Morphology, Development, and Pigment Production of Talaromyces marneffei are Diversely Modulated Under Physiologically Relevant Growth Conditions.

Talaromyces marneffei is an opportunistic pathogenic fungus that mainly affects HIV-positive individuals endemic to Southeast Asia and China. Increasing efforts have been made in the pathogenic mechanism and host interactions understanding of this pathogen in the last two decades; however, there are still no conclusions on how T. marneffei was transmitted from the donor bamboo rats to humans. A perception that the failure of fungus isolation from soil was attributed to the low salt tolerance of T. marneffei. Therefore, the effect of environmental fluctuations in fungal growth and development is fundamental for the characterization of its origin and fungal biology understanding. Herein, we characterized high osmolarity, pH, metal ions, nutrients, and oxidative stress have versatile effects on T. marneffei hyphal or yeast growth, conidia generation, and pigment production. Among these, high pH, low glucose amounts, and the inorganic nitrogen ammonium tartrate stimulated the red pigment production, whereas high osmolarity, high pH, and the inorganic nitrogen sodium nitrate could significantly accelerate the conidia generation. Specifically, zinc starvation repressed conidia generation and prevented the wrinkled yeast colony formation, indicating the function of zinc regulators in pathogenicity regulation. Since conidia are recognized as the infectious propagules, the effects characterization of different environmental factors in T. marneffei morphology in this work will not only expand the growth and pathogenic biology understanding of the fungus but also provide more clues for the T. marneffei infection transmission origin investigation.

Comparative plasma metabolomic analysis to identify biomarkers for lead-induced cognitive impairment.

BACKGROUND: Lead (Pb), an environmental neurotoxicant, is known to induce cognitive impairment. Neuroinflammation and oxidative stress in the brain tissue are common pathogenetic links to Pb-induced cognitive impairment. There are no existing biomarkers to evaluate Pb-reduced cognition. Plasma metabolites are the readout of the biological functions of the host, making it a potential biomarker for assessing heavy metal-induced cognitive impairment. METHODS: The present report aims to identify the plasma metabolite changes under conditions of high plasma Pb levels and low cognition. RESULTS: We conducted a comparative plasma metabolomic analysis on two groups of adults those with low plasma Pb level and high cognition vs. those with high plasma Pb level and low cognition and identified 20 dysregulated metabolites. In addition, we found a significant reduction in docosahexaenoic acid, glycoursodeoxycholic acid, and arachidonic acid, and significant induction of p-cresol sulfate and phenylacetyl-l-glutamine. Gene Ontology enrichment analysis highlighted the importance of these plasma metabolites in brain functions and neurodegenerative diseases such as Parkinson's disease. CONCLUSIONS: The findings of this report provide novel insights into the use of plasma metabolites to assess metal-induced cognitive impairment.

Pharmacological targets and mechanisms of calycosin against meningitis.

This report aimed to identity the potential anti-meningitis targets and mechanisms functioned by calycosin through network pharmacology approach. The bioinformatics databases were used to screen and collect the candidate genes/targets of calycosin and meningitis prior to identification of vital biotargets of calycosin-anti-meningitis. Additionally, the functional processes, signaling pathways of calycosin-anti-meningitis were screened and identified before further data visualization. As a result, all candidate and mapped biotargets of calycosin and meningitis were harvested before the vital targets of epidermal growth factor receptor (EGFR), tumor necrosis factor (TNF), epidermal growth factor (EGF), ataxia telangiectasia mutated protein (ATM), estrogen receptor alpha (ESR1), caspase-8 (CASP8), nerve growth factor (NGF) of calycosin-anti-meningitis were identified. The molecular processes of calycosin-anti-meningitis were screened and identified, including reduction of inflammatory development. Furthermore, the molecular pathways of calycosin-anti-meningitis were revealed, including suppression of NF-kappa B, Toll-like receptor, TNF signaling pathways. Molecular docking findings uncovered the docking capacity of calycosin with meningitis and potential pharmacological activity of calycosin against meningitis. In conclusion, these bioinformatic data uncovered the network targets and mechanisms of calycosin-anti-meningitis. And the current findings indicated that the vital targets might be used as potent biomarkers for detecting meningitis.

The genetic relationship between epilepsy and hemiplegic migraine.

Epilepsy and migraine are common diseases of the nervous system and share genetic and pathophysiological mechanisms. Familial hemiplegic migraine is an autosomal dominant disease. It is often used as a model of migraine. Four genes often contain one or more mutations in both epilepsy and hemiplegic migraine patients (ie, CACNA1A, ATP1A2, SCN1A, and PRRT2). A better understanding of the shared genetics of epilepsy and hemiplegic migraine may reveal new strategic directions for research and treatment of both the disorders.

Expression and significance of platelet derived growth factor and its receptor in liver tissues of patients with liver fibrosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the expression and significance of platelet derived growth factor (PDGF) and its receptor (PDGFR) in liver tissues of patients with chronic hepatitis fibrosis and liver cirrhosis.</p><p><b>METHODS</b>The expression, distribution, quantitation, and correlation of PDGF-A, PDGF-B, PDGFR-alpha, PDGFR-beta, and alpha-SMA in the liver tissues were analyzed by immunohistochemical techniques in 21 patients with chronic hepatitis and 42 patients with liver cirrhosis.</p><p><b>RESULTS</b>In the liver tissues of chronic hepatitis and liver cirrhosis, PDGF and its receptor and alpha-SMA mainly distributed in the fibrotic septa and the infiltration area of inflammation, particularly in branch spindle-shaped cells (activated HSC). The expression of PDGF-B and PDGFR-beta was stronger than that of PDGF-A and PDGFR-alpha with a significant difference between them (P<0.05 approximately 0.01). The expression and distribution of alpha-SMA was basically identical with the expression and distribution of PDGF-A, PDGF-B and PDGFR-alpha, PDGFR-beta and quantitative analysis showed a positive correlation (r=0.606, P<0.001).</p><p><b>CONCLUSIONS</b>PDGF and PDGFR play a key role in liver fibrogenesis and development. The biologic effects of PDGF are elicited through activising HSC. Inhibiting PDGF and its receptor is a new approach to the treatment of liver fibrosis.</p>