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A major challenge in human genetics is to identify the molecular mechanisms of trait-associated and disease-associated variants. To achieve this, quantitative trait locus (QTL) mapping of genetic variants with intermediate molecular phenotypes such as gene expression and splicing have been widely adopted(1,2). However, despite successes, the molecular basis for a considerable fraction of trait-associated and disease-associated variants remains unclear(3,4). Here we show that ADAR-mediated adenosine-to-inosine RNA editing, a post-transcriptional event vital for suppressing cellular double-stranded RNA (dsRNA)-mediated innate immune interferon responses(5–11), is an important potential mechanism underlying genetic variants associated with common inflammatory diseases. We identified and characterized 30,319 cis-RNA editing QTLs (edQTLs) across 49 human tissues. These edQTLs were significantly enriched in genome-wide association study signals for autoimmune and immune-mediated diseases. Colocalization analysis of edQTLs with disease risk loci further pinpointed key, putatively immunogenic dsRNAs formed by expected inverted repeat Alu elements as well as unexpected, highly over-represented cis-natural antisense transcripts. Furthermore, inflammatory disease risk variants, in aggregate, were associated with reduced editing of nearby dsRNAs and induced interferon responses in inflammatory diseases. This unique directional effect agrees with the established mechanism that lack of RNA editing by ADAR1 leads to the specific activation of the dsRNA sensor MDA5 and subsequent interferon responses and inflammation(7–9). Our findings implicate cellular dsRNA editing and sensing as a previously underappreciated mechanism of common inflammatory diseases.

Ultra-high-performance concrete (UHPC) has been regarded as promising alternative to provide reliable connections between difference segments (e.g., columns and pier footing/cap) during accelerated bridge construction (ABC) procedures. This paper proposes an innovative layered-UHPC connection for the pre-fabricated segmental (PFS) pier, whose seismic performance was validated through quasi-static experiment. The corresponding design procedure for PFS pier with this type of connections is presented based on the test results. The layered-UHPC connection ensures the emulative performance of pre-fabricated bridge as cast-in-place (CIP) ones, as well as provides greater economic efficiency than traditional UHPC connections. Based on experimental results, key issues concerning this connection, including the tensile behavior of UHPC, height of connection region, thickness of UHPC layer and steel bars in grouting bed, are presented and discussed. Then a seismic design procedure is proposed utilizing the capacity protection philosophy widely adopted in design specifications. The layered-UHPC connection is expected as capacity-protected component without damage, since it provides anchorage for steels extended from columns and pier cap/footing. While the pre-fabricated region is designed as ductile component undergoing nonlinearity during strong earthquakes. Following the detailed elaborations about the design philosophy, requirement and implementation steps, this procedure is further presented through illustration examples using PFS piers with various heights. The results show that PFS piers designed according to this procedure could meet the requirement under both frequent and rare earthquakes. Note that the PFS piers with this layered-UHPC connections could be designed similar to and emulative as CIP ones, which is believed friendly to designers in engineering practice.

Indocyanine green fluorescence cholangiography is a new type of cholangiography that has emerged in recent years. It has many advantages, such as simplicity, safety, and efficiency, and is expected to become a routine procedure for intraoperative cholangiography in the future. However, there is no bibliometric analysis of horizontal generalization in this field. Therefore, this study aims to assess the current research status and developmental trends in this field from a global perspective and to help guide the focus of future research.This study was conducted by retrieving the literature related to ICG fluorescence cholangiography published in English from 2000 to 2021 from Web of Science. The Histcite. Pro tool was used to analyze the bibliometric indicators, and VOSviewer was used to visualize the research trends and hotspots in this field.192 related studies were finally included. For the past 20 years, the number of related publications in this field have increased yearly, with 2010 being a breakthrough point for research in this field. Research has developed rapidly since 2013 and may continue to expand in the next several years. The USA and Japan play leading roles in this field. "SURG ENDOSC", "SURG INNOV", and "J LAPAROENDOSC ADV S" are core journals that publish high-quality literature and the latest developments in this field. Some authors who have a large number of high-quality publications include Ishizawa T and Kokudo N. The current research hotspots in this field are focused on exploring the factors that affect ICG cholangiography and optimization measures.In general, the number of documents related to ICG fluorescence cholangiography is growing rapidly, with the USA and Japan being influential countries and China being one of the major producers of these documents. The optimization of this new technology will affect key developments in future research.

Permeable asphalt mixtures are widely used to achieve good permeability of the pavements used for urban road surfaces. Based on the law of water migration in permeable road structures, the water-holding performance of permeable asphalt mixtures was analyzed and the evaluation indexes were determined. Open-graded asphalt friction course (OGFC-13) permeable asphalt mixture was selected, and the changes in the saturation, water retention, and water-holding rate of OGFC-13 permeable asphalt mixtures with different porosities were compared using water-holding equipment. The water-holding characteristics of permeable pavement materials under different seepage conditions were analyzed. A model of the relationship governing the water-holding capacity of the permeable asphalt mixture, water action conditions, and material porosity was established by a linear fitting method, and the reliability of the model was verified by comparison with laboratory test results, providing a foundation for related research on the water-holding and cooling behavior of permeable pavements.

Osteoclast over-activation leads to bone loss and chloride homeostasis is fundamental importance for osteoclast function. The calcium-activated chloride channel Anoctamin 1 (also known as TMEM16A) is an important chloride channel involved in many physiological processes. However, its role in osteoclast remains unresolved. Here, we identified the existence of Anoctamin 1 in osteoclast and show that its expression positively correlates with osteoclast activity. Osteoclast-specific Anoctamin 1 knockout mice exhibit increased bone mass and decreased bone resorption. Mechanistically, Anoctamin 1 deletion increases intracellular Cl− concentration, decreases H+ secretion and reduces bone resorption. Notably, Anoctamin 1 physically interacts with RANK and this interaction is dependent upon Anoctamin 1 channel activity, jointly promoting RANKL-induced downstream signaling pathways. Anoctamin 1 protein levels are substantially increased in osteoporosis patients and this closely correlates with osteoclast activity. Finally, Anoctamin 1 deletion significantly alleviates ovariectomy induced osteoporosis. These results collectively establish Anoctamin 1 as an essential regulator in osteoclast function and suggest a potential therapeutic target for osteoporosis.

Wetland is an important carbon pool, and the degradation of wetlands causes the loss of organic carbon and total nitrogen. This study aims to explore how wetland degradation succession affects soil organic carbon (SOC) and total nitrogen (TN) contents in alpine wetland. A field survey of 180 soil-sampling profiles was conducted in an alpine wetland that has been classified into three degradation succession stages. The SOC and TN contents of soil layers from 0 to 200 cm depth were studied, including their distribution characteristics and the relationship between soil water content (SWC) and microtopography. The results showed that SOC and TN of different degradation succession gradients followed the ranked order of Non Degradation (ND) > Light Degradation (LD) > Heavy Degradation (HD). SWC was positively correlated with SOC and TN (p

Low-resolution electron density maps can pose a major obstacle in the determination and use of protein structures. Herein, we describe a novel method, called quality assessment based on an electron density map (QAEmap), which evaluates local protein structures determined by X-ray crystallography and could be applied to correct structural errors using low-resolution maps. QAEmap uses a three-dimensional deep convolutional neural network with electron density maps and their corresponding coordinates as input and predicts the correlation between the local structure and putative high-resolution experimental electron density map. This correlation could be used as a metric to modify the structure. Further, we propose that this method may be applied to evaluate ligand binding, which can be difficult to determine at low resolution.

The understanding and controlling of the restrained shrinkage is critical for the application of ultra high performance concrete (UHPC). This study made an analysis of restrained shrinkage mechanism of four kinds of UHPCs based on the direct tensile test accompanied with acoustic emission (AE) source location, free shrinkage test and restrained shrinkage test. The effects of UHPC tensile properties (strain softening or strain hardening) and high performance calcium sulphoaluminate (HCSA, a new kind of expansion agent) dosages (0%, 3% and 6% by mass of total binder) were investigated. The restrained shrinkage cracking mechanism of strain hardening UHPC and strain softening UHPC was analyzed based on AE analysis method under direct tensile loading. The results indicates that strain hardening UHPC shows multiple micro-defects to relax the restrained tensile stress marginally while strain softening UHPC shows several hairline cracks to relax the restrained tensile stress evidently. In ASTM C1581-04 ring test, the restrained shrinkage of strain hardening UHPC with HCSA dosage of 0%, 3% and 6% at 80d is 141 μe, 96 μe and 16 μe, respectively. The HCSA expansion agent can effectively reduce the restrained shrinkage of UHPC and the influence on the structure.

With the advent of the information age, the Internet of Things (IoTs) technology has been favored by many industries and became another in-depth revolution of information technology industry. Under such an era, the application of the IoTs technology to the construction of intelligent buildings can broaden the practicality of intelligent systems, optimize resource allocation, and enhance the management and service capabilities of intelligent buildings, thereby improving people’s quality of life. On the basis of summarizing and analyzing previous research works, this paper elaborates the development status and future challenges of the IoTs technology, analyzes the impact of IoTs technology on intelligent buildings and intelligent manufacturing, and expounds the integrated system framework of intelligent building and building information model (BIM) technology, and proposes the system design of intelligent building and the architecture model of intelligent manufacturing based on the IoTs technology. The model verification results show that the intelligent manufacturing model of construction industry can realize the integration of human society and physical system and achieve the purpose of real-time management and control of personnel, machines, equipment, and infrastructure within the whole network. The study results of this paper provide a reference for the further research on the intelligent manufacturing model of construction industry based on the IoTs technology.

Condition monitoring (CM) and fault diagnosis are critical for the stable and reliable operation of mechanical transmissions. Mechanical transmission wear, which leads to changes in the physicochemical properties of the lubrication oil and thus severe wear, is a slow degradation process that can be monitored by oil analysis, but the actual degradation degree is difficult to evaluate. To solve this problem, we propose a new weighted evidential data fusion method to better characterize the degradation degree of the mechanical transmission through the fusion of multiple CM datasets from oil analysis. This method includes weight allocation and data fusion steps that lead to a more accurate data-based fault diagnostic result for CM. First, the weight of each evidence is modeled with a weighted average function by measuring the relative scale of the permutation entropy from each CM dataset. Then, the multiple CM datasets are fused by the Dempster combination rule. Compared with other evidential data fusion methods, the proposed method using the new weight allocation function seems more reasonable. The rationality and superiority of the proposed method were evaluated through a case study involving an oilbased CM dataset from a power-shift steering transmission.

Antibody phage display is a powerful platform for discovery of clinically applicable high affinity monoclonal antibodies against a broad range of targets. Libraries generated from immunized animals offer the advantage of in vivo affinity-maturation of V regions prior to library generation. Despite advantages, few studies have described isolation of antibodies from rats using immune phage display. In our study, we describe a novel primer set, covering the full rat heavy chain variable and kappa light chain variable regions repertoire for the generation of an unbiased immune libraries. Since the immune repertoire of rats is poorly understood, we first performed a deep sequencing analysis of the V(D)J regions of VH and VLK genes, demonstrating the high abundance of IGVH2 and IGVH5 families for VH and IGVLK12 and IGVLK22 for VLK. The comparison of gene’s family usage in naïve rats have been used to validate the frequency’s distribution of the primer set, confirming the absence of PCR-based biases. The primers were used to generate and assemble a phage display library from human CD160-vaccinated rats. CD160 represents a valid therapeutic target as it has been shown to be expressed on chronic lymphocytic leukaemia cells and on the surface of newly formed vessels. We utilised a novel phage display panning strategy to isolate a high affinity pool (KD range: 0.399–233 nM) of CD160 targeting monoclonal antibodies. Subsequently, identified binders were tested for function as third generation Chimeric Antigen Receptors (CAR) T cells demonstrating specific cytolytic activity. Our novel primer set coupled with a streamlined strategy for phage display panning enable the rapid isolation and identification of high affinity antibodies from immunised rats. The therapeutic utility of these antibodies was demonstrated in CAR format.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Ethylene plays essential roles during adaptive responses to water-saturating environments in rice, but knowledge of its signaling mechanism remains limited. Here, through an analysis of a rice ethylene-response mutant mhz1, we show that MHZ1 positively modulates root ethylene responses. MHZ1 encodes the rice histidine kinase OsHK1. MHZ1/OsHK1 is autophosphorylated at a conserved histidine residue and can transfer the phosphoryl signal to the response regulator OsRR21 via the phosphotransfer proteins OsAHP1/2. This phosphorelay pathway is required for root ethylene responses. Ethylene receptor OsERS2, via its GAF domain, physically interacts with MHZ1/OsHK1 and inhibits its kinase activity. Genetic analyses suggest that MHZ1/OsHK1 acts at the level of ethylene perception and works together with the OsEIN2-mediated pathway to regulate root growth. Our results suggest that MHZ1/OsHK1 mediates the ethylene response partially independently of OsEIN2, and is directly inhibited by ethylene receptors, thus revealing mechanistic details of ethylene signaling for root growth regulation., Ethylene regulates adaptive root growth during waterlogging in rice. Here, the authors identify MHZ1 (aka OsHK1), a histidine kinase that positively regulates the root ethylene response by interacting with the ethylene receptor ERS2 and promoting phosphorylation of the response regulator, OsRR21.

Deformation and recrystallization microtextures during the asymmetrical hot rolling (ASHR) process were investigated for a high-Mn austenitic steel by means of electron backscattered diffraction. The effects of velocity ratio and rolling reduction on the texture evolution were also analyzed. It was found that with the increase in velocity ratio and rolling reduction, the surface layer of 60% rolled ASHR plate develops a shear texture containing the γ-fiber, rotated cube and rotated copper components, but in the central layer is still a fcc rolling texture with a minor rotation around the transverse direction. The formation of surface shear texture could be understood as a consequence of the increased shear strain level, and it followed some certain crystallographic rotational relationships with the fcc rolling texture components. Additionally, the change of deformation texture under ASHR condition had an influence on the recrystallization texture, in which the proportion of {112} and {113} orientations was slightly improved, due to their rapid growth advantage and the orientation heredity of rotated copper shear texture.

Asymmetric hot rolling (ASHR) with a mismatch speed ratio of 1.15 in a single pass was applied to Fe-18Mn-18Cr-0.5N steel and was compared with symmetric hot rolling (SHR). The results indicated that a through-thickness microstructure gradient was formed in the plate due to the shear strain (0.36) introduced by ASHR. A fine-grained layer with the average size of ~3 μm was achieved at the top surface of ASHR plate, while numerous elongated grains with a few recrystallized grains were presented at the center layer. The texture was distributed randomly at the top surface of ASHR plate, and a weaker intensity of typical hot-rolled texture in austenitic steel was obtained at the center layer of ASHR plate compared to SHR plate. An excellent combination of microhardness, strength and ductility was obtained in the ASHR plate, which was attributed to gradient microstructure induced by ASHR.

Vehicle sideslip angle is one of the important indicators to determine whether vehicles are stable and is also a significant parameter for vehicle stability control. However, it is almost impossible to be measured directly without complex and expensive sensors or devices. Soft measurements are therefore generally adopted to estimate vehicle sideslip angle on the basis of easily observed physical quantities. This paper proposes an estimation method of sideslip angle based on steering torque instead of steering angle, for the fact that steering torque signal has more rapid and direct response compared with that obtained from steering angle. The frequency is analyzed between steering torque-sideslip angle and steering angle-sideslip angle transfer functions, and the extended Kalman filter (EKF) for vehicle sideslip angle based on steering torque is proposed. Both simulation results and vehicle tests prove the validity of our estimating method, indicating that the proposed method based on steering torque exhibits better accuracy and more rapid response in extreme region than the one based on steering angle.

A series of novel epoxy polymer shell microcapsules with n-tetradecane and dimethylbenzene as binary core materials are successfully synthesized via interfacial polymerization. Dimethylbenzene is used as the solvent for epoxy and n-tetradecane. The chemical structure, surface morphology, and thermal properties of the microencapsulated phase-change materials (micro-PCMs) are characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, and transmission electron microscope. Results show that the micro-PCMs have relatively spherical profiles and smooth surfaces with diameters ranging from 10 to 70 μm. The epoxy shell successfully encapsulates the binary core. Phase-change enthalpy and binary core content in the micro-PCMs increase with the increasing mass ratio of the binary core to the epoxy resin. The micro-PCMs degrade in two steps, and the resulting microcapsules exhibit good thermal stabilities. The degradation temperature decreases, as the core-to-shell mass ratio increases.

Assessing the response of flood risk caused by climate change and social development is very important in terms of determining high risk areas in different periods as well as making disaster mitigating plans. We establish a flood risk assessment model based on geographic information system and natural disaster risk assessment theory. In order to compare the index value in different periods and spaces, we utilize the spatial and temporal standardization method to standardized index. To avoid one-sidedness caused by using one weight calibration method only, we employ the least square method to synthesize weights determine by the Analytic Hierarchy Process (AHP) method and the Entropy weight method. We adopt the observed data of the Huaihe River basin from 1960 to 2010 to assess the changing of flood risk between period I (1960–1980) and period II (1980–2010). After pre-processing the atmosphere–ocean coupled global circulation models (AOGCM) data, including bias correction and downscaling, we use the corrected data to predict the flood risk during future period III (2010–2040). The results show that high risk areas and moderate to high risk areas during period I take up 17.68 and 33.88 % of the total area of the Huaihe River basin, respectively. During period II, the high risk areas show an increasing percent change of 1.93 % and a decreasing trend in moderate to high risk areas of 3.8 %. Compared with period II, the high risk areas and the moderate to high risk areas during period III show an increasing trend of 8.02 and 0.77 %, which is the result of the combined effects of climate change and social development. The results presented here can provide useful information for decision-makers.

Based on the rigid-plastic finite element method (FEM), the shear stress field of deformation region for high manganese austenite steel during hot asymmetrical rolling process was analyzed. The influences of rolling parameters, such as the velocity ratio of upper to lower rolls, the initial temperature of workpiece and the reduction rate, on the shear deformation of three nodes in the upper, center and lower layers were discussed. As the rolling parameters change, distinct shear deformation appears in the upper and lower layers, but the shear deformation in the center layer appears only when the velocity ratio is more than 1.00, and the absolute value of the shear stress in this layer is changed with rolling parameters. A mathematical model which reflected the change of the maximal absolute shear stress for the center layer was established, by which the maximal absolute shear stress for the center layer can be easily calculated and the appropriate rolling technology can be designed.

Asphalt concrete is one type of the temperature sensitive mixtures, which is the most and broadest used pavement material in the world. Asphalt pavement suffers from the impact of temperature due to the temperature variation in different districts and environments. Facing temperature sensitivity, this paper uses Indirect Tensile Test (IDT) to analyze the tensile characters of asphalt mixture under different temperatures (−20°C, −10°C, 0°C, 15°C, 20°C, 45°C, and 60°C). The influence factors of temperature, loading rate, asphalt content, asphalt types, and mixtures gradation are evaluated. Piecewise linear model, logarithm linear model and S-logistic nonlinear model are applied to simulate the variation of flexural tensile characters with temperature change. Results show that temperature has significant influence on flexural tensile properties. Loading rates also has obvious influence on flexural tensile characteristics. With temperature changes, asphalt types have evident influence on mixture’s tensile characteristics, SBR modified asphalt has better performance at the lower temperature environment. Mixtures’ gradation has important effect on tensile strength and tensile strain as well, while due the similarity between two gradations, it is hard to precisely recommend which one is better. Asphalt content has evident influence on mixtures properties at the same temperature condition. Research results provide suggestions and applications for construction and performance of asphalt pavement. The results also indicate that IDT would be a practical option to evaluate the properties of asphalt mixture in all temperature ranges.

Low average temperature, large temperature difference and continual freeze-thaw (F-T) cycles have significant impacts on mechanical property of asphalt pavement. F-T cycles test was applied to illustrate the mixtures’ compressive characteristics. Exponential model was applied to analyze the variation of compressive characteristics with F-T cycles; Loss ratio model and Logistic model were used to present the deterioration trend with the increase of F-T cycles. ANOVA was applied to show the significant impact of F-T cycles and asphalt-aggregate ratio. The experiment results show that the compressive strength and resilient modulus decline with increasing F-T cycles; the degradation is sharp during the initial F-T cycles, after 8 F-T cycles it turns to gentle. ANOVA results show that F-T cycles, and asphalt-aggregate ratio have significant influence on the compressive characteristics. Exponential model, Loss ratio model and Logistic model are significantly fitting the test data from statistics view. These models well reflect the compressive characteristics of asphalt mixture degradation trend with increasing F-T cycles.

Shape-memory epoxy is receiving considerable attention because of its superior mechanical and thermal properties and excellent shape-memory performance. In this study, a novel series of shape-memory epoxy resins are prepared using hydro-epoxy, hexahydrophthalic anhydride, and diglycidyl 4,5-epoxy tetrahydro phthalate (TDE-85) to further improve the recovery force of shape-memory epoxy resins. The thermal, mechanical, and shape-memory properties of the shape-memory epoxy resin system are investigated by differential scanning calorimetry, dynamic mechanical analysis, bend test, and shape recovery test. Results indicate that the glass transition temperature (Tg), rubber modulus, and room-temperature bend strength increase as TDE-85 content increases. Investigation of the shape-memory behavior of the resin reveals that full recovery can be achieved after only several minutes when the temperature is equal to or above Tg. The shape recovery time decreases with the increase in TDE-85 content at Tg, Tg + 10 °C, and Tg + 20 °C. These results are attributed to the increase in TDE-85 content.

Flood risk assessment and risk level zonation is very important for preventing the watershed flood disaster and making disaster mitigation plans. We establish a flood disaster risk assessment model based on GIS and natural disaster risk assessment theory. We build up a risk assessment index system based on hazard of natural environment and vulnerability of economic society. Furthermore, we propose two indices, reservoir storage modulus and flood detention basin modulus, and use them to characterize human intervention capability on flood in the hazard index set. To reduce the occurrence of the inconsistency problems when using analytic hierarchy process (AHP) method in multi-indices comparison, we use the coupled AHP and expert scoring method to determine the weights of indices. We apply the methodology to the Huaihe River basin. The results show that the multi-year average risk zonation map from 1960 to 2010 is consistent with the historical flood disaster distribution, which verifies the applicability of this method in flood disaster risk assessment.

This paper aims to investigate the wear and lubrication behaviors of wet Cu-based friction pairs. A mixed lubrication model in plane contacts is developed, and the tests of pin-on-disk are carried out. Wear losses are measured by the oil spectrum analysis method. The wear loss, the real contact area ratio, and the load sharing ratio are analyzed. Effects of sliding velocity, temperature, and pressure are considered. The results show that the temperature is the most significant influence on the wear loss of lubricated Cu-based friction pairs. As the temperature rises from 30 to 150 °C, wear loss increases from less than 0.4 mg to about 2.3 mg. The wear factor of the lubricated Cu-based friction pair in asperity contact areas is $$K_{c} = 9.4 \times 10^{ - 9}$$ (g/Nm). When the lubricated wear is slight, the oil spectrum analysis method is an effective approach to accurately determine the wear loss.

The 1,000 MPa ultra-high strength hot-rolled plate steel with low-carbon bainitic microstructure was developed in the laboratory for coal mine refuge chamber. The static recrystallization behavior, microstructure evolution, and mechanical properties of this hot-rolled plate steel were investigated by the hot compression, continuous cooling transformation, and tensile deformation test. The results show that the developed steel has excellent mechanical properties at both room and elevated temperature, and its microstructure mainly consists of lath bainite, granular bainite, and ferrite after thermal–mechanical control process (TMCP). The ultra-high strength plate steel is obtained by the TMCP process in hot rolling, strengthened by bainitic transformation, microstructure refinement, and precipitation of alloying elements such as Nb, Ti, Mo, and Cu. The experimental steel has relatively low welding crack sensitivity index and high atmospheric corrosion resistance index. Therefore, the developed steel has a good balance of strength and ductility both at room and elevated temperature, weldability and corrosion resistance, and it can suffice for the basic demands for materials in the manufacture of coal mine refuge chamber.

Nuclear factor kappa B (NF-κB) functions as a key regulator in the central nervous system and regulates the inflammatory pathway. There are two peaks of cerebral NF-κB activation after neonatal hypoxia–ischemia and subarachnoid hemorrhage. Our previous studies found that NF-κB activity was up-regulated at an early stage and remained elevated at day 7 after traumatic brain injury (TBI). However, data are lacking regarding an overview of NF-κB activity and expression of NF-κB subunits after TBI. Hence, the current study was designed to detect the time course of NF-κB activation and expression of NF-κB p65 and c-Rel subunits around the contused cortex following TBI. Adult Sprague–Dawley rats were randomly divided into sham and TBI groups at different time points. A TBI model was induced, and then the NF-κB DNA-binding activity in the surrounding areas of injured brain was detected by electrophoretic mobility shift assay. Western blotting was used to measure the protein levels of p65 and c-Rel in the nucleus. The concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay. Moreover, the distribution of c-Rel and p65 was examined by immunohistochemical studies. There were double peaks of cerebral cortical NF-κB activity, at 3 and 10 days post-injury. Additionally, protein levels of p65 were found to be elevated and peaked at 3 days after TBI, while levels of c-Rel were elevated significantly during the later phase of injury. Furthermore, TNF-α and IL-1β concentrations also showed a biphasic increase. Biphasic activation of NF-κB could be induced after experimental TBI in rats. NF-κB p65 and c-Rel subunits were elevated at different post-TBI time periods, leading to a hypothesis that different NF-κB subunits might be involved in different pathophysiological processes after TBI.

The tumor suppressor gene TP53 and its negative regulator murine double minute 2 are involved in multiple cellular pathways. Two potentially functional single nucleotide polymorphisms (SNPs) MDM2 SNP309 and TP53 R72P have been extensively investigated to be associated with breast cancer risk. However, the original studies as well as the subsequent meta-analysis, have yielded contradictory results for the individual effect of the two SNPs on breast cancer risk, plus that conflicting results also existed for the combined effects of MDM2 SNP309 and TP53 R72P on breast cancer risk. This meta-analysis aimed to clarify the individual and combined effects of these two genes on breast cancer risk. We performed a meta-analysis of publications with a total 9,563 cases and 9,468 controls concerning MDM2 SNP309 polymorphism and 19,748 cases and 19,962 controls concerning TP53 R72P. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of the association. In overall meta-analysis, individuals with the MDM2 SNP309TG genotype were associated with a borderline higher breast cancer risk than those with TT genotype (OR = 1.11, 95 % CI: 1.00-1.24, P (heterogeneity) = 0.007), whereas the TP53 R72P CC or GC genotype had no effects on breast cancer risk. In the stratified analyses, a significant association between MDM2 SNP309 and breast cancer risk were observed in Asian, but null significant association between TP53 R72P and breast cancer risk were found even in various subgroups. Moreover, no significant combined effects of MDM2 SNP309 and TP53 R72P were observed on breast cancer risk. The borderline association between MDM2 SNP309 and breast cancer risk in overall analysis should be treated with caution, and no significant combined effects for the two SNPs on breast cancer risk suggested functional investigations warranted to explore the molecular mechanism of the TP53-MDM2 circuit genes.

Soil salinity is a major environmental stress limiting plant productivity. Vacuole Na+/H+ antiporters play important roles for the survival of plants under salt stress conditions. We have developed salt stress tolerant transgenic tomato plants (Solanum lycopersicum cv. PED) by overexpression of the wheat Na+/H+ antiporter gene TaNHX2 using Agrobacterium tumefaciens strain LBA4404 harbouring a binary vector pBin438 that contains the TaNHX2 gene under the control of double CaMV 35S promoter and npt II as a selectable marker. PCR and Southern blot analysis confirmed that TaNHX2 gene has been integrated and expressed in the T1 generation transgenic tomato plants. When TaNHX2 expressing plants were exposed to 100 or 150 mM NaCl, they were found to be more tolerant to salt stress compared to wild type plants. Biochemical analyses also showed that transgenic plants have substantial amount of relative water content and chlorophyll content under salt stress conditions compared to wild type plants. The relative water content in transgenic and wild type plants ranged from 68 to 75 % and 46–73 % and chlorophyll content fall in between 1.8 to 2.4 mg/g fw and 1.0 to 2.4 mg/g fw, respectively, in all stress conditions. In the present study, we observed a better germination rate of T1 transgenic seeds under salt stress conditions compared with wild type plants. Our results indicated that TaNHX2-transgenic tomato plants coped better with salt stress than wild type plants.

Objective The aim of this study was to study changes of HER-2 expression after neoadjuvant chemotherapy in the breast cancer cases.

Taking tamoxifen orally is the main endocrine therapy of the premenopausal breast cancer with positive hormone receptor, but numerous patients developed to be advanced refractory breast cancer because of drug resistance. Our study investigated a role of the combination of bilateral oophorectomy and exemestane in the management of advanced refractory breast cancer. The bilateral oophorectomy was carried out in 17 patients. One week after the operation, exemestane was taken orally (25 mg/d). The median time to progression (TTP), the median survival time and the survival rate were calculated using Kaplan-Meier methods. Seventeen patients age ranged from 26 to 44 years (median, 36 years) were treated with an overall response rate of 64.70%, TTP was 8 months and the median survival time was 31 months. The survival rate of 1-year, 3 years and 5 years was 88.24%, 64.71%, 29.41%, respectively. There have no grade III/IV side effects appeared. Bilateral oophorectomy combined with exemestane is safe and effective for advanced refractory premenopausal breast cancer with positive hormone receptor and it is well-tolerated.

Plant-specific transcription factor NAC proteins play essential roles in many biological processes such as development, senescence, morphogenesis, and stress signal transduction pathways. In the NAC family, some members function as transcription activators while others act as repressors. In the present study we found that though the full-length GmNAC20 from soybean did not have transcriptional activation activity, the carboxy-terminal activation domain of GmNAC20 had high transcriptional activation activity in the yeast assay system. Deletion experiments revealed an active repression domain with 35 amino acids, named NARD (NAC Repression Domain), in the d subdomain of NAC DNA-binding domain. NARD can reduce the transcriptional activation ability of diverse transcription factors when fused to either the amino-terminal or the carboxy-terminal of the transcription factors. NARD-like sequences are also present in other NAC family members and they are functional repression domain when fused to VP16 in plant protoplast assay system. Mutation analysis of conserved amino acid residues in NARD showed that the hydrophobic LVFY motif may partially contribute to the repression function. It is hypothesized that the interactions between the repression domain NARD and the carboxy-terminal activation domain may finally determine the ability of NAC family proteins to regulate downstream gene expressions.

Ethylene regulates many aspects of growth, development and responses to environmental stresses in plants. Its signaling pathway has been established in model dicotyledonous plant Arabidopsis. However, its roles and signal transduction in monocotyledous rice plant remain largely unknown. In this review, we summarize the current advances in rice ethylene signaling studies and compare these with the results from Arabidopsis and other plants. Most of the components homologous to those in Arabidopsis ethylene signaling pathway have been found in rice, including five ethylene receptors, OsEIN2, OsEIL1, and OsERFs. Rice ethylene receptors are functionally more divergent than that of Arabidopsis. OsEIN2 and OsEIL1 display limited roles in regulation of rice ethylene responses compared with their Arabidopsis orthologs. ERF-like proteins OsERF1 and OsEBP-89 appear to be involved in rice ethylene signaling. However, whether they are activated through OsEIN2 and OsEIL1-mediated pathway needs further studies. Given that rice uses ethylene to control many processes that do not exist in Arabidopsis, it seems that new components or new mechanisms may exist in rice ethylene signaling pathway.

Ethylene perceived by a family of five receptors regulates many developmental processes in Arabidopsis. Here we conducted the yeast two-hybrid assay to screen for additional unidentified proteins that interact with subfamily II ethylene receptor ETR2. Three SAUR proteins, named SAUR76, 77 and 78, were identified to associate with both ETR2 and EIN4 in different assays. Interaction of SAUR76 and SAUR78 with ETR2 was further verified by co-immunoprecipitation and bimolecular fluorescence complementation (BiFC) assays. Expressions of SAUR76-78 are induced by auxin and ethylene treatments. Compared with wild type, SAUR-overexpressing plants exhibit reduced ethylene sensitivity, while SAUR-RNAi lines exhibit enhanced ethylene sensitivity. Overexpressing the three SAURs partially complements the phenotype of subfamily II ethylene receptor loss-of-function double mutant etr2-3ein4-4, which has increased ethylene response and small cotyledon and rosette. saur76 mutation partially suppresses the reduced ethylene sensitivity of etr2-2. SAUR76/78 proteins are regulated by 26S proteasome system and larger tag increases their protein stability. These findings suggest that SAUR76-78 may affect ethylene receptor signaling and promote plant growth in Arabidopsis.

Manganese peroxidase (MnP) is a major extracellular component of the lignin-degrading system of the white-rot fungus, Phanerochaete chrysosporium. Homologous expression of recombinant MnP isozyme 1 (rMnP1) in P. chrysosporium was achieved using a novel transformation system for this fungus, which utilizes the Streptomyces hygroscopicus bialaphos-resistant gene, bar, as the selectable marker. The transformation frequency for this system is approximately 100 bialaphos-resistant transformants per microgram of plasmid DNA. Transformed strains all contain plasmid DNA, ectopically integrated into the fungal genome. Using this transformation system, the promoter region of the P. chrysosporium translation elongation factor gene was used to drive expression of mnp1, encoding MnP1, in primary metabolic cultures of P. chrysosporium, where endogenous MnP was not expressed. Approximately 2-3 mg of active recombinant MnP1 per liter of extracellular medium was produced in agitated cultures of transformants.

Background Soybean is one of the most important oil crops. The regulatory genes involved in oil accumulation are largely unclear. We initiated studies to identify genes that regulate this process. Results One MYB-type gene GmMYB73 was found to display differential expression in soybean seeds of different developing stages by microarray analysis and was further investigated for its functions in lipid accumulation. GmMYB73 is a small protein with single MYB repeat and has similarity to CPC-like MYB proteins from Arabidopsis. GmMYB73 interacted with GL3 and EGL3, and then suppressed GL2, a negative regulator of oil accumulation. GmMYB73 overexpression enhanced lipid contents in both seeds and leaves of transgenic Arabidopsis plants. Seed length and thousand-seed weight were also promoted. GmMYB73 introduction into the Arabidopsis try cpc double mutant rescued the total lipids, seed size and thousand-seed weight. GmMYB73 also elevated lipid levels in seeds and leaves of transgenic Lotus, and in transgenic hairy roots of soybean plants. GmMYB73 promoted PLDα1 expression, whose promoter can be bound and inhibited by GL2. PLDα1 mutation reduced triacylglycerol levels mildly in seeds but significantly in leaves of Arabidopsis plants. Conclusions GmMYB73 may reduce GL2, and then release GL2-inhibited PLDα1 expression for lipid accumulation. Manipulation of GmMYB73 may potentially improve oil production in legume crop plants.