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Background: Electronic cigarette (e-cig) vaping has increased in the past decade in the US, and e-cig use is misleadingly marketed as a safe cessation for quitting smoking. The main constituents in e-liquid are humectants, such as propylene glycol (PG) and vegetable glycerine (VG), but different flavoring chemicals are also used. However, the toxicology profile of flavored e-cigs in the pulmonary tract is lacking. We hypothesized that menthol and tobacco-flavored e-cig (nicotine-free) exposure results in inflammatory responses and dysregulated repair in lung fibroblast and epithelium. Method: We exposed lung fibroblast (HFL-1) and epithelium (BEAS-2B) to Air, PG/VG, menthol flavored, or tobacco-flavored e-cig, and determined the cytotoxicity, inflammation, and wound healing ability in 2D cells and 3D microtissue chip models. Results: After exposure, HFL-1 showed decreased cell number with increased IL-8 levels in the tobacco flavor group compared to air. BEAS-2B also showed increased IL-8 secretion after PG/VG and tobacco flavor exposure, while menthol flavor exposure showed no change. Both menthol and tobacco-flavored e-cig exposure showed decreased protein abundance of type 1 collagen α 1 (COL1A1), α-smooth-muscle actin (αSMA), and fibronectin as well as decreased gene expression level of αSMA (Acta2) in HFL-1. After tobacco flavor e-cig exposure, HFL-1 mediated wound healing and tissue contractility were inhibited. Furthermore, BEAS-2B exposed to menthol flavor showed significantly decreased tight junction gene expressions, such as CDH1, OCLN, and TJP1. Conclusion: Overall, tobacco-flavored e-cig exposure induces inflammation in both epithelium and fibroblasts, and tobacco-flavored e-cig inhibits wound healing ability in fibroblasts. [ABSTRACT FROM AUTHOR]

Quick Access Recorders (QARs) provide an important data source for Flight Operation Quality Assurance (FOQA) and flight safety. It is generally characterized by large volume, high-dimensionality and high frequency, and these features result in extreme complexities and uncertainties in its usage and comprehension. In this study, we proposed a Time-Feature Attention (TFA)-based Convolutional Auto-Encoder (TFA-CAE) network model to extract essential flight features from QAR data. As a case study, we used the QAR data landing at the Kunming Changshui International Airport and Lhasa Gonggar International Airport as the experimental data. The results show that (1) the TFA-CAE model performs the best in extracting representative flight features in comparison to some traditional or similar approaches, such as Principal Component Analysis (PCA), Convolutional Auto-Encoder (CAE), Self-Attention-based CAE (SA-CAE), Gate Recurrent Unit based Auto-Encoder (GRU-AE) and TFA-GRU-AE models; (2) flight patterns corresponding to different runways can be recognized; and (3) anomalous flights can effectively deviate from many observations. Overall, the TFA-CAE model provides a well-established technique for further usage of QAR data, such as flight risk detection or FOQA. [ABSTRACT FROM AUTHOR]

Perfluorooctane sulfonic acid (PFOS) is a long chain per- and polyfluoroalklyl substance (PFAS) that has been used in aqueous film-forming foams. Emerging epidemiological evidence indicates that PFOS may be associated with chronic lung diseases such as asthma and analysis of human tissues demonstrates that the lungs carry a significant body burden of PFOS. Deficits in barrier function are a major risk factor for asthma. Thus, we hypothesized that PFOS exposure will lead to impaired epithelial barrier function through dysregulated tight junctions. Hence, we assessed the impact of PFOS on epithelial barrier integrity. Bronchial epithelial cells (16HBE) were grown on collagen-coated transwells and treated to 5–25 μM PFOS, and assessed for changes in barrier function and tight junction proteins. Rescue experiments were performed using the protein kinase D (PKD) inhibitor, CID755673. PFOS treatment reduced transepithelial electrical resistance (TEER) and increased 4 kDa FITC-dextran flux. Additionally, PFOS significantly decreased protein levels and the tight junction organization rate of occludin and zonula occludens 1. Increased phosphorylation (Ser744/Ser748) of PKD was observed 3 h following PFOS treatment. Pretreatment with the PKD inhibitor attenuated PFOS-mediated changes in TEER and FITC-dextran flux and restored occludin protein levels. In conclusion, PFOS causes loss of airway barrier integrity and the disruption of tight junctions in bronchial epithelial cells, which was partly attenuated through the inhibition of PKD. These findings demonstrate that PFOS is capable of disrupting airway barrier function, a potentially driving factor underlying associations between PFOS and respiratory diseases such as asthma. [ABSTRACT FROM AUTHOR]

We study a type of correlated queue in which its inter-arrival and service times are correlated, with their joint distribution being characterized by a copula function. This characterization allows for very generally correlated inter-arrival and service times. For such a queue, we first derive an infinite system of linear equations for the moments of the waiting time, based on which we design an algorithm to calculate the moments of the waiting time. In contrast with traditional methods, our algorithm incorporates a recursive procedure which is computationally much more efficient. Furthermore, we show how the moments and covariances of the inter-departure times of the queue can be obtained based on the moments of the waiting time. Numerical experiments are provided to validate our method. [ABSTRACT FROM AUTHOR]

Covalent organic framework (COF) membranes show great potential for gas separation, but their large pore size make it hard to effectively separate gases with similar kinetic diameters. A promising strategy is to cover the surface of COF membranes with an ultrathin film of ionic liquids (ILs) to improve the selectivity of gas permeation. Here, we investigated the CO 2 /CH 4 separation performance of composite membranes composed of COF (CTF-1) and 20 kinds of ILs, respectively, using molecular simulations. The [C 4 mim][PF 6 ]/COF membrane is found to exhibit the best separation performance, with CO 2 permeability up to 7.93 × 104 GPU and CO 2 /CH 4 selectivity of 12.33 when the IL thickness is 8 Å. By studying the microstructure of the composite membrane, it was found that there is a relatively dispersed distribution of cations and anions on the COF surface, which is beneficial to the diffusion of gas molecules. The gas permeation process results reveal that CO 2 rapidly achieves equilibrium in both the adsorption and dissolution layers simultaneously, thereby enhancing the permeation rate of gas molecules. The analysis of interaction energy and PMF indicates that the improved selectivity is due to the stronger interaction between IL and CO 2 than that for CH 4. [Display omitted] • 20 types of ultrathin IL-covered COF membranes for separating CO 2 /CH 4 were proposed. • [C 4 mim][PF 6 ]/COF membrane exhibits the highest separation performance. • The dispersed and uniform ionic distribution on the COF surface permits rapid gas diffusion. • The stronger IL-CO 2 interaction compared to CH 4 enhances selectivity. [ABSTRACT FROM AUTHOR]

The circadian clock is the biochemical oscillator with a near 24-h period that is responsible for generating the circadian rhythms in peripheral organs including the lung. Mounting evidence suggests that circadian clock disruption during chronic lung diseases plays an essential role in augmented oxidative stress, inflammatory response, metabolic imbalances, hypoxia/hyperoxia, mucus secretion, dysregulated autophagy, and alters pulmonary function. Here, we review circadian clock disruption and discuss candidate clock genes that are altered at the transcriptional or translational level in chronic pulmonary diseases. This review aims to provide the current knowledge and understanding of the circadian molecular clock disruption in chronic pulmonary diseases which will further advance the development of novel clock-based therapeutics in the future. Circadian clock disruption in the lung is associated with chronic pulmonary diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF), cystic fibrosis (CF), pulmonary arterial hypertension (PAH), and lung cancer. Cumulative evidence from preclinical models demonstrates the promising role of the circadian clock in modulating immune response and other associated phenotypes observed in chronic pulmonary diseases. Understanding the core molecular mechanisms contributing to circadian clock disruption in chronic lung diseases will help advance the development of novel clock-based therapeutics in the future. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cigarette smoke (CS) exposure induces mitochondrial dysregulation and abnormal mitophagy. • We employed mitoQC reporter mice, a mitochondrial reporter strain as mitophagy marker using GFP+/mCherry+. • Mitochondrial complexes and function related genes were inhibited with alterations in complexes I and III were observed. • Mitochondrial dynamic markers, mitochondrial fusion/fission, and mitochondrial translocate/transfer markers were altered. • Thus, mitoQC reporter mouse model can be employed to assess the dysregulated mitochondrial complexes and dynamics. Cigarette smoke (CS) is known to cause impaired mitophagy and mitochondrial dysregulation in the pathogenesis of chronic obstructive pulmonary disease (COPD)/emphysema. Mitochondrial complexes and dynamics are affected by acute CS exposure in lung epithelium and mouse lung. We hypothesize that chronic CS exposure (4 months) will induce lung mitochondrial dysregulation and abnormal mitophagy. In this study, we employed the mitoQC reporter mice, a mitochondrial reporter strain, which can reflect the mitophagy based on the fluorescence-tagged mitochondria. Chronic CS exposure induced lung inflammatory cell infiltration, airspace enlargement, and lung cellular senescence. We showed the higher occurrence of mitophagy (GFP/mCherry) in the lung cells by CS exposure, associated with more mitochondrial fluorescence signals (GFP+/mCherry+). After chronic CS exposure, the mitochondrial complexes and function related genes were inhibited, while protein levels of complexes I and III slightly changed. Additionally, chronic CS exposure down-regulated most of the mitochondrial dynamic markers at gene expression level, included mitochondrial fusion/fission and mitochondrial translocate/transfer markers. For the markers related to mitophagy, Pink1 and Parkin, decreased gene and protein levels of Parkin, and decreased gene expression of Pink1, were identified in the CS exposure group. Hence, CS-induced mitophagy is mediated by Pink1-Parkin independent mechanism. Thus, we have shown that the chronic CS epxosure dysregulated mitochondrial complexes and dynamics and induced mitophagy, using the state-of-the art mitoQC reporter mouse model. Our results suggested that dysregulated mitochondrial function and dynamics are associated with CS-induced lung injury and phenotypic development of chronic lung diseases, such as COPD/ emphysema. [ABSTRACT FROM AUTHOR]

Mitochondrial quality control is sustained by Miro1 (Rhot1), a calcium-binding membrane-anchored GTPase during mitophagy. The exact mechanism that operates the interaction of Miro1 with mitophagy machinery and their role in cigarette smoke (CS)-induced mitochondrial dysfunction that often results in lung inflammation is unclear. We hypothesized that Miro1 plays an important role in regulating mitophagy machinery and the resulting lung inflammation by CS exposure to mice. The lung epithelial Rhot1fl/fl (WT) and Rhot1CreCC10 mice were exposed to mainstream CS for 3 days (acute) and 4 months (chronic). Acute CS exposure showed a notable increase in the total inflammatory cells, macrophages, and neutrophils that are associated with inflammatory mediators. Chronic exposure showed increased infiltration of neutrophils versus air controls. The effects of acute and chronic CS exposure were augmented in the Rhot1CreCC10 group, indicating that epithelial Miro1 ablation led to the augmentation of inflammatory cell infiltration with alteration in the inflammatory mediators. Thus, Rhot1/Miro1 plays an important role in regulating CS-induced lung inflammatory responses with implications in mitochondrial quality control. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a central neurodegenerative disease generally among the elderly; it accounts for approximately 50-75%of total cases of dementia patients and poses a serious threat to physical and mental health. Currently available treatments for AD mainly relieves its symptoms, and effective therapy is urgently needed. Deposition of amyloid-β protein in the brain is an early and invariant neuropathological feature of AD. Currently the main efforts in developing anti-AD drugs focus on anti-amyloidogenic therapeutics that prevent amyloid-β production or aggregation and decrease the occurrence of neurotoxic events. The results of an increasing number of studies suggest that natural extracts and phytochemicals have a positive impact on brain aging. Flavonoids belong to the broad group of polyphenols and recent data indicate a favorable effect of flavonoids on brain aging. In this review, we collect relevant discoveries from 1999 to 2021, discuss 75 flavonoids that effectively influence AD pathogenesis, and summarize their functional mechanisms in detail. The data we have reviewed show that, these flavonoids belong to various subclasses, including flavone, flavanone, biflavone, etc. Our results provide a reference for further study of the effects of flavonoids on AD and the progress of anti-AD therapy. [ABSTRACT FROM AUTHOR]

Considering the effect of physiologic uptake on [ SP 18 sp F]F-FDG PET/CT images, the patient received a [ SP 68 sp Ga]Ga-DOTA-FAPI-04 PET/CT scan the next day. [ SP 68 sp Ga]Ga-DOTA-FAPI-04 PET/CT showed a soft tissue density nodule in front of the middle segment of the rectum, about 2.3 cm × 1.9 cm in size. On [ SP 18 sp F]F-FDG PET/CT, the intestinal glucose metabolism in her abdomen and pelvis was diffusely increased (SUVmax was 21.6). [Extracted from the article]

Unlike standalone embedded devices, behaviors of a cyber-physical system (CPS) are highly dynamic. Many parameter values (e.g., those related to nature environment and third party black box functions) are unknown offline. Furthermore, distributed sub-CPSs may exchange data online. In this article, we first propose the concept of parametric hybrid automata (PHA) to describe such complex CPSs. As some PHA parameter values are unknown until runtime, conventional offline model checking is infeasible. Instead, we propose to carry out PHA model checking online, as a fault prediction mechanism. However, this usage is challenged by the high time cost of state reachability verification, which is the conventional focus of model checking. To address this challenge, we propose that the model checking shall focus on online scenario reachability validation instead. Furthermore, we propose a mechanism to compose/decompose scenarios. Our scenario reachability validation can exploit linear programming to achieve polynomial time cost. Evaluations on a state-of-the-art train control system show that our approach can cut online model checking time cost from over 1 h to within 200 ms. [ABSTRACT FROM AUTHOR]

Electronic cigarette (e-cig) vaping is increasing rapidly in the United States, as e-cigs are considered less harmful than combustible cigarettes. However, limited research has been conducted to understand the possible mechanisms that mediate toxicity and pulmonary health effects of e-cigs. We hypothesized that sub-chronic e-cig exposure induces inflammatory response and dysregulated repair/extracellular matrix (ECM) remodeling, which occur through the α7 nicotinic acetylcholine receptor (nAChRα7). Adult wild-type (WT), nAChRα7 knockout (KO), and lung epithelial cell-specific KO (nAChRα7 CreCC10) mice were exposed to e-cig aerosol containing propylene glycol (PG) with or without nicotine. Bronchoalveolar lavage fluids (BALF) and lung tissues were collected to determine e-cig induced inflammatory response and ECM remodeling, respectively. Sub-chronic e-cig exposure with nicotine increased inflammatory cellular influx of macrophages and T-lymphocytes including increased pro-inflammatory cytokines in BALF and increased SARS-Cov-2 Covid-19 ACE2 receptor, whereas nAChRα7 KO mice show reduced inflammatory responses associated with decreased ACE2 receptor. Interestingly, matrix metalloproteinases (MMPs), such as MMP2, MMP8 and MMP9, were altered both at the protein and mRNA transcript levels in female and male KO mice, but WT mice exposed to PG alone showed a sex-dependent phenotype. Moreover, MMP12 was increased significantly in male mice exposed to PG with or without nicotine in a nAChRα7-dependent manner. Additionally, sub-chronic e-cig exposure with or without nicotine altered the abundance of ECM proteins, such as collagen and fibronectin, significantly in a sex-dependent manner, but without the direct role of nAChRα7 gene. Overall, sub-chronic e-cig exposure with or without nicotine affected lung inflammation and repair responses/ECM remodeling, which were mediated by nAChRα7 in a sex-dependent manner. [ABSTRACT FROM AUTHOR]

Nicotine inhalation via electronic cigarettes (e‐cigs) is an emerging concern. However, little is known about the acute toxicity in the lungs following inhalation of nicotine‐containing e‐cig aerosols. We hypothesized that acute exposure to aerosolized nicotine causes lung toxicity by eliciting inflammatory and dysregulated repair responses. Adult C57BL/6J mice were exposed 2 hours daily for 3 days to e‐cig aerosols containing propylene glycol (PG) with or without nicotine. Acute exposure to nicotine‐containing e‐cig aerosols induced inflammatory cell influx (neutrophils and CD8a+ T lymphocytes), and release of pro‐inflammatory cytokines in bronchoalveolar lavage fluid in a sex‐dependent manner. Inhalation of e‐cig aerosol containing PG alone significantly augmented the lung levels of various homeostasis/repair mediators (PPARγ, ADRP, ACTA2, CTNNB1, LEF1, β‐catenin, E‐cadherin, and MMP2) in a sex‐dependent manner when compared to air controls. These findings were accompanied by an increase in protein abundance and altered gene expression of lipogenic markers (PPARγ, ADRP) and myogenic markers (fibronectin, α‐smooth muscle actin and β‐catenin), suggesting a dysregulated repair response in mouse lungs. Furthermore, exposure to nicotine‐containing e‐cig aerosols or PG alone differentially affected the release of pro‐inflammatory cytokines in healthy and COPD human 3D EpiAirway tissues. Overall, acute exposure to nicotine‐containing e‐cig aerosols was sufficient to elicit a pro‐inflammatory response and altered mRNA and protein levels of myogenic, lipogenic, and extracellular matrix markers in mouse lung in a sex‐dependent manner. Thus, acute exposure to inhaled nicotine via e‐cig leads to dysregulated repair and inflammatory responses, which may lead to airway remodeling in the lungs. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The viscosities of the middle-lower crust of the Longmenshan Thrust Belt (LTB), China, are studied. • Rheological properties are not the main controlling factor on fault activity of the LTB. • The lower fault activity along the southern LTB may be due to a greater number of structures. Abstract Seven continuous GPS stations are located on the hanging wall of the Longmenshan Thrust Belt, and post-seismic deformation data of the 2013 Lushan earthquake have been recorded for nearly four years following the earthquake. We transform the data from a global reference frame to the South China Block reference frame, and then, the secular motion and post-seismic deformation of the Wenchuan earthquake are excluded using an exponential fit model. Based on our results, the viscosities of the low velocity zone at a depth of ∼25 km and of the middle and lower crust around the Longmenshan Thrust Belt are obtained as 2.75 × 10 17 P a · s and 2.56 × 10 18 P a · s , respectively. The post-seismic rebound, which was observed near the Lushan epicenter, may represent the occurrence of overslip during the earthquake. The more complex structural style may have produced weaker fault activity along the southern segment of the Longmenshan Thrust Belt than along its middle and northern segments. [ABSTRACT FROM AUTHOR]

Background: Disulfidptosis and the disulfidptosis-related gene SLC7A11 have recently attracted significant attention for their role in tumorigenesis and tumour management. However, its association with adrenocortical carcinoma (ACC) is rarely discussed. Methods: Differential analysis, Cox regression analysis, and survival analysis were used to screen for the hub gene SLC7A11 in the TCGA and GTEx databases and disulfidptosis-related gene sets. Then, we performed an association analysis between SLC7A11 and clinically relevant factors in ACC patients. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic value of SLC7A11 and clinically relevant factors. Weighted gene coexpression analysis was used to find genes associated with SLC7A11. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and the LinkedOmics database were used to analyse the functions of SLC7A11-associated genes. The CIBERSORT and Xcell algorithms were used to analyse the relationship between SLC7A11 and immune cell infiltration in ACC. The TISIDB database was applied to search for the correlation between SLC7A11 expression and immune chemokines. In addition, we performed a correlation analysis for SLC7A11 expression and tumour mutational burden and immune checkpoint-related genes and assessed drug sensitivity based on SLC7A11 expression. Immunohistochemistry and RT‒qPCR were used to validate the upregulation of SLC7A11 in the ACC. Results: SLC7A11 is highly expressed in multiple urological tumours, including ACC. SLC7A11 expression is strongly associated with clinically relevant factors (M-stage and MYL6 expression) in ACC. SLC7A11 and the constructed nomogram can accurately predict ACC patient outcomes. The functions of SLC7A11 and its closely related genes are tightly associated with the occurrence of disulfidptosis in ACC. SLC7A11 expression was tightly associated with various immune cell infiltration disorders in the ACC tumour microenvironment (TME). It was positively correlated with the expression of immune chemokines (CXCL8, CXCL3, and CCL20) and negatively correlated with the expression of immune chemokines (CXCL17 and CCL14). SLC7A11 expression was positively associated with the expression of immune checkpoint genes (NRP1, TNFSF4, TNFRSF9, and CD276) and tumour mutation burden. The expression level of SLC7A11 in ACC patients is closely associated withcthe drug sensitivity. Conclusion: In ACC, high expression of SLC7A11 is associated with migration, invasion, drug sensitivity, immune infiltration disorders, and poor prognosis, and its induction of disulfidptosis is a promising target for the treatment of ACC. [ABSTRACT FROM AUTHOR]

Fault locking inversion can clarify the occurrence mechanisms of large earthquakes and the seismic hazards of future earthquakes. Due to limited observations in mainland China, fault locking inversions have typically been unstable. To investigate a more suitable fault locking behavior of the Longmenshan Thrust Belt (LTB) preceding the 2008 Wenchuan earthquake, GNSS velocity field data during 1999–2007 and the least-squares collocation method (LSCM) are used in this study. Despite the limited stations, after interpolating the GNSS velocity with the LSCM, uncertainties are reduced to some extent during the inversion. Based on the interpolation data, the inversion shows two locked areas that are consistent with the coseismic slip distribution of the Wenchuan earthquake. The third locked area is located on the southern LTB. A checkerboard scheme is proposed, and historic earthquakes larger than M 3.0 since 1950 are analyzed to recheck our inversion. According to the inverted result, the Wenchuan and Lushan earthquakes are two independent events. Additionally, we propose that future destructive earthquakes may occur on the southern segment of the LTB. The maximum magnitude of a future possible earthquake is Mw 8.2. • The fault locking behavior of the Longmenshan Thrust Belt was investigated. • After interpolating the GNSS data, the fault locking inversion is more reasonable. • The southern segment of LTB is more capable of a large and destructive earthquake. [ABSTRACT FROM AUTHOR]

A wireless electrocardiogram case study suggests that current CDMA2000 cellular technology has considerable potential in medical telemetry. Modifications to the network protocol stack ensure the highest data integrity and lowest service delay. [ABSTRACT FROM PUBLISHER]

Abstract: In order to investigate the effect and mechanism of action of rosuvastatin on atherosclerotic lesion in a Wistar rat model, 16 Wistar rats were fed a cholesterol-rich, vitamin D3 overload diet and underwent balloon injury of the aorta. One day prior to injury, half of the rats began rosuvastatin treatment (5mg/kg/d) via oral gavage. Eight control rats received a basal diet and sham operation. After 14 weeks of treatment, the animals were sacrificed. Blood was collected to measure lipid and angiotensin II (Ang II) levels and morphologic analysis was performed on the aorta. Scavenger receptor-class B type I (SR-BI), Ang II type-1 (AT1) receptor and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK1/2) protein and mRNA levels were measured via Western blot and real time reverse transcriptase polymerase chain reaction, respectively. Spearman's rank correlation was utilized to examine the relationships between SR-BI and Ang II or AT1 receptor expression. The atherosclerosis model group demonstrated an increase in plasma lipid levels and aortic plaque formation. After 14 weeks of treatment with rosuvastatin, there was a significant decrease in plasma lipid and Ang II levels accompanied by an improvement in aortic lesions. Rosuvastatin increased the expression of SR-BI but significantly inhibited the expression of AT1 receptor and p-ERK1/2. SR-BI protein expression was inversely correlated with both the level of Ang II and expression of the AT1 receptor. In conclusion, rosuvastatin attenuates atherosclerosis in the Wistar rat model, and its anti-atherosclerotic activity may be through upregulation of SR-BI expression and inhibition of p-ERK1/2 levels and AT1 receptor expression. [Copyright &y& Elsevier]

In this paper, we apply the method of Granger causality which is more accurate than classical correlation analysis method to determine whether the main air pollutants — Nitrogen oxides (NO x ), SO2 (Sulfur Dioxide), CO (carbon monoxide), TSP (total suspended particulates), PM10 (particulate matter smaller than 10 microns) and the mortality of respiratory diseases of the residents in Beijing have causal relationship. After ensuring NO x , SO2 and CO as the responsible substances, we use the time series method to construct the autoregressive integrated moving average model (ARIMA) of the pollutants, so that we could predict the amount of the pollutants from 2005 to 2008. Then we use the predicted value of pollutants as the input of the neural network model and obtain the output as the change of the death rate of respiratory diseases from 2005 to 2008. In the end, reducing the amount of pollutants by 10% and inputting the data in the neural network model, we make the prediction to evaluate the level of the pollutants and concluded that NO x is the most important pollutant to control. [Copyright &y& Elsevier]

It is well-known that fish have the ability to adapt to complex water flow environments. However, most research on bionic robotic fishes has focused on static water conditions. There remains a lot of room on the control of robotic fish in water flow. While static flow serves as the fundamental element of water flow, this paper seeks to address the issue of target point approaching control for bionic robotic fish in static water environments. Recognizing the challenges posed by the proportional–integral–derivative (PID) control and model predictive control (MPC) methods encountering the complex non-linear system, this study proposes a hybrid control approach that based on model predictive decision-making strategy. The proposed hybrid control method is effective in guiding robotic fish towards target points in both static water and static flow environments and achieving rapid system convergence under the premise of significantly reducing the calculation error. This work provides a potential reference for the control of bionic robotic fish in static flow. [Display omitted] • Complete the target point approaching task of bionic robot fish in different water fields, including static water and static flow. • A dynamic model of a single joint robot fish considering the influence of the flow. • A hybrid controller combining PID controller and model predictive controller. • Comparative target point approaching experiments on PID control, MPC control and hybrid control. [ABSTRACT FROM AUTHOR]

Global Positioning System (GPS) stations installed in and around the epicenter of the Lushan earthquake (Mw 6.7), which occurred almost 5 years after the 2008 Wenchuan earthquake, recorded preseismic deformation corresponding to the Lushan earthquake within the southern Longmenshan thrust belt. A half-space dislocation model is used to simulate the theoretical values of the postseismic displacements caused by the 2008 Wenchuan earthquake, and after transforming the reference frame and filtering the GPS displacement time series, the theoretical and observed GPS values are compared to identify the geodetic anomaly preceding the Lushan earthquake. The abnormal extent of this geodetic anomaly decreases with increasing epicentral distance for each GPS site. This geodetic signal reflects preslip along a locked section of the 2013 seismogenic fault, which caused the accumulation of elastic strain energy until the faulting strength was overcome, thereby generating the Lushan earthquake. Hence, this anomaly might be used as an observable and identifiable precursor to forecast an impending earthquake within a period of less than two and half years before its occurrence. [ABSTRACT FROM AUTHOR]

Cistanche tubulosa (Schenk) R. Wight has been used frequently in traditional folk medicine for treatment of male sexual dysfunction (MSD). Phenylethanol glycosides, the main components of C. tubulosa , possess a variety of pharmacological activities due to their multiple properties. However, the underlying mechanism by which phenylethanol glycosides from C. tubulosa (CPhGs) regulates testicular steroids has not been elucidated to date. This study is to determine whether CPhGs promotes the reproductive functions of mice through CYP450-3β-HSD pathway of testosterone synthesis. The major compositions of C. tubulosa (CPhGs) were quantified by high performance liquid chromatography (HPLC). The model of reproductive injury in mice were induced by injection of hydrocortisone (HCT). Different doses of CPhGs (72, 145 and 289 mg/kg) and testosterone propionate (TP, positive control drug) were administrated intragastrically for 14 d. The reproductive functions (erectile incubation period, capture and ejaculation incubation period, number of captures and ejaculations) and organ weights (testicle, epididymis, seminal vesicle and penis) were then determined. The levels of luteinizing hormone and testosterone in serum were quantified by radioimmunoassay. The key enzymes in testosterone synthesis pathways such as steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage enzyme (P450scc/CYP11A1) and 3β-hydroxysteroid dehydrogenase (3β-HSD) in the testis were assessed by immunofluorescence (IF) staining or/and Western blot (WB) analysis. The results illustrated that the low dose of CPhGs (72 mg/kg) had no significant protective effect against the reproductive injury caused by HCT, while the moderate dose of CPhGs (145 mg/kg) improved the damaged reproductive ability and the declined levels of luteinizing hormone and testosterone in the model mice (P < 0.001, P < 0.05 , respectively). In particular, high dose of CPhGs (289 mg/kg) was most effective in improving HCT-induced changes in body weight (P < 0.01), reducing the incubation period of the erectile (P < 0.001), capture (P < 0.05) and ejaculation (P < 0.01), and increasing the number of captures and ejaculations (P < 0.01, P < 0.05, respectively). The weights of testcle, epididymis, seminal vesicle and penis (P < 0.001, P < 0.01, P < 0.01, P < 0.001, respectively) were improved by high dose of CPhGs. The levels of testosterone and its upstream luteinizing hormone were up-regulated by high dose of CPhGs (P < 0.001). Meanwhile, the expressions of the key steroidogenic enzymes including CYP11A1 and 3β-HSD were significantly up-regulated after CPhGs treatment (P < 0.001), demonstrated that CPhGs exerted the effect through enhancing testosterone biosynthesis via CYP450-3β-HSD pathway. CPhGs could significantly protect against HCT-induced deleterious reproductive dysfunction and testis injury. The protective effects were exerted by up-regulating synthesis of testosterone via the CYP450-3β-HSD pathway in Leydig cells. Image 1 [ABSTRACT FROM AUTHOR]

Glycyrrhetinic acid (GA) shows great efficiency against non-small cell lung cancer (NSCLC), but the detailed mechanism is unclear, which has limited its clinical application. Herein, we investigated the potential targets of GA against NSCLC by activity-based protein profiling (ABPP) technology and the combination of histopathology and proteomics validation. In vitro and in vivo results indicated GA significantly inhibited NSCLC via promotion of peroxiredoxin-6 (Prdx6) and caspase-3 (Casp3)-mediated mitochondrial apoptosis. This original finding will provide theoretical and data support to improve the treatment of NSCLC with the application of GA. [Display omitted] • First-time integrated analysis profiling of non-small cell lung cancer (NSCLC) and Glycyrrhetinic acid (GA) treatment by integrating activity-based protein profiling (ABPP) technology, histopathology and proteomics validation both in vitro and in vivo. • Identification of GA promoted ROS accumulation and inhibited proliferation of NSCLC cells. • Identification of Casp3 and Prdx6 were direct target proteins of GA in the treatment of NSCLC cells. [ABSTRACT FROM AUTHOR]

Objective: To determine the pharmacodynamic mechanism underlying Cordyceps sinensis relief in a murine model of non-small cell lung cancer (NSCLC). Methods: We created a murine model of NSCLC and studied the potential molecular mechanism by which C. sinensis relieved NSCLC using a combination of transcriptomics, proteomics, and experimental validation. Results: C. sinensis markedly suppressed the fluorescence values in mice with NSCLC, improved the pathologic morphology of lung tissue, ameliorated inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, interleukin-10, and the oxidative stress indicators superoxide dismutase, malondialdehyde, and glutathione peroxidase). Transcriptomics results showed that the therapeutic effect of C. sinensis was primarily involved in the differentiation and activation of T cells. Based on the proteomic results, C. sinensis likely exerted a protective effect by recruiting immune cells and suppressing tumor cell proliferation via the MAPK pathway. Finally, the experimental validation results indicated that C. sinensis significantly decreased the VEGF and Ki67 expression, downregulated RhoA, Raf-1, and c-fos expression, which are related to cell migration and invasion, increased the serum concentration of hematopoietic factors (EPO and GM-CSF), and improved the percentage of immune cells (natural killer cells, dendritic cells, and CD4+ and CD8+ lymphocytes), which enhanced immune function. Conclusions: Based on our preclinical study, C. sinensis was shown to exert a protective effect on NSCLC, primarily by inhibiting the MAPK pathway. [ABSTRACT FROM AUTHOR]

Until the Mw 6.6 Luding earthquake ruptured the Moxi section of the Xianshuihe fault (XSHF) on 5 September 2022, the region had not experienced an Mw >6 earthquake since instrumental records began. We used Global Positioning System (GPS) and Sentinel-1 interferometric synthetic aperture radar (InSAR) observations to image the coseismic deformation and constrain the location and geometry of the seismogenic fault using a Bayesian method We then present a distributed slip model of the 2022 Mw6.6 Luding earthquake, a left-lateral strike-slip earthquake that occurred on the Moxi section of the Xianshuihe fault in the southwest Sichuan basin, China. Two tracks (T26 and T135) of the InSAR data captured a part of the coseismic surface deformation with the line-of-sight displacements range from ∼−0.16 m to ~0.14 m in the ascending track and from ~−0.12 m to ~0.10 m in the descending track. The inverted best-fitting fault model shows a pure sinistral strike-slip motion on a west-dipping fault plane with a strike of 164.3°. We adopt a variational Bayesian approach and account for the uncertainties in the fault geometry to retrieve the distributed slip model. The inverted result shows that the maximum slip of ~1.82 m occurred at a depth of 5.3 km, with the major slip concentrated within depths ranging from 0.9–11 km. The InSAR-determined moment is 1.3 × 1019 Nm, with a shear modulus of 30 GPa, equivalent to Mw 6.7. The published coseismic slip models of the 2022 Luding earthquake show apparent differences despite the use of similar geodetic or seismic observations. These variations underscore the uncertainty associated with routinely performed source inversions and their interpretations for the underlying fault model. [ABSTRACT FROM AUTHOR]

The use of emerging tobacco products, such as waterpipe or hookah and electronic cigarettes (e-cigs), has gained significant popularity and are promoted as safer alternatives to conventional cigarettes. Circadian systems are internal biological oscillations that are considered important regulators of immune functions in mammals. Tobacco induced inflammatory lung diseases frequently exhibit time-of-day/night variation in lung function and symptom severity. We investigated the impact of inhaled e-cig vapor and waterpipe smoke (WPS) on pulmonary circadian molecular clock disruption by determining the changes in expression levels and abundance of core clock component genes (BMAL1, CLOCK) and clock-controlled output genes (Rev-erbα, Per2, Rev-erbβ, Cry2, Rorα) in mouse lungs. We showed that the expression levels of these pulmonary core clock genes and clock-controlled output genes were altered significantly following exposure to WPS (Bmal1, Clock, and Rev-erbα). We further showed a significant yet differential effect on expression levels of core clock and clock-controlled genes (Bmal1, Per2) in the lungs of mice exposed to e-cig vapor containing nicotine. Thus, acute exposure to WPS and e-cig vapor containing nicotine contributes to altered expression of circadian molecular clock genes in mouse lungs, which may have repercussions on lung cellular and biological functions. [ABSTRACT FROM AUTHOR]

The role of the Mas receptor in the activity of valsartan against intimal hyperplasia is unclear. Herein, we investigated the role of the angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1–7)-Mas receptor axis on the activity of valsartan against intimal hyperplasiain balloon-injured rat aortic arteries. Wistar rats were randomized equally into the sham control group, injured group, and injured plus valsartan (20 mg/kg/d)-treated group. Valsartan significantly attenuated the vascular smooth muscle cell proliferation and intimal and medial thickening on days 14 and 28 after injury. The angiotensin-(1–7) levels as well as ACE2 and Mas receptor mRNA/protein expression were significantly decreased in the injured rats, compared to the uninjured rats; meanwhile, the angiotensin II level as well as the ACE and AT 1 receptor mRNA/protein expression were increased (all P < 0.05 or < 0.01). Additionally, the p -ERK protein expression was increased (P < 0.01). Treatment with valsartan significantly increased the angiotensin-(1–7) levels as well as ACE2 and Mas receptor mRNA/protein expression but decreased the angiotensin II level, ACE and AT 1 receptor mRNA/protein expression, as well as the p -ERK protein expression, compared to the injured group (all P < 0.05 or < 0.01). These results suggest that valsartan attenuates neointimal hyperplasiain balloon-injured rat aortic arteries through activation of the ACE2-angiotensin-(1–7)-Mas axis as well as inhibition of the ACE-angiotensin II-AT1 and p -ERK pathways. [ABSTRACT FROM AUTHOR]

Networked robotics are a typical cyber–physical system (CPS). This paper presents the cyber physical interaction model to perform formation control and tracking in the presence of other robots and static obstacles. It discusses how such a model can be effectively utilized to deal with kinodynamic and operation range constraints. The cyber system is also responsible for feasible trajectory generation based upon regional path segments and to ensure that all the robots maneuver through obstacles in a safe manner. The introduction of virtual robot restructures the formation control problem into a tracking control problem between virtual reference robot and follower robots. A novel obstacle avoidance approach is proposed based upon the scaling of whole (partial) formation corresponding to centralized (distributed) framework. The involved CPS has network structure preserving properties that are key to effective distributed decision making. The novel formation control, obstacle avoidance, and trajectory tracking approaches facilitate networked robots to be effectively controlled through the cyber system. We also discuss efficient and optimal implementation of the proposed trajectory generator using computer-aided design for CPSs. Evaluation of the proposed approach is provided that demonstrate the formation control, trajectory tracking, and obstacle avoidance for multirobots using the proposed scheme. [ABSTRACT FROM AUTHOR]

Cyber-Physical Systems (CPS) integrate discrete-time computing and continuous-time physical-world entities, which are often wirelessly interlinked. The use of wireless safety-critical CPS requires safety guarantees despite communication faults. This paper focuses on one important set of such safety rules: Proper-Temporal-Embedding (PTE), where distributed CPS entities must enter/leave risky states according to properly nested temporal pattern and certain duration spacing. Our solution introduces hybrid automata to formally describe and analyze CPS design patterns. We propose a novel leasing based design pattern, along with closed-form configuration constraints, to guarantee PTE safety rules under arbitrary wireless communication faults. We propose a formal procedure to transform the design pattern hybrid automata into specific wireless CPS designs. This procedure can effectively isolate physical world parameters from affecting the PTE safety of the resultant specific designs. We conduct two wireless CPS case studies, one on medicine and the other on control, to show that the resulted system is safe against communication failures. We also compare our approach with a polling based approach. Both approaches support PTE under arbitrary communication failures. The polling approach performs better under severely adverse wireless medium conditions; while ours performs better under benign or moderately adverse wireless medium conditions. [ABSTRACT FROM AUTHOR]

Background: Tyrosine kinase inhibitors (TKIs) are mainstays of cancer treatment. However, their clinical benefits are often constrained by acquired resistance. To overcome such outcomes, we have rationally engineered APG-2449 as a novel multikinase inhibitor that is highly potent against oncogenic alterations of anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), and focal adhesion kinase (FAK). Here we present the preclinical evaluation of APG-2449, which exhibits antiproliferative activity in cells carrying ALK fusion or secondary mutations.Methods: KINOMEscan® and LANCE TR-FRET were used to characterize targets and selectivity of APG-2449. Water-soluble tetrazolium salt (WST-8) viability assay and xenograft tumorigenicity were employed to evaluate therapeutic efficacy of monotherapy or drug combination in preclinical models of solid tumors. Western blot, pharmacokinetic, and flow cytometry analyses, as well as RNA sequencing were used to explore pharmacokinetic-pharmacodynamic correlations and the mechanism of actions driving drug combination synergy.Results: In mice bearing wild-type or ALK/ROS1-mutant non-small-cell lung cancer (NSCLC), APG-2449 demonstrates potent antitumor activity, with correlations between pharmacokinetics and pharmacodynamics in vivo. Through FAK inhibition, APG-2449 sensitizes ovarian xenograft tumors to paclitaxel by reducing CD44+ and aldehyde dehydrogenase 1-positive (ALDH1+) cancer stem cell populations, including ovarian tumors insensitive to carboplatin. In epidermal growth factor receptor (EGFR)-mutated NSCLC xenograft models, APG-2449 enhances EGFR TKI-induced tumor growth inhibition, while the ternary combination of APG-2449 with EGFR (osimertinib) and mitogen-activated extracellular signal-regulated kinase (MEK; trametinib) inhibitors overcomes osimertinib resistance. Mechanistically, phosphorylation of ALK, ROS1, and FAK, as well as their downstream components, is effectively inhibited by APG-2449.Conclusions: Taken together, our studies demonstrate that APG-2449 exerts potent and durable antitumor activity in human NSCLC and ovarian tumor models when administered alone or in combination with other therapies. A phase 1 clinical trial has been initiated to evaluate the safety and preliminary efficacy of APG-2449 in patients with advanced solid tumors, including ALK+ NSCLC refractory to earlier-generation ALK inhibitors.Trial Registration: Clinicaltrial.gov registration: NCT03917043 (date of first registration, 16/04/2019) and Chinese clinical trial registration: CTR20190468 (date of first registration, 09/04/2019). [ABSTRACT FROM AUTHOR]

Hybrid systems model checking is a great success in guaranteeing the safety of computerized control cyber-physical systems (CPS). However, when applying hybrid systems model checking to Medical Device Plug-and-Play (MDPnP) CPS, we encounter two challenges due to the complexity of human body: 1) there are no good offline differential equation-based models for many human body parameters; 2) the complexity of human body can result in many variables, complicating the system model. In an attempt to address the challenges, we propose to alter the traditional approach of offline hybrid systems model checking of time-unbounded (i.e., infinite horizon, a.k.a., long run) future behavior to online hybrid systems model checking of time-bounded (i.e., finite horizon, a.k.a., short run) future behavior. According to this proposal, online model checking runs as a real-time task to prevent faults. To meet the real-time requirements, certain design patterns must be followed, which brings up the codesign issue. We propose two sets of system codesign patterns for hard real time and soft real time, respectively. To evaluate our proposals, a case study on laser tracheotomy MDPnP is carried out. The study shows the necessity of online model checking. Furthermore, test results based on real-world human subject trace show the feasibility and effectiveness of our proposed codesign. [ABSTRACT FROM AUTHOR]

[Display omitted] • The monolayer nanoporous graphene oxide supported ionic liquid membrane was proposed. • The NPGO-[EMIM][TF 2 N] membrane has a CO 2 permeance of ∼104 GPU and no CH 4 passed with 11 Å thickness. • The cations are suspended above the pore center to dynamically modulate the pore size. • The enhanced selectivity is attributed to the synergistic effect of cations and anions. Nanoporous graphene oxide (NPGO) with a single atomic layer thickness and good mechanical strength has been regarded as a promising candidate in gas separation. However, it is challenging to precisely control the pore size to match the target gas. In this work, the pore size was modulated by supporting ionic liquid (IL) on the monolayer NPGO membrane (NPGO-SILM). The separation performance and mechanism for CO 2 /CH 4 in NPGO-[EMIM][BF 4 ], NPGO-[EMIM][PF 6 ] and NPGO-[EMIM][TF 2 N] were investigated by molecular dynamics simulation. It was found that the pore size of NPGO greatly affects the permeability and selectivity, and 5.6 Å is the most suitable pore size. After coating IL on NPGO, the CO 2 /CH 4 selectivity is obviously enhanced. With the IL thickness increasing from 5 to 11 Å, the CO 2 permeance decreased from ∼105 to ∼104 GPU, while the selectivity increased, and almost no CH 4 passed through the membrane with 11 Å thickness. Among the studied three types of ILs, the NPGO-[EMIM][TF 2 N] membrane shows the best CO 2 /CH 4 separation performance due to the strongest adsorption capacity between [TF 2 N] anion and CO 2. The interaction energy, PMF and probability distribution results suggest that the improved selectivity is attributed to the synergistic effect of cations and anions. The anions are responsible for the adsorption of large amounts of CO 2. At the same time, the cations are mainly distributed around the center of the NPGO pore because of the strong interaction between cation and NPGO, which would be favorable for dynamically adjusting pore size to allow the passage of CO 2 and prevent CH 4 from passing through the membrane. [ABSTRACT FROM AUTHOR]

Previous studies have approved that Baoyuan decoction (BYD) exerted remarkable cardioprotective effects on heart failure (HF) due to its anti-apoptotic properties. As a novel biomarker and target of HF, Cardiac ankyrin repeat protein (CARP) can exacerbate apoptosis via activation by angiotensin type 1 receptor (AT1) and subsequently deteriorate heart function. Transcriptome results in our previous study indicated BYD was beneficial to HF post-acute myocardial infarction (AMI) with a promising effect on CARP. However, the mechanism remains to be validated. This study aims to elucidate whether BYD ameliorates apoptosis to protect against HF via AT1-CARP signaling pathway. Left anterior descending ligation was applied to induce an HF rat model, Ang Ⅱ-stimulated H9C2 cells apoptotic model and overexpression of Ankrd1/CARP H9C2 cells were established to clarify the effects and potential mechanism of BYD. Ethanol extracts of BYD (0.64; 1.28; 2.57 g/kg) were orally administered for four weeks and Fosinopril (4.67 mg/kg) was selected as a positive group in vivo. In vitro , BYD (400, 600, 800 μg/ml) or RNH6270 (an inhibitor of AT1, 1 μM) was co-cultured with Ang Ⅱ stimulation for 48 h in H9C2 cells. Overexpression of Ankrd1/CARP was conducted by transient transfection with H9C2 cells to further confirm the exact mechanism. Finally, to define the active ingredients of anti-cardiomyocyte apoptosis in BYD, we furtherly used the Ang Ⅱ-induced cardiomyocyte apoptosis model to evaluate the effects. Echocardiography and TUNEL results showed that BYD in different doses remarkably improved heart function and inhibited apoptosis in vivo. Further study demonstrated that AT1 and CARP expressions in cardiac tissue were suppressed by BYD, accompanied with upregulation of B cell lymphoma-2 (Bcl-2) and downregulation of several pro-apoptotic molecules, including p53, Bcl-2 Associated X Protein (Bax) and Cleaved caspase 3. In parallel with the vivo experiment, in vitro research indicated BYD dramatically reduced the apoptotic cells and regulated expressions of critical apoptosis-related molecules mediated through downregulation of AT1 and CARP simultaneously which were consistent with the results in vivo experiment. Transiently transfected CARP over-expression further confirmed that BYD could suppress severe cardiomyocytes apoptosis induced by overexpression of CARP. Especially, the active ingredients of BYD including Astragaloside IV, Ginsenoside Rg3, Rb1, Rc and Re showed significantly anti-apoptosis effects. BYD improves cardiac function and protects against cardiomyocytes injury by inhibiting apoptosis via regulating the AT1-CARP signaling pathway. Image 1 [ABSTRACT FROM AUTHOR]

The Pearl River Delta Economic Zone is one of the fastest growing areas of China's social and economic development. However, the contradiction between people and land, the deterioration of ecological environment and the damage of urban ecological security have become more serious problems. In previous studies there was single land utilization type in small-area and the evaluation method was not suitable to large areas, this study proposes a new method. Firstly, the study implements ecological land zoning from assessing the importance of ecosystem services functional in four aspects: biodiversity, water conservation, soil conservation and coastal protected zone. Then, the suitability evaluation index system of agricultural and construction land is established from the geological environment perspective, and introduces variable weight-analytical hierarchy process-comprehensive index model to evaluate the suitability of agricultural land and construction land. Re-zoning the type of land that has a special effect on the socio-economic, the mining land, protected area of geological relics and groundwater resources, respectively. Finally, considering the actual condition use status and suitability distribution of land, the results of comprehensive zoning of land utilization is got. The results of this study can provide some geological basis for the future land utilization zoning. [ABSTRACT FROM AUTHOR]

Flavored tobacco products are increasing in popularity but remain unregulated, with the exception of the ban on flavored conventional cigarettes. Lack of regulation of cigarillos and little cigars allows vendors to have their own version of popular flavors, each with different chemical components. A new classification system was created for flavored cigars in order to easily communicate our results with the scientific community. To understand the physicochemical characteristics of flavored little cigars and cigarillo smoke, size distribution and concentration of particulate matter in smoke were determined. Acellular reactive oxygen species generation was measured as an indirect measurement of the potential to cause oxidative stress in cells. In addition, cigarillo smoke extract treatment on bronchial epithelial (Beas-2b) cells were assessed to determine the flavor-induced cellular toxicity. Flavored cigars/cigarillos showed significant variability in the tested parameters between flavors as well as brands of the same flavor, but most of the cigars showed higher potential of generating oxidative stress, than research grade cigarettes. Flavored cigars produced maximum particle concentrations at 1.0μm and 4.0 μm compared with 3R4F reference research cigarettes. A differential cytotoxic response was observed with cigarillo smoke extract treatments, with "fruits/candy" and "drinks" being the most toxic, but were not more cytotoxic than smoke from cigarettes. These cigarillos with flavors must be well characterized for toxicity in order to prevent adverse effects caused by exposure to flavor chemicals. Our study provides insight into understanding the potential health effects of flavor-infused cigars/cigarillos and the need for the regulation of those flavoring chemicals in these products. Future research is directed to determine the flavoring toxicity of little cigars and cigarillos in vivo studies. [ABSTRACT FROM AUTHOR]

According to the ideas of risk assessment, the theory of support vector regression is introduced to forecast the ice thickness distribution and achieve the ice extreme value of the wire. Combined with the exponential function of failure rate when the line is under stress, the failure rate model of the line is established in the particular icing condition. The ice strengthening standard is developed by the icing thickness of transmission line, which is used to strengthen lines differentially. Especially, the lines that cross different meteorological conditions are strengthened by the method of segmentation. Finally, the method of economic assessment based on the total life cycle cost is improved, and the comprehensive failure rate is used to calculate differentiated "impairment" benefits. Different lines are made differentiated planning through the simulation example. Various economic indicators are comprehensively compared, in that case, economic assessment results of lines under different strengthening schemes are obtained, which proves the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

We propose and experimentally demonstrate a bidirectional angled multimode interferometer (Bi-AMMI) for interleaved wavelength division multiplexing applications. The spectral response of the 2 × 4 Bi-AMMI is obtained using an eigenmode expansion method, including the cross coupling between the input and output ports at the same side of the multimode waveguide. To verify our design, both the standalone and interleaved Bi-AMMIs were fabricated and measured. The Bi-AMMI exhibits an insertion loss of 0.99 to 1.21 dB, and the unwanted cross coupling is lower than −20 dB. The interleaved device exhibits a measured optical loss of 4.77 to 5.02 dB, and the average crosstalk is calculated to be −18 dB. [ABSTRACT FROM AUTHOR]

The mechanisms of tectonic transfer and strain partitioning at the eastern termination of the Kunlun fault system, particularly the role of the relatively strong Ruoergai Subblock, remain unclear. In this work, we used the finite element method to determine how the Ruoergai Subblock affects regional deformation. The results show that the Ruoergai Subblock is moving to the east or northeast in a manner that differs from the motion of the Bayan Har Block in the eastward extrusion process and thus accounts for the formation and behavior of the Awancang and Longriba faults. In addition, strain partitioning on the eastern margin of the Tibetan Plateau is progressively transferring from the Awancang fault, Ruoergai Subblock, and Longriba fault to the Longmenshan thrust. In this study, a block-controlled pattern is proposed that accounts for the distribution and behavior of most of the faults on the northern and eastern margins of the Tibetan Plateau. Our study has played a certain reference role in the consideration of railway fracture resistance parameters in the area of the southern section of the Longmenshan fault and the Xianshuihe fault during construction of the Tibet Railway. • Influence of Subblock in the consideration of Tibet railway fracture resistance parameters. • Tectonic partitioning near the eastern margin of the Tibetan Plateau. • Influence of the Ruoergai Subblock's physical properties on tectonics. • Strong block control on fault formation and behavior. [ABSTRACT FROM AUTHOR]

Four gridding methods for GPS velocities are compared in terms of their precision, applicability and robustness by analyzing simulated data with uncertainties from 0.0 to ±3.0 mm/a. When the input data are 1° × 1° grid sampled and the uncertainty of the additional error is greater than ±1.0 mm/a, the gridding results show that the least-squares collocation method is highly robust while the robustness of the Kriging method is low. In contrast, the spherical harmonics and the multi-surface function are moderately robust, and the regional singular values for the multi-surface function method and the edge effects for the spherical harmonics method become more significant with increasing uncertainty of the input data. When the input data (with additional errors of ±2.0 mm/a) are decimated by 50% from the 1° × 1° grid data and then erased in three 6° × 12° regions, the gridding results in these three regions indicate that the least-squares collocation and the spherical harmonics methods have good performances, while the multi-surface function and the Kriging methods may lead to singular values. The gridding techniques are also applied to GPS horizontal velocities with an average error of ±0.8 mm/a over the Chinese mainland and the surrounding areas, and the results show that the least-squares collocation method has the best performance, followed by the Kriging and multi-surface function methods. Furthermore, the edge effects of the spherical harmonics method are significantly affected by the sparseness and geometric distribution of the input data. In general, the least-squares collocation method is superior in terms of its robustness, edge effect, error distribution and stability, while the other methods have several positive features. [ABSTRACT FROM AUTHOR]

With social and economic development and improvement of science and technology, tunnel boring machines, raise boring machines, reaming machines and road headers have been unprecedentedly applied to underground engineering construction. Mechanical rock breakage experiments became an indispensable mean for mechanical excavation of underground engineering. It can also guide the design and operation of excavation machines. This paper introduces the new mechanical rock breakage experimental platform developed by Beijing University of Technology. The design and manufacture of this platform considered the influence of high in situ stress, cutter head rotation and rock breakage by multi-cutters at the same time on the rock breakage process. Different tools, such as rolling cutters, scraper, ripper, and pick, for different excavation machines can be tested in the platform. It can also take into account the different rock mass structure in the sample box. Different construction conditions with different cutting tools can be realistically modeled. The experimental platform consists of a mechanical system, a hydraulic system, an automatic control system and a data acquisition system. After installation of the designed experimental platform, several tests with different construction conditions were conducted. The experimental results showed that the platform reached its design requirements. [ABSTRACT FROM AUTHOR]

The Sichuan-Tibet Railway in eastern Tibet runs across numerous seismogenic faults with high seismic risks. The Lancangjiang fault (LCJF), one of the essential strike-slip faults within the Qiangtang block, traverses the railway. However, the geometry and late Quaternary activities of the LCJF remain unclear, limiting the assessment of seismic hazards on the Sichuan-Tibet Railway and the understanding of kinematic patterns in eastern Tibet. Based on the interpretation of high-resolution satellite imagery, field observations, and shallow geophysical exploration, we first mapped the detailed geometry of the northern LCJF. It consists of two branches: Yangda-Yaxu fault (YYF) and Baqing-Leiwuqi fault (BLF), which merge eastwards onto the main LCJF. Displaced landforms and multiple numerical dating techniques reveal that the YYF is a mainly sinistral fault with a late Quaternary slip rate of ~2.2 + 0.6/−0.5 mm/yr and a minor vertical component (~0.1 mm/yr). The BLF undergoes an oblique motion with a left-lateral slip rate of ~1.2 + 0.5/−0.3 mm/yr and a northeast-vergent reverse rate of ~1.2 + 0.4/−0.2 mm/yr in the Holocene. Vector analysis of slip rates suggests that the LCJF has a sinistral rate of ~3.5 + 1.1/−0.8 mm/yr with a reverse component of ~1.6 + 0.4/−0.3 mm/yr, displaying an essential role in strain partitioning of eastern Tibet. Together with slip rates of other intra-block faults, the kinematic pattern of eastern Tibet probably applies to the sub-block model. Offset geologic units yield a total displacement of ~10–11 km for the YYF. Using the slip rate of the YYF, the LCJF was initiated at ~5.9–3.9 Ma, probably related to the establishment of the present-day strain pattern and the onset of crustal thickening in eastern Tibet during the late Miocene. In addition, the active YYF and BLF across the Sichuan-Tibet Railway have a seismic potential of Mw ~7.2–7.3 that will produce a ~ 1.8–2.0 m sinistral slip on the YYF, and a ~ 2.0 m horizontal, and ~ 1.1–1.3 m reverse motion on the BLF. They will pose a high seismic hazard potential on the railway. This study provides quantitative data for regional seismic hazard analysis and shows insights into the deformation mechanism of the plateau. • The geometry of the northern LCJF is first mapped. • The northern LCJF has a late Quaternary ~3.5 mm/yr sinistral and ~ 1.6 mm/yr reverse rate. • The seismic potential of the northern LCJF on the Sichuan-Tibet Railway is estimated. • The LCJF takes an important role in strain partitioning in eastern Tibet. • The initiation of the LCJF is related to the late-Miocene tectonic event in eastern Tibet. [ABSTRACT FROM AUTHOR]

The 2021 Mw 7.3 Maduo earthquake, which hit the high mountain area of the internal Bayan Har Block in the central Tibetan Plateau, generated a ~ 154 km-long, nearly E -W-striking surface rupture zone. Field observations indicate prominent surface breaks characterized by discontinuous shear faults, en echelon tensional fissures, and mole track structures, revealing a dominantly left-lateral strike-slip motion with a maximum sinistral offset of ~2.7–2.8 m and general offset of ~1.0–1.5 m. The west part of the Maduo surface rupture zone occurred along the pre-existing Jiangcuo fault. Its east portion cut through some WNW-trending tectonics, indicating a previously unknown fault. The epicenter and slip distribution show a bilateral rupture for the Maduo quake. The complex 3D geometry of the Maduo seismogenic fault has controlled the occurrence of aftershocks and the multimodal distribution of coseismic displacements. The abnormally long Maduo surface rupture zone suggests that the rupture area-magnitude relationship might be more applicable than the rupture length-magnitude relationship for the magnitude estimation of a paleo-event. The occurrence of the Maduo earthquake challenges the active block model which used to predict little or no slip partitioning and large earthquakes in the block interior. A reappraisal of seismic hazard along intra-block faults with low strain rates is needed, especially across densely populated regions. [Display omitted] • The 2021 Maduo earthquake produced a ~ 154 km-long, dominantly sinistral surface rupture zone. • The maximum left-lateral displacement for the Maduo earthquake is ~2.7–2.8 m. • Seismic hazards along intra-block faults with low strain rates should be concerned. • 3D seismogenic structures control the distribution of aftershocks and coseismic surface displacements. [ABSTRACT FROM AUTHOR]

Background: Seven patients with chronic hepatitis C virus (HCV) infection were followed up for 10 years in order to analyze the molecular evolution of the HCV nonstructural 5A (NS5A) gene.Methods: Serum samples were obtained from seven patients with anti-HCV who were HCV-RNA positive. The HCV NS5A region, including the interferon sensitivity-determining region (ISDR), protein kinase R binding domain (PKR-BD), and V3 was amplified and cloned, and then sequenced. The nucleotide sequences of the region at the beginning and at the end of the 10 years were aligned with the CLUSTAL W program, version 1.8, and the corresponding amino-acid sequences were deduced.Results: The three serine residues at positions 2197, 2201, and 2204, suggested to be important for hyperphosphorylation of NS5A, were highly conserved in different patients and were within the quasispecies of each patient. The wild-type ISDR or minimally mutated strain was dominant in all the patients and the number of quasispecies decreased over time.Conclusions: Our findings showed that the functional domains of NS5A were generally conserved over an interval of 10 years. Quasispecies distribution was variable and distinctly clustered over time during the natural course of HCV infection. These results may contribute to better understanding of HCV natural infection. [ABSTRACT FROM AUTHOR]

Background: Programmed death-1 (PD-1) immune checkpoint blockade has achieved clinical successes in cancer therapy. However, the response rate of anti-PD-1 agents remains low. Additionally, a subpopulation of patients developed hyperprogressive disease upon PD-1 blockade therapy. Combination therapy with targeted agents may improve immunotherapy. Recent studies show that p53 activation in the myeloid linage suppresses alternative (M2) macrophage polarization, and attenuates tumor development and invasion, leading to the hypothesis that p53 activation may augment antitumor immunity elicited by anti-PD-1 therapy. Method: Using APG-115 that is a MDM2 antagonist in clinical development as a pharmacological p53 activator, we investigated the role of p53 in immune modulation and combination therapy with PD-1 blockade. Results: In vitro treatment of bone marrow-derived macrophages with APG-115 resulted in activation of p53 and p21, and a decrease in immunosuppressive M2 macrophage population through downregulation of c-Myc and c-Maf. Increased proinflammatory M1 macrophage polarization was observed in the spleen from mice treated with APG-115. Additionally, APG-115 has co-stimulatory activity in T cells and increases PD-L1 expression in tumor cells. In vivo, APG-115 plus anti-PD-1 combination therapy resulted in enhanced antitumor activity in Trp53wt, Trp53mut, and Trp53-deficient (Trp53−/−) syngeneic tumor models. Importantly, such enhanced activity was abolished in a syngeneic tumor model established in Trp53 knockout mice. Despite differential changes in tumor-infiltrating leukocytes (TILs), including the increases in infiltrated cytotoxic CD8+ T cells in Trp53wt tumors and M1 macrophages in Trp53mut tumors, a decrease in the proportion of M2 macrophages consistently occurred in both Trp53wt and Trp53mut tumors upon combination treatment. Conclusion: Our results demonstrate that p53 activation mediated by APG-115 promotes antitumor immunity in the tumor microenvironment (TME) regardless of the Trp53 status of tumors per se. Instead, such an effect depends on p53 activation in Trp53 wild-type immune cells in the TME. Based on the data, a phase 1b clinical trial has been launched for the evaluation of APG-115 in combination with pembrolizumab in solid tumor patients including those with TP53mut tumors. [ABSTRACT FROM AUTHOR]