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Introduction: Voltage-gated Kv7/M potassium channels play an essential role in the control of membrane potential and neuronal excitability. Fangchinoline, a bisbenzylisoquinoline alkaloid, displays extensive biological activities including antitumor, anti-inflammatory, and antihypertension effects. In this study, we investigated the effects of fangchinoline on Kv7/M channels. Methods: A perforated whole-cell patch technique was used to record Kv7 currents from HEK293 cells and M-type currents from mouse dorsal root ganglion (DRG) neurons. Results: Fangchinoline inhibited Kv7.2/Kv7.3 currents in a concentration-dependent manner, with an IC50 of 9.5 ± 1.2 μM. Fangchinoline significantly inhibited Kv7.1, Kv7.2, Kv7.3, Kv7.4, and Kv7.3/Kv7.5 channels without selective effects. Furthermore, fangchinoline significantly slowed the activation of Kv7.1-Kv7.5 channels and inhibited native M-channel currents of DRG neurons. Conclusion: Taken together, our findings indicate that fangchinoline concentration-dependently inhibited Kv7/M channel currents.

The aim of this investigation was to develop an etomidate intravenous lipid emulsion (ETM-ILE) and evaluate its properties in vitro and in vivo. Etomidate (ETM) is a hydrophobic drug, and organic solvents must be added to an etomidate injectable solution (ETM-SOL) to aid dissolution, that causes various adverse reactions on injection. Lipid emulsions are a novel drug formulation that can improve drug loading and reduce adverse reactions. ETM-ILE was prepared using high-pressure homogenization. Univariate experiments were performed to select key conditions and variables. The proportion of oil, egg lecithin, and poloxamer 188 (F68) served as variables for the optimization of the ETM-ILE formulation by central composite design response surface methodology. The optimized formulation had the following characteristics: particle size, 168.0 ± 0.3 nm; polydispersity index, 0.108 ± 0.028; zeta potential, −36.4 ± 0.2 mV; drug loading, 2.00 ± 0.01 mg/mL; encapsulation efficiency, 97.65% ± 0.16%; osmotic pressure, 292 ± 2 mOsmol/kg and pH value, 7.63 ± 0.07. Transmission electron microscopy images showed that the particles were spherical or spheroidal, with a diameter of approximately 200 nm. The stability study suggested that ETM-ILE could store at 4 ± 2 °C or 25 ± 2 °C for 12 months. Safety tests showed that ETM-ILE did not cause hemolysis or serious vascular irritation. The results of the pharmacokinetic study found that ETM-ILE was bioequivalent to ETM-SOL. However, a higher concentration of ETM was attained in the liver, spleen, and lungs after administration of ETM-ILE than after administration of ETM-SOL. This study found that ETM-ILE had great potential for clinical applications.

Objective: To explore the clinical therapeutic effect of Hongteng decoction combined with levofloxacin on chronic pelvic inflammatory disease (CPID) patients and its effect on the expression of inflammatory factors. Methods: 72 patients with CPID who were diagnosed and treated in the Fourth Hospital of Shijiazhuang City from January 2020 to December 2020 were selected and randomly divided into observation group (n = 36) and control group (n = 36). The control group was treated with levofloxacin and the observation group was treated with Hongteng decoction retention enema on the basis of the control group. Both groups were treated continuously for 2 courses. The clinical therapeutic effects of the two groups were compared, and the changes of related inflammatory indexes such as interleukin-2 (IL-2), interleukin-10 (IL-10), C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were compared between the two groups before and after treatment. The score of quality of life and the occurrence of adverse reactions before treatment were compared. Results: The total effective rate of the observation group was significantly higher than that of the control group, and the difference was statistically significant (P0.05). After treatment, the expression of IL-2 and IL-10 in the observation group was higher than that in the control group, and the expression of CRP and TNF-α was lower than that in the control group, with statistical significance (P0.05). After treatment, scores of physical pain, life function, social function and mental health in the observation group were higher than those in the control group, and the differences were statistically significant (P0.05). Conclusion: Hongteng decoction combined with levofloxacin has definite efficacy in the treatment of CPID, which can effectively improve the clinical symptoms of patients and inhibit inflammatory response, and is worthy of clinical promotion.

Phenolic compounds in cereal and legume seeds show numerous benefits to human health mainly because of their good antioxidant capacity. However, long-term storage and some improper preservation may reduce their antioxidant potential. It is necessary to retain or modify the phenolic antioxidants with improved technology before consumption. Radiation processing is usually applied as a physical method to extend the shelf life and retain the quality of plant produce. However, the effect of radiation processing on phenolic antioxidants in cereal and legume seeds is still not well understood. This review summarizes recent research on the effect of radiation, including ionizing and nonionizing radiation on the content and profile of phenolic compounds, and antioxidant activities in cereal and legume seeds, the influencing factors and possible mechanisms are also discussed. The article will improve the understanding of radiation effect on phenolic antioxidants, and promote the radiation modification of natural phenolic compounds in cereal and legume seeds and other sources.

Circular RNA (circRNA) is a type of non-coding RNA that is widely expressed in mammals. It is highly conserved and abundantly expressed in the brain. Here, we report the regulatory role of circRNA derived from the pantothenate kinase 1 (Pank1) gene (circ-Pank1) in Parkinson’s disease (PD). Circ-Pank1 is highly expressed in the substantia nigra (SN) of PD model mice treated with rotenone and in the MN9D cell model of dopaminergic neurons. The circ-Pank1 knockdown ameliorated dopaminergic neuron damage and locomotor dysfunction after the treatment with rotenone. We found that circ-Pank1 could adsorb miR-7a-5p and upregulate the expression of α-synuclein (α-syn), which is a molecular hallmark closely related to PD. The inhibition of miR-7a-5p reversed the circ-Pank1 knockdown-induced amelioration of dopaminergic neuron injury. In conclusion, circ-Pank1 is overexpressed in PD and enhances the locomotor dysfunction via the miR-7a-5p/α-syn signaling axis. We revealed the functional role of circRNAs in the progression of PD and provided a potential target for noncoding RNAs in delaying the progression of PD.

In order to devise more effective penetration enhancers, 4-O-acylterpineol derivatives which were expected to be hydrolyzed into nontoxic metabolites by esterase in the living epidermis, were synthesized from 4-terpineol (4-TER) enantiomers and straight chain fatty acids. Their promoting activities on the SR-flurbiprofen and its enantiomers were tested across full-thickness rabbit skin, as well as to correlate under in vitro and in vivo conditions. The permeation studies indicated that both d-4-O-acylterpineol and l-4-O-acylterpineol had significant enhancing effects, interestingly, d-4-O-aclyterpineol had higher enhancing effects than l-4-O-aclyterpineol with the exception of d-4-methyl-1-(1-methylethyl)-3-cyclohexen-1-yl octadec-9-enoate (d-4-T-dC18). The mechanism of 4-O-acylterpineol facilitating the drug penetration across the skin was confirmed by Attenuated total reflection-Fourier transformed infrared spectroscopy (ATR-FTIR) and molecular simulation. The mechanism of penetration enhancers promoting drug release was explored by the in vitro release experiment. Finally, a relative safety skin irritation of enhancers was also investigated by in vivo histological evaluation. The present research suggested that d-4-O-aclyterpineol and l-4-O-aclyterpineol could significantly promote the penetration of SR-flurbiprofen and its enantiomers both in vitro and in vivo, with the superiorities of high flux and low dermal toxicity.

To explore the structure-activity connections of amphiphilic permeation enhancers containing the length of the hydrophobic chains as well as the properties of the polar head

The aim of this investigation was to develop an etomidate intravenous lipid emulsion (ETM-ILE) and evaluate its properties in vitro and in vivo. Etomidate (ETM) is a hydrophobic drug, and organic solvents must be added to an etomidate injectable solution (ETM-SOL) to aid dissolution, that causes various adverse reactions on injection. Lipid emulsions are a novel drug formulation that can improve drug loading and reduce adverse reactions. ETM-ILE was prepared using high-pressure homogenization. Univariate experiments were performed to select key conditions and variables. The proportion of oil, egg lecithin, and poloxamer 188 (F68) served as variables for the optimization of the ETM-ILE formulation by central composite design response surface methodology. The optimized formulation had the following characteristics: particle size, 168.0 ± 0.3 nm; polydispersity index, 0.108 ± 0.028; zeta potential, −36.4 ± 0.2 mV; drug loading, 2.00 ± 0.01 mg/mL; encapsulation efficiency, 97.65% ± 0.16%; osmotic pressure, 292 ± 2 mOsmol/kg and pH value, 7.63 ± 0.07. Transmission electron microscopy images showed that the particles were spherical or spheroidal, with a diameter of approximately 200 nm. The stability study suggested that ETM-ILE could store at 4 ± 2 °C or 25 ± 2 °C for 12 months. Safety tests showed that ETM-ILE did not cause hemolysis or serious vascular irritation. The results of the pharmacokinetic study found that ETM-ILE was bioequivalent to ETM-SOL. However, a higher concentration of ETM was attained in the liver, spleen, and lungs after administration of ETM-ILE than after administration of ETM-SOL. This study found that ETM-ILE had great potential for clinical applications.

Antioxidant response transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2/Nfe2l2) is a neuroprotective agent in learning and memory impairment. This study provides a new perspective to explore the regulatory mechanisms of Nrf2. Here, we found that Nrf2 regulated circular RNA circ-Vps41 to increase hippocampal synaptic plasticity; Nrf2 bound the Vps41 promoter to activate transcription of the Vps41 gene and promote expression of circ-Vps41; circ-Vps41 positively correlated with Nrf2, synaptic plasticity, and learning and memory but negatively correlated with reactive oxygen species; and Nrf2 promoted CaMKIV expression by increasing levels of circ-Vps41, which can absorb miR-26a-5p that targets CaMKIV. Our findings revealed a new circRNA-based regulatory network regulated by Nrf2 and provided novel insights into the potential mechanism involved in the improvement of learning and memory impairment.

Self-grooming is a complex behavior with important biological functions and pathological relevance. How the brain coordinates with the spinal cord to generate the repetitive movements of self-grooming remains largely unknown. Here, we report that in the caudal part of the spinal trigeminal nucleus (Sp5C), neurons that express Cerebellin-2 (Cbln2

Today, the need for quality education forces translation talents to play a more complex role in language service and international communication. Based on teaching the above five qualities of language, intercultural, interdisciplinary, technological and moral, translation education can move to a new stage of development and provide more qualified and well-rounded talents, which will definitely affect every aspect of rapid social development in a positive way. In the new era, talented translators must have multiple qualities to meet the needs of the language service and international communication. Translator training must depend on all-round development, and quality multidimensional education needs to be strengthened, including quality language education, cross-cultural education, interdisciplinary education, educational technology and moral education. Through cutting-edge educational concept development, longterm planning of learning goals, meticulous alumni fulfillment, meticulous curriculum development and diligent innovative approaches to learning, a win-win situation with knowledge and talent quality. can be achieved in such a way as to promote economic development and social progress.

Translation specialists play an important role in economic transformations and social development of society, and the focus of their curriculum directly determines the comprehensive development of students’ knowledge, abilities and competencies. The article discusses how to optimize a translation training program based on four aspects: the principle of formulation, learning objectives, graduation requirements, and the curriculum system. Developing a talent education program is one of the key challenges in higher education reform, which is related to whether the quality of talent education can meet the needs of economic transformation and social development. An effective training program for translators will help formulate learning objectives, optimize the curriculum system, and improve the learning regimes for applied and interdisciplinary translators. The training program for the translation specialty is a multidimensional system. In accordance with the OBE principle, learning objectives and graduation requirements should be detailed and the curriculum should be installed in a module, which can contribute to improving the quality of the translation workforce. This, undoubtedly, will contribute to the further development of education reform and the penetration of innovations into the educational process, improving the quality of teaching translation., Специалисты по переводу играют важную роль в экономических преобразованиях и социальном развитии общества, а направленность их учебной программы напрямую определяет всестороннее развитие знаний, способностей и компетенций студентов. В статье обсуждается, как оптимизировать программу обучения переводческих кадров, исходя из четырех аспектов: принципа формулировки, целей обучения, требований к выпуску и системы учебного плана. Разработка программы обучения талантов – одна из ключевых задач реформы высшего образования, которая связана с тем, может ли качество обучения талантов соответствовать потребностям экономической трансформации и социального развития. Эффективная программа обучения для переводчиков поможет сформулировать цели обучения, оптимизировать систему учебных программ и усовершенствовать режимы обучения прикладных и междисциплинарных переводчиков. Программа подготовки кадров для переводческой специальности – это многомерная система. В соответствии с принципом OBE, цели обучения и требования к выпуску должны быть детально проработаны, а учебная программа должна быть установлена в модуле, что может способствовать повышению качества переводческих кадров. Это, несомненно, будет способствовать дальнейшему развитию реформы образования и проникновению инноваций в образовательный процесс, улучшению качества обучения переводу.

In the new era of rapid development of artificial intelligence (AI), the cultivation of translation talents pays more attention to the integrative application of language and technology. The construction of translation technology curriculum has become the focus of teaching reform of translation major in higher education. A multi-dimensional innovative system is about to emerge, which mainly covers the construction of course content, teaching and assessment modes, teaching staff, teaching materials, laboratories and industry-universityresearch cooperative platform. Under the function of collaborative innovation, translation technology courses will give full play to their practical application advantages, help to build a high-quality talent team of language service industry, and contribute to social progress.

Ethnopharmacological relevance Xiaoyao powder (XYP) is a traditional Chinese medicine formula which has wide scope of indications related to liver stagnation, reconcile qi and blood in TCM syndrome. Infertility can induce similar symptoms and signs to the clinical features of liver stagnation syndrome, the treatment of infertility by soothing the liver is obvious. XYP can increase the clinical pregnancy rate, follicle development, oocyte quality and improve endometrial receptivity. However, its underlying pharmacological mechanism of improving endometrial receptivity is unclear. Aim of the study The aim of the study was to investigate the effect of XYP on pregnancy rates and endometrial angiogenesis, to determine the potent mechanism in association with the pro-angiogenic behavior which closely related to improving endometrial receptivity. Materials and methods We established an animal model exhibiting decreasing endometrial receptivity by controlled ovarian hyperstimulation and a human endometrial microvascular endothelial cell (HEMEC) model. Endometrial morphology was observed by hematoxylin-eosin staining and Scanning electron microscopy. Western blot and qRT-PCR analysis were used to detect expression of PCNA, Cyclin D1, MMP9 and MAPK signaling pathway. Scratch-wound assay and tube formation assay were used to observe HEMEC migration and tubulogenesis. Results The results demonstrated that XYP pretreatment could improve endometrial receptivity, which leads to high pregnancy rates. In the endometrium, XYP facilitated angiogenesis by promoting tube formation. XYP could enhance HEMEC proliferation and migration induced by VEGF, which were observed by the microscope and Scratch-wound assays. XYP promoted HEMEC proliferation and migration via the p38 and JNK MAPK signaling pathways. Conclusion XYP promotes HEMEC proliferation and migration via the P38 and the JNK MAPK signaling pathways, which contribute to the endometrial angiogenesis mediated by VEGFR-2 that is favorable for endometrial receptivity. We firstly elucidated the molecular mechanisms by which XYP improved endometrial receptivity by promoting angiogenesis.

Vascular endothelial growth factor receptor-2 (VEGFR-2) regulates the mitogen-activated protein kinase (MAPK) signaling pathway and plays an important role in angiogenesis. Bu Shen Zhu Yun decoction (BSZYD) can improve endometrial receptivity and embryo implantation rates in patients undergoing in vitro fertilization. However, whether BSZYD improves endometrial receptivity via angiogenesis remains unclear. Here, we investigated the effects of BSZYD on the proliferation, migration, and angiogenesis of human endometrial microvascular endothelial cells (HEMECs) and found that BSZYD upregulated the expression of cyclin D1, matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen (PCNA) in HEMECs. Cell Counting Kit 8 assay, scratch-wound assay, and Tube Formation Assay results showed that BSZYD promoted the proliferation, migration, and angiogenesis of HEMECs. Western blot analysis results revealed the activation of the MAPK signaling pathway by BSZYD through the upregulation of VEGF and VEGFR-2 expression. Together, these findings highlight the novel mechanism underlying BSZYD-mediated improvement in endometrial receptivity through the MAPK signaling pathway.

Grouping genes as operons is an important genomic feature of prokaryotic organisms. The comprehensive understanding of the operon organizations would be helpful to decipher transcriptional mechanisms, cellular pathways, and the evolutionary landscape of prokaryotic genomes. Although thousands of prokaryotes have been sequenced, genome-wide investigation of the evolutionary dynamics (division and recombination) of operons among these genomes remains unexplored. Here, we systematically analyzed the operon dynamics of Rhodococcus jostii RHA1 (RHA1), an oleaginous bacterium with high potential applications in biofuel, by comparing 340 prokaryotic genomes that were carefully selected from different genera. Interestingly, 99% of RHA1 operons were observed to exhibit evolutionary events of division and recombination among the 340 compared genomes. An operon that encodes all enzymes related to histidine biosynthesis in RHA1 ( His -operon) was found to be segmented into smaller gene groups (sub-operons) in diverse genomes. These sub-operons were further reorganized with different functional genes as novel operons that are related to different biochemical processes. Comparatively, the operons involved in the functional categories of lipid transport and metabolism are relatively conserved among the 340 compared genomes. At the pathway level, RHA1 operons found to be significantly conserved were involved in ribosome synthesis, oxidative phosphorylation, and fatty acid synthesis. These analyses provide evolutionary insights of operon organization and the dynamic associations of various biochemical pathways in different prokaryotes.

Tight matrix has relatively low permeability and porosity, with abundant micro/nano pores. The capillary force in these pores are relatively strong, making the wetting liquid easier to be imbibed in the matrix. This process is called spontaneous imbibition. The complexity of pore structure is identified as one of the key factors influencing the imbibition process, but the detailed mechanism is not clear. Thus, in this work, a method is proposed to evaluate the influence of pore structure on imbibition process. Pore structure has fractal properties in a specific scale. By using the fractal theory, an imbibition model is provided to analyze the influence of microscopic structures on spontaneous imbibition, considering the pore size distribution and pore connectivity. Also, based on this model, the influencing factors on dimensionless imbibition and diffusion rate are discussed. Results show that the pore structure has more branches, larger and shorter sub-throats has higher chance to gain a high imbibition rate. Finally, a 3D imbibition parameter cube is constructed to determine the parameter combinations in favor of strong water diffusion potential. By utilizing the analysis method based on the fractal theory, we can effectively evaluate the imbibition potential. It is helpful to provide a guidance to evaluate the water imbibition to gas production.

Although hippocampus-derived androgens play an important role in hippocampal synaptic plasticity, studies at the cellular level have received relatively less attention. Furthermore, the underlying signalling pathways associated with synaptic plasticity remain unclear. Results of the present study demonstrated that testosterone treatment of primary cultured rat hippocampal neurons resulted in a rapid increase in spine density, accompanied by the elevation of protein and messenger RNA levels of synaptophysin, developmentally regulated brain protein (Drebrin), and the N-methyl-D-aspartate receptor NR1 subunit. Testosterone treatment also increased the phosphorylation levels of extracellular-regulated protein kinase (ERK)1/2 and cAMP-responsive element binding protein (CREB), rather than p38 and Jun N-terminal kinase (JNK). U0126 significantly reversed the testosterone-mediated phosphorylation of CREB. Importantly, the increase in spine density was not induced by testosterone under U0126 treatment. These findings suggest that the ERK1/2-CREB signalling pathway plays an important role in testosterone-mediated rapid spinogenesis of cultured rat hippocampal neurons. Results of this study will be helpful in further clarifying the physiological function of testosterone and related signalling pathways in vitro.

Micro-displacement behavior during hydraulic fracturing greatly influences damage formation. Formation temperature and the non-Newtonian behavior of fracturing liquid are the major influencing factors in the micro-displacement process. In this work, to investigate the influencing factors on micro-displacement process, we built a mathematical model for the micro-displacement of a fracturing liquid on the basis of the fractal theory. Then, the analytical expression for penetration equation was obtained according to the model, and explicit solution for the relationship between the volume driven into formation and time was derived. Finally, the influences of non-Newtonian behavior, formation temperature, wettability, and pore size complexity on the micro-displacement process were discussed. Results show that the decrease in formation temperature or decrease in the non-Newtonian degree of fracturing liquid reduce fracturing liquid leakage.

In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz) ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

Normal aging is characteristic with the gradual decline in cognitive function associated with the progressive reduction of structural and functional plasticity in the hippocampus. Repetitive transcranial magnetic stimulation (rTMS) has developed into a novel neurological and psychiatric tool that can be used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency rTMS (≤1Hz) affects synaptic plasticity in rats with vascular dementia (VaD), and it ameliorates the spatial cognitive ability in mice with Aβ1-42-mediated memory deficits, but there are little concerns about the effects of rTMS on normal aging related cognition and synaptic plasticity changes. Thus, the current study investigated the effects of rTMS on spatial memory behavior, neuron and synapse morphology in the hippocampus, and synaptic protein markers and brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) in normal aging mice, to illustrate the mechanisms of rTMS in regulating cognitive capacity. Relative to adult animals, aging caused hippocampal-dependent cognitive impairment, simultaneously inhibited the activation of the BDNF-TrkB signaling pathway, reduced the transcription and expression of synaptic protein markers: synaptophysin (SYN), growth associated protein 43 (GAP43) and post-synaptic density protein 95 (PSD95), as well as decreased synapse density and PSD (post-synaptic density) thickness. Interestingly, rTMS with low intensity (110% average resting motor threshold intensity, 1Hz, LIMS) triggered the activation of BDNF and TrkB, upregulated the level of synaptic protein markers, and increased synapse density and thickened PSD, and further reversed the spatial cognition dysfunction in aging mice. Conversely, high-intensity magnetic stimulation (150% average resting motor threshold intensity, 1Hz, HIMS) appeared to be detrimental, inducing thinning of PSDs, disordered synaptic structure, and a large number of lipofuscin accumulations, as well as reducing the number of synapses and downregulating BDNF-TrkB and synaptic proteins. Ultimately, HIMS further impaired the capacity for learning and memory. In conclusion, we infer that aging-induced cognitive deficits are closely associated with hippocampal structural synaptic plasticity, and low-frequency magnetic stimulation plays an important role in regulating cognitive behavior via changing structural synaptic plasticity, and BDNF signaling might participate in this event.

Repetitive transcranial magnetic stimulation (rTMS) is a neuropsychiatric tool that can be used to investigate the neurobiology of learning and cognitive function. Few studies have examined the effects of low frequency (⩽1Hz) magnetic stimulation (MS) on structural synaptic plasticity of neurons in vitro, thus, the current study examined its effects on hippocampal neuron and synapse morphology, as well as synaptic protein markers and signaling pathways. Similarly, both intensities of low frequency magnetic stimulation (1Hz) activated brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) pathways, including the pathways for mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and for phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt). Specifically, low intensity magnetic stimulation (LIMS, 1.14Tesla, 1Hz) promoted more extensive dendritic and axonal arborization, as well as increasing synapses density, thickening PSD (post synaptic density) and upregulation of synaptophysin (SYN), growth associated protein 43 (GAP43) and post synaptic density 95 (PSD95). Conversely, high intensity magnetic stimulation (HIMS, 1.55Tesla, 1Hz) appeared to be detrimental, reducing dendritic and axonal arborization and causing apparent structural damage, including thinning of PSD, less synapses and disordered synaptic structure, as well as upregulation of GAP43 and PSD95, possibly for their ability to mitigate dysfunction. In conclusion, we infers that low frequency magnetic stimulation participates in regulating structural synaptic plasticity of hippocampal neurons via the activation of BDNF-TrkB signaling pathways.

Descriptive statistics for six traits related to early maturity in four different environments. Table S2. Correlations between the WGPs and related traits based on 185 upland cotton accessions in four environments. Table S3. Single nucleotide polymorphisms (SNPs) significantly associated with traits related to early maturity in upland cotton, as determined using the GLM and MLM. Table S4. Information on 185 upland cotton germplasms. Table S5. qRT-PCR primers. (DOCX 45 kb)

This research established a sensitive and efficient pre-column derivatization HPLC method based on dispersive liquid-liquid microextraction (DLLME) for the simultaneous determination of six steroidal and phenolic endocrine disrupting chemicals (EDCs). In this study, EDCs were firstly labeled by the derivatization reagent 2-(11H-benzo[a]carbazol-11-yl) ethyl carbonochloridate (BCEC-Cl) and then extracted by DLLME. The response surface methodology was employed to investigate the key parameters of pre-column derivatization and DLLME. Under the optimal conditions, a good linear relationship between the peak area and the concentration of analytes was observed with correlation coefficients of >0.9991. Limits of detection for all EDCs derivatives were achieved within the range of 0.02-0.07 μg L(-1). The proposed method has the advantages of simple operation, low consumption of organic solvent, saving time, low output limit and good selectivity. When applied to several food and water samples analysis, it demonstrated good applicability for the determination of EDCs.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized pathologically by the abnormal deposition of extracellular amyloid-β (Aβ) oligomers. However, the nature and precise mechanism of the toxicity of Aβ oligomers are not clearly understood. Aβ oligomers have been previously shown to cause a major loss of EphB2, a member of the EphB family of receptor tyrosine kinases. To determine the effect of EphB2 on Aβ oligomer-induced neurotoxicity and the underlying molecular mechanisms, we examined the EphB2 gene in cultured hippocampal neurons. Using a cellular model of AD, Aβ1-42 oligomers were confirmed to induce neurotoxicity in a time-dependent manner and result in a major decrease of EphB2. EphB2 overexpression could prevent the neurotoxicity of hippocampal neurons from exposure to Aβ1-42 oligomers for 1h. Further analysis revealed that EphB2 overexpression increased synaptic NR1 and NR2B expression in Aβ1-42 oligomer-treated neurons. Moreover, EphB2 overexpression prevented Aβ1-42 oligomer-induced downregulation of dephosphorylated p38 MAPK and phosphorylated CREB. Together, these results suggest that EphB2 is a factor which protects hippocampal neurons against the toxicity of Aβ1-42 oligomers, and we infer that the protection of EphB2 is achieved by increasing the synaptic NMDA receptor level and downstream p38 MAPK and CREB signaling in hippocampal neurons. This study provides new molecular insights into the neuroprotective effect of EphB2 and highlights its potential therapeutic role in the management of AD.

This study was undertaken to investigate the protective effects and potential mechanism of testosterone (T) on cognitive performance in adult male rats given bilateral intrahippocampal injections of beta amyloid 1-42 oligomers (Aβ1-42) combined with gonadectomy (Aβ+GDX). A series of experiments were designed to verify the optimal administration time and dose of T and to explore its potential protective mechanisms on spatial ability in Aβ+GDX rats in the Morris water maze test. Aβ1-42 was injected only once two weeks before testing, while T and the androgen receptor (AR) antagonist flutamide (F) were administered daily beginning 2 days before and throughout the 6 days of testing. The Aβ1-42 injection and GDX individually impaired cognitive performance, and the combination of these treatments was additive, leading to even greater impairment. The serum T level peaked at 48 h after administration. T doses ranging from 0.25 to 1.00 mg corresponding to serum T levels of 4.5-21.35 ng/ml improved the spatial ability. Animals administered 0.75 mg of T corresponding to the serum T level of 15.2 ng/ml had the most significantly improved behavioral performances. However, higher T doses of 1.50 and 2.00 mg resulting in serum T levels of 34.8 and 45 ng/ml, respectively, impaired the behavioral performances. F had no effect on the serum T level and spatial ability, but it blocked the activational effect of T. These findings indicate that the effect of T on behavioral performances is partly mediated through ARs.