Stimuli directed towards activation of apoptosis mechanisms are an attractive approach to eliminate evasion of apoptosis, a ubiquitous cancer hallmark. In these in vitro studies, kinetics and electric field thresholds for several apoptosis characteristics are defined in E4 squamous carcinoma cells (SCC) exposed to ten 300 ns pulses with increasing electric fields. Cell death was >95% at the highest electric field and coincident with phosphatidylserine externalization, caspase and calpain activation in the presence and absence of cytochrome c release, decreases in Bid and mitochondria membrane potential (Δψm) without apparent changes reactive oxygen species levels or in Bcl2 and Bclxl levels. Bid cleavage was caspase-dependent (55-60%) and calcium-dependent (40-45%). Intracellular calcium as an intrinsic mechanism and extracellular calcium as an extrinsic mechanism were responsible for about 30 and 70% of calcium dependence for Bid cleavage, respectively. The results reveal electric field-mediated cell death induction and progression, activating pro-apoptotic-like mechanisms and affecting plasma membrane and intracellular functions, primarily through extrinsic-like pathways with smaller contributions from intrinsic-like pathways. Nanosecond second pulsed electric fields trigger heterogeneous cell death mechanisms in E4 SCC populations to delete them, with caspase-associated cell death as a predominant, but not an unaccompanied event.

The main objective of this study was to demonstrate the proof-of-principle for the hypothesis that conjugated linoleic acid-paclitaxel conjugate (CLA-PTX), a novel fatty acid modified anti-cancer drug conjugate, could self-assemble forming nanoparticles. The results indicated that a novel self-assembling nanomedicine, CLA-PTX@PEG NPs (about 105 nm), with Cremophor EL (CrEL)-free and organic solvent-free characteristics, was prepared by a simple precipitation method. Being the ratio of CLA-PTX:DSPE-PEG was only 1:0.1 (w/w), the higher drug loading CLA-PTX@PEG NPs (about 90%) possessed carrier-free characteristic. The stability results indicated that CLA-PTX@PEG NPs could be stored for at least 9 months. The safety of CLA-PTX@PEG NPs was demonstrated by the MTD results. The anti-tumor activity and cellular uptake were also confirmed in the in vitro experiments. The lower crystallinity, polarity and solubility of CLA-PTX compared with that of paclitaxel (PTX) might be the possible reason for CLA-PTX self-assembling forming nanoparticles, indicating a relationship between PTX modification and nanoparticles self-assembly. Overall, the data presented here confirm that this drug self-delivery strategy based on self-assembly of a CLA-PTX conjugate may offer a new way to prepare nanomedicine products for cancer therapy involving the relationship between anticancer drug modification and self-assembly into nanoparticles.

Medium spiny neurons (MSNs) in the nucleus accumbens (NAc) undergo persistent alterations in their biological and physiological characteristics upon exposure to drugs of abuse. Previous studies demonstrated that the biochemical, morphological, and intrinsic physiological properties of MSNs are heterogeneous and provided new insights into the physiological and molecular roles of individual MSNs in addictive behaviors. However, it remains unclear whether MSNs in the NAc shell (NAcSh), an important region for mediating behavioral sensitization, are electrophysiologically heterogeneous and how such heterogeneity is relevant to neuroadaptation associated with drug addiction. Here, the membrane properties, i.e., the intrinsic excitability and spike adaptation, of MSNs in the NAcSh from saline- or morphine-treated rats were investigated in vitro by whole-cell recording. In saline-treated rats, three distinct cell types were identified by their membrane properties: type I neurons showed high levels of intrinsic excitability and rapid spike adaptation; type II neurons showed moderate levels of intrinsic excitability and relatively slow spike frequency adaptation; type III neurons showed low levels of intrinsic excitability and putative strong spike adaptation. MSNs in rats undergoing withdrawal from chronic morphine treatment (10-14 days after the last injection) also exhibited the typical firing behaviors of these three types of neurons. However, the membrane properties of the MSNs were differentially altered after withdrawal. There was an enhancement in intrinsic excitability in type II MSNs and a promotion of spike adaptation in type I MSNs. The apamin-sensitive afterhyperpolarization current (I(AHP)) and the apamin-insensitive I(AHP) of the NAcSh MSNs were attenuated after chronic morphine withdrawal. These findings suggest that individual MSNs in the NAcSh manifest unique electrophysiological properties, which might contribute to psychostimulant-induced neuroadaptation.

Like the anti-angiogenic strategy, anti-vascular mimicry is considered as a novel targeting strategy for glioma. In the present study, we used NGR as a targeting ligand and prepared NGR-modified liposomes containing combretastatin A4 (NGR-SSL-CA4) in order to evaluate their potential targeting of glioma tumor cells and vasculogenic mimicry (VM) formed by glioma cells as well as their anti-VM activity in mice with glioma tumor cells. NGR-SSL-CA4 was prepared by a thin-film hydration method. The in vitro targeting of U87-MG (human glioma tumor cells) by NGR-modified liposomes was evaluated. The in vivo targeting activity of NGR-modified liposomes was tested in U87-MG orthotopic tumor-bearing nude mice. The anti-VM activity of NGR-SSL-CA4 was also investigated in vitro and in vivo. The targeting activity of the NGR-modified liposomes was demonstrated by in vitro flow cytometry and in vivo biodistribution. The in vitro anti-VM activity of NGR-SSL-CA4 was indicated in a series of cell migration and VM channel experiments. NGR-SSL-CA4 produced very marked anti-tumor and anti-VM activity in U87-MG orthotopic tumor-bearing mice in vivo. Overall, the NGR-SSL-CA4 has great potential in the multi-targeting therapy of glioma involving U87-MG cells, and the VM formed by U87-MG cells as well as endothelial cells producing anti-U87-MG cells, and anti-VM formed by U87-MG cells as well as anti-endothelial cell activity.

To investigate the impact of Ramipril (RAM) on the expressions of insulin-like growth factor-1 (IGF-1) and renal mesangial matrix (RMM) in rats with diabetic nephropathy (DN).

Most of the pathophysiology of depression are still unknown because of its numerous disease states of distinct etiology and pathogenesis. Stressful rodent models have been used to test a number of hypotheses regarding the etiology of depression. The learned helplessness rodent model demonstrates that having no control at all over aversive events produces helplessness and depression, but the role of loss of control over aversive events in helplessness is still not reliably modelled or deeply investigated. A rodent model of helplessness produced by loss of control is closer to human conditions and is therefore more useful for novel mechanistic and pre-clinic studies. The present work proposed a triadic experimental design in which a Loss Of Control (LOC) group of mice was firstly exposed to escapable mild footshocks to acquire control, and then to inescapable shocks to lose control, with a yoked (L-Yoked) group receiving identical but always uncontrollable shocks. Although both the LOC and the L-Yoked groups developed helplessness, as compared with the naive control group, the helplessness exhibited in the LOC group was significantly more serious than that in the L-Yoked group. The difference in severity between the LOC and the L-Yoked groups demonstrates the effects of loss of control over aversive events, in addition to the effects of the aversive events per se. The LOC paradigm can be used to reproduce pathology of depression induced by loss of control over aversive life events, with a good constructive validity.

A GH49 dextranase gene DexKQ was cloned from marine bacteria Arthrobacter oxydans KQ11. It was recombinantly expressed using an Escherichia coli system. Recombinant DexKQ dextranase of 66 kDa exhibited the highest catalytic activity at pH 9.0 and 55 °C. kcat/Km of recombinant DexKQ at the optimum condition reached 3.03 s-1 μM-1, which was six times that of commercial dextranase (0.5 s-1 μM-1). DexKQ possessed a Km value of 67.99 µM against dextran T70 substrate with 70 kDa molecular weight. Thin-layer chromatography (TLC) analysis showed that main hydrolysis end products were isomalto-oligosaccharide (IMO) including isomaltotetraose, isomaltopantose, and isomaltohexaose. When compared with glucose, IMO could significantly improve growth of Bifidobacterium longum and Lactobacillus rhamnosus and inhibit growth of Escherichia coli and Staphylococcus aureus. This is the first report of dextranase from marine bacteria concerning recombinant expression and application in isomalto-oligosaccharide preparation.

The reliability of MyotonPRO that can monitor the mechanical properties of tissues is still unclear. This study aimed to analyze the within-day inter-operator and between-day intra-operator reliability of MyotonPRO for assessing tone and stiffness of quadriceps femoris and patellar tendon at different knee angles. The tone and stiffness of healthy participants (15 males and 15 females, aged 24.7±1.6 years) in the supine and resting position were measured using the MyotonPRO device. The measurements were quantified at 0°, 30°, 60°, and 90° of knee flexion. The intraclass correlation coefficient (ICC), standard error of measurement (SEM), and minimal detectable change (MDC) were calculated and a Bland-Altman analysis was conducted to estimate reliability. The results indicated excellent inter-operator reliability (ICC > 0.78) and good to excellent intra-operator reliability (ICC > 0.41). The inter-operator SEM measurements ranged between 0.1-0.9 Hz and 3.8-37.9 N/m, and intra-operator SEM ranged between 0.5-1.3 Hz and 7.9-52.0 N/m. The inter-operator MDC ranged between 0.3-2.5 Hz and 10.5-105.1 N/m, and intra-operator SEM ranged between 1.1-3.3 Hz and 21.9-144.1 N/m. The agreement of inter-operator was better than that of intra-operator. The study concluded that MyotonPRO is a reliable device to detect the tone and stiffness of quadriceps femoris and patellar tendon.

Angiotensin II (AngII) caused pulmonary microvascular endothelial barrier injury, which induced acute aortic dissection (AAD) combined with acute lung injury (ALI). However, the exact mechanism is unclear. We investigated the role of dephosphorylation of Y685-VE-cadherin in the AngII induced pulmonary microvascular endothelial barrier injury. Mice or pulmonary microvascular endothelial cells (PMVECs) were divided into control group, AngII group, AngII+PP2 (Src kinase inhibitor) group, and PP2 group. PP2 was used to inhibit the phosphorylation of Y685-VE-cadherin. Pathological changes, infiltration of macrophages and neutrophils, and pulmonary microvascular permeability were used to determine the pulmonary microvascular endothelial barrier function. Flow cytometry was used to determine the apoptosis of PMVECs, and immunofluorescence was used to determine the skeletal arrangement. Transendothelial resistance was used to detect the permeability of endothelial barrier. Phosphorylation of Y685-VE-cadherin was significantly reduced after AngII stimulation (P < 0.05), together with skeletal rearrangement, and elevation of endothelial permeability which finally induced endothelial barrier injury. After PP2 interference, the phosphorylation of Y685-VE-cadherin was further reduced and the endothelial permeability was further elevated. These data indicated that AngII could induce pulmonary injury by triggering endothelial barrier injury, and such process may be related to the dephosphorylation of Y685-VE-cadherin and the endothelial skeletal rearrangement.

[This corrects the article DOI: 10.1155/2017/1917804.].

As an inflammation-related cytokine, interleukin (IL)-5 has been reported to be involved in the development of cardiovascular diseases, such as chronic heart failure and atherosclerosis. However, the role of IL-5 in acute aortic dissection (AAD) has barely been explored.

No abstract available

Individuals with autism spectrum disorder (ASD) display dysfunction in learning from environmental stimulus that have positive or negative emotional values, posing obstacles to their everyday life. Unfortunately, mechanisms of the dysfunction are still unclear. Although early intervention for ASD victims based on reinforcement learning are commonly used, the mechanisms and characteristics of the improvement are also unknown. By using a mice model of ASD produced by prenatal exposure to valproic acid (VPA), the present work discovered a delayed response-reinforcer forming, and an impaired habit forming in a negative reinforcement learning paradigm in VPA exposure male offspring. But the extinction of the learned skills was found to become faster than normal male animals. Since escape action of nosepoking and the motility remain unchanged in the VPA male offspring, the impaired learning and the accelerated extinction are caused by deficits in higher brain functions underlying association between the animals' behavioral responses and the outcomes of such responses. The results further suggest that the rodent ASD model produced by prenatal exposure to VPA reproduces the deficits in reasoning or building the contingency between one's own behaviors and the consequent outcomes of the behavior seen in ASD patients.

Cardiovascular and cerebrovascular diseases have become a severe threat for human health worldwide, however, optimal therapeutic options are still developed. Zhilong Huoxue Tongyu capsule (ZL capsule) is mainly composed of Astragalus membranaceus, Leech, Earthworm, Cinnamomum cassia and Sargentodoxa cuneata, having functions of replenishing qi and activating blood, dispelling wind and reducing phlegm. It is an expanded application on the basis of traditional uses of above TCMs, acquiring a satisfactory curative effect on cardiovascular and cerebrovascular diseases over twenty years.

Reinforcement learning relies on the reward prediction error (RPE) signals conveyed by the midbrain dopamine system. Previous studies showed that dopamine plays an important role in both positive and negative reinforcement. However, whether various reinforcement processes will induce distinct learning signals is still unclear. In a probabilistic learning task, we examined RPE signals in different reinforcement types using an electrophysiology index, namely, the feedback-related negativity (FRN). Ninety-four participants were randomly assigned into four groups: base (no money incentive), positive reinforcement (presentation of money rewards), negative reinforcement (removal of money losses), and combined reinforcement (money rewards and removal of money losses) groups. In addition, in order to evaluate the engagement of emotional activity in the different reinforcement processes, Positive and Negative Affect Schedule-Expanded Form (PANAS-X) scales were applied before and after the experiment to detect the emotional changes. The results showed that there was no difference between groups in the dopamine-related learning bias. However, compared to the other three groups, negative reinforcement elicited smaller FRN (the difference-wave measure) during the learning, stronger positive affect and joviality, and less fatigue after the learning, in which the difference between the negative and positive reinforcement groups was smaller. The results indicated that pure avoidance motivation may induce distinct emotional fluctuations, which influence the feedback processing.

The number of grains per unit land area is the most important grain yield component in Chinese milk vetch. Flower and pod survival seem to be critical determinants of grain number, which is related to the number of fertile flowers and pods during the anthesis period. Flower and pod growth are frequently considered the key determinants to establish grain number. The objective of this study was to explore the influences of paclobutrazol on flower and pod development, grain-setting characteristics and grain yield in Chinese milk vetch under different concentrations of foliar spray and try to explore the physiological regulatory mechanisms. Field experiments were carried out during the 2017-2018 and 2018-2019 growing seasons at the Dayuzhuang experimental field. The experiment involved the Chinese milk vetch cultivar "Xinzi No. 1" and six levels of foliar application of paclobutrazol, 0, 200, 300, 400, 500, and 600 mg L-1, in treatments CK, T1, T2, T3, T4, and T5, respectively. Foliar spray was applied once, at the squaring stage. In comparison with the CK treatment, all of the paclobutrazol treatments yielded, to various degrees, increased values of the number of inflorescences per unit area, number of pods per unit area, grain-setting rate of pods, and number of grains per pod in all six inflorescence layers, with the largest increases observed in the T3 treatment. In the T3 treatment compared with the CK treatment, from the first to sixth inflorescence layers, the number of inflorescences per unit area was increased by 34.07-58.97%, the number of pods per unit area was increased by 39.69-68.35%, the grain number per pod was increased by 44.31-53.69%, and the grain-setting rate of pods was increased by 1.84-4.89%. An analysis of yield composition revealed that the paclobutrazol spray treatment had little impact on the grain weight of Chinese milk vetch. The correlations between the concentration of paclobutrazol spray and the grain yield of Chinese milk vetch reached a significant level. Grain yield was highest at the paclobutrazol concentration of 373.10 mg/L. The inflorescence contents of gibberellic acid 3 (GA3), indole-3-acetic acid (IAA), and abscisic acid (ABA) were reduced, whereas that of cytokinin (CTK) was increased, by foliar application of paclobutrazol (400 mg L-1, T3 treatment) relative to CK treatment during the stages of flowers and pods developing into grains.

Autism spectrum disorders (ASD) represent a group of neurodevelopmental defects characterized by social deficits and repetitive behaviors. Alteration in Glycosylation patterns could influence the nervous system development and contribute to the molecular mechanism of ASD. Interaction of environmental factors with susceptible genes may affect expressions of glycosylation-related genes and thus result in abnormal glycosylation patterns. Here, we used an environmental factor-induced model of autism by a single intraperitoneal injection of 400 mg/kg valproic acid (VPA) to female rats at day 12.5 post-conception. Following confirmation of reduced sociability and increased self-grooming behaviors in VPA-treated offspring, we analyzed the alterations in the expression profile of glycan patterns and glycan-related genes by lectin microarrays and RNA-seq, respectively. Lectin microarrays detected 14 significantly regulated lectins in VPA rats, with an up-regulation of high-mannose with antennary and down-regulation of Siaα2-3 Gal/GalNAc. Based on the KEGG and CAZy resources, we assembled a comprehensive list of 961 glycan-related genes to focus our analysis on specific genes. Of those, transcription results revealed that there were 107 differentially expressed glycan-related genes (DEGGs) after VPA treatment. Functional analysis of DEGGs encoding anabolic enzymes revealed that the process trimming to form core structure and glycan extension from core structure primarily changed, which is consistent with the changes in glycan patterns. In addition, the DEGGs encoding glycoconjugates were mainly related to extracellular matrix and axon guidance. This study provides insights into the underlying molecular mechanism of aberrant glycosylation after prenatal VPA exposure, which may serve as potential biomarkers for the autism diagnosis.

The yellow nutsedge (Cyperus esculentus L. 1753) is an unconventional oil plant with oil-rich tubers, and a potential alternative for traditional oil crops. Here, we reported the first high-quality and chromosome-level genome assembly of the yellow nutsedge generated by combining PacBio HiFi long reads, Novaseq short reads, and Hi-C data. The final genome size is 225.6 Mb with an N50 of 4.3 Mb. More than 222.9 Mb scaffolds were anchored to 54 pseudochromosomes with a BUSCO score of 96.0%. We identified 76.5 Mb (33.9%) repetitive sequences across the genome. A total of 23,613 protein-coding genes were predicted in this genome, of which 22,847 (96.8%) were functionally annotated. A whole-genome duplication event was found after the divergence of Carex littledalei and Rhynchospora breviuscula, indicating the rich genetic resources of this species for adaptive evolution. Several significantly enriched GO terms were related to invasiveness of the yellow nutsedge, which may explain its plastic adaptability. In addition, several enriched Kyoto Encyclopedia of Genes and Genomes pathways and expanded gene families were closely related with substances in tubers, partially explaining the genomic basis of characteristics of this oil-rich tuber.

The association between spinal cord injury (SCI) and bladder symptoms has been intensively described. Human umbilical cord mesenchymal stem cell (hUC-MSC) treatment is beneficial to the recovery of bladder function after SCI, but its mechanism is unclear. We established an SCI model, and prepared hUC-MSCs in advance, followed by verification using flow cytometry. The Basso, Beattie and Bresnahan (BBB) score and urodynamic index were employed to evaluate motor function and bladder functions, respectively. Hematoxylin-eosin staining, luxol fast blue staining, and Masson's trichrome staining were utilized to assess pathological changes. Real-time quantitative PCR and Western blot were used to determine the mRNA and protein expressions in bladder tissues. The immunophenotypes of the HUC-MSCs were CD90+ and CD105+, but CD34-, CD45- and HLA-DR-. Rats appeared severe motor dysfunction after SCI, but the BBB score was increased in hUC-MSCs after the second week. Pathologically, the improvement of the lesion area on the dorsal spinal cord, augmented anterior gray horn neuron cells of the spinal cord and lessened bladder tissue remodeling (fibrosis, collagen deposition) as well as modulated inflammation could be observed. Besides, SCI increased bladder weight, bladder capacity, urine volume and residual urine volume, and decreased urination efficiency. HUC-MSCs ameliorated SCI-induced pathological changes and bladder functions, the expressions of Collagen I, Collagen III, fibroblast growth factor 2 (FGF2), phospho-p38, transient receptor potential vanilloid 1, Toll-like receptor 4 and phospho-nuclear factor-kappa B (p-NF-κB). To sum up, HUC-MSCs contribute to the reconstruction of bladder function after SCI by repressing p38 MAPK/NF-κB pathway.

Our previous studies have demonstrated a protective role of Zhilong Huoxue Tongyu capsule in atherosclerosis (AS); however, the molecular mechanisms are unclear.