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Additional file 2: Table S1. The influence of each trail for the meta-analysis.

The wave spin of an electron can be fully characterized by the current density calculated from the exact four-spinor solution of the Dirac equation. In the excited states of the electron in a magnetic field-free quantum well, the current density has a multiple vortex topology. The interaction of the current with a magnetic potential produces a finer structure of anomalous Zeeman splitting. When the magnetic potential is comparable to the size of the individual vortices, fractional or zero spin effects can be observed., Comment: 6 pages, 4 figures

In the original version of the manuscript, the image shown in Figure 4g, bottom row (Aβ1–42 + rAggregatin), under “6h” was incorrect. This image incorrectly showed the same sample as shown in the original Figure 4g, top row (Aβ1–42), under “0.5h”. The correct version of figure 4g is as follows: (Figure presented.) which replaces the previous incorrect version: (Figure presented.).

Electronic phase separation (EPS) originates from an incomplete transformation between electronic phases, causing the inhomogeneous spatial distribution of electronic properties. In the system of two-dimensional electron gas (2DEG), the EPS is usually identified based on a percolative metal-to-superconductor transition. Here, we report a metal-insulator transition (MIT) in KTaO3-based 2DEG with the width of conductive channel decreasing into micrometer scale. Hysteretic resistance-temperature relations are observed due to the competition between metallic and insulating phases, which is tunable by magnetic field. Such a size-dependent MIT effect is attributed to the coexistence and separation of metallic and insulating phases. Combining density functional theory calculation, we propose a theoretical model to simulate the dynamic process of the EPS using the percolation theory, demonstrating the mechanism of size-dependent MIT. Our work suggests a clear and simple 2DEG platform to achieve the spatial coexistence of metallic and insulating phases.

Abnormality of enhancer regulation has emerged as one of the critical features for cancer cells. KDM5C is a histone H3K4 demethylase and frequently mutated in several types of cancer. It is critical for H3K4me3 and activity of enhancers, but its regulatory mechanisms remain elusive. Here, we identify TRIM11 as one ubiquitin E3 ligase for KDM5C. TRIM11 interacts with KDM5C, catalyzes K48-linked ubiquitin chain on KDM5C, and promotes KDM5C degradation through proteasome. TRIM11 deficiency in an animal model represses the growth of breast tumor and stabilizes KDM5C. In breast cancer patient tissues, TRIM11 is highly expressed and KDM5C is lower expressed, and their expression is negatively correlated. Mechanistically, TRIM11 regulates the enhancer activity of genes involved in cell migration and immune response by targeting KDM5C. TRIM11 and KDM5C regulate MCAM expression and cell migration through targeting H3K4me3 on MCAM enhancer. Taken together, our study reveals novel mechanisms for enhancer regulation during breast cancer tumorigenesis and development.

The bimodal grain-size distribution 0.9KNbO3-0.1BaTiO3 ceramics, with a typical perovskite structure in tetragonal phase at room temperature, were successfully prepared by an induced abnormal grain growth (IAGG) method at a relatively low sintering temperature. In this bimodal grain-sized distribution structure, the extra-large grains (about 10‒50 μm) were evolved from the micron-sized filler powders and the fine grains (about 0.05‒0.35 μm) were derived from the sol precursor matrix. The 0.9KNbO3-0.1BaTiO3 ceramics exhibit relaxor-like behavior with the diffused phase transition near room temperature, and confirmed by the existence of the polar nanodomain regions (PNRs) using the HRTEM images. The large room-temperature electrocaloric (EC) effect was found, characterized by an adiabatic temperature drop of 1.5 K, an isothermal entropy change of 2.48 J kg-1 K-1, and high EC strengths of ïDT/DEï = 1.50×10-6 KmV-1 and DS/DE = 2.48×10-6 Jmkg-1K-1V-1directly measured under E = 1.0 MV/m. These excellent ECEs demonstrate that this simple IAGG method is highly appreciated for synthesizing high-performance EC materials for efficient cooling devices.

In this paper, we introduce the dual index and dual core generalized inverse (DCGI). By applying rank equation, generalized inverse and matrix decomposition, we give several characterizations of the dual index when it is equal to one. And we get that if DCGI exists, then it is unique. We derive a compact formula for DCGI and a series of equivalent characterizations of the existence of the inverse. It is worth nothing that the dual index of $\hat{M}$ is equal to one if and only if its DCGI exists. When the dual index of $\hat{M}$ is equal to one, we study dual Moore-Penrose generalized inverse (DMPGI) and dual group generalized inverse (DGGI), and consider the relationships among DCGI, DMPGI, DGGI, Moore-Penrose dual generalized inverse (MPDGI) and other dual generalized inverses. In addition, we consider symmetric dual matrix and its dual generalized inverses. At last, two examples are given to illustrate the application of DCGI in linear dual equations.

Although morphology and grain size are important to rice growth and yield, the identity of abundant natural allelic variations that determine agronomically important differences in crops is unknown. Here, we characterized the function of mitogen-activated protein kinase 3 from Oryza officinalis Wall. ex Watt encoded by OrMKK3. Different alternative splicing variants occurred in OrMKK3. Green fluorescent protein (GFP)–OrMKK3 fusion proteins localized to the cell membrane and nuclei of rice protoplasts. Overexpression of OrMKK3 influenced the expression levels of the grain size-related genes SMG1, GW8, GL3, GW2, and DEP3. Phylogenetic analysis showed that OrMKK3 is well conserved in plants while showing large amounts of variation between indica, japonica, and wild rice. In addition, OrMKK3 slightly influenced brassinosteroid (BR) responses and the expression levels of BR-related genes. Our findings thus identify a new gene, OrMKK3, influencing morphology and grain size and that represents a possible link between mitogen-activated protein kinase and BR response pathways in grain growth. Supplementary Information The online version contains supplementary material available at 10.1007/s12374-020-09290-2.

The currently recommended management for acute traumatic spinal cord injury aims to reduce the incidence of secondary injury and promote functional recovery. Elevated intraspinal pressure (ISP) likely plays an important role in the processes involved in secondary spinal cord injury, and should not be overlooked. However, the factors and detailed time course contributing to elevated ISP and its impact on pathophysiology after traumatic spinal cord injury have not been reviewed in the literature. Here, we review the etiology and progression of elevated ISP, as well as potential therapeutic measures that target elevated ISP. Elevated ISP is a time-dependent process that is mainly caused by hemorrhage, edema, and blood-spinal cord barrier destruction and peaks at 3 days after traumatic spinal cord injury. Duraplasty and hypertonic saline may be promising treatments for reducing ISP within this time window. Other potential treatments such as decompression, spinal cord incision, hemostasis, and methylprednisolone treatment require further validation.

Ferroelectrics are essential in low-dimensional memory devices for multi-bit storage and high-density integration. A polar structure is a necessary premise for ferroelectricity, mainly existing in compounds. However, it is usually rare in elemental materials, causing a lack of spontaneous electric polarization. Here, we report an unexpected room-temperature ferroelectricity in few-chain Te nanowires. Out-of-plane ferroelectric loops and domain reversal are observed by piezoresponse force microscopy. Through density functional theory, we attribute the ferroelectricity to the ion-displacement created by the interlayer interaction between lone pair electrons. Ferroelectric polarization can induce a strong field effect on the transport along the Te chain, supporting a self-gated field-effect transistor. It enables a nonvolatile memory with high in-plane mobility, zero supply voltage, multilevel resistive states, and a high on/off ratio. Our work provides new opportunities for elemental ferroelectrics with polar structures and paves a way towards applications such as low-power dissipation electronics and computing-in-memory devices.

Additional file 1. Supplementary Table S1: Targeted NGS panel for the analysis for rare congenital anaemias.

Background Low temperature is a limiting factor of rice productivity and geographical distribution. Wild rice (Oryza rufipogon Griff.) is an important germplasm resource for rice improvement. It has superior tolerance to many abiotic stresses, including cold stress, but little is known about the mechanism underlying its resistance to cold. Results This study elucidated the molecular genetic mechanisms of wild rice in tolerating low temperature. Comprehensive transcriptome profiles of two rice genotypes (cold-sensitive ce 253 and cold-tolerant Y12–4) at the germinating stage under cold stress were comparatively analyzed. A total of 42.44–68.71 million readings were obtained, resulting in the alignment of 29,128 and 30,131 genes in genotypes 253 and Y12–4, respectively. Many common and differentially expressed genes (DEGs) were analyzed in the cold-sensitive and cold-tolerant genotypes. Results showed more upregulated DEGs in the cold-tolerant genotype than in the cold-sensitive genotype at four stages under cold stress. Gene ontology enrichment analyses based on cellular process, metabolic process, response stimulus, membrane part, and catalytic activity indicated more upregulated genes than downregulated ones in the cold-tolerant genotype than in the cold-sensitive genotype. Quantitative real-time polymerase chain reaction was performed on seven randomly selected DEGs to confirm the RNA Sequencing (RNA-seq) data. These genes showed similar expression patterns corresponding with the RNA-Seq method. Weighted gene co-expression network analysis (WGCNA) revealed Y12–4 showed more positive genes than 253 under cold stress. We also explored the cold tolerance gene LTG5 (Low Temperature Growth 5) encoding a UDP-glucosyltransferase. The overexpression of the LTG5 gene conferred cold tolerance to indica rice. Conclusion Gene resources related to cold stress from wild rice can be valuable for improving the cold tolerance of crops.

Alzheimer’s disease (AD) is characterized by amyloid plaques and progressive cerebral atrophy. Here, we report FAM222A as a putative brain atrophy susceptibility gene. Our cross-phenotype association analysis of imaging genetics indicates a potential link between FAM222A and AD-related regional brain atrophy. The protein encoded by FAM222A is predominantly expressed in the CNS and is increased in brains of patients with AD and in an AD mouse model. It accumulates within amyloid deposits, physically interacts with amyloid-β (Aβ) via its N-terminal Aβ binding domain, and facilitates Aβ aggregation. Intracerebroventricular infusion or forced expression of this protein exacerbates neuroinflammation and cognitive dysfunction in an AD mouse model whereas ablation of this protein suppresses the formation of amyloid deposits, neuroinflammation and cognitive deficits in the AD mouse model. Our data support the pathological relevance of protein encoded by FAM222A in AD., In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

Low temperature is one of the important environmental factors that affect rice growth and yield. To better understand the japonica rice responses to cold stress, isobaric tags for relative and absolute quantification (iTRAQ) labeling based quantitative proteomics approach was used to detected changes in protein level. Two-week-old seedlings of the cold tolerance rice variety Kongyu131 were treated at 8°C for 24, 48 and 72 h, then the total proteins were extracted from tissues and used for quantitative proteomics analysis. A total of 5082 proteins were detected for quantitative analysis, of which 289 proteins were significantly regulated, consisting of 169 uniquely up-regulated proteins and 125 uniquely down-regulated proteins in cold stress groups relative to control group. Functional analysis revealed most of regulation proteins involved in photosynthesis, metabolic pathway, biosynthesis of secondary metabolites and carbon metabolism. Western blot analysis showed that protein regulation was consistent with the iTRAQ data. The corresponding genes of 25 regulation proteins were used for quantitative real time PCR analysis, and the results showed that the mRNA level was not always parallel to the corresponding protein level. The importance of our study is providing new insights into cold stress responses in rice on proteomic aspect.

Background Percutaneous kyphoplasty (PKP) can effectively treat osteoporotic vertebral compression fractures (OVCFs). Although satisfactory clinical outcomes can be achieved, bone cement leakage remains a primary complication of PKP. Previous studies have found many high risk factors for bone cement leakage into the spinal canal; however, less attention to the posterior wall morphologies of different vertebral bodies may be one reason for the leakage. Here, we investigated the effect of posterior vertebral wall morphology in OVCF patients on bone cement leakage into the spinal canal during PKP. Methods Ninety-eight OVCF patients with plain computed tomography (CT) scans and three-dimensional (3D) reconstruction images from T6 to L5 were enrolled. 3D-CT and multiplanar reconstructions (MPR) were used to measure the concave posterior vertebral wall depth (PVWCD) and the corresponding midsagittal diameter of the nonfractured vertebral body (VBSD), and the PVWCD/VBSD ratio was calculated. All subjects were divided into the thoracic or lumbar groups based on the location of the measured vertebrae to observe the value and differences in the PVWCD between both groups. The differences in PVWCD and PVWCD/VBSD between the thoracic and lumbar groups were compared. Three hundred fifty-seven patients (548 vertebrae) who underwent PKP within the same period were also divided into the thoracic and lumbar groups. The maximal sagittal diameter (BCSD), the area of the bone cement intrusion into the spinal canal (BCA), and the spinal canal encroachment rate (BCA/SCA × 100%) were measured to investigate the effect of the thoracic and lumbar posterior vertebral wall morphologies on bone cement leakage into the spinal canal through the Batson vein during PKP. Results The PVWCDs gradually deepened from T6 to T12 (mean, 4.6 mm); however, the values gradually became shallower from L1 to L5 (mean, 0.6 mm). The PVWCD/VBSD ratio was approximately 16% from T6 to T12 and significantly less at 3% from L1 to L5 (P 2, and the BCA/SCA ratio was 17.2 ± 2.0%. In the lumbar group, the BCSD was 1.4 ± 0.3 mm, the BCA was 14.8 ± 2.2 mm2, and the BCA/SCA ratio was 7.4 ± 1.0%. The BCSD, BCA and BCA/SCA ratio were significantly higher in the thoracic group than in the lumbar group (P Conclusions The PVWCD in the middle and lower thoracic vertebrae can help reduce bone cement leakage into the spinal canal by enabling avoiding bone cement distribution over the posterior 1/6 of the vertebral body during PKP. The effect of the difference between the thoracic and lumbar posterior vertebral wall morphology on bone cement leakage into the spinal canal through the Batson vein in OVCF patients during PKP is one reason that the rate of bone cement leakage into the thoracic spinal canal is significantly higher than that into the lumbar spinal canal.

The brown planthopper (BPH) is a serious insect pest of rice and a substantial threat to rice production. Identification of new BPH resistance genes and their transfer into modern rice cultivars are effective breeding approaches to reduce the damage caused by BPH. In this study, we mapped a BPH resistance gene to a 50-kb genomic interval between two InDel markers 4M03980 and 4M04041 on the short arm of chromosome 4 in indica rice cultivar BP60, where the BPH resistance gene was mapped in Rathu Heenati by Liu et al. (2015) and named "Bph3". This region contains two annotated genes Os04g0201900 and Os04g0202300, which encode lectin receptor kinases responsible for BPH resistance. We also developed a molecular marker "MM28T" for Bph3, and introgression Bph3 into susceptible rice restorer lines Guihui582 and Gui7571 by the marker-assisted selection (MAS) approach. The BPH resistance level is significantly enhanced in the Bph3-introgression lines, the resistance scores decrease from 8.2 to 3.6 for Guihui582 and decrease from 8.7 to around 3.8 for Gui7571. Therefore, developing molecular markers for the BPH resistance gene Bph3 and using them for molecular breeding will facilitate the creation of BPH-resistance rice cultivars to reduce damage caused by BPH.

The ideal plant architecture is a new strategy for super high yield breeding of rice. Tiller angle is an important plant architecture character of rice. A reasonable tiller angle is a key factor for the ideal plant architecture and achieving high-yield breeding. Molecular design breeding is the most potential new direction of crop breeding in the future. The development of accurate and efficient functional molecular markers of target trait genes is crucial for molecular design breeding. The TAC1 (Tiller Angle Controlling) gene is the primary gene that regulates tiller angle in rice. This gene can be used to improve the compact plant architecture of indica and japonica rice varieties. The SNP variation from A to G at the fourth intron 3′ splicing point in TAC1 changes plant architecture. Based on the SNP variation, PM-TAC1 was successfully developed as a fluorescent functional molecular marker, via the penta-primer amplification refractory mutation system. Ninety-three rice materials were genotyped using this marker, and the marker was effectively used in rice plant architecture breeding. The successful development of this marker will contribute to the molecular breeding of rice plant architecture.

In this study, the closely linked fluorescence molecular marker PM-Xa7 of Xa7 gene was developed on the basis of sequence difference between the resistant variety ‘IRBB7’ containing Xa7 and other nine bacterial blight susceptible rice varieties, and combine with PARMS technology (Penta-primer amplification refractory mutation system). Genotypes of Xa7 were identified in 72 rice germplasm and the bacterial blight resistance level of ‘Mei B’ was improved by backcross and screening with this marker. The results showed that two rice germplasms containing Xa7 were screened out from 72 rice germplasm; By introducing the resistant Xa7 gene from ‘IRBB7’ into ‘Mei B’ with PM-Xa7, a stable new maintainer with resistance to bacterial blight was successfully obtained. The bacterial blight resistant fluorescence signal was detected in 289 plants and the bacterial blight susceptible fluorescence signal was detected in 93 plants of BC 2 F 2 population generated from ‘IRBB7’ and ‘Mei B’, and the genotypes were consistent with the phenotypes of Xoo inoculation. These research results indicated that PM-Xa7 can be effectively used for the marker-assisted breeding of bacterial blight resistant rice variety with the resistant Xa7 gene.

Supplemental material, sj-pdf-1-tpp-10.1177_2045125320982720 for Current antipsychotic agent use and risk of venous thromboembolism and pulmonary embolism: a systematic review and meta-analysis of observational studies by Yinzhao Liu, Jun Xu, Kacey Fang, Yue Xu, Ju Gao, Chao Zhou, Xiaowei Tang, Xinyu Fang, Jiu Chen, Chunming Xie, Fuquan Zhang, Xiangrong Zhang and Congjie Wang in Therapeutic Advances in Psychopharmacology

Supplemental material, sj-pdf-1-tpp-10.1177_2045125320982720 for Current antipsychotic agent use and risk of venous thromboembolism and pulmonary embolism: a systematic review and meta-analysis of observational studies by Yinzhao Liu, Jun Xu, Kacey Fang, Yue Xu, Ju Gao, Chao Zhou, Xiaowei Tang, Xinyu Fang, Jiu Chen, Chunming Xie, Fuquan Zhang, Xiangrong Zhang and Congjie Wang in Therapeutic Advances in Psychopharmacology

Additional file 1: Figure S1. Development of monoclonal A��-Th1 and A��-Th17 cells. Figure S2. Modelling and explicit solvent molecular dynamics simulations. Figure S3. Adoptive transfer of A��-Teffs did not affect T cell frequency in APP/PS1 mice. Figure S4. Transcriptomic analysis of immune genes. Figure S5. Western blot images.

Perturbation theory is a kind of estimation method based on theorem of Taylor expansion, and is useful to investigate electromagnetic solutions of small changes. By considering a sharp boundary as a limit of smoothed systems, previous study has solved the problem when applying standard perturbation theory to Maxwell's equations for small shifts in isotropic dielectric interfaces. However, when dealing with anisotropic materials, an approximation is conducted and leads to an unsatisfactory error. Here we develop a modified perturbation theory for small shifts in anisotropically dielectric interfaces. By using optimized smoothing function for each component of permittivity, we obtain a method to calculate the intrinsic frequency shifts of anisotropic permittivity field when boundaries shift, without approximation. Our method shows accurate results when calculating eigenfrequency's shifts in strong-anisotropy materials, and can be widely used for small shifts in anisotropically dielectric interfaces.

Background: Nitrogen (N) is a major nutrient element for crop yield improvement, but it also causes environmental problems. Therefore, N use efficiency (NUE) enhancement is an important strategy to solve this problem. In plants, the members of the peptide transporter (PTR) gene family are involved in nitrate uptake and transport. In this study, we performed a genome-wide analysis on PTR genes in Nipponbare, R498, and Oryza glaberrima, and identified 96, 85, and 78 PTR genes respectively. Results: Phylogenetic tree showed that the 96 PTR genes could be classified into 8 groups, and the distributions of PTR genes in Asian cultivated riceand African cultivated rice were consistent. The number of PTR gene was higher in peanuts and soybeans, which were 125 and 127, respectively. The 521 PTR genes in rice, maize, sorghum, peanut, soybean and Arabidopsis could be classified into 4 groups, and the PTR gene distribution was different between monocots and dicots. In Nipponbare genome, the 25 PTR genes were distributed in 5 segmental duplication regions on chromosome 1, 2, 3, 4, 5, 7, 8, 9, and 10. Rice PTR genes have 0-11 introns and 1-12 exons , and 16 PTR genes have the NPF (NRT1/PTR family ) domain. The results of RNA-Seq showed that the number of differentially expressed genes (DEGs) between NIL15 and NIL19 were 928, 1467, and 1586 at three stages, respectively. Under low N conditions, the number of differentially expressed PTR genes increased significantly. The RNA-Seq data was analyzed using WGCNA to predict the potential interaction between genes. We classified the genes with similar expression pattern into one group, and obtained 25 target modules. Among these modules, three modules may be involved in rice nitrogen uptake and utilization, especially the brown module, in which hub genes were annotated as protein kinase that may regulate rice N metabolism. Conclusions: In this study, we comprehensively analyzed the PTR gene family in rice. Ninety-six PTR genes were identified in Nippobare genome and twenty-five genes locates on five large segmental duplication regions. The Ka/Ks ratio indicated that many PTR genes had nudergone positive selection. The RNA-seq results showed that many PTR genes were involved in rice UNE. Protein kinases may play an important role in regulating NUE in rice. These results will provide a fundamental basis for molecular breeding of NUE in rice.

Alzheimer's disease (AD) is characterized by amyloid plaques and progressive cerebral atrophy. Here, we report FAM222A as a putative brain atrophy susceptibility gene. Our cross-phenotype association analysis of imaging genetics indicates a potential link between FAM222A and AD-related regional brain atrophy. The protein encoded by FAM222A is predominantly expressed in the CNS and is increased in brains of patients with AD and in an AD mouse model. It accumulates within amyloid deposits, physically interacts with amyloid-β (Aβ) via its N-terminal Aβ binding domain, and facilitates Aβ aggregation. Intracerebroventricular infusion or forced expression of this protein exacerbates neuroinflammation and cognitive dysfunction in an AD mouse model whereas ablation of this protein suppresses the formation of amyloid deposits, neuroinflammation and cognitive deficits in the AD mouse model. Our data support the pathological relevance of protein encoded by FAM222A in AD.

Additional file 10: Appendix S2. Seqence of LTG5 from “Y12–4”.

Van der Waals (vdW) heterojunctions, based on two-dimensional (2D) materials, show great potential for the development of eco-friendly and high-efficiency nano-devices. Considerable research has been performed and has reported valuable applications of photovoltaic cells, photodetectors, etc. However, simultaneous energy conversion and storage in a single device has not been achieved. Here, we demonstrate a simple strategy to construct a vdW p-n junction between a WSe2 layer and quasi-2D electron gas. After once optical illumination, the device stores the light-generated electrons and holes for up to seven days, and then releases a very large photocurrent of 2.9 mA with bias voltage applied in darkness; this is referred to as chargeable photoconductivity (CPC), which completely differs from any previously observed photoelectric phenomenon. In normal photoconductivity, the recombination of electron-hole pairs takes place at the end of their lifetime, causing a release of heat; in contrast, infinite-lifetime photocarriers can be generated in CPC devices without a thermal loss. The photoelectric conversion and storage are completely self-excited during the charging process. The ratio between currents in full- and empty-energy states below the critical temperature reaches as high as 109, with an external quantum efficiency of 4410000% during optical charging. A theoretical model developed to explain the mechanism of this effect is in good agreement with the experimental data. This work paves a path towards storage-type photoconductors and high-efficiency entropy-decreasing devices.

Hepatofibrosis can progress to cirrhosis and hepatocellular carcinoma (HCC). Prevention, stabilization, and reversal of disease progression are vital for patients with hepatofibrosis, and identifying the risk factors for hepatofibrosis is urgently needed. In this study, we examined the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the fibrotic livers of HCC patients (n = 88) and comparied these results with activities in patients with normal livers (n = 74). A fibrosis-carcinoma rat model was used to study the activity of ADH in fibrosis and HCC and the relationship between innate ADH activity and the extent of hepatofibrosis or HCC. Substantial interindividual variations were found in the activities of ADH and ALDH in normal livers. The activity levels of total ADH, ADHI, and ADHII in fibrotic livers were significantly higher than those in normal livers (P < 0.001), whereas the activity of ALDH was slightly greater. The positive rates of ADHI and ADHII were 84.1% and 77.3%, respectively; the areas under the receiver operator characteristics (ROC) curve were 0.943 and 0.912, respectively. For the rat model compared with controls, ADH activity in liver was significantly increased at the fibrotic and HCC stages, and no significant difference was noted between ADH activity in the liver at these two stages. The innate activity of ADH in serum was well correlated with the extent of hepatofibrosis as indicated by Masson area%, Ki67+%, proliferating cell nuclear antigen +%, and GST-p average density at fibrotic stage but not at HCC stage. A higher level of activity of ADH is a risk factor for hepatofibrogenesis and might be a prevention target for hepatofibrosis.

Fog radio access networks (F-RANs) are regarded as a promising solution for the future wireless networks by incorporating the concept of fog computing into the architecture of wireless access networks. F-RANs make full use of the computing and storage capabilities of edge network devices, and can effectively alleviate the overhead of backhaul links and reduce the processing delay of the tasks. However, existing researches were mostly focused on the coupled uplink and downlink scenario which will lead to insufficient utilization of resources and high energy consumption. In order to solve above problems, we introduce the decoupled the uplink and downlink (DUDA) access mode to F-RANs and jointly optimize the user access and computation offloading decisions with the aim of energy consumption minimization. To reduce the computational complexity, we further utilize the reinforcement learning algorithm to solve this complex combinatorial optimization problem. The simulation results show that compared with other schemes, the proposed algorithm can significantly improve the energy consumption performance while meeting user demands.

Hepatofibrosis is an important susceptibility factor for hepatocarcinogenesis. However, only a handful of cases of hepatofibrosis will develop into hepatocellular carcinoma (HCC). As cytochrome P450 2E1 (CYP2E1) is involved in the metabolism and activation of many known environmental toxicants and procarcinogens, this enzyme may play a role in the development of hepatocarcinogenesis subsequent to hepatofibrosis. Herein, we evaluated whether higher CYP2E1 activity is a risk factor for the development of hepatocarcinogenesis from hepatofibrosis. CYP2E1 activity in fibrotic tissues from 72 HCC patients and in normal liver tissues from 59 control subjects was determined along with the severity of hepatofibrosis in hepatocarcinogenesis patients. Similarly, using a rat diethylnitrosamine-induced hepatocarcinogenesis model, CYP2E1 activity at the hepatofibrosis and hepatocarcinogenesis stages was determined, the correlation between CYP2E1 activity at the hepatofibrosis stage and hepatocarcinogenesis was explored, and the impact of inhibition of CYP2E1 activity on hepatocarcinogenesis was studied. The results showed that while CYP2E1 activity in HCC patients with underlying hepatofibrosis was increased, the severity of hepatofibrosis did not correlate with CYP2E1 activity. In the rat hepatocarcinogenesis model, unexpectedly, CYP2E1 activity was found to decrease from hepatofibrosis to hepatocarcinogenesis. Importantly, however, hepatofibrotic rats with higher CYP2E1 activity developed a more severe form of HCC. Moreover, inhibition of CYP2E1 activity could decrease the occurrence and development of HCC in rats. In conclusion, higher CYP2E1 activity may be a risk factor for hepatocarcinogenesis from hepatofibrosis, which raises the possibility of screening patients with hepatofibrosis for CYP2E1 activity to better estimate their risk for hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is one of the most common types of primary liver cancer and the third most frequent cause of cancer death worldwide. Diethylnitrosamine (DEN) is one of the recognized risk factors for hepatocarcinogenesis likely due to CYP2E1-mediated metabolic activation. However, CYP2E1-mediated DEN metabolic activity in non-neoplastic liver tissue from HCC patients has not been determined; the role of CYP2E1 activity, in particular CYP2E1 constitutive activity and CYP2E1 inhibited activity, with respect to the hepatocarcinogenesis induced by DEN is not yet clear. Herein, we determined CYP2E1-mediated DEN metabolic activity in non-neoplastic liver tissue from HCC patients and found that CYP2E1-mediated DEN metabolic activity was significantly elevated with a 43.3% positive rate, and clinicopathologic parameters did not affect the activity. Then, using a Sprague-Dawley rat liver tumor model induced by DEN, the relationship between CYP2E1 constitutive/inhibited activity and hepatocarcinogenesis was explored. The results showed that the CYP2E1 constitutive activity was strongly correlated with tumor incidence and severity of liver tumorigenesis (nodule numbers and size), whereas inhibition of CYP2E1 activity decreased hepatocyte proliferation, liver injury, and liver carcinogenesis in the presence of DEN. In conclusion, the higher CYP2E1 activity would lead to an increased incidence of HCC as a result of CYP2E1-mediated DEN activation. Therefore, higher CYP2E1 activity might be a risk factor for HCC induced by DEN.

Hepatofibrosis, which leads to cirrhosis and eventual hepatocellular carcinoma, is a common response to chronic toxin-mediated liver injury. Nitrosamines are potent hepatotoxic agents that cause necrosis and subsequent fibrosis in the liver as a result of cytochrome P450 2E1 (CYP2E1)-dependent metabolism, which generates toxic metabolites that form adducts with nucleic acids, leading to hepatotoxicity and mutagenesis. Herein, CYP2E1 activity and content were determined in fibrotic liver tissue from patients with hepatocellular carcinoma. The relationship between CYP2E1 innate activity and hepatofibrogenesis was evaluated, the effect of inhibition of CYP2E1 activity on hepatofibrosis was determined in a Sprague-Dawley rat model of diethylnitrosamine-induced hepatofibrosis. The results demonstrated that the CYP2E1 activities in human fibrotic tissues are significantly higher than that in normal liver tissues. In rats treated with diethylnitrosamine, the livers demonstrated various degree of fibrotic changes and collagen deposition in individual rats. The Ishak score, which determines the stage of fibrosis, correlated with CYP2E1 innate activity, with greater fibrosis in rat livers with higher CYP2E1 innate activity. Inhibition of CYP2E1 during diethylnitrosamine treatment decreased hepatofibrosis and there was an inverse correlation between the degree of inhibition and the extent of hepatofibrosis. Therefore, high CYP2E1 activity is a risk factor for hepatofibrogenesis induced by nitrosamines.

Co-crystallization of 4-hydroxyisophthalic acid (4-HIPA) with 2-methylpyrazine (MP), 2,3-dimethylpyrazine (DMP), and 2,3,5,6-tetramethylpyrazine (TMP) has been performed, resulting in the formation of three co-crystals 1 (MP:2(4-HIPA)), 2 (DMP:2(4-HIPA)), and 3 (TMP:2(4-HIPA)), respectively. The co-crystals were analyzed using single-crystal X-ray diffraction, infrared spectroscopy, thermogravimetric analysis (TGA), fluorescence spectroscopy, and UV–vis spectroscopy. Hirshfeld surface analysis revealed that the proportion of O–H⋯N interactions in the co-crystals decreased with increasing number of methyl groups on the pyrazine derivative. In comparison with 4-HIPA, the maximum absorption peaks in the UV–vis absorption spectra of co-crystals 1 – 3 exhibited a red shift, which was caused by the presence of the corresponding pyrazine derivative in each case. As the number of methyl groups on the pyrazine derivatives increased, a weak blue shift was observed in UV–vis spectrum (Fig. 5). The fluorescence emission spectra peaks of co-crystal 1–3 were nearly at same position, 440 nm for solution state, 396 nm for solid state, irrespective of the number of methyl groups.

In order to determine the effect of halogen bonding on supramolecular assemblies and photophysical properties of diaryl oxalates, diaryl oxalate itself and its derivatives with fluorine, chlorine, bromine, and iodine substituents in the p-position of phenyl rings were studied and compared. Their single-crystal structures were studied by geometrical analysis and theoretical calculation. The study reveals that different halogen bonds are formed with respect to different halogen atoms, such as C…F and X…X (bromine and iodine atoms) interactions, and molecular stacking modes would be affected by halogen bonds directly. Comparative studies of photophysical properties in dilute solution and solid state indicate that halogen substitutions would not affect the emission processes of diaryl oxalates in dilute solution; this is not the case for their solid state. This work has demonstrated that halogen bonds play an important role in regulating structures and photophysical properties of diaryl oxalates.

Investigations of spin-crossover in an iron(II) tris(diimine) system, based on the ligands L1 (4,5-dimethy-2-(pyridine-2-yl)imidazole) and L2 (1-acetic ethyl-2-(pyridine-2-yl)-imidazole), have been presented in this paper. The methyl groups at adjacent sites to the donor atoms in the ligand L1 generated the crossover situation for complexes Fe(L1)3(ClO4−)2 (1), Fe(L1)3(BF4−)2 (2), Fe(L1)3(PF6−)2 (3) and Fe(L1)3(SbF6−)2 (4), while the acetic ethyl group at the non-coordinating NH site of the ligand L2 resulted in an increase in the ligand field and generated a low-spin (LS) state for the complex Fe(L2)3(ClO4−)2 (5). Complexes 1 and 5 were structurally characterized by single-crystal X-ray diffraction at different spin-states, while the phase purity of complexes 2–4 was confirmed by PXRD. Raman, IR and UV–Vis absorption spectra and magnetic properties of 1–4 were obtained, which revealed the influence of different counter anions on the spin transition temperatures. The blue-shift of IR and Raman spectra, red-shift and decrease in molar absorptivity of UV–Vis absorption spectra all follow the sequence 1

The anthocyanin biosynthesis of rice is a major concern due to the potential nutritional value. Purple appears in various organs and tissues of rice such as pericarp, flower organs, leaves, leaf sheaths, internodes, ligules, apex, and stigma. At present, there are many studies on the color of rice pericarp, but the gene and mechanism of other organs such as leaves are still unclear, and the gene regulatory network of specific organ coloring has not been systematically understood. In this study, genetic analysis demonstrated that the purple leaf traits of rice were regulated by a recessive gene. The green leaf cultivar Y58S and purple leaf cultivar XianHongB were used to construct the mapping population. A set of near isogenicline (NIL) (BC3F1) was bred via crossing and back-crossing. The generations of BC3F2 appeared to separate four phenotypes, pl1, pl2, pl3, and pl4, due to the occurrence of a purple color in different organs. We constructed three bulked segregant analysis (BSA) pools (pl1&ndash, pl2, pl1&ndash, pl3, and pl1&ndash, pl4) by using the separated generations of BC3F5 and mapped the purple leaf gene plr4 to the vicinity of 27.9&ndash, 31.1 Mb on chromosome 4. Subsequently, transcriptome sequencing (RNA-Seq) for pl3 and pl2 was used to analyze the differentially expressed genes in the localization interval, where 12 unigenes exhibited differential expression in which two genes (Os04g0577800, Os04g0616400) were downregulated. The two downregulated genes (Os04g0577800 and Os04g0616400) are possible candidate genes because of the recessive genetic characteristics of the purple leaf genes. These results will facilitate the cloning of plr4 and illustrate the molecular mechanisms of the anthocyanin synthesis pathway.

Electronic health record is an important source for clinical researches and applications, and errors inevitably occur in the data, which could lead to severe damages to both patients and hospital services. One of such error is the mismatches between diagnoses and prescriptions, which we address as 'medication anomaly' in the paper, and clinicians used to manually identify and correct them. With the development of machine learning techniques, researchers are able to train specific model for the task, but the process still requires expert knowledge to construct proper features, and few semantic relations are considered. In this paper, we propose a simple, yet effective detection method that tackles the problem by detecting the semantic inconsistency between diagnoses and prescriptions. Unlike traditional outlier or anomaly detection, the scheme uses continuous bag of words to construct the semantic connection between specific central words and their surrounding context. The detection of medication anomaly is transformed into identifying the least possible central word based on given context. To help distinguish the anomaly from normal context, we also incorporate a ranking accumulation strategy. The experiments were conducted on two real hospital electronic medical records, and the topN accuracy of the proposed method increased by 3.91 to 10.91% and 0.68 to 2.13% on the datasets, respectively, which is highly competitive to other traditional machine learning-based approaches., 8 pages, 6 figures, submitted to BIBM 2019, accepted in workshop BHI 2019

Carotid endarterectomy (CEA) is a classical method for prevention of life-threatening strokes in patients with severe internal carotid artery stenosis (ICA), regardless of symptoms.1,2 However, there is increasing evidence that subtle cognitive dysfunction may occur in 27%–31% of patients after CEA; this may be caused by cerebral perfusion deficiency related to hemodynamic changes and cerebral emboli, as well as a variety of individual factors.3–5 Brain-derived neurotrophic factor (BDNF) is a well-known member of the neurotrophic family of growth-promoting proteins, which is essential to neuronal survival, axon growth, and synaptic plasticity.6 Elevation of BDNF in the central nervous system is known to prevent hypoxic neuronal death in animal models of stroke,7 and has been implicated in learning and memory processes,8 as well as other advanced neuronal functions. Moreover, BDNF can be detected in blood, and a direct correlation has been observed between cortical and serum levels of BDNF.9–11 Thus, the serum BDNF level may serve as an indicator of changes in BDNF levels in the central nervous system. Dexmedetomidine (DEX) is a highly selective agonist of α2-adrenergic receptors with multiple effects on the human brain, including clinical sedation, anesthesia, and analgesia.12 Moreover, DEX has drawn widespread attention for its neuroprotective effects against stroke in animal models through its actions on α2-adrenergic receptors13–16; this neuroprotection is partly related to the DEX-induced elevation of BDNF levels in the cortex and hippocampus,17,18 as well as concurrent anti-inflammatory effects.19 However, for patients who have undergone CEA, the impacts of DEX on cognition and plasma BDNF level have not yet been determined. Based on the above considerations, we hypothesized that DEX may improve cognition in aged patients after CEA. Here, we aimed to determine the effects of DEX administered intravenously during CEA on postoperative cognitive function, and to assess cerebral inflammation and plasma levels of BDNF, in order to elucidate whether DEX can prevent cognitive dysfunction in patients undergoing CEA.

Rationale: X-linked lymphoproliferative syndromes (XLPs) are rare, yet often fatal primary immunodeficiency diseases, which rarely manifest as Langerhans cell histiocytosis (LCH) complicated with hemophagocytic lymphohistiocytosis (HLH). Clinical data of a case of XLP-2 manifesting as LCH complicated with HLH was retrospectively analyzed to determine the etiology and causal gene. Patient concerns and diagnosis: The diagnosis of multisystem LCH was confirmed by skin biopsy and other examinations in a 13-month boy with recurrent ear discharge, fever and hemorrhagic papules for 3 months. A good therapeutic response to LCH-III protocol-directed induction chemotherapy was achieved but unremitting HLH developed 6 weeks after the initiation of induction chemotherapy. To identify possible underlying genetic causes, gene mutation analysis was undertaken. A novel XIAP gene mutation (c.99delT, p.F33fsX37) was documented. Interventions: After the diagnosis of HLH had been confirmed, HLH-2004-directed chemotherapy was instituted. Outcomes: The clinical condition of the patient had become progressively deteriorating after 8-week chemotherapy of HLH-2004 protocol, requiring frequent infusions of RBC suspensions and apheresis platelets. His parents decided to receive no further therapy, and the patient died soon after discharge. Lessons: Meticulous laboratory investigations including genetic studies should be undertaken in young children with LCH complicated with HLH and poor therapeutic response.

Three diaryl oxalate derivatives, bis(4-chlorophenyl)oxalate, bis(2, 6-dichlorophenyl)oxalate and bis(2, 4, 6-trichlorophenyl)oxalate, have been synthesized and characterized via X-ray single crystal diffraction, differential scanning calorimetry, thermogravimetric analysis and infrared spectra, for the purpose of studying the influence of chlorine substitution on the crystal structures of diaryl oxalate. This work has demonstrated that, depending on the position and number, chlorine substitution will influence the molecular geometries and stacking modes of diaryl oxalate by tuning the types and numbers of intermolecular interactions.

The introduce of halogen atoms (F, Cl, Br, I) to the triazole-based ligand N-benzyl-4-amino-1, 2, 4-triazole (L) have shown a significant effect on the spin-crossover (SCO) properties of the corresponding one-dimensional (1D) coordination Fe (II) polymers with chemical formula [Fe(4-X–L)3](BF4)2 (X=F, Cl, Br, and I). Compared with the [FeL3](BF4)2, the electronegative halogen atoms have increased the π-acceptor character of these ligands, which thus improved the ligand field strength and induced the occurrence of SCO for the Fe (II) polymers at higher temperatures. The SCO transition temperatures T1/2 have changed from 200 K to 249 (I), 250 (Br), 252 (Cl) and 275 (F) K, respectively. More importantly, the UV-Vis absorption spectrum and density functional theory (DFT) calculations indicated that the transition temperatures and the width of thermal hysteresis loops have shown a positive correlation with the electronegativity of the halogen atoms.

Rationale: Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular disorder consisting of multifocal venous malformations. Delayed diagnosis or misdiagnosis frequently occurs in patients without typical cutaneous lesions or gastrointestinal bleeding symptoms. This article reports a 10-year case of delayed diagnosis of BRBNS detected by capsule endoscopy. Patient concerns and diagnosis: A 15-year-old girl presented with refractory iron-deficiency anemia (IDA) for 10 years, without any hemorrhagic signs or noticeable cutaneous lesions, which led to her obvious physical growth retardation. Capsule endoscopic examination revealed dozens of vascular blebs distributed from the jejunum to the ileum and a site of active bleeding. Hence, she was diagnosed with BRBNS. Interventions: Laparotomy was performed with resection of the small bowel lesions, and iron supplementation was prescribed for 3 months. Postoperatively, the patient had an uncomplicated course. Outcomes: On follow-up after 3 years, IDA in this patient was cured and she did not require further blood transfusion and showed excellent vigor. Lessons: A high index of suspicion for BRBNS and adequate endoscopy examination will help to identify the origin of refractory IDA in older children, particularly in patients with vascular lesions of the skin.

The effect of chlormethiazole (CMZ) at single and multiple doses on the toxicokinetics of diethylnitrosamine (DEN) was investigated in normal rats and those with DEN-induced liver fibrosis. Twelve rats were treated with DEN (50 mg/kg) alone and in combination with a single dose of CMZ (10, 50, or 100 mg/kg) by intraperitoneal (i.p.) injection. In a multiple dose test, six rats were treated with CMZ (50 mg/kg) for 7 d with addition of DEN (50 mg/kg) on days 1 and 7. Lastly, 12 rats were treated with DEN (50 mg/kg) by i.p. injection twice a week for 4 consecutive weeks, followed by weekly injections for another 8 weeks to build the model of liver fibrosis. Following this induction, the 12 rats were given CMZ (50 mg/kg) combined with DEN (50 mg/kg) to study the inhibitory effect of CMZ on DEN metabolism in hepatofibrotic rats. Serial blood samples were also collected and analyzed by a validated high-performance liquid chromatography (HPLC) method. A single-dose CMZ treatment decreased DEN clearance (CL), prolonged the

Our previous studies showed that γδ T cells provided immune protection against Chlamydial muridarum (Cm), an obligate intracellular strain of chlamydia trachomatis, lung infection by producing abundant IL-17. In this study, we investigated the proliferation and activation of lung γδ T cell subsets, specifically the IL-17 and IFNγ production by them following Cm lung infection. Our results found that five γδ T cell subsets, Vγ1+ T, Vγ2+ T, Vγ4+ T, Vγ5+ T, and Vγ6+ T, expressed in lungs of naïve mice, while Cm lung infection mainly induced the proliferation and activation of Vγ4+ T cells at day 3 p.i., following Vγ1+ T cells at day 7 p.i. Cytokine detection showed that Cm lung infection induced IFNγ secretion firstly by Vγ4+ T cells at very early stage (day 3) and changed to Vγ1+ T cells at midstage (day 7). Furthermore, Vγ4+ T cell is the main γδ T cell subset that secretes IL-17 at the very early stage of Cm lung infection and Vγ1+ T cell did not secrete IL-17 during the infection. These findings provide in vivo evidence that Vγ4+T cells are the major IL-17 and IFNγ-producing γδ T cell subsets at the early period of Cm lung infection.

The Heusler alloy system is a rich source of functional materials. We studied the ternary alloy V2NiSe by first-principles calculations to explore for a new functional alloy. We performed geometry optimization for the alloy with Hg2CuTi-type structure and obtained the equilibrium lattice parameter a 0. The magnetic moment of the compound is 0.707 µ B in 1-unit cell. The total density of states and the partial density of states were calculated. The band structure was also studied. The magnetic moment of the two vanadium atoms in 1-unit cell in different space positions is different.

Nitrogen is a major nutritional element in rice production. However, excessive application of nitrogen fertilizer has caused severe environmental pollution. Therefore, development of rice varieties with improved nitrogen use efficiency (NUE) is urgent for sustainable agriculture. In this study, bulked segregant analysis (BSA) combined with whole genome re-sequencing (WGS) technology was applied to finely map quantitative trait loci (QTL) for NUE. A key QTL, designated as qNUE6 was identified on chromosome 6 and further validated by Insertion/Deletion (InDel) marker-based substitutional mapping in recombinants from F2 population (NIL-13B4×GH998). Forty-four genes were identified in this 266.5-kb region. According to detection and annotation analysis of variation sites, thirty-nine genes with large-effect single-nucleotide polymorphisms (SNPs) and large-effect InDels were selected as candidates and their expression levels were analyzed by qRT-PCR. Significant differences in the expression levels of LOC_Os06g15370 (peptide transporter PTR2) and LOC_Os06g15420 (asparagine synthetase) were observed between two parents (Y11 and GH998). Phylogenetic analysis in Arabidopsis thaliana identified two closely related homologues, AT1G68570 (AtNPF3.1) and AT5G65010 (ASN2), which share 72.3% and 87.5% amino acid similarity with LOC_Os06g15370 and LOC_Os06g15420, respectively. Taken together, our results suggested that qNUE6 is a possible candidate gene for NUE in rice. The fine mapping and candidate gene analysis of qNUE6 provide the basis of molecular breeding for genetic improvement of rice varieties with high NUE, and lay the foundation for further cloning and functional analysis.

Cisplatin is a potent antitumor drug, which is widely applied in clinical cancer treatment. However, cisplatin can hardly distinguish between healthy tissue and tumor tissue, resulting in serious toxic side effects. Indocyanine green (ICG) is a FDA-approved near-infrared (NIR) fluorescence dye which has been used in photothermal therapy and optically mediated diagnostic, but the application of ICG is limited by its concentration-dependent aggregation, poor aqueous stability in vitro, lack of target specificity and rapid elimination from the body. Herein, to overcome these limitations of cisplatin and ICG, we fabricated folate-modified, cisplatin, ICG-loaded lipid-polymer hybrid nanoparticles (FCINPs) using a single-step sonication method. The FCINPs exhibited well-defined monodispersity, significant stability and excellent NIR penetration ability. The intracellular uptake experiment showed that the targeting efficacy of the FCINPs was more effective in folate receptors (FRs) over-expressing MCF-7 cells than FRs negative A549 cells. In addition, compared with chemo or photothermal treatment alone, the treatment of FCINPs in combination with 808 nm NIR laser irradiation can significantly induce the apoptosis and necrosis of MCF-7 cells. These findings indicated that the FCINPs would be a promising nanosized drug formulation for tumor-targeted therapy in the future.

In the title compound, C18H22N4O3, the benzene ring is twisted by 63.29 (15)° with respect to the pyridine ring. In the crystal, molecules are linked by N—H...O hydrogen bonds and C—H...π interactions, forming slabs parallel to theacplane.