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BACKGROUND: Microbial infection and colonization are frequently associated with disease progression and poor clinical outcomes in bronchiectasis. Identification of pathogen spectrum is crucial for precision treatment at exacerbation of bronchiectasis. METHODS: We conducted a prospective cohort study in patients with bronchiectasis exacerbation onset and stable state. Bronchoalveolar lavage fluid (BALF) was collected for conventional microbiological tests (CMTs) and metagenomic Next-Generation Sequencing (mNGS). Bronchiectasis patients were monitored for documenting the time to the next exacerbation during longitudinal follow-up. RESULTS: We recruited 168 eligible participants in the exacerbation cohorts, and 38 bronchiectasis patients at stable state at longitudinal follow-up. 141 bronchiectasis patients at exacerbation onset had definite or probable pathogens via combining CMTs with mNGS reports. We identified that Pseudomonas aeruginosa, non-tuberculous mycobacteria, Haemophilus influenzae, Nocardia spp, and Staphylococcus aureus were the top 5 pathogens with a higher detection rate in our cohorts via combination of CMTs and mNGS analysis. We also observed strong correlations of Pseudomonas aeruginosa, Haemophilus influenzae, non-tuberculous mycobacteria with disease severity, including the disease duration, Bronchiectasis Severity Index, and lung function. Moreover, the adjusted pathogenic index of potential pathogenic microorganism negatively correlated (r = -0.7280, p < 0.001) with the time to the next exacerbation in bronchiectasis. CONCLUSION: We have revealed the pathogenic microbial spectrum in lower airways and the negative correlation of PPM colonization with the time to the next exacerbation in bronchiectasis. These results suggested that pathogens contribute to the progression of bronchiectasis.
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Bronquiectasia , Humanos , Bronquiectasia/microbiología , Bronquiectasia/diagnóstico , Femenino , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Líquido del Lavado Bronquioalveolar/microbiología , Estudios de Cohortes , Estudios de Seguimiento , Adulto , Progresión de la Enfermedad , Estudios LongitudinalesRESUMEN
Practical acoustic propagation modeling is significantly affected by ocean dynamics, and then can be exploited in numerous oceanic applications, where "practical" refers to modeling acoustic propagation in simulations that mimic real-world ocean environments. Physics-based numerical models provide approximate solutions of wave equation and rely on accurate prior environmental knowledge while the environment of practical scenarios is largely unknown. In contrast, data-driven machine learning offers a promising avenue to estimate practical acoustic propagation by learning from dataset. However, collecting such a high-quality, noise-free, and dense dataset remains challenging. Under the practical hurdle posed by the above approaches, the emergence of physics-informed neural network (PINN) presents an alternative to integrate physics and data but with limited representation capacity. In this work, a framework, termed spatial domain decomposition-based physics-informed neural networks (SPINNs), is proposed to enhance the representation capacity in spatially dependent oceanic scenarios and effectively learn from incomplete and biased prior physics and noisy dataset. Experiments demonstrate SPINNs' advantages over PINN in practical acoustic propagation estimation. The learning capacity of SPINNs toward physics and dataset during training is further analyzed. This work holds promise for practical applications and future expansion.
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BACKGROUND: Rectus sheath hematoma (RSH) is uncommon, and because people have limited knowledge about it, it is difficult to recognize the symptoms in time, often de-laying optimal treatment. CASE SUMMARY: Herein, we report a case of a 77-year-old female with RSH. The patient was treated at our hospital for coronavirus disease 2019. Anticoagulant treatment was administered during this period because of thrombosis. On the 8th d of treatment, the patient complained of abdominal pain. Ultrasonography revealed a solid cystic mass in the pelvic cavity. An emergency laparotomy was performed, and a huge hematoma was found in the deep layer of the rectus abdominis muscle. We used anticoagulants with caution based on the patient's condition. CONCLUSION: Optimal management of patients with RSH s depends on timely diagnosis and when to reintroduce anticoagulants.
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A gyroscope-free strapdown inertial navigation system (GFSINS) solves the carrier attitude through the reasonable spatial combination of accelerometers, with a particular focus on the precision of angular velocity calculation. This paper conducts an analysis of a twelve-accelerometer configuration scheme and proposes an angular velocity fusion algorithm based on the Kalman filter. To address the sign misjudgment issue that may arise when calculating angular velocity using the extraction algorithm, a sliding window correction method is introduced to enhance the accuracy of angular velocity calculation. Additionally, the data from the integral algorithm and the data from the improved extraction algorithm are fused using Kalman filtering to obtain the optimal estimation of angular velocity. Simulation results demonstrate that this algorithm significantly reduces the maximum value and standard deviation of angular velocity error by one order of magnitude compared to existing algorithms. Experimental results indicate that the algorithm's calculated angle exhibits an average difference of less than 0.5° compared to the angle measured by the laser tracker. This level of accuracy meets the requirements for attitude measurement in the laser scanning projection system.
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Objectives: CHARGE syndrome is a congenital hereditary condition involving multiple systems. Patients are easily misdiagnosed with idiopathic hypogonadotropic hypogonadism (IHH) due to the overlap of clinical manifestations. An accurate clinical diagnosis remains challenging when the predominant clinical manifestation resembles hypogonadotropic hypogonadism. Methods: This original research is conducted based on the genetic finding and analysis of clinical cases. Whole-exome sequencing (WES) and in-silico analyse were performed on two sisters to investigate the pathogenesis in this family. Homology modelling was conducted to evaluate structural changes in the variants. Results: WES and Sanger sequencing revealed two siblings carrying a nonsense mutation (NM_017780.4: c.115C > T) in exon 2 of CHD7 inherited from a mildly affected mother and a missense mutation (NM_015295.3: c.2582T > C) in exon 20 of SMCHD1 inherited from an asymptomatic father. The nonsense mutation in CHD7 was predicted to generate nonsense-mediated decay, whereas the missense mutation in SMCHD1 decreased protein stability. Conclusions: We identified digenic CHD7 and SMCHD1 mutations in IHH-associated diseases for the first time and verified the synergistic role of oligogenic inheritance. It was also determined that WES is an effective tool for distinguishing diseases with overlapping features and establishing a molecular diagnosis for cases with digenic or oligogenic hereditary disorders, which is beneficial for timely treatment, and family genetic counseling.
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Due to the growing concerns surrounding microbial contamination and food safety, there has been a surge of interest in fabricating novel food packaging with highly efficient antibacterial activity. Herein, we describe novel photodynamic antibacterial konjac glucomannan (KGM)/polyvinylpyrrolidone (PVP) nanofibers incorporated with lignin-zinc oxide composite nanoparticles (L-ZnONPs) and curcumin (Cur) via electrospinning technology. The resulting KGM/PVP/Cur/L-ZnONPs nanofibers exhibited favorable hydrophobic properties (water contact angle: 118.1°), thermal stability, and flexibility (elongation at break: 241.9%). Notably, the inclusion of L-ZnONPs and Cur endowed the nanofibers with remarkable antioxidant (ABTS radical scavenging activity: 98.1%) and photodynamic antimicrobial properties, demonstrating enhanced inhibitory effect against both Staphylococcus aureus (inhibition: 12.4 mm) and Escherichia coli (12.1 mm). As a proof-of-concept study, we evaluated the feasibility of applying nanofibers to fresh strawberries, and the findings demonstrated that our nanofibers could delay strawberry spoilage and inhibit microbial growth. This photodynamic antimicrobial approach holds promise for design of highly efficient antibacterial food packaging, thereby contributing to enhanced food safety and quality assurance.
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The recognition of silver nanoparticles (AgNPs) as a nanozyme with peroxidase-like activity has offered a promising solution to address the challenges of bacterial resistance and argyria risk. However, the catalytic efficacy of AgNPs is limited by the need for a strong acidic environment and high concentrations of hydrogen peroxide (H2O2). In this work, we developed a self-activated hydrogel cascade reactor (AUGP) for enhanced treatment of bacterial infection. The AUGP integrates the properties of glucose oxidase (GOx) and polyacrylamide (pAAm) hydrogel microsphere. The confinement effect of pAAm hydrogel microsphere enables glucose oxidation to occur in a confined space, which creates an acidic environment to activate AgNPs activity, initiating the cascade reaction between GOx and AgNPs. Meanwhile, the confinement effect facilitates the accumulation of a high local concentration of H2O2, allowing AUGP to generate hydroxyl radicals (â¢OH) without the need for external H2O2. Additionally, the release of Ag+ from AUGP is achieved upon the generation of â¢OH. The synergistic action of Ag+ and â¢OH confers exceptional antibacterial efficacy to AUGP. Importantly, the etching effect of H2O2 ensures the absence of any residual AgNPs, reducing the risk of argyria. In vivo studies validated the efficacy of AUGP in wound disinfection with minimal toxicity.
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There is a complex high-dimensional nonlinear mapping relationship between the compressive strength of High-Performance Concrete (HPC) and its components, which has great influence on the accurate prediction of compressive strength. In this paper, an efficient robust software calculation strategy combining BP Neural Network (BPNN), Support Vector Machine (SVM) and Genetic Algorithm (GA) is proposed for the prediction of compressive strength of HPC. 8 features were extracted from the previous literature, and a compressive strength database containing 454 sets of data was constructed. The model was trained and tested, and the performance of 4 Machine Learning (ML) models, namely BPNN, SVM, GA-BPNN and GA-SVM, was compared. The results show that the coupled model is superior to the single model. Moreover, because GA-SVM has better generalization ability and theoretical basis, its convergence speed and prediction accuracy are better than GA-BPNN. Then Grey Relational Analysis (GRA) and Shapley analysis were used to verify the interpretability of the GA-SVM model, which showed that the water-binder ratio had the most significant influence on the compressive strength. Finally, the combination of multiple input variables to evaluate the compressive strength supplemented this research, and again verified the significant influence of water-binder ratio, providing reference value for subsequent research.
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Objective: The article aims to provide genetic counseling to a family with two children who were experiencing growth and developmental delays. Methods: Clinical information of the proband was collected. Peripheral blood was collected from core family members to identify the initial reason for growth and developmental delays by whole exome sequencing (WES) and Sanger sequencing. To ascertain the consequences of the newly discovered variants, details of the variants detected were analyzed by bioinformatic tools. Furthermore, we performed in vitro experimentation targeting SNX14 gene expression to confirm whether the variants could alter the expression of SNX14. Results: The proband had prenatal ultrasound findings that included flattened frontal bones, increased interocular distance, widened bilateral cerebral sulci, and shortened long bones, which resulted in subsequent postnatal developmental delays. The older sister also displayed growth developmental delays and poor muscle tone. WES identified compound heterozygous variants of c.712A>T (p.Arg238Ter) and .2744A>T (p.Gln915Leu) in the SNX14 gene in these two children. Both are novel missense variant that originates from the father and mother, respectively. Sanger sequencing confirmed this result. Following the guideline of the American College of Medical Genetics and Genomics (ACMG), the SNX14 c.712A>T (p.Arg238Ter) variant was predicted to be pathogenic (P), while the SNX14 c.2744A>T (p.Gln915Leu) variant was predicted to be a variant of uncertain significance (VUS). The structural analysis revealed that the c.2744A>T (p.Gln915Leu) variant may impact the stability of the SNX14 protein. In vitro experiments demonstrated that both variants reduced SNX14 expression. Conclusion: The SNX14 gene c.712A>T (p.Arg238Ter) and c.2744A>T (p.Gln915Leu) were identified as the genetic causes of growth and developmental delay in two affected children. This conclusion was based on the clinical presentations of the children, structural analysis of the mutant protein, and in vitro experimental validation. This discovery expands the range of SNX14 gene variants and provides a foundation for genetic counseling and guidance for future pregnancies in the affected children's families.
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BACKGROUND: Cervical intraepithelial neoplasia (CIN) is an important precursor of cervical cancer. Early detection and treatment can reduce the incidence of cervical cancer. AIM: To investigate the detection rate of human papillomavirus (HPV) E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia (CIN) and its relationship with CIN progression and diagnosis. METHODS: One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected. These patients were graded CIN based on colposcopy and cervical pathology. The positive expression rates of HPV E6/E7 mRNA and HPV [polymerase chain reaction (PCR)-reverse dot crossing] were compared among all groups. Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr. The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis. RESULTS: The diagnostic sensitivity, specificity, and sensitivity of PCR-reverse point hybridization technology for secondary CIN were 70.41%, 70.66%, and 0.714, respectively. Sensitivity and specificity for secondary CIN were 752% and 7853%, respectively, the area under the curve value was 0.789. Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I (P < 0.05). In CIN grade I patients with positive for HPV E6/E7 mRNA, in its orientation to grade CIN patients, in its orientation to grade CIN patients, at 69.2%, compared with patients negative for HPV E6/E7 mRNA (30.8%), significant difference (P < 0.05). CONCLUSION: HPV E6/E7 mRNA and HPV (PCR-reverse dot hybrid) positive expression have a close relationship with CIN-grade disease progression and is an independent risk factor for high-grade CIN lesions.
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OBJECTIVE: The primary object of this study is to analyze chromosomal abnormalities in miscarriages detected by copy number variants sequencing (CNV-Seq), establish potential pathways or genes related to miscarriages, and provide guidance for birth health in the following pregnancies. METHODS: This study enrolled 580 miscarriage cases with paired clinical information and chromosomal detection results analyzed by CNV-Seq. Further bioinformatic analyses were performed on validated pathogenic CNVs (pCNVs). RESULTS: Of 580 miscarriage cases, three were excluded as maternal cell contamination, 357 cases showed abnormal chromosomal results, and the remaining 220 were normal, with a positive detection rate of 61.87% (357/577). In the 357 miscarriage cases, 470 variants were discovered, of which 65.32% (307/470) were pathogenic. Among all variants detected, 251 were numerical chromosomal abnormalities, and 219 were structural abnormalities. With advanced maternal age, the proportion of numerical abnormalities increased, but the proportion of structural abnormalities decreased. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis revealed that eleven pathways and 636 biological processes were enriched in pCNVs region genes. Protein-protein interaction analysis of 226 dosage-sensitive genes showed that TP53, CTNNB1, UBE3A, EP300, SOX2, ATM, and MECP2 might be significant in the development of miscarriages. CONCLUSION: Our study provides evidence that chromosomal abnormalities contribute to miscarriages, and emphasizes the significance of microdeletions or duplications in causing miscarriages apart from numerical abnormalities. Essential genes found in pCNVs regions may account for miscarriages which need further validation.
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Intensity-modulated radiation therapy (IMRT) has been widely used in treating head and neck tumors. However, due to the complex anatomical structures in the head and neck region, it is challenging for the plan optimizer to rapidly generate clinically acceptable IMRT treatment plans. A novel deep learning multi-scale Transformer (MST) model was developed in the current study aiming to accelerate the IMRT planning for head and neck tumors while generating more precise prediction of the voxel-level dose distribution. The proposed end-to-end MST model employs the shunted Transformer to capture multi-scale features and learn a global dependency, and utilizes 3D deformable convolution bottleneck blocks to extract shape-aware feature and compensate the loss of spatial information in the patch merging layers. Moreover, data augmentation and self-knowledge distillation are used to further improve the prediction performance of the model. The MST model was trained and evaluated on the OpenKBP Challenge dataset. Its prediction accuracy was compared with three previous dose prediction models: C3D, TrDosePred, and TSNet. The predicted dose distributions of our proposed MST model in the tumor region are closest to the original clinical dose distribution. The MST model achieves the dose score of 2.23 Gy and the DVH score of 1.34 Gy on the test dataset, outperforming the other three models by 8%-17%. For clinical-related DVH dosimetric metrics, the prediction accuracy in terms of mean absolute error (MAE) is 2.04% for D 99 , 1.54% for D 95 , 1.87% for D 1 , 1.87% for D mean , 1.89% for D 0.1 c c , respectively, superior to the other three models. The quantitative results demonstrated that the proposed MST model achieved more accurate voxel-level dose prediction than the previous models for head and neck tumors. The MST model has a great potential to be applied to other disease sites to further improve the quality and efficiency of radiotherapy planning.
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Phytochrome A (phyA) is the plant far-red (FR) light photoreceptor and plays an essential role in regulating photomorphogenic development in FR-rich conditions, such as canopy shade. It has long been observed that phyA is a phosphoprotein in vivo; however, the protein kinases that could phosphorylate phyA remain largely unknown. Here we show that a small protein kinase family, consisting of four members named PHOTOREGULATORY PROTEIN KINASES (PPKs) (also known as MUT9-LIKE KINASES), directly phosphorylate phyA in vitro and in vivo. In addition, TANDEM ZINC-FINGER/PLUS3 (TZP), a recently characterized phyA-interacting protein required for in vivo phosphorylation of phyA, is also directly phosphorylated by PPKs. We reveal that TZP contains two intrinsically disordered regions in its amino-terminal domain that undergo liquid-liquid phase separation (LLPS) upon light exposure. The LLPS of TZP promotes colocalization and interaction between PPKs and phyA, thus facilitating PPK-mediated phosphorylation of phyA in FR light. Our study identifies PPKs as a class of protein kinases mediating the phosphorylation of phyA and demonstrates that the LLPS of TZP contributes significantly to more production of the phosphorylated phyA form in FR light.
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Proteínas de Arabidopsis , Arabidopsis , Fitocromo A , Fosforilación , Fitocromo A/metabolismo , Fitocromo A/genética , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas Quinasas/metabolismo , Proteínas Quinasas/genética , Separación de FasesRESUMEN
Background: Assessments of genetic diversity are essential for germplasm characterization and exploitation. Molecular markers are valuable tools for exploring genetic variation and identifying germplasm. They play key roles in a Xanthoceras sorbifolia breeding program. Results: We analyzed the genetic diversity of populations of this species using 23 simple sequence repeat (SSR) loci and data on kernel oil content. The 11 populations included in the study were distributed across a large geographic range in China. The kernel oil content differed significantly among populations. The SSR marker analysis detected high genetic diversity among the populations. All SSRs were polymorphic, and we identified 80 alleles across the populations. The number of alleles at each locus ranged from two to six, averaging 3.48 per primer pair. The polymorphism information content values ranged from 0.35 to 0.70, averaging 0.51. Expected heterozygosity, observed heterozygosity, and Shannon's information index calculations detected large genetic variations among populations of different provenance. The high average number of alleles per locus and the allelic diversity observed in the set of genotypes analyzed indicated that the genetic base of this species was relatively wide. The statistically significant positive correlation between genetic and geographic distances suggested adaptations to local conditions. Conclusions: Microsatellite markers can be used to efficiently distinguish X. sorbifolia populations and assess their genetic diversity. The information we have provided will contribute to the conservation and management of this important plant genetic resource.