Background: The severity and outcome of COVID-19 cases has been associated with the percentage of circulating lymphocytes (LYM%), levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), lactic acid (LA), and viral load (ORF1ab Ct). However, the predictive power of each of these indicators in disease classification and prognosis remains largely unclear. Methods: We retrospectively collected information on the above parameters in 142 patients with COVID-19, stratifying them by survival or disease severity. Findings: CRP, PCT, IL-6, LYM%, and ORF1ab Ct were significantly altered between survivors and non-survivors. LYM%, CRP, and IL-6 were the most sensitive and reliable factors in distinguishing between survivors and non-survivors. These indicators were significantly different between critically ill and severe/moderate patients. Only LYM% levels were significantly different between severe and moderate types. Among all the investigated indicators, LYM% was the most sensitive and reliable in discriminating between critically ill, severe, and moderate types and between survivors and non-survivors. Conclusions: CRP, PCT, IL-6, LYM%, and ORF1ab Ct, but not LA, could predict prognosis and guide classification of COVID-19 patients. LYM% was the most sensitive and reliable predictor for disease typing and prognosis. We recommend that LYM% be further investigated in the management of COVID-19.

BackgroundPM2.5 (particulate matter ≤ 2.5 μm) is one of the leading environmental risk factors for the global burden of disease. Whereas increasing evidence has linked the adverse roles of PM2.5 with cardiovascular and respiratory diseases, limited but growing emerging evidence suggests that PM2.5 exposure can affect the nervous system, causing neuroinflammation, synaptic dysfunction and cognitive deterioration. However, the molecular mechanisms underlying the synaptic and cognitive deficits elicited by PM2.5 exposure are largely unknown.MethodsC57BL/6 mice received oropharyngeal aspiration of PM2.5 (1 and 5 mg/kg bw) every other day for 4 weeks. The mice were also stereotaxically injected with β-site amyloid precursor protein cleaving enzyme 1 (β-secretase, BACE1) shRNA or LV-miR-574-5p lentiviral constructs in the absence or presence of PM2.5 aspiration at 5 mg/kg bw every other day for 4 weeks. Spatial learning and memory were assessed with the Morris water maze test, and synaptic function integrity was evaluated with electrophysiological recordings of long-term potentiation (LTP) and immunoblot analyses of glutamate receptor subunit expression. The expression of α-secretase (ADAM10), BACE1, and γ-secretase (nicastrin) and the synthesis and accumulation of amyloid β (Aβ) were measured by immunoblot and enzyme-linked immunosorbent assay (ELISA). MicroRNA (miRNA) expression was screened with a microRNA microarray analysis and confirmed by real-time quantitative reverse transcription PCR (qRT-PCR) analysis. Dual-luciferase reporter gene and chromatin immunoprecipitation (ChIP) analyses were used to detect the binding of miR-574-5p in the 3’UTR of BACE1 and NF-κB p65 in the promoter of miR-574-5p, respectively.ResultsPM2.5 aspiration caused neuroinflammation and deteriorated synaptic function integrity and spatial learning and memory, and the effects were associated with the induction of BACE1. The action was mediated by NF-κB p65-regulated downregulation of miR-574-5p, which targets BACE1. Overexpression of miR-574-5p in the hippocampal region decreased BACE1 expression, restored synaptic function, and improved spatial memory and learning following PM2.5 exposure.ConclusionsTaken together, our findings reveal a novel molecular mechanism underlying impaired synaptic and cognitive function following exposure to PM2.5, suggesting that miR-574-5p is a potential intervention target for the prevention and treatment of PM2.5-induced neurological disorders.Electronic supplementary materialThe online version of this article (10.1186/s12989-017-0215-3) contains supplementary material, which is available to authorized users.

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Severe spinal cord injury (SCI) can cause neurological dysfunction and paralysis. However, the early dynamic changes of neurons and their surrounding environment after SCI are poorly understood. Although methylprednisolone (MP) is currently the standard therapeutic agent for treating SCI, its efficacy remains controversial. The purpose of this project was to investigate the early dynamic changes and MP's efficacy on axonal damage, blood flow, and calcium influx into axons in a mouse SCI model. YFP H-line and Thy1-GCaMP transgenic mice were used in this study. Two-photon microscopy was used for imaging of axonal dieback, blood flow, and calcium influx post-injury. We found that MP treatment attenuated progressive damage of axons, increased blood flow, and reduced calcium influx post-injury. Furthermore, microglia/macrophages accumulated in the lesion site after SCI and expressed the proinflammatory mediators iNOS, MCP-1 and IL-1β. MP treatment markedly inhibited the accumulation of microglia/macrophages and reduced the expression of the proinflammatory mediators. MP treatment also improved the recovery of behavioral function post-injury. These findings suggest that MP exerts a neuroprotective effect on SCI treatment by attenuating progressive damage of axons, increasing blood flow, reducing calcium influx, and inhibiting the accumulation of microglia/macrophages after SCI.

Metabolic reprogramming in tumor-associated macrophages (TAM) is associated with cancer development, however, the role of macrophage triglyceride metabolism in cancer metastasis is unclear. Here, we showed that TAMs exhibited heterogeneous expression of abhydrolase domain containing 5 (ABHD5), an activator of triglyceride hydrolysis, with migratory TAMs expressing lower levels of ABHD5 compared with the nonmigratory TAMs. ABHD5 expression in macrophages inhibited cancer cell migration in vitro in xenograft models and in genetic cancer models. The effects of macrophage ABHD5 on cancer cell migration were dissociated from its metabolic function as neither triglycerides nor ABHD5-regulated metabolites from macrophages affected cancer cell migration. Instead, ABHD5 deficiency in migrating macrophages promoted NFkB p65-dependent production of matrix metalloproteinases (MMP). ABHD5 expression negatively correlated with MMP expression in TAMs and was associated with better survival in patients with colorectal cancer. Taken together, our findings show that macrophage ABHD5 suppresses NFkB-dependent MMP production and cancer metastasis and may serve as a prognostic marker in colorectal cancer.

Atrophic non-union is a serious complication of fractures. The underlying biological mechanisms involved in its pathogenesis are not yet completely understood. MicroRNAs (miRNAs or miRs) are a type of endogenous small non-coding RNA, which participate in various physiological and pathophysiological processes. In this study, differentially expressed miRNAs were screened in patients with atrophic nonunion. In total, 4 miRNAs (miR-149*, miR-221, miR-628-3p and miR-654-5p) were upregulated and 7 miRNAs (let-7b*, miR-220b, miR-513a-3p, miR-551a, miR-576-5p, miR-1236 and kshv-miR-K12-6-5p) were downregulated at the fracture sites in patients with atrophic non-union. Among the upregulated miRNAs, miR-628-3p and miR-654-5p expression was found to be persistently decreased during osteoblast differentiation, indicating their possible inhibitory effect on osteogenesis. Gain-of-function experiment demonstrated that miR-628-3p, but not miR-654-5p, attenuated osteoblast differentiation. Further, in silico analysis revealed that runt-related transcription factor 2 (RUNX2), the master transcript factor for osteoblast differentiation, was the target of miR-628-3p, which had two binding site-condense regions in the 3′ untranslated region. The exact binding site of miR-628-3p was further identified with luciferase reporter assay. In addition, the overexpression of miR-628-3p appeared to be associated with the suppression of RUNX2 expression at both the mRNA and protein level, suggesting that miR-628-3p inhibits osteoblast differentiation via RUNX2. On the whole, the findings of this study provide evidence of the upregulation of miR-628-3p in patients with atrophic non-union and that miR-628-3p may exert an inhibitory effect on osteogenesis via the suppression of its target gene, RUNX2. The study provides valuable insight into the pathogenesis of atrophic non-union and suggests new potential therapeutic targets for the treatment of this disorder.

Substantial epidemiological evidence has consistently reported that fine particulate matter (PM2.5) is associated with an increased risk of cardiovascular outcomes. PM2.5 is a complex mixture of extremely small particles and liquid droplets composed of multiple components, and there has been high interest in identifying the specific health-relevant physical and/or chemical toxic constituents of PM2.5. In the present study, we analyzed 8 heavy metals (Cr, Ni, Cu, Cd, Pb, Zn, Mn and Co) in the PM2.5 collected during four different seasons in Taiyuan, a typical coal-burning city in northern China. Our results indicated that total concentrations of the 8 heavy metals differed among the seasons. Zn and Pb, which are primarily derived from the anthropogenic source, coal burning, were the dominant elements, and high concentrations of these two elements were observed during the spring and winter. To clarify whether these heavy metals in the locally collected PM2.5 were associated with health effects, we conducted health risk assessments using validated methods. Interestingly, Pb was responsible for greater potential health risks to children. Because cardiovascular disease (CVD) is a main contributor to the mortality associated with PM2.5 exposure, we performed experimental assays to evaluate the myocardial toxicity. Our in vitro experiments showed that the heavy metal-containing PM2.5 induced season-dependent apoptosis in rat H9C2 cells through a reactive oxygen species (ROS)-mediated inflammatory response. Our findings suggested that heavy metals bound to PM2.5 produced by coal burning play an important role in myocardial toxicity and contribute to season-dependent health risks.