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Two urease operons were identified in Klebsiella pneumoniae CG43, ure-1 and ure-2. This study investigates whether a differential regulation of the expression of ure-1 and ure-2 exists and how urease activity influences the acid stress response and expression of type 1 and type 3 fimbriae.The ureA1 and ureA2 gene specific deletion mutants were constructed. Promoter activity was assessed using a LacZ reporter system. The sensitivity to acid stress was determined by assessing the survival after pH 2.5 treatment. The influence on type 1 and type 3 fimbriae expression was assessed using western blotting and mannose-sensitive yeast agglutination and biofilm formation assay, respectively.Bacterial growth analysis in mM9-U or modified Stuart broth revealed that ure-1 was the principal urease system, and ure-2 had a negative effect on ure-1 activity. Deletion of the fur or nac gene had no apparent effect on the activity of Pure-1 is the primary expression system in K. pneumoniae CG43, while ure-2 is active in the absence of hns. Impairment of urease activity increases the sensitivity to acid stress, and the accumulation of urea induces the expression of type 1 fimbriae but represses type 3 fimbriae expression.

Epsilon-poly-L-lysine (EPL) is an antimicrobial peptide with low mammalian toxicity; thus, it is commonly used as food preservative. Here, the capacity of EPL to improve the efficacy of the antibiotics ampicillin (AMP), gentamycin (GEN), tetracycline (TCN), and methicillin (MET) against four bacterial pathogens, namely Pseudomonas aeruginosa PAO1, Klebsiella pneumoniae CG43, MET-sensitive Staphylococcus aureus ATCC 25923 (MSSA), and MET-resistant S. aureus ATCC 33591 (MRSA), was investigated. Some antibiotic-EPL combinations, i.e., AMP-EPL, GEN-EPL, and TCN-EPL, were particularly active against the pathogens through synergy, partial synergy, or additive effects. Additionally, MET-EPL displayed a partial synergistic effect against MRSA. GEN-EPL had the most powerful antimicrobial effect against MSSA: it eradicated the bacterium within an hour. Conversely, AMP-EPL and MET-EPL were the least potent combinations against MRSA, and TCN-EPL was least potent against K. pneumoniae; for these combinations, bactericidal activities occurred10 h after initial treatments. All antibiotic-EPL treatments showed inhibitory activities against P. aeruginosa biofilm formation and enhanced preformed biofilm disruption in vitro. Similarly, the inhibition of biofilm formation on a porcine skin model was observed. Moreover, no significant cytotoxicity was detected for any antibiotic-EPL treatment in tests using Balb/3t3 fibroblasts. Given the rise in antibiotic-resistant bacteria, combining antibiotics with EPL may enhance antibiotic effectiveness, as shown in this study, while helping to avoid antimicrobial resistance.

ObjectiveThe present study aimed to predict myocardial ischemia in coronary heart disease (CHD) patients based on the radiologic features of coronary computed tomography angiography (CCTA) combined with clinical factors.MethodsThe imaging and clinical data of 110 patients who underwent CCTA scan before DSA or FFR examination in Changzhou Second People’s Hospital, Nanjing Medical University (90 patients), and The First Affiliated Hospital of Soochow University (20 patients) from March 2018 to January 2022 were retrospectively analyzed. According to the digital subtraction angiography (DSA) and fractional flow reserve (FFR) results, all patients were assigned to myocardial ischemia (n = 58) and normal myocardial blood supply (n = 52) groups. All patients were further categorized into training (n = 64) and internal validation (n = 26) sets at a ratio of 7:3, and the patients from second site were used as external validation. Clinical indicators of patients were collected, the left ventricular myocardium were segmented from CCTA images using CQK software, and the radiomics features were extracted using pyradiomics software. Independent prediction models and combined prediction models were established. The predictive performance of the model was assessed by calibration curve analysis, receiver operating characteristic (ROC) curve and decision curve analysis.ResultsThe combined model consisted of one important clinical factor and eight selected radiomic features. The area under the ROC curve (AUC) of radiomic model was 0.826 in training set, and 0.744 in the internal validation set. For the combined model, the AUCs were 0.873, 0.810, 0.800 in the training, internal validation, and external validation sets, respectively. The calibration curves demonstrated that the probability of myocardial ischemia predicted by the combined model was in good agreement with the observed values in both training and validation sets. The decision curve was within the threshold range of 0.1–1, and the clinical value of nomogram was higher than that of clinical model.ConclusionThe radiomic characteristics of CCTA combined with clinical factors have a good clinical value in predicting myocardial ischemia in CHD patients.

Since ancient times, Banhasasim-tang (BHS) has been used to treat functional dyspepsia in East Asia. Here, we aimed to determine the protective action of BHS on hippocampal neurons against oxidative stress. We investigated the functional effect of BHS on a scopolamine-induced mouse model, and molecular analysis was performed in glutamate-induced HT22 cells. We observed that BHS administration ameliorated memory dysfunction in scopolamine-treated mice. BHS administration also increased neuronal survival and acetylcholine activity and phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB) in the hippocampus of mice. In hippocampal cells, BHS treatment rescued glutamate-induced cytotoxicity, apoptosis, and oxidative stress. We observed an increase of HO-1 and a decrease of Nrf2 protein expression in glutamate-induced oxidative stress; however, the expression level of these proteins was significantly rescued by BHS treatment. BHS treatment also regulated phosphorylation of p38, p53, ERK, and CREB. Therefore, our data indicated that BHS may reduce oxidative stress through regulation of ERK-CREB and p38-p53 signaling in the hippocampus, resulting in decreased neuronal damage and improved memory in rodent models of neurodegenerative disease.

The important factors in the pathogenesis of neurodegenerative disorders include oxidative stress and neuron-glia system inflammation. Vignae Radiatae Semen (VRS) exhibits antihypertensive, anticancer, anti-melanogenesis, hepatoprotective, and immunomodulatory properties. However, the neuroprotective effects and anti-neuroinflammatory activities of VRS ethanol extract (VRSE) remained unknown. Thus, this study aimed to investigate the neuroprotective and anti-inflammatory activities of VRSE against hydrogen peroxide (H2O2)-induced neuronal cell death in mouse hippocampal HT22 cells and lipopolysaccharide (LPS)-stimulated BV2 microglial activation, respectively. This study revealed that VRSE pretreatment had significantly prevented H2O2-induced neuronal cell death and attenuated reactive oxygen species generations in HT22 cells. Additionally, VRSE attenuated the apoptosis protein expression while increasing the anti-apoptotic protein expression. Further, VRSE showed significant inhibitory effects on LPS-induced pro-inflammatory cytokines in BV2 microglia. Moreover, VRSE pretreatment significantly activated the tropomyosin-related kinase receptor B/cAMP response element-binding protein, brain-derived neurotrophic factor and nuclear factor erythroid 2-related factor 2, and heme oxygenase-1 signaling pathways in HT22 cells exposed to H2O2 and inhibited the activation of the mitogen-activated protein kinase and nuclear factor-κB mechanism in BV2 cells stimulated with LPS. Therefore, VRSE exerts therapeutic potential against neurodegenerative diseases related to oxidative stress and pathological inflammatory responses.

PURPOSE: To establish a machine-learning (ML) model based on coronary computed tomography angiography (CTA) images for evaluating myocardial ischemia in patients diagnosed with coronary atherosclerosis. METHODS: This retrospective analysis includes CTA images acquired from 110 patients. Among them, 58 have myocardial ischemia and 52 have normal myocardial blood supply. The patients are divided into training and test datasets with a ratio 7 : 3. Deep learning model-based CQK software is used to automatically segment myocardium on CTA images and extract texture features. Then, seven ML models are constructed to classify between myocardial ischemia and normal myocardial blood supply cases. Predictive performance and stability of the classifiers are determined by receiver operating characteristic curve with cross validation. The optimal ML model is then validated using an independent test dataset. RESULTS: Accuracy and areas under ROC curves (AUC) obtained from the support vector machine with extreme gradient boosting linear method are 0.821 and 0.777, respectively, while accuracy and AUC achieved by the neural network (NN) method are 0.818 and 0.757, respectively. The naive Bayes model yields the highest sensitivity (0.942), and the random forest model yields the highest specificity (0.85). The k-nearest neighbors model yields the lowest accuracy (0.74). Additionally, NN model demonstrates the lowest relative standard deviations (0.16 for accuracy and 0.08 for AUC) indicating the high stability of this model, and its AUC applying to the independent test dataset is 0.72. CONCLUSION: The NN model demonstrates the best performance in predicting myocardial ischemia using radiomics features computed from CTA images, which suggests that this ML model has promising potential in guiding clinical decision-making.

Background The advantages and disadvantages of transperineal and transrectal biopsies remain controversial in the era of prostate targeted biopsy. In this study, we compared the cancer detection and complication rates of transperineal magnetic resonance/ultrasound (MR/US) fusion biopsy and transrectal cognitive fusion biopsy of the prostate. Methods This was a comparative study of two prospectively collected cohorts. Men with clinically suspected prostate cancer and prostate imaging reporting and data system (PI-RADS) score ≥ 3 lesions on multi-parametric magnetic resonance imaging (mpMRI) were enrolled. They underwent either transperineal software fusion biopsy or transrectal cognitive fusion biopsy and systematic biopsy. The detection rates of any prostate cancer and clinically significant prostate cancer (csPC, defined as Gleason score ≥ 3 + 4) and the complication rates between both groups were analysed. Results Ninety-two and 85 patients underwent transperineal software fusion and transrectal cognitive fusion biopsies, respectively. The detection rate for any prostate cancer was similar between both groups (60.8% vs. 56.4%, p = 0.659). In terms of csPC detection, transperineal fusion biopsy outperformed transrectal fusion biopsy (52.2% vs. 36.5%, p = 0.036). In multivariate regression analysis, age, PI-RADS score > 3, and transperineal route were significant predictors of csPC. Meanwhile, transperineal biopsy resulted in a higher rate of urinary retention than transrectal biopsy (18.5% vs. 4.7%, p = 0.009). No serious infectious complications were noted, although a patient developed sepsis after transrectal biopsy. Conclusions Transperineal software fusion biopsy provided a higher csPC detection rate than transrectal cognitive fusion biopsy and carried minimal risk for infectious complications in patients with MRI-visible prostate lesions.

Herpes simplex virus type 1 (HSV-1) is ubiquitous in many populations despite the use of acyclovir or related nucleoside analogs for treating infection. Drug resistance impairs the treatment of HSV-infected individuals who have immune deficits, underscoring the need for new safe and effective antiviral agents. Mori ramulus (the young twig of Morus alba L.) has long been used to treat diseases in Korea, Japan, and China. Recent studies have reported multiple pharmacological activities of Mori ramulus and its constituent morusin, but their effects on HSV-1 remain unknown. Here, we found that treatment with Mori ramulus ethanol extract (MRE) significantly reduced the replication of fluorescently labeled HSV-1 in Vero cells and inhibited the expression of HSV-1 envelope glycoprotein D (gD) and tegument protein VP16. MRE, furthermore, blocked HSV-1-induced production of reactive oxygen species (ROS), and this mediated the inhibition of viral replication. We identified morusin as the active antiviral component of MRE and found that morusin post-treatment was sufficient to inhibit viral gD and VP16 in addition to HSV-1-induced ROS production. Therefore, the inhibition of HSV-1-induced ROS may explain the antiviral activity of MRE against HSV-1. MRE or its component morusin may be potentially developed for anti-HSV-1 agents.

We report infrared (IR) pulse laser-activated highly efficient parallel intracellular delivery by using an array of titanium microdish (TMD) device. Upon IR laser pulse irradiation, a two-dimensional array of TMD device generated photothermal cavitation bubbles to disrupt the cell membrane surface and create transient membrane pores to deliver biomolecules into cells by a simple diffusion process. We successfully delivered the dyes and different sizes of dextran in different cell types with variations of laser pulses. Our platform has the ability to transfect more than a million cells in a parallel fashion within a minute. The best results were achieved for SiHa cells with a delivery efficiency of 96% and a cell viability of around 98% for propidium iodide dye using 600 pulses, whereas a delivery efficiency of 98% and a cell viability of 100% were obtained for dextran 3000 MW delivery using 700 pulses. For dextran 10,000 MW, the delivery efficiency was 92% and the cell viability was 98%, respectively. The device is compact, easy-to-use, and potentially applicable for cellular therapy and diagnostic purposes.

Electrodynamic systems for bioanalytical applications constantly suffer from biofouling due to electrical field-induced nonspecific bioadsorption on electrode surfaces. To minimize this issue, surface modification using anti-biofouling and conductive materials is necessary to not only protect the electrode surface from nonspecific bioadsorption but also maintain desired electrodynamic properties for electrode operation. In this study, we designed and prepared a conductive, zwitterionic, and self-doped sulfonated polyaniline (SPANI) coating on Au electrode surfaces for anti-biofouling applications. The zwitterionic coating was fabricated by electrochemical polymerization of aniline on the Au electrode surface functionalized with cysteamine (HS-CH2CH2-NH2) and then a post-polymerization treatment with fuming sulfuric acid. We found that the SPANI-coated electrodes exhibited an excellent anti-biofouling ability in dielectrophoresis (DEP) capturing-and-releasing processes, with a very low average residual mass rate of 1.44% for the SPANI-5s electrode, whereas electrodes modified with poly(ethylene glycol) (PEG) gave an average residual mass rate of 14.30%. Even under continuous operation for more than 1 h, the SPANI-5s electrode still showed stable anti-biofouling ability for an 11-cycle E. coli capturing-and-releasing DEP process, with the residual mass rate for all 11 cycles being kept at or below 2.18% to give an average residual mass rate of 1.62% with a standard deviation of 0.40%. This study demonstrates that electrodynamic systems with zwitterionic SPANI coated on open electrode surfaces can excellently function with decent conductance and anti-biofouling performance.

The ability to deliver foreign cargos into single living cells is of great interest in cell biology and therapeutic research. Here, we have reported a single or multiple position based nano-localized single-cell nano-electroporation platform. The device consists of an array of triangular shape ITO nano-electrodes with a 70 nm gap between two nano-electrodes, each having a 40 nm tip diameter. The voltage is applied between nano-electrodes to generate an intense electric field, which electroporates multiple nano-localized regions of the targeted single-cell membrane, and biomolecules are gently delivered into cells by pressurizing pump flow, without affecting cell viability. The platform successfully delivers dyes, QDs, and plasmids into different cell types with the variation of field strength, pulse duration, and the number of pulses. This new approach allows us to analyze delivery of different biomolecules into single living cells with high transfection efficiency (>96%, for CL1-0 cells) and high cell viability (∼98%), which are potentially beneficial for cellular therapy and diagnostic purposes.

OCD20015-V009 is an herbal mix of water-extracted Ginseng Radix, Poria (Hoelen), Rehmanniae Radix, Adenophorae Radix, Platycodi Radix, Crataegii Fructus, and Astragali Radix. In this study, its in vitro and in vivo antiviral activity and mechanisms against the influenza A virus were evaluated using a GFP-tagged influenza A virus (A/PR/8/34-GFP) to infect murine macrophages. We found that OCD20015-V009 pre-treatment substantially reduced A/PR/8/34-GFP replication. Also, OCD20015-V009 pre-treatment increased the phosphorylation of type-I IFN-related proteins TBK-1 and STAT1 and the secretion of pro-inflammatory cytokines TNF-α and IL-6 by murine macrophages. Moreover, OCD20015-V009 prophylactic administration increased IFN-stimulated genes-related 15, 20, and 56 and IFN-β mRNA in vitro. Thus, OCD20015-V009 likely modulates murine innate immune response via macrophages. This finding is potentially useful for developing prophylactics or therapeutics against the influenza A virus. Furthermore, pre-treatment with OCD20015-V009 decreased the mortality of the mice exposed to A/PR/8/34-GFP by 20% compared to that in the untreated animals. Thus, OCD20015-V009 stimulates the antiviral response in murine macrophages and mice to viral infections. Additionally, we identified chlorogenic acid and ginsenoside Rd as the antiviral components in OCD20015-V009. Further investigations are needed to elucidate the protective effects of active components of OCD20015-V009 against influenza A viruses.

OBJECTIVE: To develop and test an optimal machine learning model based on the enhanced computed tomography (CT) to preoperatively predict pathological grade of clear cell renal cell carcinoma (ccRCC). METHODS: A retrospective analysis of 53 pathologically confirmed cases of ccRCC was performed and 25 consecutive ccRCC cases were selected as a prospective testing set. All patients underwent routine preoperative abdominal CT plain and enhanced scans. Renal tumor lesions were segmented on arterial phase images and 396 radiomics features were extracted. In the training set, seven discrimination classifiers for high- and low-grade ccRCCs were constructed based on seven different machine learning models, respectively, and their performance and stability for predicting ccRCC grades were evaluated through receiver operating characteristic (ROC) analysis and cross-validation. Prediction accuracy and area under ROC curve were used as evaluation indices. Finally, the diagnostic efficacy of the optimal model was verified in the testing set. RESULTS: The accuracies and AUC values achieved by support vector machine with radial basis function kernel (svmRadial), random forest and naïve Bayesian models were 0.860±0.158 and 0.919±0.118, 0.840±0.160 and 0.915±0.138, 0.839±0.147 and 0.921±0.133, respectively, which showed high predictive performance, whereas K-nearest neighborhood model yielded lower accuracy of 0.720±0.188 and lower AUC value of 0.810±0.150. Additionally, svmRadial had smallest relative standard deviation (RSD, 0.13 for AUC, 0.17 for accuracy), which indicates higher stability. CONCLUSION: svmRadial performs best in predicting pathological grades of ccRCC using radiomics features computed from the preoperative CT images, and thus may have high clinical potential in guiding preoperative decision.

Among the security issues of embedded systems, electromagnetic (EM) information leakage problem is difficult to detect and prevent. When the embedded system is operating, different commands will emit different EM signals. In this paper, we propose a NN architecture to analyze the EM leakage and effectively improve the accuracy. Comparing with a previous research, the accuracy is greatly improved from 38% up to 66%.

This study aimed to develop a silk fibroin (SF)-film for the treatment of chronic diabetic wounds. Silk fibroin was purified through a newly developed heating degumming (HD) process and casted on a hydrophobic surface to form SF-films. The process allowed the fabricated film to achieve a 42% increase in transparency and a 32% higher proliferation rate for BALB/3T3 fibroblasts compared to that obtained by conventional alkaline degumming treatment. Fourier transform infrared analysis demonstrated that secondary structure was retained in both HD- and alkaline degumming-derived SF preparations, although the crystallinity of beta-sheet in SF-film after the HD processing was slightly increased. This study also investigated whether conjugating insulin-like growth factor-1 (IGF-1) would promote diabetic wound healing and what the optimal dosage is. Using BALB/3T3 cells grown in hyperglycemic medium as a model, it was demonstrated that the optimal IGF-1 dosage to promote the cell growth was approximately 0.65 pmol. Further analysis of wound healing in a diabetic mouse model indicated that SF-film loaded with 3.25 pmol of IGF-1 showed significantly superior wound closure, a 13% increase at the 13th day after treatment relative to treatment with 65 pmol of free IGF-1. Improvement in diabetic wound healing was exerted synergistically by SF-film and IGF-1, as reflected by parameters including levels of re-epithelialization, epithelial tissue area, and angiogenesis. Finally, IGF-1 increased the epithelial tissue area and micro-vessel formation in a dose-dependent manner in a low dosage range (3.25 pmol) when loaded to SF-films. Together, these results strongly suggest that SF-film produced using HD and loaded with a low dosage of IGF-1 is a promising dressing for diabetic wound therapy.

Despite the inhibitory effect of various ginsenosides on neuroinflammation, pharmacological activity of ginsenosides varies depending on their hydrolysis by individual intestinal microbial flora and may not appear in individuals with intestinal microbial deficiency. Herein, we investigated the hydrolytic selectivity of β-glucosidase from Lactobacillus antri toward sugar residues in ginsenoside to selectively enhance the effective minor ginsenoside contents and improve their anti-neuroinflammatory activity in BV2 microglia. The hydrolytic selectivity of β-glucosidase was dependent on the position and linkage type of sugar residues. Hydrolysis of ginseng extract and its mimic indicated that the predominant hydrolytic selectivity of β-glucosidase toward P1 (β1→6 linkage), P4, and P2 residues led to the selective production of minor ginsenoside Rd at the early stage and Rg3, Rh1, and A-PPD at the late stage, which resulted in the enhanced anti-neuroinflammatory activity of hydrolyzed ginseng mimic by inhibiting the production of inflammatory mediators in BV2 microglial cells, particularly at the late stage of hydrolysis. This study suggests that the insight into the hydrolytic selectivity of β-glucosidase will help in selecting appropriate substrates hydrolyzed well and in enhancing the contents of desired deglycosylated compounds, including minor ginsenosides, to improve their efficacy on specific target diseases, including those caused by neuroinflammation.

Shrimps are the most widely and increasingly cultured crustaceans in land-based ponds in Taiwan. However, few studies have investigated the phthalate contamination of and insecticide residues in shrimp. In this study, we applied a validated method to analyze the phthalate and 18 insecticides residues in shrimp. A total of 46 samples of whiteleg, grass, or giant river shrimp were collected from aquafarms and production areas in Taiwan. We detected 0.02–0.70 mg/kg of di-2-ethylhexyl phthalate (DEHP) in three shrimps; 0.02–0.03 mg/kg of chlorpyrifos in three shrimps, and 0.03 mg/kg of trichlorfon in one shrimp, indicating that 6.52% and 8.70% of the samples contained phthalate and insecticide residues, respectively. Furthermore, the assessed risk was negligible and indicated no immediate health risk associated with shrimp consumption. Continual monitoring of the residues in shrimps is critical for further assessment of possible effects on human health.

The interaction of molten materials with coolant is of significant fundamental interest and is of paramount importance for nuclear safety and material processing as well. This study explores the quenching of melts of copper spheres and a eutectic mixture of bismuth trioxide and tungsten trioxide (BTOP) in de-ionized water and natural seawater through visualization using a high-speed video camera. The results show no fragmentation in the case of molten copper owing to its high surface tension, while the quench of BTOP in de-ionized water and seawater results in extensive fragmentation. The fragmentation in seawater is characterized by a greater fraction of larger debris than that in the de-ionized water. Moreover, the examination of the debris quenched in seawater using scanning electron microscopy reveals a rougher surface, which demonstrates intensive interactions between the BTOP melts and the seawater owing to the complex ions there.

Aloe vera ethanol extract (AVE) reportedly has significant anti-influenza virus activity, but its underlying mechanisms of action and constituents have not yet been completely elucidated. Previously, we have confirmed that AVE treatment significantly reduces the viral replication of green fluorescent protein-labeled influenza A virus in Madin-Darby canine kidney (MDCK) cells. In addition, post-treatment with AVE inhibited viral matrix protein 1 (M1), matrix protein 2 (M2), and hemagglutinin (HA) mRNA synthesis and viral protein (M1, M2, and HA) expressions. In this study, we demonstrated that AVE inhibited autophagy induced by influenza A virus in MDCK cells and also identified quercetin, catechin hydrate, and kaempferol as the active antiviral components of AVE. We also found that post-treatment with quercetin, catechin hydrate, and kaempferol markedly inhibited M2 viral mRNA synthesis and M2 protein expression. A docking simulation suggested that the binding affinity of quercetin, catechin hydrate, and kaempferol for the M2 protein may be higher than that of known M2 protein inhibitors. Thus, the inhibition of autophagy induced by influenza virus may explain the antiviral activity of AVE against H1N1 or H3N2. Aloe vera extract and its constituents may, therefore, be potentially useful for the development of anti-influenza agents.

Glutamate-induced neural toxicity in autophagic neuron death is partially mediated by increased oxidative stress. Therefore, reducing oxidative stress in the brain is critical for treating or preventing neurodegenerative diseases. Selaginella tamariscina is a traditional medicinal plant for treating gastrointestinal bleeding, hematuria, leucorrhea, inflammation, chronic hepatitis, gout, and hyperuricemia. We investigate the inhibitory effects of Selaginella tamariscina ethanol extract (STE) on neurotoxicity and autophagic cell death in glutamate-exposed HT22 mouse hippocampal cells. STE significantly increased cell viability and mitochondrial membrane potential and decreased the expression of reactive oxygen species, lactate dehydrogenase release, and cell apoptosis in glutamate-exposed HT22 cells. In addition, while glutamate induced the excessive activation of mitophagy, STE attenuated glutamate-induced light chain (LC) 3 II and Beclin-1 expression and increased p62 expression. Furthermore, STE strongly enhanced the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) phosphorylation activation. STE strongly inhibited glutamate-induced autophagy by activating the PI3K/Akt/mTOR signaling pathway. In contrast, the addition of LY294002, a PI3K/Akt inhibitor, remarkably suppressed cell viability and p-Akt and p62 expression, while markedly increasing the expression of LC3 II and Beclin-1. Our findings indicate that autophagy inhibition by activating PI3K/Akt/mTOR phosphorylation levels could be responsible for the neuroprotective effects of STE on glutamate neuronal damage.

Plasmonic photocatalysis, combing noble metal nanoparticles (NMNPs) with semiconductors, has been widely studied and proven to perform better than pure semiconductors. The plasmonic effects are mainly based on the localized surface plasmon resonance (LSPR) of NMNPs. The LSPR wavelength depends on several parameters, such as size, shape, the surrounding media, and the interdistance of the NMNPs. In this study, graphene-modified plate-like BiVO4 composites, combined with silver nanoplates (AgNPts), were successfully prepared and used as a photocatalyst for CO2 photoconversion. Triangular silver nanoplates (TAgNPts), icosahedral silver nanoparticles (I-AgNPs), and decahedra silver nanoparticles (D-AgNPs) were synthesized using photochemical methods and introduced to the nanocomposites to compare the shape-dependent plasmonic effect. Among them, T-AgNPts/graphene/BiVO4 exhibited the highest photoreduction efficiency of CO2 to CH4, at 18.1 μmolg−1h−1, which is 5.03 times higher than that of pure BiVO4 under the irradiation of a Hg lamp. A possible CO2 photoreduction mechanism was proposed to explain the synergetic effect of each component in TAgNPts/graphene/BiVO4. This high efficiency reveals the importance of considering the compositions of photocatalysts for converting CO2 to solar fuels.

This study demonstrates a novel multi-functional microfluidic system, designated three dimensional Alternative Current Electrokinetic/Surface Enhanced Raman Scattering (3D-ACEK/SERS), which can concentrate bacteria from whole blood, identify bacterial species, and determine antibiotic susceptibilities of the bacteria rapidly. The system consists of a hybrid electrokinetic mechanism, integrating AC-electroosmosis (AC-EO) and dielectrophoresis (DEP) that allows thousand-fold concentration of bacteria, including S. aureus, Escherichia coli, and Chryseobacterium indologenes, in the center of an electrode with a wide range of working distance (hundreds to thousands of μm), while exclusion of blood cells through negative DEP forces. This microchip employs SERS assay to determine the identity of the concentrated bacteria in approximately 2 min with a limit of detection of 3 CFU/ml, 5 orders of magnitude lower than that using standard centrifugation−purification process. Finally, label-free antibiotic susceptibility testing has been successfully demonstrated on the platform using both antibiotic-sensitive and multidrug-resistant bacterial strains illustrating a potential utility of the system to clinical applications.

Since its introduction in December of 2019, SARS-CoV-2, the virus that causes COVID-19 disease, has rapidly spread across the world. Whilst vaccines are being rolled out, non-pharmaceutical interventions remain the most important tools for mitigating the spread of SARS-CoV-2. Quantifying the impact of these measures as well as determining what settings are prone to instigating (super)spreading events is important for informed and safe reopening of spaces and the targeting of interventions. Mathematical models can help decipher the complex interactions that underlie virus transmission. Currently, most mathematical models developed during the COVID-19 epidemic evaluate interventions at national or subnational levels. Smaller scales of transmission, such as at the level of indoor spaces, have received less attention, despite the central role they play in both transmission and control. Models that do act on this scale use simplified descriptions of human behavior, impeding a valid quantitative analysis of the impact of interventions on transmission in indoor spaces, particularly those that aim for physical distancing. To more accurately predict the transmission of SARS-CoV-2 through a pedestrian environment, we introduce a model that links pedestrian movement and choice dynamics with SARS-CoV-2 spreading models.The objective of this paper is to investigate the spread of SARS-CoV-2 in indoor spaces as it arises from human interactions and assess the relative impact of non-pharmaceutical interventions thereon. We developed a world-wide unique combined Pedestrian Dynamics - Virus Spread model (PeDViS model), which combines insights from pedestrian modelling, epidemiology, and IT-design. In particular, an expert-driven activity assignment model is coupled with the microscopic simulation model (Nomad) and a virus spread model (QVEmod).We first describe the non-linear relationships between the risks of exposure to the virus and the duration, distance, and context of human interactions. We compared virus exposure relative to a benchmark contact (1.5meters for 15 minutes): a threshold often used by public health agencies to determine ‘at risk’ contacts. We discuss circumstances under which individuals that adhere to common distancing measures may nevertheless be at risk. Specifically, we illustrate the stark increase in exposure at shorter distances, as well as longer contact durations. These risks increase when the infected individual was present in the space before the interaction occurred, as a result of buildup of virus in the environment. The latter is particularly true in poorly ventilated spaces and highlights the importance of good ventilation to prevent potential virus exposure through indirect transmission routes. Combining intervention tools that target different routes of transmission can aid in accumulating impact. We use face masks as an example, which are particularly effective at reducing virus spread that is not affected by ventilation. We then demonstrate the use of PeDViS using a simple restaurant case study, focussing on transmission between guests. In this setting the exposure risk to individuals that are not seated at the same table is limited, but guests seated at nearby tables are estimated to experience exposure risks that surpass that of the benchmark contact. These risks are larger in low ventilation scenarios. Lastly, we illustrate that the impact of intervention measures on the number of new infections heavily depends on the relative efficiency of the direct and indirect transmission routes considered. This uncertainty should be considered when assessing the risks of transmission upon different types of human interactions in indoor spaces.The PeDViS case study shows the multi-dimensionality of SARS-CoV-2 that emerges from the interplay of human behaviour and the spread of respiratory viruses in indoor spaces. A modelling strategy that incorporates this in risk assessments can be an important tool to inform policy makers and citizens. It can empower them to make better design and policy decisions pertaining to the most effective use of measures to limit the spread of SARS-CoV-2 and safely open up indoor spaces.

This study aimed to engineer an advanced wound-dressing combining Bombyx mori L. silk fibroin (SF) with insulin-like growth factor-1 (IGF-1). Silk fibroin was purified through a newly-developed high-temperature degumming process and cast on a hydrophobic surface to form SF-films. The process allowed the fabrication of a film exhibiting a 42% increase in transparency and a 32% higher proliferation rate of BALB/3T3 fibroblasts compared to that obtained by conventional alkaline treatment. This study demonstrated that the optimal concentration of IGF-1 to promote BALB/3T3 cell growth in hyperglycemic medium was approximately 130 nM. Further analysis of wound healing in a diabetic mouse model indicated that SF-film loaded with 3.25 pmol IGF-1 showed significantly superior wound closure (13% increase) at 13 days after treatment compared to treatment with 65 pmol free IGF-1. We clearly observed improvement in diabetic wound healing exerted synergistically by SF-film and IGF-1, as reflected by parameters including degree of re-epithelialization, epithelial tissue area, and angiogenesis. These results strongly suggest the great potential of IGF-1-loaded SF-film as a dressing for the treatment of diabetic wounds.

The aim of this study was to fully understand the pollution characteristics and sources of PM

Most of the IC-electromagnetic interference researches get information in the frequency domain. However, in the electromagnetic interference (EMI) leakage research field, the measurement of the time domain is crucial. We have already proposed a single point time-domain EMI signal for information leakage analysis, but a single point measurement is incompetent. This paper proposes an automated measurement platform that can measure, visualize, and plot a time-domain two-dimensional (muti-point) EMI data on Microchip dsPIC33EP512MC202. This proposed automation process can be conveniently extended and applied to a variety of different devices under test.

Background Pu'er tea, a type of post-fermented tea made from Camellia sinensis leaves, has long been widely used in East Asian countries. It is mainly produced in southern China and is effective in preventing obesity due to its ability to break down fat. However, the effects of Pu'er tea on cognitive impairment or neuroinflammation by endotoxin have not yet been studied. Purpose Here, we assessed the inhibitory activity of Pu'er tea hot water extract (PTW) on neuroinflammation and cognitive impairment and explored its mechanism. Study design The ability of PTW to inhibit cognitive impairment was investigated in a mouse model of lipopolysaccharide (LPS)-induced neuroinflammation and murine microglia BV2 cells. Methods We examined whether oral administration of PTW prevented cognitive impairment and LPS-induced neuroinflammation using behavioral tests, Nissl staining, immunohistochemistry, western blotting, real-time reverse transcription-polymerase chain reaction (real-time RT-PCR), Griess assay, and enzyme-linked immunosorbent assay (ELISA). Results First, Morris water maze (MWM) and passive avoidance (PA) tests demonstrated that oral administration of PTW effectively attenuated LPS-induced spatial memory loss and inhibited neuronal damage of mouse brains. Histopathological analysis showed that PTW repressed LPS-induced expression of the activation markers ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP). Furthermore, PTW inhibited the expression of amyloidogenesis proteins such as amyloid-β precursor protein (APP), C99, and β-secretase-1 (BACE-1); production of inflammatory proteins such as Iba-1, GFAP, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2; activation of inflammatory pathways; and expression of inflammatory mediator mRNAs in hippocampal tissue. In cultured microglia, PTW treatment inhibited the generation of various inflammatory factors activated by LPS. Conclusion Our results in vivo and in vitro demonstrate that PTW effectively prevents cognitive impairment caused by neuroinflammation and is, therefore, a potential candidate for the development of a therapeutic agent for neurodegenerative diseases.

Efficient polymer solar cells were fabricated with regioregular poly 3-hexylthiophene (P3HT):(6,6)-phenyl C61 butyric acid methyl ester (PCBM)) as active layer and molybdenum trioxide (MoO3) and (N,N′-diphenyl)-N,N′-bis(1-naphthyl)-1,1′-biphenyl-4,4′-diamine (NPB) as buffer layers. The results of transient photocurrent and electrochemical impedance spectrometry of device indicate that the insertion of NPB layer between the active layer and MoO3 layer is critical to the enhanced performance. It can effectively prevent charge recombination at the interface of MoO3 hole extraction layer, reduce interfacial resistance due to the formation of Ohmic contact and enhance the exciton dissociation because of the newly formed NPB/PCBM dissociation interface. The optimized thickness of NPB layer is 5 nm, resulting in maximized power conversion efficiency (PCE) of 3.94% under AM1.5G 100 mW cm−2 illumination.

FliA is known to be a sigma factor that regulates bacterial flagella gene expression. Accumulating evidence suggests that FliA is involved in bacterial behavior other than motility. To elucidate the contribution of FliA to Pseudomonas aeruginosa pathophysiology, we analyzed the biological properties and gene expression profiles of a ΔfliA mutant. Transcriptome analysis results demonstrated that the expression levels of flagella biogenesis genes decreased dramatically in the mutant; consequently, the Δ fliA mutant failed to synthesize flagella and exhibited reduced motility. The ΔfliA mutant displayed stronger hemolytic and caseinolytic activities, as well as pyocyanin production. The expression of type 6 secretion system-II genes and interbacterial competition activity was decreased in the ΔfliA mutant. Direct evidence of fliA participation in virulence was obtained from analysis of hypervirulent strain B136-33. Adhesion to and cytotoxicity toward mammalian cells and penetration through cell layers were noted; furthermore, the colonization ability of the fliA::Tn5 mutant in the intestines of laboratory mice was compromised. Notably, the fliA-overexpressing strain displayed phenotypes similar to that of the fliA -defective strain, indicating that optimal FliA levels are critical to bacterial physiology . Our findings indicate that FliA plays diverse roles in P. aeruginosa , not only in flagella biosynthesis, but also in pathophysiology.

The first step to defining the rights, responsibilities and interests of stakeholders and constructing a compensation mechanism is to identify the stakeholders and clarify their mutual relationships. Nature reserves are complex ecosystems involving nature, the economy and society. There exists a conflict between the public welfare benefits of ecological conservation and the private gains to be realized from social and economic development. There also exist in a nature reserve complex relationships among stakeholders, involving the utilization of ecological resources, ecological conservation and ecological-economic interests. The introduction of tourism brings substantial changes to the existing stakeholder benefit structure in a nature reserve. The implementation of tourism ecological compensation (tourism payment for ecological service) is a process for redefining the distribution of rights, responsibilities and profits among stakeholders and it is also an essential way to balance the interests of the stakeholders. This paper uses a case study of Sanya Coral Reef National Nature Reserve in China to examine the characteristics of stakeholders and analyze their interests. According to the method for defining basic attributes proposed by Mitchel and other scholars, in cases of tourism ecological compensation, stakeholders can be classified as definitive stakeholders, expectant stakeholders and latent stakeholders. This paper applies these classifications and then analyzes the relationships between the rights and responsibilities of these stakeholders and how these change after the implementation of compensation. Additionally, based on the impact compensation has on different stakeholders, changes in the relationships can be analyzed and the structure of the stakeholders can be modelled. This case study of the Sanya Coral Reef National Nature Reserve illustrates the operationalization of a new mechanism for tourism ecological compensation. The paper illustrates a method for coordinating the relationships among the stakeholders involved with this national-level nature reserve.

This study aimed to determine the anti-inflammatory and hepatoprotective effects of Lysimachiae Herba ethanolic extract (LHE) in lipopolysaccharide (LPS)-stimulated macrophages and in a LPS/D-galactosamine (GalN)-induced acute hepatitis mouse model. Then, the production of inflammatory mediators and the activation of related pathways in macrophages were explored. Finally, we assessed the serum aminotransferase levels and the expression of inflammatory/antioxidant molecules in liver tissues in mice. Results revealed that LHE treatment significantly inhibited the production of inflammatory mediators in LPS-stimulated RAW 264.7 macrophages. Molecular data showed that LHE remarkably increased the activities of the antioxidant pathway and inhibited the phosphorylation of mitogen-activated protein kinase as well as the transcriptional activity of nuclear factor-κB induced by LPS. Furthermore, it prevented acute liver damage caused by LPS/D-GalN-induced hepatitis by inhibiting aminotransferase levels and histopathological changes in mice. Moreover, treatment with LHE significantly inhibited the activation of inflammatory pathways and increased the expression of antioxidant molecules including heme oxygenase-1/Nuclear factor erythroid 2-related factor 2. In conclusion, LHE has potent anti-inflammatory and hepatoprotective effects in LPS-stimulated macrophages and the LPS/D-GalN-induced acute hepatitis mouse model. Thus, it can be a treatment option for inflammation, hepatitis, and liver injury.

This study reports on morphology dependent antibacterial activities of CuxO/ZnO nanocomposites towards Escherichia coli. The CuxO/ZnO nanocomposites were formed by aqueous photoreduction of CuxO nanostructures on solution grown ZnO nanorods on Si substrates. By controlling the photoreduction time and temperature, various CuxO nanostructures including nanocubes, nanoclusters, nanospikes, and nanowebs were created as verified by scanning electron microscopy. X-ray diffraction analysis reveals the good crystallinity of the ZnO nanorods. X-ray photoelectron spectroscopy confirms the successful deposition of CuO and Cu2O nanostructures on the nanorods. Antibacterial tests were performed in dark and under low-intensity blue-light irradiation. The nanoweb sample has an antibacterial efficiency of 95.8% for 10 min in dark and the nanospike sample has an efficiency of 99.5% for 10 min under light. For the nanospike sample, remarkable bacterial survival ratios of 3 × 10–4 and 10–5 in dark and under light both for a 60 min reaction time, respectively, have been achieved. The excellent antibacterial performance is attributed to combined effects of mechanical piercing of ZnO nanorods, release of Zn2+, Cu2+, and Cu+ ions, and effective generation of reactive oxygen species due to charge separation.

To simultaneously improve both ionic/electronic conduction in many electrochemical devices have received great attention. For example, (Ba,Sr)(Co,Fe)O3 perovskite exhibiting unique hole/oxygen ion mixed conduction behavior becomes important membrane materials for oxygen separation application. In additions, composite electrolytes consisting of multiple ionic conductors have received great attention for high temperature fuel cell application. For instance, enhanced conduction was observed when the oxygen ion conductor, doped ceria, was directly mixed with Li/K carbonates. The electrical conduction of composite electrolyte was contributed by the migration of oxygen ions in solid state and carbonate ions in liquid state. It is believed that ions tend to be highly mobile at the interface between doped ceria and carbonates. As a result, higher conductivity of the composite electrolyte was observed. In other words, the super-ionic conduction path/domain might exist at the interface between doped ceria and carbonates. However, to optimize the mixed conduction, the materials/microstructure designs play an important role. Thus, the objective of this study is to conduct (1) fabrication/design of composite electrolytes (2) microstructure development, (3) characterization of conduction/interfacial kinetics for composite electrolytes in high-temperature fuel cells. High-resolution SEM, XRD, and electrochemical Impedance Spectroscopy are employed to conduct microstructural, structural and impedance analyses. The electrical conduction behavior of composite electrolytes will be rationalized based on the pore size, pore distribution and interfacial area.

In many electrochemical devices, mixed ionic/electronic conduction have received great attention. For instance, oxygen transport membrane (OTM) based on (Ba,Sr)(Co,Fe)O3 perovskite exhibit unique hole/oxygen ion mixed conduction behavior for oxygen separation application. Accordingly, electrodes/electrolytes exhibiting both electronic and/or multiple ionic conducting properties have been used for high temperature fuel cell application. For example, mixed conducting electrodes based on composite electrode (e.g. LSM/SDC, LSM/YSZ) show improved SOFC performance in comparison to conventional electrode. Such unique conduction behavior may be rationalized based on defect chemistry consideration. Thus, the materials processing and microstructure design may become key issues to optimize their mixed conduction properties. For instance, better hole and oxygen conducing perovskite may be obtained when desired aliovalent dopant and oxidizing atmosphere are used. Thus, the objective of this work is to conduct (1) fabrication/design of MIEC through defect-favored processing, (2) microstructure development for better gas transport, (3) characterization of conduction/interfacial kinetics for better electrodes/electrolytes performance. Desired analytical equipment such as SEM, XRD, electrochemical impedance spectroscopy (EIS) and cell testing are performed to conduct microstructural, structural and impedance analyses. The electrical conduction behavior of composite electrode/electrolytes will be discussed based on defect chemistry consideration and individual microstructure and morphology including pore size, pore distribution and interface area.

Ultralight and nitrogen doped graphene aerogels (UNGAS) are developed by a hydrothermal method in the presence of graphene, dopamine (DA) and L-arginine. Analysis shows that DA can functionalize the graphene surface and also embed nitrogen atoms onto the graphene sheets upon pyrolysis, and the values of pH on the hydrothermal fabrication of UNGAS have great influence on the formation of UNGAS. By adjusting the amount of L-arginine and dopamine in the precursor mixture, UNGAS with a density as low as 2.54 mg/cm3 can be prepared. The UNGAS show high absorption capacity for various oils due to low density, N doping and large surface area.