network, respectively. Results: A total of 283 cases and 24,904 data fields were re-abstracted. The agreement rates for original and re-abstracted data elements were 96.1% overall, and 97.2, 94.3, and 96.6% for critical, important, and less important data elements, respectively. Individual site variation for discrepancies ranged between 0.0 and 18.4% for all collected data elements. Conclusion: The completeness, precision, and quality of data in the CHNN database are high, providing assurance for multipurpose use, including health service evaluation, quality improvement, clinical trials, and other research.

14.
EBioMedicine ; 72: 103592, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34619639

RESUMO

BACKGROUND: Alterations in the brain cortical structures of patients with chronic kidney disease (CKD) have been reported; however, the cause has not been determined yet. Herein, we used Mendelian randomization (MR) to reveal the causal effect of kidney damage on brain cortical structure. METHODS: Genome-wide association studies summary data of estimated glomerular filtration rate (eGFR) in 480,698 participants from the CKDGen Consortium were used to identify genetically predicted eGFR. Data from 567,460 individuals from the CKDGen Consortium were used to assess genetically determined CKD; 302,687 participants from the UK Biobank were used to evaluate genetically predicted albuminuria. Further, data from 51,665 patients from the ENIGMA Consortium were used to assess the relationship between genetic predisposition and reduced eGFR, CKD, and progressive albuminuria with alterations in cortical thickness (TH) or surficial area (SA) of the brain. Magnetic resonance imaging was used to measure the SA and TH globally and in 34 functional regions. Inverse-variance weighted was used as the primary estimate whereas MR Pleiotropy RESidual Sum and Outlier, MR-Egger and weighted median were used to detect heterogeneity and pleiotropy. FINDINGS: At the global level, albuminuria decreased TH (ß = -0.07 mm, 95% CI: -0.12 mm to -0.02 mm, P = 0.004); at the functional level, albuminuria reduced TH of pars opercularis gyrus without global weighted (ß = -0.11 mm, 95% CI: -0.16 mm to -0.07 mm, P = 3.74×10-6). No pleiotropy was detected. INTERPRETATION: Kidney damage causally influences the cortex structure which suggests the existence of a kidney-brain axis. FUNDING: This study was supported by the Science and Technology Planning Project of Guangdong Province (Grant No. 2020A1515111119 and 2017B020227007), the National Key Research and Development Program of China (Grant No. 2018YFA0902803), the National Natural Science Foundation of China (Grant No. 81825016, 81961128027, 81772719, 81772728), the Key Areas Research and Development Program of Guangdong (Grant No. 2018B010109006), Guangdong Special Support Program (2017TX04R246), Grant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, and Grants from the Guangdong Science and Technology Department (2020B1212060018).

16.
BMC Med Genomics ; 14(1): 250, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34696790

RESUMO

BACKGROUND: Pathogenic variants of PAX2 cause autosomal-dominant PAX2-related disorder, which includes variable phenotypes ranging from renal coloboma syndrome (RCS), congenital anomalies of the kidney and urinary tract (CAKUT) to nephrosis. Phenotypic variability makes it difficult to define the phenotypic spectrum associated with genotype. METHODS: We collected the phenotypes in patients enrolled in the China national multicenter registry who were diagnosed with pathogenic variant in PAX2 and reviewed all published cases with PAX2-related disorders. We conducted a phenotype-based cluster analysis by variant types and molecular modeling of the structural impact of missense variants. RESULTS: Twenty different PAX2 pathogenic variants were identified in 32 individuals (27 families) with a diagnosis of RCS (9), CAKUT (11) and nephrosis (12) from the Chinese cohort. Individuals with abnormal kidney structure (RCS or CAKUT group) tended to have likely/presumed gene disruptive (LGD) variants (Fisher test, p < 0.05). A system review of 234 reported cases to date indicated a clear association of RCS to heterozygous loss-of-function PAX2 variants (LGD variants). Furthermore, we identified a subset of PAX2 missense variants in DNA-binding domain predicted to affect the protein structure or protein-DNA interaction associated with the phenotype of RCS. CONCLUSION: Defining the phenotypic spectrum combined with genotype in PAX2-related disorder allows us to predict the pathogenic variants associated with renal and ophthalmological development. It highlighted the approach of structure-based analysis can be applied to diagnostic strategy aiding precise and timely diagnosis.

17.
Ann Transl Med ; 9(16): 1290, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532427

RESUMO

Background: Electroencephalography (EEG) monitoring is widely used in neonatal intensive care units (NICUs). However, conventional EEG report generation processes are time-consuming and labor-intensive. Therefore, an automatic, objective, and comprehensive pipeline for brain age estimation and EEG report conclusion prediction is urgently needed to assist clinician's decision-making. Methods: We recruited patients who underwent EEG monitoring from the NICU at Children's Hospital of Fudan University from Jan. 2016 to Mar. 2018. A total of 1,851 subjects were enrolled, including the patient's conceptional age (CA) and the clinical EEG report conclusion (normal, slightly abnormal, moderately abnormal, or severely abnormal). A total of 1,591 subjects were used to generate predictive models and 260 were used as the validation dataset. We developed Auto-Neo-EEG (an automatic prediction system to assist clinical neonatal EEG report generation), including signal feature extraction, supervised machine learning realized by gradient boosted models, to estimate brain age and predict EEG report conclusion. Results: The predicted results from the validation dataset were compared with the clinical observations to assess the performance. In the independent validation dataset, the model could achieve accordance 0.904 on estimating brain age for neonates with normal clinical EEG report conclusion, and differences between the predicted and observed brain age were strongly related with EEG report conclusion abnormality. Further, as for the EEG report conclusion prediction, the model could achieve area under the curve (AUC) of 0.984 for severely abnormal situations, and 0.857 for moderately abnormal ones. Conclusions: The Auto-Neo-EEG has the high accuracy of estimating brain age and EEG report conclusion, which can potentially greatly accelerate the EEG report generation processes assist in clinical decision making.

18.
Chin Med J (Engl) ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520417

RESUMO

ABSTRACT: Recent research efforts have provided compelling evidence of genome-wide DNA methylation alterations in pediatrics. It is currently well established that epigenetic clocks, composed of DNA methylation sites, can estimate the gestational and chronological age of cells and tissues from different ages. Also, extensive research is aimed at their correlation with early life exposure and pediatric diseases. This review aimed to systematically summarize the epigenetic clocks in the pediatric population. Publications were collected from PubMed and Web of Science databases up to Apr 2021. Epigenetic clocks, DNA methylation clocks, epigenetic age acceleration or deceleration, pediatric and the pediatric population were used as search criteria. Here, we first review the currently applicative pediatric epigenetic clocks. We then highlight the interpretation for epigenetic age deviations in the pediatric population and their association with external factors, developmental trajectories, and pediatric diseases. Considering the remaining unknown of pediatric clocks, research strategies into them are also discussed. In all, pediatric epigenetic clocks may act as potent tools to understand development, growth and diseases in early life.

19.
G3 (Bethesda) ; 11(9)2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34544147

RESUMO

Threonyl-tRNA synthetase (ThrRS), one of the aminoacyl-tRNA synthetases (AARSs), plays a crucial role in protein synthesis. However, the AARS functions on rice chloroplast development and growth were not fully appraised. In this study, a thermo-sensitive virescent mutant tsv2, which showed albino phenotype and lethal after the 4-leaf stage at 20°C but recovered to normal when the temperatures rose, was identified and characterized. Map-based cloning and complementation tests showed that TSV2 encoded a chloroplast-located ThrRS protein in rice. The Lys-to-Arg mutation in the anticodon-binding domain hampered chloroplast development under cold stress, while the loss of function of the ThrRS core domain in TSV2 fatally led to seedling death regardless of growing temperatures. In addition, TSV2 had a specific expression in early leaves. Its disruption obviously resulted in the downregulation of certain genes associated with chlorophyll biosynthesis, photosynthesis, and chloroplast development at cold conditions. Our observations revealed that rice nuclear-encoded TSV2 plays an important role in chloroplast development at the early leaf stage under cold stress.


Assuntos
Oryza , Treonina-tRNA Ligase , Cloroplastos/genética , Cloroplastos/metabolismo , Resposta ao Choque Frio , Regulação da Expressão Gênica de Plantas , Mutação , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plântula/genética , Plântula/metabolismo
20.
BMC Pediatr ; 21(1): 409, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535106

RESUMO

BACKGROUND: The prevalence of allergic diseases (ADs), such as asthma and allergic rhinitis (AR), is increasing worldwide in both adults and children. Although ADs are common and frequently coexist in outpatient care, city-level data regarding the characteristics of childhood AD remain limited in China. This study aimed to assess the profile and characteristics of ADs in the city of Shanghai. METHODS: A multicenter retrospective study was designed to collect routine administrative data from outpatient and emergency departments from 66 hospitals in Shanghai, China, from 2016 to 2018. Children with asthma, AR, allergic conjunctivitis (AC), and allergic skin diseases were investigated. Demographic characteristics, patients visit pattern, spectrum of diagnosis, and comorbidities were analyzed. RESULTS: A total of 2,376,150 outpatient and emergency visits for ADs were included in the period from 2016 to 2018. Allergic skin diseases accounted for 38.9%, followed by asthma (34.8%), AR (22.9%), and AC (3.3%), with a male predominance in all four diseases. Asthma and allergic skin diseases were most frequent in the 1 to < 4 years of age group, while AR and AC were more common in the 4 to < 7 years of age group. Asthma accounted for the greatest number of annual and emergency visits. The most frequent comorbidity of asthma was lower respiratory tract infection (LRTI) (49.3%), followed by AR (20.5%) and upper respiratory tract infection (14.1%). The most common comorbidities of AR were otitis media (23.4%), adenoid hypertrophy/obstructive sleep apnea (22.1%), followed by LRTI (12.1%), asthma (9.4%) and chronic pharyngitis (8.9%). CONCLUSIONS: Asthma and allergic skin diseases were the most common ADs in outpatient and emergency departments in the study period. Respiratory tract infection was the most common comorbidity of asthma in children. More attention should be devoted to the treatment of comorbidities to improve childhood AD outcomes with a better understanding of the characteristics of ADs in outpatient care.


Assuntos
Pacientes Ambulatoriais , Rinite Alérgica , Adulto , Criança , China/epidemiologia , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Estudos Retrospectivos , Rinite Alérgica/epidemiologia
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