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China is rich in karst resources and famous for its karst landscape. As a part of karst, the popularity of red karst is obviously low and has received little attention; moreover, the related scientific research and tourism development are relatively immature. Therefore, this paper takes the red karst in Tongren, Guizhou as the research object, analyzes the characteristics and causes of the red karst, comprehensively evaluates its landscape value, and puts forward development strategies and protection suggestions. Through the above research, the following three research results are obtained. (1) On the basis of a field investigation and a literature review, the geographical situation, background, and landscape characteristics of the red karst landform and its surrounding areas in Tongren City were investigated in detail. It forms isolated peaks, rock walls, protruding rocks, stone pillars, and other forms. The most prominent features of the red karst landscape in Tongren City are that the color is red and white, and the shape is concave and convex in order. (2) Geochemical test and structural data collection and analyses of the collected samples were performed. The obtain concave layer rock is dolomitic limestone, and that convex lay rock is argillaceous dolomitic limestone. Because the convex layer rock sample is high in silicon element content, the convex layer rock sample is not easy to be weathered, is rich in clay mineral, and is not easy to be corrode; the convex layer rock sample gradually protrudes with the passage of time to form an uneven shape. The red karst landform is developed in either the rock stratum or tectonic zone with moderate tectonic deformation intensity. First, the formation of a single-layer honeycomb morphology requires that the rock stratum is subjected to a sufficient horizontal compressive stress at a certain burial depth. Second, it is necessary to widely exist in areas with relatively gentle rock formation occurrence; too strong of a structural deformation will make the rock formation occurrence steep, which is not conducive to the occurrence of differential dissolution between adjacent strata. (3) Through the construction of an evaluation index system, the red karst in Tongren City is evaluated, and it is concluded that the geological heritage value is high, and the development and utilization conditions are weak. The conclusion of this article is a supplement to the geological and geomorphological system characteristics of southern karst. From the perspective of world natural heritage, the study enriches the academic evidence of red karst and enables its exemplary role to be well played. From the perspective of the tourism development value, more people should be made aware of the diverse types of karst landforms, which provide experience and suggestions for the value of landforms, tourism resources, and tourism development in similar areas.

Abstract Background Frailty is a health condition linked to adverse health outcomes and lower life quality. The PRISMA-7, a 7-item questionnaire from the Program on Research for Integrating Services for the Maintenance of Autonomy (PRISMA), is a validated case-finding tool for frailty with good sensitivity and specificity. This study aimed to translate, culturally adapt, and validate the PRISMA-7 questionnaire for Chinese use. Methods A prospective observational study with convenience sampling recruited bilingual adults aged 65 and over living in the community. The Functional Autonomy Measurement System (SMAF) was the gold standard benchmark. The English PRISMA-7 questionnaire was culturally adapted to Chinese using forward and backward translation. Intra- and inter-rater reliability were determined using the intraclass correlation coefficient (ICC). Face, content and criterion validity were determined. The Receiver Operator characteristic (ROC) curve determined the optimal cut-off score. Results One-hundred-twenty participants (55 females and 65 males) were recruited. The Chinese PRISMA-7 questionnaire had excellent intra-rater and inter-rater reliability (ICC = 1.000). The rigorous forward and backward translation established the face and content validity. The moderately high correlations between the English PRISMA-7 with SMAF (r = − 0.655, p

In order to ensure a precisely controlled electro hydraulic servo system, a sliding mode control algorithm based on nonlinear disturbance observers (NDOB-SMC) is developed in this study. Firstly, the basic principles of hydraulic actuators and electro-hydraulic position servo control mathematics are studied, and theoretical models are utilized to derive the state equations of the controlled system. Furthermore, considering that the sliding mode control is invariant to external disturbances and parameter changes, it is designed to be resilient against the unreliable hydraulic position servo system. In the meanwhile, nonlinear disturbance observers are added to the system to offset its output and enhance tracking capabilities even more. The Lyapunov theory is used to demonstrate the stability of the control strategy. Finally, the efficacy and dynamic performance of the NDOB-SMC method are preliminary confirmed using the co-simulation platform of AMESim and Matlab/Simulink. The numerical simulation results show that the suggested approach offers greater control accuracy and improved robustness for hydraulic position servo systems when compared to the conventional PI and sliding mode control methods.

High-resolution three-dimensional VP, VS and VP/VS images in the Houziyan Reservoir Area were obtained by using Fast Marching Tomography Package (FMTOMO) with the travel time data from 6330 seismic events monitored by the Houziyan Reservoir Seismic Network. This analysis yielded the 3-D velocity structure, including longitudinal wave velocity (VP), shear wave velocity (VS), and the ratio of longitudinal and shear wave velocity (VP/VS) at different impoundment stages. The data changes at various impoundment times, depths of sections, and directions of profiles were analyzed to obtain these results. The final findings demonstrate the following results: 1) Through tomographic analysis, it was determined that the underground velocity structure in the Houziyan reservoir area was anisotropic before impoundment. 2) The area of high wave velocity increases in stage 1, stage 3, and stage 4. The area of low wave velocity increases in stage 2, especially in depth, indicating significant changes in the underground velocity structure at different impoundment stages. 3) Compared to the changes in underground velocity structures in other reservoirs after impoundment, the Houziyan reservoir exhibited a unique pattern. 4) In general, the underground velocity structure displayed an overall increasing trend after impoundment. However, it also exhibited instances of decreasing velocity, reflecting continuous dynamic adjustments to the underground velocity structure after impoundment. These conclusions highlight the impact of impoundment in the reservoir area on the underground velocity structure and provide scientific theoretical support for seismic risk assessment following impoundment in the reservoir area.

Abstract Background Observational studies reported an association between psoriasis and risk of lung cancer. However, whether psoriasis is causally associated with lung cancer is unclear. Methods Genetic summary data of psoriasis were retrieved from two independent genome-wide association studies (GWAS). Genetic information of lung cancer was retrieved from GWAS of International Lung Cancer Consortium. A set of quality control steps were conducted to select instrumental tools. We performed two independent two-sample Mendelian randomization (MR) analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between psoriasis and lung cancer (LUCA) as well as its subtypes, squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD). Results Between-SNP heterogeneity was present for most MR analyses, whereas horizontal pleiotropy was not detected for all MR analyses. Multiplicative random-effect inverse variance weighted (IVW-MRE) method was therefore selected as the primary MR approach. Both IVW-MRE estimates from the two independent MR analyses suggested that there was no significant causal relationship between psoriasis and LUCA as well as its histological subtypes. Sensitivity analyses using other four MR methods gave similar results. Meta-analysis of the two IVW-MRE derived MR estimates yielded an odds ratio (OR) of 1.00 (95% CI 0.95–1.06) for LUCA, 1.01 (95% CI 0.93–1.08) for LUSC, and 0.97 (95% CI 0.90–1.06) for LUAD. Conclusion Our results do not support a genetic association between psoriasis and lung cancer and its subtypes. More population-based and experimental studies are warranted to further dissect the complex correlation between psoriasis and lung cancer.

A new wheel-clamping type inspection robot for bridge stay cables was designed. Its clamping mechanism adopts a four-auxiliary-two-drive wheel clamping scheme, and the driving unit utilizes a single motor with double output shaft. A simple automatic control system of the robot was designed based on Arduino. Then, the diameter range of the stay cable that the robot can hold was calculated. The mechanical model of the robot under clamping condition was established. The curves for the minimum thrust F e and driving force F required by the robot under different stay cable diameters Φ and inclined angles γ were obtained through Matlab data processing. Based on Adams dynamic simulation, the appropriate shape and material of the wheel, the optimal position of the centroid distribution and how to improve the wind resistance of the wheel were determined. Finally, a prototype robot was developed and a climbing experiment was carried out. The results show that the inspection robot is easy to clamp, simple to operate and control, and the detection speed is 0–5 m/min. The robot can grab stay cables with diameters ranging from 70 to 245 mm and can be used for stay cables with angles ranging from 0° to 90°.

Advanced non-small cell lung cancer (NSCLC) with MET amplification primarily relies on MET inhibitors for treatment, but once resistance occurs, the available treatment options are limited and the prognosis is typically poor. A 57-year-old man with advanced NSCLC and C-MET amplification was initially treated with crizotinib but developed progressive disease. After the antirotinib treatment, he achieved a partial response for a year. Genetic testing showed high PD-L1 expression, and he was treated with pembrolizumab and chemotherapy for 3 months, with partial response. Maintenance therapy with pembrolizumab and local I-125 seeds brachytherapy (ISB) was given after the lung lesion progressed but other lesions remained stable. The therapy resulted in significant resolution of the right upper lung lesion. It demonstrates the effectiveness of ISB-ICI combination in treating MET amplification advanced NSCLC. Ongoing research and treatment innovation are important in managing advanced NSCLC with complex genetic aberrations. To explore the candidate mechanism of ISB therapy response, we download public genetic data and conduct different expression Lncrnas analysis and pathway analysis to discover radiotherapy related sensitive or resistance lncRNAs and pathways, we found that AL654754.1 is a key lncRNA with radiotherapy response, and it also include in classical p53 and Wnt signaling pathway. Overall, the clinical case reports, combined with the exploration of underlying mechanisms, provide positive guidance for the precise treatment of lung cancer.

The Pingzhai Reservoir, a water source project of the Central Guizhou Province hydro-junction project, is located in the deep canyon karst area of the Sancha river in the Guizhou Plateau. It is an important water conservancy infrastructure to ensure the safety of water resources in central Guizhou. In this paper, the hydrological and hydrochemical automatic monitoring technology is used to study the hydrological and hydrochemical regime of the Santang underground river system, an important tributary in the interval basin of the Pingzhai Reservoir, which lacks the early basic research of hydrogeology. On this basis, the karst development and conduit model of the deep canyon karst subterraneous river system are preliminarily discussed. The results show that the hydrochemical regimes are mainly controlled by the cover CO2 effect, effective rainfall dilution effect and opening effect of runoff-discharge channels. In different time scales and atmospheric precipitation conditions, the variation characteristics of hydrochemical regime are different, and the corresponding dominant effect is also different. The annual variation of water temperature is high in summer and low in winter, and the daily variation is high in day and low at night. The annual variations of electrical conductivity and partial pressure of CO2 of the groundwater is high in normal-water level period and low in high-water level period because of the combined effects of land cover CO2 and rainfall dilution. On the monthly scale, the cover CO2 effect can be observed during the initial stage of rainfall, but after rainfall the dilution effect control the variation of electrical conductivity and Pco2. On the daily scale in the dry season, the daily hydrochemical regime controlled by the opening effect of the runoff-discharge channels can be observed. The identified opening effect of the runoff-discharge channels can provide a hydrochemical basis for judging the pressure state of karst conduit in the modeling study of the karst water system. This study provides a hydrogeological basis for the joint scheduling of surface and underground reservoirs and the reasonable utilization of water resources in this area in the future.

Abstract Input saturation and disturbances often exist in hydraulic systems, reducing internal state stability and tracking response performances of the system as well as complicating the design of advanced non‐linear controllers. A practical method named active disturbance rejection controller is proposed by backstepping method for full‐state constrained hydraulic systems to constrain tracking errors in the desired boundaries and deal with input saturation as well as disturbances. To achieve the previously mentioned objectives, the disturbance compensation strategy and dynamic auxiliary systems are integrated into the barrier Lyapunov theory for the first time. It is proved that all states of hydraulic systems are kept within the ultimate boundaries with satisfactory dynamic performance and high steady‐state accuracy. In addition, when disturbances are constants, asymptotic tracking is theoretically achieved. The performance of the control strategy is verified by experimental results.

Extended-spectrum beta-lactamase-producing Gram-negative bacteria are common in the community and hospitals. To monitor ESBLs mediated by the CTX-M genotype, we collected clinical ESBL pathogenic strains from a hospital in central China and observed a strain of Escherichia coli, namely Ec15103 carrying blaCTX–M–14, blaCTX–M–64 and blaTEM–1, isolated from the blood of a 7-day-old infant in 2015. Strain Ec15103 contains two drug resistance plasmids: pEc15103A, an IncFI-type plasmid that cannot be conjugatively transferred and carries the drug resistance genes blaTEM–1, aacC2, aadA5, sul1, mph(A), sul2, strAB, and tetA(A); and pEc15103B, an IncK2/Z-type plasmid that carries the conjugation transfer gene and blaCTX–M–14. In addition, blaCTX–M–64 is located on the chromosome of Ec15103, and it is the first report of pathogen with blaCTX–M–64 located on its chromosome (the search terms used “blaCTX-M-64” and “chromosome”). blaCTX–M–14 and blaCTX–M–64 are carried by ISEcp1-mediated transposon Tn6503a and Tn6502, respectively. The conjugation transfer ability of pEc15103B was significantly inhibited by zidovudine (AZT) and linoleic acid (LA) and that expression of blaCTX–M–14, blaCTX–M–64 and blaTEM–1 at the mRNA level did not change based on the concentration of cefotaxime or ampicillin. Co-occurrence of blaCTX–M–14 and blaCTX–M–64 in a single isolate will enhance the drug resistance of bacteria, and the presence of blaCTX–M–64 in the chromosome may make the resistance more maintain. This fact will facilitate its dissemination and persistence under different antimicrobial selection pressures. It is essential to prevent these strains from further spreading in a hospital environment.

We perceived a trend in the study and practice of petroleum-contaminate sites. Monitored natural attenuation (MNA) can reduce the contaminant concentrations in the soil and groundwater, and it is a method that can remediate the petroleum-contaminated site effectively. MNA is becoming a research focus. This study evaluated MNA using a series of lab-based bench-scale experiments and a large amount of monitoring data from field samplings. Based on the in-site total petroleum hydrocarbon (TPH) results, we used statistical methods, the Mann-Kendall test, and mass fluxes in order to evaluate the MNA of petroleum-contaminated sites in groundwater. The results showed that the TPH concentrations were decreasing, and the plume became smaller. The attenuation rate was from 0.00876 mg/d to 0.10095 mg/d; remediating the petroleum contamination site would cost 1.3 years to 10.6 years. The plume reached a quasi-steady state, and mass flux declined. The most essential process of MNA was biodegradation, and the second was sorption. During the monitoring period, 393 g of TPH was attenuated, including 355 g of TPH gradated by microbes. Biodegradation upstream of the plume was more serious. Iron(Ⅲ) and manganese were the main electron acceptors utilized by microbes during the monitored period. MNA was in progress, and it can be an effective method to remediate the petroleum-contaminated site. Lab-based bench-scale experiments were performed with much monitoring data from the field samplings in order to understand the fate and transport mechanism of the petroleum contamination from the land surface to shallow groundwater according to site conditions.

BackgroundThe validated Incremental Shuttle Walk Test (ISWT) is widely used for evaluating maximal exercise capacity, with the distance-walked (IWSD) as the primary outcome. However, there are no normative reference values (NRV) and reference equations to predict ISWD for the Singaporean population.ObjectivesThis study aims to establish the NRV and reference equations for ISWD in healthy Singaporeans aged 21 to 80 and investigate the determining variables during ISWT.MethodsThis cross-sectional study recruited community-dwelling healthy subjects aged 21-80 from the community via convenience sampling. Each subject completed two trials of the ISWT according to the standard protocol. Variables measured during the trials included ISWD, pre-and post-test heart rate (HR), oxygen saturation, blood pressure (BP), modified Borg's dyspnoea score and Borg's rate of perceived exertion (RPE).Results199 healthy Singaporean (females = 114, males = 85) participated in the study. The overall median ISWD was 660.0 metres (m) [interquartile range (IQR):440.0-850.0]. The age-stratified mean ISWD ranged from 430.0 m (IQR:350.0-450.0) (aged 60-80) to 480.0 m (IQR:438.0-650.0) (aged 40-59) to 780.0 m (IQR:670.0-960.0) (aged 21-39). Gender, age, weight, height and HR change (highest post-test HR minus pre-test HR) were the most significant variables (p < 0.001). IWSD (m) = 651.4(Height, m) +89.7(Gender, male = 1; female = 0) -6.31(Age, years) -3.61(Weight, kilograms) +2.54(HR change, beats per minute); R2 = 0.741. Previously published ISWT reference equations cannot accurately predict the ISWD in the Singaporean population.ConclusionsThis study investigated the ISWD NRV and established reference equations for healthy Singaporeans aged 21-80. The information would be beneficial in setting performance benchmarks to guide physical assessment, intervention and rehabilitation.

Background: Previous studies have suggested that patients with lung adenocarcinoma (LUAD) will significantly benefit from epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). However, many LUAD patients will develop resistance to EGFR-TKI. Thus, our study aims to develop models to predict EGFR-TKI resistance and the LUAD prognosis.Methods: Two Gene Expression Omnibus (GEO) datasets (GSE31625 and GSE34228) were used as the discovery datasets to find the common differentially expressed genes (DEGs) in EGFR-TKI resistant LUAD profiles. The association of these common DEGs with LUAD prognosis was investigated in The Cancer Genome Atlas (TCGA) database. Moreover, we constructed the risk score for prognosis prediction of LUAD by LASSO analysis. The performance of the risk score for predicting LUAD prognosis was calculated using an independent dataset (GSE37745). A random forest model by risk score genes was trained in the training dataset, and the diagnostic ability for distinguishing sensitive and EGFR-TKI resistant samples was validated in the internal testing dataset and external testing datasets (GSE122005, GSE80344, and GSE123066).Results: From the discovery datasets, 267 common upregulated genes and 374 common downregulated genes were identified. Among these common DEGs, there were 59 genes negatively associated with prognosis, while 21 genes exhibited positive correlations with prognosis. Eight genes (ABCC2, ARL2BP, DKK1, FUT1, LRFN4, PYGL, SMNDC1, and SNAI2) were selected to construct the risk score signature. In both the discovery and independent validation datasets, LUAD patients with the higher risk score had a poorer prognosis. The nomogram based on risk score showed good performance in prognosis prediction with a C-index of 0.77. The expression levels of ABCC2, ARL2BP, DKK1, LRFN4, PYGL, SMNDC1, and SNAI2 were positively related to the resistance of EGFR-TKI. However, the expression level of FUT1 was favorably correlated with EGFR-TKI responsiveness. The RF model worked wonderfully for distinguishing sensitive and resistant EGFR-TKI samples in the internal and external testing datasets, with predictive area under the curves (AUC) of 0.973 and 0.817, respectively.Conclusion: Our investigation revealed eight genes associated with EGFR-TKI resistance and provided models for EGFR-TKI resistance and prognosis prediction in LUAD patients.

Robot knee exoskeletons can not only help the rehabilitation training function of the elderly and disabled patients, but also enhance the performance of healthy people in normal walking and weigh-bearing walking by providing sufficient torques. In recent years, the exoskeletons of knee joints have been extensively explored. The review is to summarize the existing research results of mechanical structure design and actuation technologies, propose the future development trend, and promote the further development of the powered knee exoskeletons, related theories, and engineering applications. In this study, the mechanical structures of knee exoskeletons are first illustrated. Their mechanical structures are classified into two types: simple mechanical structures with one purely rotary DOF and biological geometry-based multi-DOF structures. Subsequently, the actuation design of wearable knee exoskeletons includes conventional driving actuators, pneumatic muscle actuators, variable stiffness actuators, and other actuators are compared and the driving compliance and the difficulty in the accurate control are analyzed. Furthermore, other crucial technologies such as motion intention recognition, control strategy and performance evaluation methods of most knee assistive devices are reviewed. Finally, the key technologies of structural design and actuation design in the research of knee exoskeletons are summarized and future research hotspots are proposed.

Mitogen-activated protein kinase (MAPK) pathways play a vital role in multiple plant processes, including growth, development, and stress signaling, but their involvement in response to Ralstonia solanacearum is poorly understood, particularly in pepper plants. Herein, CaMAPK7 was identified from the pepper genome and functionally analyzed. The accumulations of CaMAPK7 transcripts and promoter activities were both significantly induced in response to R. solanacearum strain FJC100301 infection, and exogenously applied phytohormones, including methyl jasmonate (MeJA), brassinolide (BR), salicylic acid (SA), and ethephon (ETN), were decreased by abscisic acid (ABA) treatment. Virus-induced gene silencing (VIGS) of CaMAPK7 significantly enhanced the susceptibility of pepper plants to infection by R. solanacearum and downregulated the defense-related marker genes, including CaDEF1, CaPO2, CaSAR82A, and CaWRKY40. In contrast, the ectopic overexpression of CaMAPK7 in transgenic tobacco enhanced resistance to R. solanacearum and upregulated the defense-associated marker genes, including NtHSR201, NtHSR203, NtPR4, PR1a/c, NtPR1b, NtCAT1, and NtACC. Furthermore, transient overexpression of CaMAPK7 in pepper leaves triggered intensive hypersensitive response (HR)-like cell death, H2O2 accumulation, and enriched CaWRKY40 at the promoters of its target genes and drove their transcript accumulations, including CaDEF1, CaPO2, and CaSAR82A. Taken together, these data indicate that R. solanacearum infection induced the expression of CaMAPK7, which indirectly modifies the binding of CaWRKY40 to its downstream targets, including CaDEF1, CaPO2, and CaSAR82A, ultimately leading to the activation of pepper immunity against R. solanacearum. The protein that responds to CaMAPK7 in pepper plants should be isolated in the future to build a signaling bridge between CaMAPK7 and CaWRKY40.

In order to realize precise position tracking of a novel circular hydraulic actuator with parameter uncertainties and bounded disturbances, an adaptive sliding mode controller (ASMC) that incorporates a fuzzy tuning technique is proposed in this paper. The mechanical structure and basic principle of the actuator are first introduced, and the mathematical model of its corresponding valve-controlled hydraulic servo system is constructed. Based on Lyapunov stability theory, online parameter estimation and sliding mode controller design are effectively integrated to approximate the equivalent control of sliding mode. To mitigate the undesired chattering phenomenon and further improve system performance, a fuzzy tuning scheme is employed to regulate the proportional gain of the approaching control term. In addition, a real-time control platform is established, and the controllers parameter identification and position tracking are verified by preliminary experiments. Finally, the traditional PID controller and the exponent approaching sliding controller are also conduced to further evaluate the control performances of the designed controller, and the comparative results demonstrate that the proposed control scheme has better control performance in reducing errors for trajectory tracking.

Abstract Background Sarcoidosis is a systemic inflammatory multi-organ disease almost always affecting the lungs. The etiology remains unknown, but the hallmark of sarcoidosis is formation of non-caseating epithelioid cells granulomas in involved organs. In Scandinavia, > 30% of sarcoidosis patients have Löfgren’s syndrome (LS), an acute disease onset mostly indicating a favorable prognosis. The impact of dysregulation of lipid mediators, which has been investigated in other inflammatory disorders, is still unknown. Methods Using three different liquid chromatography coupled to tandem mass spectrometry targeted platforms (LC-MS/MS), we quantified a broad suite of lipid mediators including eicosanoids, sphingolipids and endocannabinoids in bronchoalveolar lavage (BAL) fluid from pulmonary sarcoidosis patients (n = 41) and healthy controls (n = 16). Results A total of 47 lipid mediators were consistently detected in BAL fluid of patients and controls. After false discovery rate adjustment, two products of the soluble epoxide hydrolase (sEH) enzyme, 11,12-dihydroxyeicosa-5,8,14-trienoic acid (11,12-DiHETrE, p = 4.4E-5, q = 1.2E-3, median fold change = 6.0) and its regioisomer 14,15-dihydroxyeicosa-5,8,11-trienoic acid (14,15-DiHETrE, p = 3.6E-3, q = 3.2E-2, median fold change = 1.8) increased in patients with sarcoidosis. Additional shifts were observed in sphingolipid metabolism, with a significant increase in palmitic acid-derived sphingomyelin (SM16:0, p = 1.3E-3, q = 1.7E-2, median fold change = 1.3). No associations were found between these 3 lipid mediators and LS, whereas levels of SM 16:0 and 11,12-DiHETrE associated with radiological stage (p

Abstract Background Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). Methods To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort. Multivariate statistical modeling, multivariate correlations with clinical data, and pathway enrichment analysis were performed. Results Smoking exerted a significant impact on the BAL cell proteome, with more than 500 proteins representing 15 molecular pathways altered due to smoking. The majority of these alterations occurred in a gender-independent manner. The phagosomal- and leukocyte trans endothelial migration (LTM) pathways significantly correlated with FEV1/FVC as well as the percentage of CD8+ T-cells and CD8+CD69+ T-cells in smokers. The correlations to clinical parameters in healthy never-smokers were minor. Conclusion The significant correlations of proteins in the phagosome- and LTM pathways with activated cytotoxic T-cells (CD69+) and the level of airway obstruction (FEV1/FVC) in smokers, both hallmarks of COPD, suggests that these two pathways may play a role in the molecular events preceding the development of COPD in susceptible smokers. Both pathways were found to be further dysregulated in COPD patients from the same cohort, thereby providing further support to this hypothesis. Given that not all smokers develop COPD in spite of decades of smoking, it is also plausible that some of the molecular pathways associated with response to smoking exert protective mechanisms to smoking-related pathologies in resilient individuals. Trial registration ClinicalTrials.gov identifier NCT02627872; Retrospectively registered on December 9, 2015.

Abstract Background Smoking is the main risk factor for chronic obstructive pulmonary disease (COPD). Women with COPD who smoke experienced a higher risk of hospitalization and worse decline of lung function. Yet the mechanisms of these gender-related differences in clinical presentations in COPD remain unknown. The aim of our study is to identify proteins and molecular pathways associated with COPD pathogenesis, with emphasis on elucidating molecular gender difference. Method We employed shotgun isobaric tags for relative and absolute quantitation (iTRAQ) proteome analyses of bronchoalveolar lavage (BAL) cells from smokers with normal lung function (n = 25) and early stage COPD patients (n = 18). Multivariate modeling, pathway enrichment analysis, and correlation with clinical characteristics were performed to identify specific proteins and pathways of interest. Results More pronounced alterations both at the protein- and pathway- levels were observed in female COPD patients, involving dysregulation of the FcγR-mediated phagocytosis-lysosomal axis and increase in oxidative stress. Alterations in pathways of the phagocytosis-lysosomal axis associated with a female-dominated COPD phenotype correlated well with specific clinical features: FcγR-mediated phagocytosis correlated with FEV1/FVC, the lysosomal pathway correlated with CT

MOTIVATION: DNA microarray analysis is characterized by obtaining a large number of gene variables from a small number of observations. Cluster analysis is widely used to analyze DNA microarray data to make classification and diagnosis of disease. Because there are so many irrelevant and insignificant genes in a dataset, a feature selection approach must be employed in data analysis. The performance of cluster analysis of this high-throughput data depends on whether the feature selection approach chooses the most relevant genes associated with disease classes. RESULTS: Here we proposed a new method using multiple Orthogonal Partial Least Squares-Discriminant Analysis (mOPLS-DA) models and S-plots to select the most relevant genes to conduct three-class disease classification and prediction. We tested our method using Golub's leukemia microarray data. For three classes with subtypes, we proposed hierarchical orthogonal partial least squares-discriminant analysis (OPLS-DA) models and S-plots to select features for two main classes and their subtypes. For three classes in parallel, we employed three OPLS-DA models and S-plots to choose marker genes for each class. The power of feature selection to classify and predict three-class disease was evaluated using cluster analysis. Further, the general performance of our method was tested using four public datasets and compared with those of four other feature selection methods. The results revealed that our method effectively selected the most relevant features for disease classification and prediction, and its performance was better than that of the other methods.

Fructus Xanthii (FX) has been widely used as a traditional herbal medicine for rhinitis, headache, cold, etc. Modern pharmacological studies revealed that FX possesses anti-inflammatory, anti-oxidative, and anti-hyperglycemic properties. The present study was designed to investigate the effects of FX on glucose and insulin tolerance, and hepatic lipid metabolism in rats fed on high-fat diet (HFD). Hepatic steatosis was induced by HFD feeding. Aqueous extraction fractions of FX or vehicle were orally administered by gavage for 6 weeks. Body weight and blood glucose were monitored. Glucose and insulin tolerance test were performed. Liver morphology was visualized by hematoxylin and eosin, and oil red O staining. Expression of liver lipogenic and lipolytic genes was measured by real-time PCR. We showed here that FX improved glucose tolerance and insulin sensitivity in HFD rats. FX significantly decreased the expression of lipogenic genes and increased the expression of lipolytic genes, ameliorated lipid accumulation and decreased the total liver triglyceride (TG) content, and thus attenuated HFD-induced hepatic steatosis. In conclusion, FX improves glucose tolerance and insulin sensitivity, decreases lipogenesis and increases lipid oxidation in the liver of HFD rats, implying a potential application in the treatment of non-alcoholic fatty liver disease.

Technological pedagogical content knowledge (TPACK) is pivotal for enhancing both learning and teaching processes, and it has garnered a share of scholarly attention in recent years, although few quantitative studies have been found on English as a foreign language (EFL) teachers of higher education in Guizhou, China. This study provides a comprehensive quantitative analysis of the integration of TPACK among EFL teachers in higher education in Guizhou province, China. A detailed EFL-TPACK framework coding protocol was employed to analyze the teaching videos of six EFL teachers with varying proficiency levels. These six teachers were selected from a survey that investigated 286 EFL teachers in higher education in Guizhou Province. The analysis categorized the teaching behaviors observed in the videos into seven distinct factors, meticulously quantifying the integration of technological (TK), pedagogical (PK), and content knowledge (CK), revealing significant disparities between the teachers. High-level teachers excelled in TPACK integration more than medium-level and low-level teachers, especially older ones. This study not only enables a deeper understanding of the practical application of TPACK in classroom settings but also emphasizes the dynamic nature of EFL-TPACK frameworks. The findings highlight the urgent need for targeted professional development strategies, including comprehensive technological training, a balanced emphasis on pedagogical and content knowledge, and the establishment of collaborative learning environments. These strategies are essential for enhancing TPACK integration skills across proficiency levels. [ABSTRACT FROM AUTHOR]

The study aims to unveil how translators deal with confrontational responses through their visibility in translating the diplomatic discourse of China’s diplomatic press conferences. Distinct from past theoretical frameworks, this study is grounded in the impoliteness strategies model (Bousfield, 2008) and the concept of translator’s visibility. The corpus focuses on the English-translated responses using the “challenge” strategy, delivered by the spokesperson Hua Chunying throughout 2020. Findings show that the translator’s visibility is mainly presented at the syntactical and lexical levels, and the discursive level is hardly found. The translation strategy of modulation is used most in syntax and reduction most in lexicon. Additionally, the translator’s visibility by using translation strategies can mediate the degree of confrontation. In maintaining the confrontational tone, the main strategies involve modulation in syntax and reduction in lexicon. Linguistic compression and reduction are employed more commonly in weakening the confrontational implication in lexicon, and reduction in syntax. Linguistic amplification is observed more frequently in the lexicon and modulation is more often used in syntax in strengthening the confrontation. This research sheds light on the dynamic interplay between impoliteness strategies and the translator’s visibility, contributing to a deeper understanding of the translator’s engagement in institutional discourse. [ABSTRACT FROM AUTHOR]

Technological Pedagogical Content Knowledge illustrates the interconnected nature of knowledge required to effectively integrate technology in enhancing student learning. While numerous review studies on Technological Pedagogical Content Knowledge exist, those that employ a bibliometric analysis are limited. In this comprehensive bibliometric review, we analyzed 209 Technological Pedagogical Content Knowledge studies focusing on in-service teachers in higher education, sourced from the Scopus database from 2012 through April 2023. The significance of this study lies in its effort to map the research landscape of Technological Pedagogical Content Knowledge by addressing the main question: What are the primary trends, key contributors, thematic areas, and keyword co-occurrence networks in Technological Pedagogical Content Knowledge research on in-service teachers in higher education? We adopted PRISMA guidelines into the standard bibliometric workflow and used VOSviewer as the visualization tool. Publication trends, major contributors, research areas, and keyword co-occurrence networks were identified. The analysis indicated an increasing trend in the number of publications on in-service teachers' Technological Pedagogical Content Knowledge in higher education, with the highest number recorded in 2022. We also identified representative articles, institutions, the most contributing journals, and funding agencies, most from developed countries/regions. The analysis highlights prolific researchers, key research areas, and keyword co-occurrence networks. Overall, this analysis has provided a comprehensive overview of the current research in higher education. Based on these findings, we recommend that future research focus on Technological Pedagogical Content Knowledge training modules and AI-based Technological Pedagogical Content Knowledge frameworks for teachers in higher education. [ABSTRACT FROM AUTHOR]

The Tianhu East turquoise deposit is located 180 km southeast of the city of Hami (also known as Kumul) in the Xinjiang Uyghur Autonomous Region of China. This deposit has been mined since as early as 1279-379 BCE. New mining activity took place around 2015, and some of the production emerged briefly on the Chinese market. Mining was subsequently prohibited because of the location's protected status as an archaeological site. The geology of Tianhu East turquoise as well as updated reports and field exploration are systematically summarized in this study. The turquoise usually occurs as blue and bluish green veins in the fissures and shear zones of quartzite in the Cambrian Pochengshan Formation. It is characterized by high lithium, vanadium, chromium, strontium, and gallium concentrations and low barium content. Multiple associated minerals (e.g., quartz, apatite, goethite, hematite, jarosite, bonattite, muscovite, atacamite, svanbergite, and gypsum) were identified using Raman spectroscopy and electron probe microanalysis. This study contains the first report of atacamite in Chinese turquoise. Petrography, mineralogy, and geochemistry of the bedrock as well as the crystallization sequences of the associated minerals are highlighted. Based on the results, the authors propose a supergene weathering origin and elemental derivation for Tianhu East turquoise. Black shale was likely the main original source of the aluminum, phosphorus, and copper necessary for formation, while quartzite provided enough space for precipitation. [ABSTRACT FROM AUTHOR]

Extended-spectrum beta-lactamase-producing Gram-negative bacteria are common in the community and hospitals. To monitor ESBLs mediated by the CTX-M genotype, we collected clinical ESBL pathogenic strains from a hospital in central China and observed a strain of Escherichia coli, namely Ec15103 carrying blaCTX-M-14, blaCTX-M-64 and blaTEM-1, isolated from the blood of a 7-day-old infant in 2015. Strain Ec15103 contains two drug resistance plasmids: pEc15103A, an IncFI-type plasmid that cannot be conjugatively transferred and carries the drug resistance genes blaTEM-1, aacC2, aadA5, sull, mph(A), sul2, strAB, and tetA(A); and pEc15103B, an IncK2/Z-type plasmid that carries the conjugation transfer gene and blaCTX-M-14. In addition, blaCTX-M-64 is located on the chromosome of Ec15103, and it is the first report of pathogen with blaCTX-M-64 located on its chromosome (the search terms used "blaCTX-M-64" and "chromosome"). blaCTX-M-14 and blaCTX-M-64 are carried by ISEcpl-mediated transposon Tn6503a and Tn6502, respectively. The conjugation transfer ability of pEc15103B was significantly inhibited by zidovudine (AZT) and linoleic acid (LA) and that expression of blaCTX-M-14, blaCTX-M-64 and blaTEM-1 at the mRNA level did not change based on the concentration of cefotaxime or ampicillin. Co-occurrence of blaCTX-M-14 and blaCTX-M-64 in a single isolate will enhance the drug resistance of bacteria, and the presence of blaCTX-M-64 in the chromosome may make the resistance more maintain. This fact will facilitate its dissemination and persistence under different antimicrobial selection pressures. It is essential to prevent these strains from further spreading in a hospital environment. [ABSTRACT FROM AUTHOR]