RT-RPA-PfAgo detection platform for one-tube simultaneous typing diagnosis of human respiratory syncytial virus.

Human respiratory syncytial virus (HRSV) is the most prevalent pathogen contributing to acute respiratory tract infections (ARTI) in infants and young children and can lead to significant financial and medical costs. Here, we developed a simultaneous, dual-gene and ultrasensitive detection system for typing HRSV within 60 minutes that needs only minimum laboratory support. Briefly, multiplex integrating reverse transcription-recombinase polymerase amplification (RT-RPA) was performed with viral RNA extracted from nasopharyngeal swabs as a template for the amplification of the specific regions of subtypes A (HRSVA) and B (HRSVB) of HRSV. Next, the Pyrococcus furiosus Argonaute (PfAgo) protein utilizes small 5'-phosphorylated DNA guides to cleave target sequences and produce fluorophore signals (FAM and ROX). Compared with the traditional gold standard (RT-qPCR) and direct immunofluorescence assay (DFA), this method has the additional advantages of easy operation, efficiency and sensitivity, with a limit of detection (LOD) of 1 copy/µL. In terms of clinical sample validation, the diagnostic accuracy of the method for determining the HRSVA and HRSVB infection was greater than 95%. This technique provides a reliable point-of-care (POC) testing for the diagnosis of HRSV-induced ARTI in children and for outbreak management, especially in resource-limited settings.

Search flavor labels in beverages: An electrophysiological investigation of color-flavor congruency and association strength in visual search.

Individuals are apt to link various characteristics of an object or event through different sensory experiences. We conducted two electrophysiological experiments to investigate the effects of color-flavor congruency and association strength on visual search efficiency and the in-depth cognitive mechanisms underlying multisensory processes. Participants were prompted with a flavor label and asked to identify the primed flavor from four beverage bottle images. Experiment 1 focused on color-flavor congruency and noted faster searches for congruent targets than incongruent ones. EEG data exhibited smaller N2, larger P3 and LPC, and increased parietal-occipital midline (POM) alpha power for incongruent targets than congruent ones. Experiment 2 manipulated color-flavor association strength within each flavor. Behavioral findings showed that searches for targets with weak association strength took longer than those with strong association strength. Moreover, time-frequency analysis displayed that the former evoked greater frontal midline (FM) theta power and higher alpha power than the latter. Altogether, our research indicated that (1) color expectations based on prior experience can automatically guide people's attentional selection, (2) the color-flavor congruency and association strength impact the visual search efficiency via distinct pathways, and (3) theta and alpha activities make a pivotal role in unraveling multisensory information processing. These findings shed some light on the intricate cognitive processes involved in crossmodal visual search and the underlying neurocognitive dynamics.

Effect of dental chew on reducing dental plaque, dental calculus and halitosis in beagle dogs.

Periodontosis is the most common clinical disease in adult dogs, which is mainly caused by plaque accumulation and seriously endangers the oral health of dogs and even cause kidney, myocardial, and liver problems in severe cases. The aim of this study was to determine the clinical efficacy of dental chew (Cature Brushing Treats product) with mechanical and chemical properties in beagles. The dogs in the experimental group were fed with a dental chew twice a day after meals; The control group had no treatment. Dental plaque was evaluated on the 14th day and 29th day, respectively. The concentration of volatile sulfur compounds (VSC) in the breath and dental calculus were also evaluated on the 29th day. The results showed that there was no significant difference in the indexes of dental plaque on the 14th day. While they had significantly reduced accumulation of plaque (37.63%), calculus (37.61%), and VSC concentration (81.08%) compared to when receiving no chew on the 29th day.

Long Non-coding RNA Linc01224 Regulates Hypopharyngeal Squamous Cell Carcinoma Growth Through Interactions with miR-485-5p and IGF2BP3.

Increasing evidence illustrates that long non-coding RNAs (lncRNAs) play significant oncogenic roles, including hypopharyngeal squamous cell carcinoma (HSCC). The function and mechanism of long non-coding RNAs (lncRNAs) in hypopharyngeal squamous cell carcinoma (HSCC) have not been fully elucidated. Therefore, this study aimed to investigate the role of a specific lncRNA, linc01224, in regulating the miR-485-5p/IGF2BP3 axis in HSCC. We confirmed the lncRNA expression profiles in 5 pairs of HSCC and normal tissues by lncRNA sequencing. Another 28 HSCC tissues were further validated by quantitative real-time PCR (qRT-PCR). qRT-PCR was also used to detect the expression levels of linc01224, miR-485-5p and IGF2BP3 in HSCC cell lines. Next, functional experiments in vitro and in vivo were applied to determine the effects of linc01224 silencing on tumor proliferation, migration, apoptosis and progression in HSCC. Linc01224 expression was significantly higher in HSCC tissues than in adjacent normal tissues. In addition, HSCC patients with low IGF2BP3 expression had good survival. In vitro assays were mechanistically performed to explore whether linc01224 positively regulates IGF2BP3 expression via its competitive inhibition of miR-485-5p. An in vivo animal model also confirmed that linc01224 could promote the occurrence and development of HSCC. Our study first identified that linc01224 plays an oncogenic role in HSCC. It suggests that linc01224 may act as a prognostic biomarker and potential therapeutic target for HSCC.

A Pilot Study to Investigate the Role of Virtual Reality in the Preservice Training of Nursing Staff in Isolation Wards.

Healthcare providers without working experience in isolation wards experience enormous challenges. Traditional ward orientation is constrained by space, time, and even infection risk in particular periods (eg, the coronavirus disease 2019 pandemic). Virtual reality has been used widely, but rarely in wards. This study aimed to explore the experience of utilizing virtual reality for isolation ward training among nurses. In this study, nurses completed virtual reality training via an online platform and were then trained in isolation wards, after which their perceptions were explored by questionnaire and interviews. A total of 1868 participants completed the training. Most participants thought the preservice training was important and believed the virtual reality experience was consistent with the in-person training. Virtual reality was found not only to be convenient and valuable for training but also to have the benefits of occupational protection. However, whereas 50.48% of participants wanted to learn the ward via virtual reality, 87.21% of participants wanted to learn via in-person training before working in the wards. As a substitute for in-person training, virtual reality is a feasible and practical instrument to provide preservice training in particular periods. However, there is room for improvement due to general discomfort and technological problems.

Concentration-Dependent Decitabine Effects on Primary NK Cells Viability, Phenotype, and Function in the Absence of Obvious NK Cells Proliferation-Original Article.

Acute myeloid leukemia (AML) cells can evade innate immune killing by modulating natural killer (NK) cells receptors and their cognate ligands in tumor cells, thus it may be possible to restore proper expression of immune receptors or ligands with immune sensitive drugs. Decitabine, as a hypomethylation agent, was approved for the treatment of AML and myelodysplastic syndrome. While clinical responses were contributed by epigenetic effects and the induction of cancer cell apoptosis, decitabine also has immune-mediated anti-tumor effects. After exposure to various concentration of decitabine for 24 h, the primary NK cells (AML-NK cells) cytotoxicity and receptor expression (NKG2D and NKp46) displayed parabola-shaped response, while U-shaped response was seen in cytokine release (IFN-γ and IL-10), and these effects were regulated by ERK and STAT3 phosphorylation level. Furthermore, AML-NK cells function displayed different response when the competitive MEK and STAT3 inhibitors applied respectively. Thus, we could conclude that the different dose of decitabine makes various effects on AML-NK cells function and receptors expression.

Role of autoimmune hemolytic anemia as an initial indicator for chronic myeloid leukemia: A case report.

INTRODUCTION: We report here the case of a patient with chronic myeloid leukemia (CML) in the chronic phase who was diagnosed 1 year after receiving a diagnosis of autoimmune hemolytic anemia (AIHA). The objective was to assess if the CML patient progressed from AIHA and explore the underlying factors of the poor outcome after the achievement of molecular complete remission (MCR). PATIENT CONCERNS: A patient with AIHA underwent splenectomy because of poor response to immune inhibitors. The spleen biopsy showed reactive hyperplasia. DIAGNOSIS: The patient was diagnosed with CML because of over-expression of the BCR-ABL (P210) gene in the bone marrow (BM), 1 year after receiving the diagnosis of AIHA. INTERVENTIONS: The splenectomy was performed as the patient was unresponsive to the standard treatments consisting of immunoglobulin and dexamethasone. The removed spleen was sent for pathological examination. After she was diagnosed with CML, she received imatinib treatment. OUTCOMES: The spleen biopsy confirmed the translocation of 22q11/9q34. No BCR-ABL kinase domain mutation was detected and there was no expression of the WT1 or EVI1 genes. After splenectomy, the number of peripheral white blood cells was consistently higher than normal during the total therapy time for CML even though she showed MCR. Two years after CML was diagnosed, the patient died from severe infection. The BM gene array analysis displayed 3 types of chromosomal abnormalities: gain (14q32.33), uniparental disomy (UPD) Xp11.22-p11.1), and UPD Xp11.1-q13.1. LESSONS: AIHA may be a clinical phase of CML progression in this patient. Both splenectomy and prolonged oral tyrosine kinase inhibitors may have contributed to the high risk of infection and her subsequent death. In addition, the gain of chromosome 14q32.33 may be related to her poor outcome.

Treatment of multicentric Castleman disease through combination of tocilizumab, lenalidomide and glucocorticoids: Case report.

RATIONALE: Castleman's disease (CD) is a rare lymphoproliferative disease. Compared to unicentric CD, multicentric Castleman disease (MCD) displays poorer prognosis and great variance to different therapies. Though chemotherapy, immunization therapy, and glucocorticoids have been used in the treatment of MCD, its optimal treatment is still controversial. PATIENT CONCERNS: A 47-year-old woman was admitted due to poor appetite, general fatigue, puffiness of face, systemic rash, and abdominal distension. On physical examination, the patient displayed as general lymphadenopathy, splenomegaly, hepatomegaly, and shifting dullness. DIAGNOSES: After biopsy of her swollen lymph node and laboratory tests, her initial diagnosis was hyaline vascular-CD. INTERVENTIONS: She was treated with combination of tocilizumab, lenalidomide, and glucocorticoids. OUTCOMES: This patient achieved complete remission (CR) with all her indexes returned to be normal. Her blood routines and biochemical examinations were still normal during the following period. LESSONS: We reported a case with multicentric Castleman's disease (MCD) which acquired quite good remission after combination treatment with tocilizumab, lenalidomide, and glucocorticoids. Our report provided powerful evidence for displaying the efficiency and safety of target therapy against unicentric Castleman disease.

Early Detection of Myelodysplastic Syndrome/Leukemia-associated Mutations Using NGS Is Critical in Treating Aplastic Anemia.

Distinguishing between aplastic anemia (AA) and hypoblastic myelodysplastic syndrome (hMDS) with a low percentage of bone marrow (BM) blasts (<5%) can be difficult due to the overlap in clonality and a spectrum of genetic alternations between the two subtypes of diseases. However, due to recent advances in DNA sequencing technology, both spectrum and frequency of mutations can be accurately determined and monitored by next-generation sequencing (NGS) at initial diagnosis and during immunosuppressive therapy (IST) in patients with AA or hMDS. This improvement in acquiring a patient's genetic status and clonal evolution can provide more proper, precise, and on-time information to guide disease management, which is especially helpful in the absence of traditional morphologic/cytogenetic evidence.

Macrocyclic amine-linked oligocarbazole hollow microspheres: facile synthesis and efficient lead sorbents.

Novel macrocyclic amine-linked oligocarbazole hollow microspheres are synthesized via a one-step oxidative method in aqueous solution. Upon altering the oxidants and acidic media, the average diameters of the obtained hollow microspheres are tunable from 0.23 to 2.0 µm. With attractive amine and carbazole functionalities, exposed surface area, thermostability, and photoluminescent properties, the amine-linked oligocarbazole hollow microspheres are directly assembled to yield heavy metal sorbents with excellent selectivity and recyclability, shown to efficiently remove lead from contaminated water.

Identification of two severe fever with thrombocytopenia syndrome virus strains originating from reassortment.

Recently, a novel bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), was isolated in central China. The virus can cause multi-clinical symptoms: severe fever, thrombocytopenia, leukocytopenia, with a mortality rate of ~10%. Several studies show that SFTSV could undergo rapid evolution via gene mutation and homologous recombination. However, as an important evolutionary force for segmented-genome viruses, reassortment has not been reported in SFTSV. In this study, we identified two SFTSV strains of which the S segment has different origin from M and L, suggesting that reassortment might be potential force driving rapid change of SFTSV. This result might shed new light on the evolutionary behavior of the novel virus.

Regulation of proteolytic cleavage of retinoid X receptor-α by GSK-3ß.

We recently reported that an N-terminally truncated retinoid X receptor-α (tRXRα) produced in cancer cells acts to promote cancer cell growth and survival through AKT activation. However, how RXRα is cleaved and how the cleavage is regulated in cancer cells remain undefined. In this study, we demonstrated that calpain II could cleave RXRα protein in vitro, generating two truncated RXRα products. The cleavage sites in RXRα were mapped by Edman N-terminal sequencing to Gly(90)↓Ser(91) and Lys(118)↓Val(119). Transfection of the resulting cleavage product RXRα/90, but not RXRα/118, resulted in activation of AKT in cancer cells, similar to the effect of tRXRα. In support of the role of calpain II in cancer cells, transfection of calpain II expression vector or its activation by ionomycin enhanced the production of tRXRα, whereas treatment of cells with calpain inhibitors reduced the levels of tRXRα. Co-immunoprecipitation assays also showed an interaction between calpain II and RXRα. In studying the regulation of tRXRα production, we observed that treatment of cells with lithium chloride or knockdown of glycogen synthase kinase-3ß (GSK-3ß) significantly increased the production of tRXRα. Conversely, overexpression of GSK-3ß reduced tRXRα expression. Furthermore, we found that the inhibitory effect of GSK-3ß on tRXRα production was due to its suppression of calpain II expression. Taken together, our data demonstrate that GSK-3ß plays an important role in regulating tRXRα production by calpain II in cancer cells, providing new insights into the development of new strategies and agents for the prevention and treatment of tRXRα-related cancers.