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This study developed a new tool, differential staining fluorescence microscopy (DSFM), to measure the biovolume and track the location of enteric pathogens in mixed-species biofilms which can pose a risk to food safety in beef processing facilities. DSFM was employed to examine the impact of pathogenic bacteria, Escherichia coli O157:H7 and three different Salmonella enterica strains on mixed-species biofilms of beef processing facilities. Fourteen floor drain biofilm samples from three beef processing plants were incubated with overnight BacLight stained enteric pathogens at 7 °C for 5 days on stainless steel surface then counter-stained with FM-1-43 biofilm stain and analyzed using fluorescence microscopy. Notable variations in biovolume of biofilms were observed across the fourteen samples. The introduction of E. coli O157:H7 and S. enterica strains resulted in diverse alterations of biofilm biovolume, suggesting distinct impacts on mixed-species biofilms by different enteric pathogens which were revealed to be located in the upper layer of the mixed-species biofilms. Pathogen strain growth curve comparisons and verification of BacLight Red Stain staining effectiveness were validated. The findings of this study show that the DSFM method is a promising approach to studying the location of enteric pathogens within mixed-species biofilms recovered from processing facilities. Understanding how foodborne pathogens interact with biofilms will allow for improved targeted antimicrobial interventions. [ABSTRACT FROM AUTHOR]

To improve the detection speed of cow mounting behavior and the lightness of the model in dense scenes, this study proposes a lightweight rapid detection system for cow mounting behavior. Using the concept of EfficientNetV2, a lightweight backbone network is designed using an attention mechanism, inverted residual structure, and depth-wise separable convolution. Next, a feature enhancement module is designed using residual structure, efficient attention mechanism, and Ghost convolution. Finally, YOLOv5s, the lightweight backbone network, and the feature enhancement module are combined to construct a lightweight rapid recognition model for cow mounting behavior. Multiple cameras were installed in a barn with 200 cows to obtain 3343 images that formed the cow mounting behavior dataset. Based on the experimental results, the inference speed of the model put forward in this study is as high as 333.3 fps, the inference time per image is 4.1 ms, and the model mAP value is 87.7%. The mAP value of the proposed model is shown to be 2.1% higher than that of YOLOv5s, the inference speed is 0.47 times greater than that of YOLOv5s, and the model weight is 2.34 times less than that of YOLOv5s. According to the obtained results, the model proposed in the current work shows high accuracy and inference speed and acquires the automatic detection of cow mounting behavior in dense scenes, which would be beneficial for the all-weather real-time monitoring of multi-channel cameras in large cattle farms. [ABSTRACT FROM AUTHOR]

To improve the detection speed of cow mounting behavior and the lightness of the model in dense scenes, this study proposes a lightweight rapid detection system for cow mounting behavior. Using the concept of EfficientNetV2, a lightweight backbone network is designed using an attention mechanism, inverted residual structure, and depth-wise separable convolution. Next, a feature enhancement module is designed using residual structure, efficient attention mechanism, and Ghost convolution. Finally, YOLOv5s, the lightweight backbone network, and the feature enhancement module are combined to construct a lightweight rapid recognition model for cow mounting behavior. Multiple cameras were installed in a barn with 200 cows to obtain 3343 images that formed the cow mounting behavior dataset. Based on the experimental results, the inference speed of the model put forward in this study is as high as 333.3 fps, the inference time per image is 4.1 ms, and the model mAP value is 87.7%. The mAP value of the proposed model is shown to be 2.1% higher than that of YOLOv5s, the inference speed is 0.47 times greater than that of YOLOv5s, and the model weight is 2.34 times less than that of YOLOv5s. According to the obtained results, the model proposed in the current work shows high accuracy and inference speed and acquires the automatic detection of cow mounting behavior in dense scenes, which would be beneficial for the all-weather real-time monitoring of multi-channel cameras in large cattle farms. [ABSTRACT FROM AUTHOR]

This study developed a new tool, differential staining fluorescence microscopy (DSFM), to measure the biovolume and track the location of enteric pathogens in mixed-species biofilms which can pose a risk to food safety in beef processing facilities. DSFM was employed to examine the impact of pathogenic bacteria, Escherichia coli O157:H7 and three different Salmonella enterica strains on mixed-species biofilms of beef processing facilities. Fourteen floor drain biofilm samples from three beef processing plants were incubated with overnight BacLight stained enteric pathogens at 7 °C for 5 days on stainless steel surface then counter-stained with FM-1-43 biofilm stain and analyzed using fluorescence microscopy. Notable variations in biovolume of biofilms were observed across the fourteen samples. The introduction of E. coli O157:H7 and S. enterica strains resulted in diverse alterations of biofilm biovolume, suggesting distinct impacts on mixed-species biofilms by different enteric pathogens which were revealed to be located in the upper layer of the mixed-species biofilms. Pathogen strain growth curve comparisons and verification of BacLight Red Stain staining effectiveness were validated. The findings of this study show that the DSFM method is a promising approach to studying the location of enteric pathogens within mixed-species biofilms recovered from processing facilities. Understanding how foodborne pathogens interact with biofilms will allow for improved targeted antimicrobial interventions. [ABSTRACT FROM AUTHOR]

When plates with edge cracks in the rolling process is straightened by cyclic tensile and compressive stress, the tip of edge crack always accompanied by stress concentration, which leads to crack propagation. In this paper, damage parameters are imported into the plate straightening model based on determining the GTN damage parameters of magnesium alloy materials by inverse finite element calibration method, the influence of different straightening process schemes and prefabricated V-shaped crack geometry on crack growth is analyzed through the way of the combination of simulation and straightening experiment. The results show that the peak values of equivalent stress and equivalent strain under each straightening roll appear at the crack tip. The value of longitudinal stress and equivalent stain decrease with the distance to crack tip becomes larger. The peak value of longitudinal stress appears when the crack circumferential angle is about 100°, and the crack tip is easy to form crack propagation; when the plate passes roll 2 and roll 4, the equivalent stress and strain concentration at the crack tip are most obvious; when the reduction reaches a certain degree, the void volume fraction (VVF) reaches the VVF of the material breaking; with the increase of the entrance reduction, the number of VVF at the crack tip which reaches the material fracture increases, and the length of crack propagation increases; the stress concentration at the tip of V-shaped crack with large length–width ratio is obvious, and the VVF is more likely to reach the VVF at the time of material fracture, crack initiates and propagates easily. [ABSTRACT FROM AUTHOR]

Due to the interest in the potential pharmacological application of dandelion, the chemical constituents and activities of Taraxacum mongolicum Hand.-Mazz were studied. Box–Behnken response surface methodology was employed to optimize the protocol for extraction of flavonoid from dandelion. The molecular structures of different flavonoid compounds were acquired and analyzed by liquid chromatography-mass spectrometry (LC–MS) and nuclear magnetic resonance (NMR) spectroscopy. Several major flavonoid compounds were isolated and purified, namely, hesperetin-5′-O-β-rhamnoglucoside, hesperetin-7-glucuronide, kaempferol-3-glucoside, baicalein, hyperseroside, which were extracted for the first time from dandelion. Hesperetin-5′-O-β-rhamnoglucoside was identified as a new type of flavonoid that had never reported in the literature. This new flavonoid has outstanding antioxidant activity, as shown by its IC50 value (8.72 mg/L) for scavenging DPPH free radicals. The determination of the structure-related antioxidant activities could be interpreted based on DFT calculations. As such, we have not only illustrated the rich flavonoid contents in Taraxacum mongolicum Hand.-Mazz, but also revealed new types of flavonoid compounds in dandelion in terms of structure and antioxidant properties. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children (age 0–14 years); however, the etiology remains incompletely understood. Several environmental exposures have been linked to risk of childhood ALL, including air pollution. Closely related to air pollution and human development is artificial light at night (ALAN), which is believed to disrupt circadian rhythm and impact health. We sought to evaluate outdoor ALAN and air pollution on risk of childhood ALL. The California Linkage Study of Early-Onset Cancers is a large population-based case–control in California that identifies and links cancer diagnoses from the California Cancer Registry to birth records. For each case, 50 controls with the same year of birth were obtained from birth records. A total of 2,782 ALL cases and 139,100 controls were identified during 2000–2015. ALAN was assessed with the New World Atlas of Artificial Night Sky Brightness and air pollution with an ensemble-based air pollution model of particulate matter smaller than 2.5 microns (PM2.5). After adjusting for known and suspected risk factors, the highest tertile of ALAN was associated with an increased risk of ALL in Hispanic children (odds ratio [OR] = 1.15, 95% confidence interval [CI] 1.01–1.32). There also appeared to be a borderline association between PM2.5 level and risk of ALL among non-Hispanic White children (OR per 10 µg/m3 = 1.24, 95% CI 0.98–1.56). We observed elevated risk of ALL in Hispanic children residing in areas of greater ALAN. Further work is needed to understand the role of ALAN and air pollution in the etiology of childhood ALL in different racial/ethnic groups. [ABSTRACT FROM AUTHOR]

At present, prognostic biomarkers of acute coronary syndrome (ACS) are fewer. The aim of this study was to explore the predictive value of soluble osteoclast-associated receptor (sOSCAR) level for the major adverse cardiovascular events (MACE) occurring within 30 days after ACS. From January to August 2020, a total of 108 patients with ACS who were admitted to our hospital, were enrolled in this study. Of the 108 patients, 79 were men and 29 women. Patient-related data, including age, sex, body mass index, history of type 2 diabetes, history of hyperlipidemia and serum sOSCAR level, were collected. All patients were followed up for 30 days. Based on MACE occurrence, the 108 patients were divided into MACE group (n = 17) and non-MACE group (n = 91). The baseline data were compared between the two groups, MACE-independent risk factors were identified by multivariate regression analysis, and the predictive value of sOSCAR for MACE occurring within 30 days after CAS was analyzed using receiver operating characteristic (ROC) curve. At the same time, according to the type of ACS, the 108 patients with ACS were divided into unstable angina (UA) group (n = 29), non ST-segment elevation myocardial infarction (USTEMI) group (n = 45) and ST-segment elevation myocardial infarction (STEMI) group (n = 34), and then the sOSCAR level and MACE incidence were observed in each group. The serum sOSCAR level was significantly lower in the MACE group [130(100,183)] than in the non-MACE group [301(220,370)] (P = 0.000). The area under ROC curve of sOSCAR level for MACE occurring within 30 days after CAS was 0.860 with 95%CI 0.782–0.919, P < 0.001. Multivariate regression analysis indicated that the sOSCAR level was an independent risk factor for the MACE occurring within 30 days after CAS (OR 0.26, 95%CI 0.087–0.777, P = 0.04). The MACE incidence (0%) was the lowest but the sOSCAR level was the highest in the UA group, while in the STEMI group, the MACE incidence (23.53%) was the higest but the sOSCAR level was the lowest among the UA, STEMI and NSTEMI groups. Serum sOSCAR level may be used as a predictor of MACE occurring within the short-term after ACS. The higher the sOSCAR level, the lower the MACE incidence. [ABSTRACT FROM AUTHOR]

We designed this study to assess if surgical safety can be improved by intraoperative use of intraocular lens (IOL) for cataract phacoemulsification. We performed phacoemulsification cataract removal on 401 patients. We randomly assigned these patients into three groups: the standard setting (Group I, n = 134), with reduced vacuum and flow rate (Group II, n = 137), and with IOL insertion before the last quadrant was emulsified with standard setting (Group III, n = 130). The primary outcomes included the risk of posterior capsular rupture (PCR), ultrasound time, energy, and complications. The secondary outcomes included central corneal thickness (CCT), CCT changes, endothelial cells (ETC) counting, ETC loss, and the best corrected distance visual acuity (BCVA) measured on day 1, day 7 and day 30. If PCR occurred, we emulsified the residual lens materials after insertion of IOL and clean of the prolapsed vitreous. We found that the risk of PCR in Group III (0/130) was lower than Group I (9/134, corrected relative risk (RR) = 18.44, 95% CI: 1.08–313.56) and Group II (3/137, corrected RR = 6.64, 95% CI: 0.35–27.41). Group III showed better BCVA on day 1 and 7, less ECC loss on day 7 and 30, and less CCT increase on day 1 and 7. No cases converted to extracapsular cataract extraction. No residual lens materials misdirected into vitreous cavity. Intraoperative use of IOL can improve surgical safety for dense cataract phacoemulsification. [ABSTRACT FROM AUTHOR]

Behavior is one of the important factors reflecting the health status of dairy cows, and when dairy cows encounter health problems, they exhibit different behavioral characteristics. Therefore, identifying dairy cow behavior not only helps in assessing their physiological health and disease treatment but also improves cow welfare, which is very important for the development of animal husbandry. The method of relying on human eyes to observe the behavior of dairy cows has problems such as high labor costs, high labor intensity, and high fatigue rates. Therefore, it is necessary to explore more effective technical means to identify cow behaviors more quickly and accurately and improve the intelligence level of dairy cow farming. Automatic recognition of dairy cow behavior has become a key technology for diagnosing dairy cow diseases, improving farm economic benefits and reducing animal elimination rates. Recently, deep learning for automated dairy cow behavior identification has become a research focus. However, in complex farming environments, dairy cow behaviors are characterized by multiscale features due to large scenes and long data collection distances. Traditional behavior recognition models cannot accurately recognize similar behavior features of dairy cows, such as those with similar visual characteristics, i.e., standing and walking. The behavior recognition method based on 3D convolution solves the problem of small visual feature differences in behavior recognition. However, due to the large number of model parameters, long inference time, and simple data background, it cannot meet the demand for real-time recognition of dairy cow behaviors in complex breeding environments. To address this, we developed an effective yet lightweight model for fast and accurate dairy cow behavior feature learning from video data. We focused on four common behaviors: standing, walking, lying, and mounting. We recorded videos of dairy cow behaviors at a dairy farm containing over one hundred cows using surveillance cameras. A robust model was built using a complex background dataset. We proposed a two-pathway X3DFast model based on spatiotemporal behavior features. The X3D and fast pathways were laterally connected to integrate spatial and temporal features. The X3D pathway extracted spatial features. The fast pathway with R(2 + 1)D convolution decomposed spatiotemporal features and transferred effective spatial features to the X3D pathway. An action model further enhanced X3D spatial modeling. Experiments showed that X3DFast achieved 98.49% top-1 accuracy, outperforming similar methods in identifying the four behaviors. The method we proposed can effectively identify similar dairy cow behaviors while improving inference speed, providing technical support for subsequent dairy cow behavior recognition and daily behavior statistics. [ABSTRACT FROM AUTHOR]

Ectoine has gained considerable attention as a high-value chemical with significant application potential and market demand. This study aimed to increase ectoine yields by blocking the metabolic shunt pathway of l-aspartate-4-semialdehyde, the precursor substrate in ectoine synthesis. The homoserine dehydrogenase encoded by hom in H. campaniensis strain XH26 is responsible for the metabolic shunt of l-aspartate-4-semialdehyde to glycine. CRISPR/Cas9 technology was used to seamlessly knockout hom, blocking the metabolic shunt pathway to increase ectoine yields. The ectoine yield of XH26/Δhom was 351.13 mg (g CDW)−1 after 48 h of incubation in 500 mL shake flasks using optimal medium with 1.5 mol L−1 NaCl, which was significantly higher than the 239.18 mg (g CDW)−1 of the wild-type strain. Additionally, the absence of the ectoine metabolic shunt pathway affects betaine synthesis, and thus the betaine yields of XH26/Δhom was 19.98 mg (g CDW)−1, considerably lower than the 69.58 mg (g CDW)−1 of the wild-type strain. Batch fermentation parameters were optimized, and the wild-type strain and XH26/Δhom were fermented in 3 L fermenters, resulting in a high ectoine yield of 587.09 mg (g CDW)−1 for the defective strain, which was significantly greater than the ectoine yield of 385.03 mg (g CDW)−1 of the wild-type strain. This study showed that blocking the metabolic shunt of synthetic substrates effectively increases ectoine production, and a reduction in the competitively compatible solute betaine appears to promote increased ectoine synthesis. [ABSTRACT FROM AUTHOR]

Probe-based confocal laser endomicroscopy (pCLE), also known as optical biopsy, is a new endoscopic technique that provides real-time magnification of 1000 × microscopic tissue information to diagnose indeterminate biliary strictures. Tissue sampling by endoscopic retrograde cholangiopancreatography (ERCP) is routinely performed to evaluate indeterminate biliary strictures. To evaluate the accuracy of pCLE and tissue sampling by ERCP in the diagnosis of indeterminate biliary strictures, 18 articles were included from 2008 to 2021 through Embase, PubMed, Web of Science, and Cochrane library databases. The summary estimates for the pCLE diagnosis of indeterminate biliary strictures were: sensitivity 0.88 (95% confidence interval (CI), 0.84–0.91); specificity 0.79 (95% CI 0.74–0.83); and Diagnostic Odds Ratio (DOR) 24.63 (95% CI 15.76–38.48). The summary estimates for tissue sampling by ERCP diagnosis for indeterminate biliary strictures were: sensitivity 0.54 (95% CI 0.49–0.59); specificity 0.96 (95% CI 0.94–0.98); and DOR 11.31 (95% CI 3.90–32.82). The area under the sROC curve of pCLE diagnosis of indeterminate biliary strictures is 0.90 higher than 0.65 of tissue sampling by ERCP. The pCLE is a better approach than tissue sampling by ERCP for the diagnosis of indeterminate biliary strictures by providing real-time microscopic images of the bile ducts. [ABSTRACT FROM AUTHOR]

To investigate the ability of theaflavins (TF) from black tea to protect dentin collagen against enzymatic degradation via cross-linking effect under clinically relevant conditions. 10-µm-thick dentin films were microtomed from dentin slabs of human molars. Following demineralization, films or slabs were treated with TF at two concentrations (0.4% and 2%) for 30 s. A well-known collagen cross-linker grape seed proanthocyanidins (PA) was used as control. Collagen cross-linking interactions and stabilization against enzymatic degradation were investigated by Fourier transform infrared spectroscopy, weight loss, hydroxyproline release, and scanning/transmission electron microscopy. Data were analyzed by ANOVA, Tukey's and Student's T test (α = 0.05%). The results showed collagen cross-linking and stabilization efficacy was dependent on TF/PA concentrations. At 2.0%, TF and PA offered nearly full protection to collagen; at 0.4%, TF exhibited a significantly better collagen stabilization effect than PA (P < 0.05), while untreated collagen was completely digested. It's concluded that TF cross-links dentin collagen within a clinically relevant time (30 s) and offers excellent collagen protection against enzymatic degradation, with efficacy comparable to or better than PA. The study supports the potential use of TF as a novel, promising collagen cross-linker for degradation resistant, long-lasting dentin bonding in composite restorations. [ABSTRACT FROM AUTHOR]

Developed through evolution, brain neural system self-organizes into an economical and dynamic network structure with the modulation of repetitive neuronal firing activities through synaptic plasticity. These highly variable electric activities inevitably produce a spontaneous magnetic field, which also significantly modulates the dynamic neuronal behaviors in the brain. However, how this spontaneous electromagnetic induction affects the self-organization process and what is its role in the formation of an economical neuronal network still have not been reported. Here, we investigate the effects of spontaneous electromagnetic induction on the self-organization process and the topological properties of the self-organized neuronal network. We first find that spontaneous electromagnetic induction slows down the self-organization process of the neuronal network by decreasing the neuronal excitability. In addition, spontaneous electromagnetic induction can result in a more homogeneous directed-weighted network structure with lower causal relationship and less modularity which supports weaker neuronal synchronization. Furthermore, we show that spontaneous electromagnetic induction can reconfigure synaptic connections to optimize the economical connectivity pattern of self-organized neuronal networks, endowing it with enhanced local and global efficiency from the perspective of graph theory. Our results reveal the critical role of spontaneous electromagnetic induction in the formation of an economical self-organized neuronal network and are also helpful for understanding the evolution of the brain neural system. [ABSTRACT FROM AUTHOR]

Internal carotid artery occlusion (ICAO) is a relatively uncommon but important cause of transient ischaemic attack and cerebral infarction. Hybrid surgery (HS) improves cerebral perfusion, but its impact on neurocognitive function has been controversial. Patients with symptomatic chronic ICAO treated by hybrid surgery or medical treatment from 2016 to 2019 were included. We recorded and analysed the clinical characteristics, angiographic data, outcomes and cognitive status. Functional assessments, including the National Institutes of Health Stroke Scale (NIHSS), the Barthel Index, and a battery of neuropsychological tests, including the Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale–Cognitive Subtest (ADAS-cog), verbal fluency, and Colour Trail test Parts 1 and 2, were administered. Significant improvements in the ADAS (before, 7.5 ± 6.2 versus after, 5.2 ± 5.7; P = 0.022), MMSE (before, 25.5 ± 2.8 versus after, 28.1 ± 2.3; P = 0.013), and Colour Trail test Part 1 (before, 118.3 ± 26.5 versus after, 96.2 ± 23.1; P = 0.016) were observed six months after HS. Moreover, the abovementioned postprocedure scales were ameliorated in the HS group. This study found that in patients with multiple symptomatic ICAO and objective ipsilateral ischaemia, successful HS leads to improvement in the scores of three cognitive tests. [ABSTRACT FROM AUTHOR]

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a complicated maternally inherited disorder lacking of sensitive and specific biomarkers. The objective of this study was to investigate the serum neurofilament light chain (NfL) as a novel biomarker of neurological dysfunction in MELAS. Patients with different status of MELAS were enrolled in this study. The Mini-Mental State Examination (MMSE) was given to the participants to evaluate cognition status. Multiple functional MRI was performed on the participants. Blood samples were collected and the serum NfL concentrations were determined by the single-molecule array technology (Simoa). This study enrolled 23 patients with MELAS, 15 people in the acute attack phase of MELAS and 10 people in the remission phase, including 2 patients in both acute attack and remission phase. Sixteen healthy controls (HCs) were also enrolled. Serum NfL level increased significantly in patients with MELAS. Serum NfL level in the acute attack group (146.73 [120.91–411.31] pg/ml, median [IQR]) was higher than in the remission group (40.31 [19.54–151.05] pg/ml, median [IQR]) and HCs group (7.70 [6.13–9.78] pg/ml, median [IQR]) (p < 0.05). The level of NfL in the remission phase group was higher than in HCs group (p < 0.05). A negative correlation was found between the serum NfL level and MMSE (p = 0.006, r = -0.650). The NfL concentration correlated positively with stroke-like lesion volume in the brain (r = 0.740, p < 0.001). Serum NfL may serve as a novel biomarker for the neurological dysfunction in MELAS patients. [ABSTRACT FROM AUTHOR]

This corrects the article DOI: 10.1038/srep23934 [ABSTRACT FROM AUTHOR]

Atherosclerosis is a serious public health concern. Excessive inflammatory responses of vascular cells are considered a pivotal pathogenesis mechanism underlying atherosclerosis development. It is known that Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signalling plays an important role in atherosclerosis progression. Protein inhibitor of activated STAT3 (PIAS3) is the key negative regulator of JAK/STAT3 signalling. However, its effect on atherogenesis is unknown. Here, we observed that PIAS3 levels are reduced in atherosclerotic lesions and that PIAS3 expression decreases in conjunction with increases in interleukin-6 expression and atherosclerosis severity. Oxidized low-density lipoprotein (ox-LDL), an atherogenic stimulus, reduced PIAS3 expression, an effect that may be attributed to nitric oxide synthesis upregulation. In turn, PIAS3 overexpression effectively suppressed ox-LDL-induced inflammation, lipid accumulation and vascular smooth muscle cell proliferation. These results indicate that PIAS3 is a critical repressor of atherosclerosis progression. The findings of this study have contributed to our understanding on the pathogenesis of atherosclerosis and have provided us with a potential target through which we can inhibit atherosclerosis-related cellular responses. [ABSTRACT FROM AUTHOR]

Moyamoya disease (MMD) is a chronic and progressive cerebrovascular stenosis or occlusive disease that occurs near Willis blood vessels. The aim of this study was to investigate the mutation of DIAPH1 in Asian population, and to compare the angiographic features of MMD patients with and without the mutation of the DIAPH1 gene. Blood samples of 50 patients with MMD were collected, and DIAPH1 gene mutation was detected. The angiographic involvement of the posterior cerebral artery was compared between the mutant group and the non-mutant group. The independent risk factors of posterior cerebral artery involvement were determined by multivariate logistic regression analysis. DIAPH1 gene mutation was detected in 9 (18%) of 50 patients, including 7 synonymous mutations and 2 missense mutations. However, the incidence of posterior cerebral artery involvement in mutation positive group was very higher than that in mutation negative group (77.8% versus 12%; p = 0.001). There is an association between DIAPH1 mutation and PCA involvement (odds ratio 29.483, 95% confidence interval 3.920–221.736; p = 0.001). DIAPH1 gene mutation is not a major genetic risk gene for Asian patients with moyamoya disease but may play an important role in the involvement of posterior cerebral artery. [ABSTRACT FROM AUTHOR]

Ion channels are important regulators in cell proliferation, migration, and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel genes in glioma. We designate 18 ion channel genes that are differentially expressed in high-grade glioma as a prognostic molecular signature. This ion channel gene expression based signature predicts glioma outcome in three independent validation cohorts. Interestingly, 16 of these 18 genes were down-regulated in high-grade glioma. This signature is independent of traditional clinical, molecular, and histological factors. Resampling tests indicate that the prognostic power of the signature outperforms random gene sets selected from human genome in all the validation cohorts. More importantly, this signature performs better than the random gene signatures selected from glioma-associated genes in two out of three validation datasets. This study implicates ion channels in brain cancer, thus expanding on knowledge of their roles in other cancers. Individualized profiling of ion channel gene expression serves as a superior and independent prognostic tool for glioma patients. [ABSTRACT FROM AUTHOR]

Hemorrhagic events are the main focus of attention during antithrombosis therapy in patients with coronary artery disease (CAD). This study aims to investigate the potential of using photoplethysmography (PPG) and machine learning techniques to assess hemorrhagic risk in patients with CAD. A total of 1638 patients with CAD were enrolled from January 2018 to October 2019, among which 114 patients were observed to have at least one positive event. Importantly, 102 patients with 9933 records were finally retained for analysis in this study. Participants were required to collect data using the portable PPG acquisition device and the specially designed Android APP. The data was collected and uploaded to a remote server. Based on collected PPG signals, we extracted features in a total of 30 dimensions from time-domain, frequency-domain, and wavelet packet decomposition. Logistic regression, support vector regression, random forest, and XGBoost regression models were established to achieve hemorrhagic risk evaluation, and then, their performances were compared. In total, 10 features extracted from PPG showed statistical significance (p < 0.01) between negative and positive groups. The newly established XGBoost model performed best in the hemorrhagic risk evaluation experiment, wherein the mean area under the curve (AUC) with tenfold cross-validation was 0.762 ± 0.024 and the sensitivity and specificity were 0.679 ± 0.051 and 0.714 ± 0.014, respectively. We established a data acquisition system for PPG signal collection, and demonstrated that a set of features extracted from PPG and the proposed machine learning model are promising in the evaluation of hemorrhagic risk among patients with CAD. In comparison with the traditional HAS-BLED score, the proposed method can obtain the quantitative risk prediction probability from a single PPG record, which has the advantages of dynamics and continuity, and can provide timely feedback for doctors' antithrombotic treatment, which is of great significance for doctors to quickly determine the effectiveness of the treatment and adjust the timely treatment plans accordingly. [ABSTRACT FROM AUTHOR]

High-altitude pulmonary edema (HAPE) is a common acute altitude sickness. This study was designed to investigate the effect of MIR17HG polymorphisms on HAPE risk in the Chinese population. The Agena MassARRAY platform was used to genotype six single-nucleotide polymorphisms (SNPs) in the MIR17HG gene in 244 HAPE patients and 243 non-HAPE controls. The odds ratio (OR) and 95% confidence interval were used to evaluate the association between each MIR17HG polymorphisms and the risk of HAPE under a polygenetic model. Statistical analysis was performed using the χ2 test. Multifactor dimensionality reduction (MDR) analysis was used to analyze the impacts of SNP–SNP interactions on the risk of HAPE. According to the allele model, the HAPE risk of people with the rs7318578 A allele of MIR17HG was lower than that of people with the C allele (OR 0.74, p = 0.036).Logistic regression analysis of four models for all selected MIR17HG SNPs showed significant differences in the frequencies of rs7318578 (OR 0.74, p = 0.037) and rs17735387 (OR 1.51, p = 0.036) between cases and controls. The results of the sex stratification analysis showed that among males, rs17735387 in the MIR17HG gene is associated with an increased risk of HAPE. MDR analysis showed that the best combination model was a three-locus model incorporating rs72640334, rs7318578, and rs7336610. This study revealed the correlations between rs7318578 and rs17735387 on the MIR17HG gene and the risk of HAPE in the Chinese population, providing a theoretical basis for the early screening, prevention, and diagnosis of HAPE in high-risk populations. [ABSTRACT FROM AUTHOR]

The total flavone of Abelmoschus manihot (TFA), a compound extracted from the flowers of Abelmoschus manihot (L.) Medic, has been widely used for the treatment of Crohn's disease, chronic glomerulonephritis and other diseases. The aim of this study was to investigate the effect of TFA on the gut microbiota and intestinal barrier in dextran sulfate sodium (DSS)-induced experimental colitis. C57BL/6J mice were treated with 2.5% DSS in drinking water to induce colitis. Mice were orally administered TFA (62.5 mg/kg, 125 mg/kg) or prednisone acetate (PAT, 2.5 mg/kg) once daily for 7 days. Biological samples were collected for analysis of inflammatory cytokines, gut microbiota and intestinal barrier integrity. TFA-H (125 mg/kg) markedly attenuated DSS-induced colon shortening and histological injury in experimental colitis. The therapeutic effect was similar to that of PAT administration. TFA-H notably modulated the dysbiosis of gut microbiota induced by DSS and greatly enriched Akkermansia muciniphila (A. muciniphila). Moreover, TFA-H remarkably ameliorated the colonic inflammatory response and intestinal epithelial barrier dysfunction. Interestingly, TFA directly promotes the growth of A. muciniphila in vitro. Taken together, the results revealed for the first time that TFA, as a prebiotic of A. muciniphila, improved DSS-induced experimental colitis, at least partly by modulating the gut microflora profile to maintain colonic integrity and inhibit the inflammatory response. [ABSTRACT FROM AUTHOR]

MicroRNAs have emerged as key regulators in vascular diseases and are involved in the formation of atherosclerotic lesions. However, the atherosclerotic-specific MicroRNAs and their functional roles in atherosclerosis are unclear. Here, we report that miR-378c protects against atherosclerosis by directly targeting Sterile Alpha Motif Domain Containing 1 (Samd1), a predicted transcriptional repressor. miR-378c was strikingly reduced in atherosclerotic plaques and blood of acute coronary syndrome (ACS) patients relative to healthy controls. Suppression of miR-378c promoted vascular smooth muscle cells (VSMCs) phenotypic transition during atherosclerosis. We also reported for the first time that Samd1 prolonged immobilization of LDL on the VSMCs, thus facilitated LDL oxidation and subsequently foam cell formation. Further, we found that Samd1 contains predicted DNA binding domain and directly binds to DNA regions as a transcriptional repressor. Together, we uncovered a novel mechanism whereby miR-378c-Samd1 circuit participates in two key elements of atherosclerosis, VSMCs phenotypic transition and LDL oxidation. Our results provided a better understanding of atherosclerosis pathophysiology and potential therapeutic management by targeting miR-378c-Samd1 circuit. [ABSTRACT FROM AUTHOR]

A novel coronavirus (SARS-CoV-2) has spread worldwide and led to high disease burden around the world. This study aimed to explore the key parameters of SARS-CoV-2 infection and to assess the effectiveness of interventions to control the coronavirus disease 2019 (COVID-19). A susceptible—exposed—infectious—asymptomatic—recovered (SEIAR) model was developed for the assessment. The information of each confirmed case and asymptomatic infection was collected from Ningbo Center for Disease Control and Prevention (CDC) to calculate the key parameters of the model in Ningbo City, China. A total of 157 confirmed COVID-19 cases (including 51 imported cases and 106 secondary cases) and 30 asymptomatic infections were reported in Ningbo City. The proportion of asymptomatic infections had an increasing trend. The proportion of elder people in the asymptomatic infections was lower than younger people, and the difference was statistically significant (Fisher's Exact Test, P = 0.034). There were 22 clusters associated with 167 SARS-CoV-2 infections, among which 29 cases were asymptomatic infections, accounting for 17.37%. We found that the secondary attack rate (SAR) of asymptomatic infections was almost the same as that of symptomatic cases, and no statistical significance was observed (χ2 = 0.052, P = 0.819) by Kruskal–Wallis test. The effective reproduction number (Reff) was 1.43, which revealed that the transmissibility of SARS-CoV-2 was moderate. If the interventions had not been strengthened, the duration of the outbreak would have lasted about 16 months with a simulated attack rate of 44.15%. The total attack rate (TAR) and duration of the outbreak would increase along with the increasing delay of intervention. SARS-CoV-2 had moderate transmissibility in Ningbo City, China. The proportion of asymptomatic infections had an increase trend. Asymptomatic infections had the same transmissibility as symptomatic infections. The integrated interventions were implemented at different stages during the outbreak, which turned out to be exceedingly effective in China. [ABSTRACT FROM AUTHOR]

Investigation of the prevalence and diversity of Bartonella infections in small mammals in the Qaidam Basin, western China, could provide a scientific basis for the control and prevention of Bartonella infections in humans. Accordingly, in this study, small mammals were captured using snap traps in Wulan County and Ge'ermu City, Qaidam Basin, China. Spleen and brain tissues were collected and cultured to isolate Bartonella strains. The suspected positive colonies were detected with polymerase chain reaction amplification and sequencing of gltA, ftsZ, RNA polymerase beta subunit (rpoB) and ribC genes. Among 101 small mammals, 39 were positive for Bartonella, with the infection rate of 38.61%. The infection rate in different tissues (spleens and brains) (χ2 = 0.112, P = 0.738) and gender (χ2 = 1.927, P = 0.165) of small mammals did not have statistical difference, but that in different habitats had statistical difference (χ2 = 10.361, P = 0.016). Through genetic evolution analysis, 40 Bartonella strains were identified (two different Bartonella species were detected in one small mammal), including B. grahamii (30), B. jaculi (3), B. krasnovii (3) and Candidatus B. gerbillinarum (4), which showed rodent-specific characteristics. B. grahamii was the dominant epidemic strain (accounted for 75.0%). Furthermore, phylogenetic analysis showed that B. grahamii in the Qaidam Basin, might be close to the strains isolated from Japan and China. Overall, we observed a high prevalence of Bartonella infection in small mammals in the Qaidam Basin. B. grahamii may cause human disease, and the pathogenicity of the others Bartonella species needs further study, the corresponding prevention and control measures should be taken into consideration. [ABSTRACT FROM AUTHOR]

The effects of antibiotics on the intestinal flora can create potential drug-drug interactions. The combination of amoxicillin and aspirin is high and there is a high probability of interaction. We used 16S rRNA, incubation experiments and liquid chromatography-tandem mass spectrometry to analyze rat biological samples to characterize the effect of amoxicillin on the pharmacokinetics of aspirin metabolites. We first discovered that amoxicillin reduced the species and number of intestinal flora in rats, such as reducing the abundance of Helicobacter pylori and Prevotella_copri. After 12, 24, and 36 hours of incubation, the remaining amount of aspirin in the aspirin and amoxicillin treatment groups decreased, and salicylic acid production increased, suggesting that aspirin is metabolized by the intestinal flora, and the main metabolite is salicylic acid. As the incubation time prolonged, the reduction of aspirin and the production of salicylic acid in the amoxicillin treatment group were slower. It is indicated that the metabolic activity of aspirin through the intestinal flora is slowed down after administration of amoxicillin. The pharmacokinetic experiments showed that after administration of amoxicillin, the area under the salicylic acid curve increased by 91.38%, the peak concentration increased by 60.43%, and the clearance rate decreased by 43.55%.The results demonstrated that amoxicillin affected the pharmacokinetics of aspirin active metabolite salicylic acid by slowing down the metabolic activity of intestinal flora on aspirin. The interaction between amoxicillin and aspirin mediated by the intestinal flora may affect the efficacy of aspirin and cause more significant adverse effects. [ABSTRACT FROM AUTHOR]

Tumor metastasis is the major cause of cancer-related death especially in human hepatocellular carcinoma (HCC). Although microRNAs have been implicated in tumor development, the roles of miR-124 in HCC metastasis are still not well understood. We conducted functional analysis in this study to investigate miR-124. We observed that miR-124 significantly retarded the wound healing and migration of HCC SMMC-7721 and BEL-7404 cells. Further analysis indicated miR-124 directly targeting the transcriptional factor Sp1 which is an important transcription factor for the integrin αV subunit gene transcription. Co-transfection of miR-124 with the luciferase reporter containing Sp1 3′ untranslated region (UTR) significantly suppressed the luciferase activities. While mutation of the binding site of miR-124 in Sp1 mRNA 3′UTR completely abrogated the suppression of miR-124. Overexpression of miR-124 resulted in robust downregulation of Sp1 and integrin αV expression at either mRNA or protein level. Ectopic expression of miR-124 in HCC dramatically repressed the wound healing and migration in vitro and tumor metastasis in mouse experiments. Our findings demonstrated that miR-124 played as an important role in regulation of integrin αV expression in HCC, and reintroduction of miR-124 might be an alternative therapeutic strategy for controlling integrin αV expression in HCC. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome virus (PRRSV) strain A2MC2 induces type I interferons in cultured cells. The objective of this study was to attenuate this strain by serial passaging in MARC-145 cells and assess its virulence and immunogenicity in pigs. The A2MC2 serially passaged 90 times (A2MC2-P90) retains the feature of interferon induction. The A2MC2-P90 replicates faster with a higher virus yield than wild type A2MC2 virus. Infection of primary pulmonary alveolar macrophages (PAMs) also induces interferons. Sequence analysis showed that the A2MC2-P90 has genomic nucleic acid identity of 99.8% to the wild type but has a deletion of 543 nucleotides in nsp2. The deletion occurred in passage 60. The A2MC2-P90 genome has a total of 35 nucleotide variations from the wild type, leading to 26 amino acid differences. Inoculation of three-week-old piglets showed that A2MC2-P90 is avirulent and elicits immune response. Compared with Ingelvac PRRS® MLV strain, A2MC2-P90 elicits higher virus neutralizing antibodies. The attenuated IFN-inducing A2MC2-P90 should be useful for development of an improved PRRSV vaccine. [ABSTRACT FROM AUTHOR]

Mitochondria-related microRNAs (miRNAs) have recently emerged as key regulators of cell metabolism and can modulate mitochondrial fusion and division. In order to investigate the roles of mitochondria-related miRNAs played in obesity, we conducted comprehensive molecular analysis in vitro and in vivo. Based on high-fat-diet (HFD) induced obese mice, we found that hepatic mitochondrial function was markedly altered. Subsequently, we evaluated the expression levels of selected mitochondria-related miRNAs and found that miR-141-3p was up-regulated strikingly in HFD mice. To further verify the role of miR-141-3p in obesity, we carried out gain-and-loss-of-function study in human HepG2 cells. We found that miR-141-3p could modulate ATP production and induce oxidative stress. Through luciferase report gene assay, we identified that phosphatase and tensin homolog (PTEN) was a target of miR-141-3p. Inhibiting PTEN could alter the mitochondrial function, too. Our study suggested that mitochondria-related miR-141-3p induced mitochondrial dysfunction by inhibiting PTEN. [ABSTRACT FROM AUTHOR]

To determine whether transplanted amniotic membrane mesenchymal stem cells (AMSCs) ameliorated the premature senescent phenotype of Bmi-1-deficient mice, postnatal 2-day-old Bmi-1−/− mice were injected intraperitoneally with the second-passage AMSCs from amniotic membranes of β-galactosidase (β-gal) transgenic mice or wild-type (WT) mice labeled with DiI. Three reinjections were given, once every seven days. Phenotypes of 5-week-old β-gal+ AMSC-transplanted or 6-week-old DiI+ AMSC-transplanted Bmi-1−/− mice were compared with vehicle-transplanted Bmi-1−/− and WT mice. Vehicle-transplanted Bmi-1−/− mice displayed growth retardation and premature aging with decreased cell proliferation and increased cell apoptosis; a decreased ratio and dysmaturity of lymphocytic series; premature osteoporosis with reduced osteogenesis and increased adipogenesis; redox imbalance and DNA damage in multiple organs. Transplanted AMSCs carried Bmi-1 migrated into multiple organs, proliferated and differentiated into multiple tissue cells, promoted growth and delayed senescence in Bmi-1−/− transplant recipients. The dysmaturity of lymphocytic series were ameliorated, premature osteoporosis were rescued by promoting osteogenesis and inhibiting adipogenesis, the oxidative stress and DNA damage in multiple organs were inhibited by the AMSC transplantation in Bmi-1−/− mice. These findings indicate that AMSC transplantation ameliorated the premature senescent phenotype of Bmi-1-deficient mice and could be a novel therapy to delay aging and prevent aging-associated degenerative diseases. [ABSTRACT FROM AUTHOR]

Nuclear factor κB (NF-κB) is a key transcription factor in inflammatory immune responses and cell survival. Multiple types of ubiquitination play critical roles in the activation of NF-κB signaling, yet the molecular mechanisms responsible for their reversible deubiquitination are still poorly understood. In this study, we identified a member of the deubiquitinases family, ubiquitin-specific protease 18 (USP18), as a novel negative regulator in Toll-like receptor (TLR)-mediated NF-κB activation in human macrophages. USP18 is an interferon inducible gene, which is also upregulated by various TLR ligands in human monocytes and macrophages. Knockdown of USP18 enhanced the phosphorylation of IKK, the degradation of IκB, and augmented the expression of pro-inflammatory cytokines. Furthermore, USP18 interacted with TAK1-TAB1 complex and IKKα/β-NEMO complex, respectively. USP18 cleaved the K63-linked polyubiquitin chains attached to TAK1 in a protease-dependent manner. Moreover, USP18 targeted the IKK complex through the regulatory subunit NEMO of IKK, and specifically inhibited K63-linked ubiquitination of NEMO. Mutation analysis revealed direct binding of USP18 to the UBAN motif of NEMO. Our study has identified a previously unrecognized role for USP18 in the negative regulation of NF-κB activation by inhibiting K63-linked ubiquitination of TAK1 and NEMO through distinct mechanisms. [ABSTRACT FROM AUTHOR]