SARS-CoV-2 induces illness and death in humans by causing systemic infections. Evidence suggests that SARS-CoV-2 can induce brain pathology in humans and other hosts. In this study, we used a canine ...transmission model to examine histopathologic changes in the brains of dogs infected with SARS-CoV-2. We observed substantial brain pathology in SARS-CoV-2–infected dogs, particularly involving blood–brain barrier damage resembling small vessel disease, including changes in tight junction proteins, reduced laminin levels, and decreased pericyte coverage. Furthermore, we detected phosphorylated tau, a marker of neurodegenerative disease, indicating a potential link between SARS-CoV-2–associated small vessel disease and neurodegeneration. Our findings of degenerative changes in the dog brain during SARS-CoV-2 infection emphasize the potential for transmission to other hosts and induction of similar signs and symptoms. The dynamic brain changes in dogs highlight that even asymptomatic individuals infected with SARS-CoV-2 may develop neuropathologic changes in the brain.
Phytoalexins are inducible secondary metabolites possessing antimicrobial activity against phytopathogens. Rice produces a wide array of phytoalexins in response to pathogen attacks and environmental ...stresses. With few exceptions, most phytoalexins identified in rice are diterpenoid compounds. Until very recently, flavonoid sakuranetin was the only known phenolic phytoalexin in rice. However, recent studies have shown that phenylamides are involved in defense against pathogen attacks in rice. Phenylamides are amine-conjugated phenolic acids that are induced by pathogen infections and abiotic stresses including ultra violet (UV) radiation in rice. Stress-induced phenylamides, such as N-trans-cinnamoyltryptamine, N-p-coumaroylserotonin and N-cinnamoyltyramine, have been reported to possess antimicrobial activities against rice bacterial and fungal pathogens, an indication of their direct inhibitory roles against invading pathogens. This finding suggests that phenylamides act as phytoalexins in rice and belong to phenolic phytoalexins along with sakuranetin. Phenylamides also have been implicated in cell wall reinforcement for disease resistance and allelopathy of rice. Synthesis of phenolic phytoalexins is stimulated by phytopathogen attacks and abiotic challenges including UV radiation. Accumulating evidence has demonstrated that biosynthetic pathways including the shikimate, phenylpropanoid and arylmonoamine pathways are coordinately activated for phenolic phytoalexin synthesis, and related genes are induced by biotic and abiotic stresses in rice.
Owing to climate change, abnormal climate phenomena occur frequently, damaging aging highway facilities. Therefore, it is necessary to develop adaptation projects for highway systems. Adaptation ...projects focus on mitigating the impact of climate change on highway facilities and enabling safe use. The present study aims to develop quantified evaluation indicators that are necessary for planning and selecting appropriate climate change adaptation projects. By analysing previous studies, the most important factors to be considered in the evaluation process of climate change adaptation projects were defined, and 20 preliminary evaluation indicators were divided into three layers. A feasibility study for each class was performed on the preliminary evaluation indicators by an expert panel; 16 evaluation indicators were selected through a feasibility study, and the weight of each indicator was calculated using the analytical hierarchy process (AHP) method. The priority of the evaluation indicators was service improvement through adaptation projects (weight 8.76), cost reduction and job creation (weight 8.46), and climate change impact reduction and vulnerability reduction (weight 8.31). These quantified evaluation indicators can help organizations that manage highways respond to climate change and establish adaptation projects.
The present study aims to develop quantified evaluation indicators that are necessary for planning appropriate climate change adaptation projects. A feasibility study was performed, and 16 evaluation indicators were selected. The weight of each indicator was calculated using the AHP method. The priority of the evaluation indicators was service improvement through adaptation projects (weight 8.76), cost reduction and job creation (weight 8.46). These quantified indicators can help organizations that manage highways respond to climate change and establish adaptation projects.
Background Although focal ground-glass opacity (GGO) lung nodules are generally reported to grow slowly, their natural course is unclear. The purpose of this study was to elucidate the natural course ...of screening-detected pure GGO lung nodules in patients with no history of malignancy. Methods We retrospectively reviewed the database of subjects who had undergone screenings involving low-dose CT scans. We included patients with pure GGO lung nodules who were followed for > 2 years after the initial screening. Results Between June 1997 and September 2006, 122 pure GGO nodules were found in 89 patients. The median nodule size was 5.5 mm (range, 3-20 mm) in the largest diameter on initial low-dose CT scan. The median follow-up period per patient was 59 months. On a per-person basis, the frequency of growth was 13.5% (12 of 89 patients). On a per-nodule basis, the frequency of growth was 9.8% (12 of 122 nodules). Nodule growth was significantly associated with initial size and new development of an internal solid portion. The median volume doubling time was 769 days for growing pure GGO nodules. A total of 11 growing nodules were surgically validated, and all lesions were confirmed as primary lung cancer. Conclusions About 90% of the screening-detected pure GGO lung nodules did not grow during long-term follow-up in subjects with no history of malignancy and most growing nodules had an indolent clinical course. A strategy of long-term follow-up and selective surgery for growing nodules should be considered for pure GGO lung nodules.
Methylation is a common structural modification that can alter and improve the biological activities of natural compounds.
-Methyltransferases (OMTs) catalyze the methylation of a wide array of ...secondary metabolites, including flavonoids, and are potentially useful tools for the biotechnological production of valuable natural products. An
gene (
) was isolated from perilla leaves as a putative flavonoid OMT (FOMT). Phylogenetic analysis and sequence comparisons showed that PfOMT3 is a class II OMT. Recombinant PfOMT3 catalyzed the methylation of flavonoid substrates, whereas no methylated product was detected in PfOMT3 reactions with phenylpropanoid substrates. Structural analyses of the methylation products revealed that PfOMT3 regiospecifically transfers a methyl group to the 7-OH of flavonoids. These results indicate that PfOMT3 is an FOMT that catalyzes the 7-
-methylation of flavonoids. PfOMT3 methylated diverse flavonoids regardless of their backbone structure. Chrysin, naringenin and apigenin were found to be the preferred substrates of PfOMT3. Recombinant PfOMT3 showed moderate OMT activity toward eriodictyol, luteolin and kaempferol. To assess the biotechnological potential of PfOMT3, the biotransformation of flavonoids was performed using
-transformed
. Naringenin and kaempferol were successfully bioconverted to the 7-methylated products sakuranetin and rhamnocitrin, respectively, by
harboring
.
This article presents an open-switch fault detection method for a hybrid active neutral-point clamped (HANPC) inverter based on deep learning technology. The HANPC inverter generates a three-level ...output voltage with four silicon switches and two silicon carbide switches per phase. The probability of open fault in switching devices increases because of the large number of switches of the entire power converter. The open-switch fault causes distortion of output currents. A convolution neural network (CNN) comprising several convolution layers and fully connected layers is used to extract features of distorted currents. A CNN network was trained using three-phase current information to determine the location of the open-switch fault. Our proposed CNN model can accurately detect approximately 99.6% of open-switch faults without requiring additional circuitry and regardless of the current level within an average time of 1.027ms. The feasibility and effectiveness of the proposed method are verified by experimental results.
Glycyrrhizin is the major active component extracted from licorice (Glycyrrhiza glabra) roots, one of the most widely used herbal preparations for the treatment of liver disorders. This study ...evaluated the potential beneficial effect of glycyrrhizin in a mouse model of carbon tetrachloride (CCl4)-induced liver injury. The mice were treated intraperitoneally with CCl4 (0.5 ml/kg). They received glycyrrhizin (50, 100, 200, 400 mg/kg) 24 h and 0.5 h before and 4 h after administering CCl4. The serum activities of aminotransferase and the hepatic level of malondialdehyde were significantly higher 24 h after the CCl4 treatment, while the concentration of reduced glutathione was lower. These changes were attenuated by glycyrrhizin. CCl4 increased the level of circulating tumor necrosis factor-α markedly, which was reduced by glycyrrhizin. The levels of hepatic inducible nitric oxide synthase, cyclooxygenase-2, and heme oxygenase-1 protein expression were markedly higher after the CCl4 treatment. Glycyrrhizin diminished these alterations for inducible nitric oxide and cyclooxygenase-2 but the protein expression of heme oxygenase-1 was further elevated by the treatment of glycyrrhizin. CCl4 increased the level of tumor necrosis factor-α, inducible nitric oxide synthase, cyclooxygenase-2, and heme oxygenase-1 mRNA expressions. The mRNA expression of heme oxygenase-1 was augmented by the glycyrrhizin treatment, while glycyrrhizin attenuated the increase in tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 mRNA expressions. These results suggest that glycyrrhizin alleviates CCl4-induced liver injury, and this protection is likely due to the induction of heme oxygenase-1 and the downregulation of proinflammatory mediators.
Microbial biofilm formation on indwelling medical devices causes persistent infections that cannot be cured with conventional antibiotics. To address this unmet challenge, we engineer tunable active ...surface topographies with micron-sized pillars that can beat at a programmable frequency and force level in an electromagnetic field. Compared to the flat and static controls, active topographies with the optimized design prevent biofilm formation and remove established biofilms of uropathogenic Escherichia coli (UPEC), Pseudomonas aeruginosa, and Staphylococcus aureus, with up to 3.7 logs of biomass reduction. In addition, the detached biofilm cells are found sensitized to bactericidal antibiotics to the level comparable to exponential-phase planktonic cells. Based on these findings, a prototype catheter is engineered and found to remain clean for at least 30 days under the flow of artificial urine medium, while the control catheters are blocked by UPEC biofilms within 5 days.
We evaluated chemokine expression and its correlation with disease activity in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) (MPA/GPA). Serum CCL2, CCL4, ...CCL19, CXCL1, CXCL2, and CX3CL1 level in 80 patients were analysed using multiple enzyme-linked immunosorbent assays. Correlations between variables were investigated using Pearson's correlation analysis, and receiver operator curve analysis was performed to identify optimal CX3CL1 values in determining active disease. Multivariate logistic regression analysis was done to evaluate predictors of active disease. CCL4 (r = 0.251, p = 0.025), CXCL1 (r = 0.270, p = 0.015), and CX3CL1 (r = 0.295, p = 0.008) significantly correlated with BVAS, while CX3CL1 was associated with five-factor score (r = - 0.290, p = 0.009). Correlations were revealed between CCL2 and CCL4 (r = 0.267, p = 0.017), CCL4 and CXCL1 (r = 0.368, p < 0.001), CCL4 and CXCL2 (r = 0.436, p < 0.001), and CXCL1 and CXCL2 (r = 0.518, p < 0.001). Multivariate analysis revealed serum CX3CL1 levels > 2408.92 pg/mL could predict active disease (odds ratio, 27.401, p < 0.001). Serum chemokine levels of CCL4, CXCL1, and CX3CL1 showed association with disease activity and especially, CX3CL1 > 2408.92 pg/mL showed potential in predicting active MPA/GPA.
Interferon lambda (IFNλ), classified as a type III IFN, is a representative cytokine that plays an important role in innate immunity along with type I IFN. IFNλ can elicit antiviral states by ...inducing peculiar sets of IFN‐stimulated genes (ISGs). In this study, an adenoviral vector expression system with a tetracycline operator system was used to express human IFNλ4 in cells and mice. The formation of recombinant adenovirus (rAd‐huIFNλ4) was confirmed using immunohistochemistry assays and transmission electron microscopy. Its purity was verified by quantifying host cell DNA and host cell proteins, as well as by confirming the absence of the replication‐competent adenovirus. The transduction of rAd‐huIFNλ4 induced ISGs and inhibited four subtypes of the influenza virus in both mouse‐derived (LA‐4) and human‐derived cells (A549). The antiviral state was confirmed in BALB/c mice following intranasal inoculation with 109 PFU of rAd‐huIFNλ4, which led to the inhibition of four subtypes of the influenza virus in mouse lungs, with reduced inflammatory lesions. These results imply that human IFNλ4 could induce antiviral status by modulating ISG expression in mice.
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