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Breast cancer is the most diagnosed cancer in women worldwide and the leading cause of most cancer-related deaths, posing a serious threat to women′s health worldwide. At present, although the prognosis of some patients with breast cancer has improved, the emergence of drug resistance and the metastasis and recurrence of breast cancer are still the main reasons for poor prognosis. CD36 is a multiligand transmembrane glycoprotein expressed on various cell types. In recent years, studies have confirmed that CD36 can reshape the lipid metabolism of cancer cells; promote the differentiation of tumor-related macrophages into M2 type and recruitment into tumor tissues; regulate the function of Treg cells, CD8+ T cells, DCs, and other immune cells, and thus promote tumor development. In addition, CD36 is also associated with breast cancer stem cells, metastasis-initiating cells, and breast drug resistant cells. Therefore, CD36 could be an important potential therapeutic target for breast cancer.

Low temperatures pose a significant threat to plant growth and development. Studies have shown that aquaporins (AQPs), as the main functional proteins on the cell membrane regulating water ingress and egress, play a vital role in maintaining dynamic water balance when plants face cold stress. Catalpa bungei, an important timber and ornamental tree species, has its cultivation range significantly limited by its poor cold tolerance. However, no study has been found aiming to identify its aquaporin gene family. This study aims to fill this gap using two C. bungei cultivars with differing cold tolerance as experimental material: “Qiuza 1”, which is less cold-tolerant, and “Qiuza 2”, which is more cold-tolerant. The plants were subjected to low-temperature stress at 4 °C for 24 h. Using high-throughput molecular sequencing technology, a transcriptome sequencing of the leaves was performed at 0, 6, 12, and 18 h of cold stress. Fifteen candidate aquaporin genes in C. bungei (CbAQP) were identified. Phylogenetic analysis showed that the CbAQP gene family is divided into five subfamilies: 5 PIPs, 4 TIPs, 3 NIPs, 2 SIPs, and 1 XIP. By analyzing AQPs related to cold stress in other plants and the expression patterns of CbAQP genes, 12 CbAQP genes related to cold stress were identified. The genes that responded positively include CbPIP2;5, CbPIP1;2, CbTIP4;1, and CbNIP2;1. The results provide a foundation for further analysis of the biological functions of candidate CbAQP genes related to cold tolerance and offer theoretical support for improving seedling quality, cold-resistant genetic breeding, and expanding its distribution range.

The microclimate environment can be conveniently controlled with accuracy by plant incubators, in which the cuttings propagation method can efficiently enhance seedling production. To ensure air flow evenly throughout the incubator, the scientific design of the air inlet is crucial. This study utilized a computational fluid dynamics (CFD) model to simulate the airflow patterns in a culture layer under different air inlet conditions. Furthermore, the optimal design parameters were determined by way of response surface methodology (RSM) and the Non-dominated Sorting Genetic Algorithm-II (NSGA-II). Adopting the optimal parameters, a prototype was manufactured, and a cuttings experiment was carried out with apple cuttings in the incubator. The results showed that the optimal air inlet radius is 90 mm, the optimal air inlet height is 188 mm, and the optimal uniform flow plate hole diameter is 13 mm. Meanwhile, the apple cuttings were able to root. Therefore, this incubator with optimal parameters can be used for cuttings. The study provides a methodological and theoretical basis for the future optimizing of air inlet parameters and promoting cuttings rooting.

The corrosion of reinforced concrete (RC) is one of the most serious durability problems in civil engineering structures, and the corrosion detection of internal reinforcements is an important basis for structural durability assessment. In this paper, the appropriate frequency required to cause excitation signals in the specimen is first analyzed by means of frequency dispersion curves. Subsequently, the effectiveness of five damage indexes (DIs) is discussed using random corrosion in finite elements. Finally, guided ultrasonic wave (GUW) tests are conducted on reinforcement and RC specimens at different corrosion degrees, and the test results are verified using a theoretical corrosion model. The results show that the larger the covered thickness is at the same frequency, the higher the modal order of the GUW in the frequency dispersion curve is, and the smaller the group velocity is. The SAD is the most sensitive to the corrosion state of the reinforcement compared with the other DIs, and it shows a linear increasing trend with the increase in the corrosion degree of the reinforcement. The SAD values of the RC specimens showed a three-stage change with the increase in the corrosion time, and the time until the appearance of corrosion cracks was increased with the increase in the covered thickness. It can be seen that increasing the covered thickness is an effective method to delay the time until the appearance of corrosion cracks in RC specimens.

Abstract Background Osteosarcoma (OS) is the most common primary malignant bone tumors in children and adolescents. Large numbers of studies have focused on the long non-coding RNA (lncRNA) that plays essential roles in the progression of osteosarcoma. Nevertheless, the functions and underlying mechanisms of LncRNA NDRG1 in osteosarcoma remain unknown. Methods Differentially expressed lncRNAs between osteosarcoma and adjacent normal tissues were identified through RNA sequencing. The role of LncRNA NDRG1 in osteosarcoma proliferation and metastasis were investigated through in vitro and in vivo functional experiments. The interaction between LncRNA NDRG1 and miR-96-5p was verified through bioinformatic analysis and luciferase reporter assay. Regulation relationship between LncRNA NDRG1 and miR-96-5p was further evaluated by the rescue experiments. Additionally, the changes in the expression of epithelial-mesenchymal transition (EMT) and the PI3K/AKT pathway were verified by Western blot. Results LncRNA NDRG1 was up-regulated in osteosarcoma cell lines and tissues and the expression of LncRNA NDRG1 was correlated with the overall survival of osteosarcoma patients. Functional experiments exhibited that LncRNA NDRG1 aggravated osteosarcoma proliferation and migration in vitro; meanwhile, animals experiments showed that LncRNA NDRG1 promoted osteosarcoma growth and metastasis in vivo. Mechanistically, LncRNA NDRG1 was found to aggravate osteosarcoma progression and regulate the PI3K/AKT pathway by sponging miR-96-5p. Conclusions LncRNA NDRG1 aggravates osteosarcoma progression and regulates the PI3K/AKT pathway by sponging miR-96-5p. Therefore, LncRNA NDRG1 could act as a prognostic marker and a therapeutic target for osteosarcoma in the future.

Abstract Background P16INK4A is a surrogate signature compensating for the specificity and/or sensitivity deficiencies of the human papillomavirus (HPV) DNA and Papanicolaou smear (Pap) co‐test for detecting high‐grade cervical squamous intraepithelial lesions or worse (HSIL+). However, traditional p16INK4A immunostaining is labour intensive and skill demanding, and subjective biases cannot be avoided. Herein, we created a high‐throughput, quantitative diagnostic device, p16INK4A flow cytometry (FCM) and assessed its performances in cervical cancer screening and prevention. Methods P16INK4A FCM was built upon a novel antibody clone and a series of positive and negative (p16INK4A‐knockout) standards. Since 2018, 24 100‐women (HPV‐positive/‐negative, Pap‐normal/‐abnormal) have been enrolled nationwide for two‐tier validation work. In cross‐sectional studies, age‐ and viral genotype‐dependent expression of p16INK4A was investigated, and optimal diagnostic parameter cut‐offs (using colposcopy and biopsy as a gold standard) were obtained. In cohort studies, the 2‐year prognostic values of p16INK4A were investigated with other risk factors by multivariate regression analyses in three cervicopathological conditions: HPV‐positive Pap‐normal, Pap‐abnormal biopsy‐negative and biopsy‐confirmed LSIL. Results P16INK4A FCM detected a minimal ratio of 0.01% positive cells. The p16INK4A‐positive ratio was 13.9 ± 1.8% among HPV‐negative NILM women and peaked at the ages of 40–49 years; after HPV infection, the ratio increased to 15.1 ± 1.6%, varying with the carcinogenesis of the viral genotype. Further increments were found in women with neoplastic lesions (HPV‐negative: 17.7 ± 5.0–21.4 ± 7.2%; HPV‐positive: 18.0 ± 5.2–20.0 ± 9.9%). Extremely low expression of p16INK4A was observed in women with HSILs. As the HPV‐combined double‐cut‐off‐ratio criterion was adopted, a Youden's index of 0.78 was obtained, which was significantly higher than that (0.72) of the HPV and Pap co‐test. The p16INK4A‐abnormal situation was an independent HSIL+ risk factor for 2‐year outcomes in all three cervicopathological conditions investigated (hazard ratios: 4.3–7.2). Conclusions FCM‐based p16INK4A quantification offers a better choice for conveniently and precisely monitoring the occurrence of HSIL+ and directing risk‐stratification‐based interventions.

In this paper, firstly, the effects of graphene oxide on the mechanical properties of concrete were investigated. Secondly, the degradation and mechanism of the mechanical properties of graphene oxide concrete (GOC) under sulfate attack and a freeze–thaw environment were investigated. In addition, the dynamic modulus of elasticity (MOEdy) and uniaxial compressive strength (UCS) of the GOC were measured under different environmental conditions. According to the test results, the incorporation of graphene oxide in appropriate admixtures could improve the mechanical properties of concrete in these two working environments. It is worth noting that this effect is most pronounced when 0.05 wt% graphene oxide is incorporated. In the sulfate attack environment, the MOEdy and UTS of the GOC0.05% specimen at 120 cycles decreased by 22.28% and 24.23%, respectively, compared with the normal concrete specimens. In the freeze–thaw environment, the MOEdy and UTS of the GOC0.05% specimen at 90 cycles decreased by 13.96% and 7.58%, respectively, compared with the normal concrete specimens. The scanning electron microscope (SEM) analysis showed that graphene oxide could adjust the aggregation state of cement hydration products and its own reaction with some cement hydration crystals to form strong covalent bonds, thereby improving and enhancing the microstructure density.

The orthotropic steel deck is a prevalent stiffening girder structure utilized in long-span cable-stayed bridges and suspension bridges. Nonetheless, the issue of fatigue cracking has persisted in in-service orthotropic steel decks, significantly impacting the longevity of bridges. This study examines the analysis of the distribution of residual stress during the rewelding process of a fatigue crack at the U-rib-to-deck-plate joint of an orthotropic steel bridge deck. Additionally, the impact of the initial welding and the stiffness of the boundary constraint on the residual stress field during rewelding is discussed. The findings indicate that the removal of the fatigue crack prior to rewelding alleviates the transverse residual stress caused by the initial welding. After undergoing the rewelding procedure, both the transverse residual stress and the longitudinal residual stress exhibited a significant stress peak. More precisely, the transverse tensile stress underwent a rise from 21 MPa to 385 MPa, while the longitudinal tensile stress experienced an increase from 345 MPa to 525 MPa. Furthermore, the range of tensile stress within the longitudinal residual distribution expanded by 88%. Moreover, the stress redistribution during the rewelding of the local fatigue crack varied depending on the constraints imposed on the steel bridge deck. Notably, the transverse residual stress increases by 40.6% when compared to the absence of constraints. The findings of this research offer valuable insights for the implementation of rewelding repair techniques on steel bridge decks, emphasizing the significance of considering the effects of residual stresses induced during the rewelding process.

It is of great significance to design and innovate electrode materials with unique structures to effectively optimize the electrochemical properties of the secondary battery. Herein, inspired by neuron networks, an ingenious synthesis is proposed to fabricate NiSe with multidimensional micro-nano structures, followed by in situ construction of NiSe/NiO heterostructures via a temporary calcination. The major structure of bulk NiSe synthesized by the solvothermal method is 3-dimensional micron cluster spherical particles interwoven by uniform one-dimensional nanofibers. Such structures possess the synergistic advantages of nano and micro materials. After a temporary calcination in air, NiSe/NiO heterostructures should be formed in the bulk NiSe, which provides a built-in electric field to enhance diffusion kinetics of sodium ions. This special neural-like network and heterojunction structures ensure the excellent structural stability combined with rapid kinetics of the electrode, releasing 310.9 mAh g−1 reversible capacity after 2,000 cycles at 10 A g−1. Furthermore, the electrochemical storage and ion transport mechanisms are elaborated by electrochemical analysis and theoretical calculation in more detail.

Abstract Developing effective strategies to improve the initial Coulombic efficiency (ICE) and cycling stability of hard carbon (HC) anodes for sodium‐ion batteries is the key to promoting the commercial application of HC. In this paper, homotype heterojunctions are designed on HC to induce the generation of stable solid electrolyte interfaces, which can effectively increase the ICE of HC from 64.7% to 81.1%. The results show that using a simple surface engineering strategy to construct a homotypic amorphous Al2O3 layer on the HC could shield the active sites, and further inhibit electrolyte decomposition and side effects occurrence. Particularly, due to the suppression of continuous decomposition of NaPF6 in ester‐based electrolytes, the accumulation of NaF could be reduced, leading to the formation of thinner and denser solid electrolyte interface films and a decrease in the interface resistance. The HC anode can not only improve the ICE but elevate its sodium storage performance based on this homotype heterojunction composed of HC and Al2O3. The optimized HC anode exhibits an outstanding reversible capacity of 321.5 mAh g−1 at 50 mA g−1. The cycling stability is also improved effectively, and the capacity retention rate is 86.9% after 2000 cycles at 1 A g−1 while that of the untreated HC is only 52.6%. More importantly, the improved sodium storage behaviors are explained by electrochemical kinetic analysis.

Abstract Nondestructive testing of plant roots is a hot topic in recent years. The traditional measurement process is time-consuming and laborious, and it is impossible to analyze the state of plant roots without destroying the sample. Recent studies have shown that as an excellent nondestructive measurement method, although electrical impedance spectroscopy (EIS) has made great achievements in many botanical research fields such as plant morphology and stress resistance, there are still limitations. This review summarizes the application of EIS in plant root measurement. The experiment scheme, instrument and electrode, excitation frequency range, root electrical characteristics, equivalent circuit, and combination of EIS and artificial intelligence (AI) are discussed. Furthermore, the review suggests that future research should focus on miniaturization of measurement equipment, standardization of planting environment and intelligentization of root diagnosis, so as to better apply EIS technology to in situ root nondestructive measurement.

ObjectiveConvolutional Neural Network(CNN) is increasingly being applied in the diagnosis of gastric cancer. However, the impact of proportion of internal data in the training set on test results has not been sufficiently studied. Here, we constructed an artificial intelligence (AI) system called EGC-YOLOV4 using the YOLO-v4 algorithm to explore the optimal ratio of training set with the power to diagnose early gastric cancer.DesignA total of 22,0918 gastroscopic images from Yixing People’s Hospital were collected. 7 training set models were established to identify 4 test sets. Respective sensitivity, specificity, Youden index, accuracy, and corresponding thresholds were tested, and ROC curves were plotted.Results1. The EGC-YOLOV4 system completes all tests at an average reading speed of about 15 ms/sheet; 2. The AUC values in training set 1 model were 0.8325, 0.8307, 0.8706, and 0.8279, in training set 2 model were 0.8674, 0.8635, 0.9056, and 0.9249, in training set 3 model were 0.8544, 0.8881, 0.9072, and 0.9237, in training set 4 model were 0.8271, 0.9020, 0.9102, and 0.9316, in training set 5 model were 0.8249, 0.8484, 0.8796, and 0.8931, in training set 6 model were 0.8235, 0.8539, 0.9002, and 0.9051, in training set 7 model were 0.7581, 0.8082, 0.8803, and 0.8763.ConclusionEGC-YOLOV4 can quickly and accurately identify the early gastric cancer lesions in gastroscopic images, and has good generalization.The proportion of positive and negative samples in the training set will affect the overall diagnostic performance of AI.In this study, the optimal ratio of positive samples to negative samples in the training set is 1:1~ 1:2.

Abstract Background Electrical impedance tomography (EIT) has rarely been applied in plant science, particularly to study plant resistance to abiotic and biotic stresses. In this study, we evaluated the freezing resistance of floribunda roses (Rosa Floribunda) during frost dehardening using the EIT technique to identify a new method for rapid and non-destructive measurement of plant freezing resistance. Results The current was the excitation source, the boundary voltage value was measured, and then the boundary voltage reconstructed value was formed. Using an imaging algorithm, the two-dimensional (2D) distribution of impedance or impedance variation was reconstructed. The EIT reconstructed values decreased obviously with the decline in freezing temperatures. The EIT reconstructed values of stems had the best fit to the logistic equation, and subsequently, the semi-lethal temperatures were calculated. The freezing resistance results evaluated using EIT reconstructed values were linearly correlated with the results of the traditional electrolyte leakage (EL) method (r = 0.93, P

Abstract Soluble sugars and starches are important metabolites of plant life and physiological markers of plant stress response. There is an urgent need to develop a non-destructive and rapid method for determining plant starch and soluble sugar contents. Electrical impedance tomography (EIT) technology has been used to determine the physiological state and cold resistance of select plant tissues. However, so far there have been no reports on the use of EIT for the rapid estimation of soluble sugar and starch contents. In this study, EIT was used to obtain reconstructed voltage values and estimate starch and soluble sugar contents in the stems of three Rosa hybrida cultivars during February to May, which were grown in the Specimen Park (38° 50′ N, 115° 26′ E) of Hebei Agricultural University, Baoding City, Hebei Province, China. Stems from two of the cultivars were used for establishing regression models for starch and soluble sugar contents as functions of reconstructed voltage values. The third cultivar was used to test the accuracy of the regression models. The quadratic regression model was best for determining soluble sugar content and the logarithmic regression model was best for determining starch content. Thus, this research provided technical support for using EIT to analyze changes in physiological parameters and to rapidly estimate physiological indexes of plants. More studies were now needed to validate the results in this paper.

Abstract Background Traditional measurements of apple seedling roots often rely on manual measurements and existing root scanners on the market. Manual measurement requires a lot of labor and time, and subjective reasons may cause the uncertainty of data; root scanners have limited scanning size and expensive. In case of fruit roots, coverage and occlusion issues will occur, resulting in inaccurate results, but our research solved this problem. Results The background plate was selected according to the color of the seedling roots; the image of the roots of the collected apple seedlings was preprocessed with Vision Development Module by combining image and Labview. The root surface area, average root diameter, root length and root volume of apple seedlings were measured by combining root characteristic parameters algorithm. In order to verify the effectiveness of the proposed method, a set of measurement system for root morphology of apple seedlings was designed, and the measurement result was compared with the Canadian root system WinRHIZO 2016 (Canada). With application of SPSS v22.0 analysis, the significance P > 0.01 indicated that the difference was not significant. The relative error of surface area was less than 0.5%. The relative error of the average diameter and length of the root system was less than 0.1%, and the relative error of the root volume was less than 0.2%. Conclusions It not only proved that the root surface area, average root diameter, root length and root volume of apple seedlings could be accurately measured by the method described herein, which was handy in operation, but also reduced the cost by 80–90% compared with the conventional scanner.

Heterostructures exhibit intriguing and significant properties for functional material applications, such as photosensing devices, semiconductor materials, and supercapacitors. Rechargeable batteries as typical energy‐storage devices have drawn widespread attention in the past several decades, on account of high energy density, being low‐cost, and ecofriendly. Preparing superior active materials is the critical technology to ameliorate the electrochemical performance of batteries. In recent years, the concept of constructing heterostructures for the application of electrode materials has been considered as a promising design approach. Among all the electrode materials, metal chalcogenides (MCs) have presented excellent properties due to their high theoretical capacity based on multielectron reaction. Herein, the progress on MCs with heterostructures is summarized in terms of various material species and their specific application for several typical battery systems. Finally, possible challenges and comprehensive perspectives are given to provide an instructive direction for the thoughtful design strategies of heterostructures and the development of MCs for next‐generations rechargeable batteries.

Hard carbon (HC) has attracted extensive attention due to its rich material source, environmental non-toxicity, superior sodium storage capacity, and lower sodium storage potential, and is considered most likely to be a commercial anode material for sodium-ion batteries (SIBs). Nevertheless, the limited initial Coulombic efficiency (ICE) of HC is the main bottleneck hindering its practical application. To alleviate this issue, herein, a ZrO2 coating was skillfully constructed by using a facile liquid phase coating method. The ZrO2 coating can act as a physical barrier to prevent direct contact between the HC surface and the electrolyte, thus effectively reducing irreversible sodium adsorption and inhibiting the continuous decomposition of the electrolyte. Meanwhile, this fresh interface can contribute to the generation of a thinner solid electrolyte interface (SEI) with high ionic conductivity. As a result, the ICE of the ZrO2-coated HC electrode can be optimized up to 79.2% (64.4% for pristine HC). Furthermore, the ZrO2-coated HC electrode delivers outstanding cyclic stability so that the capacity retention rate can reach 82.6% after 2000 cycles at 1 A g−1 (55.8% for pristine HC). This work provides a flexible and versatile surface modification method to improve the electrochemical property of HC, and hopefully accelerate the practical application of HC anodes for SIBs.

Drought area expansion has a great impact on the growth and development of plants. To contribute to the water management of strawberry, this work aims to study the chronological relationship between the electrical signals and representative physiological parameters of strawberry seedlings under drought stress. This study analyzed the characteristic variables of the electrical signals; physiological parameters under drought; and control treatments. Moreover, we compared the chronological sequence of the appearance of significant differences between drought and control treatment in terms of their physiological parameters and electrical signals. The results showed that with the increase of drought treatment, the time domain parameters (peak-to-peak value, standard deviation) and frequency domain parameters (spectral of central gravity, power spectrum entropy) of the drought-treated electrical signals showed significant differences from the control on Day 2 and Day 6, respectively (p < 0.05). The root vitality of the drought treatment was significantly different from the control on Day 4 (p < 0.05); the Fv/Fm and the SPAD were significantly different (p < 0.05) on Day 7. Electrical signals first start to show a significant difference between drought and control treatment, followed by physiological parameters. Therefore, the electrical signal can be used as an early indicator of drought stress conditions. This will provide a scientific basis for the actual water management of strawberry seedlings. It also provides a methodological and theoretical basis for other studies analyzing the relationship between plant physiological parameters and electrical signals under other stress conditions.

Plants are susceptible to a variety of abiotic stresses during the growing period, among which low temperature is one of the more frequent stress factors. Maintaining water balance under cold stress is a difficult and critical challenge for plants. Studies have shown that aquaporins located on the cytomembrane play an important role in controlling water homeostasis under cold stress, and are involved in the tolerance mechanism of plant cells to cold stress. In addition, the aquaporin gene family is closely related to the cold resistance of plants. As a major greening tree species in urban landscaping, Ligustrum× vicaryi Rehd. is more likely to be harmed by low temperature after a harsh winter and a spring with fluctuating temperatures. Screening the target aquaporin genes of Ligustrum × vicaryi responding to cold resistance under natural cold stress will provide a scientific theoretical basis for cold resistance breeding of Ligustrum × vicaryi. In this study, the genome-wide identification of the aquaporin gene family was performed at four different overwintering periods in September, November, January and April, and finally, 58 candidate Ligustrum × vicaryi aquaporin (LvAQP) genes were identified. The phylogenetic analysis revealed four subfamilies of the LvAQP gene family: 32 PIPs, 11 TIPs, 11 NIPs and 4 SIPs. The number of genes in PIPs subfamily was more than that in other plants. Through the analysis of aquaporin genes related to cold stress in other plants and LvAQP gene expression patterns identified 20 LvAQP genes in response to cold stress, and most of them belonged to the PIPs subfamily. The significantly upregulated LvAQP gene was Cluster-9981.114831, and the significantly downregulated LvAQP genes were Cluster-9981.112839, Cluster-9981.107281, and Cluster-9981.112777. These genes might play a key role in responding to cold tolerance in the natural low-temperature growth stage of Ligustrum × vicaryi.

As a result of the continuous global warming in recent years, the average annual number of rain days in China has been on the decline, while the number of rainstorm days has gradually increased. These conditions make it extremely easy to form a waterlogging environment, which has an adverse impact on plant growth and development. In many apple-producing areas in China, apples are subject to severe flooding during planting. In this study, two-year-old apple rootstock M9T337 was used to explore the effects of interval water stress on the morphological and physiological parameters of apple leaves. The purpose was to determine the plant’s adaptability to waterlogged environments and provide theoretical reference for management and maintenance after waterlogging. The results showed that the effect on flooded (T2) on apple stock was greater than that of waterlogged (T1), Short-term (7 d) waterlogging (T1) did not affect the growth of seedlings but was conducive to the accumulation of dry matter. Furthermore, the initial stress was be imprinted on the plants, which could directly affect their response to later stress. The results of principal component analysis (PCA) revealed that PC1, PC2, and PC3 explained 26.92%, 17.46%, and 13.03% of the physiological changes under water stress, respectively. By calculating the weight of each indicator, we concluded that high-frequency resistance r, relative chlorophyll content (SPAD) and maximum photochemical efficiency Fv/Fm are important parameters for apple rootstocks affected by water stress.

The JNK and P38α pathways play an important role in the sensitivity and outcomes of chemotherapy. We hypothesize that functional single nucleotide polymorphisms (SNPs) of genes of these pathways modulate outcomes of patients with advanced non–small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy (PBC). We selectively genotyped 11 independent, potentially functional SNPs of 9 genes in the JNK and P38α pathways first in a discovery group of 355 patients with advanced NSCLC treated with PBC, and we evaluated their associations with progression-free survival (PFS) and overall survival (OS) by Cox proportional hazards regression analysis. Then, resultant significant SNPs were further validated in a replication group of 355 patients. In both discovery and validation groups as well as their combined analysis, the MAPK14 rs3804451GA/AA genotypes showed a strong association with a reduced PFS (adjusted hazards ratio [HR] = 1.39; 95% confidence interval [CI] = 1.16–1.66; P = .0003) and OS (adjusted HR = 1.41; 95% CI = 1.11-1.80; P = .005) compared with the wild-type GG genotype. In contrast, patients with or without the MAPK14 rs3804451A allele had no significant difference in OS in response to tyrosine-kinase inhibitor treatment (adjusted HR = 0.86; 95% CI = 0.56-1.33; P = .505). The present study provides evidence that the MAPK14 rs3804451 G>A variant may modulate survival outcomes in patients with advanced NSCLC treated with PBC. Larger studies of additional patient populations are needed to validate our findings.

Abstract Rechargeable high‐energy lithium–sulfur batteries suffer from rapid capacity decay and poor rate capability due to intrinsically intermediate polysulfides' shuttle effect and sluggish redox kinetics. To tackle these problems simultaneously, a layer‐by‐layer electrode structure is designed, each layer of which consists of ultrafine CoS2‐nanoparticle‐embedded porous carbon evenly grown on both sides of reduced graphene oxide (rGO). The CoS2 nanoparticles derived from metal–organic frameworks (MOFs) have an average size of ≈10 nm and can facilitate the conversion between Li2S6 and Li2S2/Li2S in the liquid electrolyte by a catalytic effect, leading to improved polysulfide redox kinetics. In addition, the interconnected conductive frameworks with hierarchical pore structure afford fast ion and electron transport and provide sufficient space to confine polysulfides. As a result, the layer‐by‐layer electrodes exhibit good rate capabilities with 1180.7 and 700 mAh g−1 at 1.0 and 5.0 C, respectively, and maintain an impressive cycling stability with a low capacity decay of 0.033% per cycle within ultralong 1000 cycles at 5.0 C. Even with a high sulfur loading of 3.0 mg cm−2, the electrodes still show high rate performance and stable cycling stability over 300 cycles.

Steel strands are crucial components of a prestressed structure, but their performance degrades inevitably with time. Among the existing nondestructive testing methods for measuring the stress state of steel strands, ultrasonic guided wave methods have received the most research attention and are most likely to be applied to actual engineering. This work views the propagation of ultrasonic guided wave as an individual system, and the variations in the stress state in steel strands can be related to the parameters gained by the system identification model. The finite element simulation and experimental results show the propagation characteristics of the guided wave are influenced distinctly by the stress state. The index constructed by the system parameters exhibits good monotonic linear with stress level variation, and the slope of the fitted line from experimental data is similar to the simulation result. The sensor placement and loading path have a limited effect on the stress state and the proposed index.

In this paper, the effect of pre-injection timing on the combustion and emission performance of methanol/diesel high premixed charge compression ignition (HPCCI) combustion mode at low load was studied by three-dimensional numerical simulation. The simulation is carried out under the conditions of 1900 r/min and 25% load, and the pre-injection diesel mass remains constant and the pre-injection timing is changed under the conditions of 50% and 60% methanol ratio respectively. The results show that with the delay of pre-injection timing, the evaporation of pre-injected fuel in cylinder becomes faster, the low temperature reaction is enhanced, and the peak value of heat release rate is higher. In addition, the distribution of pre-injected diesel in cylinder and the position of impact wall are the important factors affecting the combustion and emission performance in cylinder, and when the injection timing is -35 °CA ATDC, the combustion and emission characteristics of the engine are optimal. Finally, by comparing with the traditional RCCI combustion mode, the enhancement ability of HPCCI combustion mode on methanol combustion efficiency under low load is verified and analyzed.

The effects of methanol/polyoxymethylene dimethyl ethers (PODE) mixture with different blending ratios on premixed charge compression ignition (PCCI) combustion and emission performance have been researched through the anlysis of CFD software CONVERGE. Premixed combustion is achieved by a single early injection of fuel into the cylinder. The results show that the combustion start point delays and the peak pressure decreases with the increase of methanol blend ratio. The effects of injection timing on the combustion and emission characteristics of PCCI were studied by using a mixture of the same proportion of methanol. The results show that the advance of injection time leads to more homogeneous mixture and higher peak heat release. But too early injection reduces the temperature in the cylinder and makes the combustion worse, resulting in the increase of HC, soot and CO emissions. NOx emissions decrease with the advance of the injection time.

Degradation and low conductivity of transition metal oxide anodes cause capacity fading in lithium ion batteries. Here the authors make freestanding 3D copper oxide/carbon nitride core-shell nanoarrays which accommodate volume change, provide electro-active zones and facilitate rapid charge transport.

The research of marine antifouling is mainly conducted from the aspects of chemistry, physics, and biology. In the present work, the movement model of microorganisms along or against the flow direction on the microstructural surface was established. The model of globose algae with a diameter of 5 μm in the near-wall area was simulated by computational fluid dynamics (CFD), and the fluid kinematic characteristics and shear stress distribution over different-sized microstructures and in micropits were compared. Simulation results revealed that the increase of the β value (height to width ratio) was prone to cause vortexes in micropits. In addition, the closer the low-velocity region of the vortex center to the microstructural surface, the more easily the upper fluid of the microstructure slipped in the vortex flow and reduced the microbial attachment. Moreover, the shear stress in the micropit with a height and width of 2 μm was significantly higher than those in others; thus, microbes in this micropit easily fell off.

Accurate identification of tension in multiwire strands is a key issue to ensure structural safety and durability of prestressed concrete structures, cable-stayed bridges, and hoist elevators. This paper proposes a method to identify strand tensions based on scale energy entropy spectra of ultrasonic guided waves (UGWs). A numerical method was first developed to simulate UGW propagation in a seven-wire strand, employing the wavelet transform to extract UGW time-frequency energy distributions for different loadings. Mode separation and frequency band loss of L(0,1) were then found for increasing tension, and UGW scale energy entropy spectra were extracted to establish a tension identification index. A good linear relationship was found between the proposed identification index and tensile force, and effects of propagation distance and propagation path were analyzed. Finally, UGWs propagation was examined experimentally for a long seven-wire strand to investigate attenuation and long distance propagation. Numerical and experimental results verified that the proposed method not only can effectively identify strand tensions but can also adapt to long distance tests for practical engineering.

TERT is of great importance in cancer initiation and progression. Many studies have demonstrated the TERT polymorphisms as risk factors for many cancer types, including lung cancer. However, the impacts of TERT variants on cancer progression and treatment efficacy have remained controversial. This study aimed to investigate the association of TERT polymorphisms with clinical outcome of advanced non-small cell lung cancer (NSCLC) patients receiving first-line platinum-based chemotherapy, including response rate, clinical benefit, progression-free survival (PFS), overall survival (OS), and grade 3 or 4 toxicity. Seven polymorphisms of TERT were assessed, and a total of 1004 inoperable advanced NSCLC patients treated with platinum-based chemotherapy were enrolled. It is exhibited that the variant heterozygote of rs4975605 showed significant association with a low rate of clinical benefit, and displayed a much stronger effect in never-smoking female subset, leading to the clinical benefit rate decreased from 82.9% (C/C genotype) to 56.4% (C/A genotype; adjusted OR, 3.58; P=1.40×10(-4)). It is also observed that the polymorphism rs2736109 showed significant correlation with PFS (log-rank P=0.023). In age > 58 subgroup, patients carrying the heterozygous genotype had a longer median PFS than those carrying the wild-type genotypes (P=0.002). The results from the current study, for the first time to our knowledge, provide suggestive evidence of an effect of TERT polymorphisms on disease progression variability among Chinese patients with platinum-treated advanced NSCLC.

In this article, we report a simple, rapid, and efficient method to detect telomerase activity: the premature termination of telomeric extension-PCR (PTEP). Similar to the telomeric repeat amplification protocol (TRAP), this method is based on PCR amplification following the in vitro telomerase reaction, while the in vitro telomerase reaction here is prematurely, rather than randomly, terminated. Apart from this, the telomeric extension products are used as initial primers, instead of as templates, to trigger the amplification with a specially constructed plasmid DNA as the template that cannot be directly amplified with the telomerase primer. The end product is a specific 159-bp DNA fragment that reflects telomerase activity. Because its product can be clearly identified with routine agarose gel electrophoresis and ethidium bromide staining, PTEP allows even lesser-equipped laboratories to easily detect telomerase activity.

High altitude acclimatization is a series of physiological responses taking places when subjects go to altitude. Many factors could influence these processes, such as altitude, ascending speed and individual characteristics. In this study, based on a repeated measurement design of three sequential measurements at baseline, acute phase and chronic phase, we evaluated the effect of BMI, smoking and drinking on a number of physiological responses in high altitude acclimatization by using mixed model and partial least square path model on a sample of 755 Han Chinese young males. We found that subjects with higher BMI responses were reluctant to hypoxia. The effect of smoking was not significant at acute phase. But at chronic phase, red blood cell volume increased less while respiratory function increased more for smoking subjects compared with nonsmokers. For drinking subjects, red blood cell volume increased less than nondrinkers at both acute and chronic phases, while blood pressures increased more than nondrinkers at acute phase and respiratory function, red blood cell volume and oxygen saturation increased more than nondrinkers at chronic phase. The heavy and long-term effect of smoking, drinking and other factors in high altitude acclimatization needed to be further studied.

RAD52 is an important but not well characterized homologous recombination repair gene that can bind to single-stranded DNA ends and mediate the DNA-DNA interaction necessary for the annealing of complementary DNA strands. To evaluate the role of RAD52 variants in the response of tumor cells to platinum agents, we investigated their associations with platinum resistance and prognosis in cervical cancer patients. We enrolled 154 patients with cervical squamous cell carcinoma, who had radical surgery between 2008 and 2009, and genotyped three potentially functional RAD52 variants by the SNaPshot assay. We tested in vitro platinum resistance and RAD52 expression by using the MTT and immunohistochemistry methods, respectively. In 144 cases who had genotyping data, we found that both the rs1051669 variant and RAD52 protein expression were significantly associated with carboplatin resistance (P = 0.024 and 0.028, respectively) and rs10774474 with nedaplatin resistance (P = 0.018). The rs1051669 variant was significantly associated with RAD52 protein expression (adjusted OR = 4.7, 95% CI = 1.4-16.1, P = 0.013). When these three RAD52 variants were combined, progression-free survival was lower in patients who carried at least one (≥1) variant allele compared to those without any of the variant alleles (P = 0.047). Therefore, both RAD52 variants and protein expression can predict platinum resistance, and RAD52 variants appeared to predict prognosis in cervical cancer patients. Large studies are warranted to validate these findings.

Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV-related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV-positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV-positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×10⁻¹⁹) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×10⁻⁸), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×10⁻⁴; rs455804: OR = 0.84, P = 6.92×10⁻³). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV-related HCC, suggesting the involvement of glutamate signaling in the development of HBV-related HCC.

PURPOSE: Xeroderma pigmentosum group D (XPD) codes for a DNA helicase involved in nucleotide excision repair that removes platinum-induced DNA damage. Genetic polymorphisms of XPD may affect DNA repair capacity and lead to individual differences in the outcome of patients after chemotherapy. This study aims to identify whether XPD polymorphisms affect clinical efficacy among advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. EXPERIMENTAL DESIGN: 353 stage III-IV NSCLC patients receiving platinum-based chemotherapy as the first-line treatment were enrolled in this study. Four potentially functional XPD polymorphisms (Arg(156)Arg, Asp(312)Asn, Asp(711)Asp and Lys(751)Gln) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or PCR-based sequencing. RESULTS: Variant genotypes of XPD Asp(312)Asn, Asp(711)Asp and Lys(751)Gln were significantly associated with poorer NSCLC survival (P = 0.006, 0.006, 0.014, respectively, by log-rank test). The most common haplotype GCA (in order of Asp(312)Asn, Asp(711)Asp and Lys(751)Gln) also exhibited significant risk effect on NSCLC survival (log-rank P = 0.001). This effect was more predominant for patients with stage IIIB disease (P = 2.21×10(-4), log-rank test). Increased risks for variant haplotypes of XPD were also observed among patients with performance status of 0-1 and patients with adenocarcinoma. However, no significant associations were found between these polymorphisms, chemotherapy response and PFS. CONCLUSIONS: Our study provides evidence for the predictive role of XPD Asp(312)Asn, Asp(711)Asp and Lys(751)Gln polymorphisms/haplotype on NSCLC prognosis in inoperable advanced NSCLC patients treated with platinum-based chemotherapy.

BACKGROUND: Recent genome-wide association studies (GWAS) have found a single nucleotide polymorphism (SNP, rs2274223 A>G) in PLCE1 to be associated with risk of gastric adenocarcinoma. In the present study, we validated this finding and also explored the risk associated with another unreported potentially functional SNP (rs11187870 G>C) of PLCE1 in a hospital-based case-control study of 1059 patients with pathologically confirmed gastric adenocarcinoma and 1240 frequency-matched healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: We determined genotypes of these two SNPs by the Taqman assay and used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). We found that a significant higher gastric adenocarcinoma risk was associated with rs2274223 variant G allele (adjusted OR = 1.35, 95% CI = 1.14-1.60 for AG+GG vs. AA) and rs11187870 variant C allele (adjusted OR = 1.26, 95% CI = 1.05-1.50 for CG+CC vs. GG). We also found that the number of combined risk alleles (i.e., rs2274223G and rs11187870C) was associated with risk of gastric adenocarcinoma in an allele-dose effect manner (P(trend) = 0.0002). Stratification analysis indicated that the combined effect of rs2274223G and rs11187870C variant alleles was more evident in subgroups of males, non-smokers, non-drinkers and patients with gastric cardia adenocarcinoma. Further real-time PCR results showed that expression levels of PLCE1 mRNA were significantly lower in tumors than in adjacent noncancerous tissues (0.019±0.002 vs. 0.008±0.001, P

BACKGROUND: Longevity is a multifactorial trait with a genetic contribution, and mitochondrial DNA (mtDNA) polymorphisms were found to be involved in the phenomenon of longevity. METHODOLOGY/PRINCIPAL FINDINGS: To explore the effects of mtDNA haplogroups on the prevalence of extreme longevity (EL), a population based case-control study was conducted in Rugao--a prefecture city in Jiangsu, China. Case subjects include 463 individuals aged > or = 95 yr (EL group). Control subjects include 926 individuals aged 60-69 years (elderly group) and 463 individuals aged 40-49 years (middle-aged group) randomly recruited from Rugao. We observed significant reduction of M9 haplogroups in longevity subjects (0.2%) when compared with both elderly subjects (2.2%) and middle-aged subjects (1.7%). Linear-by-linear association test revealed a significant decreasing trend of N9 frequency from middle-aged subjects (8.6%), elderly subjects (7.2%) and longevity subjects (4.8%) (p = 0.018). In subsequent analysis stratified by gender, linear-by-linear association test revealed a significant increasing trend of D4 frequency from middle-aged subjects (15.8%), elderly subjects (16.4%) and longevity subjects (21.7%) in females (p = 0.025). Conversely, a significant decreasing trend of B4a frequency was observed from middle-aged subjects (4.2%), elderly subjects (3.8%) and longevity subjects (1.7%) in females (p = 0.045). CONCLUSIONS: Our observations support the association of mitochondrial DNA haplogroups with exceptional longevity in a Chinese population.

BACKGROUND: Multiplexing technologies, which allow for simultaneous detection of multiple nucleic acid sequences in a single reaction, can save a lot of time, cost and labor compared to traditional single reaction detection methods. However, the multiplexing method currently used requires precise handiwork and many complicated steps, making a new, simpler technique desirable. Oligonucleotides containing locked nucleic acid residues are an attractive tool because they have strong affinities for their complementary targets, they have been used to avoid dimer formation and mismatch hybridization and to enhance efficient priming. In this study, we aimed to investigate the use of locked nucleic acid pentamers for genomic DNA amplification and multiplex genotyping. RESULTS: We designed locked nucleic acid pentamers as universal PCR primers for genomic DNA amplification. The locked nucleic acid pentamers were able to prime amplification of the selected sequences within the investigated genomes, and the resulting products were similar in length to those obtained by restriction digest. In Real Time PCR of genomic DNA from three bacterial species, locked nucleic acid pentamers showed high priming efficiencies. Data from bias tests demonstrated that locked nucleic acid pentamers have equal affinities for each of the six genes tested from the Klebsiella pneumoniae genome. Combined with suspension array genotyping, locked nucleic acid pentamer-based PCR amplification was able to identify a total of 15 strains, including 3 species of bacteria, by gene- and species-specific probes. Among the 32 species used in the assay, 28 species and 50 different genes were clearly identified using this method. CONCLUSION: As a novel genomic DNA amplification, the use of locked nucleic acid pentamers as universal primer pairs in conjunction with suspension array genotyping, allows for the identification of multiple distinct genes or species with a single amplification procedure. This demonstrates that locked nucleic acid pentamer-based PCR can be utilized extensively in pathogen identification.