Helicobacter pylori colonization and persistence could precede gastric adenocarcinoma. Elucidating immune recognition strategies of H. pylori is therefore imperative to curb chronic persistence in ...the human host. Toll-like receptor 7 (TLR7) and TLR8 are widely known as viral single-stranded RNA (ssRNA) sensors yet less studied in the bacteria context. Here, we investigated the involvement of these receptors in the immunity to H. pylori. Human THP-1 monocytic cells were infected with H. pylori, and the expression levels of human Toll-like receptors (TLRs) were examined. The roles of TLR7 and TLR8 in response to H. pylori infection were further investigated using receptor antagonists. Among all TLR transcripts examined, TLR8 exhibited the most prominent upregulation, followed by TLR7 in the THP-1 cells infected with H. pylori J99 or SS1 strains. H. pylori infection-mediated IFN-α and IFN-β transactivation was significantly abrogated by the TLR7/8 (but not TLR7) antagonist. Additionally, TLR7/8 antagonist treatment reduced H. pylori infection-mediated phosphorylation of interferon regulatory factor 7 (IRF7). Our study suggests a novel role of TLR8 signaling in host immunity against H. pylori through sensing live bacteria to elicit the production of type I interferon.
Three (60%) of five patients with coronavirus disease 2019 (COVID-19) had olfactory disorder. Two exhibited anosmia at the onset of COVID-19, while one had hyposmia 4 days after the onset of ...COVID-19. All patients with olfactory disorder were completely recovered with a mean recovery length of 11.3 days.
Trichoderma spp. represent one of the most important fungal genera to mankind and in natural environments. The genus harbors prolific producers of wood-decaying enzymes, biocontrol agents against ...plant pathogens, plant-growth-promoting biofertilizers, as well as model organisms for studying fungal-plant-plant pathogen interactions. Pursuing highly accurate, contiguous, and chromosome-level reference genomes has become a primary goal of fungal research communities. Here, we report the chromosome-level genomic sequences and whole-genome annotation data sets of four strains used as biocontrol agents or biofertilizers (
Gv29-8,
FT-333,
FT-101, and
P1). Our results provide comprehensive categorization, correct positioning, and evolutionary detail of both nuclear and mitochondrial genomes, including telomeres, AT-rich blocks, centromeres, transposons, mating-type loci, nuclear-encoded mitochondrial sequences, as well as many new secondary metabolic and carbohydrate-active enzyme gene clusters. We have also identified evolutionarily conserved core genes contributing to plant-fungal interactions, as well as variations potentially linked to key behavioral traits such as sex, genome defense, secondary metabolism, and mycoparasitism. The genomic resources we provide herein significantly extend our knowledge not only of this economically important fungal genus, but also fungal evolution and basic biology in general.
Telomere-to-telomere and gapless reference genome assemblies are necessary to ensure that all genomic variants are studied and discovered, including centromeres, telomeres, AT-rich blocks, mating type loci, biosynthetic, and metabolic gene clusters. Here, we applied long-range sequencing technologies to determine the near-completed genome sequences of four widely used biocontrol agents or biofertilizers:
Gv29-8 and FT-333,
FT-101, and
P1. Like those of three Trichoderma reesei wild isolates QM6a, CBS999.97(
) and CBS999.97(
) we reported previously, these four biocontrol agent genomes each contain seven nuclear chromosomes and a circular mitochondrial genome. Substantial intraspecies and intragenus diversities are also discovered, including single nucleotide polymorphisms, chromosome shuffling, as well as genomic relics derived from historical transposition events and repeat-induced point (RIP) mutations.
To assess the use of a framework to provide structured peer feedback and compare the effects of peer video feedback, peer verbal feedback versus faculty feedback on nursing students and peer tutors’ ...learning outcomes and experiences
Peer feedback has been utilized widely in health professions education to fill the gap for timely feedback, but some students were concerned with its quality, leading to perceptions that peer feedback may not be useful.
Sequential explanatory mixed-methods study
The study took place from January to February 2022. In phase 1, a quasi-experimental pretest-posttest design was used. First-year nursing students (n = 164) were allocated to peer video feedback, peer verbal feedback or faculty feedback arms. Senior nursing students (n = 69) were recruited to be peer tutors or the control group. The Groningen Reflective Ability Scale was used by first-year students to assess their reflective abilities, while the Simulation-based Assessment Tool was used by peer or faculty tutors to evaluate nursing students’ clinical competence of a nursing skill during the simulation. The Debriefing Assessment for Simulation in Healthcare-Student Version was used by students to assess their peer/faculty tutors’ feedback quality. Senior students’ empowerment levels were measured using the Qualities of an Empowered Nurse scale. In phase 2, six semi-structured focus group discussions with peer tutors (n = 29) were conducted and thematically analyzed.
Peer video feedback and peer verbal feedback significantly improved students’ reflective abilities but not in the faculty feedback arm. Students’ clinical competence in a technical nursing skill significantly improved in all three arms. Improvements were significantly larger in those receiving peer video feedback and peer verbal feedback than faculty feedback, with no significant differences between peer video feedback and peer verbal feedback. Debriefing Assessment for Simulation in Healthcare-Student Version scores were not significantly different among the 3 arms. Empowerment levels of peer tutors significantly improved after providing peer feedback but not those in the control group. Seven themes were generated from the focus group discussions.
Although peer video feedback and peer verbal feedback were similarly effective in improving clinical competencies, peer video feedback was more time-consuming and stressful to students. The use of structured peer feedback improved peer tutors’ feedback practices and were comparable to quality of faculty feedback. It also significantly increased their sense of empowerment. Peer feedback was widely supported by peer tutors who agreed that it should supplement faculty teaching.
Metastasis is a predominant cause of death in patients with cancer. It is a complex multistep process that needs to be better understood if we are to develop new approaches to managing tumor ...metastasis. Tumor cell invasion of the local stroma is suppressed by collapsin response mediator protein-1 (CRMP-1). Recently, we identified a long isoform of CRMP-1 (LCRMP-1), expression of which correlates with cancer cell invasiveness and poor clinical outcome in patients with non-small-cell lung cancer (NSCLC). Here, we report that LCRMP-1 overexpression in noninvasive human cell lines enhanced filopodia formation, cancer cell migration, and invasion via stabilization of actin. This effect required a highly conserved N-terminal region of LCRMP-1 as well as the WASP family verprolin-homologous protein-1/actin nucleation pathway (WAVE-1/actin nucleation pathway). Furthermore, LCRMP-1 appeared to act downstream of Cdc42, a Rho family protein known to be involved in actin rearrangement. In addition, LCRMP-1 associated with CRMP-1, which downregulated cancer cell metastasis by interrupting the association of LCRMP-1 and WAVE-1. Finally, we found that high-level expression of LCRMP-1 and low-level expression of CRMP-1 were associated with lymph node metastasis and poor survival in patients with NSCLC. In sum, we show that LCRMP-1 and CRMP-1 have opposing functions in regulating cancer cell invasion and metastasis and propose that this pathway may serve as a potential anticancer target.
The progressive decline of CD8+ cytotoxic T cells in human immunodeficiency virus (HIV)-infected patients due to infection-triggered cell exhaustion and cell death is significantly correlated with ...disease severity and progression into the life-threatening acquired immunodeficiency syndrome (AIDS) stage. T cell exhaustion is a condition of cell dysfunction despite antigen engagement, characterized by augmented surface expression of immune checkpoint molecules such as programmed cell death protein 1 (PD-1), which suppress T cell receptor (TCR) signaling and negatively impact the proliferative and effector activities of T cells. T cell function is tightly modulated by cellular glucose metabolism, which produces adequate energy to support a robust reaction when battling pathogen infection. The transition of the T cells from an active to an exhausted state following pathogen persistence involves a drastic change in metabolic activity. This review highlights the interplay between immune checkpoint molecules and glucose metabolism that contributes to T cell exhaustion in the context of chronic HIV infection, which could deliver an insight into the rational design of a novel therapeutic strategy.
The reemergence of the Zika virus (ZIKV) infection in recent years has posed a serious threat to global health. Despite being asymptomatic or mildly symptomatic in a majority of infected individuals, ...ZIKV infection can result in severe manifestations including neurological complications in adults and congenital abnormalities in newborns. In a human host, ZIKV is primarily recognized by RIG-like receptors and Toll-like receptors that elicit anti-viral immunity through the secretion of type I interferon (IFN) to limit viral survival, replication, and pathogenesis. Intriguingly, ZIKV evades its host immune system through various immune evasion strategies, including suppressing the innate immune receptors and signaling pathways, mutation of viral structural and non-structural proteins, RNA modulation, or alteration of cellular pathways. Here, we present an overview of ZIKV recognition by the host immune system and the evasion strategies employed by ZIKV. Characterization of the host-viral interaction and viral disease mechanism provide a platform for the rational design of novel prophylactic and therapeutic strategies against ZIKV infection.
Surveillance and control of tuberculous infection in pediatric patients, especially in those with a contact history, is important to prevent tuberculous infection in the general population. Totally ...26 patients, younger than 14 years of age, who had a diagnosis of pulmonary Mycobacterium tuberculosis (TB), underwent both chest radiographs and computed tomography (CT), which were retrospectively reviewed and compared with those of 20 patients with community-acquired bacterial pneumonia (CABP). TB patients were commonly afebrile and had less cavitating lesions or pleural fluid than CABP patients had. Focal or sub-segmental lung opacities suggested the diagnosis of TB than of CABP. Chest CT could also help to identify enlarged, calcified, necrotic mediastinal lymph nodes, which are less frequently found in CABP and frequently obscured by thymic shadows on chest radiographs of children. Low-dose CT for children or infants suspected to have pulmonary TB infection could help to make the decision of further antibiotic treatment.
Prevalence of hearing loss in children with autism spectrum disorder (ASD) is uncertain, as it is more challenging to assess hearing function in children with developmental difficulties (DD). We ...aimed to determine the prevalence and profiles of hearing loss in preschool children with ASD in a Southeast-Asian population who passed newborn hearing screening. A retrospective study of preschool children with DD (ASD, Global Developmental Delay (GDD), and Speech and Language Delay (SLD)) attending the Child Development Unit (CDU) at our hospital was performed. Three hundred and thirty-three children (ASD: n = 129; GDD: n = 110; and SLD: n = 94) underwent hearing assessments. Of these, 10.8% of children (n = 36, comprising 15 with ASD, 12 with GDD and 9 with SLD) had confirmed hearing loss. Hearing loss was predominantly bilateral in children with ASD and GDD; in those with SLD, unilateral and bilateral hearing loss were equally common. Conductive hearing loss occurred as frequently as sensorineural hearing loss in children with ASD and SLD, but was the dominant subtype in those with GDD. Moderate to severe hearing loss (n = 2) was noted only in children with ASD. Children with ASD and GDD required significantly more audiology visits and procedures to obtain conclusive hearing test results, compared to those with SLD. The need to identify hearing loss and monitor for resolution is particularly important in vulnerable populations with communication deficits, such as in those with ASD.
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