Background: Weighted co-expression network analysis (WGCNA) is a powerful systems biology method to describe the correlation of gene expression based on the microarray database, which can be used to facilitate the discovery of therapeutic targets or candidate biomarkers in diseases. Objective: To explore the key genes in the development of Alzheimer’s disease (AD) by using WGCNA. Methods: The whole gene expression data GSE1297 from AD and control human hippocampus was obtained from the GEO database in NCBI. Co-expressed genes were clustered into different modules. Modules of interest were identified through calculating the correlation coefficient between the module and phenotypic traits. GO and pathway enrichment analyses were conducted, and the central players (key hub genes) within the modules of interest were identified through network analysis. The expression of the identified key genes was confirmed in AD transgenic mice through using qRT-PCR. Results: Two modules were found to be associated with AD clinical severity, which functioning mainly in mineral absorption, NF- κB signaling, and cGMP-PKG signaling pathways. Through analysis of the two modules, we found that metallothionein (MT), Notch2, MSX1, ADD3, and RAB31 were highly correlated with AD phenotype. Increase in expression of these genes was confirmed in aged AD transgenic mice. Conclusion: WGCNA analysis can be used to analyze and predict the key genes in AD. MT1, MT2, MSX1, NOTCH2, ADD3, and RAB31 are identified to be the most relevant genes, which may be potential targets for AD therapy.

This study reports the simplified carbapenem inactivation method (sCIM) to detect carbapenemase-producing gram-negative bacilli in a simple and accurate manner. This method is based on the modified carbapenem inactivation method (mCIM) with the improvement of experimental procedures. Instead of incubating the antibiotic disk in the organism culture media, the organism to be tested was smeared directly onto the antibiotic disk in the sCIM. For evaluating the sensitivity and specificity of the method, a total of 196 Enterobacteriaceae, 73 Acinetobacter baumannii, and 158 Pseudomonas aeruginosa isolates were collected. Polymerase chain reaction (PCR) was used to detect the carbapenemase genes. Phenotypic evaluations were performed using both the sCIM and the mCIM. PCR results showed that, of the 196 Enterobacteriaceae strains, 147 expressed the carbapenemase genes bla_KPC−2 (58.5%), bla_IMP−4 (21.8%), bla_IMP−2 (2.0%), bla_VIM−1 (6.1%), bla_NDM−1 (10.2%), and bla_OXA−48 (1.4%). sCIM results had high concordance with PCR results (99.5%) and mCIM results (100%) with the exception of one Klebsiella pneumoniae strain, which had an minimal inhibitory concentration (MIC) for imipenem of 0.25 mg/L. PCR demonstrated that 53 of the 73 A. baumannii isolates expressed the carbapenemase genes bla_OXA−23 (98.1%) and bla_VIM−2 (1.8%). sCIM and PCR results corresponded but all A. baumannii isolates were carbapenemase negative by the mCIM. PCR demonstrated that 25 of the 158 P. aeruginosa isolates expressed carbapenemase genes bla_VIM−1 (52%)_, bla_VIM−2 (8%)_, bla_VIM−4 (36%), and bla_IMP−4 (4%). sCIM results had high concordance with PCR results (100%) and the mCIM results (99.4%) with the exception of one P. aeruginosa isolate that expressed the bla_VIM−4 gene. The sCIM offers specificity and sensitivity comparable to PCR but has the advantage of being more user-friendly. This method is suitable for routine use in most clinical microbiology laboratories for the detection of carbapenemase-producing gram-negative bacilli.

Summary: Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase which participates in the regulation of multiple cellular processes. As a confirmed tumor suppressor, PP2A activity is downregulated in tumors and its re-activation can induce apoptosis of cancer cells. In the brains of Alzheimer’s disease (AD) patients, decreased PP2A activity also plays a key role in promoting tau hyperphosphorylation and Aβ generation. In this review, we discussed compounds aiming at modulating PP2A activity in the treatment of cancer or AD. The upstream factors that inactivate PP2A in diseases have not been fully elucidated and further studies are needed. It will help for the refinement and development of novel and clinically tractable PP2A-targeted compounds or therapies for the treatment of tumor and AD.

Purpose. Group B Streptococcus (GBS) is one of the major pathogens in severe materno-neonatal infections. We aimed to describe the clinical and molecular characteristics of GBS isolates causing infections in 45 maternal and 50 neonatal subjects, collected from eight healthcare centres in mainland China over the period 2010– 2017. Methodology. The phenotypic and genotypic features of the GBS isolates, including capsular polysaccharide (cps) serotypes, pilus island (PI) genes and antibiotic resistance profiles and genes, were characterized by both conventional and molecular methods. The clonal relationship between these strains was investigated using multilocus sequence typing (MLST). Results. Of the 95 isolates, the predominant serotypes were III (51, 53.7 %), V (13, 13.7 %) and Ib (13, 13.7 %). All GBS strains carried at least one pilus island, with 32.6 % carrying PI-2b and 67.4 % PI-2a, singly or in combination. The most frequently-detected pilus island pattern was the combination of PI-1 and PI-2a, accounting for 56.8 % (54 isolates), followed by PI-1 combined with PI-2b (28, 29.5 %), PI-2a (10, 10.5 %) and PI-2b (3, 3.2 %). The strains were classified into 17 individual sequence types, and further clustered into six clonal complexes (CCs). A high prevalence of CC17/PI-1 and PI-2b (17, 34.0 %) was detected in 50 GBS isolates causing neonatal infections. No strain was resistant to penicillin, ampicillin, ceftriaxone or vancomycin, whereas 78.9, 76.8 and 81.5 % were resistant to erythromycin, clindamycin and tetracycline, respectively. Conclusion. Our study highlights the high genotypic diversity of GBS strains causing materno-neonatal infections, and the CC17/PI-1 and PI-2b sublineages should be noted in neonatal infections.

Helicobacter pylori (H. pylori) infection has been found associated with Alzheimer’s disease (AD) with unclear mechanisms. Outer Membrane Vesicles (OMVs) are spherical particles secreted by Gram-negative bacteria. Here we explore the effect of H. pylori OMVs on Aβ aggregation and toxicity. We show intraperitoneally-injected H. pylori OMVs enter the brain and co-localize with Aβ plaques in APP/PS1 mice, accompanied by aggravated Aβ pathology, exacerbated cognitive deficits and synaptic impairment, indicating that H. pylori OMVs promote β-amyloidosis and AD development. The in vitro results further identify that H. pylori OMVs significantly accelerate Aβ aggregation and increase Aβ-induced neurotoxicity. Through lipidomic analysis, we reveal that lipid components, particularly LPC 18:0 in H. pylori OMVs accelerate Aβ aggregation and enhance Aβ neurotoxicity. Moreover, H. pylori OMVs-enhanced Aβ neurotoxicity is mediated by Ca²⁺. These findings reveal a mechanism of H. pylori OMVs in accelerating AD development in which the bacterial OMVs-originated lipid components play a key role in promoting Aβ aggregation and neurotoxicity.