Search

Nasopharyngeal carcinoma (NPC) is a neoplasm related to inflammation; the expression of cytokines, such as CCL3, CCL4, CCL20, IL-1α, IL-1β, IL-6, IL-8, and IL-10, among others, is presumed to be associated with NPC occurrence and development. Therefore, the circulating levels of these cytokines may be potential biomarkers for assessing tumor aggressiveness, exploring cellular interactions, and monitoring tumor therapeutic responses. Numerous scholars have comprehensively explored the putative mechanisms through which these inflammatory factors affect NPC progression and therapeutic responses. Moreover, investigations have focused on elucidating the correlation between the systemic levels of these cytokines and the incidence and prognosis of NPC. This comprehensive review aims to delineate the advancements in research concerning the relationship between inflammatory factors and NPC while considering their prospective roles as novel prognostic and predictive biomarkers in the context of NPC.

During corn harvesting operations, machine–straw–soil contact often occurs, but there is a lack of research related to the role of straw–soil contact. Therefore, in this study, a composite contact model of corn straw‒soil particles was established based on the discrete element method (DEM). First, the discrete element Hertz‒Mindlin method with bonding particle contact was used to establish a numerical model of the double-bonded bimodal distribution of corn straw, and bonding particle models of the outer skin‒outer skin, inner pulp‒inner pulp, and outer skin‒inner pulp were developed. The nonhomogeneous and deformable material properties were accurately expressed. The straw compression test combined with simulation calibration was used to determine some of the bonding contact parameters by means of the PB (Plackett–Burman) test, the steepest ascent test, and the BB (Box–Behnken) test. Additionally, Additionally, the Hertz-Mindlin with JKR (Johnson-Kendall-Roberts) + bonding key model was used to establish the numerical model of the soil particles, which was used to describe the irregularity and adhesion properties of the soil particles. The geometric model of the soil particles was established using the multisphere filling method. Finally, a composite contact model of corn straw‒soil particles was established, the contact parameters between straw and soil were calibrated via collision tests, inclined tests and inclined rolling tests, and the established composite contact model was further verified through direct shear tests between straw and soil. A theoretical foundation for the optimal design of equipment linked to maize harvesting is provided by this work.

To improve the crushing efficiency and crushing pass rate of high-moisture corn ears (HMCEs), a multi-stage crushing scheme is proposed in this paper. A two-stage crushing device for HMCEs is designed, and the ear crushing process is analyzed. Firstly, a simulation model for HMCEs was established in EDEM software (2018), and the accuracy of the model was verified by the shear test. Subsequently, single-factor simulation experiments were conducted, with the crushing rate serving as the evaluation index. The optimal working parameter ranges for the HMCE device were identified as a primary crushing roller speed of 1200–1600 revolutions per minute (r/min), a secondary crushing roller clearance of 1.5–2.5 mm, and a secondary crushing roller speed of 2750–3750 r/min. A Box–Behnken experiment was conducted to establish a multiple regression equation. With the objective of maximizing the qualified crushing pass rate, the optimal combination of parameters was revealed: a primary crushing roller speed of 1500 r/min, a secondary crushing roller clearance of 2.5 mm, and a secondary crushing roller speed of 3280 r/min. The pass rate of corn cob crushing in the simulation test was 98.2%. The physical tests, using the optimized parameter combination, yielded a qualified crushing rate of 97.5%, which deviates by 0.7% from the simulation results, satisfying the requirement of a qualified crushing rate exceeding 95%. The experimental outcomes validate the rationality of the proposed crushing scheme and the accuracy of the model, providing a theoretical foundation for subsequent research endeavors.

Paddy field leveling is an essential step before rice transplanting. During the operation of a paddy field grader, a common issue is the wrapping of rice straw around the blades, resulting in a low rice straw burial rate. This study focused on analyzing the operating parameters of a disc spring–tooth-combined paddy field grader. A soil–straw mechanism simulation model was created using EDEM 2021 software to simulate the field operation status. Firstly, the single-factor test was carried out, with the working speed, the working depth of the disc cutter roller, and the rotation speed of the cutter roller as the factors and the straw-buried rate (SBR) and the machine forward resistance (MFR) as the test indexes, and the parameter range was optimized. The parameters were optimized by the response surface method (RSM) and machine learning algorithms. The results indicated that the genetic algorithm–back propagation (GA-BP) neural network outperformed other optimization models in terms of prediction accuracy and stability. By utilizing the GA-BP regression model and RSM model for regression fitting, two sets of optimal parameter combinations were obtained. Verification experiments were carried out using two sets of parameter combinations. Taking the average of the experimental results, the simulation results showed that the straw burial rate was 93.47% and the forward resistance was 6487 N for the parameter combinations of RSM, and the straw burial rate was 94.86% and the forward resistance was 6352 N for the parameter combinations of GA-BP; the field experiments showed that the straw burial rate was 92.86% and the forward resistance was 6518 N for the parameter combinations of RSM, and the straw burial rate was 95.17% and the forward resistance was 6249 N for the parameter combinations of GA-BP. The results demonstrated that the GA-BP prediction model exhibited better predictive capabilities compared to the traditional RSM, providing more accurate predictions of the paddy field grader’s field operation performance.

Blueberries are one of the more economically rewarding fruits for fruit growers. Identifying blueberry fruit at different stages of maturity is economically important and can aid fruit growers in planning pesticide applications, estimating yields, and efficiently conducting harvesting operations, among other benefits. Visual methods for identifying the different ripening stages of fruits are increasingly receiving widespread attention. However, due to the complex natural environment and the serious shading caused by the growth characteristics of blueberries, the accuracy and efficiency of blueberry detection are reduced to varying degrees. To address the above problems, in the study presented herein, we constructed an improved YOLOv9c detection model to accurately detect and identify blueberry fruits at different ripening stages. The size of the network was reduced by introducing the SCConv convolution module, and the detection accuracy of the network in complex and occluded environments was improved by introducing the SE attention module and the MDPIoU loss function. Compared to the original model, the mAP0.5 and mAP0.5:0.95 of the improved YOLOv9c network improved by 0.7% and 0.8%, respectively. The model size was reduced by 3.42 MB, the number of model parameters was reduced by 1.847 M, and the detection time of a single image was reduced by 4.5 ms. The overall performance of the detection model was effectively improved to provide a valuable reference for accurate detection and localization techniques for agricultural picking robots.

In situ electric heating is an important method used to increase production capacity during the extraction of natural gas hydrates. This work numerically evaluated the sensitivity of different heating parameters on gas production behavior with a vertical well depressurization in the Shenhu Sea area hydrate reservoir, the production pressure difference of 4 MPa, and continuous depressurization for 1080 days. The results showed that the in situ electric heating method can effectively enhance production capability by promoting hydrate dissociation and eliminating secondary hydrates. Compared with scenarios without heating, implementing whole wellbore heating (100 W/m) increases cumulative gas production (Vg) by 118.56%. When intermittent heating is applied to the local wellbore (15 m) located in the three-phase layer (with an interval of 30 days) and stops heating in advance at 480 days, there is no significant difference in Vg compared to the whole wellbore heating case, and the cumulative heat input is only 4.76%. We recommend considering intermittent heating of the local wellbore and stopping heating in advance during vertical well depressurization as this approach significantly reduces heating energy consumption while simultaneously improving production capacity.

Stepwise depressurization is an important depressurization strategy in the development of natural gas hydrates. This work numerically analyzes the effects of different depressurization gradients and constant pressure durations on gas and water production during stepwise depressurization extraction with a vertical well in the Shenhu Sea area hydrate reservoir of the South China Sea. The results indicate that stepwise depressurization can reduce water production and raise the gas-to-water ratio in the early stages of production while ensuring cumulative gas output. When the vertical well is deployed at the model’s center with a completion length of 70 m and a constant pressure duration of 10 days, a depressurization gradient of 0.5 MPa, stepwise depressurization by 6 MPa, and continuous production for one year is achieved. Compared with direct depressurization, its cumulative gas production is 2.966 × 106 ST m3, which only decreases by 2.94%. However, it maintains a higher gas-to-water ratio in the early stages of production. Considering factors such as engineering operability, cumulative gas output, and gas-to-water ratio, it is recommended to use a small pressure gradient and a medium constant pressure stabilization time for stepwise depressurization Stepwise depressurization can maintain a high gas-to-water ratio while ensuring gas production and reducing water production can alleviate sand production problems and improve economic efficiency. The understanding gained from this work has reference value for the development of similar hydrate reservoirs worldwide.

Improving the production capacity of natural gas hydrates (NGHs) is crucial for their commercial development. Based on the data of the first on-site testing production of NGHs in the Shenhu Sea area, numerical methods were used to analyze the production behavior of radial lateral well (RLW) and horizontal snake well (HSW) with different completion lengths when they deployed at different layers of the Class-1 type hydrate reservoir (with a fixed pressure difference of 6 MPa and continuous production for 360 days). The results indicate that compared with the single vertical well production, RLW and HSW can effectively increase production capacity by enlarging drainage area and the productivity is directly proportional to the total completion length. The RLW and HSW deployed at the three-phase layer (TPL) have optimal mining performance within a 360-day production period. Different to the previous research findings, during a short-term production period of 360 days, regardless of the deployment layer, the overall production capacity of HSW is better than RLW’s. The total gas production of HSW-2 circles well type is about four times that of a single vertical well, reaching 1.554 × 107 ST m3. Moreover, the HSW-1 lateral well type stands out with an average Qg of 3.63 × 104 ST m3/d and a specific production index J of 16.93; it has the highest J-index among all well types, which means the best mining efficiency. It is recommended to choose the HSW-1 circle well type, if the coiled tubing drilling technique is used for on-site testing production of NGHs in the future. The research results provide insights into the potential applications of RLW and HSW in this sea area.

The complex pathogenesis of preeclampsia (PE), a significant contributor to maternal and neonatal mortality globally, is poorly understood despite substantial research. This review explores the involvement of exosomal microRNAs (exomiRs) in PE, focusing on their impact on the protein kinase B (AKT)/hypoxia-inducible factor 1-α (HIF1α)/vascular endothelial growth factor (VEGF) signaling pathway as well as endothelial cell proliferation and migration. Specifically, this article amalgamates existing evidence to reveal the pivotal role of exomiRs in regulating mesenchymal stem cell and trophoblast function, placental angiogenesis, the renin–angiotensin system, and nitric oxide production, which may contribute to PE etiology. This review emphasizes the limited knowledge regarding the role of exomiRs in PE while underscoring the potential of exomiRs as non-invasive biomarkers for PE diagnosis, prediction, and treatment. Further, it provides valuable insights into the mechanisms of PE, highlighting exomiRs as key players with clinical implications, warranting further exploration to enhance the current understanding and the development of novel therapeutic interventions.

We propose a concept of a high-order mode (HOM) pass filter based on the inverse-designed mode-routing, which enables an ultra-compact footprint and broad bandwidth. To validate the concept, we experimentally demonstrate two types of HOM pass filters using the direct-binary search topology optimization algorithm. In the first HOM pass filter, the mode-routing region is constructed using an inverse-designed adiabatic coupler, while the second filter utilizes a tapered asymmetric directional coupler. The subwavelength units based on the functional regions of both filters have an ultra-compact footprint of 4 µm × 800 nm. The experimental results indicate that the insertion losses of two HOM-pass filters are 3.13 and 1.94 dB, respectively, and their mode cross-talks are −15.8 and −27.36 dB at the center wavelength of 1550 nm. Both HOM pass filters exhibit high performance over a broad bandwidth of 130 nm.

Soil nutrients are essential for plant growth, and it is crucial to accurately detect their levels. However, current methods for detecting soil nutrients still have low accuracy and high costs. In this study, we propose a multi-source fusion feature approach that combines multispectral image technology with electronic nose gas response technology to achieve rapid, high-precision, and cost-effective detection of soil nutrients, including soil organic matter (SOM), total nitrogen (TN), available potassium (AK), and available phosphorus (AP). To begin, a multispectral camera was used to collect spectral images and extract seven index features. Additionally, an electronic nose was used to collect soil pyrolysis gases to obtain the response curve and extract seven response features. These two sets of features were effectively fused to form a 106 × 98 fusion feature space. Secondly, principal component analysis (PCA) and Pearson correlation coefficient (PCC) algorithms were used to optimize and reduce the dimensionality of the fused feature space. Finally, a predictive model of the relationship between the feature space and the nutrient content of the soil samples was established using the random forest (RF) and partial least squares regression (PLSR) algorithms. The predictive performance of the model was used to evaluate the accuracy of soil nutrient detection. The results showed that the PLSR modeling of the optimized feature space of PCA achieved high accuracy in predicting the levels of main soil nutrients, with R2 values for SOM, TN, AK, and AP of 0.96, 0.95, 0.84, and 0.73, and the RMSE values of 0.56, 0.07, 3.21, and 3.70, respectively. Compared to using only electronic nose gas response technology, the soil nutrient detection with multi-source data features method in this study not only improved the accuracy for SOM and TN but also for metal elements AK and AP in soil. The spectral index features proposed in this study were able to compensate for the limitations of the electronic nose response features, and modeling with the fusion feature space resulted in an accurate prediction of SOM, TN, AK, and AP levels.

This paper examined Chinese undergraduate students' perceptions of using videoconferencing in learning English as a foreign language (EFL) during the COVID-19 pandemic. The data were collected among 348 Chinese university students who attended sixteen-week learning of Integrated English Course through Tencent Meeting, the most widely used videoconferencing application in China. We adopted voluntary response sampling method in this cross-sectional study. Students completed an online survey on “Wenjuanxing”, China's biggest online questionnaire distribution platform. A structural equation model (SEM) was constructed and analyses revealed that perceived ease of use and perceived usefulness were significant predictors of students' satisfaction and participation intention. Students' computer self-efficacy had a positive effect on their perceived ease of use, perceived usefulness, and participation intention while their frequency of using videoconferencing did not influence these variables. This study contributes to the existing literature on the acceptance of videoconferencing in the context of EFL learning and offers insights for developing up-to-date videoconferencing teaching strategies.

Valleytronic devices employ the electronic valley degree of freedom to realize potential low-power electronic applications. Here, the authors utilize a topological semiconductor to engineer valley polarization transistors with long lifetimes and demonstrate low-power neuromorphic functionality at room temperature.

Enhancing the production capacity of natural gas hydrates (NGHs) is critical for its commercial development. Complex structure wells may efficiently increase drainage areas while enhancing exploitation efficiency. Based on the field data of China’s first offshore NGH test production, the numerical method was used to analyze the production performance of different complex structure well types by continuous depressurization production for 360 days under the preconditions of fixed effective completion length of 300 m and a pressure difference of 6 MPa. Results indicated that the complex structure well types deployed at the three-phase layer demonstrated superior production performance within 240 days of production; the DLW2 and HW2 well types stood out, with an average gas production rate Qg reaching 43,333 m3/d and a specific production index J of 24.1. After 360 days of production, benefiting from multi-layer combined production, the Cluster vertical well deployed at the multi-layer had the best production performance, with an average Qg of 34,444 m3/d and a J-index of 19.1. The research results provided insights into the complex structure well-type selection strategy for NGH depressurization in this sea area.

During precision sowing, the contact process between the soil and seeds cannot be ignored. The constitutive relationship of soil is relatively complex, with characteristics such as high nonlinearity, while the contact mechanism between the soil and seeds is unclear. To better understand the contact between seeds and soil, it is necessary to establish a reasonable contact model. Ellipsoidal seeds, such as soybean, red bean, and kidney bean seeds, were adopted as research objects. In this paper, we used the discrete element method to establish an ellipsoidal seed–soil contact model. The JKR + bonding model was adopted for describing the adhesion between soil particles, and the Hertz–Mindlin new restitution (HMNS) model was used for ellipsoidal seed particles to eliminate the multiple contact point issue when modeling with the multi-sphere filling method. Moreover, both simulations and experiments were conducted to calibrate the interaction parameters between soil and seeds. The path of steepest ascent test and Box‒Behnken design (BBD) tests were also used, as well as direct shear tests. Thus, certain soil parameter values were obtained, namely the JKR surface energy was 4.436 J/m2, the normal stiffness per unit area was 2.86 × 106 N/m3, the shear stiffness per unit area was 5.54 × 105 N/m3, the critical normal stress was 1833 Pa, and the critical shear stress was 3332 Pa. In addition, the simulation parameters for ellipsoidal seeds were obtained from previous works. Moreover, to obtain more accurate ellipsoidal seed–soil interaction parameters, collision tests, static friction tests, and rolling friction tests were adopted. A single-factor test was used to calibrate the ellipsoidal seed–soil interaction parameters. The calibration results were as follows: the collision restitution coefficients of ellipsoidal seeds with soil were all 0.25. The static friction coefficient of soybeans with soil was 0.6, that of red beans with soil was 0.65, and that of kidney beans with soil was 0.5. The rolling friction coefficient of soybeans with soil was 0.1, that of red beans with soil was 0.14, and that of kidney beans with soil was 0.14. Finally, the rationality of parameter selection was verified through piling tests between ellipsoidal seeds and soil. The relative error of the angle of repose of soybean/soil was 2.99%, that of red bean/soil was 0.60%, and that of kidney bean/soil was 0.55%. Thus, the feasibility and rationality of the contact models between the ellipsoidal seeds and soil established in this paper, as well as the parameter selection, were verified.

Early blight and late blight are two of the most prevalent and severe diseases affecting potato crops. Efficient and accurate grading of their severity is crucial for effective disease management. However, existing grading methods are limited to assessing the severity of each disease independently, often resulting in low recognition accuracy and slow grading processes. To address these challenges, this study proposes a novel two-stage approach for the rapid severity grading of both early blight and late blight in potato plants. In this research, two lightweight models were developed: Coformer and SegCoformer. In the initial stage, Coformer efficiently categorizes potato leaves into three classes: those afflicted by early blight, those afflicted by late blight, and healthy leaves. In the subsequent stage, SegCoformer accurately segments leaves, lesions, and backgrounds within the images obtained from the first stage. Furthermore, it assigns severity labels to the identified leaf lesions. To validate the accuracy and processing speed of the proposed methods, we conduct experimental comparisons. The experimental results indicate that Coformer achieves a classification accuracy as high as 97.86%, while SegCoformer achieves an mIoU of 88.50% for semantic segmentation. The combined accuracy of this method reaches 84%, outperforming the Sit + Unet_V accuracy by 1%. Notably, this approach achieves heightened accuracy while maintaining a faster processing speed, completing image processing in just 258.26 ms. This research methodology effectively enhances agricultural production efficiency.

Gas production efficiency is a key indicator in the commercial development of natural gas hydrates (NGHs). Based on the data from the first natural gas hydrate field test production in the Shenhu Sea area of China, the gas production capability of Class 1-type hydrate reservoirs was numerically evaluated by vertical well depressurization with different deployment schemes for radial laterals. The results showed that the radial laterals can effectively improve production efficiency and that the radial laterals deployed at the three-phase layer (TPL) have the best production performance. Compared with the single vertical well production, the completion length of the radial laterals is 150 m with a radius of 0.05 m, and the production pressure difference is set to 6 MPa. The cumulative gas production Vg reaches up to 594.10 × 104 ST m3, increased by about 208.53% after 360 days of production, which provides a reference for the development of natural gas hydrates with radial jet drilling (RJD) technology.

Soil classification stands as a pivotal aspect in the domain of agricultural practices and environmental research, wielding substantial influence over decisions related to real-time soil management and precision agriculture. Nevertheless, traditional methods of assessing soil conditions, primarily grounded in labor-intensive chemical analyses, confront formidable challenges marked by substantial resource demands and spatial coverage limitations. This study introduced a machine olfaction methodology crafted to emulate the capabilities of the human olfactory system, providing a cost-effective alternative. In the initial phase, volatile gases produced during soil pyrolysis were propelled into a sensor array comprising 10 distinct gas sensors to monitor changes in gas concentration. Following the transmission of response data, nine eigenvalues were derived from the response curve of each sensor. Given the disparate sample counts for the two distinct classification criteria, this computational procedure yields two distinct eigenspaces, characterized by dimensions of 112 or 114 soil samples, each multiplied by 10 sensors and nine eigenvalues. The determination of the optimal feature space was guided by the “overall feature information” derived from mutual information. Ultimately, the inclusion of random forest (RF), multi-layer perceptron (MLP), and multi-layer perceptron combined with random forest (MLP-RF) models was employed to classify soils under four treatments (tillage and straw management) and three fertility grades. The assessment of model performance involved metrics such as overall accuracy (OA) and the Kappa coefficient. The findings revealed that the optimal classification model, MLP-RF, achieved impeccable performance with an OA of 100.00% in classifying soils under both criteria, which showed almost perfect agreement with the actual results. The approach proposed in this study provided near-real-time data on the condition of the soil and opened up new possibilities for advancing precision agriculture management.

Quantitative metal grade inversion based on hyperspectral data is an effective approach to achieve the real-time in situ determination of ore body grades and has the advantages of low cost compared with traditional chemical analysis methods. However, the redundant nature of hyperspectral data and the parameter-limiting nature of machine learning algorithms reduce the modeling accuracy and precision, resulting in severe limitations on the application of hyperspectral techniques for the grade inversion of Deerni copper ore bodies. In this paper, we first obtained visible-NIR hyperspectral data for 190 ore samples using a spectrometer and determined the copper content of the sample set using chemical analysis; then, we processed the raw hyperspectral data using three dimensionality reduction algorithms and optimized a BP neural network based on an evolutionary algorithm. Finally, a Deerni copper grade inversion model was established using the hyperspectral data before and after dimensionality reduction, and the inversion accuracy and precision was compared and analyzed with that obtained by the BP neural network, the random forest and the variable hidden layer nodes models. The combination of the LLE dimensionality reduction algorithm and the optimized BP neural network algorithm achieves the highest modeling precision, with an R2 of 0.950.

Abstract Background As a rare mitochondrial disease, combined oxidative phosphorylation deficiency 14 (COXPD14) is caused by biallelic variants in the phenylalanyl-tRNA synthetase 2, mitochondrial gene (FARS2) with clinical features of developmental delay, an elevated lactate level, early-onset encephalopathy, liver failure, and hypotonia. The objectives of this study were to analyze the clinical and molecular features of two Chinese siblings affected with COXPD14, and to review relevant literature. Methods Mutation screening was performed by whole exome sequencing (WES) in combination with Sanger sequencing validation to identify the disease-causing variants of the two patients. Results The two siblings presented with severe clinical features and both progressed aggressively and failed to survive after treatment abandonment. We identified two compound heterozygous FARS2 variants c.925G>A p.Gly309Ser and c.943G>C p.Gly315Arg in this proband, which were inherited from the unaffected father and mother, respectively. In addition, Sanger sequencing confirmed that the elder affected sister carried the same compound heterozygous variants. The c.925G>A p.Gly309Ser variant is known and commonly reported in COXPD14 patients, while c.943G>C p.Gly315Arg is a novel one. Neither of the variants was found in 100 Chinese healthy controls. Both variants were classified as “deleterious” and were located in the highly conserved regions of the protein. The above results suggested that the two variants were likely causative in this COXPD14-affected pedigree. Conclusions Our study expands the mutation spectrum of FARS2 and highlights the importance of genetic testing in the diagnosis of diseases with a wide variety of phenotypes, especially in the differential diagnosis of diseases.

Early warning information dissemination capacity is insufficient in timeliness, accuracy and wide coverage compared with the national emergency management system requirements.The dissemination demands were analyzed from early warning information receivers, emergency degree, receiving area and other factors.The early warning information transmission channels were extended to including cell broadcasting, Tiantong satellite and other communication networks.Then these channels were compared in the aspects of timeliness, accuracy, coverage and cost.For emergency responders and the public, according to typical scenarios, the matching scheme of early warning information communication channel selection was proposed, which laid a foundation for the optimization of communication channel.

To apply the discrete element method (DEM) to simulate the interaction process between soda saline–alkali soil and subsoiling component in Northeast China, establishing the soda saline–alkali soil particle model and selecting more accurate simulation parameters are important. In this paper, we studied the soda saline–alkali soil of the Songnen Plain in China. First, we studied the geometric shape of soda saline–alkali soil particles and proposed a modeling method for single soil particles based on the multisphere combination method. Considering the cohesion of soda saline–alkali soil particles, the Hertz–Mindlin with JKR (JKR) model was used as the contact model between soil particles. Then, the calibration method was used to obtain simulation parameters of soils that are difficult to obtain experimentally. We conducted soil angle of repose (AoR) tests, the Plackett–Burman (PB) tests, and steepest ascent (SA) tests in turn to perform a sensitivity analysis for microscopic contact parameters and select the parameters that have a significant effect on the response value (static AoR), i.e., soil surface energy, soil–soil static friction coefficient, and soil–soil rolling friction coefficient. Then, the optimal combination of simulation parameters was obtained via the Box–Behnken (BB) tests, using ANOVA to optimize the multiple regression equation. Finally, the optimal parameter combination was verified by the AoR test and the direct shear (DS) test. The results showed that the parameters had good adaptability for the AoR test. However, the simulation results of the DS test were significantly different from the experimental values. Therefore, the contact model needs to be further modified by adding Bonding bonds between soil particles based on the JKR model and further correcting for Rayleigh time step, shear modulus, and surface energy. By comparing the simulation and the experimental results, it was found that the simulation results obtained from both the DS test and AoR test had relatively small errors relative to physical tests, the two trends are the same, and the values are similar. This verified the feasibility and effectiveness of the soda saline–alkali soil particle modeling method and parameter selection proposed in this paper.

In 2020, China successfully conducted the second round of natural gas hydrate pilot production with horizontal wells at W11-W17 deposits in the Shenhu sea area of South China Sea, but the average daily gas production is far from reaching the commercial exploitation. Low productivity has become one of the key factors hindering the commercial exploitation of gas hydrate reservoir. This work taking SHSC-4 well as an example, uses numerical simulation method to analyze the impact of the placement of horizontal well section, length and the production system on productivity of horizontal well in depressurization exploitation. From the analysis of simulation results, it can be seen that the best performance of production capacity can be achieved when horizontal section placed in layer II, which is compared with that placed in layer I and III. More importantly, hydrate in layer I and free gas in layer III can be effectively utilized to improve productivity when layer II is exploited. When the horizontal section is arranged in layer II and produced by depressurization with small pressure difference (1 MPa), the longer the horizontal section length is, the better the productivity will be. However, the average cumulative gas production increment per meter is gradually decreasing. According to the simulation results, 300 m is a reasonable horizontal section length for the exploitation of layer II, and the cumulative gas production reaches 2.55 million cubic meters after 60 days of continuous exploitation. In addition, due to the limitations of convective heat transfer in the low-permeability reservoir in the Shenhu sea area, sensible heat can significantly improve the secondary hydrate generated in the wellbore and the reservoir around the wellbore due to throttling expansion effect, which has a good effect on productivity improvement. Compared with the situation without heating, when the horizontal section is arranged in layer II and the length is 300 m, the production mode of depressurization and combined heating is adopted, and the cumulative gas production of 60 days with different pressure difference (1–5 MPa) is 0.14, 5.55, 14.75, 23.72, and 29.5 times higher than that without heating.

Abstract Background Xeroderma pigmentosum complementation group C (XPC) is a DNA damage recognition protein that plays an important role in nucleotide excision repair and can reduce oxidative stress, which may be involved in the development of preeclampsia (PE). Therefore, the aim of this study was to explore whether XPC polymorphisms were relevant to the genetic susceptibility to PE in Chinese Han women. Method A total of 1276 healthy pregnant women were included as the control group and 958 pregnant women with PE as the case group. DNA was extracted from peripheral blood samples to perform genotyping of loci rs2228001 and rs2228000 in XPC through real-time quantitative polymerase chain reaction (PCR). The relationship between XPC and susceptibility to PE was evaluated by comparing the genotypic and allelic frequencies between the two groups of pregnant women. Results Polymorphism of rs2228000 may be associated with PE risk and allele T may play a protective role (genotype, χ2 = 38.961, P

Geochemical investigation on the origin and circulation of geothermal water is crucial for better understanding the interaction between hydrosphere and lithosphere. Previous studies on the Himalayan geothermal belt mainly distributed in the central and eastern Tibetan Plateau. In this study, water samples (8 hot springs and 1 cold spring) from the Karakorum fault (KKF) zone of western Tibetan Plateau were analyzed for the hydrogeochemical characteristics and isotopic compositions. Three types of spring water along the KKF were classified on basis of ionic concentration and Sr isotopic composition: type A water (HCO3–Mg or Ca), type B water (HCO3–Na) and type C water (Cl–Na). Type A water is originated from the infiltration of meteoric water and the dissolution of silicate/evaporite. Type B water is mainly leached from the metamorphic and granitoid rocks. Type C water is formed by the dissolution of chlorides and sulphates. δD and δ18O isotopes indicate that geothermal fluid along the fault zone was mainly recharged by local precipitation. Moreover, reservoir temperatures of 144.2–208.6°C were estimated by the silica–enthalpy mixing model, and the thermal waters have a relatively deep circulation depth (≥ 7.0 km). Meanwhile, the thermal waters are characterized by extremely high Li, B, Fe and As concentrations and earthquakes frequently happened in the vicinity, suggesting that the KKF is a deep and active fault, which also indicates that the thermal fluids are strongly associated with seismicity. Therefore, thermal fluid can potentially be used as continuous monitoring sites for earthquake forecasting.

Highly active Ti/Sb–SnO2 electrodes were fabricated using sol-gel spin coating procedure, which exhibited a rough, uniform and multilayer coating structure. The effects of different Sb-SnO2 film layers on the physiochemical, electrochemical properties and pollutant degradability of electrodes and the mechanism were evaluated on a systematic basis. The electrodes with more active layers exhibited higher electro-catalytic performance. Upon exceeding 8 layers, the promotion effect of the coating was reduced. Considering various factors, this paper recommends preparing Ti/Sb–SnO2 electrodes coated with 8 layers to obtain higher electro-catalytic ability in landfill leachate treatment. The specific number of coating layers should be determined according to the electrode requirements. This work provided a theoretical basis and technical support for the preparation of Ti-SnO2 electrodes with high electro-catalytic activity and stability, while it still remains a great challenge to achieve an excellent balance between performance and stability before Ti/Sb-SnO2 electrodes can be implemented on a large scale in wastewater treatment. HIGHLIGHTS Sol-gel spin coating method could be used to exhibit a multilayer coating structure.; Electrodes with more active layers had higher electro-catalytic performance.; Upon exceeding 8 layers, the promotion effect of the coating was reduced.; Ti/Sb-SnO2 electrodes coated with 8 layers could obtain higher electro-catalytic ability during leachate treatment.;

ObjectivesThis study aimed to explore the effect of subjective age on loneliness in old adults, and the mediating role of resilience and self-esteem in subjective age and loneliness.MethodsApproximately 450 old adults from Jiangxi, Hunan, Henan provinces completed the third edition of the Loneliness Scale (UCLA-LS III), Age Decade Scale (ADS), Connor-Davidson Resilience Scale (CD-RISC), and Self-Esteem Scale (SES).Results(1) Subjective age was significantly positively correlated with loneliness. (2) Resilience, self-esteem, and loneliness were significantly negatively correlated. (3) Subjective age affected loneliness through the mediating effects of resilience and self-esteem, respectively. (4) Resilience and self-esteem played a chain mediating role between subjective age and loneliness.ConclusionResilience and self-esteem can directly affect the loneliness of the old adults alone and can also affect the loneliness of the old adults through the chain mediating effect of resilience and self-esteem.

The discovery of gas hydrates in the Muli Depression has made the South Qilian Basin (SQB) a hotspot for oil and gas exploration. Although many studies have been carried out on the gas hydrates, the geochemical characteristics have rarely been reported, which can effectively indicate the genetic type, diffusion, biodegradation, and thermal maturity of natural gas. In this contribution, the molecular composition and carbon isotopes of alkane gases were collected from gas hydrates and free gases in drilled boreholes of the Muli Depression. The results show that the majority of natural gases are oil-type gases, with a little coal-type gases. The natural gases have undergone biodegradation, leading to a decrease in the propane content and an increase in the methane content, with a heavier carbon isotope of propane and a lighter carbon isotope of methane. Some of the natural gases have experienced diffusion, resulting in a decrease in the methane content and an increasing value of Δ(δ13C1-δ13C2). Furthermore, the wet gases from natural gases were derived from the cracking of kerogen and crude oil at the thermal maturity stage. The dry gases in small quantities were produced by biodegradation of the wet gases. We propose that the potential for light oil and condensate exists in the Jurassic Yaojie Formation. Our new findings on the geochemical characteristics of natural gases provide new constraints for the study of petroleum systems and deeply buried sediments in the SQB.

Over 90% of the global hydrate resources are stored in very-low-permeability clayey silt reservoirs. The low permeability significantly restricts the efficiency of gas and water flow into the production well. To enhance gas production efficiency in low-permeability hydrate reservoirs, the high-pressure rotating water jets (HPRWJ) technology is proposed to construct near wellbore artificial fractures (NWAFs) in hydrate reservoirs. The HPRWJ avoid the risks of hydraulic fracturing as well as large-scale reservoir damage, which makes it more suitable for constructing fractures in hydrate-bearing sediments (HBS). In this article, the site SH7 in the South China Sea is studied to evaluate the feasibility of this technology for enhancing gas production of low-permeability hydrate reservoirs by numerical simulation. The results show that the gas productivity is increased by approximately three times by using the HPRWJ technology to construct NWAFs with a depth of 3 m. It is suggested that the proposed technology is a promising method for improving gas production from the low-permeability hydrate reservoirs. Furthermore, the gas production performance is closely related to NWAF depth, NWAF permeability, and NWAF spacing. For the site SH7 in the South China Sea, the NWAF depth, permeability, and spacing are recommended as 3 m, 3D, and 3 m, respectively.

Abstract Background Gestational diabetes mellitus (GDM) is a pregnancy-specific carbohydrate intolerance Which can cause a large number of perinatal and postpartum complications. The members of Transforming growth factor-β (TGF-β) superfamily play key roles in the homeostasis of pancreatic β-cell and may involve in the development of GDM. This study aimed to explore the association between the polymorphisms of TGF-β1, TGF-β3 and the risk to GDM in Chinese women. Methods This study included 919 GDM patients (464 with preeclampsia and 455 without preeclampsia) and 1177 healthy pregnant women. TaqMan allelic discrimination real-Time PCR was used to genotype the TGF-β1 (rs4803455) and TGF-β3 (rs2284792 and rs3917201), The Hardy-Weinberg equilibrium (HWE) was evaluated by chi-square test. Results An increased frequency of TGF-β3 rs2284792 AA and AG genotype carriers was founded in GDM patients (AA vs. AG + GG: χ2 = 6.314, P = 0.012, OR = 1.270, 95%CI 1.054–1.530; AG vs. GG + AA: χ2 = 8.545, P = 0.003, OR = 0.773, 95%CI 0.650–0.919). But there were no significant differences in the distribution of TGF-β1 rs4803455 and TGF-β3 rs3917201 between GDM and healthy women. In addition, no significant differences were found in allele and genotype frequencies among GDM patients with preeclampsia (PE). Conclusions The AA and AG genotype of TGF-β3 rs2284792 polymorphism may be significantly associated with increased risk of GDM in Chinese population.

Abstract Background The aim of this study was to identify the key differentially expressed genes (DEGs) and high-risk gene mutations in breast ductal carcinoma in situ (DCIS). Methods Raw data (GSE36863) were downloaded from the database of Gene Expression Omnibus (GEO), including three DCIS samples (DCIS cell lines MCF10.DCIS, Sum102, and Sum225) and one normal control sample (normal mammary epithelial cell line MCF10A). The DEGs were analyzed using NOIseq and annotated via DAVID. Motif scanning in the promoter region of DEGs was performed via SeqPos. Additionally, single nucleotide variations (SNVs) were identified via GenomeAnalysisTK and SNV risk was assessed via VarioWatch. Mutant genes with a high frequency and risk were validated by RT-PCR analyses. Results Finally, 5391, 7073, and 7944 DEGs were identified in DCIS, Sum102, and Sum22 cell lines, respectively, when compared with MCF10A. VENN analysis of the three cell lines revealed 603 upregulated and 1043 downregulated DEGs, including 16 upregulated and 36 downregulated transcription factor (TF) genes. In addition, six TFs each (e.g., E2F1 and CREB1) were found to regulate the core up- and downregulated DEGs, respectively. Furthermore, SNV detection results revealed 1104 (MCF10.DCIS), 2833 (Sum102), and 1132 (Sum22) mutation sites. Four mutant genes (RWDD4, SDHC, SEPT7, and SFN) with high frequency and risk were identified. The results of RT-PCR analysis as well as bioinformatics analysis consistently demonstrated that the expression of RWDD4, SDHC, SEPT7, and SFN was downregulated in the tumor tissues as compared with that in adjacent non-tumor tissues. Conclusions The differentially expressed TFs, TFs regulating DEGs (e.g., E2F1 and CREB1), and high-frequency mutant genes (RWDD4, SDHC, SEPT7, and SFN) might play key roles in the pathogenesis of DCIS.

Objectives: The involvement of oxidative stress in the pathophysiology of preeclampsia (PE) has been already suggested. In this present study, we aimed to investigate the association of the genetic frequency of heme oxygense-1 (HMOX1) polymorphism with PE in Chinese Han women. Methods: We researched the genetic distribution of rs2071746 polymorphism in HMOX1 by the TaqMan allelic discrimination real-time PCR between 1235 PE patients and 1720 healthy women. Results: We found there were′t significant differences in the distribution of HMOX1 rs2071746 polymorphism in PE compared to the control group (rs2071746, genotype χ2 = 0.282, P = 0.869 and allele χ2 = 0.027, P = 0.869, OR = 1.009, 95% = 0.909–1.120). Conclusion: The rs2071746 polymorphism in HMOX1 might not be related to PE in Chinese women, although further investigations should be conducted to confirm our findings.

Abstract Background Excessive reactive oxygen species from endothelial mitochondria in type 2 diabetes individuals (T2DM) may occur through multiple related mechanisms, including production of mitochondrial reactive oxygen species (mtROS), inner mitochondrial membrane (Δψm) hyperpolarization, changes in mitochondrial mass and membrane composition, and fission of the mitochondrial networks. Inner mitochondrial membrane proteins uncoupling protein-2 (UCP2) and prohibitin (PHB) can favorably impact mtROS and mitochondrial membrane potential (Δψm). Circulating levels of UCP2 and PHB could potentially serve as biomarker surrogates for vascular health in patients with and without T2DM. Methods Plasma samples and data from a total of 107 individuals with (N = 52) and without T2DM (N = 55) were included in this study. Brachial artery flow mediated dilation (FMD) was measured by ultrasound. ELISA was performed to measure serum concentrations of PHB1 and UCP2. Mitochondrial membrane potential was measured from isolated leukocytes using JC-1 dye. Results Serum UCP2 levels were significantly lower in T2DM subjects compared to control subjects (3.01 ± 0.34 vs. 4.11 ± 0.41 ng/mL, P = 0.04). There were no significant differences in levels of serum PHB. UCP2 levels significantly and positively correlated with FMDmm (r = 0.30, P = 0.03) in T2DM subjects only and remained significant after multivariable adjustment. Within T2DM subjects, serum PHB levels were significantly and negatively correlated with UCP2 levels (ρ = − 0.35, P = 0.03). Conclusion Circulating UCP2 levels are lower in T2DM patients and correlate with endothelium-dependent vasodilation in conduit vessels. UCP2 could be biomarker surrogate for overall vascular health in patients with T2DM and merits additional investigation.

Abstract Black phosphorus (BP) has been shown as a promising two‐dimensional (2D) material for electronic devices owing to its high carrier mobility. To realize complementary electronic circuits with 2D materials, it is important to fabricate both n‐type and p‐type transistors with the same channel material. By engineering the contact region with copper (Cu)‐doped BP, here we demonstrate an n‐type carrier transport in BP field‐effect transistors (FETs), which usually exhibit strongly p‐type characteristics. Cu metal atoms are found to severely penetrate into the BP flakes, which forms interstitial Cu (Cuint)‐doped edge contact and facilitates the electron transport in BP. Our BP FETs in back‐gated configuration exhibit n‐type dominant characteristics with a high electron mobility of ~ 138 cm2 V−1 s−1 at room temperature. The Schottky barrier height for electrons is relatively low because of the edge contact between Cuint‐doped BP and pristine BP channel. The contact doping of BP by highly mobile Cu atoms gives rise to n‐type transport property of BP FETs. Furthermore, we demonstrate a p‐n junction on the same BP flake with asymmetric contact. This strategy on contact engineering can be further extended to other 2D materials.

The hydrate reservoir in the Shenhu Area of the South China Sea is a typical clayey-silt porous media with high clay mineral content and poor cementation, in which gas hydrate formation and dissociation characteristics are unclear. In this study, the CO 2 hydrate saturation, growth rate, and permeability were studied in sandstone, artificial samples, and clayey-silt sediments using a custom-built measurement apparatus based on the low-field NMR technique. Results show that the T 2 spectra amplitudes decrease with the hydrate formation and increase with the dissociation process. For the artificial samples and Shenhu sediments, the CO 2 hydrate occupies larger pores first and the homogeneity of the sandstone pores becomes poor. Meanwhile, compared with the clayey-silt sediments, CO 2 hydrate is easier to form and with higher hydrate saturation for the sandstone and artificial samples. In hydrate dissociation process, there exists a protection mechanism, i.e. the dissociation near the center of hydrates grain is suppressed when gas pressure drops suddenly and quickly. For permeability of those samples, it decreased with hydrate forms, and increases with hydrate dissociation. Meanwhile, with the same hydrate saturation, permeability is higher in hydrate formation than in dissociation.

Unbalanced inflammatory reactions and oxidative stress are inseparably interconnected, and both may play crucial roles in the pathophysiological mechanisms of preeclampsia (PE). In the published previous studies, we have genotyped for SNPs that related to inflammation (rs2227485, rs153109, rs17855750, rs2027432, rs2275913, rs763780, rs4819554, and rs13015714) and oxidative stress (rs1695, rs4680, rs1800566, rs4807542, rs713041, rs7579, rs230813, rs1004467, rs3824755, and rs9932581) to investigate whether these polymorphisms were associated with susceptibility to PE in a Chinese Han population. In this present study, we collected these data of experimental and clinical from above studies for haplotype analysis of inflammation-related SNPs in 631 PE patients and 720 normal pregnancy and oxidative stress-related SNPs in 342 PE patients and 457 normal pregnancies for susceptibility to PE. The data of genotype distribution and allele frequency comparisons after correction for multiple comparisons (P/8 or P/10) showed 2 among the 8 candidate inflammation-related SNPs have significant differences (rs2027432 genotype χ2=407.377,p0.9), and the GT and GC haplotypes of rs4807542 and rs713041 in GPX4 showed significant differences between the PE and control groups (χ2=5.143,p=0.0233,p

Abstract We investigated the role of microRNAs (miRNA) in endothelial dysfunction in the setting of cardiometabolic disorders represented by type 2 diabetes mellitus (T2DM). miR‐29 was dysregulated in resistance arterioles obtained by biopsy in T2DM patients. Intraluminal delivery of miR‐29a‐3p or miR‐29b‐3p mimics restored normal endothelium‐dependent vasodilation (EDVD) in T2DM arterioles that otherwise exhibited impaired EDVD. Intraluminal delivery of anti‐miR‐29b‐3p in arterioles from non‐DM human subjects or rats or targeted mutation of Mir29b‐1/a gene in rats led to impaired EDVD and exacerbation of hypertension in the rats. miR‐29b‐3p mimic increased, while anti‐miR‐29b‐3p or Mir29b‐1/a gene mutation decreased, nitric oxide levels in arterioles. The mutation of Mir29b‐1/a gene led to preferential differential expression of genes related to nitric oxide including Lypla1. Lypla1 was a direct target of miR‐29 and could abrogate the effect of miR‐29 in promoting nitric oxide production. Treatment with Lypla1 siRNA improved EDVD in arterioles obtained from T2DM patients or Mir29b‐1/a mutant rats or treated with anti‐miR‐29b‐3p. These findings indicate miR‐29 is required for normal endothelial function in humans and animal models and has therapeutic potential for cardiometabolic disorders.

Objective: We investigated whether the CXCL12-801G/A polymorphism was associated with preeclampsia (PE) susceptibility in a Chinese Han population. Methods: We examined 912 PE women and 1025 controls for the CXCL12-801G/A polymorphism by polymerase chain reaction (PCR) and correlations with clinical characteristics were examined. Results: No significant differences in genotypic and allelic frequencies of CXCL12-G801A were found between cases and controls (genotype: χ2 = 2.095, p = 0.351; allele: χ2 = 1.713, p = 0.191). There were also no significant differences between early/late-onset or mild/severe PE and control groups. Conclusion: The results indicate that 801G/A in CXCL12 may not play a major role in pathogenesis of PE in a Chinese Han population.

Abstract We provide a novel design of atmosphere visibility measurement system with the contrast principle used in the naked eye visibility observation. The new digital photography visiometer system (DPVS), composed of a CCD camera and two identical targets, utilizes the contrast of dual targets to measure the visibility. Two operational modes are designed to enable the DPVS to accommodate the lighting conditions of the day and night. Two passive targets, black bodies, are employed for daytime visibility measurement, and two active lights, LED panels, are utilized for nighttime. The mathematical models of the dual targets for both daytime and nighttime are developed, and the sensitivity analysis shows the requirements of the hardware to achieve desired accuracy. The design of the target including the blackbody and the LED panel is briefly discussed, and the temperature dependence and stability of the LED panels are measured experimentally. Finally, the DPVS is compared with two commercial visibility devices, a forward scatter meter and a transmission meter for field validation. A 5‐day comparative experiment shows that the measurements of the DPVS generally well agree with those of the transmissometer and the forward scatter meter for visibility up to 15 km, and the relative bias of 87% of the DPVS measurements lies between −0.2 and 0.2.

Background/Aims: Several lines of evidence have been reported that oxidative stress plays an important role in the pathogenesis of Preeclampsia (PE). Therefore, this research is aimed to investigate whether polymorphisms of CYBA are related to susceptibility to PE in Chinese Han women. Methods: We studied the genetic frequency of the rs9932581 and 1049255 polymorphisms in CYBA in 1029 PE patients and 1400 controls of later pregnant women by the TaqMan allelic discrimination real-time PCR and a case-control model. Results: Our research indicated that no significant differences were found for the genotypic or allelic frequencies at the two polymorphic sites in CYBA between PE patients and controls. To further study the relationship between the polymorphic sites and PE, we also found that there is no significant difference in the genetic distributions identified between the mild or severe PE and early or the late-onset PE and controls. Conclusion: The study demonstrated that the genetic variants of rs9932581 and rs1049255 in CYBA might not be associated with PE. However, investigations of genetic variability that influence on the disease outcome are needed in other large prospective populations or regions, so the complicated interconnection of genetic and environmental elements can be emulated for better understanding.

Intra-tumor heterogeneity represents a major barrier to anti-cancer therapies. One strategy to minimize this limitation relies on bystander effects via diffusion of cytotoxins from targeted cells. Hypoxia-activated prodrugs (HAPs) have the potential to exploit hypoxia in this way, but robust methods for measuring bystander effects are lacking. The objective of this study is to develop experimental models (monolayer, multilayer, and multicellular spheroid co-cultures) comprising ‘activator’ cells with high expression of prodrug-activating reductases and reductase-deficient ‘target’ cells, and to couple these with agent-based models (ABMs) that describe diffusion and reaction of prodrugs and their active metabolites, and killing probability for each cell. HCT116 cells were engineered as activators by overexpressing P450 oxidoreductase (POR) and as targets by knockout of POR, with fluorescent protein and antibiotic resistance markers to enable their quantitation in co-cultures. We investigated two HAPs with very different pharmacology: SN30000 is metabolized to DNA-breaking free radicals under hypoxia, while the dinitrobenzamide PR104A generates DNA-crosslinking nitrogen mustard metabolites. In anoxic spheroid co-cultures, increasing the proportion of activator cells decreased killing of both activators and targets by SN30000. An ABM parameterized by measuring SN30000 cytotoxicity in monolayers and diffusion-reaction in multilayers accurately predicted SN30000 activity in spheroids, demonstrating the lack of bystander effects and that rapid metabolic consumption of SN30000 inhibited prodrug penetration. In contrast, killing of targets by PR104A in anoxic spheroids was markedly increased by activators, demonstrating that a bystander effect more than compensates any penetration limitation. However, the ABM based on the well-studied hydroxylamine and amine metabolites of PR104A did not fit the cell survival data, indicating a need to reassess its cellular pharmacology. Characterization of extracellular metabolites of PR104A in anoxic cultures identified more stable, lipophilic, activated dichloro mustards with greater tissue diffusion distances. Including these metabolites explicitly in the ABM provided a good description of activator and target cell killing by PR104A in spheroids. This study represents the most direct demonstration of a hypoxic bystander effect for PR104A to date, and demonstrates the power of combining mathematical modeling of pharmacokinetics/pharmacodynamics with multicellular culture models to dissect bystander effects of targeted drug carriers.

Pressure drop is an important parameter in the study of gas-liquid two-phase flow (Beggs and Brill, 1973). The phenomenon of negative frictional pressure drop is observed in an experiment. In the process of the experiment, it is necessary to research the law of negative pressure drop. In this paper, the two-phase flow experiment is carried out in a vertical pipe of 60mm in diameter and 8m in length. The apparent liquid velocity is from 0.08 to 0.20 m/s, the apparent gas velocity is from 1 to 19 m/s. Air and mineral oil are used as the working fluids, and the viscosities of the oil are 25, 50, 70, 150, and 200 cp, respectively. The multiphase flow test platform is used to research the negative pressure drop. A criterion is given to judge the phenomenon of negative frictional pressure drop; the smaller the apparent gas-liquid velocity, the greater the influence of viscosity on the negative frictional pressure drop.

Background/Aims: Accumulating evidence suggests that an excessive maternal systemic inflammatory response to pregnancy with exaggerated activation of the innate immune system plays a critical role in the development of preeclampsia (PE). In this study, we investigated whether polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with susceptibility to PE in the Chinese Han population. Methods: We recruited 987 PE patients and 1227 healthy pregnant women. Two polymorphisms (rs3775291 and rs3775296) located in TLR3 were genotyped by TaqMan allelic discrimination real-time PCR. The association between the genotype or allele frequencies and PE was examined using chi-square tests. Clinical data were compared between cases and controls using Student's t test. Results: No significant difference was determined in the genetic distribution of rs3775291 and rs3775296 between cases and controls. There were also no significant differences in the genotype and allele frequencies of either SNP between healthy pregnant women and patients with late or early onset PE, or with mild or severe PE. Conclusion: Although this is the first study of the association between TLR3 polymorphisms and preeclampsia, we found that TLR3 polymorphisms are unlikely to play a significant role in the development of preeclampsia in the Chinese Han population.

3-(3-Morpholinopropyl)-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1,4-dioxide (SN30- 000), an analog of the well-studied bioreductive prodrug tirapazamine (TPZ), has improved activity against hypoxic cells in tumor xenografts. However, little is known about its biotransformation in normal tissues. Here, we evaluate implications of biotransformation of SN30000 for its toxicokinetics in NIH-III mice. The metabolite profile demonstrated reduction to the 1-N-oxide (M14), oxidation of the morpholine side-chain (predominantly to the alkanoic acid M18) and chromophore, and subsequent glucuronidation. Plasma pharmacokinetics of SN30000 and its reduced metabolites was unaffected by the presence of HT29 tumor xenografts, indicating extensive reduction in normal tissues. This bioreductive metabolism, as modeled by hepatic S9 preparations, was strongly inhibited by oxygen indicating that it proceeds via the one-electron (radical) intermediate previously implicated in induction of DNA double strand breaks and cytotoxicity by SN30000. Plasma pharmacokinetics of SN30000 and M14 (but not M18) corresponded closely to the timing of reversible acute clinical signs (reduced mobility) and marked hypothermia (rectal temperature drop of ∼8°C at nadir following the maximum tolerated dose). Similar acute toxicity was elicited by dosing with TPZ or M14, although M14 did not induce the kidney and lung histopathology caused by SN30000. M14 also lacked antiproliferative potency in hypoxic cell cultures. In addition M14 showed much slower redox cycling than SN30000 in oxic cultures. Thus a non-bioreductive mechanism, mediated through M14, appears to be responsible for the acute toxicity of SN30000 while late toxicities are consistent with DNA damage resulting from its one-electron reduction. A two-compartment pharmacokinetic model, in which clearance of SN30000 is determined by temperature-dependent bioreductive metabolism to M14, was shown to describe the non-linear PK of SN30000 in mice. This study demonstrates the importance of non-tumor bioreductive metabolism in the toxicology and pharmacokinetics of benzotriazine di-oxides designed to target tumor hypoxia.

Genetic algorithm (GA) is a search algorithm based on the theory of Darwin. For the purpose of improving the convergent rate and maintaining the population diversity in GA, this paper presents a new genetic operator called trisecting group and directional selection mechanism (TDGA), in which the worst 2/3 of parent individuals are removed from the population before other manipulations. With 1/3 individuals that are selected randomly from the removed parent individuals, the best 1/3 of the parent individuals is manipulated to reproduce offspring. Simulation results based on 10 test functions show that TDGA is feasible and effective. In addition, inspired by the graph of the function () = , a new self-adaptation adjusting the tactics of crossover operator and mutation operator (SAGA) is proposed so that individuals with higher fitness cross each other with smaller values of crossover probability, and individuals with lower fitness cross each other with larger values of crossover probability. Combining the two improvements, TA-SAGA is applied to study the layout of drilling equipment in semi- submersible drilling platforms. In addition, the simulated best centroid transverse deviator just only is 0.120 m, which is far less than the allowable value 0.7m.

Previous studies have suggested an important role for IL-17, mainly secreted by Th17 cells, in the development of systemic inflammation in preeclampsia (PE). This study therefore investigated the association between genetic variants in IL-17A, IL-17F, and IL-17RA and susceptibility to PE in Chinese Han women. We recruited 1,031 PE patients and 1,298 controls of later pregnant women, and used TaqMan allelic discrimination real-time PCR to genotype the polymorphisms of IL17A rs2275913, IL-17F rs763780, and IL-17RA rs4819554. No significant differences in genotypic or allelic frequencies were found at all three polymorphic sites between PE patients and controls (rs2275913: genotype χ2 = 0.218, p = 0.897 and allele χ2 = 0.157, p = 0.692, OR = 1.024, 95%CI 0.911-1.152; rs763780: genotype χ2 = 1.948, p = 0.377 and allele χ2 = 1.242, p = 0.265, OR = 0.897, 95%CI 0.741-1.086; rs4819554: genotype χ2 = 0.633, p = 0.729 and allele χ2 = 0.115, p = 0.735, OR = 1.020, 95%CI 0.908-1.146). There were also no significant differences in genetic distributions between mild/severe PE or early/late-onset PE and control subgroups. Our data indicate that the genetic variants of rs2275913 in IL-17A, rs763780 in IL-17F, and rs4819554 in IL-17RA may not play a role in the pathogenesis of PE in Chinese Han women. However, these findings should be confirmed in other ethnic populations.

We used the standard comet assay successfully to generate in vitro dose-response curves under oxic and hypoxic conditions. We then made mixtures of cells that had been irradiated with 3 and 9 Gy of X-rays to simulate two subpopulations in a tumor, but efforts to accurately detect and quantify the subpopulations using the standard comet assay were unsuccessful. Therefore, we investigated a modified comet assay to determine whether it could be used for measuring hypoxia in our model systems. U251 MG cells were grown as subcutaneous tumors in athymic mice; U251 MG and U87 MG cells were grown as intracerebral (i.c.) tumors in athymic rats. Animals were injected with RSU 1069, irradiated, and euthanized. Tumors and normal brains were removed, and the cells were analyzed using a modified comet assay. Differences in comet tail moment distributions between tumor and contralateral normal brain, using tail moments at either the 25th or 50th percentile in each distribution, were taken as measures of the degree of tumor hypoxia. For U251 MG tumors, there was a positive relationship between tumor size and the degree of hypoxia, whereas preliminary data from U87 MG i.c. tumors showed less hypoxia and no apparent relationship between tumor size and hypoxia.

The transcription factor SOX2 is essential for maintaining pluripotency in a variety of stem cells. It has important functions during embryonic development, is involved in cancer stem cell maintenance, and is often deregulated in cancer. The mechanism of SOX2 regulation has yet to be clarified, but the SOX2 gene lies in an intron of a long multi-exon non-coding RNA called SOX2 overlapping transcript (SOX2OT). Here, we show that the expression of SOX2 and SOX2OT is concordant in breast cancer, differentially expressed in estrogen receptor positive and negative breast cancer samples and that both are up-regulated in suspension culture conditions that favor growth of stem cell phenotypes. Importantly, ectopic expression of SOX2OT led to an almost 20-fold increase in SOX2 expression, together with a reduced proliferation and increased breast cancer cell anchorage-independent growth. We propose that SOX2OT plays a key role in the induction and/or maintenance of SOX2 expression in breast cancer.