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Background: Mutations and/or duplications in the chromosome 2q24.3 region are known to be responsible for various epilepsy phenotypes. However, microdeletion in childhood epilepsy is rarely reported. Case presentation: A two-and-a-half-year-old girl with no history of hypocalcemia or seizures developed new symptoms of generalized tonic-clonic epilepsy. The clinical manifestations were growth retardation, prominent forehead, closed anterior fontanelle, and poor muscle tension. Peripheral blood, echocardiography, abdominal ultrasound, and electroencephalogram (EEG) examinations were all normal. No karyotype abnormality was found in the patient, but a single nucleotide polymorphism (SNP) array test detected that a 3.5 Mb single-copy microdeletion had occurred in the q24.2-q24.3 region on chromosome 2. Fluorescence in situ hybridization (FISH) tests revealed that the 2q24 fragment was inserted into the q11.2 region of the patient's chromosome 15, as well as that of her sister. In both cases, the patient's mother is the source carrier of the chromosome 15 insertion. Conclusions: The deletion of the sodium channel gene cluster (SCN1A, SCN2A, and SCN3A), but not SCN1A haploinsufficiency ​alone, may contribute to complex infant epilepsy syndromes. However, the pathogenic mechanism still needs to be studied further.

Abstract Biological applications of nanomaterials as delivery carriers have been embedded in traditional biomedical research for decades. Despite lagging behind, recent significant breakthroughs in the use of nanocarriers as tools for plant biotechnology have created great interest. In this Perspective, we review the outstanding recent works in nanocarrier‐mediated plant transformation and its agricultural applications. We analyze the chemical and physical properties of nanocarriers determining their uptake efficiency and transport throughout the plant body.

Corticocortical neuroplastic changes from higher-order cortices to primary motor cortex (M1) have been described for procedural sequence learning. The dorsolateral prefrontal cortex (DLPFC) plays critical roles in cognition, including in motor learning and memory. However, neuroplastic changes in the DLPFC and their influence on M1 and on motor learning are not well understood. The present study examined bilateral DLPFC–M1 changes in plasticity induced by procedural motor sequence learning in a serial reaction time task. DLPFC plasticity induced by procedural sequence learning was examined by comparing before vs. after training assessments of ipsilateral/contralateral DLPFC–M1 interactions between sequence order and random order trials performed using either the left or right hand. Intra-hemispheric (inter-stimulus interval [ISI] = 10 ms) and inter-hemispheric (ISI = 10 or 50 ms) DLPFC–M1 interactions and single-pulse motor-evoked potentials (MEPs) were measured with transcranial magnetic stimulation (TMS). The reaction times of participants measured during motor training were faster for sequence learning than for random learning with either hand. Paired-pulse TMS induced DLPFC–M1 interactions that were disinhibited after motor sequence learning, especially for left DLPFC–left M1 interactions with right hand task performance and for left DLPFC–right M1 interactions with left hand task performance. These findings indicate that motor sequence learning induces neuroplastic changes to enhance DLPFC–M1 interactions. This manifestation of plasticity showed hemispheric specificity, favoring the left DLPFC. DLPFC plasticity may be a useful index of DLPFC function and may be a treatment target for enhancing DLPFC function and motor learning.

Calmodulin (CaM) and calmodulin-like (CML) proteins are Ca2+ relays and play diverse and multiple roles in plant growth, development and stress responses. However, CaM/CML gene family has not been identified in barley (Hordeum vulgare). In the present study, 5 HvCaMs and 80 HvCMLs were identified through a genome-wide analysis. All HvCaM proteins possessed 4 EF-hand motifs, whereas HvCMLs contained 1 to 4 EF-hand motifs. HvCaM2, HvCaM3 and HvCaM5 coded the same polypeptide although they differed in nucleotide sequence, which was identical to the polypeptides coded by OsCaM1-1, OsCaM1-2 and OsCaM1-3. HvCaMs/CMLs were unevenly distributed over barley 7 chromosomes, and could be phylogenetically classified into 8 groups. HvCaMs/CMLs differed in gene structure, cis-acting elements and tissue expression patterns. Segmental and tandem duplication were observed among HvCaMs/CMLs during evolution. HvCML16, HvCML18, HvCML50 and HvCML78 were dispensable genes and the others were core genes in barley pan-genome. In addition, 14 HvCaM/CML genes were selected to examine their responses to salt, osmotic and low potassium stresses by qRT-PCR, and their expression were stress-and time-dependent. These results facilitate our understanding and further functional identification of HvCaMs/CMLs.

ObjectivesThis study aimed to provide an assessment of chlorothalonil's possible carcinogenic risk posed to the public. In combination and comparison with the non-carcinogenic risk, the results hopefully could provide useful insights, early warning, and references for policy formulation.MethodsThis study firstly investigated the occurrence of chlorothalonil on selected key vegetables for different scenarios, and then conducted an exposure assessment with officially published data. Lastly, both the non-carcinogenic and carcinogenic risk of chlorothalonil were calculated by using Monte-Carlo simulation.ResultsEven though mean non-carcinogenic risks of chlorothalonil for all scenarios were below threshold value, the mean carcinogenic risks for maximum-risk scenario and most-likely risk scenario were mostly above threshold value. High probabilities of exceedance of threshold value existed for carcinogenic risk under all scenarios.ConclusionPotential threat to public health existed for conventionally ‘safe' pesticide if considering the possible carcinogenicity. Extra caution should be taken and the potential carcinogenic effects should be included into consideration for better protection of public health during the policy formulation process.

Plant-derived phytochemicals have gifted humans with vast therapeutic potentials. Yet, the unique features of the blood–brain barrier significantly limit their accession to the target tissue and thus clinical translation in brain disease treatment. Herein, we explore the medicinal outcomes of both the rare examples of phytochemicals that can easily translocate across the blood–brain barrier and most of the phytochemicals that were reported with brain therapeutic effects, but a bizarre amount of dosage is required due to their chemical nature. Lastly, we offer the nanodelivery platform that is capable of optimizing the targeted delivery and application of the non-permeable phytochemicals as well as utilizing the permeable phytochemicals for boosting novel applications of nanodelivery toward brain therapies.

Direct interspecies electron transfer (DIET) is an effective mechanism for microbial species to exchange electrons cooperatively during syntrophic metabolism. It is generally accepted that DIET is mainly mediated by electrically conductive pili and outer surface c-type cytochromes (c-Cyts). However, as an extracellular matrix is ubiquitous and abundant on the surface of microorganisms, the effect and mechanism of exopolysaccharides on DIET are still unclear. This study constructed a co-culture of exopolysaccharides-deficient Geobacter sulfurreducens with Geobacter metallireducens to explore the role of exopolysaccharides in DIET. Results revealed that the deficiency of exopolysaccharides extended the metabolic period of the co-culture by 44.4% and changed the proportions of each species in the co-culture. The exopolysaccharides-deficient co-culture failed to form large, tight spherical aggregates and the expression of c-Cyts and pili was decreased. The addition of magnetite and granular activated carbon (GAC), respectively, might compensate for the functions of c-Cyts and pili in the first generation of co-culture, but the stimulatory effect on the metabolic stable period co-culture was fairly limited. These findings demonstrate that non-conductive exopolysaccharides are an important component of DIET aggregates and an extracellular matrix for DIET-required c-Cyts.

Abstract Background Although increasing evidence showed the correlations between white matter hyperintensities (WMHs) and cognitive impairment, the relationship between them is still modest. Many researchers began to focus on the variation caused by the heterogeneity of WMH. We tried to explore the pathological heterogeneity in WMH by using diffusion tensor imaging (DTI), so as to provide a new insight into the future research. Methods Diffusion weighted images (DWIs) of the brain were acquired from 73 patients with WMH and 18 healthy controls, which were then modeled by DTI. We measured fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of white matter of the periventricular frontal lobe (pFL), periventricular occipital lobe (pOL), periventricular parietal lobe (pPL) and deep centrum ovales (dCO), and grouped these measures according to the Fazekas scale. Then we compared the DTI metrics of different regions with the same Fazekas scale grade. Results Significantly lower FA values (all p

Preimplantation embryo arrest (PREMBA) is a common cause of female infertility and recurrent failure of assisted reproductive technology. However, the genetic basis of PREMBA is largely unrevealed. Here, using whole-exome sequencing data from 606 women experiencing PREMBA compared with 2,813 controls, we performed a population and gene-based burden test and identified a candidate gene, karyopherin subunit [alpha]7 (KPNA7). In vitro studies showed that identified sequence variants reduced KPNA7 protein levels, impaired KPNA7 capacity for binding to its substrate ribosomal L1 domain-containing protein 1 (RSL1D1), and affected KPNA7 nuclear transport activity. Comparison between humans and mice suggested that mouse KPNA2, rather than mouse KPNA7, acts as an essential karyopherin in embryonic development. [Kpna2.sup.-/-] female mice showed embryo arrest due to zygotic genome activation defects, recapitulating the phenotype of human PREMBA. In addition, female mice with an oocyte-specific knockout of Rsl1d1 recapitulated the phenotype of [Kpna2.sup.-/-] mice, demonstrating the vital role of substrate RSL1D1. Finally, complementary RNA (cRNA) microinjection of human KPNA7, but not mouse Kpna7, was able to rescue the embryo arrest phenotype in [Kpna2.sup.-/-] mice, suggesting mouse KPNA2 might be a homologue of human KPNA7. Our findings uncovered a mechanistic understanding for the pathogenesis of PREMBA, which acts by impairing nuclear protein transport, and provide a diagnostic marker for PREMBA patients., Introduction Successful human reproduction requires normal embryonic development. Preimplantation embryo arrest (PREMBA) is a common reason for recurrent failure of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and [...]

Inhibins suppress the FSH production in pituitary gonadotrope cells by robustly antagonizing activin signaling by competitively binding to activin type II receptors (ACTR II). The binding of inhibin A to ACTR II requires the presence of its co-receptor, namely, betaglycan. In humans, the critical binding site for betaglycan to inhibin A was identified on the inhibin α subunit. Through conservation analysis, we found that a core 13-amino-acid peptide sequence within the betaglycan-binding epitope on human inhibin α subunit is highly conserved across species. Based on the tandem sequence of such a conserved 13-amino-acid betaglycan-binding epitope (INHα13AA-T), we developed a novel inhibin vaccine and tested its efficacy in promoting female fertility using the female rat as a model. Compared with placebo-immunized controls, INHα13AA-T immunization induced a marked (p < 0.05) antibody generation, enhanced (p < 0.05) ovarian follicle development, and increased ovulation rate and litter sizes. Mechanistically, INHα13AA-T immunization promoted (p < 0.05) pituitary Fshb transcription and increased (p < 0.05) serum FSH and 17β-estradiol concentrations. In summary, active immunization against INHα13AA-T potently increased FSH levels, ovarian follicle development, ovulation rate and litter sizes, thus causing super-fertility in females. Therefore, immunization against INHα13AA is a promising alternative to the conventional approach of multiple ovulation and super-fertility in mammals.

High dropout rate exists universally in massive open online courses (MOOCs) due to the separation of teachers and learners in space and time. Dropout prediction using the machine learning method is an extremely important prerequisite to identify potential at-risk learners to improve learning. It has attracted much attention and there have emerged a few reviews. However, current reviews of MOOC dropout prediction exist some common limitations. Firstly, different definitions of course dropout are not summarized. Secondly, there lacks an overall framework of MOOC dropout prediction. Thirdly, some key challenges are not fully explored. Thus, unlike past reviews, this systematic review concludes with three categories of definitions of course dropout. Then it proposes an overall framework including factors affecting dropout, general feature extraction methods, various machine learning methods and evaluation methods. Finally, the key challenges of interpretability, imbalanced data and semantic learning trajectory modeling are proposed. This study aims to enable researchers to capture a whole picture of dropout prediction from the perspective of machine learning. [ABSTRACT FROM AUTHOR]

Silicon (Si) plays an important role in enhancing the tolerance of plants to biotic and abiotic stress in soil ecosystems. Root‐lesion nematodes (Pratylenchus scribneri; RLNs) cause root damage and diseases that result in quality deterioration and economic loss. This study investigated the effects of Si application on maize plants and its interaction with RLN infection. We set up different treatments to evaluate the role of silicon application in maize root growth and RLN resistance. This study conducted analysis by combining measurements of the metabolism and root activity of maize under different conditions. The results suggested that Si application (0.5 g/kg) significantly promoted fresh shoot weight, plant height, SPAD value (chlorophyll content), and root activity of maize, regardless of RLN inoculation. The highest SPAD value was observed in the Si treatment, which was significantly higher than in the control (CK) and RLN (N) treatments. Analysis of enzyme activity revealed that nematode inoculation reduced catalase (CAT) activity and increased malondialdehyde (MDA) concentration, while Si application increased CAT activity and decreased MDA concentration. In the SiN treatment, there was increased CAT activity at 0, 12, 48, 72 and 96 h compared with the N treatment. In parallel, nematode inoculation increased phenylalanine ammonia‐lyase (PAL), and polyphenol oxidase (PPO) activities, while SiN treatment further enhanced their activities. These findings indicate that Si application enhances maize resistance to nematode infection and improves plant growth and antioxidant defence mechanisms. [ABSTRACT FROM AUTHOR]

The high‐power characteristic of the coaxial to waveguide transition plays an important role in modern communication and radar systems. In this letter, a novel design of a high‐power transition from a 50 Ω coaxial line with an N‐type connector to a WR‐90 rectangular waveguide. The power handling capability (PHC) of the proposed structure is significantly enhanced by a cone‐shaped excitation probe with a bold end, a transitional cavity, and a mode conversion cavity with a curved shorted back wall. The simulated results reveal that the transition possesses high PHC of 257 kW at 8.5 GHz, which is the upper limit of the power tolerance for the N‐type connector. The measured results show that the return loss and insertion loss are better than 15 and 0.15 dB, respectively, in the range of 7.96–9.16 GHz. In addition, experimental validation confirms the normal operation of the structure under a 250 kW power level test, demonstrating the applicability of the proposed transition in high‐power microwave systems. [ABSTRACT FROM AUTHOR]

Pesticide treatment of rice seeds has been used for decades to control pests. The efficacy of chlorantraniliprole seed treatment to control pests is now well established and can last for > 90 days, even though the residue content of chlorantraniliprole in rice plants is sharply reduced by this time. We found that 60 days after chlorantraniliprole seed treatment, the dose of chlorantraniliprole in rice plants was much lower than the LC50 of chlorantraniliprole for the arthropod pests Cnaphalocrocis medinalis, Chilo suppressalis and Sesamia inferens; however, the treatment still provided control, raising the issue of how chlorantraniliprole seed treatment exerts long-term control. Untargeted metabolomics analyses showed that jasmonic acid (JA) and its metabolic derivatives were induced after seed treatment. In rice shoots and roots, the expression levels of three key genes in the JA biosynthesis pathway, AOS2, AOC and OPR7, were up-regulated. After mechanical damage, there were significant differences in gene expression patterns between the seed treated plants and the controls. Using a bioassay with two JA-deficient lines (AOC and MYC2 knockouts) and a wildtype line (XS11), we showed that the mortality rate of C. suppressalis fed on XS11 plants from treated seeds was higher than the mortality rate on JA-deficient plants from treated seeds. Thus, JA seems to play an important role in pest mortality after chlorantraniliprole seed treatment, providing a possible basis for long-term pest control from the seed treatment. These results point to better ways of using seed treatment to reduce pesticide applications. [ABSTRACT FROM AUTHOR]

Based on a newly proposed planar Yagi antenna with magnetic and electric dipoles, a compact $1\times 4$ broadband dual-polarized (DP) array with endfire radiation is designed in this paper. The magnetic Yagi antenna operates on the vertical polarization while the electric one operates on the horizontal one. The compact configuration of $0.5\,\,\lambda _{0}\times 0.63\,\,\lambda _{0}\times 0.09\,\,\lambda _{0}$ benefits from the novel half-mode magnetic Yagi antenna and the arrangement with the electric Yagi antenna. The broadband characteristic comes from the directors of the magnetic and electric Yagi antennas and the reflector of magnetic Yagi antenna. The simulation and the measurement verify this design. The measured common bandwidth of $\vert S_{11}\vert < -10$ dB for both polarization ports is 23.8–30.1 GHz (23.7%), and the gains vary between 3 dBi and 4 dBi within 24.2–30 GHz band range. The $1\times 4$ DP array with $0.5~\lambda _{0}$ element space has the beam scanning range of ±43 ° at the endfire direction and the gain of higher than 7.1 dBi. The scanning performances are experimentally validated by two phase-shift feed networks for 0 ° and 30 ° main beam directions. The proposed endfire DP array has the good features of compact structure, a low profile and no clearance requirement, which is easy to integrate in 5G terminals.

Most plants in nature establish symbiotic associations with endophytic fungi in soil. Beneficial endophytic fungi induce a systemic response in the aboveground parts of the host plant, thus promoting the growth and fitness of host plants. Meanwhile, temperature elevation from climate change widely affects global plant biodiversity as well as crop quality and yield. Over the past decades, great progresses have been made in the response of plants to high ambient temperature and to symbiosis with endophytic fungi. However, little is known about their synergistic effect on host plants. The endophytic fungus Serendipita indica colonizes the roots of a wide range of plants, including Arabidopsis. Based on the Arabidopsis-S. indica symbiosis experimental system, we analyzed the synergistic effect of high ambient temperature and endophytic fungal symbiosis on host plants. By transcriptome analysis, we found that DNA replication-related genes were significantly upregulated during the systemic response of Arabidopsis aboveground parts to S. indica colonization. Plant hormones, such as jasmonic acid (JA) and ethylene (ET), play important roles in plant growth and systemic responses. We found that high ambient temperature repressed the JA and ET signaling pathways of Arabidopsis aboveground parts during the systemic response to S. indica colonization in roots. Meanwhile, PIF4 is the central hub transcription factor controlling plant thermosensory growth under high ambient temperature in Arabidopsis. PIF4 is also involving JA and/or ET signaling pathway. We found that PIF4 target genes overlapped with many differentially expressed genes (DEGs) during the systemic response, and further showed that the growth promotion efficiency of S. indica on the pif4 mutant was higher than that on the wild-type plants. In short, our data showed that high ambient temperature strengthened the growth promotion effect of S. indica fungi on the aboveground parts of the host plant Arabidopsis, and the growth promotion effect of the systemic response under high ambient temperature was regulated by PIF4.

Background: Rheumatoid arthritis (RA) is a chronic disabling inflammatory disease that causes synovial angiogenesis in an invasive manner and leads to joint destruction. Currently available pharmacotherapy for RA has unwanted side effects and limitations. Although anti-angiogenic therapy is regarded as a new potential treatment for RA, only a few anti-angiogenic drugs are available. An increasing number of studies have shown that β-sitosterol (BSS) may exert inhibitory effects against angiogenesis. However, the mechanisms involved are still unclear.Methods: Based on the results of the gene set enrichment analysis (GSEA) of the transcriptome data of endothelial cells from RA patients, we evaluated the pharmacological effects of BSS on the tube formation, cell proliferation, and migration of human umbilical vein endothelial cells (HUVECs). Furthermore, the effects of BSS treatment on vascular endothelial growth factor receptor 2 (VEGFR2) were determined using molecular docking and Western blotting. Additionally, in the presence or absence of BSS, synovial angiogenesis and joint destruction of the ankle were investigated in collagen-induced arthritis (CIA) mice. The effect of BSS treatment on VEGFR2/p-VEGFR2 expression was verified through immunohistochemical staining.Results: The immunohistochemistry results revealed that BSS treatment inhibited angiogenesis both in vitro and in vivo. In addition, the results of 5-ethynyl-2′-deoxyuridine and cell cycle analysis showed that BSS treatment suppressed the proliferation of HUVECs, while the Transwell migration and stress fiber assays demonstrated that BSS treatment inhibited the migration of HUVECs. Notably, the inhibitory effect of BSS treatment on VEGFR2/p-VEGFR2 was similar to that of axitinib. In CIA mice, BSS also exerted therapeutic effects on the ankles by reducing the degree of swelling, ameliorating bone and cartilage damage, preventing synovial angiogenesis, and inhibiting VEGFR2 and p-VEGFR2 expression.Conclusion: Therefore, our findings demonstrate that BSS exerts an inhibitory effect on synovial angiogenesis by suppressing the proliferation and migration of endothelial cells, thereby alleviating joint swelling and bone destruction in CIA mice. Furthermore, the underlying therapeutic mechanisms may involve the inhibition of VEGF signaling pathway activation.