A novel β-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other ...countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal-oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.
Summary
Strategy of managing antibiotic‐resistant Vibrio alginolyticus, a bacterial pathogen that threatens human health and animal farming, is not available due to the lack of knowledge about the ...underlying mechanism of antibiotic resistance. Here, we showed that gentamicin‐resistant V. alginolyticus (VA‐RGEN) has four mutations on metabolism and one mutation on a two‐component system by whole‐genome and PCR‐based sequencing, indicating the metabolic shift in VA‐RGEN. Thus, metabolic profile was investigated by GC–MS based metabolomics. Glucose was identified as a crucial biomarker, whose abundance was decreased in VA‐RGEN. Further analysis with iPath, and gene expression and enzyme activity of the pyruvate cycle (the P cycle) demonstrated a global depressed metabolic pathway network in VA‐RGEN. Consistently, NADH, sodium‐pumping NADH:ubiquinone oxidoreductase (Na(+)‐NQR) system, membrane potential and intracellular gentamicin were decreased in VA‐RGEN. These findings indicate that the reduced redox state contributes to antibiotic resistance. Interestingly, exogenous glucose potentiated gentamicin to efficiently kill VA‐RGEN through the promotion of the P cycle, NADH, membrane potential and intracellular gentamicin. The potentiation was further confirmed in a zebrafish model. These results indicate that the gentamicin resistance reduces the P cycle and Na(+)‐NQR system and thereby decreases redox state, membrane potential and gentamicin uptake, which can be reversed by exogenous glucose.
Summary
Colistin is a last‐line antibiotic against Gram‐negative multidrug‐resistant bacteria, but the increased resistance poses a huge challenge to this drug. However, the mechanisms underlying ...such resistance are largely unexplored. The present study first identified the mutations of two genes encoding AceF subunit of pyruvate dehydrogenase (PDH) and TetR family transcriptional regulator in colistin‐resistant Vibrio alginolyticus (VA‐RCT) through genome sequencing. Then, gas chromatography‐mass spectroscopy‐based metabolomics was adopted to investigate metabolic responses since PDH plays a role in central carbon metabolism. Colistin resistance was associated with the reduction of the central carbon metabolism and energy metabolism, featuring the alteration of the pyruvate cycle, a recently characterized energy‐producing cycle. Metabolites in the pyruvate cycle reprogramed colistin‐resistant metabolome to colistin‐sensitive metabolome, resulting in increased gene expression, enzyme activity or protein abundance of the cycle and sodium‐translocating nicotinamide adenine dinucleotide‐ubiquinone oxidoreductase. This reprogramming promoted the production of the proton motive force that enhances the binding between colistin and lipid A in lipopolysaccharide. Moreover, this metabolic approach was effective against VA‐RCT in vitro and in vivo as well as other clinical isolates. These findings reveal a previously unknown mechanism of colistin resistance and develop a metabolome‐reprogramming approach to promote colistin efficiency to combat with colistin‐resistant bacteria.
Oral bacteria directly affect the disease status of dental caries and periodontal diseases. The dynamic oral microbiota cooperates with the host to reflect the information and status of immunity and ...metabolism through two-way communication along the oral cavity and the systemic organs. The oral cavity is one of the most important interaction windows between the human body and the environment. The microenvironment at different sites in the oral cavity has different microbial compositions and is regulated by complex signaling, hosts, and external environmental factors. These processes may affect or reflect human health because certain health states seem to be related to the composition of oral bacteria, and the destruction of the microbial community is related to systemic diseases. In this review, we discussed emerging and exciting evidence of complex and important connections between the oral microbes and multiple human systemic diseases, and the possible contribution of the oral microorganisms to systemic diseases. This review aims to enhance the interest to oral microbes on the whole human body, and also improve clinician's understanding of the role of oral microbes in systemic diseases. Microbial research in dentistry potentially enhances our knowledge of the pathogenic mechanisms of oral diseases, and at the same time, continuous advances in this frontier field may lead to a tangible impact on human health.
Metabolomics is emerging as a powerful tool for studying metabolic processes, identifying crucial biomarkers responsible for metabolic characteristics and revealing metabolic mechanisms, which ...construct the content of discovery metabolomics. The crucial biomarkers can be used to reprogram a metabolome, leading to an aimed metabolic strategy to cope with alteration of internal and external environments, naming reprogramming metabolomics here. The striking feature on the similarity of the basic metabolic pathways and components among vastly differentspeciesmakesthe reprogrammingmetabolomics possible when the engineered metabolites play biological roles in cellular activity as a substrate of enzymes and a regulator to other molecules including proteins. The reprogramming metabolomics approach can be used to clarify metabolic mechanisms of responding to changed internal and external environmental factors and to establish a framework to develop targeted tools for dealing with the changes such as controlling and/or preventing infection with pathogens and enhancing host immunity against pathogens. This review introduces the current state and trends of discovery metabolomics and reprogramming metabolomics and highlights the importance of reprogramming metabolomics.
Summary
Antibiotic‐resistant Vibrio alginolyticus poses a big challenge to human health and food safety. It is urgently needed to understand the mechanisms underlying antibiotic resistance to develop ...effective approaches for the control. Here we explored the metabolic difference between gentamicin‐resistant V. alginolyticus (VA‐RGEN) and gentamicin‐sensitive V. alginolyticus (VA‐S), and found that the reactive oxygen species (ROS) generation was altered. Compared with VA‐S, the ROS content in VA‐RGEN was reduced due to the decreased generation and increased breakdown of ROS. The decreased production of ROS was attributed to the decreased central carbon metabolism, which is associated with the resistance to gentamicin. As such a mechanism, we exogenously administrated VA‐RGEN with the glucose that activated the central carbon metabolism and promoted the generation of ROS, but decreased the breakdown of ROS in VA‐RGEN. The gentamicin‐mediated killing was increased with the elevation of the ROS level by a synergistic effect between gentamicin and exogenous glucose. The synergistic effect was inhibited by thiourea, a scavenger of ROS. These results reveal a reduced ROS‐mediated antibiotic resistance mechanism and its reversal by exogenous glucose.
In the MOOC forum discussions, emotional and cognitive engagement are two prominent aspects of learning engagement. Moreover, emotional and cognitive engagement have an interactive relationship and ...can jointly predict learning achievement. However, these interwoven relationships have not been thoroughly explored. Furthermore, the limitations on detection methods for emotional and cognitive engagement have hindered the practice and theory progress. This study aimed to develop a novel text classification model to automatically detect emotional and cognitive engagement and investigate their complex relationships with achievement, which are beneficial for improving learning engagement and historically low completion rates of MOOCs. Firstly, this study proposed a robust and interpretable NLP model called the bidirectional encoder representation from the transformers-convolutional neural network (BERT-CNN). Compared with models in previous studies, it improved the F1 values of emotional and cognitive engagement recognition tasks by 10% and 8%, respectively. Secondly, this study used BERT-CNN to analyze 8867 learners’ discussions in a MOOC forum. Structural equation modeling indicated that emotional and cognitive engagement have an interactive relationship and a combined effect on learning achievement. Specifically, positive and confused emotions contributed more to higher-level cognition than negative emotions. Co-occurring emotion and cognition indicators jointly predicted learning achievement with higher reliability. In summary, this study has significant methodological implications for the automated measurement of emotional and cognitive engagement. Moreover, the study revealed the dominant role of emotional engagement on cognitive engagement and provided suggestions for improving MOOC learners' achievement.
•A deep learning model for detecting emotional and cognitive engagement is developed.•The model realizes interpretable and robust automatic discourse analysis.•The mathematic model of emotional, cognitive engagement, and achievement is validated.•Positive and confused emotions are associated with higher-order cognitive engagement.•Using emotional and cognitive engagement to predict achievement is more reliable.
microRNA (miR) has been shown to be involved in the treatment of diseases such as osteoarthritis (OA). This study aims to investigate the role of miR‐206 in regulating insulin‐like growth factor‐1 ...(IGF‐1) in chondrocyte autophagy and apoptosis in an OA rat model via the phosphoinositide 3‐kinase (P13K)/protein kinase B (AKT)‐mechanistic target of rapamycin (mTOR) signaling pathway. Wistar rats were used to establish the OA rat model, followed by the observation of histopathological changes, Mankin score, and the detection of IGF‐1‐positive expression and tissue apoptosis. The underlying regulatory mechanisms of miR‐206 were analyzed in concert with treatment by an miR‐206 mimic, an miR‐206 inhibitor, or small interfering RNA against IGF‐1 in chondrocytes isolated from OA rats. Then, the expression of miR‐206, IGF‐1, and related factors in the signaling pathway, cell cycle, and apoptosis, as well as inflammatory factors, were determined. Subsequently, chondrocyte proliferation, cell cycle distribution, apoptosis, autophagy, and autolysosome were measured. OA articular cartilage tissue exhibited a higher Mankin score, promoted cell apoptotic rate, increased expression of IGF‐1, Beclin1, light chain 3 (LC3), Unc‐51‐like autophagy activating kinase 1 (ULK1), autophagy‐related 5 (Atg5), caspase‐3, and Bax, yet exhibited decreased expression of miR‐206, P13K, AKT, mTOR, and Bcl‐2. Besides, miR‐206 downregulated the expression of IGF‐1 and activated the P13K/AKT signaling pathway. Moreover, miR‐206 overexpression and IGF‐1 silencing inhibited the interleukins levels (IL‐6, IL‐17, and IL‐18), cell apoptotic rate, the formation of autolysosome, and cell autophagy while promoting the expression of IL‐1β and cell proliferation. The findings from our study provide a basis for the efficient treatment of OA by investigating the inhibitory effects of miR‐206 on autophagy and apoptosis of articular cartilage in OA via activating the IGF‐1‐mediated PI3K/AKT‐mTOR signaling pathway.
The findings from our study provide a basis for the efficient treatment of OA by investigating the inhibitory effects of miR‐206 on autophagy and apoptosis of articular cartilage in OA via activating the IGF‐1‐mediated PI3K/AKT‐mTOR signaling pathway.
The microbial coinfection in COVID-19 Chen, Xi; Liao, Binyou; Cheng, Lei ...
Applied microbiology and biotechnology,
09/2020, Letnik:
104, Številka:
18
Journal Article
Recenzirano
Odprti dostop
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel β-coronavirus, is the main pathogenic agent of the rapidly spreading pneumonia called coronavirus disease 2019 (COVID-19). ...SARS-CoV-2 infects much more people, especially the elder population, around the world than other coronavirus, such as SARS-CoV and MERS-CoV, which is challenging current global public health system. Beyond the pathogenesis of SARS-CoV-2, microbial coinfection plays an important role in the occurrence and development of SARS-CoV-2 infection by raising the difficulties of diagnosis, treatment, prognosis of COVID-19, and even increasing the disease symptom and mortality. We summarize the coinfection of virus, bacteria and fungi with SARS-CoV-2, their effects on COVID-19, the reasons of coinfection, and the diagnosis to emphasize the importance of microbial coinfection in COVID-19.
Key points
•
Microbial coinfection is a nonnegligible factor in COVID-19.
•
Microbial coinfection exacerbates the processes of the occurrence, development and prognosis of COVID-19, and the difficulties of clinical diagnosis and treatment.
•
Different virus, bacteria, and fungi contributed to the coinfection with SARS-CoV-2.
We present a theory of the spin Hall magnetoresistance of metals in contact with magnetic insulators. We express the spin mixing conductances, which govern the phenomenology of the effect, in terms ...of the microscopic parameters of the interface and the spin–spin correlation functions of the local moments on the surface of the magnetic insulator. The magnetic-field and temperature dependence of the spin mixing conductances leads to a rich behavior of the resistance due to an interplay between the Hanle effect and the spin mixing at the interface. We describe an unusual negative magnetoresistance originating from a nonlocal Hanle effect. Our theory provides a useful tool for understanding the experiments on heavy metals in contact with magnetic insulators of different kinds, and it enables the spin Hall magnetoresistance effect to be used as a technique to study magnetism at interfaces.
PDF
