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Amyloid-related diseases, such as Alzheimer's disease, are all considered to be related to the deposition of amyloid fibrils in the body. Insulin is a protein hormone that easily undergoes aggregation and fibrillation to form more toxic amyloid-like fibrils. So far, it is still challenging to develop a new protocol to study the

Introduction: Dysregulation of spinal cord development can lead to serious neuronal damage and dysfunction, causing significant health problems in newborns. MiRNA-138 appears to be crucial for proliferation, differentiation, and apoptosis of cells. However, the regulation of miRNA-138 and downstream molecules in embryonic spinal cord development remain elusive. The aim of this experiment is to determine whether overexpression of miRNA-138 or RNA interference (RNAi) can regulate the development of spinal cord in fetal rats. Methods: Two plasmid vectors including pLenti-III-mico-GFP (miRNA-138 open reading frame [ORF]) and pLenti-III-miR-Off (miRNA-138 short hairpin) were constructed and injected into the tail vein of rats on the 14th day of pregnancy. Hematoxylin-eosin (HE) staining was used to observe the cell morphology. QRT-PCR, Western blot, and immunostaining confirmed the regulatory relationship between miRNA-138 and downstream molecules sonic hedgehog (Shh). Results: Overexpression of miRNA-138 increased neuron regeneration significantly and decreased neuronal apoptosis when compared with the control. Silencing of miRNA-138 increased neuronal apoptosis and spinal cord atrophy significantly. Furthermore, miRNA-138 ORF treatment effectively increased the expression level of miRNA-138 and also upregulated the level of Shh. Comparatively, knockdown of miRNA-138 downregulated Shh levels in myelodysplastic regions. Conclusion: These findings indicated that miRNA-138 overexpression could protect the spinal cord development of fetal rats, and the underlying mechanisms were associated with Shh expression. The present study provides a novel strategy to promote the molecular mechanism of embryonic spinal cord development.

Governor Vessel electro-acupuncture (GV), as a traditional Chinese medicine, has been proved that it can reduce scar and promote axon regeneration. However, the underlying mechanism remains unclear. Herein, complexin I (CPLX1), as a candidate protein involved in the process of GV treatment on spinal cord contusion (SCC), was found by using protein chip. Therefore, using a CRISPR/Cas9 knockout approach, we silenced CPLX1 to assess its role in the process of GV treatment. Additionally, eIF5A1 promotes translation of CPLX1 with PPG sequence, we attempt to uncover whether eIF5A1 play a role in GV treatment. Indeed, GV can reduce scar and promote axon regeneration after SCC. CPLX1-/+ SCC rats demonstrated that decreased CPLX1 improved the microenvironment of injured area via reducing the components of fibrotic scar and further enhanced the synaptic plasticity, which benefit the regeneration of axons. And eIF5A1 could regulate the expression of CPLX1 in the process of GV treatment. Therefore, GV contributes to axon regeneration and synapse plasticity via eIF5A1 regulating CPLX1 following SCC, providing a convincible mechanism for improving the therapeutic efficacy of GV for SCC.

The synthesis of O-, C-, and N-glycoconjugates has continuously been an attractive research subject due to the growing biological importance of various glycoconjugates. In recent years, by careful changing the glycosylation reaction conditions, especially the amount of activators and the preactivation temperature, (p-Tol)2SO/Tf2O preactivition strategy was developed as a general method for the synthesis of various O-, C-, and N-glycoconjugates, including related biological active glycoconjugates, such as nucleosides and antigen Lewisa etc. High yields and excellent stereoselectivities were obtained even without the anchimeric assistance at the adjacent position of anomeric carbon. In this review, we predominantly make a review on the progress of the (p-Tol)2SO/Tf2O preactivition strategy from O-, C-sialylation to general O-, N-glycosylation.

Imaging-based total bacterial count and type identification of bacteria play crucial roles in clinical diagnostics, public health, biological and medical science, and environmental protection. Herein, we designed and synthesized a series of tetraphenylethenes (TPEs) functionalized with one or two aldehyde, carboxylic acid, and quaternary ammonium groups, which were successfully used as fluorescent materials for rapid and efficient staining of eight kinds of representative bacterial species, including pathogenic bacteria Vibrio cholera, Klebsiella pneumoniae, and Listeria monocytogenes and potential bioterrorism agent Yersinia pestis. By comparing the fluorescence intensity changes of the aggregation-induced-emission (AIE) materials before and after bacteria incubation, the sensing mechanisms (electrostatic versus hydrophobic interactions) were simply discussed. Moreover, the designed AIE materials were successfully used as an efficient artificial tongue for bacteria discrimination, and all of the bacteria tested were identified via linear discriminant analysis. Our current work provided a general method for simultaneous broad-spectrum bacterial imaging and species discrimination, which is helpful for bacteria surveillance in many fields.

Based on a preactivation strategy using ( p -Tol) 2 SO/Tf 2 O, a new O -fucosylation method with thioglycoside as donor under mild conditions was reported. High yields and excellent α-stereoselectivities of the fucosylation were obtained with secondary sugar alcohol as acceptors. Moreover, the novel fucosylation strategy was successfully applied to the synthesis of an important Lewis blood group antigen Lewis a , which was obtained in nine linear steps with 27% overall yield.

Electroacupuncture at Governor Vessel (GV), as a traditional chinese medicine, has been proved that it can reduce scar and promote axon regeneration. However, the underlying mechanism remains unclear. Herein, complexin1 (CPLX1), as a candidate protein, was found using protein chip. Therefore, using a CRISPR/Cas9 knockout approach, we deleted CPLX1 specifically in the SD rats to assess the role of CPLX1 in GV treatment. Additionally, eIF5A1 stimulate the translation of CPLX1 with PPG sequence, we attempt to uncover whether eIF5A1 play a role in the GV treatment. In fact, GV can reduce scar and promote axon regeneration after SCC. CPLX1−/+ SCC rats demonstrated that decreased CPLX1 improved the microenvironment of injured area via reducing the components of fibrotic scar and further enhanced the synaptic plasticity, which benefit the regeneration of axons. And eIF5A1 could regulate the expression of CPLX1 in the process of GV treatment. Therefore, GV contributes to axon regeneration and synapse plasticity via eIF5A1 regulating CPLX1 following SCC, providing a convincible mechanism for improving the therapeutic efficacy of GV for SCC.

Two water-soluble carbohydrate-coated AIE-activate fluorescent organic nanoparticles TPE3G and TPE4G were designed and synthesized for the detection of heparin. Different from the reported strategy, we not only utilized the general detection mechanism of electrostatic interactions, but also introduced the concept of carbohydrate-carbohydrate interactions (CCIs) to enrich the detection mechanism of heparin. TPE3G can serve as an efficient "turn-on" probe with higher selectivity towards heparin than TPE4G. TEM studies revealed that the micro-aggregated TPE3G was encapsulated with the heparin chain to form a complex self-assemblied composite and emits strong fluorescence. It is believed that the results illustrated in this study provide a novel strategy based on CCls to design water-soluble and more efficient bio-probes for various biological and clinical applications.

Cross-sectional TEM observation can be used as an important method in the microstructure investigation of thin films. However, the specimen preparation for cross-sectional TEM observation is generally regarded as a challenging task. In this paper, we discussed the preparation of TEM cross-sectional specimens. An example from GaN thin films grown on Si substrate was discussed correspondingly.

ZnO will become a new pattern optoelectronic material because of its many excellent properties. But the defects in ZnO crystal are the key factors for restricting the luminescence properties of the material. In this paper, we summarized the defect types that exist in ZnO thin films and reviewed on the relationship between the luminescence mechanism and the structure defects of ZnO thin films reported in recent years.

We aimed to investigate the effects of microRNA-98 (miR-98) on apoptosis in cartilage cells of osteoarthritis (OA) patients.Knee cartilage tissue samples were collected from 31 OA patients, 21 autopsies, and 26 amputation patients due to trauma. The clinicopathological data were recorded. Quantitative real-time polymerase chain reaction was performed to compare the miR-98 expression levels from cartilage cells obtained from the OA and non-OA patients. Clinicopathological characteristics of the patients were also analyzed. Primary chondrocytes were separated from cartilage tissues and transfected with plasmids or siRNA to overexpress or inhibit miR-98. Annexin V-PI double staining and TUNEL assays were used to examine apoptosis in the primary chondrocytes after transfection. Finally, a rat OA model was used to confirm the effects of miR-98 on apoptosis in cartilage cells in vivo.Compared with the normal cartilage tissues, miR-98 expression was reduced in the OA cartilage tissues (p 0.01). The miR-98 expression levels were also significantly correlated with the OA stage (p 0.05). In vitro, transfection with the miR-98 inhibitor increased apoptosis in the cartilage cells (p 0.05), and transfection with a miR-98 mimic inhibited apoptosis in cartilage cells (p 0.05). In the OA rat model, exogenous injection of the miR-98 mimic inhibited apoptosis in the rat cartilage cells thus alleviating OA.MiR-98 expression is reduced in the cartilage cells of OA patients and the overexpression of miR-98 inhibits cartilage cell apoptosis, while inhibition of microRNA-98 leads to cartilage cell apoptosis. These findings provide a theoretical basis for the development of novel targeted therapies for OA.

A dialdehyde–diboronate-functionalized tetraphenylethene (TPE-DABF) was reported as a H2O2-specific AIE luminogen. TPE-DABF, bearing multiple reductive units (aldehyde, boronate and fructose) in one molecule, afforded an excellent H2O2 selectivity over other ROS in biological buffer, and can be used for sensitive detection of glucose under neutral conditions.

Genistein, one of the predominant isoflavones derived from soybeans, has been shown beneficial effects in cancer prevention and treatment. There is an accumulating body of experimental evidences suggesting that genistein affects cancer progression by increasing apoptosis, inducing cell cycle arrest,modulating intracellular signaling pathways, and inhibiting invasion and metastasis of cancer cells. During last decade, many researchers have conducted extensive studies by synthesizing amounts of structurally-modified derivatives based on the isoflavone skeleton of genistein to enhance its anticancer activity, some analogs of which possess more potent activities of the prevention and/or treatment of various cancers. In this review, we summarized the current knowledge regarding anticancer effects,structure-activity relationships and action mechanisms of genistein and its synthesized analogs, which would be beneficial to the rational design of new genistein derivatives as anticancer drugs.

The RAF-MEK-ERK cascade appears to be intimately involved in the regulation of cell cycle progression and apoptosis. The BRAF(V600E) mutant results in constitutive activation of the ERK pathway, which can lead to cellular growth dysregulation. A series of 5-phenyl-1H-pyrazol derivatives (3a-5e) have been designed and synthesized, and their biological activities were evaluated as potential BRAF(V600E) inhibitors. All the compounds were reported for the first time except 3e, and compound 1-(4-bromo-2-hydroxybenzyl)-3-phenyl-1-(5-phenyl-1H-pyrazol-3-yl)urea (5c) displayed the most potent inhibitory activity (BRAF(V600E) IC50 = 0.19 μM). Antiproliferative assay results indicated that compound 5c possessed high antiproliferative activity against cell lines WM266.4 and A375 in vitro, with IC50 values of 1.50 and 1.32 μM, respectively, which were comparable with the positive control vemurafenib. Docking simulations showed that compound 5c binds tightly to the BRAF(V600E) active site and acts as BRAF(V600E) inhibitor. A 3D-QSAR model was also built to provide more pharmacophore understanding towards designing new agents with more potent BRAF(V600E) inhibitory activity.

A series of novel 4,5-dihydropyrazole derivatives containing niacinamide moiety as potential V600E mutant BRAF kinase (BRAFV600E) inhibitors were designed and synthesized. Results of the bioassays against BRAFV600E and WM266.4 human melanoma cell line showed several compounds to be endowed potent activities with IC50 and GI50 value in low micromolar range, among which compound 27e, (5-(4-Chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)6-methylpyridin-3-yl methanone (IC50 = 0.20 μM, GI50 = 0.89 μM) was bearing the best bioactivity comparable with the positive control Sorafenib. Docking simulation was performed to determine the probable binding model and 3D-QSAR model was built to provide more pharmacophore understanding that could use to design new agents with more potent BRAFV600E inhibitory activity.

Activating mutations in the BRAF serine/threonine kinase are found in more than 70% of human melanomas, >90% of which are BRAF V600E . It provides new therapeutic opportunities in malignant melanoma. In silico and in vitro screening of our compound collection has identified Hit 2 as BRAF V600E inhibitor. Based on its structure, a series of novel (E)-α-benzylsulfonyl chalcone derivatives ( 13 – 40 ) were designed and synthesized. Compound 38 exhibited the most potent inhibitory activity with an IC 50 value of 0.17 μM for BRAF V600E and GI 50 value of 0.52 μM for mutant BRAF-dependent cells. The results of cell based pERK activity and cellular selectivity suggested that those compounds could selectively inhibit proliferation of mutant BRAF-dependent melanoma cell line through inhibition of oncogenic BRAF.

To assess the safety, immunogenicity and efficacy of group A and C meningococcal polysaccharide vaccine (A/C MPV) in response to an outbreak of group C meningococcal disease.A vaccination campaign with A/C MPV was prompted 6 weeks after the use of group A MPV in Laibin city, Guangxi, where an outbreak of group C meningococcal meningitis occurred in 2002. Vaccinees were observed for local and systemic reactions after the vaccination and followed up for the meningococcal disease for 5 years. Blood samples were collected from 71 people in the epidemic and 43 in the non-epidemic areas before and 1 month after the vaccination and examined by ELISA to detect IgG antibodies to group A and C polysaccharides.The vaccination coverage was 97%. No significant adverse reactions were observed. The positive rates of group C antibodies after vaccination was between 97.67% and 100% among the populations in the epidemic and non-epidemic areas, as well as among those negative and positive for group C antibodies prior to the vaccination. The geometric mean anti-C concentrations ranged 30.81 microg/ml to 37.44 microg/ml, showing no significant difference between groups. The incidence rate of meningococcal disease in students with timely immunization (218.58/100,000) dropped by 69.02%, when compared to that in those with delayed immunization (705.72/100,000). No clinical cases were identified during the follow-up period of 15,760 person-years.The vaccination campaign with the Chinese group A/C MPV seemed successful in controlling the group C meningococcal outbreak. The vaccine was shown to be safe even administered after the group A vaccine only 6 weeks apart. It could induce high levels of antibodies in vulnerable population and significantly increase antibody levels in seropositive individuals, thus providing a protection of at least 5 years.

Particle filtering shows great promise in addressing a wide variety of non-linear and/or non-Gaussian problem. A crucial issue in particle filtering is to remove degeneracy phenomenon and alleviate the sample impoverishment problem. In this paper, Variations, using techniques from the genetic algorithm with Markov chain Monte Carlo mutation, to standard PFprocedures are proposed to solve these problem simultaneously. The simulation results show that the new particle filter superiors to the standard particle filter and the other filters.

To describe the design and application of cluster randomized controlled method on typhoid Vi vaccine trial, and to assess the effect of implementation.Simple size calculation of cluster-randomized trial was used to determine the sample size of the two groups and a vaccination campaign was conducted. The study group was given typhoid Vi vaccine and the control group was given meningococcal A vaccine.According to sample size calculation, a total sample of 96,121 participants was required and the study areas were divided into 108 clusters. In practice, 53 study clusters with 44,054 participants and 54 control clusters with 48,422 participants were stratified and matched according to size, location (urban or rural), characteristics (school, department, factory, demography) were randomized respectively. Confounding factors of two groups including age, sex, resident area, income, level of education were compared. It was found that the ratio of all confounding factors between the two groups were comparable and balanced.Confounding factors can be better controlled between study group and the control group by applying cluster-randomized method on vaccine trail which enabled the intervention to be more scientifically evaluated; The implementation of cluster randomization trial was simple and easy to be accepted.

To characterize the incidence, epidemiologic features, etiologic agents and sequelae of bacterial meningitis in children under 5 years of age in Nanning, Guangxi.A population-based surveillance was conducted to evaluate children with signs and symptoms of meningitis. All hospitals, township health centers and village clinics in the surveillance area were structured to participate in the case referral and evaluation. Cerebrospinal fluid (CSF) and blood specimens were obtained and processed using standardized microbiologic methods.During the 26-month surveillance period, among the children under 5 years old, a total of 1272 cases who met the screening criteria of meningitis were studied. 265 of 1272 cases were identified as clinically diagnosed meningitis, with an incidence rate of 86.36 per 100 000 population. The annual incidence rate under the 38 cases of confirmed bacterial meningitis appeared to be 12.38/100 000. Staphylococcus species accounted for the largest proportion of laboratory-confirmed bacterial meningitis, followed by E. coli and S. pneumoniae. The highest attack rate occurred in neonates1 month, followed by children aged 1 - 12 months in the confirmed patients. Meningitis caused by Sp and Hi mainly occurred in children aged 1 - 12 months. All cases of meningitis due to Hi and Sp were children aged 1 - 24 months. 13.16% and 0.00% of the cases survived with complications and sequelae, and the case-fatality rate was 18.42%. 40 bacterial isolates were identified from 1193 blood cultures and 23 from 1211 cerebrospinal fluid samples, but no Neisseria meningitidis was found.Meningitis due to Hi was first confirmed in Guangxi with the incidence of 0.98 per 100 000 population. The annual incidence rate of confirmed bacterial meningitis was 12.38 per 100 000, which was considered an important public health problem in children. Staphylococci was the predominant pathogen in confirmed bacterial meningitis.

Background One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS) and group A meningococcal PS vaccines in southern China. Methods The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. Results The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged ≤ 15 years (90%) than in adolescents and young adults (70%). Planned mop-up activities increased the coverage by 17%. The overall vaccine wastage was 11%. The cold chain was maintained and documented. 66 individuals reported of adverse events out of all vaccinees, where fever (21%), malaise (19%) and local redness (19%) were the major symptoms; no life-threatening event occurred. Three needle-sharp events were reported. Conclusion The mass immunization proved feasible and safe, and vaccine coverage was high. Emphasis should be placed on: injection safety measures, community involvement and incorporation of mop-up strategies into any vaccination campaign. School-based and all-age Vi mass immunizations programs are potentially important public health strategies for prevention of typhoid fever in high-risk populations in southern China.