Esophageal squamous precancerous lesions (ESPL) are the precursors of esophageal squamous cell carcinoma (ESCC) including low-grade and high-grade intraepithelial neoplasia. Due to the absence of ...molecular indicators, which ESPL will eventually develop into ESCC and thus should be treated is not well defined. Indicators, for predicting risks of ESCC at ESPL stages, are an urgent need. We perform spatial whole-transcriptome atlas analysis, which can eliminate other tissue interference by sequencing the specific ESPL regions. In this study, the expression of TAGLN2 significantly increases, while CRNN expression level decreases along the progression of ESCC. Additionally, TAGLN2 protein level significantly increases in paired after-progression tissues compared with before-progression samples, while CRNN expression decreases. Functional studies suggest that TAGLN2 promotes ESCC progression, while CRNN inhibits it by regulating cell proliferation. Taken together, TAGLN2 and CRNN are suggested as candidate indicators for the risk of ESCC at ESPL stages.
The geological units in Shandong Province, North China are important parts of the North China Craton and offer important insights into their crustal evolutionary history. This work compiled 611 sets ...of Nd isotopic data of Archean-Mesozoic rocks from Shandong including the Luxi, Jiaobei, and Sulu terranes, which provided important constraints for crustal growth and reactivation. Nd-depleted mantle model ages (
T
DM
) of Archean rocks with positive
ε
Nd
(
t
) values showed that ca. 2.9 and 2.8-2.7 Ga were the most important periods of crustal growth in the Jiaobei and Luxi terranes, respectively, while the period of ca. 2.6-2.5 Ga in the Jiaobei terrane likely indicated a coherent event of crustal growth and reworking. During the Proterozoic, multi-stage rifting and collisional orogenic events possibly led to the reworking of Archean crust in the source region. The Nd isotopic data of the Paleoproterozoic and Neoproterozoic rocks from Sulu indicated significant reworking of older crust with juvenile magmatic input. Crustal reactivation occurred during the Mesozoic. The younger
T
DM
ages of the Mesozoic rocks with low negative
ε
Nd
(
t
) values indicated that a juvenile crustal/mantle component was added to the ancient basement. The reactivation reflected significant crust-mantle interaction via the mechanism of crustal subduction and mantle-derived magma un-derplating, or possibly asthenospheric upwelling. Our work also attempted to establish the crustal correlation between Shandong and Korea (including the Gyeonggi massif, Ogcheon belt, and Yeongnam massif). The
T
DM
age distribution provided evidence favoring the affinity relationship between the Gyeonggi massif and Ogcheon belt of South Korea and the Jiaobei and Sulu terranes of Shandong, while the Yeongnam massif was more correlated with the South China Block.
Metamaterials, artificially engineered structures with extraordinary physical properties, offer multifaceted capabilities in interdisciplinary fields. To address the looming threat of stealthy ...monitoring, the detection and identification of metamaterials is the next research frontier but have not yet been explored. Here, we show that the crypto-oriented convolutional neural network (CNN) makes possible the secure intelligent detection of metamaterials in mixtures. Terahertz signals were encrypted by homomorphic encryption and the ciphertext was submitted to the CNN directly for results, which can only be decrypted by the data owner. The experimentally measured terahertz signals were augmented and further divided into training sets and test sets using 5-fold cross-validation. Experimental results illustrated that the model achieved an accuracy of 100% on the test sets, which highly outperformed humans and the traditional machine learning. The CNN took 9.6 s to inference on 92 encrypted test signals with homomorphic encryption backend. The proposed method with accuracy and security provides private preserving paradigm for artificial intelligence-based material identification.
RationaleDespite high prevalence of e-cigarette use (vaping), little is currently known regarding the health effects of secondhand nicotine vape exposure.ObjectiveTo investigate whether exposure to ...secondhand nicotine vape exposure is associated with adverse respiratory health symptoms among young adults.MethodWe investigated the effect of secondhand nicotine vape exposure on annually reported wheeze, bronchitic symptoms and shortness of breath in the prospective Southern California Children Health Study cohort. Data were collected from study participants (n=2097) with repeated annual surveys from 2014 (average age: 17.3 years) to 2019 (average age: 21.9). We used mixed effect logistic regression to evaluate the association between secondhand nicotine vape and respiratory symptoms after controlling for relevant confounders.ResultsPrevalence of secondhand nicotine vape increased from 11.7% to 15.6% during the study period in this population. Prevalence of wheeze, bronchitic symptoms and shortness of breath ranged from 12.3% to 14.9%, 19.4% to 26.0% and 16.5% to 18.1%, respectively, during the study period. Associations of secondhand nicotine vape exposure with bronchitic symptoms (OR 1.40, 95% CI 1.06 to 1.84) and shortness of breath (OR 1.53, 95% CI 1.06 to 2.21) were observed after controlling for vaping, active and passive exposure to tobacco or cannabis, and demographic characteristics (age, gender, race/ethnicity and parental education). Stronger associations were observed when analysis was restricted to participants who were neither smokers nor vapers. There were no associations with wheezing after adjustment for confounders.ConclusionSecondhand nicotine vape exposure was associated with increased risk of bronchitic symptoms and shortness of breath among young adults.
Statins, a class of hyperlipidemic drugs, are widely used cholesterol lowering drugs that selectively inhibit 3-hydroxy-3-methylglutaryl CoA reductase, which is the rate-limiting enzyme in ...cholesterol biosynthesis, leading to decreasing of cholesterol biosynthesis. Statins exert anti-tumoral effects on various cancer, including breast cancer. However, the molecular mechanisms for the actions were not fully elucidated. The purpose of this study was to elucidate the effects of statins on proliferation and apoptosis in the ER-negative breast cancer cell line MDA-MB-231. Our results showed that simvastatin increased the expression of miR-140-5p in a dose dependent manner via activating transcription factor NRF1, reduced cell proliferation and induced apoptosis, and we also found that SLC2A1 was a new target of miR-140-5p. In conclusion, data in this study shed light on the potential anti-tumoral effects of simvastatin in breast cancer and presents a highly promising therapeutic option, using drug and miRNA for combined treating cancers.
Potent antibacterial fibers with the functional “triad” of photothermal, silver, and Dex were prepared by electrospinning, which can simultaneously kill multidrug-resistant bacteria and accelerate ...bone tissue healing due to the photothermal effect and release of Dex, which is good for photothermal therapy and bone regeneration of infectious bone defects.
Display omitted
•Potent antibacterial electrospun fibers with the functional “triad” of photothermal, silver, and Dex.•Multidrug-resistant bacteria and accelerate bone tissue healing due to photothermal effect and release of Dex.•Induce differentiation of BMSCs into osteoblasts via local drug release.•Excellent osteogenic and angiogenic properties via functional electrospun fibers.
Bacteria-induced bone infections disrupt the healing and repair ability of bone tissue, posing a serious challenge to the treatment of clinical bone defects. In this study, novel composite fibers (PLLA/Dex/Ag fibers) with light-responsive rapid antibiosis and osteogenesis were obtained by mixing the photothermal agent silver nanoparticles (Ag-NPs) and the osteogenic drug dexamethasone (Dex) in polylactic acid (PLLA) using electrospinning, which can simultaneously kill multidrug-resistant bacteria and accelerate bone tissue healing due to the photothermal effect and release of Dex. Ag-NPs can act as antimicrobial agents released from the fibers and as photothermal agents to generate local high temperature and singlet state oxygen (1O2) under 808 nm light radiation, thereby killing the bacteria. The antimicrobial tests in vitro showed that PLLA/Dex/Ag fibers had an excellent antimicrobial effect on Escherichia coli and Staphylococcus aureus under NIR light radiation, shortening the effective antimicrobial time from 24 h to 6 h and achieving light-responsive antibiosis rapidly. Meanwhile, the released Dex could induce the differentiation of bone marrow mesenchymal stem cells into osteoblasts, thus promoting the healing of bone defects. In conclusion, this study provided a simple and effective strategy for the clinical treatment of bone infections.
HBV capsid assembly has been viewed as an attractive target for new antiviral therapies against HBV. On the basis of a lead compound 4r, we further investigated this target to identify novel active ...compounds with appropriate anti-HBV potencies and improved pharmacokinetic (PK) properties. Structure–activity relationship studies based on metabolic pathways of 4r led to the identification of a phthalazinone derivative 19f with appropriate anti-HBV potencies (IC50 = 0.014 ± 0.004 μM in vitro), which demonstrated high oral bioavailability and liver exposure. In the AAV-HBV/mouse model, administration of 19f resulted in a 2.67 log reduction of the HBV DNA viral load during a 4-week treatment with 150 mg/kg dosing twice daily.
The objective of this paper is to investigate the effects of initial particle gradation and rock content on the crushing behavior (i.e. grain size before and after crushing) of weathered phyllite ...fills. Compaction tests were conducted on weathered phyllite fills with rock contents of 35%, 45%, 55%, 65% and 75% (by weight). First, the particle size distributions (PSDs) were observed before and after compaction, and then the particle breakage of weathered phyllite fills was analyzed by fractal dimension. Relative fractal dimension was proposed to evaluate the effects of initial rock content and initial gradation on the particle breakage. It was found that the fractal dimension method can well characterize the crushing behaviors of the weathered phyllite fills. The finer the fills were, the more they were compacted. That is, after the first compaction, the relative fractal dimension of the weathered phyllite fills increased as the rock content increased, reaching the values of 0.013, 0.016, 0.024, 0.037 and 0.08, respectively. After the second compaction, these relative fractal dimension values, dominated by the initial particle gradation, became 0.059, 0.072, 0.052, 0.095 and 0.118, respectively. In conclusion, the weathered phyllite fills with 55% rock content exhibited the least breakage and were most suitable for filling the subgrade. Findings in this paper will provide significant guidance for the construction of weathered phyllite filling subgrade in future projects.
Particulate matter pollution could increase the risk of kidney disease, while evidence for ozone exposure is less well-established. Here, we aimed to evaluate the effect of ozone pollution on renal ...function and explore mechanisms. We first conducted a cross-sectional study based on Wuhan Chronic Disease Cohort Study baseline information. We recruited 2699 eligible participants, estimated their residential ozone concentrations, collected fasting peripheral blood samples for biochemical analysis and calculated the estimated glomerular filtration rate (eGFR). The linear regression model was applied to evaluate the long-term association between ozone pollution and eGFR. Then, we recruited another 70 volunteers as a panel with 8 rounds follow-up visits. We calculated the eGFR and measured fasting blood glucose and lipid levels. The linear mixed-effect model along with mediation analysis were performed to confirm the short-term association and explore potential mechanisms, respectively. For the long-term association, a 10.95 μg/m
increment of 3-year ozone exposure was associated with 2.96 mL/min/1.73 m
decrease in eGFR (95%CI: -4.85, -1.06). Furthermore, the drinkers exhibited a pronounced declination of eGFR (-7.46 mL/min/1.73 m
, 95%CI: -11.84, -3.08) compared to non-drinkers in relation to ozone exposure. Additionally, a 19.02 μg/m
increase in 3-day ozone concentrations was related to 2.51 mL/min/1.73 m
decrease in eGFR (95%CI: -3.78, -1.26). Hyperglycemia and insulin resistance mediated 12.2% and 16.5% of the aforementioned association, respectively. Our findings indicated that higher ozone pollution could affect renal function, and the hyperglycemia and insulin resistance linked to ozone might be the underlying mechanisms.
Cardiovascular disease is a serious health problem. Continuous Electrocardiograph (ECG) monitoring plays a vital role in the early detection of cardiovascular disease. As the Internet of Things ...technology continues to mature, wearable ECG signal monitors have been widely used. However, dynamic ECG signals are extremely susceptible to contamination. Therefore, it is necessary to evaluate the quality of wearable dynamic ECG signals. The topological data analysis method (TDA) with persistent homology, which can effectively capture the topological information of high-dimensional data space, has been widely studied. In this study, a brand-new quality assessment method of wearable dynamic ECG signals was proposed based on the TDA with persistent homology method. The point cloud of an ECG signal was constructed, and then the complex sequence was generated and displayed as a persistent barcode. Finally, GoogLeNet based on the transfer learning model with a 10-fold cross-validation method was used to train the classification model. A total of 12-leads ECGs Dataset and single-lead ECGs Dataset, established based on the 2011 PhysioNet/CinC challenge dataset, were both used to verify the performance of this method. In the study, 773 "acceptable" and 225 "unacceptable" signals were used as 12-leads ECGs Dataset. We relabeled 12,000 ECG signals in the challenge dataset, and treated them as single-lead ECGs Dataset after empty lead detection and balance datasets. Compared with the traditional ECG signal quality assessment method mainly based on waveform characteristics and time-frequency characteristics, the performance of the quality assessment method proposed. In this study, the classification performance of the proposed method are fairly great,
= 98.04%,
1 = 98.40%,
= 97.15%,
= 98.93% for 12-leads ECGs Dataset and
= 98.55%,
1 = 98.62%,
= 98.37%,
= 98.85% for single-lead ECGs Dataset.
PDF
