ABSTRACT
Various animal toxins pose a significant threat to human safety, necessitating urgent attention to their treatment and research. The clinical potential of programmed cell death (PCD) is widely regarded as a target for envenomation, given its crucial role in regulating physiological and pathophysiological processes. Current research on animal toxins examines their specific components in pathomechanisms and injuries, as well as their clinical applications. This review explores the relationship between various toxins and several types of PCD, such as apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis, to provide a reference for future understanding of the pathophysiology of toxins and the development of their potential clinical value.
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An increased risk for human infection with avian influenza A(H5N1) viruses is of concern. We developed an internally controlled, dual-target reverse transcription PCR for influenza A(H5) subtyping. This test could be used to detect influenza A(H5) in clinical samples.
Subject(s)
Influenza in Birds , Influenza, Human , Reverse Transcriptase Polymerase Chain Reaction , Humans , Animals , Influenza in Birds/virology , Influenza in Birds/diagnosis , Influenza, Human/virology , Influenza, Human/diagnosis , Reverse Transcriptase Polymerase Chain Reaction/methods , Influenza A Virus, H5N1 Subtype/genetics , Influenza A Virus, H5N1 Subtype/classification , Influenza A Virus, H5N1 Subtype/isolation & purification , Birds/virology , Multiplex Polymerase Chain Reaction/methods , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Influenza A virus/genetics , Influenza A virus/classification , Influenza A virus/isolation & purificationABSTRACT
Snakebite envenomation often induces acute kidney injury (AKI) and acute liver injury (ALI), leading to augmented injuries and poor rehabilitation. Phospholipase A2 (PLA2) and metalloproteinase (SVMP) present in venom are responsible for the envenomation-associated events. In this study, mice envenomed with Deinagkistrodon acutus, Naja atra, or Agkistrodon halys pallas venom exhibited typical AKI and ALI symptoms, including significantly increased plasma levels of myoglobin, free hemoglobin, uric acid, aspartate aminotransferase, and alanine aminotransferase and upregulated expression of kidney NGAL and KIM-1. These effects were significantly inhibited when the mice were pretreated with natural inhibitors of PLA2 and SVMP isolated from Sinonatrix annularis (SaPLIγ and SaMPI). The inhibitors protected the physiological structural integrity of the renal tubules and glomeruli, alleviating inflammatory infiltration and diffuse hemorrhage in the liver. Furthermore, the dual therapy alleviated oxidative stress and apoptosis in the kidneys and liver by mitigating mitochondrial damage, thereby effectively reducing the lethal effect of snake venom in the inhibitor-treated mouse model. This study showed that dual therapy with inhibitors of metalloproteinase and phospholipase can effectively prevent ALI and AKI caused by snake bites. Our findings suggest that intrinsic inhibitors present in snakes are prospective therapeutic agents for multi-organ injuries caused by snake envenoming.
Subject(s)
Acute Kidney Injury , Metalloproteases , Snake Bites , Animals , Acute Kidney Injury/drug therapy , Acute Kidney Injury/pathology , Mice , Male , Metalloproteases/antagonists & inhibitors , Metalloproteases/metabolism , Snake Bites/drug therapy , Snake Bites/complications , Phospholipase A2 Inhibitors/pharmacology , Phospholipases A2/metabolism , Liver/drug effects , Liver/pathology , Liver/metabolism , Crotalinae , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/etiology , Oxidative Stress/drug effects , Kidney/drug effects , Kidney/pathology , Crotalid Venoms/toxicity , Snake Venoms , Apoptosis/drug effects , Elapid VenomsABSTRACT
Respiratory syncytial virus (RSV) causes a large burden of respiratory illness globally. It has two subtypes, RSV A and RSV B, but little is known regarding the predominance of these subtypes during different seasons and their impact on morbidity and mortality. Using molecular methods, we quantified RSV A and RSV B RNA in wastewater solids across multiple seasons and metropolitan areas to gain insight into the predominance of RSV subtypes. We determined the predominant subtype for each group using the proportion of RSV A to total RSV (RSV A + RSV B) in each wastewater sample (PA,WW) and conducted a comparative analysis temporally, spatially, and against clinical specimens. A median PA,WW of 0.00 in the first season and 0.58 in the second season indicated a temporal shift in the predominant subtype. Spatially, while we observed dominance of the same subtype, PA,WW was higher in some areas (PA,WW = 0.58-0.88). The same subtype predominated in wastewater and clinical samples, but clinical samples showed higher levels of RSV A (RSV A positivity in clinical samples = 0.79, median PA,WW = 0.58). These results suggest that wastewater, alongside clinical data, holds promise for enhanced subtype surveillance.IMPORTANCERespiratory syncytial virus (RSV) causes a large burden of respiratory illness globally. It has two subtypes, RSV A and RSV B, but little is known regarding the predominance of these subtypes during different seasons and their impact on morbidity and mortality. The study illustrates that information on subtype predominance can be gleaned from wastewater. As a biological composite sample from the entire contributing population, wastewater monitoring of RSV A and B can complement clinical surveillance of RSV.
Subject(s)
RNA, Viral , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Seasons , Wastewater , Wastewater/virology , Humans , Respiratory Syncytial Virus, Human/genetics , Respiratory Syncytial Virus, Human/classification , Respiratory Syncytial Virus, Human/isolation & purification , Respiratory Syncytial Virus Infections/virology , RNA, Viral/genetics , Spatio-Temporal AnalysisABSTRACT
The severe shuttle effect of polysulfides (LiPSs) and the slow liquid-solid phase conversion are the main obstacles hindering the practical application of lithium-sulfur (Li-S) batteries. Separator modification with a high-activity catalyst can boost LiPSs conversion and suppress their shuttle effect. In this work, multi-heterostructured MXene/NiS2/Co3S4 with rich S-vacancies was constructed facilely with a hydrothermal and high-temperature annealing strategy for separator modification. The MXene sheet not only provides a physical barrier but also ensures a high conductivity and adsorption capacity of the catalyst; the dual active centers of NiS2 and Co3S4 catalyze LiPSs conversion. In addition, the vacancies and heterostructures can modulate the electronic structure of the catalyst, improve its intrinsic activity, and reduce the polysulfides reaction barrier, thus facilitating ion/electron transport and inhibiting the shuttle effect. Benefiting from these advantages, the Li-S battery with MXene/NiS2/Co3S4 modified separator exhibits exciting discharge capacities (1495.4 mAh g-1 at 0.1C and 549.0 mAh g-1 at 6C) and an excellent ultra-long cycle life (average capacity decay rate of 0.026% for 2000 cycles at 2C); at a high sulfur loading of 10.0 mg cm-2, the battery operates for nearly 80 cycles at 0.2C, giving a capacity retention rate of 75.76%. This work provides a high-activity catalyst for Li-S batteries.
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Lung adenocarcinoma (LUAD) is a serious threat to public health and is accompanied by increased morbidity and mortality worldwide. Neuronal PAS domain protein2 (NPAS2) has been confirmed as an oncogene in LUAD; however, little is known about its molecular mechanism. Here, the expression level of NPAS2 was detected in LUAD cell lines and 16HBE cells. Gain- and loss-of-function experiments were performed. Cell Counting Kit-8, colony formation, flow cytometry, wound-healing and Transwell assays were conducted to assess cell proliferation, apoptosis, migration and invasion, respectively. Reprogramming of glucose metabolism was evaluated via oxygen consumption rate (OCR), complexes activities, lactic production and glucose consumption. The expression of critical proteins was examined by western blot. We demonstrated aberrant upregulation of NPAS2 and ß-arrestin-1 (ARRB1) in LUAD cell lines. ARRB1 was found to be a critical transcription factor of NPAS2 with binding sites within the promoter region of NPAS2, thereby causing its transcriptional activation. Functional experiments revealed that NPAS2 depletion significantly inhibited the malignant behaviours of A549 cells by suppressing cell proliferation, migration, invasion and epithelial-mesenchymal transition and promoting cell apoptosis. Meanwhile, NPAS2 depletion increased OCR and activities of complexes (I, II, III and V), and reduced lactic acid production and glucose uptake in A549 cells, indicating that NPAS2 depletion inhibited aerobic glycolysis, accompanied by reduced expression of glycolytic enzymes. However, the changes caused by NPAS2 knockdown were partly restored by ARRB1 overexpression. In conclusion, our study suggests that ARRB1 could transcriptionally activate NPAS2, facilitating malignant activities and glycolysis, and ultimately promoting the progression of LUAD, proving a novel therapeutic strategy for the treatment of LUAD.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Carbohydrate Metabolism , Glycolysis/genetics , Adenocarcinoma of Lung/genetics , Cell Proliferation/genetics , Glucose , Lung Neoplasms/genetics , Cell Movement/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Nerve Tissue Proteins/genetics , Basic Helix-Loop-Helix Transcription Factors/genetics , beta-Arrestin 1ABSTRACT
Despite having high analytical sensitivities and specificities, qualitative SARS-CoV-2 nucleic acid amplification tests (NAATs) cannot distinguish infectious from non-infectious virus in clinical samples. In this study, we determined the highest cycle threshold (Ct) value of the SARS-CoV-2 targets in the Xpert Xpress SARS-CoV-2/Flu/RSV (Xpert 4plex) test that corresponded to the presence of detectable infectious SARS-CoV-2 in anterior nasal swab samples. A total of 111 individuals with nasopharyngeal swab specimens that were initially tested by the Xpert Xpress SARS-CoV-2 test were enrolled. A healthcare worker subsequently collected anterior nasal swabs from all SARS-CoV-2-positive individuals, and those specimens were tested by the Xpert 4plex test, viral culture, and laboratory-developed assays for SARS-CoV-2 replication intermediates. SARS-CoV-2 Ct values from the Xpert 4plex test were correlated with data from culture and replication intermediate testing to determine the Xpert 4plex assay Ct value that corresponded to the presence of infectious virus. Ninety-eight of the 111 (88.3%) individuals initially tested positive by the Xpert Xpress SARS-CoV-2 test. An anterior nasal swab specimen collected from positive individuals a median of 2 days later (range, 0-9 days) tested positive for SARS-CoV-2 by the Xpert 4plex test in 39.8% (39/98) of cases. Of these samples, 13 (33.3%) were considered to contain infectious virus based on the presence of cultivable virus and replication intermediates, and the highest Ct value observed for the Xpert 4plex test in these instances was 26.3. Specimens that yielded Ct values of ≤26.3 when tested by the Xpert 4plex test had a likelihood of containing infectious SARS-CoV-2; however, no infectious virus was detected in specimens with higher Ct values.IMPORTANCEUnderstanding the correlation between real-time PCR test results and the presence of infectious SARS-CoV-2 may be useful for informing patient management and workforce return-to-work or -duty. Further studies in different patient populations are needed to correlate Ct values or other biomarkers of viral replication along with the presence of infectious virus in clinical samples.
Subject(s)
COVID-19 , Communicable Diseases , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , Nasopharynx , Molecular Diagnostic Techniques/methods , COVID-19 TestingABSTRACT
Snakebite envenomation often leads to severe visceral injuries, including acute liver injury (ALI). However, the toxicity mechanism remains unclear. Moreover, varespladib can directly inhibit phospholipase A2 (PLA2) in snake venom, but its protective effect on snakebite-induced ALI and the mechanism have not been clarified. Previous studies have shown that snake venom PLA2 leads to neuron cell death via reactive oxygen species (ROS), one of the initial factors related to the mitophagy pathway. The present study group also found that ROS accumulation occurred after Naja atra envenoming. Hematoxylin and eosin (H/E) staining and immunohistochemistry (IHC) were performed to identify the expression of inflammatory factors in the liver tissue, and flow cytometry and immunofluorescence were used to detect ROS levels and mitochondrial function. Immunofluorescence and western blotting were also used for detecting mitophagy pathway-related proteins. The results showed that N. atra bite induced ALI by activating mitophagy and inducing inflammation and that varespladib had a protective effect. Collectively, these results showed the pathological mechanism of ALI caused by N. atra bite and revealed the protective effect of varespladib.
Subject(s)
Acetates , Indoles , Mitophagy , Phospholipases A2 , Snake Bites , Animals , Mice , Mitophagy/drug effects , Phospholipases A2/metabolism , Snake Bites/drug therapy , Snake Bites/complications , Keto Acids/pharmacology , Male , Reactive Oxygen Species/metabolism , Elapid Venoms/toxicity , Liver/drug effects , Liver/pathology , Chemical and Drug Induced Liver InjuryABSTRACT
An integrated and projected-based laboratory course was described, integrating interconnected knowledge points and biochemistry and molecular biology techniques on a research project-based system. The program, which served as an essential extension of theoretical courses to practice, was conducted with a sophomore of basic medical science who had completed the course in medical biochemistry and molecular biology. This course engaged students in learning "genetic manipulation" and "recombinant DNA technology" to understand the target gene's role in disease mechanics, thus altering evaluation and treatment for clinical disease. Students could master applied and advanced techniques, such as cell culture, transfection, inducing exogenous fusion protein expression, purifying protein and its concentration assay, quantitative polymerase chain reaction, and western bot analysis. This laboratory exercise links laboratory practices with the methods of current basic research. Students need to complete the experimental design report and laboratory report, which could be advantageous for improving their ability to write lab summaries and scientific papers in the future. The reliability and validity analyses were conducted on the questionnaire, and we examined students' satisfaction with the course and their gains from the course. The student feedback was generally positive, indicating that the exercise helped consolidate theoretical knowledge, increase scientific research enthusiasm, and provide a powerful tool to be a better person and make informed decisions.
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Biochemistry , Laboratories , Molecular Biology , Molecular Biology/education , Biochemistry/education , Humans , Curriculum , Students , Surveys and Questionnaires , Educational MeasurementABSTRACT
Systemic inflammation is related to disease progression and prognosis in patients with advanced cirrhosis. However, the mechanisms underlying the initiation of inflammation are still not fully understood. The role of CD169+ monocyte/macrophage in cirrhotic systemic inflammation was undetected. Flow cytometry analysis was used to detect the percentage and phenotypes of CD169+ monocytes as well as their proinflammatory function in patient-derived cirrhotic tissue and blood. Transcriptome differences between CD169+ and CD169- monocytes were also compared. Additionally, a mouse model with specific depletion of CD169+ monocytes/macrophages was utilized to define their role in liver injury and fibrosis. We observed increased CD169 expression in monocytes from cirrhotic patients, which was correlated with inflammatory cytokine production and disease progression. CD169+ monocytes simultaneously highly expressed M1- and M2-like markers and presented immune-activated profiles. We also proved that CD169+ monocytes robustly prevented neutrophil apoptosis. Depletion of CD169+ monocytes/macrophages significantly inhibited inflammation and liver necrosis in acute liver injury, but the spontaneous fibrin resolution after repeated liver injury was impaired. Our results indicate that CD169 defines a subset of inflammation-associated monocyte that correlates with disease development in patients with cirrhosis. This provides a possible therapeutic target for alleviating inflammation and improving survival in cirrhosis.
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Liver Cirrhosis , Monocytes , Animals , Mice , Humans , Liver Cirrhosis/pathology , Inflammation , Disease Progression , Macrophages/metabolismABSTRACT
Non-venomous snakes commonly evolve natural resistance to venom to escape predators. Sinonatrix annularis serum has been shown to inhibit Deinagkistrodon acutus venom-induced hemorrhage and upregulation of serum CK, CK-MB, LDH, AST and ALT levels. Using TMT-labeled proteomics analysis, 168 proteins were found to be altered significantly in the envenomed gastrocnemius muscle and categorized into pathways such as complement and coagulation cascades, leukocyte transendothelial migration, and JAK/STAT signaling. These alterations were mitigated by S. annularis serum. Subsequently, a novel metalloproteinase inhibitor, SaMPI, was isolated from S. annularis serum by two-step chromatography. It showed strong antidotal effects against D. acutus envenomation, including inhibition of subcutaneous bleeding caused by crude venom and DaMP (a metalloproteinase derived from D. acutus) activity in a 1:1 ratio. Histology and immunoblotting analyses demonstrated that SaMPI mitigated myonecrosis, reduced neutrophil infiltration and local inflammatory factor release, and retarded JAK/STAT and MAPK signaling activation. Analysis of the SaMPI gene cloned by 5'-RACE revealed a shared sequence identity of 58-79% with other SVMP inhibitors. These findings demonstrate the protective effects of SaMPI and indicate its potential value as a candidate for viper bite adjuvant therapy.
Subject(s)
Crotalid Venoms , Humans , Crotalid Venoms/toxicity , Hemorrhage , Antidotes , MetalloproteasesABSTRACT
BACKGROUND: Cytomegalovirus (CMV) causes significant morbidity and mortality in immunocompromised patients, particularly transplant recipients. Quantitation of CMV DNA in peripheral blood is used to monitor prophylactic and pre-emptive approaches to prevent CMV disease, whereas CMV DNA testing of non-plasma specimens may aid in the diagnosis of end-organ disease. METHODS: The analytical performance of the FDA-approved Aptima CMV Quant Assay was evaluated using reference CMV (SeraCare) diluted in defibrinated human plasma, as well as negative bronchoalveolar lavage fluid and tissue. Agreement was determined using 100 clinical acid-citrate-dextrose (ACD) plasma specimens, 77 bronchoalveolar lavage (BAL) fluids, and 101 tissues previously tested using artus CMV qPCR. RESULTS: Aptima CMV lower limit of detection (LLOD) was 169 IU/mL for ACD plasma, 100 IU/mL for BAL, and 50 IU/mL for tissue. Positive percent agreement (PPA) was 100.0% (50/50; 95% CI: 92.9% - 100.0%) and negative percent agreement (NPA) was 94.0% (47/50; 95% CI: 83.5% - 98.8%) for ACD plasma. Bland-Altman analysis revealed a bias of 0.20 log10 IU/mL (Aptima - artus) with 95% limits of agreement of -0.53 to 0.93. For BAL fluids, PPA was 70.0% (14/20; 95% CI: 45.7% - 88.1%) and NPA was 82.4% (43/51; 95% CI: 69.1% - 91.6%). For tissues, PPA was 90.0% (45/50; 95% CI: 78.2% - 96.7%) and NPA was 94.0% (47/50; 95% CI: 83.5% - 98.8%). CONCLUSIONS: The Aptima CMV Quant Assay demonstrates high analytical sensitivity and good overall agreement using clinical plasma and tissue specimens.
Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Humans , Cytomegalovirus/genetics , Bronchoalveolar Lavage , Cytomegalovirus Infections/diagnosis , Bronchoalveolar Lavage Fluid , Nucleic Acid Amplification Techniques , Viral Load , DNA , DNA, Viral/geneticsABSTRACT
To promote polysulfide conversion in lithium sulfur batteries (LSB) and alleviate the shuttle effect, we designed and fabricated a novel catalyst of vanadium-doped graphite phase carbon nitride with nitrogen defects (V@gC3N4-ND) and high vanadium loading (3.46 at%) by defect engineering and two-step pyrolysis. Employing a V@gC3N4-ND modified separator, the LSB yielded capacities of 934 mA h g-1 at 1C and 404 mA h g-1 at 4C; the former was retained by 61% and 45% after 500 and 1000 cycles, respectively. In particular, the initial capacity of the battery reached 969 mA h g-1 at a sulfur loading of 10.0 mg cm-2. This work provides a facile route to the preparation of high-loading vanadium active site catalysts with nitrogen defects in the support, which are promising for high performance LSB applications.
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Chemotherapy resistance of breast cancer cells is one of the major factors affecting patient survival rate. Heat shock protein 27 (Hsp27) is a member of the small heat shock protein family that has been reported to be associated with chemotherapy resistance in tumor cells, but the exact mechanism is not fully understood. Here, we explored the regulation of Hsp27 in adriamycin-resistant pathological conditions of breast cancer in vitro and in vivo. We found that overexpression of Hsp27 in MCF-7 breast cancer cells reversed DNA damage induced by adriamycin, and thereby reduced subsequent cell apoptosis. Non-phosphorylated Hsp27 accelerated ubiquitin-mediated degradation of c-Myc under normal physiological conditions. After stimulation with adriamycin, Hsp27 was phosphorylated and translocated from the cytoplasm into the nucleus, where phosphorylated Hsp27 upregulated c-Myc and Nijmegen breakage syndrome 1 (NBS1) protein levels thus leading to ATM activation. We further showed that phosphorylated Hsp27 promoted c-Myc nuclear import and stabilization by regulating T58/S62 phosphorylation of c-Myc through a protein phosphatase 2A (PP2A)-dependent mechanism. Collectively, the data presented in this study demonstrate that Hsp27, in its phosphorylation state, plays a critical role in adriamycin-resistant pathological conditions of breast cancer cells.
Subject(s)
Breast Neoplasms , Doxorubicin , Female , Humans , Apoptosis , Breast Neoplasms/metabolism , Doxorubicin/pharmacology , HSP27 Heat-Shock Proteins/metabolism , PhosphorylationABSTRACT
Snake envenomation is well known to cause grievous pathological signs, including haemorrhagic discharge, necrosis, and respiratory distress. However, inflammatory reactions are also common envenoming manifestations that lead to successive damage, such as oedema, ulceration, lymphadenectasis, systemic inflammatory response syndrome (SIRS) and even multiple organ dysfunction syndrome (MODS). Interference with the inflammatory burst is hence important in the clinical treatment of snake envenomation. Here, we summarize the typical snake toxins (or venoms) that cause inflammatory reactions and the underlying signaling pathways. In brief, inflammatory reactions are usually triggered by snake venom phospholipase A2 (svPLA2), snake venom metalloprotease (SVMP), snake venom serine protease (SVSP) and C-type lectin/snaclec (CTL) as well as disintegrin (DIS) via multiple signaling pathways. They are nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3), nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), janus kinase/signal transducer and activator of transcription (JAK-STAT) and phosphoinositide 3-Kinase/protein kinase B (PI3K/PKB also called PI3K-AKT) signaling pathways. Activation of these pathways promotes the expression of pro-inflammatory molecules such as cytokines, especially interleukin-1ß (IL-1ß) which causes further inflammatory cascades and manifestations, such as swelling, fever, pain, and severe complications. Remarkably, almost half of introduced snake toxins (or venoms) have anti-inflammatory effects through blocking these pathways and suppressing the expression of pro-inflammatory molecules. Investigation of affected inflammation-related signaling pathways is meaningful to achieve better clinical treatment.
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As part of an epidemiologic survey, we screened remnant samples collected for STI testing for mpox virus. We identified two cases of presumed MPXV infection in pregnant, heterosexual cisgender women. Here, we describe their pregnancy and birth outcomes. Both patients required induction of labor and experienced labor complicated by chorioamnionitis.
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There is an increasing burden of circulating vaccine-derived polioviruses (cVDPVs) due to the continued use of oral poliovirus vaccine (OPV). However, the informativeness of routine OPV VP1 sequencing for the early identification of viruses carrying virulence-associated reversion mutations has not been directly evaluated in a controlled setting. We prospectively collected 15,331 stool samples to track OPV shedding from children receiving OPV and their contacts for ten weeks following an immunization campaign in Veracruz State, Mexico and sequenced VP1 genes from 358 samples. We found that OPV was genetically unstable and evolves at an approximately clocklike rate that varies across serotypes and by vaccination status. Overall, 61% (11/18) of OPV-1, 71% (34/48) OPV-2, and 96% (54/56) OPV-3 samples with available data had evidence of a reversion at the key 5' UTR attenuating position and 28% (13/47) of OPV-1, 12% (14/117) OPV-2, and 91% (157/173) OPV-3 of Sabin-like viruses had ≥1 known reversion mutations in the VP1 gene. Our results are consistent with previous work documenting rapid reversion to virulence of OPV and underscores the need for intensive surveillance following OPV use.
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Background: Quantitation of human herpesvirus-6 (HHV-6) DNA in clinical specimens is important for the diagnosis and management of HHV-6-associated infection and reactivation in immunocompromised patients, particularly transplant recipients. Methods: The analytical performance of the Altona RealStar ASR HHV-6 qPCR on the semi-automated AltoStar AM16 system was assessed using HHV-6 reference material in plasma and cerebral spinal fluid (CSF). Qualitative and quantitative agreement was determined using 123 clinical EDTA plasma specimens tested using a laboratory-developed HHV-6 qPCR. Results: The 95% Lower Limit of Detection was 20 IU/mL [95% confidence interval (CI): 10 to 29] in plasma and 78 IU/mL (95% CI: 55 to 146) in CSF. The assay was linear from 7.0 to 2.0 log10 IU/mL in both matrices. Overall agreement of the RealStar ASR HHV-6 qPCR on the AltoStar AM16 with a laboratory-developed test was 95.9% (95% CI: 90.8 to 98.7). Passing-Bablok analysis of specimens quantifiable by both methods and at levels >1000 copies/mL revealed a regression line of Y = 1.00*X-0.20, with neither systematic (95% CI Y-intercept: -0.66 to 0.26) nor proportional (95% CI slope: 0.89 to 1.10) bias compared to the reference. Conclusions: The RealStar ASR HHV-6 qPCR on the AltoStar AM16 provides accurate quantitation for clinical monitoring of HHV-6 in immunocompromised hosts.
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Due to the "shuttle effect" and low conversion kinetics of polysulfides, the cycle stability of lithium sulfur (Li-S) battery is unsatisfactory, which hinders its practical application. The Mott-Schottky heterostructures for Li-S batteries not only provide more catalytic/adsorption active sites, but also facilitate electrons transport by a built-in electric field, which are both beneficial for polysulfides conversion and long-term cycle stability. Here, MXene@WS2 heterostructure was constructed by in-situ hydrothermal growth for separator modification. In-depth ultraviolet photoelectron spectroscopy and ultraviolet visible diffuse reflectance spectroscopy analysis reveals that there is an energy band difference between MXene and WS2 , confirming the heterostructure nature of MXene@WS2 . DFT calculations indicate that the Mott-Schottky MXene@WS2 heterostructure can effectively promote electron transfer, improve the multi-step cathodic reaction kinetics, and further enhance polysulfides conversion. The built-in electric field of the heterostructure plays an important role in reducing the energy barrier of polysulfides conversion. Thermodynamic studies reveal the best stability of MXene@WS2 during polysulfides adsorption. As a result, the Li-S battery with MXene@WS2 modified separator exhibits high specific capacity (1613.7â mAh g-1 at 0.1â C) and excellent cycling stability (2000 cycles with 0.0286 % decay per cycle at 2â C). Even at a high sulfur loading of 6.3â mg cm-2 , the specific capacity could be retained by 60.0 % after 240 cycles at 0.3â C. This work provides deep structural and thermodynamic insights into MXene@WS2 heterostructure and its promising prospect of application in high performance Li-S batteries.
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BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) is an underrecognized and emerging infectious disease that may threaten the safety of donor blood supply in many parts of the world. We sought to elucidate whether our local community blood supply is at increased susceptibility for transmission of transfusion-associated HEV infections. MATERIALS AND METHODS: We screened 10,002 randomly selected donations over an 8-month period between 2017 and 2018 at the Stanford Blood Center for markers of HEV infection using commercial IgM/IgG serological tests and reverse transcriptase quantitative polymerase chain reaction assays (RT-qPCR). Donor demographic information, including gender, age, self-identified ethnicity, location of residence and recent travel, were obtained from the donor database and used to generate multivariate binary logistic regressions for risk factors of IgG seropositivity. RESULTS: A total of 10,002 blood donations from 7507 unique donors were screened, and there was no detectable HEV RNA by RT-qPCR. The overall seropositivity rate was 12.1% for IgG and 0.56% for IgM. Multivariate analysis of unique donors revealed a significantly higher risk of IgG seropositivity with increasing age, White/Asian ethnicities and residence in certain local counties. CONCLUSION: Although HEV IgG seroprevalence in the San Francisco Bay Area is consistent with ongoing infection, the screening of a large donor population did not identify any viraemic blood donors. While HEV is an underrecognized and emerging infection in other regions, there is no evidence to support routine blood screening for HEV in our local blood supply currently; however, periodic monitoring may still be required to assess the ongoing risk.