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Exosomes are the key mediator for intercellular communication and participate in malignancies. Short non-coding RNAs derived from BMSCs-originated exosomes (BMSCs-exosomes) can be employed as biomolecules for tumor treatment. Here to we aim to dissect the function of microRNA-2158 from BMSCs-exosomes in breast malignant disease. Breast malignant cells received a separated transfection of miR-2158-mimics and miR-2158-inhibitor, and also treated with BMSCoriginated exosomes followed by analysis of cell viability by MTT method, cell invading and migrating capabilities via Transwell assays and protein levels of EMT-related and RAI2/NLRP3-related proteins by Western-blot. Breast cancer cells exhibited a significantly enhanced miR-2158 expression after transfection with miR-2158-mimics or treatment with BMSC-EXO, while it was reduced by miR-2158-inhibitor. As the miR-2158 was up-regulated, a significant impediment of proliferation and migration was denoted, along with a down-regulation of RAI2/NLRP3 signal transduction pathway and a retarded EMT process. Furthermore, cell proliferating and migrating capabilities were strengthened by miR-2158-inhibitor, together with an enhanced RAI2/NLRP3 signal and a strengthened EMT process. In conclusion, miR-2158 retarded the in vitro proliferating and migrating activities of breast malignant cells, leading to the inactivation of RAI2/NLRP3 signal transduction pathway, thereby exerting its tumor-suppressing function.

The oviduct of Chinese brown frog (Rana dybowskii) displays seasonal morphological and functional changes, which expands specifically during pre-brumation. To uncover the molecular mechanism underlying this phenomenon, we firstly confirmed the increased weight and enlarged diameter of the oviduct in pre-brumation by morphological observation. Interestingly, the glycogen content in the oviduct increased significantly during pre-brumation, indicating Rana dybowskii stores energy in the oviduct before brumation. Transcriptome analysis further identified the differentially expressed genes in the synthesis and metabolism pathways of carbohydrates in the oviduct during pre-brumation. Based on that evidence, we focused on the mRNA and protein expression of glycogenic genes in the oviduct of Rana dybowskii. qPCR confirmed that the expression of glycolysis and glycogenesis-related genes were up-regulated while gluconeogenesis-related genes were down-regulated during pre-brumation. Western blot data showed that glucose transporter GLUT1 and glycogen synthesis-regulation proteins including GYS, and p-GSK-3β were highly expressed in the oviduct during pre-brumation. Moreover, immunohistochemical data showed that GLUT1, GYS, p-GYS, GSK-3β and p-GSK-3β were expressed regionally in the oviduct of Rana dybowskii. The data suggests that glycogen synthesis may be involved in the oviductal expansion of Rana dybowskii during the pre-brumation.

Breast cancer (BC), a common malignancy, is intractable at present. Cuprous oxide nanoparticles (Conps) are new nanoparticles crucial in inhibiting tumor progression according to early studies, but their role in BC remains unclear. Field emission-scanning electron microscopy (FESEM) and field emission–transmission electron microscopy (FETEM) were used for the morphological observation of Conps, and energy-dispersive X-ray spectroscopy was used for their elemental composition analysis. Multipoint nitrogen adsorption was used to determine the Brunauer–Emmet–Teller of Conps, and their mean hydrodynamic size and zeta potential in water and intact cell medium were determined by dynamic light scattering (DLS). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Cell Counting Kit-8, Transwell assay, and flow cytometry were used to determine the effects of Conps on the biological function of BC cells. Western blotting was used to determine the changes in apoptosis-related proteins. Using FESEM and FETEM based on DLS and zeta potential determination, Conps was successfully constructed. Conps significantly lowered the viability of BC cells in a dose-dependent manner, significantly inhibited cell proliferation, invasion, and migration activities, and induced cell apoptosis. Western blotting demonstrated that Conps up-regulated Bax and caspase-3 proteins and down-regulated Bcl-2 protein. The results suggest that Conps can suppress the proliferation, invasion, and migration of BC cells and accelerate their apoptosis. This is a new potential strategy for the clinical treatment of BC.

Recombinant adeno-associated viruses (rAAVs) are currently considered the safest and most reliable gene delivery vehicles for human gene therapy. Three serotype capsids, AAV1, AAV2, and AAV9, have been approved for commercial use in patients, but they may not be suitable for all therapeutic contexts. Here, we describe a novel capsid identified in a human clinical sample by high-throughput, long-read sequencing. The capsid, which we have named AAVv66, shares high sequence similarity with AAV2. We demonstrate that compared to AAV2, AAVv66 exhibits enhanced production yields, virion stability, and CNS transduction. Unique structural properties of AAVv66 visualized by cryo-EM at 2.5-Å resolution, suggest that critical residues at the three-fold protrusion and at the interface of the five-fold axis of symmetry likely contribute to the beneficial characteristics of AAVv66. Our findings underscore the potential of AAVv66 as a gene therapy vector., Adeno-associated viruses (AAVs) are vehicles for gene therapy in humans, but currently only a limited amount of AAV serotypes is available. Here, the authors identify a novel AAV, AAVv66, and demonstrate enhanced production yields, virion stability, and CNS transduction compared to the clinically approved serotype AAV2.

In the past few decades, quantum computation has become increasingly attractive due to its remarkable performance. Quantum image scaling is considered a common geometric transformation in quantum image processing, however, the quantum floating-point data version of which does not exist. Is there a corresponding scaling for 2-D and 3-D floating-point data? The answer is yes. In this paper, we present a quantum scaling up and down scheme for floating-point data by using trilinear interpolation method in 3-D space. This scheme offers better performance (in terms of the precision of floating-point numbers) for realizing the quantum floating-point algorithms than previously classical approaches. The Converter module we proposed can solve the conversion of fixed-point numbers to floating-point numbers of arbitrary size data with $$p+q$$ p + q qubits based on IEEE-754 format, instead of 32-bit single-precision, 64-bit double-precision and 128-bit extended-precision. Usually, we use nearest-neighbor interpolation and bilinear interpolation to achieve quantum image scaling algorithms, which are not applicable in high-dimensional space. This paper proposes trilinear interpolation of floating-point data in 3-D space to achieve quantum algorithms of scaling up and down for 3-D floating-point data. Finally, the quantum scaling circuits of 3-D floating-point data are designed.

Background: The oviduct of Chinese brown frog (Rana dybowskii) expands specifically during pre-hibernation. However, the underlying molecular mechanism remains unclear. Results: This study investigated the mRNA and protein expression levels of glycogenic genes in the oviduct of Rana dybowskii during the breeding season and pre-hibernation. Morphological studies revealed increased weight and enlarged diameter of the oviduct in pre-hibernation. Furthermore, significantly increased glycogen level was detected in the oviduct during pre-hibernation when compared to the breeding season. Transcriptome analysis further identified that the differentially expressed genes in the synthesis and metabolism pathways of carbohydrates in the oviduct during pre-hibernation. The relative mRNA levels of glycolysis and glycogenesis-related genes were up-regulated, while gluconeogenesis-related genes were down-regulated during pre-hibernation. Also, Western blot showed that glucose transporter and glycogen synthesis-related proteins, such as total-GYS, and p-GSK-3β were highly expressed in the oviduct during pre-hibernation. In addition, immunohistochemical data showed that glucose transporter and total-GYS, p-GYS, total-GSK-3β and p-GSK-3β related to glycogen synthesis were both expressed regionally in the oviduct of Rana dybowskii during the breeding season and pre-hibernation. Conclusions: The data suggests that carbohydrate metabolism plays an important role in the hibernation process of Rana dybowskii, and provides a new insight into the mechanism underlying the expansion of the oviduct of Rana dybowskii during pre-hibernation.

Recombinant adeno-associated viruses (rAAVs) have become favorable gene delivery vehicles for expressing therapeutic transgenes. Capsid engineering efforts to produce novel AAVs with improved trans...

Capacitors with high energy density are pressingly demanded in pulsed power systems and recent achievements in polymer-based nanocomposites with increasingly high energy storage capacity demonstrat...

A novel adsorbent for antibiofouling and highly selective uranium recovery from seawater is developed in this work. Specifically, the polypropylene nonwoven fabric modified with oxime and guanidine was obtained by subsequent radiation-grafting, ring-opening and oximation reaction. The adsorbent demonstrates outstanding selectivity for uranium(VI) against other competing metal ions in real seawater. The antibacterial assay indicated the adsorbent has good antibacterial properties against Escherichia coli and Staphylococcus aureus. XPS spectra indicate that uranium(VI) is adsorbed on the non-woven through the interaction with multiple groups. This work shows that the sorbent may be a hopeful material for the extraction of uranium from seawater.

In the past few decades, quantum computation has become increasingly attractive due to its remarkable performance. However, few results of 2-D data and their transformation based on quantum computation have emerged in recent years. A generalized floating-point representation of 2-D data (QR2-DD) is proposed, which can represent a quantum data with arbitrary size by the element of $$p + q$$ qubits. And then, we provide a method to convert a 3-D data into 2-D data, which leads to a reduction in the number of qubits for position. Based on QR2-DD, the quantum circuits of elementary transformation of 2-D data are designed, such as interchanging two-row module, multiplying a row by a constant module and adding two-row module. In order to verify the effectiveness of these circuits, an example is given below each module.

Reticuloendotheliosis virus (REV) can cause runting, immunosuppression, acute reticulum cell neoplasia, and chronic lymphoid tumors in a variety of domestic and wild birds. We diagnosed a case of reticuloendotheliosis with obvious tumors in liver and kidney. We isolated and sequenced the virus and performed pathogenicity testing of the REV strain. Immunohistochemistry and PCR confirmed that the diseased layer chickens were infected with REV. The strain, named BJ1503, was successfully isolated from the case by inoculation of tissue homogenates onto chicken embryo fibroblasts. The length of the proviral REV genome is 8,293 nucleotides. The isolate had 99.7% identity with REV-HA9901 (AY842951.1), which was isolated from Jiangsu, China, in 1999. The chickens infected with REV-BJ1503 had depressed weight gain and lymphoid atrophy. Our findings suggest that REV isolate BJ1503 was phylogenetically close to the earlier strain found in China, with minor variations, and the virus was associated with severe production problems.

Malathion (MT) and chlorpyrifos (CPF) are immunotoxic organophosphate pesticides that are used extensively in agriculture worldwide. Dietary polyphenols protect against a variety of toxins. In this study, walnut polyphenol extract (WPE) prevents MT- or CPF-induced toxicity to splenic lymphocytes in vitro. WPE promotes the proliferation of MT-exposed splenocytes, as indicated by increases in the proportions of splenic T-lymphocyte subpopulations (CD3+, CD4+, and CD8+ T cells) and levels of T-cell-related cytokines interleukin (IL)-2, interferon-&gamma, IL-4, and granzyme B, and decreases the apoptosis-associated proteins Bax and p53. WPE also significantly enhances the proliferation of CPF-exposed splenic B lymphocytes (CD19+ B cells) and levels of the B-cell-related cytokine IL-6, leading to decreases of the apoptosis-associated proteins Bax and p53. These effects are related to reduced production of reactive oxygen species (ROS), as evidenced by normalized hydroxyl radical (&bull, OH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and glutathione (GSH) levels, which are associated with decreased expression of NADPH oxidase 2 (NOX2) and dual oxidase 1 (DUOX1). WPE inhibits the production of ROS and expression of NOX by regulating toll-like receptors 4 and 7 in MT- and CPF-exposed splenic lymphocytes. In conclusion, WPE protects against MT- or CPF-mediated immunotoxicity and inhibits oxidative damage by modulating toll-like receptor (TLR)x-NOX-ROS.

Supplemental material, Supplemental_material for Isolation and pathogenicity testing of avian reticuloendotheliosis virus from layer chickens in China by Ahui Xu, Caiyun Huo, Qi Zhong, Meiyu Xu, Yurong Yang, Haiyan Tian, Guozhong Zhang and Yanxin Hu in Journal of Veterinary Diagnostic Investigation

Our previous work showed that a proliferation-inducing ligand (APRIL) was involved in the development of acute lymphoblastic leukemia (ALL) in children. However, the precise role of APRIL in ALL remains unknown. To investigate this issue, we silenced and overexpressed APRIL in Nalm-6 ALL cells using short hairpin RNA targeting the APRIL gene and recombinant human APRIL, respectively, and evaluated the effects on cell proliferation, apoptosis, and migration. APRIL mRNA and APRIL and matrix metalloproteinase-2 protein levels were evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and western blott, respectively. We found that APRIL expression was reduced by shRNA-mediated knockdown in Nalm-6 cells; this was associated with a decrease in cell proliferation (P

Toll-Like Receptors (TLRs) are membrane-bound proteins that recognize invading organisms with Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Related Molecular Patterns (DAMPs)...

Background Interneuronal pathology is implicated in many neuropsychiatric disorders, including autism spectrum disorder (ASD) and Tourette syndrome (TS). Interneurons of the striatum, including the parvalbumin-expressing fast-spiking interneurons (FSIs) and the large cholinergic interneurons (CINs), are affected in patients with TS and in preclinical models of both ASD and TS. Methods To test the causal importance of these neuronal abnormalities, we recapitulated them in vivo in developmentally normal mice using a combination transgenic–viral strategy for targeted toxin-mediated ablation. Results We found that conjoint ~50% depletion of FSIs and CINs in the dorsal striatum of male mice produces spontaneous stereotypy and marked deficits in social interaction. Strikingly, these behavioral effects are not seen in female mice; because ASD and TS have a marked male predominance, this observation reinforces the potential relevance of the finding to human disease. Neither of these effects is seen when only one or the other interneuronal population is depleted; ablation of both is required. Depletion of FSIs, but not of CINs, also produces anxiety-like behavior, as has been described previously. Behavioral pathology in male mice after conjoint FSI and CIN depletion is accompanied by increases in activity-dependent signaling in the dorsal striatum; these alterations were not observed after disruption of only one interneuron type or in doubly depleted female mice. Conclusions These data indicate that disruption of CIN and FSI interneurons in the dorsal striatum is sufficient to produce network and behavioral changes of potential relevance to ASD, in a sexually dimorphic manner.

In this paper, our main goal is to introduce the construction of the -stage periodic wave packet frames in a discrete setting. We first establish a general characterization of wave packet systems to be Parseval frames in using discrete Fourier transforms, and provide a sufficient condition for the system to be a first-stage discrete periodic wave packet frame for . And then, we construct a class of -stage discrete periodic wave packet frame by iterating the filter sequence, and establish the associated decomposition and reconstruction algorithms for these wave packet frames, which include the corresponding results of wavelet analysis and Gabor theory as the special cases. Finally, we give an illustrative example to demonstrate the validity of the proposed scheme.

The oviduct of Chinese brown frog ( Rana dybowskii) expands specifically during prehibernation instead of in the breeding period. In this study, we investigated the expression of leptin receptor (Ob-Rb) in Rana dybowskii oviduct during the breeding period and prehibernation. Histologically, the oviduct of Rana dybowskii consists of glandular cells, tubule lumen, and epithelial cells. The oviductal weight and pipe diameter also revealed significant differences, which were higher in prehibernation than that of the breeding period. Ob-Rb was observed in stromal cells of oviductal tissue in both the breeding period and prehibernation. The mean protein and mRNA levels of the Ob-Rb were significantly higher in prehibernation as compared with the breeding period. In addition, oviductal content of leptin was also higher in prehibernation than that of the breeding period. These results suggested that oviduct of Rana dybowskii might be a target organ of leptin, and leptin may play an autocrine/paracrine role mediated by Ob-Rb in regulating the oviductal hypertrophy during prehibernation.

The cytokine interleukin-1 beta (IL-1β) is an evolutionarily conserved molecule that was originally identified in the immune system. Nuclear factor κB (NF-κB) plays a critical role in the activation of immune cells by upregulating the expression of many cytokines. In this study, we investigated the localization and expression level of IL-1β, its functional membrane receptor type I (IL-1R1) and NF-κB in the skin of Rana dybowskii during the breeding period and pre-hibernation. Histologically, the skin of Rana dybowskii consists of epidermis and dermis, and four kinds of cells were identified in the epidermis during the breeding period and pre-hibernation, while the dermis was composed of homogenous gel, mucous glands and granular glands. IL-1β, IL-1R1 and NF-κB were immunolocalized in the epithelial and glandular cells in both periods. Western blotting showed that there was no significant difference in the expression of IL-1β between the breeding period and pre-hibernation, whereas IL-1R1 and NF-κB were significantly higher in the pre-hibernation compared to the breeding period. These results suggested that IL-1β and NF-κB may collectively play important roles in the skin immune system of Rana dybowskii during the breeding period and pre-hibernation.

One special physiological phenomenon of the Chinese brown frog (Rana dybowskii) is that its oviduct goes through expansion prior to pre-hibernation instead of expanding during the breeding period. Our previous study discovered that some cytokines such as interleukin-1 beta (IL-1β) and its receptor type I (IL1R1) proteins were expressed in the oviduct of Rana dybowskii. In this study, we continued to investigate the localizations and expression levels of cytokines including toll-like receptor 4 (TLR4) and its related factors, myeloid differentiation factor 88 (MyD88), interleukin-1 receptor-associated kinase (IRAK) and nuclear factor kappa B (NF-κΒ) in the oviduct of Rana dybowskii during the breeding period and pre-hibernation. Morphological results showed that there were significant differences in oviductal weight and pipe diameter with significantly higher values in pre-hibernation than those of the breeding period. Strong immunostaining of TLR4, MyD88, IRAK4 and NF-κΒ were observed in the pre-hibernation. These proteins levels had no significant difference between these two periods except MyD88 which was significantly higher in the pre-hibernation. The mRNA expression levels of MyD88 and NF-κΒ were obviously higher in pre-hibernation than those of the breeding period. These findings suggested that TLR4/MyD88 signal pathway might participate in the oviductal functions of Rana dybowskii during the breeding period and pre-hibernation.

Recombinant adeno-associated viruses (rAAVs) have become favorable gene delivery vehicles for expressing therapeutic transgenes. Capsid engineering efforts to produce novel AAVs with improved transduction efficiencies, unique tissue specificities, and reduced host immunities are a direct response to the high demand for treatment needs that preexisting rAAVs cannot currently fulfill. New AAV capsids discovered by directed evolution methods, in silico design, or from natural proviral sequences ultimately require extensive characterization in relevant in vivo models. Consequently, quantitative screening of candidate capsid libraries now requires reliable high-throughput sequencing approaches. In this study, we have developed a vector/transgene tracking system that employs the indexing of a non-coding RNA. Specifically, a barcoded Tough Decoy (bcTuD) that express highly stable RNA transcripts that can be used as readouts for transduction efficiency. The pseudo-hairpin structure of the bcTuD contains a variable region that is amenable to barcode insertion, which can be detected by target amplicon sequencing. The described approach, named AAV-bcTuD screening, offers a new alternative for in vivo assessment of rAAV that can accurately quantify vector genomes and transcript abundances in tissues, as exampled by the demonstration in liver and brain infections. Proof-of-concept is provided to show that vector genome and transcript detection in tissues with this method is accurate and consistent for a vector dose range of upwards to four logs in a mixed vector injection, showing that this technique is robust, sensitive, and applicable for multiplexed screening of capsid performance in vivo.

Flexible piezoelectric generators (PEGs) are receiving considerable attention due to the increasing demands on lightweight and sustainable power supply for wearable electronics. Combing piezoelectric nanofillers with polymers have been extensively investigated as a promising strategy. Here, piezotronic ZnO nanorods are introduced into poly (vinylidene fluoride-hexafluoropropylene) [P(VDF-HFP)] considering that piezoelectric functions of both components can be united for high performance PEGs. ZnO/P(VDF-HFP) nanocomposites were designed with fillers distribution controlled via different processing, and the relationship between the filler orientation and the crystallization behaviors, dielectric and electromechanical conversion performances with respect to filler content were studied. The microcapacitor model and percolation theory were employed to understand the dielectric anisotropy in oriented nanocomposites, and furthermore, finite element analyses were utilized to reveal the distribution of local electric field. Finally, a maximum output voltage 11.8 V has been achieved in oriented ZnO/P(VDF-HFP) film, which is 2.3 times and 7.9 times the value of random nanocomposites (5.1 V) and pure P(VDF-HFP) film (1.5 V), respectively. With the piezoelectric responses obtained from piezoelectric force microscopy, significant enhancement in electromechanical conversion performance has been thoroughly discussed. The results thus demonstrate a promising strategy towards high-performance flexible piezoelectric generator.

The Chinese brown frog (Rana dybowskii) has one special physiological phenomenon, which is that its oviduct expands prior to hibernation rather than in the breeding period. In this study, we investigated the immunolocalization and expression levels of prostaglandin-E2 (PGE2), cyclooxygenase (COX)-1 and COX-2, as well as one of its receptor subtypes 4 (EP4) in the oviduct of Rana dybowskii during the pre-hibernation and breeding period. PGE2, COX-1, COX-2 and EP4 have been observed in glandular and epithelial cells in the breeding period, whereas only in the epithelial cells during the pre-hibernation. Consistently, the protein levels of COX-2 and EP4 were higher in the pre-hibernation as compared to the breeding period, but the diversity of COX-1 was not obvious. In addition, oviductal PGE2 concentration was also significantly higher in the pre-hibernation. These results suggested that prostaglandin-E2 may play an important autocrine or paracrine role in oviductal cell proliferation and differentiation of Rana dybowskii during pre-hibernation.

Tic disorders, including Tourette syndrome (TS), are thought to involve pathology of cortico-basal ganglia loops, but their pathology is not well understood. Post-mortem studies have shown a reduced number of several populations of striatal interneurons, including the parvalbumin-expressing fast spiking interneurons (FSIs), in individuals with severe, refractory TS. We tested the causal role of this interneuronal deficit by recapitulating it in an otherwise normal adult mouse using a combination transgenic-viral cell ablation approach. FSIs were reduced bilaterally by ~40%, paralleling the deficit found post-mortem. This did not produce spontaneous stereotypies or tic-like movements, but there was increased stereotypic grooming after acute stress in two validated paradigms. Stereotypy after amphetamine, in contrast, was not elevated. FSI ablation also led to increased anxiety-like behavior in the elevated plus maze, but not to alterations in motor learning on the rotorod or to alterations in prepulse inhibition, a measure of sensorimotor gating. These findings indicate that a striatal FSI deficit can produce stress-triggered repetitive movements and anxiety. These repetitive movements may recapitulate aspects of the pathophysiology of tic disorders.

In this study, we investigated the mRNA expression and protein levels of B-cell activating factor (BAFF)/a proliferation-inducing ligand (APRIL) and their receptors in acute lymphoblastic leukemia (ALL) cell lines and pediatric patients with ALL using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting. The location and level of the BAFF/APRIL proteins in ALL cell lines were also detected by immunofluorescence cytochemistry and flow cytometry. Correlations between plasma protein levels of BAFF/APRIL and primary clinical parameters were analyzed. We found that BAFF/APRIL was highly expressed in pediatric ALL patients and ALL cell lines. The BAFF/APRIL proteins were located on the cell membrane, and the proportion of positive cells and mean fluorescence intensity were significantly higher than in the healthy control group (P

The Chinese brown frog (Rana dybowskii) has one special physiological phenomenon, which is that its oviduct goes through expansion prior to hibernation instead of during the breeding period. In this study, we investigated the localization and expression level of interleukin-1 (IL-1β) and its functional membrane receptor type I (IL1R1) proteins in the oviduct of R. dybowskii during pre-hibernation and the breeding period. There were significant differences in both oviductal weight and pipe diameter, with values markedly higher in pre-hibernation than in the breeding period. Histologically, epithelium cells, glandular cells and tubule lumen were identified in the oviduct during pre-hibernation and the breeding period, while sizes of both cell types are larger in the pre-hibernation than those of the breeding period. IL-1β was immunolocalized in the cytoplasm of epithelial and glandular cells in both periods, whereas IL-1R1 was observed in the membrane of epithelial and glandular cells in the breeding period, whereas only in epithelial cells during pre-hibernation. Consistently, the protein levels of IL-1β and IL-1R1 were higher in pre-hibernation as compared to the breeding period. These results suggested that IL-1β may play an important autocrine or paracrine role in oviductal cell proliferation and differentiation of R. dybowskii.

Polymer-based dielectric capacitors have attracted increasing attention in advanced electronics and pulsed power systems due to their high power density and ultrafast charge–discharge speed. However, most of recent achievements focus on polymer-based nanocomposites employing high-k inorganic nanofillers, generating mismatched filler/matrix interfaces that need careful modification. Herein, all-organic hybrid polymers have been explored to achieve ultrahigh energy storage density. Ferroelectric poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) with large polarization was introduced into poly(vinylidene fluoride) (PVDF) with smaller polarization forming blend films, and next sandwich structures constructed by PVDF and P(VDF-TrFE)/PVDF blend films were elaborately designed. A high discharge energy density (Ue) of 23.6 J/cm3 at 636 MV/m has been achieved in 30/70 (volume ratio) P(VDF-TrFE)/PVDF blend film, which is 55% and 130% higher than that of PVDF and P(VDF-TrFE), respectively. Further, by designing sandwich structured all-organic films with 50/50 (volume ratio) P(VDF-TrFE)/PVDF blend film as middle layer to provide high electric displacement and PVDF as two outer layers to withstand high electric field, high Ue = 20–24 J/cm3 and charge–discharge efficiency (>65%) have been achieved. In-depth understanding on the microscopic mechanism for achieving high Ue is gained via finite element analysis showing that the volume fraction of ferroelectric phase in the hybrid system and the mesoscopic layer/layer interfaces are crucial. This work thus provides a promising alternative strategy for high-density energy storage via all-organic films design.

Fenitrothion (FNT), an organophosphate pesticide, exerts an immunotoxic effect on splenocytes. Dietary polyphenol compounds exert antioxidant, anticancer and antihypertensive effects. In this study, we investigated the effect of walnut polyphenol extract (WPE) on FNT-induced immunotoxicity in splenic lymphocytes in vitro. Treatment with WPE significantly increased the proliferation of FNT-exposed splenocytes, as evidenced by increases in the proportions of splenic T lymphocytes (CD3+ T cells) and T-cell subsets (CD8+ T cells), as well as the secretion of the T-cell-related cytokines interleukin (IL)-2, interferon-&gamma, IL-4 and granzyme B. These effects were associated with a reduction in oxidative stress, as evidenced by changes in the levels of hydroxyl radical, superoxide dismutase, glutathione peroxidase and malondialdehyde. Moreover, WPE decreased the FNT-induced overexpression of NADPH oxidase 2 and dual oxidase 1 by regulating Toll-like receptor 4 signaling in splenic T-cells. Taken together, these findings suggest that WPE protects against FNT-mediated immunotoxicity and improves immune function by inhibiting oxidative stress.

EphA5 and its ligand ephrin-A5 interaction can trigger synaptogenesis during early hippocampus development. We have previously reported that abnormal EphA5 expression can result in synaptogenesis disorder in congenital hypothyroidism (CH) rats. To better understand its precise molecular mechanism, we further analyzed the characteristics of ephrin-A5 expression in the hippocampus of CH rats. Our study revealed that ephrin-A5 expression was downregulated by thyroid hormone deficiency in the developing hippocampus and hippocampal neurons in rats. Thyroxine treatment for hypothyroid hippocampus and triiodothyronine treatment for hypothyroid hippocampal neurons significantly improved ephrin-A5 expression but could not restore its expression to control levels. Hypothyroid hippocampal neurons in-vitro showed synaptogenesis disorder characterized by a reduction in the number and length of neurites. Furthermore, the synaptogenesis-associated molecular expressions of NMDAR-1 (NR1), PSD95 and CaMKII were all downregulated correspondingly. These results suggest that ephrin-A5 expression may be decreased in CH, and abnormal activation of ephrin-A5/EphA5 signaling affects synaptogenesis during brain development. Such findings provide an important basis for exploring the pathogenesis of CH genetically.

Background Previous studies reported that miR-1908 was highly expressed in mature human adipocytes. Adipokines tumor necrosis factor α (TNF-α) that was known to activate NF-kappaB signaling could affect the expression of miR-1908 in adipocytes. However, little is known about the underlying mechanisms. Methods In this study, we identified miR-1908 promoter using polymerase chain reaction (PCR) from human genomic DNA. Bioinformatic analysis was applied to predict the NF-kappaB binding sites in miR-1908 promoter. Real-time PCR, dual luciferase reporter assay, Mutagenesis analysis and electrophoretic mobility shift assay (EMSA) were performed to demonstrate the function of NF-kappaB binding sites in miR-1908 promoter. Results 1243 bp miR-1908 promoter located in the intron of host gene fatty acid desaturase 1 (FADS1). Bioinformatic analysis revealed the presence of two putative NF-kappaB binding sites. TNF-α restricts miR-1908 expression in preadipocytes, and TNF-α decreases miR-1908 promoter activity in HEK293T cells. In addition, those two NF-kappaB transcription factor binding sites in miR-1908 promoter were functional. Conclusion Our findings demonstrated that miR-1908 has its own transcription unit, and revealed the transcriptional mechanisms of miR-1908 expression based on NF-kappaB signaling. This study offers a theoretical basis for understanding the transcriptional mechanism of miR-1908 expression and may provide a new strategy for obesity clinical therapy.

Thyroid hormones (THs) are essential for normal development of the mammalian central nervous system through regulation of TH-responsive genes. EphA5, an important TH-responsive gene encoding the tyrosine kinase receptor EphA5, regulates synaptogenesis initiation and synaptic remodeling during brain development. Abnormal EphA5 expression is involved in the development of congenital hypothyroidism (CH). To show the regulatory mechanism of EphA5 expression in CH rats, we analyzed the correlation between methylation of the EphA5 promoter and its expression in the hypothyroid hippocampus and hippocampal neurons. Demethylation treatment using 5'-azadeoxycytidine upregulated EphA5 expression and rescued the effects of hypermethylation, suggesting a novel regulatory mechanism of EphA5 expression in CH rats. Our results suggest a potentially new approach for the development of drugs to restore neurocognitive impairments associated with CH.