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Pulmonary invasive fungal infection in immunocompromised hosts is difficult to diagnose, and current tools for diagnosis or monitoring of response to antifungal treatments have inherent limitations. Droplet digital PCR (ddPCR) has emerged as a promising tool for pulmonary pathogen detection with high sensitivity. This study presents a novel ddPCR panel for rapid and sensitive identification of pulmonary fungal pathogens. First, a ddPCR method for detecting three fungal genera, including Pneumocystis, Aspergillus, and Cryptococcus, was established and evaluated. Then, the clinical validation performance of ddPCR was compared with that of qPCR using 170 specimens, and the 6 specimens with inconsistent results were further verified by metagenomics next-generation sequencing, which yielded results consistent with the ddPCR findings. Finally, the area under the ROC curve (AUC) was used to evaluate the efficiency of ddPCR. While the qPCR identified 16 (9.41%) cases of Aspergillus and 6 (3.53%) cases of Pneumocystis, ddPCR detected 20 (11.76%) Aspergillus cases and 8 (4.71%) Pneumocystis cases. The AUC for Aspergillus, Cryptococcus, and Pneumocystis was 0.974, 0.998, and 0.975, respectively. These findings demonstrated that the ddPCR assay is a highly sensitive method for identifying pathogens responsible for invasive fungal pulmonary infections, and is a promising tool for early diagnosis. [ABSTRACT FROM AUTHOR]

Tripartite motif‐containing protein 21 (TRIM21), identified as both a cytosolic E3 ubiquitin ligase and FcR (Fragment crystallizable receptor), primarily interacts with proteins via its PRY/SPRY domains and promotes their proteasomal degradation to regulate intracellular immunity. But how TRIM21 involves in intracellular immunity still lacks systematical understanding. Herein, it is probed into the TRIM21‐related literature and raises an interacting model about how TRIM21 orchestrates proteins in cytosol. In this novel model, TRIM21 generally interacts with miscellaneous protein in intracellular immunity in two ways: For one, TRIM21 solely plays as an E3, ubiquitylating a glut of proteins that contain specific interferon‐regulatory factor, nuclear transcription factor kappaB, virus sensors and others, and involving inflammatory responses. For another, TRIM21 serves as both E3 and specific FcR that detects antibody‐complexes and facilitates antibody destroying target proteins. Correspondingly delineated as Fc‐independent signaling and Fc‐dependent signaling in this review, how TRIM21's interactions contribute to intracellular immunity, expecting to provide a systematical understanding of this important protein and invest enlightenment for further research on the pathogenesis of related diseases and its prospective application is elaborated. [ABSTRACT FROM AUTHOR]

Abstract: Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) is a highly promising therapeutic agent for cancer treatment, owing to its ability to selectively target tumor cells for cell death while [...]

The activity of glycogen synthase kinase beta (GSK3β) is mainly regulated by its Ser9 phosphorylation. It has been believed for a long time that Ser9 phosphorylation regulates the functions of GSK3β through inhibition of its kinase activity. In this study, we have confirmed the interaction of Ser9-phosphorylated GSK3β with 14-3-3θ by using GST pull- down assays. We show that 14-3-3θ enhances Ser9 phosphorylation of GSK3β by PKC. Surprisingly, using a NF-κB luciferase reporter system, we find that Ser9-phosphorylation of GSK3β promoted by 14-3-3θ is critical for the activation of NF-κB pathway, which may thwart the pro-apoptotic activity of GSK3β. Inhibition of either NF-κB or GSK3β significantly abolishes the anti-apoptotic effect of 14-3-3θ and Ser9-phosphorylated GSK3β, suggesting that Ser9-phosphorylated GSK3β actively antagonizes cell apoptosis in a NF-κB dependent manner. Keywords: 14-3-3θ, GSK3β, Ser9 phosphorylation, interaction, apoptosis. L'activite de la glycogene synthase kinase beta (GSK3β) est principalement regulee par sa phosphorylation sur la Ser9. On croit depuis longtemps que la phosphorylation sur la Ser9 regule les fonctions de la GSK3β au moyen de l'inhibition de son activite kinase. Dans cette etude, les auteurs ont confirme l'interaction de la GSK3β phosphorylee sur la Ser9 et la proteine 14-3-3θ a l'aide d'un test de precipitation sur GST. Ils montrent que la 14-3-3θ accroit la phosphorylation de la GSK3β sur la Ser9 par la PKC. De maniere inattendue, les auteurs ont trouve a l'aide d'un systeme rapporteur NF-κB luciferase que la phosphorylation de la GSK3β sur la Ser9 favorisee par la 14-3-3θ est critique a l'activation de la voie du NF-κB, ce qui pourrait bloquer l'activite pro-apoptotique de la GSK3β. L'inhibition du NF-κB ou de la GSK3β diminue significativement l'effet anti-apoptotique de la 14-3-3θ et de la GSK3β phosphorylee sur la Ser9, ce qui suggere que la GSK3β phosphorylee sur la Ser9 agit activement comme antagoniste de l'apoptose de maniere dependante du NF-κB. [Traduit par la Redaction] Mots-cles: 14-3-3θ, GSK3β, phosphorylation sur la Ser9, interaction, apoptose., Introduction Glycogen synthase kinase beta (GSK3β), a ubiquitous serine/ threonine kinase and a member of the GSK3 family, was initially identified as an enzyme capable of phosphorylating glycogen synthase (Embi [...]

Abstract Low power laser irradiation (LPLI) promotes proliferation of multiple cells, which (especially red and near infrared light) is mainly through the activation of mitochondrial respiratory chain and the initiation of cellular signaling. Recently, the signaling proteins involved in LPLI-induced proliferation merit special attention, some of which are regulated by mitochondrial signaling. Hepatocyte growth factor receptor (c-Met), a member of tyrosine protein kinase receptors (TPKR), is phosphorylated during LPLI-induced proliferation, but tumor necrosis factor alpha (TNF-alpha) receptor has not been affected. Activated TPKR could activate its downstream signaling elements, like Ras/Raf/MEK/ERK, PI3K/Akt/eIF4E, PI3K/Akt/eNOS and PLC-gamma/PKC pathways. Other two pathways, ΔΨm/ATP/cAMP/JNK/AP-1 and ROS/Src, are also involved in LPLI-induced proliferation. LPLI-induced cell cycle progression can be regulated by the activation or elevated expressions of cell cycle-specific proteins. Furthermore, LPLI induces the synthesis or release of many molecules, like growth factors, interleukins, inflammatory cytokines and others, which are related to promotive effects of LPLI.