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Rapid advancements and proliferation of electronic devices in the past decades have significantly intensified electromagnetic interference (EMI) issues, driving the demand for more effective shielding materials. Herein, we introduce a novel two-layer graphene nonwoven fabric (2-gNWF) that shows excellent EMI shielding properties. The 2-gNWF fabric comprises a porous fibrous upper layer and a dense conductive film-like lower layer, specifically designed to enhance EMI shielding through the combined mechanisms of reflection, multiple internal reflections, and absorption of electromagnetic waves. The 2-gNWF exhibits a remarkable EMI shielding effectiveness (SE) of 80 dB while maintaining an impressively low density of 0.039 g/cm3, surpassing the performance of many existing graphene-based materials. The excellent EMI shielding performance of 2-gNWF is attributed to the multiple interactions of incident electromagnetic waves with its highly conductive network and porous structure, leading to efficient energy dissipation. The combination of high EMI SE and low density makes 2-gNWF ideal for applications that require lightweight yet effective shielding properties, demonstrating the significant potential for advanced EMI shielding applications.
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BACKGROUND: A major challenge in prevention and early treatment of acute kidney injury (AKI) is the lack of high-performance predictors in critically ill patients. Therefore, we innovatively constructed U-AKIpredTM for predicting AKI in critically ill patients within 12 h of panel measurement. METHODS: The prospective cohort study included 680 patients in the training set and 249 patients in the validation set. After performing inclusion and exclusion criteria, 417 patients were enrolled in the training set and 164 patients were enrolled in the validation set finally. AKI was diagnosed by Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: Twelve urinary kidney injury biomarkers (mALB, IgG, TRF, α1MG, NAG, NGAL, KIM-1, L-FABP, TIMP2, IGFBP7, CAF22 and IL-18) exhibited good predictive performance for AKI within 12 h in critically ill patients. U-AKIpredTM, combined with three crucial biomarkers (α1MG, L-FABP and IGFBP7) by multivariate logistic regression analysis, exhibited better predictive performance for AKI in critically ill patients within 12 h than the other twelve kidney injury biomarkers. The area under the curve (AUC) of the U-AKIpredTM, as a predictor of AKI within 12 h, was 0.802 (95% CI: 0.771-0.833, P < 0.001) in the training set and 0.844 (95% CI: 0.792-0.896, P < 0.001) in validation cohort. A nomogram based on the results of the training and validation sets of U-AKIpredTM was developed which showed optimal predictive performance for AKI. The fitting effect and prediction accuracy of U-AKIpredTM was evaluated by multiple statistical indicators. To provide a more flexible predictive tool, the dynamic nomogram (https://www.xsmartanalysis.com/model/U-AKIpredTM) was constructed using a web-calculator. Decision curve analysis (DCA) and a clinical impact curve were used to reveal that U-AKIpredTM with the three crucial biomarkers had a higher net benefit than these twelve kidney injury biomarkers respectively. The net reclassification index (NRI) and integrated discrimination index (IDI) were used to improve the significant risk reclassification of AKI compared with the 12 kidney injury biomarkers. The predictive efficiency of U-AKIpredTM was better than the NephroCheck® when testing for AKI and severe AKI. CONCLUSION: U-AKIpredTM is an excellent predictive model of AKI in critically ill patients within 12 h and would assist clinicians in identifying those at high risk of AKI.
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ETHNOPHARMACOLOGICAL RELEVANCE: Chromolaenaodorata (L.) R.M. King & H. Rob, a perennial herb, has been traditionally utilized as a herbal remedy for treating leech bites, soft tissue wounds, burn wounds, skin infections, and dento-alveolitis in tropical and subtropical regions. AIM OF THE STUDY: The present study was to analyze the active fraction of C. odorata ethanol extract and investigate its hemostatic, anti-inflammatory, wound healing, and antimicrobial properties. Additionally, the safety of the active fraction as an external preparation was assessed through skin irritation and allergy tests. MATERIALS AND METHODS: The leaves and stems of C. odorata were initially extracted with ethanol, followed by purification through AB-8 macroporous adsorption resin column chromatography to yield different fractions. These fractions were then screened for hemostatic activity in mice and rabbits to identify the active fraction. Subsequently, the hemostatic effect of the active fraction was assessed through the bleeding time of the rabbit ear artery in vivo and the coagulant time of rabbit blood in vitro. The anti-inflammatory activity of the active fraction was tested on mice ear edema induced by xylene and rat paw edema induced by carrageenin. Furthermore, the active fraction's promotion effect on wound healing was evaluated using a rat skin injury model, and skin safety tests were conducted on rabbits and guinea pigs. Lastly, antimicrobial activities against two Gram-positive bacteria (G+, Staphylococcus aureus and S. epidermidis) and three Gram-negative bacteria (G-, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were determined using the plate dilution method. RESULTS: The ethanol extract of C. odorata leaves and stems was fractionated into 30%, 60%, and 90% ethanol eluate fractions. These fractions demonstrated hemostatic activity, with the 30% ethanol eluate fraction (30% EEF) showing the strongest effect, significantly reducing bleeding time (P < 0.05). A concentration of 1.0 g/mL of the 30% EEF accelerated cutaneous wound healing in rats on the 3rd, 6th, and 9th day post-operation, with the healing effect increasing over time. No irritation or allergy reactions were observed in rabbits and guinea pigs exposed to the 30% EEF. Additionally, the 30% EEF exhibited mild inhibitory effect on mice ear and rat paw edema, as well as antimicrobial activity against tested bacteria, with varying minimal inhibitory concentration (MIC) values. CONCLUSIONS: The 30% EEF demonstrated a clear hemostatic effect on rabbit bleeding time, a slight inhibitory effect on mice ear edema and rat paw edema, significant wound healing activity in rats, and no observed irritation or allergic reactions. Antibacterial activity was observed against certain clinically isolated bacteria, particularly the G- bacteria. This study lays the groundwork for the potential development and application of C. odorata in wound treatment.
Subject(s)
Anti-Inflammatory Agents , Chromolaena , Edema , Ethanol , Hemostatics , Plant Extracts , Wound Healing , Animals , Rabbits , Wound Healing/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/isolation & purification , Mice , Male , Hemostatics/pharmacology , Ethanol/chemistry , Chromolaena/chemistry , Edema/drug therapy , Edema/chemically induced , Rats , Skin/drug effects , Female , Anti-Infective Agents/pharmacology , Anti-Infective Agents/isolation & purification , Plant Leaves/chemistry , Hypersensitivity/drug therapy , Xylenes , Plant Stems/chemistryABSTRACT
INTRODUCTION: Smilacis Glabrae Rhizoma (SGR) is rich in chemical constituents with a variety of pharmacological activities. However, in-depth research has yet to be conducted on the chemical and pharmacodynamic constituents of SGR. MATERIALS AND METHODS: In this study, the chemical constituents of SGR were analyzed using liquid chromatography-mass spectrometry, and the pharmacodynamic compounds responsible for the medicinal effects of SGR were elucidated through a literature review. RESULTS: In total, 20 potentially new compounds, including 16 flavonoids (C19, C20, and C27-C40) and four phenylpropanoids (C107, C112, C113, and C118), together with 161 known ones were identified in the ethanol extract of SGR using liquid chromatography-mass spectrometry, and 25 of them were unequivocally identified by comparison with reference compounds. Moreover, 17 known constituents of them were identified in the plants of genus Smilax for the first time, and 16 were identified in the plant Smilax glabra Roxb. for the first time. Of 161 known compounds, 84 constituents (including isomers) have been reported to have 17 types of pharmacological activities, covering all known pharmacological activities of SGR; among these 84 bioactive constituents, six were found in the plants of genus Smilax for the first time and five were found in S. glabra for the first time, which are new bioactive constituents found in the plants of genus Smilax and the plant S. glabra, respectively. CONCLUSION: The results provide further information on the chemical composition of SGR, laying the foundation for the elucidation of the pharmacodynamic substances of SGR.
Subject(s)
Rhizome , Smilax , Spectrometry, Mass, Electrospray Ionization , Chromatography, High Pressure Liquid/methods , Rhizome/chemistry , Smilax/chemistry , Spectrometry, Mass, Electrospray Ionization/methods , Flavonoids/analysis , Flavonoids/chemistry , Flavonoids/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Molecular StructureABSTRACT
KCNA1 is the coding gene for Kv1.1 voltage-gated potassium-channel α subunit. Three variants of KCNA1 have been reported to manifest as paroxysmal kinesigenic dyskinesia (PKD), but the correlation between them remains unclear due to the phenotypic complexity of KCNA1 variants as well as the rarity of PKD cases. Using the whole exome sequencing followed by Sanger sequencing, we screen for potential pathogenic KCNA1 variants in patients clinically diagnosed with paroxysmal movement disorders and identify three previously unreported missense variants of KCNA1 in three unrelated Chinese families. The proband of one family (c.496G>A, p.A166T) manifests as episodic ataxia type 1, and the other two (c.877G>A, p.V293I and c.1112C>A, p.T371A) manifest as PKD. The pathogenicity of these variants is confirmed by functional studies, suggesting that p.A166T and p.T371A cause a loss-of-function of the channel, while p.V293I leads to a gain-of-function with the property of voltage-dependent gating and activation kinetic affected. By reviewing the locations of PKD-manifested KCNA1 variants in Kv1.1 protein, we find that these variants tend to cluster around the pore domain, which is similar to epilepsy. Thus, our study strengthens the correlation between KCNA1 variants and PKD and provides more information on genotype-phenotype correlations of KCNA1 channelopathy.
Subject(s)
Dystonia , Kv1.1 Potassium Channel , Mutation, Missense , Pedigree , Humans , Kv1.1 Potassium Channel/genetics , Male , Female , Dystonia/genetics , Dystonia/pathology , Mutation, Missense/genetics , Exome Sequencing , Loss of Function Mutation/genetics , Adult , Gain of Function Mutation/genetics , Child , Adolescent , Genetic Predisposition to Disease , HEK293 Cells , Ataxia , MyokymiaABSTRACT
Using fiber-reinforced polymer composite to replace metal in window frames has become a trend in aircraft manufacturing to achieve structural weight reduction. This study proposes an innovative winding compression molding process for continuous production of aircraft window frames using continuous carbon fiber-reinforced polyamide 6 thermoplastic composite filaments (CF/PA6). Through process parameter optimization, the production cycle of CF/PA6 composite window frames was controlled within 5 min, with an ultra-low porosity of 0.69%, meeting aviation application standards. Combining mechanical property experimental tests and finite element analysis, the mechanical performance of window frames made from three different materials was compared and evaluated. In the hoop direction, the mechanical performance of the continuous CF/PA6 thermoplastic window frames were significantly higher than that of chopped CF/epoxy compression molding window frames and aluminum alloy window frames. In the radial direction, the maximum strain occurred at the corner with the highest curvature of the frame due to the absence of fiber reinforcement, resulting in weak pure interlayer shear. Nevertheless, the thermoplastic CF/PA6 winding compression molded window frame still exhibited a high resistance to crack propagation and damage, as evidenced by the absence of any detectable sound of microdamage during testing with a 9000 N load. It is believed that achieving a further-balanced design of hoop-radial performance by appropriately introducing radial ply reinforcement can lead to a significant weight reduction goal in the window frame. The findings in this study provide an innovative process reference that can be universally applicable to high-speed and near-net-shape manufacturing without material waste of continuous fiber-reinforced thermoplastic composite products.
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This study addresses the challenge of achieving foam with a high expansion ratio and poor mechanical properties, caused by the low melt viscosity of semi-crystalline polypropylene (PP). We systematically employ a modification approach involving blending PP with polyolefin elastomers (POE), irradiation crosslinking, and fiber reinforcement to prepare fiber-reinforced crosslinked PP/POE composite foam. Through optimization and characterization of material composition and processing conditions, the obtained fiber-reinforced crosslinked PP/POE composite foam exhibits both low density and high performance. Specifically, at a crosslinking degree of 12%, the expansion ratio reaches 16 times its original value, and a foam density of 0.057 g/cm3 is reduced by 36% compared to the non-crosslinked PP/POE system with a density of 0.089 g/cm3. The density of the short-carbon-fiber-reinforced crosslinked sCF/PP/POE composite foam is comparable to that of the crosslinked PP/POE system, but the tensile strength reaches 0.69 MPa, representing a 200% increase over the crosslinked PP/POE system and a 41% increase over the non-crosslinked PP/POE system. Simultaneously, it exhibits excellent impact strength, tear resistance, and low heat shrinkage. Irradiation crosslinking is beneficial for enhancing the melt strength and resistance to high temperature thermal shrinkage of PP/POE foam, while fiber reinforcement contributes significantly to improving mechanical properties. These achieve a good complementary effect in low-density and high-performance PP foam modification.
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The inherent π-π interfacial interaction between carbon nanotubes (CNTs) and polystyrene (PS) makes the CNT/PS composite a representative thermoplastic nanocomposite. However, the strong van der Waals force among CNTs poses challenges to achieving effective dispersion. This review provides an overview of various CNT functionalization methods for CNT/PS composites, encompassing covalent grafting with PS-related polymers and non-covalent modification. A focus in this section involves the pre-introduction surface modification of CNTs with PS or PS-related polymers, substantially enhancing both CNT dispersibility and interfacial compatibility within the PS matrix. Furthermore, a comprehensive summary of the mechanical, electrical, thermal, and electromagnetic shielding properties of CNT/PS nanocomposites is provided, offering an overall understanding of this material. The surface modification methods of CNTs reviewed in this paper can be extended to carbon material/aromatic polymer composites, assisting researchers in customizing the optimal surface modification methods for CNTs, maximizing their dispersibility, and fully unleashing the various properties of CNTs/polymer composites. Additionally, high-performance CNTs/PS composites prepared using appropriate CNT modification methods have potential applications in areas such as electronic devices, sensors, and energy storage and conversion.
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Polyvinyl chloride (PVC) foam, valued for its mechanical and thermal properties along with cost-effectiveness, is extensively utilized across diverse industries. However, its high volatile organic compound (VOC) emissions hinder its adoption in eco-friendly synthetic leather. This study proposes a solution by optimizing the formulation design and foaming processes and achieving mechanical property enhancement via carbon-fiber-reinforced PVC composite foam (CF/PVC). The aim is to reduce PVC usage via enhancing its intrinsic properties. Systematic investigations were carried out on the impact of foaming raw materials, foaming processes, fiber content, and fiber length on the foaming performance, mechanical properties, and VOC emissions. The material formulation and process parameters were successfully optimized. Further assessment of various indicators such as the density, mechanical properties, and tear resistance of synthetic leather samples confirmed that the innovative CF/PVC foam developed in this study meets the requirements for automotive interior applications. Notably, the tensile strength and tear resistance of CF/PVC composite synthetic leather increased by 50% and 29%, respectively, compared to pure PVC, while VOC emissions decreased by 28%. It is anticipated that a more pronounced reduction in VOC emissions will be achieved in practical automotive interior leather applications when further considering the reinforcing effect of fibers, which leads to a reduction in PVC usage. The findings present a technical reference for innovative applications, aiming to enhance PVC foam performance and minimize emissions.
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To address the challenge of balancing the mechanical, thermal insulation, and flame-retardant properties of building insulation materials, this study presented a facile approach to modify the rigid polyurethane foam composites (RPUFs) via commercial expandable graphite (EG), ammonium polyphosphate (APP), and silica aerogel (SA). The resulting EG/APP/SA/RPUFs exhibited low thermal conductivity close to neat RPUF. However, the compressive strength of the 6EG/2APP/SA/RPUF increased by 49% along with achieving a V-0 flame retardant rating. The residual weight at 700 °C increased from 19.2 wt.% to 30.9 wt.%. Results from cone calorimetry test (CCT) revealed a 9.2% reduction in total heat release (THR) and a 17.5% decrease in total smoke production (TSP). The synergistic flame-retardant mechanism of APP/EG made significant contribution to the excellent flame retardant properties of EG/APP/SA/RPUFs. The addition of SA played a vital role in reducing thermal conductivity and enhancing mechanical performance, effectively compensating for the shortcomings of APP/EG. The cost-effective EG/APP/SA system demonstrates a positive ternary synergistic effect in achieving a balance in RPUFs properties. This study provides a novel strategy aimed at developing affordable building wall insulation material with enhanced safety features.
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The challenge of wheat leaf rust on wheat production is a recurring issue. Race identification of Puccinia triticina (Pt) serves as the foundation for preventing and controlling this disease. In a 15-year study, we identified 2,900 isolates of Pt from 20 provinces, cities, or autonomous regions in China during 2007 to 2021 and found 332 virulence phenotypes with 11 predominant phenotypes: PHT (8.3%), THT (5.4%), PHK (4.5%), PHJ (3.7%), THJ (3.6%), SHJ (3.5%), THS (3.3%), FGD (2.9%), THK (2.6%), PHS (2.4%), and PHD (2.0%). The virulence frequency for 40 Lr genes was identified across different years and areas; one major reason for the race dynamics was the attenuation to Lr1 and Lr26, which was more evident in southwest China. Lr9, Lr24, Lr28, Lr38, and Lr42 maintained effectiveness in China, while Lr2c, Lr10, Lr12, Lr14a, Lr14b, Lr22a, Lr33, and Lr36 nearly lost their effectiveness against wheat leaf rust disease. No significant difference was found among predominant phenotypes in different areas (P > 0.1). However, 12 Lr sites were found to have differences in virulence frequencies with values greater than 20% across various locations; furthermore, the lowest and highest virulence values were observed in north China (Area 1) and northwest China (Area 5), respectively. According to phenotype dynamics, PHT, THT, FGD, THK, and PHS are more likely to persist over time. In addition, much attention should be given toward discovering rising combinations of virulent phenotypes.
Subject(s)
Basidiomycota , Puccinia , Basidiomycota/genetics , Virulence/genetics , Plant Diseases/genetics , ChinaABSTRACT
Bile acids (BAs) have increasingly been implicated in the onset and progression of necrotizing enterocolitis (NEC); multiple findings have demonstrated their ability to induce damage to the intestinal epithelium, thereby exacerbating disease severity. Although we previously showed that melatonin was able to treat NEC by correcting the Treg/Th17 imbalance, the modulatory effect of melatonin on BAs remains unclear. In this study, we conducted transcriptome analysis on intestinal tissues from patients with NEC and validated these findings. Subsequently, we treated mice with melatonin alone or in combination with an agonist/inhibitor of Sirtuin 1 (SIRT1) to assess faecal and serum BA levels, the expression levels of BA transporters and regulators, and the extent of intestinal injury. Our transcriptome results indicated dysregulation of BA metabolism and abnormal expression of BA transporters in patients with NEC, which were also observed in our NEC mouse model. Furthermore, exogenous BAs were found to aggravate NEC severity in mice. Notably, melatonin effectively restored the aberrant expression of BA transporters, such as apical membrane sodium-dependent bile acid transporters (ASBT), ileal bile acid-binding protein (IBABP), and organic solute transporter-alpha (OST-α), by upregulating SIRT1 expression while reducing farnesoid X receptor (FXR) acetylation, consequently leading to decreased serum and faecal BA levels and mitigated NEC severity. Thus, we propose a potential mechanism through which melatonin reduces BA levels via the SIRT1/FXR signalling axis in an NEC mouse model. Collectively, these results highlight that melatonin holds promise for reducing BA levels and represents a promising therapeutic strategy for treating NEC.
Subject(s)
Enterocolitis, Necrotizing , Melatonin , Animals , Humans , Mice , Bile Acids and Salts/metabolism , Disease Models, Animal , Enterocolitis, Necrotizing/drug therapy , Enterocolitis, Necrotizing/metabolism , Intestines , Liver , Melatonin/pharmacology , Melatonin/therapeutic use , Sirtuin 1/metabolismABSTRACT
The utilization of hot carriers as a means to surpass the Shockley-Queasier limit represents a promising strategy for advancing highly efficient photovoltaic devices. Quantum dots, owing to their discrete energy states and limited multi-phonon cooling process, are regarded as one of the most promising materials. However, in practical implementations, the presence of numerous defects and discontinuities in colloidal quantum dot (CQD) films significantly curtails the transport distance of hot carriers. In this study, the harnessing of excess energies from hot-carriers is successfully demonstrated and a world-record carrier diffusion length of 15 µm is observed for the first time in colloidal systems, surpassing existing hot-carrier materials by more than tenfold. The observed phenomenon is attributed to the specifically designed honeycomb-like topological structures in a HgTe CQD superlattice, with its long-range periodicity confirmed by High-Resolution Transmission Electron Microscopy(HR-TEM), Selected Area Electron Diffraction(SAED) patterns, and low-angle X-ray diffraction (XRD). In such a superlattice, nonlocal hot carrier transport is supported by three unique physical properties: the wavelength-independent responsivity, linear output characteristics and microsecond fast photoresponse. These findings underscore the potential of HgTe CQD superlattices as a feasible approach for efficient hot carrier collection, thereby paving the way for practical applications in highly sensitive photodetection and solar energy harvesting.
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Silver nanoparticles (AgNPs) by green synthesis from fungi polysaccharides are attracting increasing attention owing to their distinctive features and special applications in numerous fields. In this study, a cost-effective and environmentally friendly biosynthesizing AgNPs method with no toxic chemicals involved from the fruiting body polysaccharide of Phlebopus portentosus (PPP) was established and optimized by single factor experiment and response surface methodology. The optimum synthesis conditions of polysaccharide-AgNPs (PPP-AgNPs) were identified to be the reaction time of 140 min, reaction temperature of 94 °C, and the PPP: AgNO3 ratio of 1:11.5. Formation of PPP-AgNPs was indicated by visual detection of colour change from yellowish to yellowish brown. PPP-AgNPs were characterized by different methods and further evaluated for biological activities. That the Ultraviolet-visible (UV-Vis.) spectroscopy displayed a sharp absorption peak at 420 nm confirmed the formation of AgNPs. Fourier transform infrared (FTIR) analysis detected the presence of various functional groups. The lattice indices of (111), (200), (220), and (331), which indicated a faced-centered-cubic of the Ag crystal structure of PPP-AgNPs, was confirmed by X-ray diffraction (XRD) and the particles were found to be spherical through high resolution transmission electron microscopy (HRTEM). Energy dispersive X-ray spectroscopy (EDS) determined the presence of silver in PPP-AgNPs. The percentage relative composition of elements was determined as silver (Ag) 82.5 % and oxygen (O) 17.5 % for PPP-AgNPs, and did not exhibit any nitrogen peaks. The specific surface area of PPP-AgNPs was calculated to be 0.5750 m2/g with an average pore size of 24.33 nm by BET analysis. The zeta potential was -4.32 mV, which confirmed the stability and an average particle size of 64.5 nm was calculated through dynamic light scattering (DLS). PPP-AgNPs exhibited significant free radical scavenging activity against DPPH with an IC50 value of 0.1082 mg/mL. The MIC values of PPP-AgNPs for E. coli, S. aureus, C. albicans, C. glabrata, and C. parapsilosis are 0.05 mg/mL. The IC50 value of the inhibition of PPP-AgNPs against α-glucosidase was 11.1 µg/mL, while the IC50 values of PPP-AgNPs against HepG2 and MDA-MB-231 cell lines were calculated to be 14.36 ± 0.43 µg/mL and 40.05 ± 2.71 µg/mL, respectively. According to the evaluation, it can be concluded that these green-synthesized and eco-friendly PPP-AgNPs are helpful to improve therapeutics because of significant antioxidant, antimicrobial, antidiabetic, and anticancer properties to provide new possibilities for clinic applications.
Subject(s)
Anti-Infective Agents , Metal Nanoparticles , Silver/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Staphylococcus aureus , Hypoglycemic Agents/pharmacology , Metal Nanoparticles/chemistry , Escherichia coli , Plant Extracts/chemistry , Anti-Infective Agents/chemistry , Spectrometry, X-Ray Emission , Polysaccharides/pharmacology , Anti-Bacterial Agents/pharmacologyABSTRACT
INTRODUCTION: Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders characterized by progressive degeneration of upper motor neurons. Homozygous or compound heterozygous variants in COQ4 have been reported to cause primary CoQ10 deficiency-7 (COQ10D7), which is a mitochondrial disease. AIMS: We aimed to screened COQ4 variants in a cohort of HSP patients. METHODS: A total of 87 genetically unidentified HSP index patients and their available family members were recruited. Whole exome sequencing (WES) was performed in all probands. Functional studies were performed to identify the pathogenicity of those uncertain significance variants. RESULTS: In this study, five different COQ4 variants were identified in three Chinese HSP pedigrees and two variants were novel, c.87dupT (p.Arg30*), c.304C>T (p.Arg102Cys). More importantly, we firstly described two early-onset pure HSP caused by COQ4 variants. Functional studies in patient-derived fibroblast lines revealed a reduction cellular CoQ10 levels and the abnormal mitochondrial structure. CONCLUSIONS: Our findings revealed that bilateral variants in the COQ4 gene caused HSP predominant phenotype, expanding the phenotypic spectrum of the COQ4-related disorders.
Subject(s)
Mitochondrial Diseases , Spastic Paraplegia, Hereditary , Humans , Spastic Paraplegia, Hereditary/genetics , Mutation/genetics , Phenotype , Pedigree , Mitochondrial Proteins/geneticsABSTRACT
Paroxysmal kinesigenic dyskinesia (PKD), the most common type of paroxysmal movement disorder, is characterized by sudden and brief attacks of choreoathetosis or dystonia triggered by sudden voluntary movements. PKD is mainly caused by mutations in the PRRT2 or TMEM151A gene. The exact pathophysiological mechanisms of PKD remain unclear, although the function of PRRT2 protein has been well characterized in the last decade. Based on abnormal ion channels and disturbed synaptic transmission in the absence of PRRT2, PKD may be channelopathy or synaptopathy, or both. In addition, the cerebellum is regarded as the key pathogenic area. Spreading depolarization in the cerebellum is tightly associated with dyskinetic episodes. Whereas, in PKD, other than the cerebellum, the role of the cerebrum including the cortex and thalamus needs to be further investigated.
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Introduction: With the advancement of RNA-seq technology and machine learning, training large-scale RNA-seq data from databases with machine learning models can generally identify genes with important regulatory roles that were previously missed by standard linear analytic methodologies. Finding tissue-specific genes could improve our comprehension of the relationship between tissues and genes. However, few machine learning models for transcriptome data have been deployed and compared to identify tissue-specific genes, particularly for plants. Methods: In this study, an expression matrix was processed with linear models (Limma), machine learning models (LightGBM), and deep learning models (CNN) with information gain and the SHAP strategy based on 1,548 maize multi-tissue RNA-seq data obtained from a public database to identify tissue-specific genes. In terms of validation, V-measure values were computed based on k-means clustering of the gene sets to evaluate their technical complementarity. Furthermore, GO analysis and literature retrieval were used to validate the functions and research status of these genes. Results: Based on clustering validation, the convolutional neural network outperformed others with higher V-measure values as 0.647, indicating that its gene set could cover as many specific properties of various tissues as possible, whereas LightGBM discovered key transcription factors. The combination of three gene sets produced 78 core tissue-specific genes that had previously been shown in the literature to be biologically significant. Discussion: Different tissue-specific gene sets were identified due to the distinct interpretation strategy for machine learning models and researchers may use multiple methodologies and strategies for tissue-specific gene sets based on their goals, types of data, and computational resources. This study provided comparative insight for large-scale data mining of transcriptome datasets, shedding light on resolving high dimensions and bias difficulties in bioinformatics data processing.
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Although multi-parent populations (MPPs) integrate the advantages of linkage and association mapping populations in the genetic dissection of complex traits and especially combine genetic analysis with crop breeding, it is difficult to detect small-effect quantitative trait loci (QTL) for complex traits in multiparent advanced generation intercross (MAGIC), nested association mapping (NAM), and random-open-parent association mapping (ROAM) populations. To address this issue, here we proposed a multi-locus linear mixed model method, namely mppQTL, to detect QTLs, especially small-effect QTLs, in these MPPs. The new method includes two steps. The first is genome-wide scanning based on a single-locus linear mixed model; the P-values are obtained from likelihood-ratio test, the peaks of negative logarithm P-value curve are selected by group-lasso, and all the selected peaks are regarded as potential QTLs. In the second step, all the potential QTLs are placed on a multi-locus linear mixed model, all the effects are estimated using expectation-maximization empirical Bayes algorithm, and all the non-zero effect vectors are further evaluated via likelihood-ratio test for significant QTLs. In Monte Carlo simulation studies, the new method has higher power in QTL detection, lower false positive rate, lower mean absolute deviation for QTL position estimate, and lower mean squared error for the estimate of QTL size (r2) than existing methods because the new method increases the power of detecting small-effect QTLs. In real dataset analysis, the new method (19) identified five more known genes than the existing three methods (14). This study provides an effective method for detecting small-effect QTLs in any MPPs.
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Objective: The purpose of this study was to analyse the clinical, microbiological and molecular epidemiological characteristics of patients with pyogenic liver abscess (PLA) caused by Klebsiella pneumoniae (KPN) in Inner Mongolia, China. Methods: The KPN isolates from 78 KPN-PLA cases admitted to a tertiary teaching hospital in Baotou, Inner Mongolia, from 2016 to 2019 were studied systematically and described comprehensively. The virulence factors, drug resistance and sequence types of KPN in different samples were identified by a wire-drawing test, polymerase chain reaction, a drug susceptibility test and multi-site sequence typing. Results: There were more male than female KPN-PLA patients (P<0.05). The mortality rate was 2.5%, and KPN-PLA was significantly associated with diabetes mellitus (P<0.05). Most of the KPN isolates in the puncture fluid of patients with KPN-PLA were hypervirulent KPN (HvKP). The positive rate of the KPN-PLA specimens was higher than that of the blood and urine specimens. The KPN isolates of the urine specimens had higher drug resistance than the other two (P<0.05). The hypermucoviscous KPN, aerobic actin (aero) (+), K1 and K2 serotypes accounted for 80.8%, 89.7%, 56.4% and 26.9%, respectively. In addition to ironB (3.8%), the detection rates of virulence factors rmpA, irp2, entB, iucD, aero, wcaG, iutA, kfu, ybtA, iron, fimH and mrkD were higher (69.2%-100.0%). The positive rate of KPN isolates of the KPN-PLA puncture fluid was higher than that of the blood and urine samples (P<0.05). In addition, ST23 was found to be the dominant ST (32.1%) of KPN-PLA in the Baotou region. Conclusion: In the KPN-PLA specimens, the KPN isolates were more virulent than those in the blood and urine specimens, and a carbapenem-resistant HvKP strain emerged. This research will help improve the understanding of HvKP and provide useful suggestions for KPN-PLA treatments.
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Polysaccharides from the species of Boletaceae (Boletales, Agaricomycetes, Basidiomycota) are economically significant to both functional foods and medicinal industries. The crude polysaccharide from Butyriboletus pseudospeciosus (BPP) was prepared, and its physicochemical properties were characterized through the use of consecutive experimental apparatus, and its impact on the gut microbiota of Kunming mice was evaluated. Analyses of the structure characteristics revealed that BPP was mainly composed of Man, Glc, and Gal, possessing the pyranose ring and ß/α-glycosidic linkages. TG analysis exhibited that BPP had great heat stability. The SEM observation performed demonstrated that BPP appeared with a rough, dense, and porous shape. Through the BPP intervention, the serum and fecal biochemical index in mice can be improved obviously (p < 0.05). The abundance of beneficial microbiota in the BPP-treated group was significantly increased, while the abundance of harmful microbiota was significantly decreased (p < 0.05). Based on the Tax4Fun, we also revealed the relationship between the species of gut microbiota and showed that the high dose of BPP has significantly changed the functional diversities compared with those in other groups (p < 0.05). The results suggest that B. pseudospeciosus could serve as potential functional food or medicine.