Search

The objective of this study was to investigate the effects and molecular mechanisms of tetrahedral framework nucleic acids‐microRNA22 (tFNAs‐miR22) on inhibiting pathological retinal neovascularization (RNV) and restoring physiological retinal vessels. A novel DNA nanocomplex (tFNAs‐miR22) was synthesised by modifying microRNA‐22 (miR22) through attachment onto tetrahedral frame nucleic acids (tFNAs), which possess diverse biological functions. Cell proliferation, wound healing, and tube formation were employed for in vitro assays to investigate the angiogenic function of cells. Oxygen‐induced retinopathy (OIR) model was utilised to examine the effects of reducing pathological neovascularization (RNV) and inhibiting vascular occlusion in vivo. In vitro, tFNAs‐miR22 demonstrated the ability to penetrate endothelial cells and effectively suppress cell proliferation, tube formation, and migration in a hypoxic environment. In vivo, tFNAs‐miR22 exhibited promising results in reducing RNV and promoting the restoration of normal retinal blood vessels in OIR model through modulation of the Wnt pathway. This study provided a theoretical basis for the further understanding of RNV, and highlighted the innovative and potential of tFNAs‐miR22 as a therapeutic option for ischemic retinal diseases. [ABSTRACT FROM AUTHOR]

Preparation of cellulose nanofibrils (CNFs) with the pretreatments using alkanolamine‐based protic ionic liquids (PILs) with dimeric oxalic acid anions ([(HOA)(H2OA)]−) was fully investigated. The cation type [ethanolamine ([MEA]+), diethanolamine ([DEA]+), triethanolamine ([TEA]+)], and water addition greatly influenced the CNF yields. Under the pretreatment conditions of 110 °C and 3 h, the CNF yields with different PIL‐based systems followed the order: [MEA][(HOA)(H2OA)]>[DEA][(HOA)(H2OA)]>[TEA][(HOA)(H2OA)], similar to their swelling capacities. The highest CNF yield of 85.0 % was obtained after the pretreatment with [MEA][(HOA)(H2OA)]‐water containing 30 wt % PILs. The optimal pH range of PILs‐water was 1.10–1.15. The good recyclability indicated that these inexpensive PILs can be employed as a simple and efficient pretreatment system for preparing CNFs. The physicochemical properties of the prepared CNFs were greatly changed by varying the PILs' pretreatment systems. The thermal stability of CNFs was intimately connected with the crystalline structures and hydrogen bonding modes. [ABSTRACT FROM AUTHOR]

The preparation of high‐efficiency perovskite light‐emitting devices (PeLEDs) in the air‐ambient has always been a challenge. Herein, the authors propose a Si‐based near‐infrared air‐processed PeLED through the anti‐solvent engineering. Two materials, poly(methyl methacrylate) (PMMA) and tetrabutylammonium hexafluorophosphate (TBAPF6) are co‐doped into the anti‐solvent, the former protects the perovskite from degradation in a high‐humidity atmosphere, and the latter passivates the defects on perovskite surface and increases the conductivity. Through the anti‐solvent engineering, the efficiency of PeLEDs has been significantly enhanced and obtains a maximum external quantum efficiency (EQE) of 10.4%, which is the highest among similar devices. This work shows that it is possible to prepare high‐efficiency near‐infrared PeLEDs in air‐ambient through a simple method. [ABSTRACT FROM AUTHOR]

The existing interface defect states between perovskite and the transport layer is one of the dominant reasons to limit the performance of near‐infrared (NIR) perovskite light‐emitting devices (PeLEDs). Herein, a quaternary ammonium halide choline chloride layer is introduced to improve the wettability of the hole transport layer (HTL) and passivate defect states. As a consequence, the performance of the NIR PeLEDs is obviously enhanced. A maximum output power density of 4.7 mW cm−2 has been achieved by optimizing the concentration of choline chloride. Furthermore, the alternating current (AC) driving mode is introduced to reduce thermal degradation and charge accumulation in the interface region. It is demonstrated that the emission intensity as well as the stability of PeLEDs can be further improved. [ABSTRACT FROM AUTHOR]

The existing interface defect states between perovskite and the transport layer is one of the dominant reasons to limit the performance of near‐infrared (NIR) perovskite light‐emitting devices (PeLEDs). Herein, a quaternary ammonium halide choline chloride layer is introduced to improve the wettability of the hole transport layer (HTL) and passivate defect states. As a consequence, the performance of the NIR PeLEDs is obviously enhanced. A maximum output power density of 4.7 mW cm−2 has been achieved by optimizing the concentration of choline chloride. Furthermore, the alternating current (AC) driving mode is introduced to reduce thermal degradation and charge accumulation in the interface region. It is demonstrated that the emission intensity as well as the stability of PeLEDs can be further improved. [ABSTRACT FROM AUTHOR]

Plasmonic nanostructures with large absorption areas under resonant excitation have been utilized extensively in photon‐assisted applications. In this work, dodecahedral Au nanobowls were first prepared by an easy and template‐free method only through the introduction of H2PtCl6 and I− during the growth procedure. The Au nanobowls show electron‐field enhancement due to the high curvature of the bowl edge, the open region, and dodecahedral morphology. Au/Pt nanobowls, which couple plasmonic Au and catalytic Pt, were then constructed as plasmonic electrocatalysts for methanol oxidation. The mass activity reached 497.6 mA mg−1 under visible‐light illumination, which is 1.9 times that measured in the dark. Simultaneously, the electrocatalytic stability is also greatly improved under light excitation. The enhanced properties of the plasmonic Au/Pt electrocatalysts are ascribed to the synergistic effect of the plasmon‐enhanced photothermal and hot‐carrier effects on the basis of experimental investigations. This work thus offers an effective methodology to construct efficient plasmonic electrocatalysts for fuel cells. [ABSTRACT FROM AUTHOR]

Background: Valproic acid (VPA) is a clinical medicine primarily prescribed to control epileptic symptoms. VPA has potential side‐effects, such as hepatotoxicity. Fibroblast growth factor 21 (FGF21) is a functional cytokine for metabolic regulation. In this article, we aimed to evaluate the possible clinical application of FGF21 in VPA‐treated livers in early undetected liver injury (EULI). Methods: Methodologically, plasma samples of VPA‐treated epileptic patients were isolated for biochemical and high‐performance liquid chromatography tests. In addition, VPA‐dosed mice were subjected to determinations of serological parameters, key regulatory effectors and FGF21 expressions through biochemical analyses, enzyme‐linked immunosorbent assay, immunohistochemistry stain, immunofluorescence stain, and reverse transcription‐polymerase chain reaction (RT‐PCR) test, respectively. Results: The serological data suggested that VPA‐treated epileptic patients showed visibly elevated FGF21 contents in plasma samples. However, other diagnostic parameters showed inconspicuous changes. As revealed in animal study, VPA‐dosed mice exhibited undetected morphological alterations and hormonal changes in the liver, pancreas, and kidneys. Furthermore, serological parameters and key regulatory proteins in VPA‐dosed livers and controls showed inconspicuous changes. Interestingly, endogenous FGF21 expressions in VPA‐dosed mice were increased in sera. In further experiments, the findings showed that intracellular expressions of FGF21 mRNA and protein were upregulated in VPA‐dosed livers as revealed in RT‐PCR and immunoassay. Conclusions: Taken together, these preliminary data reveal that functional FGF21 cytokine may serve as a potent predictor in VPA‐related EULI. [ABSTRACT FROM AUTHOR]

The accurate processing of sound temporal information is crucial to human speech perception and other species-specific communication. During postnatal development, the auditory cortex shows environmental and experience-dependent plasticity. However, how the postnatal environment affects cortical processing of sound temporal information is not fully understood. The aim of the present study was to determine whether postnatal noise exposure impairs neural temporal resolution in the auditory cortex, and, if so, whether environmental enrichment can rescue this degraded neural temporal acuity. Using the neural gap detection threshold determined in anesthetized rats as an index of temporal acuity, we found that exposure of juvenile rats to moderate-level noise induced much higher neural gap detection thresholds in adulthood than exposure of adult rats to the same noise. Environmental enrichment did not affect cortical neural gap detection thresholds in normally developing rats. However, rearing of rats with early noise exposure in an enriched environment promoted recovery from the noise-induced degraded neural temporal resolution. In addition, the tonal stimuli in the enriched environment contributed to only a portion of the recovery. These results provide evidence for noise-induced developmental impairment in neural gap detection thresholds in the auditory cortex, and suggest a therapeutic potential for environmental enrichment as a non-invasive approach to rescue developmentally degraded auditory temporal processing. [ABSTRACT FROM AUTHOR]

This study aimed to explore the effect and the molecular mechanism of tetrahedral framework nucleic acids (tFNAs), a novel self‐assembled nanomaterial with excellent biocompatibility and superior endocytosis ability, in inhibition of pathological retinal neovascularization (RNV) and more importantly, in amelioration of vaso‐obliteration (VO) in ischaemic retinopathy. tFNAs were synthesized from four single‐stranded DNAs (ssDNAs). Cell proliferation, wound healing and tube formation assays were performed to explore cellular angiogenic functions in vitro. The effects of tFNAs on reducing angiogenesis and inhibiting VO were explored by oxygen‐induced retinopathy (OIR) model in vivo. In vitro, tFNAs were capable to enter endothelial cells (ECs), inhibit cell proliferation, tube formation and migration under hypoxic conditions. In vivo, tFNAs successfully reduce RNV and inhibit VO in OIR model via the PI3K/AKT/mTOR/S6K pathway, while vascular endothelial growth factor fusion protein, Aflibercept, could reduce RNV but not inhibit VO. This study provides a theoretical basis for the further understanding of RNV and suggests that tFNAs might be a novel promising candidate for the treatment of blind‐causing RNV. [ABSTRACT FROM AUTHOR]

The ability of the auditory system to resolve sound temporal information is crucial for the understanding of human speech and other species-specific communications. Gap detection threshold, i.e. the ability to detect the shortest duration of a silent interval in a sound, is commonly used to study the auditory temporal resolution. Behavioral studies in humans and rats have shown that normal developing infants have higher gap detection thresholds than adults; however, the underlying neural mechanism is not fully understood. In the present study, we determined and compared the neural gap detection thresholds in the primary auditory cortex of three age groups of rats: the juvenile group (postnatal day 20-30), adult group I (8-10 weeks), and adult group II (28-30 weeks). We found age-related changes in auditory temporal acuity in the auditory cortex, i.e. the proportion of cortical units with short neural gap detection thresholds (< 5 ms) was much lower in juvenile groups compared with that in both adult groups at a constant sound level, and no significant differences in neural gap detection thresholds were found between the two adult groups. In addition, units in the auditory cortex of each group generally showed better gap detection thresholds at higher sound levels than at lower sound levels, exhibiting a level-dependent temporal acuity. These results provided evidence for neural correlates of age-related changes in behavioral gap detection ability during postnatal hearing development. [ABSTRACT FROM AUTHOR]

Background and Aim: This study was undertaken to evaluate the clinical characteristics, prognostic factors, and long-term outcomes of patients with mucosa-associated lymphoid tissue (MALT) lymphoma in the gastrointestinal (GI) tract. Methods: Clinical and pathological features of patients with MALT lymphoma in the GI tract, who were treated consecutively at Tianjin Medical University Cancer Institute and Hospital from 2001 to 2011, were evaluated retrospectively. Results: Among a total of 99 identified cases, 79.79% of lymphomas were localized in the stomach, 20.20% in the intestinal tract, and disseminated disease was detected in 35.4% of cases. The estimated 5-year overall survival (OS) and 5-year progression-free survival (PFS) rates were 73.1% and 65.1%, respectively. The comparison between stomach and intestinal tract lymphomas demonstrated no significant difference in characteristics, but nodal involvement was significantly lower in gastric MALT lymphoma (26.6%) as compared with intestinal tract MALT lymphoma (60%, P = 0.006). The outcomes of gastric and intestinal MALT lymphomas were similar (OS, P = 0.492; PFS, P = 0.408), and so was the survival between proximal and distal gastric lymphomas (OS, P = 0.077; PFS, P = 0.181). Serum lactate dehydrogenase level above normal was identified as the only adverse prognostic factor for both OS and PFS. Conclusion: The clinical characteristics and outcomes demonstrated no significant differences between gastric and intestinal tract MALT lymphomas. Serum lactate dehydrogenase level was an independent prognostic factor for the survival of GI MALT lymphoma. [ABSTRACT FROM AUTHOR]

Perovskite light‐emitting devices (PeLEDs) have emerged as a highly promising contender for the next generation of lighting and display technologies. During the nucleation and crystallization process, numerous defects are commonly formed on the surface and grain boundaries as a result of the ionic characteristics of perovskite, especially in an air environment. These defects ultimately contribute to the deterioration of the photoelectron properties. In this study, CsPbI3 nanocrystals (NCs) solution is introduced into ethyl acetate antisolvent as an additive, resulting in the high‐quality perovskite films under ambient conditions. The introduction of CsPbI3 NCs has been found to increase the grain size and improve the uniformity of perovskite films while also effectively passivating defects. More significantly, the utilization of CsPbI3 NCs leads to the formation of a 0D/3D local heterojunction that is distributed throughout the MAPbI3 film. These distributed heterojunctions significantly increase both the carrier concentration and the photoluminescence performance. With the incorporation of doped perovskite films, Silicon (Si) ‐based PeLEDs demonstrate enhanced efficiency, achieving a maximum external quantum efficiency of 12.6% in ambient conditions. Additionally, these devices exhibit a prolonged operational half‐life of 80 minutes. This study presents a novel methodology for fabricating high‐efficiency Si‐based PeLEDs that exhibit exceptional electroluminescence characteristics. [ABSTRACT FROM AUTHOR]

Summary: Engineered Saccharomyces cerevisiae strains are good cell factories, and developing additional genetic manipulation tools will accelerate construction of metabolically engineered strains. Highly repetitive rDNA sequence is one of two main sites typically used for multicopy integration of genes. Here, we developed a simple and high‐efficiency strategy for rDNA‐mediated multicopy gene integration based on the dynamic balance of rDNA in S. cerevisiae. rDNA copy number was decreased by pre‐treatment with hydroxyurea (HU). Then, heterologous genes were integrated into the rDNA sequence. The copy number of the integrated heterologous genes increased along with restoration of the copy number of rDNA. Our results demonstrated that HU pre‐treatment doubled the number of integrated gene copies; moreover, compared with removing HU stress during transformation, removing HU stress after selection of transformants had a higher probability of resulting in transformants with high‐copy integrated genes. Finally, we integrated 18.0 copies of the xylose isomerase gene into the S. cerevisiae genome in a single step. This novel rDNA‐mediated multicopy genome integration strategy provides a convenient and efficient tool for further metabolic engineering of S. cerevisiae. [ABSTRACT FROM AUTHOR]

Age‐related macular degeneration (AMD) and diabetic retinopathy (DR) are the world's leading causes of blindness. The retinal pigment epithelium (RPE) and vascular endothelial cell exposed to oxidative stress is the major cause of AMD and DR. DJ‐1, an important endogenous antioxidant, its overexpression is considered as a promising antioxidant treatment for AMD and DR. Here, we modified the tetrahedral frame nucleic acids (tFNAs) with DJ‐1 saRNAs as a delivery system, and synthesized a novel nanocomplex (tFNAs‐DJ‐1 saRNAs). In vitro studies show that tFNAs‐DJ‐1 saRNAs can efficiently transfer DJ‐1 saRNAs to human umbilical vein endothelial cells (HUVECs) and ARPE‐19s, and significantly increased their cellular DJ‐1 level. Reactive oxygen species expression in H2O2‐treated HUVECs and ARPE‐19s were decreased, cell viability was enhanced and cell apoptosis were inhibited when tFNAs‐DJ‐1 saRNAs were delivered. Moreover, tFNAs‐DJ‐1 saRNAs preserved mitochondrial structure and function under oxidative stress conditions. In the aspect of molecular mechanism, tFNAs‐DJ‐1 saRNAs activated Erk and Nrf2 pathway, which might contribute to its protective effects against oxidative stress damage. To conclude, this study shows the successfully establishment of a simple but effective delivery system of DJ‐1 saRNAs associated with antioxidant effects in AMD and DR, which may be a promising agent for future treatment in oxidative stress‐related retinal disorders. [ABSTRACT FROM AUTHOR]

Yes‐associated protein 1 (YAP1), the core downstream effector of the Hippo signaling cascade, was involved in the regulation of osteoblast and osteoclast differentiation and in bone metabolism. However, the regulatory effects and mechanisms of YAP1 on bone‐remodeling molecules in osteoblasts under inflammation remain unknown. In this study, YAP1 expression level was downregulated after treatment with inflammatory cytokine tumor necrosis factor‐α (TNF‐α) in MC3T3‐E1 cells. The key osteoclastogenic molecules induced by TNF‐α, namely, interleukin‐6 and receptor activator of nuclear factor‐κB (NF‐κB) ligand, were suppressed after lentivirus‐induced YAP1 overexpression, which dramatically increased the expression level of osteoprotegerin. Conversely, the expression levels of the above factors showed opposite trends in the YAP1 small interfering RNA and YAP1 inhibitor (verteporfin) group. Mechanistically, YAP1 attenuated the TNF‐α‐induced activation of the NF‐κB signaling pathway as revealed by the reduced expression of phosphorylated‐p65 and NF‐κB reporter activity and the nuclear translocation of p65. Moreover, the expression level of YAP1 suppressed by TNF‐α was reversed by berberine in concentration‐dependent manner. Taken together, our study suggests that YAP1 plays a critical role in the regulation of bone metabolism and is a potential therapeutic target for treating inflammatory bone resorption. [ABSTRACT FROM AUTHOR]

Objective: A comprehensive network meta‐analysis was designed to clarify contradictions and offer valuable clinical guidance in the treatment of recurrent spontaneous abortion (RSA). Method: The included clinical trials were selected from the relevant medical journal databases and screened. Treatments were ranked by the surface under the cumulative ranking curve. Heat plots were constructed to analyze the inconsistency between direct data and network results, and adjusted funnel plots were constructed to assess publication bias. Results: Forty‐nine randomized controlled trials involving a total of 8496 RSA patients were selected. With placebo as control, corticosteroid plus low dose aspirin (LDA) plus unfractionated heparin (UFH), granulocyte colony‐stimulating factor (G‐CSF) alone, and LDA plus low molecular weight heparin (LMWH) all demonstrated effectiveness in increasing successful live birth rates and reducing the incidences of miscarriage. However, no treatment was demonstrably superior to placebo in terms of pregnancy success. For all 3 endpoints (live birth, abortion and success pregnancy), the adjusted funnel plots were symmetric to zero and indicated no publication bias. In terms of live birth and abortion rates, no treatment outperformed placebo in patients with antiphospholipid syndrome. Conclusion: In consideration of live birth and abortion rates, corticosteroid plus LDA plus UFH appeared to be the optimum treatment strategy; G‐CSF was second, followed by LDA with LMWH, LDA plus LMWH plus intravenous immunoglobulin, corticosteroid with LDA and others. Subgroup analysis demonstrated no benefit of antithrombotic therapy in patients with antiphospholipid syndrome. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is a non‐specific chronic inflammatory disease of the intestine. In addition to genetic susceptibility, environmental factors and dysregulated host immunity, the gut microbiota is implicated in the pathogenesis of Crohn's disease (CD) or ulcerative colitis (UC), the two primary types of IBD. The P2X4 receptor has been demonstrated to have a crucial role in preventing infection, inflammation, and organ damage. However, it remains unclear whether the P2X4 receptor affects IBD and the underlying mechanisms. Methods: Colitis was induced in mice administrated with dextran sodium sulphate (DSS). 16S rDNA sequencing was used to analyze the gut microbiota in knockout and wild‐type mice. Clinical and histopathological parameters were monitored throughout the disease progression. Results: Gene Expression Omnibus analysis showed the downregulation of P2RX4 (P2rx4) expression in colonic tissues from patients or mice with IBD. However, its expression at the protein levels was upregulated on day 4 or 6 and then downregulated on day 7 in C57BL/6 mice treated with DSS. Gene ablation of P2rx4 aggravated DSS‐induced colitis accompanying gut microbiota dysbiosis in mice. Moreover, P2X4 receptor‐positive modulator ivermectin alleviated colitis and corrected dysregulated microbiota in wild‐type C57BL/6 mice. Further antibiotic‐treated gut microbiota depletion, cohousing experiment, and fecal microbiota transplantation proved that gut microbiota dysbiosis was associated with the aggravation of colitis in the mouse model initiated by P2rx4. Conclusions: Our findings elaborate on an unrevealed etiopathophysiological mechanism by which microbiota dysbiosis induced by the P2X4 receptor influences the development of colitis, indicating that the P2X4 receptor represents a promising target for treating patients with CD and UC. [ABSTRACT FROM AUTHOR]

Ginsenoside Rb1 (GRb1), a major ingredient of ginseng, has been found to be a potential protective agent in spinal cord injury (SCI) and in activated microglia‐induced neuronal injury. This study discovered that GRb1 could facilitate miR‐130b‐5p expression in SCI rats and Toll‐like receptor 4 (TLR4; a crucial player in inflammation) was a potential target of miR‐130b‐5p. Hence, we further investigated whether GRb1 could relieve SCI by reducing microglia‐mediated inflammatory responses and neuronal injury via miR‐130b‐5p/TLR4 pathways. The results showed that GRb1 alleviated SCI through inhibiting neuronal apoptosis and proinflammatory factor expression via increasing miR‐130b‐5p.GRb1 weakened the damage of activated microglia to neurons through upregulating miR‐130b‐5p. miR‐130b‐5p attenuated activated microglia‐induced neuron injury via targeting TLR4. GRb1 inactivated TLR4/nuclear factor‐κB (NF‐κB) activation and inhibited proinflammatory cytokine secretion by increasing miR‐130b‐5p in activated microglia. As a conclusion, GRb1 alleviated SCI through reducing activated microglia‐induced neuronal injury via miR‐130b‐5p/TLR4/NF‐κB axis, providing a deep insight into the molecular basis of GRb1 in the treatment of SCI. [ABSTRACT FROM AUTHOR]

2D/3D Perovskites: Introduction of Hydrophobic Ammonium Salts with Halogen Functional Groups for High-Efficiency and Stable 2D/3D Perovskite Solar Cells (Adv. Funct. In article number 1807565, Xu Pan, Songyuan Dai, and co-workers design novel type 2D/3D perovskites by firstly introducing hydrophobic ammonium salt cations with halogen functional groups into 3D perovskite. Owing to the notable hydrophobicity of alkylammonium cations with halogen functional groups and the formed 2D/3D perovskite structure, the highly efficienct 2D/3D perovskite solar cells exhibit superior moisture resistance and thermal stability. [Extracted from the article]

2D perovskites have attracted extensive attention due to their excellent stability compared with 3D perovskites. However, the intrinsic hydrophilicity of introduced alkylammonium salts effects the humidity stability of 2D/3D perovskites. Devices based on longer chain alkylammonium salts show improvement in hydrophobicity but lower efficiency due to the poorer charge transport among various layers. To solve this issue, two hydrophobic short‐chain alkylammonium salts with halogen functional groups (2‐chloroethylamine, CEA+ and 2‐bromoethylamine, BEA+) are introduced into (Cs0.1FA0.9)Pb(I0.9Br0.1)3 3D perovskites to form 2D/3D perovskite structure, which achieve high‐quality perovskite films with better crystallization and morphology. The optimal 2D/3D perovskite solar cells (PSCs) with 5% CEA+ display a power conversion efficiency (PCE) as high as 20.08% under 1 sun irradiation. Because of the notable hydrophobicity of alkylammonium cations with halogen functional groups and the formed 2D/3D perovskite structure, the optimal PSCs exhibit superior moisture resistance and retain 92% initial PCE after aging at 50 ± 5% relative humidity for 2400 h. This work opens up a new direction for the design of new‐type 2D/3D PSCs with improved performance by employing proper alkylammonium salts with different functional groups. [ABSTRACT FROM AUTHOR]

Background: To investigate the relationships among phenotypes, genotypes, and funotypes of SCN2A‐related developmental epileptic encephalopathy (DEE). Methods: We enrolled five DEE patients with five de novo variants of the SCN2A. Functional analysis and pharmacological features of Nav1.2 channel protein expressed in HEK293T cells were characterized by whole‐cell patch‐clamp recording. Results: The phenotypes of c.4712T>C(p. I1571T), c.2995G>A(p.E999K), and c.4015A>G(p. N1339D) variants showed similar characteristics, including early seizure onset with severe to profound intellectual disability. Electrophysiological recordings revealed a hyperpolarizing shift in the voltage dependence of the activation curve and smaller recovery time constants of fast‐inactivation than in wild type, indicating a prominent gain of function (GOF). Moreover, pharmacological electrophysiology showed that phenytoin inhibited over a 70% peak current and was more effective than oxcarbazepine and carbamazepine. In contrast, c.4972C>T (p.P1658S) and c.5317G>A (p.A1773T) led to loss of function (LOF) changes, showing reduced current density and enhanced fast inactivation. Both showed seizure onset after 3 months of age with moderate development delay. Interestingly, we discovered that choreoathetosis was a specific phenotype feature. Conclusion: These findings provided the insights into the phenotype–genotype–funotype relationships of SCN2A‐related DEE. The preliminary evaluation using the distinct hints of GOF and LOF helped plan the treatment, and the next precise step should be electrophysiological study. [ABSTRACT FROM AUTHOR]

Epilepsy is a common and genetically heterogeneous disorder among children. Advances in next‐generation sequencing have revealed that numerous epilepsy genes, helped us improve the understanding of mechanisms underlying epileptogenesis, and guided the development of treatments. We identified 39 candidate variants in 21 genes, including 37 that were pathogenic or likely pathogenic variants according to the American College of Medical Genetics and Genomics scoring system and two variants of uncertain significance that were considered causative after they were associated with clinical characteristics. Thirty were de novo variants (76.9%), and 20 variants had not previously been reported (51.3%). We obtained a diagnosis in 39 of the 141 probands (27.7%). The most frequently mutated gene was SCN1A; KCNQ2, KCNT1, PCDH19, STXBP1, SCN2A, TSC2, and PRRT2 were mutated in more than one individual; ANKRD11, CDKL5, DCX, DEPDC5, GABRB3, GRIN2A, IQSEC2, KCNA2, KCNB1, KCNJ6, TSC1, SCN9A, and SCN1B were mutated in a single individual. In addition, we detected a nonsense variant in a candidate gene KCND1 and considered it as a new candidate epilepsy gene, which needed further functional study. Consequently, large number of unreported variants were detected, diverse phenotypes were associated with known epilepsy genes. Changes in clinical management beyond genetic counseling were suggested. [ABSTRACT FROM AUTHOR]

Noble metal nanostructures are promising electrocatalysts with their performance determined by their size, shape, and architecture. This study reports the facile preparation of Au/(PdAg alloy) electrocatalysts with diverse architectures, including nanodumbbells, yolk/shell nanoframes, and yolk/shell nanoboxes, from Au nanorod core/Ag shell bimetallic nanostructures. The fine tuning of the nanostructure architecture is realized by combining galvanic replacement reaction, etching/growth, Ostwald ripening, and coreduction processes. The adding sequence of surfactants and Pd precursors, and the Ag shell thicknesses of the starting core/shell nanocrystals, determine the growth routines and therefore the architectures of the obtained Au/(PdAg alloy) nanostructures. Electrocatalytic performances of all Au/(PdAg alloy) nanostructures toward ethanol oxidation reaction (EOR) in alkaline are examined. Compared with the commercial Pd/C electrocatalyst, the nanodumbbells (Au19Pd19Ag62) display 6.3 times higher specific activity and 4.25 times higher mass activity. The nanoframes (Au14Pd14Ag72) are superior as well, with their specific and mass activities 4.4 and 5.5 times higher than those of the Pd/C electrocatalyst, respectively. The nanoboxes also show slight improvement in electrocatalysis. Moreover, the nanodumbbells exhibit greatly improved stability toward EOR in comparison to the Pd/C electrocatalyst. These results can enrich the manufacturing techniques of noble metal nanostructure catalysts and promote their development for fuel cell applications. A synthetic strategy for fine tuning the morphology of novel Au/(PdAg alloy) nanostructures including nanodumbbells, yolk/shell nanoframes, and yolk/shell nanoboxes is successfully developed. Au/(PdAg alloy) nanostructures with designed architectures exhibit highly improved electrocatalytic performances. It is believed that the synthetic methodology of these sophisticated nanostructures is versatile and can be extended to prepare other nanostructure catalysts. [ABSTRACT FROM AUTHOR]

Coating an oxide shell is an attractive method to overcome the aggregation and biological cytotoxicity brought by the surfactant on Au nanorods in photothermal therapy. (Au nanorod)/SnO2 core/shell nanostructures are ideal candidates. However, developing an easy‐operation and versatile method to prepare this hybrid is still a great challenge. Herein, a simple and rapid routine is developed to the synthesis of SnO2 shelled Au nanorod. The plasmonic bands of the core/shell nanostructures are tuned in the biological transparency window by changing the shell thickness and the core size. Additionally, this synthetic strategy is versatile when the monometallic and bimetallic Au, Pt, and Pd with various shapes are employed as the core. It is further demonstrated that the (Au nanorod)/SnO2 core/shell nanostructures show a good biocompatibility and a high photothermal conversion efficiency in photothermal therapy. This study therefore provides a versatile way to synthesizing (metal nanocrystal)/semiconductor nanostructures, which will therefore be beneficial for widening their applications. A versatile synthetic strategy for (metal nanocrystal)/SnO2 core/shell nanostructure is successfully developed. Particularly, the plasmonic bands are readily tuned in the biological transparency window by employing different sized Au nanorods and varying the shell thickness. Au nanorod/SnO2 core/shell nanostructures exhibit excellent photothermal therapy performances. The synthetic method will extend the applications of metal/oxide hybrids. [ABSTRACT FROM AUTHOR]