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To promote the controlled release efficacy of nanocomposites based on alginate and bentonite, (3-chloro-2-hydroxypropyl)trimethyl ammonium grafted starch was prepared and used as modifying agent of the clay. The nanocomposites were characterized by FTIR, XRD, SEM and TG analysis, to reveal the structural effects on the swelling property of the matrix and the release of alachlor, the model compound. Thermodynamics study indicated that the adsorption of alachlor on the bentonite was dominated by hydrophobic interaction with the siloxane surface of the clay and enhanced by the binding of the cationic starch. The electrostatic attraction between alginate and cationic starch bound on the surface also decreased the aggregation of bentonite platelets, leading to a more compact structure of the nanocomposites. The higher adsorption capability and lower permeability of the matrix resulted in a slower release of alachlor, which was dominated by Fickian diffusion mechanism. The release of alachlor first decreased and then increased with increasing content of bentonite and cationic starch modified bentonite in the nanocomposites, reaching a minimum around weight percentage 10%, at which the time taken for 50% of active ingredient to be released were 4.4 and 7.3 times that for the release from pure alginate hydrogel.

The nanocomposite gel prepared from nanoclay and natural polysaccharides showed a good sustained-release property. Herein, a cationic cellulose-modified bentonite-alginate nanocomposite gel was prepared and used to enhance the sustained release of alachlor. The underlying effect and mechanism of the structure of modified bentonite-alginate nanocomposite gels on the release behavior of alachlor were explored by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric (TG) analysis. The results showed that the release of alachlor from the nanocomposite gels was dominated by Fickian diffusion and closely related to the adsorption capacity and permeability of the matrix. The cationic cellulose intercalated into the interlayer space of bentonite through an ion exchange reaction, which significantly enhanced the hydrophobicity of bentonite and its interaction with alachlor. The stacking aggregation of bentonite nanoplatelets and permeability of the gel network were decreased through the electrostatic interaction between cationic cellulose and alginate molecular chains, thus remarkably enhancing the sustained-release property of the nanocomposite gel. The release kinetics revealed that the release rate of alachlor from the nanocomposite gel first decreased and then increased as the content of bentonite and modified bentonite gradually increased. Also, the best sustained-release property of the nanocomposite gel was obtained at bentonite and modified bentonite additions of about 10%, under which the release time of 50% alachlor (

RNAs (circRNAs) play critical roles in many diseases, including atherosclerosis (AS). However, the role and underlying mechanism of circ_0002984 in AS remain unclear. Vascular smooth muscle cells (VSMCs) treated with oxidized low-density lipoprotein (ox-LDL) were used as a AS cell model. Quantitative real-time polymerase chain reaction was conducted to detect the expression of circ_0002984, miR-181b-5p and vascular endothelial growth factor A (VEGFA). Cell proliferation was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide assay and 5-ethynyl-2'-deoxyuridine assays. Cell migration was assessed using wound healing assay and transwell assay. All protein levels were analyzed by western blot assay. The interaction between miR-181b-5p and circ_0002984 or VEGFA was confirmed by dual-luciferase reporter, RNA Immunoprecipitation, and RNA pull-down assays. Circ_0002984 and VEGFA were overexpressed, and miR-181b-5p was downregulated in serum of AS patients and ox-LDL-stimulated VSMCs. Circ_0002984 silencing inhibited ox-LDL-induced proliferation and migration in VSMCs. MiR-181b-5p was a target of circ_0002984, and miR-181b-5p inhibition counteracted the suppressing effects of circ_0002984 downregulation on proliferation and migration in ox-LDL-stimulated VSMCs. Additionally, VEGFA was a downstream target of miR-181b-5p and VEGFA upregulation abolished the suppressive influence of miR-181b-5p on proliferation and migration in ox-LDL-exposed VSMCs. Furthermore, circ_0002984 depletion blocked phosphatidylinositol 3 kinase-AKT signaling pathway by regulating miR-181b-5p and VEGFA. Circ_0002984 downregulation suppressed cell proliferation and migration by regulating miR-181b-5p/VEGFA axis and phosphatidylinositol 3 kinase-AKT pathway in ox-LDL-stimulated VEGFA, providing a new mechanism for AS pathogenesis.

Objective: To explore the molecular mechanism by which hippocampal neural stem cell (HNSC) exosome (exo)-derived MIAT improves cognitive disorders in rats with vascular dementia (VD). Methods: Rat hippocampal tissues were collected, and HNSCs and hippocampal neuronal cells (HNCs) were isolated, purified, and identified. Then the exosomes (exo) of the HNSCs were extracted and identified. A VD rat model was constructed. HE staining was used to evaluate the hippocampal pathology in each group. The expressions of the RNAs in the HNSCs were intervened, and the cells were then grouped. ELISA was used to measure the of TNF-α, IL-1, and Aβ1-42 expression levels. The kits were used to determine the oxidative stress factor levels. The targeting relationships among MIAT, miR-34b-5p, and CALB1 were measured using dual-luciferase assays. The MIAT expressions in exo were measured using qRT-PCR. The proliferation and apoptosis of the HNCs were determined using CCK-8 and Annexin V-FITC/PI staining, respectively. The CALB1, TH, and Bcl-2 protein expressions were determined using Western blot. The Morris water maze test was used for the spatial learning and memory testing. Results: The hippocampal tissues in the model group were clearly damaged, but the pathological characteristics were significantly improved in the exo group. The exo group also showed an increased SOD level, decreased MDA and ROS levels, and down-regulated TNF-α, IL-1, and Aβ1-42 expressions (all P

An injectable biomaterial has been prepared through co-assembly of lipopeptides C4–Bhc–Glu–Glu–NH2 and C14–Phe–Lys–Lys–NH2. This biomaterial contained a large number of nanofibre bundles (nano-bundles, NBs) of lipopeptide co-assemblies and performed like hydrogels. The morphologies of the NBs were observed by transmission electron microscopy (TEM) and atomic force microscopy (AFM). The rheological properties were investigated with a rheometer. Excitingly, the NB biomaterials exhibited shear thinning and self-healing properties, and could be used as injectable biomaterials. The coumarin group in the lipopeptides endowed the NB biomaterials with both ultraviolet (UV, a one photon process) and near-infrared (NIR) light (a two photon process) responsiveness. A small molecule (Doxorubicin, DOX) and a large molecule (bovine serum albumin, BSA) were used as model drugs, and both of them could be encapsulated in the NB biomaterials and could also be released sustainably or explosively under different conditions (with or without one- and two-photon irradiation). DOX and BSA have different release behaviors because of the NBs. Cell assays showed that the co-assembled NB biomaterials exhibited low cytotoxicity to normal cells. However, when DOX was loaded, the NB biomaterials could kill HeLa cells sustainably. Under UV and NIR irradiation, HeLa cells could be killed rapidly because of the burst release of DOX. The co-assembled supramolecular NB biomaterials with dual-responsiveness, tunable rheological properties and multi-drug encapsulating ability might have potential in biomedical engineering.

To facilitate remote data acquisition and control of devices, Internet of things is a popular research field. Various factors are involved in the construction phase of highway engineering. In order to make proper decisions according to status of the engineering project, corresponding data should be obtained and processed in time. In this work, on-site construction site monitoring station is implemented with embedded Linux system, various kinds of sensors can be connected with it. Data can be stored and process at the station and uploaded to the data sharing cloud platform. Browser and Android App clients can connect to the on-site monitoring station or the data sharing platform. With the help of the data and instruction relay function, in both sceneries, data can be shared in real time and instructions can be sent to the on-site monitoring station instantly.

Varicella-zoster virus (VZV) lurks in cranial nerves and other brain ganglias after infection. Because middle cerebral artery (MCA) receives the ipsilateral trigeminal ganglia afferent innervations, the reactivated VZV infects the adventitia and intima of cerebral artery wall probably through this way and causes vascular inflammation, finally resulting in artery remodeling, vessel occlusion, and ischemia. In fact, there is a growing clinical recognition that there is an association between VZV reactivation and subsequent stroke. Here, we showed a case of ischemic stroke secondary to varicella-zoster virus meningoencephalitis and reviewed the literature to emphasize the importance of VZV-associated vasculopathy.

Nowadays, the demand for an alternative to linear PID controllers has increased because of the rising expectations of the high-precision industry. The potential of reset controllers to solve this important challenge has been extensively demonstrated in the literature. However, similarly to other non-linear controllers, the stability analysis for these controllers is complex and relies on parametric models of the systems which may hinder the applicability of these controllers in industry. The well-known Hbeta method tries to solve this significant issue. However, assessing the H\b{eta} condition in the frequency-domain is complex, especially for high dimensional plants. In addition, it cannot be used to assess UBIBS stability of reset control systems in the case of reseting to non-zero values. These problems have been solved in this paper for the first order reset elements, and an easy-to-use frequency approach for assessing stability of reset control systems is proposed. The effectiveness of the proposed approach is demonstrated through a practical example.

Due to development of technology, linear controllers cannot satisfy requirements of high-tech industry. One solution is using nonlinear controllers such as reset elements to overcome this big barrier. In literature, the Constant in gain Lead in phase (CgLp) compensator is a novel reset element developed to overcome the inherent linear controller limitations. However, a tuning guideline for these controllers has not been proposed so far. In this paper, a recently developed method named higher-order sinusoidal input describing function (HOSIDF), which gives deeper insight into the frequency behaviour of non-linear controllers compared to sinusoidal input describing function (DF), is used to obtain a straight-forward tuning method for CgLp compensators. In this respect, comparative analyses on tracking performance of these compensators are carried out. Based on these analyses, tuning guidelines for CgLp compensators are developed and validated on a high-tech precision positioning stage. The results show the effectiveness of the developed tuning method.

Pin1 is a unique isomerase that regulates protein conformation and function after phosphorylation. Pin1 aberration contributes to some neurological diseases, notably Alzheimer’s disease, but its role in epilepsy is not fully understood. We found that Pin1-deficient mice had significantly increased seizure susceptibility in multiple chemical inducing models and developed age-dependent spontaneous epilepsy. Electrophysiologically, Pin1 ablation enhanced excitatory synaptic transmission to prefrontal cortex (PFC) pyramidal neurons without affecting their intrinsic excitability. Biochemically, Pin1 ablation upregulated AMPA receptors and GluA1 phosphorylation by acting on phosphorylated CaMKII. Clinically, Pin1 was decreased significantly, whereas phosphorylated CaMKII and GluA1 were increased in the neocortex of patients with epilepsy. Moreover, Pin1 expression restoration in the PFC of Pin1-deficient mice using viral gene transfer significantly reduced phosphorylated CaMKII and GluA1 and effectively suppressed their seizure susceptibility. Thus, Pin1-CaMKII-AMPA receptors are a novel axis controlling epileptic susceptibility, highlighting attractive new therapeutic strategies.

Controllable self-assembly systems have attracted increasing attention in both the academic and industrial fields recently. Herein, we designed and synthesized a new photo-degradable anionic surfactant (PAS) with a coumarin group which could be degraded by both UV and NIR light. Thus, the micelles that are formed by sodium salts of PAS (PAS-Na) could be broken controllably under UV or NIR irradiation. Surface tension measurements, DLS, and Cryo-TEM were adopted to investigate the formation and disruption of PAS-Na micelles. PAS could also form wormlike micelles and vesicles when they co-assembled with common surfactant tetradecyldimethylamine oxide (C14DMAO). These wormlike micelles and vesicles could be degraded by UV and NIR irradiation due to the participation of PAS. Accordingly, the rheology properties of the wormlike micelles and vesicles were also changed significantly. Finally, the stimulus-responsive system was used to control the diffusion of hydrophobic and hydrophilic molecules. And it has shown controllable release effects on both the hydrophobic and hydrophilic molecules.

Restarting with speed for PMSM is critical to Rail Train application. And the switching frequencies must be restricted to several hundred hertz to minimize the switching losses. In order to output more torque with limited DC supply voltage, square wave should be used in the condition of high speeds. Hybrid synchronized PWM control schemes are often used to satisfy these restrictions. The restart and control schemes contain a variety of PWM patterns which is applicable to the whole speed range. And a simple but very effective method is proposed to determine the PWM patterns that should be used when restart is enabled. The motor speed feedback as a flag is employed in this method. An improved current controller for IPMSM is proposed to solve the zero speed start problem.

For high power rectifiers, due to the limit restriction of the switching loss, operating at low switching frequency is necessary. In this paper, an effective approach is proposed to restrain grid harmonic current and DC-link pulsating voltage. A discrete-time domain of the complex vector current regulator combined with a synchronized PWM modulation strategies at low switching frequency are employed in this approach. The method to keep synchronization is also illustrated in details. The results of simulations and experiments verifies the validity, effectiveness of the proposed rectifier strategies.

In this paper, the behavior of doubly-fed induction generator (DFIG) under unbalanced grid voltage conditions is analyzed and a control strategy based on complex-vector-resonant regulator is proposed. Compared with the traditional PI regulator, the positive and negative sequence currents can be regulated without sequential-decomposition process and this control structure has strong robustness in parameter variations. Simulation and experimental studies validate the effectiveness of the proposed control strategy and ride-through capability of DFIG under unbalance grid voltage conditions can be enhanced.

The aim of this study was to investigate the effects of transplantation of Schwann cells (SCs) co-cultured with brain-derived neurotrophic factor (BDNF) for the treatment of experimental autoimmune neuritis (EAN). Primary SCs were co-cultured with various BDNF concentrations, and the optimum concentration was determined by cell proliferation, and NGF and FGF levels. A rat model of EAN was established by immunization with 400μg of P2 peptide dissolved in Freund's complete adjuvant. SCs were labeled with CFSE and injected into the cisterna magna 14days after immunization. We found proliferation of SCs, and NGF and FGF levels were highest at a BDNF concentration of 50ng/mL. Compared with EAN group, SCs+BDNF group showed the lower paralysis scores from day 34 to day 45, and in sciatic nerves showed a significant decrease in inflammatory cell infiltration (involved CD4-, CD8- and CD68-positive cells) at days 25 and 35, an alleviated demyelination at days 35 and 45, and an increase in S-100-positive cells and a decrease in NGF-positive cells at each time point (P

The genomic DNA of Clostridium botulinum F str. 230613 includes a chromosome (3 993 083 bp, 3502 coding sequences (CDs)) and a plasmid (17 531 bp, 25 CDs). The arrangement of the botulinum neurotoxin serotype F (BoNT/F) gene cluster, a 15-kb (or longer) fragment including the bont gene and other relevant genes, and its different insertion sites in C. botulinum A2 and C. botulinum F were formulated. Mobile elements and virulence factors were analysed. We also found a cell adhesion and pectin lyase domain–containing protein, which may function in attaching to the host and as a pectin lyase. The nine BoNT gene clusters of group I C. botulinum strains were located at three sites in the chromosome of C. botulinum F str. 230613. This study showed the inserting inclination of BoNT/A1 tend to have gene clusters inserted at site 3, BoNT/F at site 2, and BoNT/A2 at site 1. Additionally, we found the recombination event between the BoNT gene clusters of sites 2 and 3, a mechanism that contributed to the diversity of the BoNT gene cluster arrangement.

Shiga toxins (Stxs) which include Stx1 and Stx2 produced by EHEC O157:H7 are responsible for severe diseases, including hemolytic uremic syndrome (HUS) in humans. In our previous study, a fusion protein Stx2B-Stx1B (2S for short) was prepared and displayed immunogenicity against low lethal dose challenge of E. coli O157:H7. To enhance the immunogenicity against both toxins above, we constructed a novel fusion protein carrying the Stx1B subunit and enzyme-inactive Stx2A subunit, designated Stx2Am-Stx1B (SAmB for short). The fusion protein SAmB elicited high level humoral IgG and IgG1 in mice and induced Th2-typical cytokines IL-4/IL-10 but not Th1-typical cytokine INF-γ, indicating a partial to humoral immunoresponse mediated by Th2-type cells that contributed to this humoral reactivity. Higher level neutralizing antibodies against Stx2 were elicited by SAmB than 2S. An enhanced effect of protection (93.3%) against high lethal dose challenge of lysed E. coli O157:H7 was observed, and the SAmB also provided cross protection against purified Stx1 and Stx2.

Botulinum neurotoxins (BoNts) pose a biological hazard to humans and a serious potential bioweapon threat. Given the safety concern regarding the currently used equine antitoxin therapy for botulism, it is imperative to develop agents that are effective binding inhibitors. The aim of this study was to identify a novel neutralizing antibody against botulinum neurotoxin B (BoNtb) that recognizes the protein receptor binding sites for synaptotagmins II. This antibody showed significant dose-dependent protection against lethal toxin challenge in vivo at an intraperitoneal (i.p.) dose 10 times the half lethal dose (LD50). We proved that the efficacy of SC12 was based on its counteraction on the recognition and binding of BoNtb to target cells, resulting from the combination of antibody with the high affinity (KD: 1.34 nM) to protein receptor binding sites of BoNt by targeting a 25-mer dominant antigenic site on Hcc region (residues 1253–1277). The structure of the site targeted by this antibody overlaps the pocket-like protein receptor binding sites located at the distal tip of toxin molecule. Information gained from this study will facilitate the development of potent inhibitors that prevent the binding of BoNts with its receptors.

A novel human antibody AR16, targeting the G5 linear epitope of rabies virus glycoprotein (RVG) was shown to have promising antivirus potency. Using AR16, the minimal binding region within G5 was identified as HDFR (residues 261–264), with key residues HDF (residues 261–263) identified by alanine replacement scanning. The key HDF was highly conserved within phylogroup I Lyssaviruses but not those in phylogroup II. Using computer-aided docking and interaction models, not only the key residues (Asp30, Asp31, Tyr32, Trp53, Asn54, Glu99, Ile101, and Trp166) of AR16 that participated in the interaction with G5 were identified, the van der Waals forces that mediated the epitope–antibody interaction were also revealed. Seven out of eight presumed key residues (Asp30, Asp31, Tyr32, Trp53, Asn54, Glu99, and Ile101) were located at the variable regions of AR16 heavy chains. A novel mAb cocktail containing AR16 and CR57, has the potential to recognize non-overlapping, non-competing epitopes, and neutralize a broad range of rabies virus.

Botulinum neurotoxin serotype A (BoNT/A) is an extremely potent bacterial protein toxin. The Hc fragment of BoNT/A (AHc) was shown to be non-toxic, antigenic, and capable of eliciting a protective immunity in animals challenged with homologous BoNT. In this study, we synthesized AHc gene by using T4 DNA ligase and PCR. The AHc was expressed at a high level in Escherichia coli successfully. Because of using the Trx co-expression strain, the expressed AHc is in a soluble and active form. The yield of the purified AHc was about 70mg/L, and its purity was up to 90% through one-step affinity chromatography. The AHc was positively identified by the antibodies raised against BoNT/A using immunological-dot-blot and Western blot assays. AHc was shown to bind with gangliosides and elicit immunity against BoNT/A, indicating that the expressed and purified AHc protein retains a functionally active conformation. Furthermore, the purified AHc has a strong immunogenicity and can be used as a potential subunit candidate vaccine for botulinum toxin serotype A.

The entire stx2 region from Escherichia coli O157:H7, containing two open reading frames (stx2a and stx2b), was cloned into pET-32a with a single promoter, and transformed into E. coli BL21 (DE3) pLysS. We used two methods of IPTG induction using LB medium and auto-induction using ZYM-5052 medium to express recombinant Shiga toxin 2 (rStx2). rStx2 was expressed in the E. coli periplasm in a completely soluble, biologically active form. The final yield of purified rStx2 from each liter of culture in LB medium and ZYM-5052 medium was approximately 2.3 mg and 3.5 mg, respectively. The highest amount of rStx2 accounted for 27.8% of total bacteria protein in ZYM-5052 medium. rStx2A and rStx2B isolated from rStx2 by electroelution were, respectively, identified by N-terminal protein sequencing. Signal peptides with the sequence MKCILFKWVLCLLLGFSSVSYS and MKKMFMAVLFALASVNAMA were identified at the N terminus of rStx2A and rStx2B, respectively. Our rStx2 possessed Vero cell CD 50 value about 500 pg and LD 50 value approximately 6 ng. rStx2 can be substitute for natural toxin Stx2, which can be used for animal models, drug screening, vaccine research, and so on.

Botulism toxicity is caused by botulinum neurotoxins (BoNTs) that bind to the surface of the nerve terminals through the C-terminal portion of the heavy chain (Hc) and gain access to the neuron cells, thereby blocking the release of neurotransmitters into the synapse by the light chain. It has been recently found that synaptotagmin II (syt II) is the specific protein receptor of BoNTs; however, the molecular basis underlying the interaction between BoNTs and the receptor has been poorly understood. In this study, the recombinant fragment from the luminal domain of the human protein receptor syt II was prepared. Further, the Hc antigenic peptides of BoNTs type B (BoNTb) containing the possible epitopes were synthesized and analyzed for checking their ability for specific recognition and binding by using completely protective polyclonal antibody and were then evaluated for checking their ability to elicit protective immunity in mice against lethal toxin challenge. Finally, the interaction between the Hc-dominant antigenic peptides and syt II was analyzed. We found that two peptides located at the Hc terminal of the BoNTb showed the general character of the dominant antigenic epitopes in terms of protection against BoNTb intoxication. Further, they were found to contain the receptor-binding sites through the specific recognition of the receptor syt II. Both were derived from the uninterrupted segments of the amino acid residues H1241–1277 of BoNTb. Kinetic data of the antigen–receptor interaction were depicted in real-time and calculated as affinity constant of 2.99 × 10–7 M.

Therapeutic cloning, whereby embryonic stem cells (ESCs) are derived from nuclear transfer (NT) embryos, may play a major role in the new era of regenerative medicine. In this study we established forty nuclear transfer-ESC (NT-ESC) lines that were derived from NT embryos of different donor cell types or passages. We found that NT-ESCs were capable of forming embryoid bodies. In addition, NT-ESCs expressed pluripotency stem cell markers in vitro and could differentiate into embryonic tissues in vivo. NT embryos from early passage R1 donor cells were able to form full term developed pups, whereas those from late passage R1 ES donor cells lost the potential for reprogramming that is essential for live birth. We subsequently established sequential NT-R1-ESC lines that were developed from NT blastocyst of late passage R1 ESC donors. However, these NT-R1-ESC lines, when used as nuclear transfer donors at their early passages, failed to result in live pups. This indicates that the therapeutic cloning process using sequential NT-ESCs may not rescue the developmental deficiencies that resided in previous donor generations.

In this study, the effects of pH on the growth, relative expressions of bontA and botR genes, and neurotoxin formation of foodborne pathogens Clostridium botulinum type A were systematically studied throughout its growth stage. As in the previous reports, no C. botulinum growth was observed at extremely acidic pH. However, the effect of alkaline pH on the growth and neurotoxin production of C. botulinum was first revealed in this study. The maximum growth rate at pH 9.0 was similar to that at other pH values, although the lag phase at pH 9.0 was 16 h longer than that at pH 8.0. The peak of bontA mRNA expression at pH 9.0 was only 15.5% compared with that at pH 7.0. However, the neurotoxin concentration quantified in the cultures did not differ significantly. BotR is a known regulatory protein of bontA. The quantitative relationship between bontA and botR at different growth stages was first determined in this study. The mRNA levels of bontA were found to be positively correlated with those of botR, and the ratio of the mRNA transcript varied with pH. All these findings provide important physiological information on C. botulinum and thereby contribute to the improvement of food safety.

New Delhi metallo-β-lactamase (NDM-1) is a new metallo-β-lactamase (MBL) that has recently emerged as a global threat because it confers bacteria with resistance to almost all clinically used β-lactam antibiotics. To determine the molecular basis of this threat, NDM-1 was purified from Escherichia coli TransB (DE3) carrying cloned blaNDM-1 gene by an anion-exchange chromatography step followed by a gel permeation chromatography step. The purified enzyme was stable even in extremely alkaline buffer (pH 11) and reached its highest activity at a low temperature (15°C), which was different from other MBLs. The 50% inhibition concentration of EDTA against NDM-1 was 412 nM, which showed that NDM-1 was more susceptible to EDTA than other MBLs. The effects of zinc on NDM-1 differed between cephem and carbapenem complexes, but inhibition at high Zn(2+) concentration was observed for all of tested β-lactam compounds.

Multiple sclerosis (MS) is the most prevalent demyelinating disease and the principal cause of neurological disability in young adults. Recent microarray gene expression profiling studies have identified several genetic variants contributing to the complex pathogenesis of MS, however, expressional and functional studies are still required to further understand its molecular mechanism. The present study aimed to analyze the molecular mechanism of MS using microarray analysis combined with bioinformatics techniques. We downloaded the gene expression profile of MS from Gene Expression Omnibus (GEO) and analysed the microarray data using the differentially coexpressed genes (DCGs) and links package in R and Database for Annotation, Visualization and Integrated Discovery. The regulatory impact factor (RIF) algorithm was used to measure the impact factor of transcription factor. A total of 1,297 DCGs between MS patients and healthy controls were identified. Functional annotation indicated that these DCGs were associated with immune and neurological functions. Furthermore, the RIF result suggested that IKZF1, BACH1, CEBPB, EGR1, FOS may play central regulatory roles in controlling gene expression in the pathogenesis of MS. Our findings confirm the presence of multiple molecular alterations in MS and indicate the possibility for identifying prognostic factors associated with MS pathogenesis.

Aims Radiation-induced lung injury is one of the limiting factors for radiation therapy. SOD-TAT, a fusion protein of HIV-1 Tat protein transduction domain and hCuZn-superoxide dismutase (SOD), has been proved to be effective in preventing and treating the damage of the skin of guinea pigs by UVB radiation. In this study, we demonstrated SOD-TAT's radioprotective effects on lung injury in irradiated mice. Main methods SOD-TAT was purified from yeast culture with ion exchange chromatography. Kunming mice were randomly divided into three groups: a control group, a group injected with wild SOD and a group injected with SOD-TAT. Pulmonary SOD activity of mice was determined 4.5 h after injection. C57BL/6 mice were randomly divided into four groups: a control group, an irradiation group, an irradiation group treated with amifostine 0.5 h before the irradiation and an irradiation group treated with SOD-TAT 4.5 h before irradiation. The monthly growth rate of every mouse's weight was calculated and the level of hydroxyproline content and antioxidant activity in lung were determined 5 months after irradiation. Key findings SOD-TAT was transduced into the lung in vivo. SOD-TAT pretreatment could improve the growth rate of irradiated mice, significantly reduce the pulmonary hydroxyproline content, and maintain the SOD activity, glutathione peroxidase (GSH-Px) activity and total anti-oxidation capacity (T-AOC). Compared with amifostine, SOD-TAT was more effective in increasing the activities of pulmonary antioxidant enzymes. Significance Compared with amifostine, SOD-TAT treatment more effectively enhanced pulmonary antioxidant ability, reduced radiation-induced pulmonary fibrosis and improved the living quality of irradiated mice.

A 57-year-old male patient with gastric carcinoma underwent radical distal gastrectomy type II + Braun anastomosis, and received total parenteral nutrition for 10 days after surgery, followed by small amounts of semi-liquid nutrition for 3 days and liquid nutrition for 2 days. The patient developed refractory hypotension for more than 1 week in the early course of disease, and on Day 15 after surgery presented with characteristic signs of Wernicke's encephalopathy, including diplopia and mental confusion. The hypotension did not improve despite appropriate fluid replacement soon after admission. Treatment with moderate dose of thiamine for 3 months partly relieved ophthalmoplegia and confusion, but not Korsakoff syndrome. This extraordinary presentation with refractory hypotension and the unusual course of the disease encouraged us to present this case.

Infection with Escherichia coli (E. coli) O157:H7 may develop into bloody diarrhea, or hemorrhagic uremic syndrome (HUS), which usually causes kidney failure or even death. Considered as the pathogenesis mechanism of E. coli O157:H7 infection, attachment or adhesion that is directly mediated by intimin is the first step of E. coli O157:H7 interaction with its host, and all these serious sequelae are mainly due to Shiga toxins (Stxs) released by E. coli O157:H7. In this study, a novel SSI fusion protein that contains the critical toxin-antigens Stx2B and Stx1B, and the critical adhesion-antigen fragment Int281 was constructed. The protein induced complete immune protection, with both anti-toxin and anti-adhesion effects. The dominant increase in IgG1 and the high level of Th2-typical cytokine (IL-4 and IL-10) expression showed that SSI significantly induced Th2-mediated humoral immune response. In the mouse model, the SSI fusion protein not only elicited neutralizing antibodies against both Stx1 and Stx2 toxins, but also induced a high level of anti-adhesion antibodies. The SSI-immunized mice did not show any pathologic changes. SSI provides evident protection with two-time immunization against a highly lethal dose of E. coli O157:H7.

Shiga toxin type 2, a major virulence factor produced by the Shiga toxin-producing Escherichia coli, is a potential toxin agent of bioterrorism. In this study, iodine-125 (125I) was used as an indicator to describe the in vivo Stx2 biodistribution profile. The rats were injected intravenously (i.v.) with 125I-Stx2 at three doses of 5.1-127.5 μg/kg body weight. Stx2 had a short distribution half-life (t (1/2)α, less than 6 min) and a long elimination half-life in rat. The toxicokinetics of Stx2 in rats was dose dependent and nonlinear. Stx2 concentrations in various tissues were detected at 5-min, 0.5-h, and 72-h postinjection. High radioactivity was found in the lungs, kidneys, nasal turbinates, and sometimes in the eyes, which has never been reported in previous studies. In a preliminary assessment, lesions were found in the kidney and thymus.