Valleytronics rooted in the valley degree of freedom is of both theoretical and technological importance as it offers additional opportunities for information storage, as well as electronic, magnetic ...and optical switches. In analogy to ferroelectric materials with spontaneous charge polarization, or ferromagnetic materials with spontaneous spin polarization, here we introduce a new member of ferroic family, that is, a ferrovalley material with spontaneous valley polarization. Combining a two-band k·p model with first-principles calculations, we show that 2H-VSe
monolayer, where the spin-orbit coupling coexists with the intrinsic exchange interaction of transition-metal d electrons, is such a room-temperature ferrovalley material. We further predict that such system could demonstrate many distinctive properties, for example, chirality-dependent optical band gap and, more interestingly, anomalous valley Hall effect. On account of the latter, functional devices based on ferrovalley materials, such as valley-based nonvolatile random access memory and valley filter, are contemplated for valleytronic applications.
► We report recent advances in the research on durability of steel reinforced concrete. ► Role of mineral admixtures in the durability of concrete is reviewed. ► Methods of measuring the chloride ...ingress into concrete are reviewed. ► Challenges in assessing concrete durability from chloride diffusivity are discussed. ► Service life modeling of reinforced concrete in chloride environments are reviewed.
Concrete is a unique composite material that is porous and highly heterogeneous. The durability of steel reinforced concrete in chloride environments is of great interest to design engineers, infrastructure owners and maintainers, and researchers. This review reports recent advances in the knowledge base relevant to the durability of steel reinforced concrete in chloride environments, including: the role of mineral admixtures in concrete durability, the methods of measuring the chloride ingress into concrete, the challenges in assessing concrete durability from its chloride diffusivity, and the service life modeling of reinforced concrete in chloride-laden environments. It concludes with a look to the future, including research needs to be addressed.
Objective
To develop a deep learning–based artificial intelligence (AI) scheme for predicting the likelihood of the ground-glass nodule (GGN) detected on CT images being invasive adenocarcinoma (IA) ...and also compare the accuracy of this AI scheme with that of two radiologists.
Methods
First, we retrospectively collected 828 histopathologically confirmed GGNs of 644 patients from two centers. Among them, 209 GGNs are confirmed IA and 619 are non-IA, including 409 adenocarcinomas in situ and 210 minimally invasive adenocarcinomas. Second, we applied a series of pre-preprocessing techniques, such as image resampling, rescaling and cropping, and data augmentation, to process original CT images and generate new training and testing images. Third, we built an AI scheme based on a deep convolutional neural network by using a residual learning architecture and batch normalization technique. Finally, we conducted an observer study and compared the prediction performance of the AI scheme with that of two radiologists using an independent dataset with 102 GGNs.
Results
The new AI scheme yielded an area under the receiver operating characteristic curve (AUC) of 0.92 ± 0.03 in classifying between IA and non-IA GGNs, which is equivalent to the senior radiologist’s performance (AUC 0.92 ± 0.03) and higher than the score of the junior radiologist (AUC 0.90 ± 0.03). The Kappa value of two sets of subjective prediction scores generated by two radiologists is 0.6.
Conclusions
The study result demonstrates using an AI scheme to improve the performance in predicting IA, which can help improve the development of a more effective personalized cancer treatment paradigm.
Key Points
• The feasibility of using a deep learning method to predict the likelihood of the ground-glass nodule being invasive adenocarcinoma.
• Residual learning–based CNN model improves the performance in classifying between IA and non-IA nodules.
• Artificial intelligence (AI) scheme yields higher performance than radiologists in predicting invasive adenocarcinoma.
Abstract
Background
Intermittent hypoxia (IH) caused by obstructive sleep apnea (OSA) leads to neuroinflammation. Pinocembrin has been shown to have neuroprotective effects, while the therapeutic ...functions under IH condition are still unknown.
Methods
An OSA model was established by CIH exposure inside custom-made chambers. C57BL/6 mice were intraperitoneally injected with pinocembrin (40 mg/kg, i.p.) or vehicle (PBS containing 5% povidone; i.p.), and the changes of behavior on mice were detected by the Morris water maze test. Immunohistochemical staining, western blotting, immunofluorescence assays, and immunoprecipitation were used to investigate the association between NLRP3 inflammasome and BNIP3-dependent mitophagy. The mitochondrial morphology and mitophagosomes were detected under a transmission electron microscope. The detrimental effects of IH were tested by annexin V-FITC/PI staining, Mito SOX Red staining, and JC-1 mitochondrial membrane potential assay.
Results
In this study, our observations in vivo indicated that the administration of pinocembrin can restore spatial learning and memory ability and reduce neuronal apoptosis and hippocampal inflammation. Pinocembrin treatment significantly inhibited the formation of NLRP3 inflammasome and infiltration of microglia and enhanced BNIP3-mediated mitophagy in the hippocampus of IH mice. Additionally, our in vitro results show that pinocembrin protects microglial cells against IH-induced cytotoxicity by activating BNIP3-dependent mitophagy through the JNK-ERK signaling pathway.
Conclusions
In summary, our findings demonstrated that pinocembrin can act as a potential therapeutic strategy for IH-induced neuroinflammation.
The epithelial-to-mesenchymal transition (EMT) is important for the development of cancer metastases and organ fibrosis, conditions prevalent in aging. Because sirtuins affect the pathology of aging, ...we tested the effect of SirT1 on EMT. Reduced SIRT1 levels in HMLER breast cancer cells led to increased metastases in nude mice, and the loss of SIRT1 in kidney tubular epithelial cells exacerbated injury-induced kidney fibrosis. SIRT1 reduces EMT in cancer and fibrosis by deacetylating Smad4 and repressing the effect of TGF-β signaling on MMP7, a Smad4 target gene. Consequently, less E-cadherin is cleaved from the cell surface and β-catenin remains bound to E-cadherin at the cell-cell junctions. Our findings suggest that the SIRT1/Smad4/β-catenin axis may be a target for diseases driven by EMT.
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•SIRT1 suppresses breast cancer metastases and kidney fibrosis•SIRT1 deacetylates Smad4 and represses its activity on MMP7•Reduced MMP7 leads to less E-cadherin cleavage and β-catenin remains at adherens junctions•SIRT1 suppresses TGF-β-driven EMT in breast cancer and kidney epithelial cells
Sirtuins are longevity-related molecules that affect aging-related diseases. Guarente and colleagues now show that SIRT1, a member of the sirtuin family, reduces organ fibrosis and cancer metastases, conditions prevalent in aging. Reduced SIRT1 levels in breast cancer cells led to increased metastases and mortality in mice, and loss of SIRT1 in kidney tubular cells exacerbated injury-induced kidney fibrosis and progression to chronic kidney disease. SIRT1 mitigates fibrosis and metastases by suppressing the epithelial-to-mesenchymal transition, a shared event in these diseases.
Background
N6‐methyladenosine (m6A) is the most prevalent methylation modification of eukaryotic RNA, and methyltransferase‐like 3 (METTL3) plays a vital role in multiple cell functions. This study ...aimed to investigate the role of m6A methylase METTL3 in slow transit constipation (STC).
Material and Method
The expression of METTL3 and DGCR8 was measured in STC tissues and glutamic acid‐induced interstitial cells of Cajal (ICCs). The effects of METTL3, miR‐30b‐5p, and DGCR8 on the biological characteristics of ICCs were investigated on the basis of loss‐of‐function analyses. Luciferase reporter assay was used to identify the direct binding sites of miR‐30b‐5p with PIK3R2.
Results
The results showed that the METTL3, DGCR8, miR‐30b‐5p, and the methylation level of m6A were significantly increased in STC tissues and glutamic acid‐induced ICCs. Silencing of METTL3 and miR‐30b‐5p inhibited apoptosis, autophagy, and pyroptosis of glutamic acid‐induced ICCs. Moreover, overexpression of miR‐30b‐5p reversed the cytoprotection of METTL3 knockdown in glutamic acid‐induced ICCs. Besides, DGCR8 knockdown could facilitate cell growth and decrease apoptotic glutamic acid‐induced ICCs. Mechanically, we illustrated that METTL3 in glutamic acid‐induced ICCs significantly accelerated the maturation of pri‐miR‐30b‐5p by m6A methylation modification, resulting in the reduction of PIK3R2, which results in the inhibition of PI3K/Akt/mTOR pathway and ultimately leads to the cell death of STC.
Conclusions
Collectively, these data demonstrated that METTL3 promoted the apoptosis, autophagy, and pyroptosis of glutamic acid‐induced ICCs by interacting with the DGCR8 and successively modulating the miR‐30b‐5p/PIK3R2 axis in an m6A‐dependent manner, and METTL3 may be a potential therapeutic target for STC.
Airborne bacteria have an important role in atmospheric processes and human health. However, there is still little information on the transmission and distribution of bacteria via the airborne route. ...To characterize the impact of foggy, haze, haze-fog (HF) and dust days on the concentration and viability of bacteria in atmospheric aerosols, size-segregated bioaerosol samples were collected in the Qingdao coastal region from March 2018 to February 2019. The total airborne microbes and viable/non-viable bacteria in the bioaerosol samples were measured using an epifluorescence microscope after staining with DAPI (4′, 6-diamidino-2-phenylindole) and a LIVE/DEAD® BacLight Bacterial Viability Kit. The average concentrations of total airborne microbes on haze and dust days were 6.75 × 105 and 1.03 × 106 cells/m3, respectively, which increased by a factor of 1.3 and 2.5 (on average), respectively, relative to those on sunny days. The concentrations of non-viable bacteria on haze and dust days increased by a factor of 1.2 and 3.6 (on average), respectively, relative to those on sunny days. In contrast, the concentrations of viable bacteria on foggy and HF days were 7.13 × 103 and 5.74 × 103 cells/m3, decreases of 38% and 50%, respectively, compared with those on sunny days. Foggy, haze, dust and HF days had a significant effect on the trend of the seasonal variation in the total airborne microbes and non-viable bacteria. Bacterial viability was 20.8% on sunny days and significantly higher than the 14.1% on foggy days, 11.2% on haze days, 8.6% during the HF phenomenon and 6.1% on dust days, indicating that special weather is harmful to some bacterial species. Correlation analysis showed that the factors that influenced the bacterial concentration and viability depended on different weather conditions. The main influential factors were temperature, NO2 and SO2 concentrations on haze days, and temperature, particulate matter (PM2.5) and NO2 concentrations on foggy days. The median size of particles containing viable bacteria was 1.94 μm on sunny days and decreased to 1.88 μm and 1.74 μm on foggy and haze days, respectively, but increased to 2.18 μm and 2.37 μm on dust and HF days, respectively.
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•The concentration of non-viable bacteria increased and viable bacteria decreased on foggy and haze-fog days.•Bacterial viability was higher on sunny days than on polluted days.•The median size of particles containing viable bacteria increased on haze-fog and dust days.•Temperature, PM2.5 and NO2 affected bacteria viability on polluted days.
Furan derivatives (DMF (2,5-dimethylfuran), MF (2-methylfuran), and furan) are the attractive oxygenated fuels to reduce the consumption of fossil fuel and engine emissions due to their comparable ...combustion properties to those of commercial gasoline and the productivities from lignocellulosic raw materials. Many experimental studies have been focused on these promising fuel characteristics including laminar burning velocities, laminar flame structures, ignition delay times, and pyrolysis species. Various kinetic mechanisms have been developed in detail as well based on up to date experimental data in accordance with the quantum chemical calculations. In the present study, the vast amount of experimental data have been collected, consolidated, and reviewed along with the kinetic model validations in order to envision a future fuel research on furan derivatives for minimizing the experimental uncertainties, improving the data fidelity, and developing accurate kinetic models.
Bacteria are important components of bioaerosols with the potential to influence human health and atmospheric dynamics. However, information on the concentrations and influencing factors of viable ...bacteria is poorly understood. In this study, size-segregated bioaerosol samples were collected from Aug. 2017 to Feb. 2018 in the coastal region of Qingdao, China. The total microbes and viable/non-viable bacteria in the samples were measured using an epifluorescence microscope after staining with the DAPI (4′, 6-diamidino-2-phenylindole) and LIVE/DEAD® BacLight™ Bacterial Viability Kit, respectively. The concentrations of non-viable bacteria increased when the air quality index (AQI) increased from <50 to 300, with the proportion of non-viable bacteria to total microbes increasing from (11.1 ± 12.0)% at an AQI of <50 to (18.4 ± 14.7)% at an AQI of >201. However, the concentrations of viable bacteria decreased from (2.12 ± 2.04) × 104 cells·m−3 to (9.00 ± 1.72) × 103 cells·m−3 when the AQI increased from <50 to 150. The ratio of viable bacteria to total bacteria (viability) decreased from (31.0 ± 14.7)% at 0 < AQI<50 to (8.6 ± 1.0)% at 101 < AQI<150 and then increased to (9.6 ± 5.3)% at an AQI of 201–300. The results indicated that the bacterial viability decreased when air pollution occurred and increased again when pollution became severe. The mean size distribution of non-viable bacteria exhibited a bimodal distribution pattern at an AQI<50 with two peaks at 2.1–3.3 μm and >7.0 μm, while the viable bacteria had two peaks at 1.1–2.1 μm and >7 μm. When the AQI increased from 101 to 300, the size distribution of viable/non-viable bacteria varied with an increased proportion of fine particles. The multiple linear regression analysis results verified that the AQI and PM10 had important effects on the concentrations of non-viable bacteria. These results highlight impacts of air pollution on viable/non-viable bacteria and the interactions between complex environmental factors and bacteria interactions, improving our understanding of bioaerosols under air pollution conditions.
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•The contribution of non-viable bacteria to total microbes increased with the AQI.•The bacterial viability decreased when air pollution occurred and increased slightly when pollution lasted and became severe.•The proportion of bacteria in fine particles increased greatly on pollution days.•The AQI and PM10 effect the concentrations of non-viable bacteria.
Background & Aims
In about 20% of children with cholestasis and normal or low serum gamma‐glutamyltransferase (GGT) activity, no aetiology is identified. We sought new genes implicated in paediatric ...hepatobiliary disease.
Methods
We conducted whole‐exome sequencing in 69 children evaluated at our centre from 2011 to 2018 who had low‐GGT cholestasis and in whom homozygous/compound heterozygous predictedly pathogenic variants (PPVs) in ATP8B1, ABCB11, NR1H4, MYO5B or TJP2 were not found. Clinical records and findings on light microscopy and transmission electron microscopy of liver biopsy materials were reviewed.
Results
In seven patients from seven unrelated families, biallelic PPVs (10 in total) were found in USP53, recently associated with intrahepatic cholestasis. Seven variants were classified as pathogenic: one canonical splicing, c.569 + 2T > C, and six nonsense or frameshifting: c.169C > T (p.Arg57Ter), c.581delA (p.Arg195GlufsTer38), c.831_832insAG (p.Val279GlufsTer16), c.1012C > T (p.Arg338Ter), c.1426C > T (p.Arg476Ter) and c.1558C > T (p.Arg520Ter). Three were likely pathogenic: c.297G > T (p.Arg99Ser), c.395A > G (p.His132Arg) and c.878G > T (p.Gly293Val). In all patients, jaundice began at age <7 months. Cholestasis was transient, with documented resolution of hyperbilirubinaemia in all (oldest patient now aged 5 years) except one, who was lost to follow‐up. Light microscopy identified intralobular cholestasis, giant‐cell change of hepatocytes and perisinusoidal‐perihepatocytic and portal‐tract fibrosis. Ultrastructural study revealed elongated hepatocyte‐hepatocyte tight junctions. One patient was deaf.
Conclusion
USP53 interacts with the tight junction constituent TJP2. TJP2 mutation can cause low‐GGT intrahepatic cholestasis, with elongated hepatocyte‐hepatocyte tight junctions, as well as deafness. Our findings extend a preliminary report of USP53 disease and indicate that USP53 mutation may generate a partial phenocopy of TJP2 disease.
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