No abstract

Depression is a global disease that places a significant burden on human health. Neuroinflammation and disturbance of glutamate metabolism in brain regions, such as the hippocampus, play vital roles in the development of depression. Previous studies have shown that cyanidin chloride (Cycl) has anti-inflammatory and antioxidant properties with neuroprotective effects in peripheral tissues. However, the effects of Cycl on depression and the possible mechanism by which this compound targets brain regions remain less elucidated. We investigated the role of Cycl in lipopolysaccharide (LPS)-induced depression and examined the influence of the drug on central inflammation and the expression of excitatory amino acid transporters in the hippocampus. We found that prophylactic i.p. application of Cycl at 20 or 40 mg/kg for 5 days significantly reduced the immobility time assessed by the tail suspension test (TST) and forced swim test (FST) in LPS-challenged mice, suggesting an effective antidepressant activity of the drug. Western blotting and immunofluorescence staining in the hippocampus revealed that Cycl inhibited the upregulation of proinflammatory cytokines, including TNF-α and IL-6, and suppressed the hyperactivity of microglia induced by LPS, indicating an anti-inflammatory role in the hippocampus. Moreover, treatment with Cycl also recovered the downregulated expression of glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), and glutamate–aspartate transporter (GLAST) and excitatory amino acid transporter 2 (EAAT2), two members in the excitatory amino acid transporter family. The role of Cycl was also verified in cultured BV2 and U251 cells. In conclusion, the present in vivo and in vitro studies demonstrate that Cycl exerts potent antidepressant action in an LPS-induced depression model and the underlying mechanism is associated with reduced hippocampal inflammation, improved neurotrophic function, and attenuated excitotoxicity induced by glutamate.

Helicobacter pylori (H. pylori) has infected more than half of the world’s population and is still a threat to human health. The urea breath test, despite being widely used in clinical diagnosis, still faces huge challenges in the immediate detection of H. pylori. Thus, a rapid, sensitive, and highly specific point of care diagnosis is particularly important for preventing the further transmission of H. pylori and for real-time monitoring of the disease in a given population. Recently, the clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostics have been applied to various types of nucleic acid testing; however, there are often shortcomings of complex operation and high signal transmission background. In this study, we proposed a new platform for the assay of H. pylori using one-tube-based CRISPR/Cas12a diagnostic methods and designed a detector for this platform, which is a portable array detector for visible analysis of thermostatic nucleic acid amplification (Pad-VATA). By incorporating isothermal recombinase polymerase amplification, our platform could detect the conserved gene fragments of H. pylori with a constant low as 2 copies/μl. The assay process can be performed at a single temperature in about 30 min and integrated into the reactor in the palm-sized Pad-VATA to facilitate rapid diagnosis of H. pylori. We also verified the accuracy of our platform using 10 clinical samples and found that the platform can quickly detect H. pylori infection in a given population. We believe that this fast, convenient, efficient, and inexpensive screening and diagnostic platform can be widely used in various settings, including homes and clinics.

The eutrophication of lake and followed cyanobacteria bloom are the most apparently ecoenvironmental problem in freshwater lakes in China. Lake Dianchi is the largest and the most serious eutrophic freshwater lake in southwest China that has experienced cyanobacterial blooms annually during the last few decades. The temporal distribution of phytoplankton biomass (estimated using chlorophyll-a concentration) and its correlation with related physical and chemical viriables including water temperature, pH, total phosphorus(TP) and total nitrogen(TN) in Lake Dianchi were investigated from March 2009 to January 2010. Due to the combined effects of high temperature, nutrient conditions and neutral to alkaline pH values in this lake, the phytoplankton biomass were higher and more uniform compared to other cyanobacterial blooms reported in temperate regions. This study advances our understanding of nutrient enrichment and high water temperature influences on phytoplankton biomass.

Cyanobacteria are widespread in eutrophic freshwater lakes and can produce potent toxins which pose serious risk for human and animal health, aquatic ecosystem sustainability and economic vitality. There are 9 major lakes, which eutrophication and related ecological problem had occurred in most of these lakes in Yunnan, China. In this study, water samples were collected at different sampling time from five freshwater plateau lakes, which located in the middle area of Yunnan province, to assess the cyanobacteria diversity vary with the seasons. The morphological character of cyanobacteria were observed by light microscope (LM), the genetic diversity of cyanobacteria had been demonstrated by constructed phylogenetic trees based on DNA sequence of cyanobacteria 16S-23S rRNA internal space (ITS).The results showed that a variety of cyanobacterial species were distributed in five plateau freshwater lakes. The cyanobacterial population consisted mainly of several Microcystis species as dominants in Dianchi Lake and the dominant species of cyanobacteria found in June to October of 2009 was Microcystis aeruginosa. The diversity of cyanobacteria in Caohai was higher than that of Waihai in Dianchi Lake.

Background: Sepsis is a fatal condition commonly caused by Methicillin-resistant Staphylococcus aureus (MRSA) with a high death rate. Macrophages can protect the host from various microbial pathogens by recognizing and eliminating them. Earlier we found that Quaking (QKI), an RNA binding protein (RBP), was involved in differentiation and polarization of macrophages. However, the role of QKI in sepsis caused by pathogenic microbes, specifically MRSA, is unclear. This study aimed to investigate the role of QKI in regulation of host-pathogen interaction in MRSA-induced sepsis and explored the underlying mechanisms.Methods: Transmission electron microscope and immunofluorescence were used to observe the autophagy level in macrophages. Real-time PCR and western blot were used to analyzed the expression of mRNA and protein respectively. The potential protein interaction was analyzed by iTRAQ mass spectrometry and Immunoprecipitation. RNA fluorescence in situ hybridization, dual-luciferase reporter assay and RNA immunoprecipitation were used to explore the mechanism of QKI regulating mRNA of PI3K-p110β.Results: The mRNA level of QKI was aberrantly decreased in monocytes and PBMCs of septic patients with the increasing level of plasma procalcitonin (PCT). Then the mice with myeloid specific knockout of QKI was challenged with MRSA or Cecal Ligation and Puncture (CLP). Mice in these two models displayed higher survival rates and lower bacterial loads. Mechanistically, QKI deletion promoted phagocytosis and autophagic degradation of MRSA via activating p110β (a member of Class IA phosphoinositide 3-kinases) mediated autophagic response. QKI expression in macrophages led to the sequestration of p110β in mRNA processing (P) bodies and translational repression. Upon infection, the direct interaction of RNF6, a RING-type E3 ligase, mediated QKI ubiquitination degradation and facilitated PI3K-p110β related autophagic removal of pathogen. The administration of nanoparticles with QKI specific siRNA significantly protected mice from MRSA infection. Conclusions: This study disclosed the novel function of QKI in the P body mRNA regulation during infection. QKI degradation in macrophage by RNF6 protects mice from MRSA infection via enhancing PI3K-p110β dependent autophagy. It suggested that QKI may serve as a potential theranostic marker in MRSA-induced sepsis.