•All types and characteristics of available laboratory testing for SARS-CoV-2 were reviewed.•The selection strategies of testing and sampling sites were examined at different disease stages.•The ...choice of test depends on technical characteristics, clinical scenarios and requirements.
The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which began in Wuhan, Hubei Province, China, has rapidly spread to produce a global pandemic. It is now clear that person-to-person transmission of SARS-CoV-2 has been occurring and that the virus has been dramatically growing in recent months. Early, rapid and accurate diagnosis is of great significance for curtailing the spread of SARS-CoV-2. There are currently several diagnostic techniques (e.g. viral culture and nucleic acid amplification test) being used to detect the virus. However, the sensitivity and specificity of these methods are quite different, with the sample source and detection limit varying greatly. This study reviewed all types and characteristics of the currently available laboratory diagnostic assays for detecting SARS-CoV-2 infection and summarized the selection strategies of testing and sampling sites at different disease stages to improve the diagnostic accuracy of Coronavirus Disease 2019 (COVID-19).
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is the leading lethal infectious disease with 1.3 million deaths in 2020. Despite significant advances have been made in detection ...techniques and therapeutic approaches for tuberculosis, no suitable diagnostic tools are available for early and precise screening. Many studies have reported that Long non-coding RNAs (lncRNAs) play a regulatory role in gene expression in the host immune response against Mtb. Dysregulation of lncRNAs expression patterns associated with immunoregulatory pathways arose in mycobacterial infection. Meanwhile, host-induced lncRNAs regulate antibacterial processes such as apoptosis and autophagy to limit bacterial proliferation. In this review, we try to summarize the latest reports on how dysregulated expressed lncRNAs influence host immune response in tuberculosis infection. We also discuss their potential clinical prospects for tuberculosis diagnosis and development as molecular biomarkers.
A novel two-dimensional (2D) solid composite polymer electrolyte (SPE) was synthesized by co-assembling ionic liquid crystals 1-hexadecyl-3-methyl tetrafluoroborate (C16mimBF4) and polycationic ...liquids 1-(hexyl methacrylate)-3-butyimidazolium tetrafluoroborate (PMOBIm-BF4) along with the imidazolium moieties using a flexible spacer. Ionic liquid crystals were used to induce ion-conductive 2D pathways in the ionic liquid cationic polymer, and polymer cationic ionic liquids acted as ion-conductive media for lithium-ion batteries. Owing to its excellent thermal stability, non-inflammability, and high ionic conductivity, the PMPC0.5 electrolyte containing 3/1/0.5 ratio of polyMOBIm-BF4/PEGDA/C16mimBF4 exhibited anenhanced lithium-storage performance within a wide electrochemical window of up to 4.2 V vs. Li+/Li, and high ionic conductivity of 7.14 × 10−5 and 2.17 × 10−3 S cm−1 at 25 and 95 °C, respectively. The assembling ability of ionic liquid crystals can not only develop lamella structure and ordered channel for improved Li-ion transportation, but also could show efficient enhancement for ionic conductivity of the polyionic liquid. The Li/SPE/LiFePO4 coin cells using the PMPC0.5 as electrolyte delivered a specific capacity of 136.7 mAh g−1 in the first cycle and118.9 mAh g−1 in the 40th cycle at a rate of 0.1C.
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•Solid composite polymer electrolytes are prepared by a co-assembly method.•Ionic liquid crystals are used to induce 2-dimensional ion-conductive pathways in the electrolyte.•The polymer electrolytes are flexible, thermal stable, non-flammable, high ion conductivity.•The lamella structures and ordered channels efficiently enhance the Li ion transportation.
Background:
Hepatocellular carcinoma (HCC) is extremely malignant and difficult to treat. The adenoviral early region 2 binding factors (E2Fs) target pathway is thought to have a major role in tumor ...growth. This study aimed to identify a predictive E2F target signature and facilitate individualized treatment for HCC patients.
Methods:
We constructed an E2F target-related gene profile using univariate COX and LASSO regression models and proved its predictive efficacy in external cohorts. Furthermore, we characterized the role of the E2F target pathway in pathway enrichment, immune cell infiltration, and drug sensitivity of HCC.
Results:
Lasso Cox regression created an E2F target-related gene signature of GHR, TRIP13, and CDCA8. HCC patients with high risk were correlated with shorter survival time, immune evasion, tumor stem cell characteristics and high sensitivity to Tipifarnib and Camptothecin drugs.
Conclusion:
Hepatocellular carcinoma prognosis was predicted by an E2F target signature. This finding establishes the theoretical usefulness of the E2F target route in customized identification and treatment for future research.
Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB) causing high mortality and disability. TBM arises due to immune dysregulation, but the underlying immune mechanisms are ...unclear.
We performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF) cells isolated from children (n=6) with TBM using 10 xGenomics platform. We used unsupervised clustering of cells and cluster visualization based on the gene expression profiles, and validated the protein and cytokines by ELISA analysis.
We revealed for the first time 33 monocyte populations across the CSF cells and PBMCs of children with TBM. Within these populations, we saw that CD4_C04 cells with Th17 and Th1 phenotypes and Macro_C01 cells with a microglia phenotype, were enriched in the CSF. Lineage tracking analysis of monocyte populations revealed myeloid cell populations, as well as subsets of CD4 and CD8 T-cell populations with distinct effector functions. Importantly, we discovered that complement-activated microglial Macro_C01 cells are associated with a neuroinflammatory response that leads to persistent meningitis. Consistently, we saw an increase in complement protein (C1Q), inflammatory markers (CRP) and inflammatory factor (TNF-α and IL-6) in CSF cells but not blood. Finally, we inferred that Macro_C01 cells recruit CD4_C04 cells through CXCL16/CXCR6.
We proposed that the microglial Macro_C01 subset activates complement and interacts with the CD4_C04 cell subset to amplify inflammatory signals, which could potentially contribute to augment inflammatory signals, resulting in hyperinflammation and an immune response elicited by
-infected tissues.
Cell-free RNAs (cfRNAs) offer an opportunity to detect diseases from a transcriptomic perspective, however, existing techniques have fallen short in generating a comprehensive cell-free transcriptome ...profile. We develop a sensitive library preparation method that is robust down to 100 µl input plasma to analyze cfRNAs independent of their 5'-end modifications. We show that it outperforms adapter ligation-based method in detecting a greater number of cfRNA species. We perform transcriptome-wide characterizations in 165 lung cancer, 30 breast cancer, 37 colorectal cancer, 55 gastric cancer, 15 liver cancer, and 133 cancer-free participants and demonstrate its ability to identify transcriptomic changes occurring in early-stage tumors. We also leverage machine learning analyses on the differentially expressed cfRNA signatures and reveal their robust performance in cancer detection and classification. Our work sets the stage for in-depth study of the cfRNA repertoire and highlights the value of cfRNAs as cancer biomarkers in clinical applications.
Oxygen uptake (V˙ O2) was measured during a non-exhaustive high-intensity intermittent cross-exercise (HIICE) protocol consisting of four alternating bouts of 20 s running (R) and three bouts of ...bicycle exercise (BE) at ∼160% and ∼170% maximal oxygen uptake (V˙ O2max), respectively, with 10 s between-bout rests (sequence R-BE-R-BE-R-BE-R). The V˙ O2 during the last BE (52.2 ± 5.0 mL·kg−1·min−1) was significantly higher than the V˙ O2max of the BE (48.0 ± 5.4 mL·kg−1·min−1, n = 30) and similar to that of running. For clarifying the underlying mechanisms, a corresponding HIICE-protocol with BE and arm cranking ergometer exercise (AC) was used (sequence AC-AC-BE-AC-BE-AC-AC-BE). In some experiments, thigh blood flow was occluded by a cuff around the upper thigh. Without occlusion, the V˙ O2 during the AC (39.2 ± 7.1 mL·kg−1·min−1 6th bout) was significantly higher than the V˙ O2max of AC (30.2 ± 4.4 mL·kg−1·min−1, n = 7). With occlusion, the corresponding V˙ O2 (29.8 ± 3.9 mL·kg−1·min−1) was reduced to that of the V˙ O2max of AC and significantly less than the V˙ O2 without occlusion. These findings suggest that during the last bouts of HIICE may exceed the of the specific exercise, probably because it is a summation of the V˙ O2 for the ongoing exercise plus excess post-oxygen consumption (EPOC) produced by the previous exercise with a higher V˙ O2max.
Drug-resistant tuberculosis (TB) poses a major threat to global TB control; consequently, there is an urgent need to develop novel anti-TB drugs or strategies. Host-directed therapy (HDT) is emerging ...as an effective treatment strategy, especially for drug-resistant TB. This study evaluated the effects of berbamine (BBM), a bisbenzylisoquinoline alkaloid, on mycobacterial growth in macrophages. BBM inhibited intracellular
Mycobacterium tuberculosis
(Mtb) growth by promoting autophagy and silencing ATG5, partially abolishing the inhibitory effect. In addition, BBM increased intracellular reactive oxygen species (ROS), while the antioxidant
N
-acetyl-L-cysteine (NAC) abolished BBM-induced autophagy and the ability to inhibit Mtb survival. Furthermore, the increased intracellular Ca
2+
concentration induced by BBM was regulated by ROS, and BAPTA-AM, an intracellular Ca
2+
-chelating agent, could block ROS-mediated autophagy and Mtb clearance. Finally, BBM could inhibit the survival of drug-resistant Mtb. Collectively, these findings provide evidence that BBM, a Food and Drug Administration (FDA)–approved drug, could effectively clear drug-sensitive and -resistant Mtb through regulating ROS/Ca
2+
axis-mediated autophagy and has potential as an HDT candidate for TB therapy.
Tuberculosis (TB), which is caused by the single pathogenic bacterium, Mycobacterium tuberculosis, is among the top 10 lethal diseases worldwide. This situation has been exacerbated by the increasing ...number of cases of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Histamine is an organic nitrogenous compound that mediates a plethora of cell processes via different receptors. The expression of histamine receptor H1 (HRH1), one of the four histamine receptors identified to date was previously reported to be augmented by M. tuberculosis infection, although the underlying mechanism is unclear. In the present study, we applied confocal microscopy, flow cytometry, and Western blotting to show that HRH1 expression was enhanced in macrophages following mycobacterial infection. Furthermore, by combining techniques of gene knockdown, immunoprecipitation, intracellular bacterial burden analysis, fluorescence labeling, and imaging, we found that M. tuberculosis targeted the host HRH1 to suppress NOX2-mediated cROS production and inhibit phagosome maturation and acidification via the GRK2-p38MAPK signaling pathway. Our findings clarified the underlying mechanism of the M. tuberculosis and host HRH1 interaction and may provide useful information for the development of novel antituberculosis treatments. IMPORTANCE Once engulfed in macrophage phagosomes, M. tuberculosis adopts various strategies to take advantage of the host environment for its intracellular survival. Histamine is an organic nitrogen-containing compound that mediates a plethora of cellular processes via different receptors, but the crosstalk mechanism between M. tuberculosis and HRH1 in macrophages is not clear. Our results revealed that M. tuberculosis infection enhanced HRH1 expression, which in turn restrained macrophage bactericidal activity by modulating the GRK2-p38MAPK signaling pathway, inhibiting NOX2-mediated cROS production and phagosome maturation. Clarification of the underlying mechanism by which M. tuberculosis utilizes host HRH1 to favor its intracellular survival may provide useful information for the development of novel antituberculosis treatments.
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