RESUMO
Parvalbumin-positive neurons (PVs) are the main class of inhibitory neurons in the mammalian central nervous system. By examining diurnal changes in synaptic and neuronal activity of PVs in the supragranular layer of the mouse primary visual cortex (V1), we found that both PV input and output are modulated in a time- and sleep-dependent manner throughout the 24-h day. We first show that PV-evoked inhibition is stronger by the end of the light cycle (ZT12) relative to the end of the dark cycle (ZT0), which is in line with the lower inhibitory input of PV neurons at ZT12 than at ZT0. Interestingly, PV inhibitory and excitatory synaptic transmission slowly oscillate in opposite directions during the light/dark cycle. Although excitatory synapses are predominantly regulated by experience, inhibitory synapses are regulated by sleep, via acetylcholine activating M1 receptors. Consistent with synaptic regulation of PVs, we further show in vivo that spontaneous PV activity displays daily rhythm mainly determined by visual experience, which negatively correlates with the activity cycle of surrounding pyramidal neurons and the dorsal lateral geniculate nucleus-evoked responses in V1. These findings underscore the physiological significance of PV's daily modulation.
Assuntos
Neurônios , Parvalbuminas , Animais , Camundongos , Parvalbuminas/metabolismo , Neurônios/metabolismo , Células Piramidais/metabolismo , Transmissão Sináptica , Sono , MamíferosRESUMO
Inertia-less viscoelastic channel flow displays a supercritical nonnormal mode elastic instability due to finite-size perturbations despite its linear stability. The nonnormal mode instability is determined mainly by a direct transition from laminar to chaotic flow, in contrast to normal mode bifurcation leading to a single fastest-growing mode. At higher velocities, transitions to elastic turbulence and further drag reduction flow regimes occur accompanied by elastic waves in three flow regimes. Here, we demonstrate experimentally that the elastic waves play a key role in amplifying wall-normal vorticity fluctuations by pumping energy, withdrawn from the mean flow, into wall-normal fluctuating vortices. Indeed, the flow resistance and rotational part of the wall-normal vorticity fluctuations depend linearly on the elastic wave energy in three chaotic flow regimes. The higher (lower) the elastic wave intensity, the larger (smaller) the flow resistance and rotational vorticity fluctuations. This mechanism was suggested earlier to explain elastically driven Kelvin-Helmholtz-like instability in viscoelastic channel flow. The suggested physical mechanism of vorticity amplification by the elastic waves above the elastic instability onset recalls the Landau damping in magnetized relativistic plasma. The latter occurs due to the resonant interaction of electromagnetic waves with fast electrons in the relativistic plasma when the electron velocity approaches light speed. Moreover, the suggested mechanism could be generally relevant to flows exhibiting both transverse waves and vortices, such as Alfven waves interacting with vortices in turbulent magnetized plasma, and Tollmien-Schlichting waves amplifying vorticity in both Newtonian and elasto-inertial fluids in shear flows.
RESUMO
As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to wreak havoc worldwide, the "Cytokine Storm" (CS, also known as the inflammatory storm) or Cytokine Release Syndrome has reemerged in the public consciousness. CS is a significant contributor to the deterioration of infected individuals. Therefore, CS control is of great significance for the treatment of critically ill patients and the reduction of mortality rates. With the occurrence of variants, concerns regarding the efficacy of vaccines and antiviral drugs with a broad spectrum have grown. We should make an effort to modernize treatment strategies to address the challenges posed by mutations. Thus, in addition to the requirement for additional clinical data to monitor the long-term effects of vaccines and broad-spectrum antiviral drugs, we can use CS as an entry point and therapeutic target to alleviate the severity of the disease in patients. To effectively combat the mutation, new technologies for neutralizing or controlling CS must be developed. In recent years, nanotechnology has been widely applied in the biomedical field, opening up a plethora of opportunities for CS. Here, we put forward the view of cytokine storm as a therapeutic target can be used to treat critically ill patients by expounding the relationship between coronavirus disease 2019 (COVID-19) and CS and the mechanisms associated with CS. We pay special attention to the representative strategies of nanomaterials in current neutral and CS research, as well as their potential chemical design and principles. We hope that the nanostrategies described in this review provide attractive treatment options for severe and critical COVID-19 caused by CS.
Assuntos
COVID-19 , Vacinas , Humanos , Síndrome da Liberação de Citocina/tratamento farmacológico , SARS-CoV-2 , Estado Terminal , Citocinas , Antivirais/farmacologia , Antivirais/uso terapêuticoRESUMO
Oomycete pathogens secrete numerous crinkling and necrosis proteins (CRNs) to manipulate plant immunity and promote infection. However, the functional mechanism of CRN effectors is still poorly understood. Previous research has shown that the Phytophthora sojae effector PsCRN108 binds to the promoter of HSP90s and inhibits their expression, resulting in impaired plant immunity. In this study, we found that in addition to HSP90, PsCRN108 also suppressed other Heat Shock Protein (HSP) family genes, including HSP40. Interestingly, PsCRN108 inhibited the expression of NbHSP40 through its promoter, but did not directly bind to its promoter. Instead, PsCRN108 interacted with NbCAMTA2, a negative regulator of plant immunity. NbCAMTA2 was a negative regulator of NbHSP40 expression, and PsCRN108 could promote such inhibition activity of NbCAMTA2. Our results elucidated the multiple roles of PsCRN108 in the suppression of plant immunity and revealed a new mechanism by which the CRN effector hijacked transcription factors to affect immunity. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
Assuntos
Phytophthora , Phytophthora/genética , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Choque Térmico/metabolismo , Imunidade Vegetal , Doenças das PlantasRESUMO
Recent studies based on animal models of various neurological disorders have indicated that mitophagy, a selective autophagy that eliminates damaged and superfluous mitochondria through autophagic degradation, may be involved in various neurological diseases. As an important mechanism of cellular stress response, much less is known about the role of mitophagy in stress-related mood disorders. Here, we found that tumor necrosis factor-α (TNF-α), an inflammation cytokine that plays a particular role in stress responses, impaired the mitophagy in the medial prefrontal cortex (mPFC) via triggering degradation of an outer mitochondrial membrane protein, NIP3-like protein X (NIX). The deficits in the NIX-mediated mitophagy by TNF-α led to the accumulation of damaged mitochondria, which triggered synaptic defects and behavioral abnormalities. Genetic ablation of NIX in the excitatory neurons of mPFC caused passive coping behaviors to stress, and overexpression of NIX in the mPFC improved TNF-α-induced synaptic and behavioral abnormalities. Notably, ketamine, a rapid on-set and long-lasting antidepressant, reversed the TNF-α-induced behavioral abnormalities through activation of NIX-mediated mitophagy. Furthermore, the downregulation of NIX level was also observed in the blood of major depressive disorder patients and the mPFC tissue of animal models. Infliximab, a clinically used TNF-α antagonist, alleviated both chronic stress- and inflammation-induced behavioral abnormalities via restoring NIX level. Taken together, these results suggest that NIX-mediated mitophagy links inflammation signaling to passive coping behaviors to stress, which underlies the pathophysiology of stress-related emotional disorders.
RESUMO
Despite the advances of multistep enzymatic cascade reactions, their incorporation with abiotic reactions in living organisms remains challenging in synthetic biology. Herein, we combined microbial metabolic pathways and Pd-catalyzed processes for in-situ generation of bioactive conjugated oligomers. Our biocompatible one-pot coupling reaction utilized the fermentation process of engineered E. coli that converted glucose to styrene, which participated in the Pd-catalyzed Heck reaction for in-situ synthesis of conjugated oligomers. This process serves a great interest in understanding resistance evolution by utilizing the inhibitory activity of the synthesized conjugated oligomers. The approach allows for the in-situ combination of biological metabolism and CC coupling reactions, opening up new possibilities for the biosynthesis of unnatural molecules and enabling the in-situ regulation of the bioactivity of the obtained products.
Assuntos
Escherichia coli , Paládio , Escherichia coli/metabolismo , Catálise , FermentaçãoRESUMO
We report the free energy barriers for the elementary reactions in the 2e- and 4e- oxygen reduction reaction (ORR) steps on Au(100) in an alkaline solution. Due to the weak adsorption energy of O2 on Au(100), the barrier for the association channel is very low, and the 2e- pathway is clearly favored, while the barrier for the O-O dissociation channel is significantly higher at 0.5 eV. Above 0.7 V reversible hydrogen electrode (RHE), the association channel becomes thermodynamically unfavorable, which opens up the O-O dissociation channel, leading to the 4e- pathway. The low adsorption energy of oxygenated species on Au is now an advantage, and residue ORR current can be observed up to the 1.0-1.2 V region (RHE). In contrast, the O-O dissociation barrier on Au(111) is significantly higher, at close to 0.9 eV, due to coupling with surface reorganization, which explains the lower ORR activity on Au(111) than that on Au(100). In combination with the previously suggested outer sphere electron transfer to O2 for its initial adsorption, these results provide a consistent explanation for the features in the experimentally measured polarization curve for the alkaline ORR on Au(100) and demonstrate an ORR mechanism distinct from that on Pt(111). It also highlights the importance to consider the spin state of O2 in ORR and to understand the activation barriers, in addition to the adsorption energies, to account for the features observed in electrochemical measurements.
RESUMO
The enhanced permeability and retention (EPR) effect has become the guiding principle for nanomedicine against cancer for a long time. However, several biological barriers severely resist therapeutic agents' penetration and retention into the deep tumor tissues, resulting in poor EPR effect and high tumor mortality. Inspired by lava, we proposed a proteolytic enzyme therapy to improve the tumor distribution and penetration of nanomedicine. A trypsin-crosslinked hydrogel (Trypsin@PSA Gel) was developed to maintain trypsin's activity. The hydrogel postponed trypsin's self-degradation and sustained the release. Trypsin promoted the cellular uptake of nanoformulations in breast cancer cells, enhanced the penetration through endothelial cells, and degraded total and membrane proteins. Proteomic analysis reveals that trypsin affected ECM components and down-regulated multiple pathways associated with cancer progression. Intratumoral injection of Trypsin@PSA Gel significantly increased the distribution of liposomes in tumors and reduced tumor vasculature. Combination treatment with intravenous injection of gambogic acid-loaded liposomes and intratumoral injection of Trypsin@PSA Gel inhibited tumor growth. The current study provides one of the first investigations into the enhanced tumor distribution of liposomes induced by a novel proteolytic enzyme therapy.
Assuntos
Hidrogéis , Lipossomos , Polietilenoglicóis , Tripsina , Xantonas , Lipossomos/química , Animais , Polietilenoglicóis/química , Hidrogéis/química , Humanos , Tripsina/metabolismo , Tripsina/química , Feminino , Camundongos , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Neoplasias da Mama/tratamento farmacológico , ProteóliseRESUMO
The ethylene-regulated hypocotyl elongation of Arabidopsis thaliana involves many transcription factors. The specific role of MYC transcription factors in ethylene signal transduction is not completely understood. The results here revealed that two MYCs, MYC2 and MYC3, act as negative regulators in ethylene-suppressed hypocotyl elongation. Etiolated seedlings of the loss-of-function mutant of MYC2 or MYC3 were significantly longer than wild-type seedlings. Single- or double-null mutants of MYC2 and MYC3 displayed remarkably enhanced response to ACC(1-aminocyclopropane-1-carboxylate), the ethylene precursor, compared to wild-type seedlings. MYC2 and MYC3 directly bind to the promoter zone of ERF1, strongly suppressing its expression. Additionally, EIN3, a key component in ethylene signaling, interacts with MYC2 or MYC3 and significantly suppresses their binding to ERF1's promoter. MYC2 and MYC3 play crucial roles in the ethylene-regulated expression of functional genes. The results revealed the novel role and functional mechanism of these transcription factors in ethylene signal transduction. The findings provide valuable information for deepening our understanding of their role in regulating plant growth and responding to stress.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Etilenos , Regulação da Expressão Gênica de Plantas , Hipocótilo , Regiões Promotoras Genéticas , Fatores de Transcrição , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Etilenos/metabolismo , Hipocótilo/crescimento & desenvolvimento , Hipocótilo/genética , Hipocótilo/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Plântula/crescimento & desenvolvimento , Plântula/genética , Plântula/metabolismo , Transdução de Sinais , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Terminação de Peptídeos , TransativadoresRESUMO
OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Spastic paraplegia type 5A (SPG5A). METHODS: A pedigree suspected for Hereditary spastic paraplegia (HSP) at Henan Children's Hospital on August 15 2022 was selected as the study subject. Clinical data of the pedigree was collected. Peripheral blood samples were collected from members of the pedigree. Following extraction of genomic DNA, trio-WGS was carried out, and candidate variant was verified by Sanger sequencing. RESULTS: The child, a 1-year-old boy, had presented with microcephaly, hairy face and dorsal side of distal extremities and trunk, intellectual and motor development delay, increased muscle tone of lower limbs, hyperreflexes of bilateral knee tendons, and positive pathological signs. His parents and sister both had normal phenotypes. Trio-WGS revealed that the child has harbored a homozygous c.1250G>A (p.Arg417His) variant of the CYP7B1 gene, for which his mother was heterozygous, the father and sister were of the wild type. The variant was determined to have originated from maternal uniparental disomy (UPD). The result of Sanger sequencing was in keeping with the that of trio-WGS. SPG5A due to maternal UPD of chromosome 8 was unreported previously. CONCLUSION: The child was diagnosed with SPG5A, a complex type of HSP, for which the homozygous c.1250G>A variant of the CYP7B1 gene derived from maternal UPD may be accountable.
Assuntos
Paraplegia Espástica Hereditária , Humanos , Lactente , Masculino , China , Mutação , Paraplegia/genética , Linhagem , Fenótipo , Paraplegia Espástica Hereditária/genéticaRESUMO
BACKGROUND: This study investigated the effect of carbodiimide (EDC) combined with Clearfil SE self-etch adhesive on the shear bond strength (SBS), crosslinking degree, denaturation temperature, and enzyme activity of dentin in vitro. MATERIALS AND METHODS: Collected human sound third molars were randomly divided into different groups with or without EDC treatment (0.01-1 M). The specimens (n = 16)were stored for 24 h (immediate) or 12 months (aging) before testing the SBS. Fine dentin powder was obtained and treated with the same solutions. Then the crosslinking degree, denaturation temperature (Td), and enzyme activity were tested. Statistical analysis was performed using a one-way analysis of variance (ANOVA) to compare the differences of data between groups (α = 0.05). RESULTS: There was a significant drop in immediate SBS and more adhesive fracture of 1.0 M EDC group, while there were no significant differences among the other groups. SEM showed a homogeneous interface under all treatments. After 12 months of aging, the SBS significantly decreased. Less decreases of SBS in the 0.3 and 0.5 M groups were found. Due to thermal and enzymatical properties consideration, the 0.3 and 0.5 M treatments also showed higher cross-link degree and Td with lower enzyme activity. CONCLUSION: 0.3 and 0.5 M EDC may be favorable for delaying the aging of self-etch bond strength for 12 months. But it is still needed thoroughly study.
Assuntos
Carbodi-Imidas , Cimentos de Resina , Resistência ao Cisalhamento , Humanos , Carbodi-Imidas/química , Cimentos de Resina/química , Teste de Materiais , Dentina , Microscopia Eletrônica de Varredura , Adesivos Dentinários/química , Análise do Estresse Dentário , Reagentes de Ligações Cruzadas/química , Colagem Dentária/métodos , Técnicas In Vitro , Condicionamento Ácido do Dente/métodos , Dente Serotino , Temperatura , Fatores de Tempo , Propriedades de SuperfícieRESUMO
OBJECTIVE: To explore the effects of different polymers on in vitro biomimetic mineralization of small intestinal submucosa (SIS) scaffolds, and to evaluate the physicochemical properties and biocompatibility of the SIS scaffolds. METHODS: The SIS scaffolds prepared by freeze-drying method were immersed in simulated body fluid (SBF), mineralized liquid containing polyacrylic acid (PAA) and mine-ralized liquid containing PAA and polyaspartic acid (PASP). After two weeks in the mineralized solution, the liquid was changed every other day. SBF@SIS, PAA@SIS, PAA/PASP@SIS scaffolds were obtained. The SIS scaffolds were used as control group to evaluate their physicochemical properties and biocompatibility. We observed the bulk morphology of the scaffolds in each group, analyzed the microscopic morphology by environment scanning electron microscopy and determined the porosity and pore size. We also analyzed the surface elements by energy dispersive X-ray spectroscopy (EDX), analyzed the structure of functional groups by Flourier transformed infrared spectroscopy (FTIR), detected the water absorption rate by using specific gravity method, and evaluated the compression strength by universal mechanical testing machine. The pro-cell proliferation effect of each group of scaffolds were evaluated by CCK-8 cell proliferation method. RESULTS: Under scanning electron microscopy, the scaffolds of each group showed a three-dimensional porous structure with suitable pore size and porosity, and crystal was observed in all the mineralized scaffolds of each group, in which the crystal deposition of PAA/PASP@SIS scaffolds was more regular. At the same time, the collagen fibers could be seen to thicken. EDX analysis showed that the characteristic peaks of Ca and P were found in the three groups of mineralized scaffolds, and the highest peaks were found in the PAA/PASP@SIS scaffolds. FTIR analysis proved that all the three groups of mineralized scaffolds were able to combine hydroxyapatite with SIS. All the scaffolds had good hydrophilicity. The compressive strength of the mineralized scaffold in the three groups was higher than that in the control group, and the best compressive strength was found in PAA/PASP@SIS scaffold. The scaffolds of all the groups could effectively adsorb proteins, and PAA/PASP@SIS group had the best adsorption capacity. In the CCK-8 cell proliferation experiment, the PAA/PASP@SIS scaffold showed the best ability to promote cell proliferation with the largest number of living cells observed. CONCLUSION: Compared with other mineralized scaffolds, PAA/PASP@SIS scaffolds prepared by mineralized solution containing both PAA and PASP have better physicochemical properties and biocompatibility and have potential applications in bone tissue engineering.
Assuntos
Polímeros , Alicerces Teciduais , Alicerces Teciduais/química , Polímeros/química , Biomimética , Sincalida , Engenharia Tecidual/métodos , Intestino Delgado , PorosidadeRESUMO
Modifying catalyst surface with small molecular-additives presents a promising avenue for enhancing electrocatalytic performance. However, challenges arise in preserving the molecular-additives and maximizing their tuning effect, particularly at high current-densities. Herein, we develop an effective strategy to preserve the molecular-additives on electrode surface by applying a thin protective layer. Taking 4-dimethylaminopyridine (DMAP) as an example of a molecular-additive, the hydrophobic protection layer on top of the DMAP-functionalized Cu-catalyst effectively prevents its leaching during CO2 electroreduction (CO2R). Consequently, the confined DMAP molecules substantially promote the CO2-to-multicarbon conversion at low overpotentials. For instance, at a potential as low as -0.47 V vs. reversible hydrogen electrode, the DMAP-functionalized Cu exhibits over 80% selectivity towards multi-carbon products, while the pristine Cu shows only ~35% selectivity for multi-carbon products. Notably, ethanol appears as the primary product on DMAP-functionalized Cu, with selectivity approaching 50% at a high current density of 400 mA cm-2. Detailed kinetic analysis, in-situ spectroscopies, and theoretical calculations indicate that DMAP-induced electron accumulations on surface Cu-sites decrease the reaction energy for C-C coupling. Additionally, the interactions between DMAP and oxygenated intermediates facilitate the ethanol formation pathway in CO2R. Overall, this study showcases an effective strategy to guide future endeavors involving molecular tuning effects.
RESUMO
OBJECTIVE: The objective of this study was to investigate the pathogenesis and inheritance pattern of a Chinese Han family with hereditary spastic paraplegia and to retrospectively analyze the characteristics of KIF1A gene variants and related clinical manifestations. METHODS: High-throughput whole-exome sequencing was performed on members of a Chinese Han family with a clinical diagnosis of hereditary spastic paraplegia, and the sequencing results were validated by Sanger sequencing. Deep high-throughput sequencing was performed on subjects with suspected mosaic variants. The previously reported pathogenic variant loci of the KIF1A gene with complete data were collected, and the clinical manifestations and characteristics of the pathogenic KIF1A gene variant were analyzed. RESULTS: A pathogenic heterozygous variant located in the neck coil of the KIF1A gene (c.1139G>C, p.Arg380Pro) was identified in the proband and four additional members of the family. It was derived from the de novo low-frequency somatic-gonadal mosaicism of the proband's grandmother and had a rate of 10.95%. INTERPRETATION: This study helps us to better understand the pathogenic mode and characteristics of mosaic variants, and to understand the location and clinical characteristics of pathogenic variants in KIF1A.
Assuntos
Paraplegia Espástica Hereditária , Humanos , Paraplegia Espástica Hereditária/genética , Estudos Retrospectivos , Cinesinas/genética , Sequenciamento de Nucleotídeos em Larga Escala , Heterozigoto , Mutação , LinhagemRESUMO
After decades of research in the conservation of cultural heritage, nanolime (NL) has emerged as a potential alternative inorganic material to the frequently used organic materials. However, its poor kinetic stability in water has been a major challenge that restricted its penetration depth through cultural relics and resulted in unsatisfactory conservation outcomes. Here, for the first time, we realize NL water dispersion by modification of ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate) via a sample aqueous solution deposit method. Our findings indicate that the cation of the ionic liquid (IL) binds strongly to the surface of NL particles (IL-NL) by forming hydrogen bonds with Ca(OH)2 facets. The absorption of IL causes an unexpected significant alteration in the morphology of NL particles and results in a drastic reduction in NL's size. More importantly, this absorption endows NL excellent kinetic stability dispersed into water and implements NL water dispersion, which makes a breakthrough in terms of extreme poor kinetic stability of as-synthesized NL and commercial NL in water. The mechanism driving IL-NL water dispersion is explained by Stern theory. In the context of consolidating weathered stone, the presence of IL may delay carbonation of NL but the penetration depth of IL-NL through stone samples is three times deeper than that of as-synthesized and commercial NLs. Additionally, the consolidation strength of IL-NL is similar to that of as-synthesized NL and commercial NL. Moreover, IL-NL has no significant impact on the permeability, pore size, and microstructure of consolidated stone relics. Our research contributes to the field of NL-related materials and will enhance the dissemination and utilization of NL-based materials in the preservation of water-insensitive cultural heritage.
RESUMO
For effective wavefront management in the optical infrared range, dynamic all-dielectric metasurfaces, always based on phase transition materials, particularly G e 2 S b 2 T e 5 (GST), can be used. In this paper, we propose a GST-based tunable metasurface by structuring the phase-change material GST. We confirm that the nanopillar we designed has high transmittance in the wavelength band around 1550 nm and can fully cover the 0â¼2π phase. Based on these characteristics, we can achieve beam steering and a focusing effect in amorphous phase by elaborately arranging GST nanopillars, while the aforementioned optical phenomena disappear in crystalline phase. Additionally, by arranging the array of vortex phases, we also realize switching the perfect composite vortex beam (PCVB) when changing the crystal state of GST, and simulate the generation of PCVB with different topological charges and sizes in amorphous phase. We believe that our research results can serve as a reference for multifunctional optical surfaces, dynamic optical control, optical communication, and information processing.
RESUMO
Accurate and quantitative identification of unbalanced force during operation is of utmost importance to reduce the impact of unbalanced force on a hypergravity centrifuge, guarantee the safe operation of a unit, and improve the accuracy of a hypergravity model test. Therefore, this paper proposes a deep learning-based unbalanced force identification model, then establishes a feature fusion framework incorporating the Residual Network (ResNet) with meaningful handcrafted features in this model, followed by loss function optimization for the imbalanced dataset. Finally, after an artificially added, unbalanced mass was used to build a shaft oscillation dataset based on the ZJU-400 hypergravity centrifuge, we used this dataset to train the unbalanced force identification model. The analysis showed that the proposed identification model performed considerably better than other benchmark models based on accuracy and stability, reducing the mean absolute error (MAE) by 15% to 51% and the root mean square error (RMSE) by 22% to 55% in the test dataset. Simultaneously, the proposed method showed high accuracy and strong stability in continuous identification during the speed-up process, surpassing the current traditional method by 75% in the MAE and by 85% in the median error, which provided guidance for counterweight and guaranteed the unit's stability.
RESUMO
OBJECTIVE: To analyze the clinical phenotype and genetic variant of a child with Snijders Blok-Campeau syndrome (SBCS). METHODS: A child who was diagnosed with SBCS in June 2017 at Henan Children's Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and the extraction of genomic DNA, which was subjected to trio-whole exome sequencing (trio-WES) and genome copy number variation (CNV) analysis. Candidate variant was verified by Sanger sequencing of his pedigree members. RESULTS: The main clinical manifestations of the child have included language delay, intellectual impairment and motor development delay, which were accompanied with facial dysmorphisms (broad forehead, inverted triangular face, sparse eyebrows, widely spaced eyes, narrow palpebral fissures, broad nose bridge, midface hypoplasia, thin upper lip, pointed jaw, low-set ears and posteriorly rotated ears). Trio-WES and Sanger sequencing revealed that the child has harbored a heterozygous splicing variant of the CHD3 gene, namely c.4073-2A>G, for which both of his parents were of wild-type. No pathogenic variant was identified by CNV testing. CONCLUSION: The c.4073-2A>G splicing variant of the CHD3 gene probably underlay the SBCS in this patient.
Assuntos
Variações do Número de Cópias de DNA , Splicing de RNA , Heterozigoto , Linhagem , Fenótipo , MutaçãoRESUMO
The aryl-to-vinyl nickel 1,4-migration (1,4-Ni migration) reaction has been reported for the first time. The generated alkenyl Ni species undergo a reductive coupling reaction with unactivated brominated alkanes affording a series of trisubstituted olefins. This tandem reaction exhibits mild conditions, a broad substrate scope, high regioselectivity, and excellent Z/E stereoselectivity. A series of controlled experiments have shown that the critical 1,4-Ni migration process is reversible. In addition, the alkenyl nickel intermediates obtained after migration are highly Z/E stereoselective and do not undergo Z/E isomerization. The obtained trace isomerization products are caused by the instability of the product.
RESUMO
The bound state in the continuum (BIC) is widely applied to metamaterial study in order to obtain robust resonance and high quality (Q) factor. In this paper, we propose a metallic metasurface structure that can support double types of BICs, and acquire quasi-BIC state by restructuring each type with a specific approach. Electric field distribution is investigated to explore the physic mechanism behind the evolution of BICs. Moreover, we substitute structured graphene with corresponding metal counterparts. The promoted design is able to switch freely between BIC and quasi-BIC state even after the fabrication, as the graphene would convert from semiconductor-like to metal-like when increasing the Fermi level. Further exploration on electric field distribution demonstrates the metallicity difference between graphene and gold, which leads to the exotic phenomenon emerge on the proposed metal-graphene structure. Finally, the proposed metal-graphene structure is applied to a digital coding display through Fermi level regulating. Therefore, our work provides deep insights to the BIC metasurface investigation, and introduces a desirable improvement for current BIC metasurface design to achieve the free conversion between BIC and quasi-BIC states.