A Gram-stain-negative, aerobic, coccoid to small rod-shaped bacterium, designated X1T, was isolated from sludge collected from the vicinity of pesticide manufacturer in Nantong, Jiangsu Province, China. Based on 16S rRNA gene sequence analysis, strain X1T belonged to the genus Cupriavidus, and was most closely related to C. taiwanensis LMG 19424T (99.1% 16S rRNA gene sequence similarity) and C. alkaliphilus LMG 26294T (98.9%). Strain X1T showed 16S rRNA gene sequence similarities of 97.2%-98.2% with other species of the genus Cupriavidus. The major cellular fatty acids of strain X1T were C16:0, C16:1ω7c and/or iso-C15:0 2-OH (Summed feature 3), C18:1ω7c and C17:0 cyclo, and the major respiratory quinone was ubiquinone Q-8 (94%). The major polar lipids of strain X1T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, aminophospholipid and hydroxyphosphatidylethanolamine. The DNA G+C content was 66.6 mol%. The DNA-DNA relatedness values of strain X1T with five reference strains Cupriavidus taiwanensis LMG 19424T, Cupriavidus alkaliphilus LMG 26294T, Cupriavidus necator LMG 8453T, Cupriavidus gilardii LMG 5886T and Cupriavidus yeoncheonense KCTC 42053T were lower than 70%. The results obtained from phylogenetic analysis, phenotypic characterization and DNA-DNA hybridization indicated that strain X1T should be proposed to represent a novel species of the genus Cupriavidus, for which the name Cupriavidus nantongensis sp. nov. is proposed. The type strain is X1T (=KCTC 42909T=LMG 29218T).

Polyphyllin II (PPII) is a natural steroidal saponin occurring in Rhizoma Paridis. It has been demonstrated to exhibit anti-cancer activity against a variety of cancer cells. However, the anti-colorectal cancer (CRC) effects and mechanism of action of PPII are rarely reported. In the present study, we showed that PPII inhibited the proliferation of HCT116 and SW620 cells. Moreover, PPII induced G2/M-phase cell cycle arrest and apoptosis, as well as protective autophagy, in CRC cells. We found that PPII-induced autophagy was associated with the inhibition of PI3K/AKT/mTOR signaling. Western blotting results further revealed that PPII lowered the protein levels of phospho-Src (Tyr416), phospho-JAK2 (Tyr1007/1008), phospho-STAT3 (Tyr705), and STAT3-targeted molecules in CRC cells. The overactivation of STAT3 attenuated the cytotoxicity of PPII against HCT116 cells, indicating the involvement of STAT3 inhibition in the anti-CRC effects of PPII. PPII (0.5 mg/kg or 1 mg/kg, i.p. once every 3 days) suppressed HCT116 tumor growth in nude mice. In alignment with the in vitro results, PPII inhibited proliferation, induced apoptosis, and lowered the protein levels of phospho-STAT3, phospho-AKT, and phospho-mTOR in xenografts. These data suggest that PPII could be a potent therapeutic agent for the treatment of CRC.

Colistin is used as one of the last-resort drugs against lethal infections caused by carbapenem-resistant Enterobacteriaceae family of pathogens. Enterobacteriaceae bacteria carrying the mcr-1 colistin resistance gene are emerging in livestock and poultry, posing a serious threat to human health. However, the prevalence and transmission of mcr-1 along the regional chicken supply chain remain rarely reported. In this study, the complete sequences of mcr-1 -positive Escherichia coli ST2705 and ST206 isolates obtained by screening 129 chilled chicken samples and 251 chicken fecal samples were investigated. Both of these isolates showed resistance to colistin, and importantly, the complete sequence of the mcr-1 -positive E. coli ST2705 in China was reported for the first time. The mcr-1 gene was located on the IncHI2 plasmids pTBMCR421 (254,365 bp) and pTBMCR401 (230,964 bp) in strains ECCNB20-2 and ECZP248, respectively. Comparative analysis of mcr-1 -bearing IncHI2 plasmids showed a marked similarity, indicating that these plasmids are very common and have the ability to be efficient vehicles for mcr-1 dissemination among humans, animals and food. Furthermore, an insertion (IS Kpn26 ) in Tn 6330 (IS Apl1 - mcr- 1- pap2 -IS Apl1 ) was identified in the plasmid pTBMCR401 and then compared; this insertion might affect the adaptability and stability of Tn 6330 . Taken together, these findings suggest that the IncHI2 plasmid might be a main factor affecting the transmission of mcr-1 in the chicken supply chain and that the genetic context of the mcr-1 -bearing IncHI2 plasmid is constantly evolving.

Methamphetamine (Meth) is a highly addictive substance and the largest drug threat across the globe. There is evidence to indicate that Meth use has serious damage on central nervous system (CNS) and heart in several animal and human studies. However, the connection in the process of Meth addiction between these two systems has not been determined. Emerging data suggest that extracellular vesicles (EVs) carrying behavior-altering microRNA (miRNAs) play a crucial role in cell communication between CNS and peripheral system. Rhynchophylline (Rhy), an antiaddictive alkaloid, was used to protect the brain and heart from Meth-induced damage, which has caught our attention. Here, we used Meth-dependent conditioned place preference (CPP) animal model and cell model to verify the protective effect of Rhy-treated EVs. Further, small RNA sequencing analysis, qPCR, dual-luciferase reporter assay, and transfection test were used to identify the key EVs-encapsulated miRNAs, isolated from cultured H9c2 cells with different treatments, involved in the therapeutic effect and the underlying mechanisms of Rhy. The results demonstrate that Rhy-treated EVs exert protective effects against Meth dependence through the pathway of miR-183-5p-neuregulin-1 (NRG1). Our collective findings provide novel insights into the roles of EVs miRNAs in Meth addiction and support their potential application in the development of novel therapeutic approaches.

Neuroinflammation, characterized by microglial activation and the subsequent secretion of inflammatory cytokines, plays a pivotal role in neurodegenerative diseases and brain injuries, often leading to neuronal damage and death. Alleviating neuroinflammation has thus emerged as a promising strategy to protect neurons and ameliorate neurodegenerative disorders. While peroxisome proliferator-activated receptor gamma (PPARγ) agonists have demonstrated potential therapeutic actions on neuroinflammation, their prolonged use, such as with rosiglitazone, can lead to cardiac risks and lipid differentiation disorders. In this study, we investigated the effects of a newly synthesized PPARγ agonist, VSP-2, on secretion of inflammatory cytokines in BV2 cells. Treatment with VSP-2 significantly reduced the mRNA and protein levels of proinflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Furthermore, VSP-2 attenuated the phosphorylation of nuclear factor kappa B (NF-κB) (65 kD) and IκBα, as well as the nuclear translocation of NF-κB (65 kD). Additionally, the use of PPARγ small interfering RNA was able to attenuate the effects of VSP-2 on proinflammatory cytokines and the NF-κB pathway. In conclusion, our findings suggest that VSP-2 effectively suppressed the expressions of IL-1β, IL-6, and TNF-α via the PPARγ/NF-κB signaling pathway. Given its potential therapeutic benefits, VSP-2 may emerge as a promising candidate for the treatment of neurodegenerative diseases or brain injuries associated with neuroinflammation.