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In previous studies, GA20 oxidase (GA20ox) has been identified to be an important enzyme in the biosynthesis of GA, and SHOOTMERISTEMLESS (STM) can repress the expression of GA20ox. In this study, the GATA transcription factor PdeGATA3 was identified in the poplar line NL895, and its overexpression (OE) transgenic lines showed a dwarf phenotype. RNA sequencing (RNA-Seq) analysis suggested that OE PdeGATA3 could promote the expression of PdeSTM and repress the expression of PdeGA20ox. Therefore, we hypothesized that PdeGATA3 would directly promote the expression of PdeSTM and that PdeSTM would repress the expression of PdeGA20ox. Four experiments, a dual-luciferase reporter assay, GUS transient coexpression assay, yeast one-hybrid assay and electrophoretic mobility shift assay, were conducted and verified that PdeGATA3 could promote the expression of PdeSTM by binding GATA-Boxes in its promoter. OE PdeSTM in poplar resulted in a dwarf phenotype and repressed the expression of PdeGA20ox. GA measurement of the OE PdeSTM and PdeGATA3 lines showed that GA3 and GA4 contents were significantly lower than those in the wild type (WT). Accordingly, we put forward a regulation model involving plant height regulation by PdeGATA3 , PdeSTM and PdeGA20ox. [ABSTRACT FROM AUTHOR]

Magnetic particle imaging (MPI) is a radiation-free vessel- and target-imaging modality that can sensitively detect nanoparticles. A static magnetic gradient field, referred to as a selection field, is required in MPI to provide a field-free region (FFR) for spatial encoding. The image resolution of MPI is closely related to the size of the FFR, which is determined by the selection field gradient amplitude. Because of the limitations of existing gradient coil hardware, the image resolution of MPI cannot satisfy the clinical requirements of human in vivo imaging. Pulsed excitation has been confirmed to improve the image resolution of MPI by breaking down the ‘relaxation wall.’ This work proposes the use of a pulsed waveform magnetic gradient from magnetic resonance imaging to further improve the image resolution of MPI. Through alignment of the gradient direction along the field-free line (FFL), each location on the FFL is able to have a unique excitation field strength that generates a specific relaxation-induced decay signal. Through excitation of nanoparticles on the FFL with many gradient profiles, a high-resolution, one-dimensional (1D) image can be reconstructed on the FFL. For larger magnetic nanoparticles, simulation results revealed that a pulsed excitation field with a greater flat portion generates a 1D bar pattern phantom image with a higher correlation and spatial resolution. With parallel FFL and gradient coil movements, high-resolution, two-dimensional (2D) Shepp–Logan phantom and brain vessel maps were reconstructed through repetition of the spatially resolved measurement of magnetic nanoparticles on the FFL. [ABSTRACT FROM AUTHOR]

Vortex beams carrying orbital angular momentum (OAM) modes offer a compelling avenue for increasing optical communication capacity. Despite significant efforts in OAM mode (de)multiplexing, challenges persist in signal demodulation and noise monitoring of multiplexed channels. This challenge largely stems from the absence of efficient feature extraction methods capable of analyzing the OAM spectrum, which delineates mode components and intensity weights. Herein, we introduce a novel strategy for OAM mode spectrum analysis using a residual neural network incorporating interference techniques. By introducing interference between target vortex beams and a spherical wave, resulting in the mapping of OAM distributions onto the stripe features observed in the interferogram. To effectively extract spectrum details from these interferograms, we construct a residual neural network exhibiting high feature processing capabilities, which enables precise analysis of intricate OAM mode spectrum. We demonstrate the effectiveness of this OAM spectrum analysis by obtaining the intensity weights for 15 superimposed modes ranging from −10 to +10, achieving a mean-square-error of 2.3 × 10−4. To validate its practicality, we showcase an 80-channel three-dimensional multiplexing communication system including five OAM modes, two polarizations, and eight wavelengths. The 4 Tbit/s quadrature-phase-shift-keying signals are successfully demodulated with a bit-error rate below 3.34 × 10−6. Additionally, the measured optical signal-to-noise ratio reaches 11.5 dB, indicating the potential applications of this OAM spectrum analysis strategy in signal demodulation and noise monitoring. • A novel strategy for OAM mode spectrum analysis was investigated for signal demodulation and noise monitoring. • The MSE for spectral analysis of 15 superimposed modes in the mode range −10∼+10 was 2.3 × 10−4. • The QPSK signals were demodulated with a BER below 3.34 × 10−6, and the measured OSNR reached 11.5 dB. [ABSTRACT FROM AUTHOR]

• An LDPC coded strategy to enhances the performance of CVB multiplexing communication over few-mode fiber was proposed. • A 4-channel CVB multiplexing communication was demonstrated, and 96 Gbit/s QPSK-OFDM signals were successfully transmitted over a 5 km FMF. • After equalization using LDPC coded, the bit error rate decreased by ∼ 2.5 orders of magnitude, and the communication sensitivity improved by ∼ 8 dB. Cylindrical vector beams (CVBs) have attracted significant research interest in mode-division multiplexing communication thanks to their capacity to carry orthogonal vector modes. Because CVB modes are the eigen-solutions of few-mode fiber (FMF), they are well-suited for long-distance transmission. Nevertheless, the application of CVB multiplexing communication is impeded by mode coupling in FMF, which leads to mode crosstalk and signal fading. Herein we propose an LDPC coded strategy to provide a channel equalization solution, which enhances the performance of CVB multiplexing communication. Digital signals are encoded using a sparse parity-check matrix that establishes a specific parity-check relationship between the original data bits and the check bits. This enables the correction of error bits for channel equalization. To demonstrate the concept, we built a 4-channel CVB multiplexing communication system that transmitted 24 × 4 Gbit/s QPSK-OFDM signals over 5 km FMF. After equalization, the bit error rate decreased by ∼ 2.5 orders of magnitude, and the communication sensitivity improved by ∼ 8 dB. This proof of concept demonstrates the potential of the proposed LDPC coded strategy to enhance the performance of CVB multiplexing communication systems. [ABSTRACT FROM AUTHOR]

Grain weight and grain number, the two important yield traits, are mainly determined by grain size and panicle architecture in rice. Herein, we report the identification and functional analysis of OsSPL4 in panicle and grain development of rice. Using CRISPR/Cas9 system, two elite alleles of OsSPL4 were obtained, which exhibited an increasing number of grains per panicle and grain size, resulting in increase of rice yield. Cytological analysis showed that OsSPL4 could regulate spikelet development by promoting cell division. The results of RNA-seq and qRT-PCR validations also demonstrated that several MADS-box and cell-cycle genes were up-regulated in the mutation lines. Co-expression network revealed that many yield-related genes were involved in the regulation network of OsSPL4. In addition, OsSPL4 could be cleaved by the osa-miR156 in vivo, and the OsmiR156-OsSPL4 module might regulate the grain size in rice. Further analysis indicated that the large-grain allele of OsSPL4 in indica rice might introgress from aus varieties under artificial selection. Taken together, our findings suggested that OsSPL4 could be as a key regulator of grain size by acting on cell division control and provided a strategy for panicle architecture and grain size modification for yield improvement in rice. [ABSTRACT FROM AUTHOR]

Integration of transcriptomics and metabolomics data can provide detailed information for better understanding the molecular mechanisms underlying salt tolerance in rice. In the present study, we report a comprehensive analysis of the transcriptome and metabolome of rice overexpressing the OsDRAP1 gene, which encodes an ERF transcription factor and was previously identified to be conferring drought tolerance. Phenotypic analysis showed that OsDRAP1 overexpression (OE) improved salt tolerance by increasing the survival rate under salt stress. OsDRAP1 affected the physiological indices such as superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) to enhance redox homeostasis and membrane stability in response to salt stress. Higher basal expression of OsDRAP1 resulted in differential expression of genes that potentially function in intrinsic salt tolerance. A core set of genes with distinct functions in transcriptional regulation, organelle gene expression and ion transport were substantially up-regulated in the OE line in response to salt stress, implying their important role in OsDRAP1-mediated salt tolerance. Correspondingly, metabolome profiling detected a number of differentially metabolites in the OE line relative to the wild type under salt stress. These metabolites, including amino acids (proline, valine), organic acids (glyceric acid, phosphoenolpyruvic acid and ascorbic acid) and many secondary metabolites, accumulated to higher levels in the OE line, demonstrating their role in salt tolerance. Integration of transcriptome and metabolome analysis highlights the crucial role of amino acids and carbohydrate metabolism pathways in OsDRAP1-mediated salt tolerance. [ABSTRACT FROM AUTHOR]

Background: Bacterial blight, which is caused by Xanthomonas oryzae pv. oryzae (Xoo), is a devastating rice disease worldwide. Rice introgression line H471, derived from the recurrent parent Huang-Hua-Zhan (HHZ) and the donor parent PSBRC28, exhibits broad-spectrum resistance to Xoo, including to the highly virulent Xoo strain PXO99A, whereas its parents are susceptible to PXO99A. To characterize the responses to Xoo, we compared the proteome profiles of the host and pathogen in the incompatible interaction (H471 inoculated with PXO99A) and the compatible interaction (HHZ inoculated with PXO99A). Results: In this study, a total of 374 rice differentially abundant proteins (DAPs) and 117 Xoo DAPs were detected in the comparison between H471 + PXO99A and HHZ + PXO99A. Most of the Xoo DAPs related to pathogen virulence, including the outer member proteins, type III secretion system proteins, TonB-dependent receptors, and transcription activator-like effectors, were less abundant in the incompatible interaction than in the compatible interaction. The rice DAPs were mainly involved in secondary metabolic processes, including phenylalanine metabolism and the biosynthesis of flavonoids and phenylpropanoids. Additionally, some DAPs involved in the phenolic phytoalexin and salicylic acid (SA) biosynthetic pathways accumulated much more in H471 than in HHZ after the inoculation with PXO99A, suggesting that phytoalexin and SA productions were induced faster in H471 than in HHZ. Further analyses revealed that the SA content increased much more rapidly in H471 than in HHZ after the inoculation, suggesting that the SA signaling pathway was activated faster in the incompatible interaction than in the compatible interaction. Conclusions: Overall, our results indicate that during an incompatible interaction between H471 and PXO99A, rice plants prevent pathogen invasion and also initiate multi-component defense responses that inhibit disease development. [ABSTRACT FROM AUTHOR]

Antiviral therapies are integral in the fight against SARS‐CoV‐2 (i.e. severe acute respiratory syndrome coronavirus 2), the causative agent of COVID‐19. Antiviral therapeutics can be divided into categories based on how they combat the virus, including viral entry into the host cell, viral replication, protein trafficking, post‐translational processing, and immune response regulation. Drugs that target how the virus enters the cell include: Evusheld, REGEN‐COV, bamlanivimab and etesevimab, bebtelovimab, sotrovimab, Arbidol, nitazoxanide, and chloroquine. Drugs that prevent the virus from replicating include: Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, and Kaletra. Drugs that interfere with protein trafficking and post‐translational processing include nitazoxanide and ivermectin. Lastly, drugs that target immune response regulation include interferons and the use of anti‐inflammatory drugs such as dexamethasone. Antiviral therapies offer an alternative solution for those unable or unwilling to be vaccinated and are a vital weapon in the battle against the global pandemic. Learning more about these therapies helps raise awareness in the general population about the options available to them with respect to aiding in the reduction of the severity of COVID‐19 infection. In this 'A Guide To' article, we provide an in‐depth insight into the development of antiviral therapeutics against SARS‐CoV‐2 and their ability to help fight COVID‐19. [ABSTRACT FROM AUTHOR]

• Mendelian randomization study is an epidemiological research method that can be used to explore the causal relationship between exposure and outcome. • Gut microbiota has both protective and promotive effects on obstructive sleep apnea. • In the diagnosis and prevention of obstructive sleep apnea, the role of gut microbiota should be emphasized Although observational studies have identified relations between gut microbiota and obstructive sleep apnea (OSA), their causal links remain elusive. Hence, we aimed to investigate this causal relation using the Mendelian randomization (MR) approach. Summary-level gut microbiota data were acquired using the maximum available genome-wide association study (GWAS) from the MiBioGen consortium while obtaining summary-level OSA data using publicly available GWAS from the FinnGen Consortium. A two-sample MR analysis was used for assessing gut microbiota and OSA causal effect, using the inverse variance-weighted (IVW) approach as the primary analysis method. The results were further examined for pleiotropy and heterogeneity. Moreover, the reverse MR analysis did not find a causal relationship. Four gut microbiota were found to have nominally significant association to OSA according to the IVW method. Among them, the family Peptostreptococcaceae (OR = 1.171, 95% CI: 1.027-1.334) and genus Coprococcus3 (OR = 1.163, 95% CI: 1.007-1.343), these two florae that may increase the risk of OSA. Family Acidaminococcaceae (OR = 0.843, 95% CI: 0.729-0.975) and genus Blautia (OR = 0.830, 95% CI: 0.708-0.972) may have an ameliorative effect on OSA. No evidence of pleiotropy or heterogeneity was found. MR analysis indicated that a causal relation is existed between specific gut microbiota and OSA at the genetic prediction level, offering innovative perspectives into the mechanisms underlying gut microbiota-mediated OSA development. [ABSTRACT FROM AUTHOR]

Rice (Oryza sativa) is very sensitive to chilling stress at seedling and reproductive stages, whereas wild rice, O. longistaminata, tolerates non-freezing cold temperatures and has overwintering ability. Elucidating the molecular mechanisms of chilling tolerance (CT) in O. longistaminata should thus provide a basis for rice CT improvement through molecular breeding. In this study, high-throughput RNA sequencing was performed to profile global transcriptome alterations and crucial genes involved in response to long-term low temperature in O. longistaminata shoots and rhizomes subjected to 7 days of chilling stress. A total of 605 and 403 genes were respectively identified as up- and down-regulated in O. longistaminata under 7 days of chilling stress, with 354 and 371 differentially expressed genes (DEGs) found exclusively in shoots and rhizomes, respectively. GO enrichment and KEGG pathway analyses revealed that multiple transcriptional regulatory pathways were enriched in commonly induced genes in both tissues; in contrast, only the photosynthesis pathway was prevalent in genes uniquely induced in shoots, whereas several key metabolic pathways and the programmed cell death process were enriched in genes induced only in rhizomes. Further analysis of these tissue-specific DEGs showed that the CBF/DREB1 regulon and other transcription factors (TFs), including AP2/EREBPs, MYBs, and WRKYs, were synergistically involved in transcriptional regulation of chilling stress response in shoots. Different sets of TFs, such as OsERF922, OsNAC9, OsWRKY25, and WRKY74, and eight genes encoding antioxidant enzymes were exclusively activated in rhizomes under long-term low-temperature treatment. Furthermore, several cis-regulatory elements, including the ICE1-binding site, the GATA element for phytochrome regulation, and the W-box for WRKY binding, were highly abundant in both tissues, confirming the involvement of multiple regulatory genes and complex networks in the transcriptional regulation of CT in O. longistaminata. Finally, most chilling-induced genes with alternative splicing exclusive to shoots were associated with photosynthesis and regulation of gene expression, while those enriched in rhizomes were primarily related to stress signal transduction; this indicates that tissue-specific transcriptional and post-transcriptional regulation mechanisms synergistically contribute to O. longistaminata long-term CT. Our findings provide an overview of the complex regulatory networks of CT in O. longistaminata. [ABSTRACT FROM AUTHOR]

Bariatric surgery is currently the most effective strategy in treating severe obesity and its comorbidities, such as type 2 diabetes (T2D). However, the mechanism through which bariatric surgery mediates its benefits is not completely understood. Since obesity and T2D represent yet another inflammatory disease, and follicular helper T (Tfh) cells play important roles in inflammatory disorders, we investigated whether the Tfh activity was altered after Roux-en-Y gastric bypass ( RYGB), one of the most common bariatric surgery procedures. We found that the Tfh cells after RYGB were not significantly changed in number, but presented altered cytokine secretion profile, including lower interferon ( IFN)-γ, interleukin ( IL)-2, IL-4, and IL-17 secretion. Tfh cells after RYGB also downregulated inducible co-stimulator and programmed death-1. Interestingly, after Tfh cell-naive B cell coculture, Tfh cells after RYGB secreted more IL-10 than autologous Tfh cells before RYGB. The frequencies of IL-10-expressing and transforming growth factor ( TGF)-β-expressing regulatory B cells after Tfh cell-naive B cell coculture were directly correlated with the frequency of IL-10-expressing Tfh cells. Depletion of IL-10 in the coculture, however, resulted in fewer regulatory B cells. Finally, patients with greater increase in IL-10-expressing Tfh cells presented further reductions in body mass index, glycaemia, and body fat percentage. Together, these data demonstrated that the Tfh cells after RYGB presented lower inflammatory status and secreted higher IL-10, through which these Tfh cells promoted the development of regulatory B cells. Higher IL-10-expressing Tfh cell level also predicted better patient response to RYGB. [ABSTRACT FROM AUTHOR]

A novel modifier, 1H, 1H, 2H, 2H-Perfluorooctyltriethoxysilane (PFOES), was introduced for the covalent functionalization of graphene for the first time. TEM, XPS, FT-IR, Raman, AFM and TGA were employed to characterize the morphology and structure of the PFOES-rGO. Furthermore, PVDF/PFOES-rGO composite films with different PFOES-rGO loadings were prepared by solution mixing. The dispersion of such PFOES-rGO containing fluorine ended-groups in PVDF was effectively improved compared to graphene as SEM showed. Thus, the PFOES-rGO could nucleate the PVDF crystallization and induce the formation of nearly all β phase. The dielectric, piezoelectric and dynamic mechanical properties of the PVDF/PFOES-rGO composite films were then comprehensively studied. The dielectric (at 1 kHz) and the piezoelectric constants of the PVDF/PFOES-rGO composite film at 0.3 wt% PFOES-rGO compared with the neat PVDF was greatly improved by 370% and 80.9%, respectively. The PFOES-rGO also greatly enhanced the mechanical property of PVDF composites. It is proved the modification method for graphene used in this study is very effective. [ABSTRACT FROM AUTHOR]

We used resting-state functional magnetic resonance imaging (fMRI) to investigate changes in the thalamus functional connectivity in early and late stages of amnestic mild cognitive impairment. Data of 25 late stages of amnestic mild cognitive impairment (LMCI) patients, 30 early stages of amnestic mild cognitive impairment (EMCI) patients and 30 well-matched healthy controls (HC) were analyzed from the Alzheimer’s disease Neuroimaging Initiative (ADNI). We focused on the correlation between low frequency fMRI signal fluctuations in the thalamus and those in all other brain regions. Compared to healthy controls, we found functional connectivity between the left/right thalamus and a set of brain areas was decreased in LMCI and/or EMCI including right fusiform gyrus (FG), left and right superior temporal gyrus, left medial frontal gyrus extending into supplementary motor area, right insula, left middle temporal gyrus (MTG) extending into middle occipital gyrus (MOG). We also observed increased functional connectivity between the left/right thalamus and several regions in LMCI and/or EMCI including left FG, right MOG, left and right precuneus, right MTG and left inferior temporal gyrus. In the direct comparison between the LMCI and EMCI groups, we obtained several brain regions showed thalamus-seeded functional connectivity differences such as the precentral gyrus, hippocampus, FG and MTG. Briefly, these brain regions mentioned above were mainly located in the thalamo-related networks including thalamo-hippocampus, thalamo-temporal, thalamo-visual, and thalamo-default mode network. The decreased functional connectivity of the thalamus might suggest reduced functional integrity of thalamo-related networks and increased functional connectivity indicated that aMCI patients could use additional brain resources to compensate for the loss of cognitive function. Our study provided a new sight to understand the two important states of aMCI and revealed resting-state fMRI is an appropriate method for exploring pathophysiological changes in aMCI. [ABSTRACT FROM AUTHOR]

Peroxidase (Prx)-related genes are reported to be involved in the metabolism of hydrogen peroxide (H2O2) in plants. Here, we found that the expression of the PdePrx12 gene was upregulated in wild-type (WT) poplar line NL895 infected with the pathogens Botryosphaeria dothidea strain 3C and Alternaria alternata strain 3E. The PdePrx12 gene was cloned in the poplar line NL895 and its overexpression (OE) and reduced-expression (RE) vectors were constructed. OE and RE transgenic lines were then generated. The H2O2 content in the leaves was measured by DAB staining and spectrophotometric analysis, and the data revealed that the OE line had a reduced H2O2 content, whereas the RE line had an increased H2O2 content. These transgenic and WT plants were also inoculated with the 3C/3E pathogens. The leaf area infected by pathogen 3C/3E was determined and the OE line was found to have a larger area of infection, whereas the RE line was found to have a smaller area of infection. This result suggested PdePRX12 is involved in disease resistance in poplar. Given these results, this study demonstrated that when poplar is infected by pathogens, the expression of PdePrx12 is inhibited, leading to an increase in H2O2 content, thereby enhancing disease resistance. [ABSTRACT FROM AUTHOR]

A composite right/left-handed transmission line (CRLH-TL) composed of a substrate and X-shaped metal patches is proposed and investigated theoretically as well as experimentally. The scattering parameters are investigated both in electromagnetic (EM) simulation and equivalent circuit model simulation, it is found that the structure works as a dual band CRLH-TL having the first right-handed passband and the second balanced CRLH frequency band at the resonant frequencies of 6.27 GHz and 13.45 GHz, respectively. Moreover, the required equations and the dispersion diagram derived from the equivalent circuit model to analyze the proposed CRLH structure give strong support to the interpretation of all EM phenomena. The effect of the equivalent circuit model parameters on the dispersion diagram is investigated. A parallel-plate waveguide (PPW) measurement system is employed to validate the characteristics of the CRLH-TL whose features show that the design of the novel artificial TLs is more flexible and convenient. [ABSTRACT FROM AUTHOR]

Background: Delta‐like homologue 1 (DLK1), a transmembrane protein, is highly expressed in hepatocellular carcinoma (HCC). We explored whether DLK1‐directed chimeric antigen receptor (CAR) T cells can specifically eliminate DLK1‐positive HCC cells and serve as a therapeutic strategy for HCC immunotherapy. Methods: We first characterized a homemade anti‐human DLK1 monoclonal antibody, sequenced the single‐chain Fragment variable (scFv) and integrated it into the second‐generation CAR lentiviral vector, and then developed the DLK1‐directed CAR‐T cells. The cytotoxic activities of DLK1‐directed CAR‐T cells against different HCC cells were evaluated in vitro and in vivo. Results: The genetically modified human T cells with the DLK1‐directed CARs produced cytotoxic activity against DLK1‐positive HCC cells. Additionally, the DLK1‐directed CARs enhanced T cell proliferation and activation in a DLK1‐dependent manner. Interestingly, the DLK1‐targeted CAR‐T cells significantly inhibited both subcutaneous and peritoneal xenograft tumours derived from human liver cancer cell lines HepG2 or Huh‐7. Conclusion: DLK1‐directed CAR‐T cells specifically suppresses DLK1‐positive HCC cells in vitro and in vivo. This study provides a novel transmembrane antigen DLK1 as a potential therapeutic target appropriate for CAR‐T cell therapy, which may be further developed as a clinical therapeutic strategy for HCC immunotherapy. [ABSTRACT FROM AUTHOR]

The precise classification for the electroencephalogram (EEG) in different mental tasks in the research on brain-computer interface (BCI) is the key for the design and clinical application of the system. In this paper, a new combination classification algorithm is presented and tested using the EEG data of right and left motor imagery experiments. First, to eliminate the low frequency noise in the original EEGs, the signals were decomposed by empirical mode decomposition (EMD) and then the optimal kernel parameters for support vector machine (SVM) were determined, the energy features of the first three intrinsic mode functions (IMFs) of every signal were extracted and used as input vectors of the employed SVM. The output of the SVM will be classification result for different mental task EEG signals. The study shows that mean identification rate of the proposed algorithm is 95%, which is much better than the present traditional algorithms. [ABSTRACT FROM AUTHOR]

Abstract: No doubt a noninvasive technique for detection of cerebral ischemic extent, before the formation of the focus, is extremely valuable. This paper presents a new approach to early evaluate the degree of ischemic injury by combining bispectrum estimation of electroencephalograms (EEGs) with artificial neural network (ANN). The graded ischemic injuries in 24 Sprague–Dawley (SD) rats were induced for different periods of 8, 18, 30min by infusing physiological saline along the left blood stream, based on the model for rat ischemic cerebral injury described in this paper. Four channels of EEG were collected in each rat at scheduled time of ischemia. The maximum bicoherence index and the weighted center of bispectrum (WCOB) were extracted from the EEGs and were used as input feature vector of a four-layer (12-7-2-1) ANN for prediction. Training and testing the ANN used the ‘leave one out’ strategy. The levels of ischemic injury were verified and classified by observing the ischemic area by conventional hematoxylin and eosin (HE) staining and the heat shock protein (HSP70) test. The proposed method was able to correctly detect ischemic extent in average accuracy of 91.67% of the cases. The results show that this scheme can be expected to diagnose ischemic cerebral injury in its earlier phases. [Copyright &y& Elsevier]

Summary: Callus formation is important for numerous biological processes in plants. Previously, we revealed that the PdeWRKY75–PdeRBOHB module positively regulates hydrogen peroxide (H2O2) accumulation, thereby affecting callus formation in poplar.In this study, we identified and confirmed a transcription factor, PdeERF114, that interacts with PdeWRKY75 both in vitro and in vivo. Gene expression analysis identified both PdeRBOHB and PdeEXPB2 as downstream genes of PdeERF114 and PdeWRKY75. Overexpression (OE) and reduced‐expression (RE) transgenic poplar lines for these four genes were generated, and the observation of callus formation was also performed in all plant materials.We demonstrated that PdeERF114 and PdeWRKY75 formed a protein complex and that this complex could bind W‐Box motifs in the promoters of PdeRBOHB and PdeEXPB2, thereby positively regulating the expression of PdeRBOHB and PdeEXPB2. The OE/RE transgenic lines for these four genes also showed enhanced/reduced callus formation.Overall, we revealed a novel gene regulatory network for the regulation of callus formation in plants that involves four genes and regulates callus formation through two pathways: the accumulation of H2O2 in explants and the relaxation of cell walls. In the future, the four genes could be used to enhance transformation effectiveness in genetic engineering. [ABSTRACT FROM AUTHOR]

Summary: Rice grain is a poor dietary source of zinc (Zn) but the primary source of cadmium (Cd) for humans; however, the molecular mechanisms for their accumulation in rice grain remain incompletely understood.This study functionally characterized a tonoplast‐localized transporter, OsMTP1. OsMTP1 was preferentially expressed in the roots, aleurone layer, and embryo of seeds. OsMTP1 knockout decreased Zn concentration in the root cell sap, roots, aleurone layer and embryo, and subsequently increased Zn concentration in shoots and polished rice (endosperm) without yield penalty. OsMTP1 haplotype analysis revealed elite alleles associated with increased Zn level in polished rice, mostly because of the decreased OsMTP1 transcripts.OsMTP1 expression in yeast enhanced Zn tolerance but did not affect that of Cd. While OsMTP1 knockout resulted in decreased uptake, translocation and accumulation of Cd in plant and rice grain, which could be attributed to the indirect effects of altered Zn accumulation.Our results suggest that rice OsMTP1 primarily functions as a tonoplast‐localized transporter for sequestrating Zn into vacuole. OsMTP1 knockout elevated Zn concentration but prevented Cd deposition in polished rice without yield penalty. Thus, OsMTP1 is a candidate gene for enhancing Zn level and reducing Cd level in rice grains. [ABSTRACT FROM AUTHOR]

Background: Magnetic nanoparticles (MNPs) are used as tracers without ionizing radiation in vascular imaging, molecular imaging, and neuroimaging. The relaxation mechanisms of magnetization in response to excitation magnetic fields are important features of MNPs. The basic relaxation mechanisms include internal rotation (Néel relaxation) and external physical rotation (Brownian relaxation). Accurate measurement of these relaxation times may provide high sensitivity for predicting MNP types and viscosity‐based hydrodynamic states. It is challenging to separately measure the Néel and Brownian relaxation components using sinusoidal excitation in conventional MPI. Purpose: We developed a multi‐exponential relaxation spectral analysis method to separately measure the Néel and Brownian relaxation times in the magnetization recovery process in pulsed vascular MPI. Methods: Synomag‐D samples with different viscosities were excited using pulsed excitation in a trapezoidal‐waveform relaxometer. The samples were excited at different field amplitudes ranging from 0.5 to 10 mT at intervals of 0.5 mT. The inverse Laplace transform‐based spectral analysis of the relaxation‐induced decay signal in the field‐flat phase was performed by using PDCO, a primal‐dual interior method for convex objectives. Néel and Brownian relaxation peaks were elucidated and measured on samples with various glycerol and gelatin concentrations. The sensitivity of viscosity prediction of the decoupled relaxation times was evaluated. A digital vascular phantom was designed to mimic a plaque with viscous MNPs and a catheter with immobilized MNPs. Spectral imaging of the digital vascular phantom was simulated by combining a field‐free point with homogeneous pulsed excitation. The relationship between the Brownian relaxation time from different tissues and the number of periods for signal averages was evaluated for a scan time estimation in the simulation. Results: The relaxation spectra of synomag‐D samples with different viscosity levels exhibited two relaxation time peaks. The Brownian relaxation time had a positive linear relationship with the viscosity in the range 0.9 to 3.2 mPa · s. When the viscosity was >3.2 mPa · s, the Brownian relaxation time saturated and did not change with increasing viscosity. The Néel relaxation time decreased slightly with an increase in the viscosity. The Néel relaxation time exhibited a similar saturation effect when the viscosity level was >3.2 mPa · s for all field amplitudes. The sensitivity of the Brownian relaxation time increased with the field amplitude and was maximized at approximately 4.5 mT. The plaque and catheter regions were differentiated from the vessel region in the simulated Brownian relaxation time map. The simulation results show that the Néel relaxation time was 8.33±0.09 μs in the plaque region, 8.30±0.08 μs in the catheter region, and 8.46±0.11 μs in the vessel region. The Brownian relaxation time was 36.60±2.31 μs in the plaque region, 30.17±1.24 μs in the catheter region, and 31.21±1.53 μs in the vessel region. If we used 20 excitation periods for image acquisition in the simulation, the total scan time of the digital phantom was approximately 100 s. Conclusion: Quantitative assessment of the Néel and Brownian relaxation times through inverse Laplace transform‐based spectral analysis in pulsed excitation, highlighting their potential for use in multi‐contrast vascular MPI. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is a deadly tumor with dynamic evolutionary process. Although much endeavors have been made in identifying the temporal patterns of cancer progression, it remains challenging to infer and interpret the molecular alterations associated with cancer development and progression. To this end, we developed a computational approach to infer the progression trajectory based on cross-sectional transcriptomic data. Analysis of the LUAD data using our approach revealed a linear trajectory with three different branches for malignant progression, and the results showed consistency in three independent cohorts. We used the progression model to elucidate the potential molecular events in LUAD progression. Further analysis showed that overexpression of BUB1B, BUB1 and BUB3 promoted tumor cell proliferation and metastases by disturbing the spindle assembly checkpoint (SAC) in the mitosis. Aberrant mitotic spindle checkpoint signaling appeared to be one of the key factors promoting LUAD progression. We found the inferred cancer trajectory allows to identify LUAD susceptibility genetic variations using genome-wide association analysis. This result shows the opportunity for combining analysis of candidate genetic factors with disease progression. Furthermore, the trajectory showed clear evident mutation accumulation and clonal expansion along with the LUAD progression. Understanding how tumors evolve and identifying mutated genes will help guide cancer management. We investigated the clonal architectures and identified distinct clones and subclones in different LUAD branches. Validation of the model in multiple independent data sets and correlation analysis with clinical results demonstrate that our method is effective and unbiased. Author summary: Lung adenocarcinoma (LUAD) is a deadly tumor that remains approximately 15% survival rate in 5 years. The diverse reasons that made cancer progression and metastasis include genetic mutation, gene expression alteration, and so on. Understanding this dynamic process and identifying pivotal molecular events driving tumor progression is essential for improving LUAD diagnosis and treatment. Studying time-series data can simulate cancer evolution and determine the temporal patterns of molecular alterations. Unfortunately, it is difficult to collect complete time-series data from individual patients due to various reasons. In this study, we developed a trajectory model based on gene expression of LUAD patients and identified distinct progression branches. Moreover, we found a key gene BUB1B that could lead to aberrant spindle assembly checkpoint (SAC) signaling, and this appeared to be one of the key factors promoting LUAD progression. The trajectory shows clear evident mutation accumulation and clonal expansion along with the LUAD progression. We also investigated the clonal architectures and identified distinct clones and subclones in different LUAD branches. This clones and subclones can be used to identify combination therapy for LUAD. Our results demonstrate the biological utility and clinical application prospects of this progression model. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration and an abnormal accumulation of α-synuclein aggregates. A number of genetic factors have been shown to increase the risk of PD. Exploring the underlying molecular mechanisms that mediate PD's transcriptomic diversity can help us understand neurodegenerative pathogenesis. In this study, we identified 9897 A-to-I RNA editing events associated with 6286 genes across 372 PD patients. Of them, 72 RNA editing events altered miRNA binding sites and this may directly affect miRNA regulations of their host genes. However, RNA editing effects on the miRNA regulation of genes are more complex. They can (1) abolish existing miRNA binding sites, which allows miRNAs to regulate other genes; (2) create new miRNA binding sites that may sequester miRNAs from regulating other genes; or (3) occur in the miRNA seed regions and change their targets. The first two processes are also referred to as miRNA competitive binding. In our study, we found 8 RNA editing events that may alter the expression of 1146 other genes via miRNA competition. We also found one RNA editing event that modified a miRNA seed region, which was predicted to disturb the regulation of four genes. Considering the PD-related functions of the affected genes, 25 A-to-I RNA editing biomarkers for PD are proposed, including the 3 editing events in the EIF2AK2, APOL6, and miR-4477b seed regions. These biomarkers may alter the miRNA regulation of 133 PD-related genes. All these analyses reveal the potential mechanisms and regulations of RNA editing in PD pathogenesis. [ABSTRACT FROM AUTHOR]

A-to-I RNA editing diversifies human transcriptome to confer its functional effects on the downstream genes or regulations, potentially involving in neurodegenerative pathogenesis. Its variabilities are attributed to multiple regulators, including the key factor of genetic variants. To comprehensively investigate the potentials of neurodegenerative disease-susceptibility variants from the view of A-to-I RNA editing, we analyzed matched genetic and transcriptomic data of 1596 samples across nine brain tissues and whole blood from two large consortiums, Accelerating Medicines Partnership-Alzheimer's Disease and Parkinson's Progression Markers Initiative. The large-scale and genome-wide identification of 95 198 RNA editing quantitative trait loci revealed the preferred genetic effects on adjacent editing events. Furthermore, to explore the underlying mechanisms of the genetic controls of A-to-I RNA editing, several top RNA-binding proteins were pointed out, such as EIF4A3 , U2AF2 , NOP58 , FBL , NOP56 and DHX9 , since their regulations on multiple RNA-editing events were probably interfered by these genetic variants. Moreover, these variants may also contribute to the variability of other molecular phenotypes associated with RNA editing, including the functions of 3 proteins, expressions of 277 genes and splicing of 449 events. All the analyses results shown in NeuroEdQTL (https://relab.xidian.edu.cn/NeuroEdQTL/) constituted a unique resource for the understanding of neurodegenerative pathogenesis from genotypes to phenotypes related to A-to-I RNA editing. [ABSTRACT FROM AUTHOR]

SUMMARY: Phosphorus (P) is an important nutrient for plants. Here, we identify a WRKY transcription factor (TF) in poplar (Populus deltoides × Populus euramericana) (PdeWRKY65) that modulates tissue phosphate (Pi) concentrations in poplar. PdeWRKY65 overexpression (OE) transgenic lines showed reduced shoot Pi concentrations under both low and normal Pi availabilities, while PdeWRKY65 reduced expression (RE) lines showed the opposite phenotype. A gene encoding a Pi transporter (PHT), PdePHT1;9, was identified as the direct downstream target of PdeWRKY65 by RNA sequencing (RNA‐Seq). The negative regulation of PdePHT1;9 expression by PdeWRKY65 was confirmed by DNA–protein interaction assays, including yeast one‐hybrid (Y1H), electrophoretic mobility shift assay (EMSA), co‐expression of the promoters of PdePHT1;9 and PdeWRKY65 in tobacco (Nicotiana benthamiana) leaves, and chromatin immunoprecipitation–quantitative PCR. A second WRKY TF, PdeWRKY6, was subsequently identified and confirmed to positively regulate the expression of PdePHT1;9 by DNA–protein interaction assays. PdePHT1;9 and PdeWRKY6 OE and RE poplar transgenic lines were used to confirm their positive regulation of shoot Pi concentrations, under both normal and low Pi availabilities. No interaction between PdeWRKY6 and PdeWRKY65 was observed at the DNA or protein levels. Collectively, these data suggest that the low Pi‐responsive TFs PdeWRKY6 and PdeWRKY65 independently regulate the expression of PHT1;9 to modulate tissue Pi concentrations in poplar. Significance Statement: The genes PdeWRKY65 and PdeWRKY6, encoding WRKY transcription factors, and PdePHT1;9, encoding a phosphate (Pi) transporter, form a regulatory network to modulate tissue Pi concentrations in response to low Pi availability in poplar (Populus deltoides × Populus euramericana). In the regulatory network, PdeWRKY65 and PdeWRKY6 negatively and positively regulate the expression of PdePHT1;9 by binding to W‐Boxes within the PdePHT1;9 promoter, respectively. [ABSTRACT FROM AUTHOR]

The Chinese tallow tree (Triadica sebifera) can produce oil with high content of unsaturated fatty acids in seeds and shows attractive leaf color in autumn and winter. Here, the 739 Mb chromosome-scale genome sequence of the Chinese tallow tree was assembled and it reveals the Chinese tallow tree is a tetraploid. Numerous genes related to nutrition assimilation, energy utilization, biosynthesis of secondary metabolites and resistance significantly expanded or are specific to the Chinese tallow tree. These genes would enable the Chinese tallow tree to obtain high adaptability. More genes in fatty acids biosynthesis in its genome, especially for unsaturated fatty acids biosynthesis, and higher expression of these genes in seeds would be attributed to its high content of unsaturated fatty acids. Cyanidin 3-O-glucoside was identified as the major component of anthocyanin in red leaves. All structural genes in anthocyanin biosynthesis show significantly higher expression in red leaves than in green leaves. Transcription factors, seven MYB and one bHLH, were predicted to regulate these anthocyanin biosynthesis genes. Collectively, we provided insight into the polyploidization, high adaptability and biosynthesis of the high content of unsaturated fatty acids in seeds and anthocyanin in leaves for the Chinese tallow tree. A chromosome-level assembly of the economically-important Chinese tallow tree is presented alongside functional analyses into biosynthetic products in the leaves and seeds. [ABSTRACT FROM AUTHOR]

Background: Trigeminal neuralgia (TN) is a neuropathic pain that occurs in branches of the trigeminal nerve. MicroRNAs (miRNAs) have been considered key mediators of neuropathic pain. This study was aimed to elucidate the pathophysiological function and mechanisms of miR‐223‐3p in mouse models of TN. Methods: Infraorbital nerve chronic constriction injury (CCI‐ION) was applied in male C57BL/6J mice to establish mouse models of TN. Pain responses were assessed utilizing Von Frey method. The expression of miR‐223‐3p, MKNK2, and MAPK/ERK pathway protein in trigeminal ganglions (TGs) of CCI‐ION mice was measured using RT‐qPCR and Western blotting. The concentrations of inflammatory cytokines were evaluated using Western blotting. The relationship between miR‐223‐3p and MKNK2 was tested by a luciferase reporter assay. Results: We found that miR‐223‐3p was downregulated, while MKNK2 was upregulated in TGs of CCI‐ION mice. MiR‐223‐3p overexpression by an intracerebroventricular injection of Lv‐miR‐223‐3p attenuated trigeminal neuropathic pain in CCI‐ION mice, as well as reduced the protein levels of pro‐inflammatory cytokines in TGs of CCI‐ION mice. MKNK2 was verified to be targeted by miR‐223‐3p. Additionally, miR‐223‐3p overexpression decreased the phosphorylation levels of ERK1/2, JNK, and p38 protein in TGs of CCI‐ION mice to inhibit MAPK/ERK signaling. Conclusions: Overall, miR‐223‐3p attenuates the development of TN by targeting MKNK2 to suppress MAPK/ERK signaling. [ABSTRACT FROM AUTHOR]

Hydrogen peroxide (H2O2) plays important roles in plant development. Adventitious roots (AR), lateral buds (LB) and callus formation are important traits for plants. Here, a gene encoding RESPIRATORY BURST OXIDASE HOMOLOG B (PdeRBOHB) from poplar line 'NL895' (Populus. deltoides × P. euramericana) was predicted to be involved in H2O2 accumulation, and lines with reduced expression were generated. H2O2 content was decreased, and the development of adventitious roots, lateral buds, and callus was inhibited in reduced expression PdeRBOHB lines. A gene encoding PdeWRKY75 was identified as the upstream transcription factor positively regulating PdeRBOHB. This regulation was confirmed by dual luciferase reporter assay, GUS transient expression analysis and electrophoretic mobility shift assay. In the reduced expression PdeWRKY75 lines, H2O2 content was decreased and the development of adventitious roots, lateral buds, and callus development was inhibited, while in the overexpression lines, H2O2 content was increased and the development of adventitious roots and lateral buds was inhibited, but callus formation was enhanced. Additionally, reduced expression PdeRBOHB lines showed lowered expression of PdeWRKY75 , while exogenous application of H2O2 showed the opposite effect. Together, these results suggest that PdeWRKY75 and PdeRBOHB are part of a regulatory module in H2O2 accumulation, which is involved in the regulation of multiple biological processes. [ABSTRACT FROM AUTHOR]

Ovarian tumor (OTU) subfamily deubiquitinases are involved in various cellular processes, such as inflammation, ferroptosis and tumorigenesis; however, their pathological roles in prostate cancer (PCa) remain largely unexplored. In this study, we observed that several OTU members displayed genomic amplification in PCa, among which ovarian tumor deubiquitinase 6A (OTUD6A) amplified in the top around 15–20%. Further clinical investigation showed that the OTUD6A protein was highly expressed in prostate tumors, and increased OTUD6A expression correlated with a higher biochemical recurrence risk after prostatectomy. Biologically, wild-type but not a catalytically inactive mutant form of OTUD6A was required for PCa cell progression. In vivo experiments demonstrated that OTUD6A oligonucleotides markedly suppressed prostate tumorigenesis in PtenPC−/− mice and patient-derived xenograft (PDX) models. Mechanistically, the SWI/SNF ATPase subunit Brg1 and the nuclear receptor AR (androgen receptor) were identified as essential substrates for OTUD6A in PCa cells by a mass spectrometry (MS) screening approach. Furthermore, OTUD6A stabilized these two proteins by erasing the K27-linked polyubiquitination of Brg1 and K11-linked polyubiquitination of AR. OTUD6A amplification exhibited strong mutual exclusivity with mutations in the tumor suppressors FBXW7 and SPOP. Collectively, our results indicate the therapeutic potential of targeting OTUD6A as a deubiquitinase of Brg1 and AR for PCa treatment. OTUD6A, a deubiquitinase, is amplified in prostate cancer and correlates with poor survivability, increasing the growth of prostate cancer cell lines and PDX models. OTUD6A stabilizes the expression of Brg1 and AR through the removal of K27- and K11-linked polyubiquination. [ABSTRACT FROM AUTHOR]

Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of rice bacterial blight, which is a major rice disease in tropical Asian countries. An attempt has been made to investigate gene expression patterns of three Xoo strains on the minimal medium XOM2, PXO99 (P6) and PXO86 (P2) from the Philippines, and GD1358 (C5) from China, which exhibited different virulence in 30 rice varieties, with putative virulence factors using deep sequencing. In total, 4,781 transcripts were identified in this study, and 1,151 and 3,076 genes were differentially expressed when P6 was compared with P2 and with C5, respectively. Our results indicated that Xoo strains from different regions exhibited distinctly different expression patterns of putative virulence-relevant genes. Interestingly, 40 and 44 genes involved in chemotaxis and motility exhibited higher transcript alterations in C5 compared with P6 and P2, respectively. Most other genes associated with virulence, including exopolysaccharide (EPS) synthesis, Hrp genes and type III effectors, including Xanthomonas outer protein (Xop) effectors and transcription activator-like (TAL) effectors, were down-regulated in C5 compared with P6 and P2. The data were confirmed by real-time quantitative RT-PCR, tests of bacterial motility, and enzyme activity analysis of EPS and xylanase. These results highlight the complexity of Xoo and offer new avenues for improving our understanding of Xoo-rice interactions and the evolution of Xoo virulence. [ABSTRACT FROM AUTHOR]

Sorghum (Sorghum bicolor) is one of the world's most important cereal crops. S. propinquum is a perennial wild relative of S. bicolor with well-developed rhizomes. Functional genomics analysis of S. propinquum, especially with respect to molecular mechanisms related to rhizome growth and development, can contribute to the development of more sustainable grain, forage, and bioenergy cropping systems. In this study, we used a whole rice genome oligonucleotide microarray to obtain tissue-specific gene expression profiles of S. propinquum with special emphasis on rhizome development. A total of 548 tissue-enriched genes were detected, including 31 and 114 unique genes that were expressed predominantly in the rhizome tips (RT) and internodes (RI), respectively. Further GO analysis indicated that the functions of these tissue-enriched genes corresponded to their characteristic biological processes. A few distinct cis-elements, including ABA-responsive RY repeat CATGCA, sugar-repressive TTATCC, and GA-responsive TAACAA, were found to be prevalent in RT-enriched genes, implying an important role in rhizome growth and development. Comprehensive comparative analysis of these rhizome-enriched genes and rhizome-specific genes previously identified in Oryza longistaminata and S. propinquum indicated that phytohormones, including ABA, GA, and SA, are key regulators of gene expression during rhizome development. Co-localization of rhizome-enriched genes with rhizome-related QTLs in rice and sorghum generated functional candidates for future cloning of genes associated with rhizome growth and development. [ABSTRACT FROM AUTHOR]

Connected consciousness refers to the state when external stimuli can enter into the stream of our consciousness experience. Emerging evidence suggests that although patients may not respond behaviorally to external stimuli during anesthesia, they may be aware of their surroundings. In this work, we investigated whether EEG based brain decoding could be used for detecting connected consciousness in the absence of behavioral responses during propofol infusion. A total of 14 subjects participated in our experiment. Subjects were asked to discriminate two types of auditory stimuli with a finger press during an ultraslow propofol infusion. We trained an EEG based brain decoding model using data collected in the awakened state using the same auditory stimuli and tested the model on data collected during the propofol infusion. The model provided a correct classification rate (CCR) of 7 8. 7 4 ± 1 1. 1 5 % when subjects were able to respond to the stimuli during the propofol infusion. The CCR dropped to 6 7. 2 9 ± 8. 2 1 % when subjects ceased responding and further decreased to 5 8. 1 1 ± 8. 1 5 % when we increased the propofol concentration by another 0.2 μ g/ml. After terminating the propofol infusion, we observed that the CCR rebounded to 6 5. 3 1 ± 7. 1 1 % before the subjects regained consciousness. With the classification results, we provided evidence that loss of consciousness is a gradual process and may progress from full consciousness to connected consciousness and then to disconnected consciousness. [ABSTRACT FROM AUTHOR]

Propofol and dexmedetomidine are popular used for sedation in ICU, however, inadequate attention has been paid to their effect on gastrointestinal tract (GIT) motility. Present study aimed to compare the effect of propofol and dexmedetomidine on GIT motility at parallel level of sedation and explore the possible mechanism. Male C57BL/6 mice (8–10 weeks) were randomly divided into control, propofol and dexmedetomidine group. After intraperitoneal injection of propofol or dexmedetomidine, comparable sedative level was confirmed by sedative score, physiological parameters and electroencephalogram (EEG). Different segments of GIT motility in vivo (gastric emptying, small intestine transit, distal colon bead expulsion, stool weight and number of fecal pellets, gastrointestinal transit and whole gut transit time) and colonic migrating motor complexes (CMMCs) pattern in vitro were evaluated. The Ca2+ response of primary enteric glia was examined under the treatment of propofol or dexmedetomidine. There is little difference in physiological parameters and composite permutation entropy index (CPEI) between administration of 50 mg/kg propofol and 40 μg/kg dexmedetomidine, indicated that parallel level of sedation was reached. Data showed that propofol and dexmedetomidine had significantly inhibitory effect on GIT motility while dexmedetomidine was stronger. Also, the amplitude (ΔF/F0) of Ca2+ response in primary enteric glia was attenuated after treated with the sedatives while the effect of dexmedetomidine was greater than propofol. These findings demonstrated that dexmedetomidine caused stronger inhibitory effects on GIT motility in sedative mice, which may involve impaired Ca2+ response in enteric glia. Hence, dexmedetomidine should be carefully applied especially for potential GIT dysmotility patient. [ABSTRACT FROM AUTHOR]

Objectives: A machine learning model was developed to evaluate the severity of aortic coarctation (CoA) in infants based on anatomical features measured on CTA. Methods: In total, 239 infant patients undergoing both thorax CTA and echocardiography were retrospectively reviewed. The patients were assigned to either mild or severe CoA group based on their pressure gradient on echocardiography. They were further divided into patent ductus arteriosus (PDA) and non-PDA groups. The anatomical features were measured on double-oblique multiplanar reconstructed CTA images. Then, the optimal features were identified by using the Boruta algorithm. Subsequently, the coarctation severity was classified using linear discriminant analysis (LDA). We further investigated the relationship between the anatomical features and re-coarctation using Cox regression. Results: Four anatomical features showed significant differences between the mild and severe CoA groups, including the smallest aortic cross-sectional area indexed to body surface area (p < 0.001), the narrowest aortic diameter (CoA diameter) indexed to height (p < 0.001), the diameter of the descending aorta at the diaphragmatic level (p < 0.001) and weight (p = 0.005). With these features, accuracy of 88.6% and 90.2%, sensitivity of 65.0% and 72.1%, and specificity of 92.9% and 100% were obtained for classifying the CoA severity in the non-PDA and PDA groups, respectively. Moreover, CoA diameter indexed to weight was associated with the risk of re-coarctation. Conclusions: CoA severity can be evaluated by using LDA with anatomical features. When quantifying the severity of CoA and risk of re-coarctation, both anatomical alternations at the CoA site and the growth of the patients need to be considered. Key Points: • CTA is routinely ordered for infants with coarctation of the aorta; however, whether anatomical variations observed with CTA could be used to assess the severity of CoA remains unknown. • Using the diameter and area of the coarctation site adjusted to body growth as features, the LDA model achieved an accuracy of 88.6% and 90.2% in differentiating between the mild and severe CoA patients in the non-PDA group and PDA group, respectively. • The narrowest aortic diameter (CoA diameter) indexed to weight has a hazard ratio of 10.29 for re-coarctation. [ABSTRACT FROM AUTHOR]

• Response time evaluates responsiveness levels continuously during slow propofol induction. • Time-resolved spectral slope correlates better with RT at the beta-gamma band. • Frontal spectral slopes perform best for predicting response time. • Spectral slope decreases during anesthesia induction and increases during recovery. The level of consciousness undergoes continuous alterations during anesthesia. Prior to the onset of propofol-induced complete unconsciousness, degraded levels of behavioral responsiveness can be observed. However, a reliable index to monitor altered consciousness levels during anesthesia has not been sufficiently investigated. In this study, we obtained 60-channel EEG data from 24 healthy participants during an ultra-slow propofol infusion protocol starting with an initial concentration of 1 μg/ml and a stepwise increase of 0.2 μg/ml in concentration. Consecutive auditory stimuli were delivered every 5 to 6 s, and the response time to the stimuli was used to assess the responsiveness levels. We calculated the spectral slope in a time-resolved manner by extracting 5-second EEG segments at each auditory stimulus and estimated their correlation with the corresponding response time. Our results demonstrated that during slow propofol infusion, the response time to external stimuli increased, while the EEG spectral slope, fitted at 15–45 Hz, became steeper, and a significant negative correlation was observed between them. Moreover, the spectral slope further steepened at deeper anesthetic levels and became flatter during anesthesia recovery. We verified these findings using an external dataset. Additionally, we found that the spectral slope of frontal electrodes over the prefrontal lobe had the best performance in predicting the response time. Overall, this study used a time-resolved analysis to suggest that the EEG spectral slope could reliably track continuously altered consciousness levels during propofol anesthesia. Furthermore, the frontal spectral slope may be a promising index for clinical monitoring of anesthesia depth. [ABSTRACT FROM AUTHOR]

BACKGROUND: A large proportion of gastric cancer patients are susceptible to chemoresistance, while the underlying mechanism remains obscure. Stress granules (SGs) play a self-defence role for tumour cells in inhibiting chemotherapy-induced apoptosis. As an SG assembly effector, G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein) has been reported to be overexpressed in gastric cancer; thus, here we aim to explore its potent roles in gastric cancer chemoresistance. METHODS: Kaplan–Meier analysis was used to compare survival rates in gastric cancer patients with different G3BP1 expression. The influence of G3BP1 on gastric cancer cell chemoresistance and apoptosis were evaluated by in vitro and in vivo approaches. The interaction between G3BP1 and YWHAZ was assessed by immunohistochemistry, immunoprecipitation and immunofluorescence. RESULTS: G3BP1 was associated with the poor outcome of gastric cancer patients who received adjuvant chemotherapy. G3BP1 knockdown significantly increased the sensitivity of gastric cancer cells to chemotherapy drugs. Mechanically, cell apoptosis and pro-apoptotic-associated molecules were significantly elevated upon G3BP1 depletion. Gene co-expression network analyses identified YWHAZ as the critical interlayer of G3BP1; as a result, G3BP1 interacted with YWHAZ to sequester Bax into the cytoplasm. Clinically, G3BP1highYWHAZhigh gastric cancer patients displayed the worst outcome compared with other patients after chemotherapy. CONCLUSIONS: The expression of G3BP1 and YWHAZ could predict the adjuvant chemotherapy benefit in gastric cancer patients. [ABSTRACT FROM AUTHOR]

Background: A large proportion of gastric cancer patients are susceptible to chemoresistance, while the underlying mechanism remains obscure. Stress granules (SGs) play a self-defence role for tumour cells in inhibiting chemotherapy-induced apoptosis. As an SG assembly effector, G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein) has been reported to be overexpressed in gastric cancer; thus, here we aim to explore its potent roles in gastric cancer chemoresistance.Methods: Kaplan-Meier analysis was used to compare survival rates in gastric cancer patients with different G3BP1 expression. The influence of G3BP1 on gastric cancer cell chemoresistance and apoptosis were evaluated by in vitro and in vivo approaches. The interaction between G3BP1 and YWHAZ was assessed by immunohistochemistry, immunoprecipitation and immunofluorescence.Results: G3BP1 was associated with the poor outcome of gastric cancer patients who received adjuvant chemotherapy. G3BP1 knockdown significantly increased the sensitivity of gastric cancer cells to chemotherapy drugs. Mechanically, cell apoptosis and pro-apoptotic-associated molecules were significantly elevated upon G3BP1 depletion. Gene co-expression network analyses identified YWHAZ as the critical interlayer of G3BP1; as a result, G3BP1 interacted with YWHAZ to sequester Bax into the cytoplasm. Clinically, G3BP1highYWHAZhigh gastric cancer patients displayed the worst outcome compared with other patients after chemotherapy.Conclusions: The expression of G3BP1 and YWHAZ could predict the adjuvant chemotherapy benefit in gastric cancer patients. [ABSTRACT FROM AUTHOR]

• Propofol susceptibility correlates well with pre-anesthesia dynamic frontal-parietal communication. • Robustness of the results is verified on three data sets. • Propofol administration should take pre-operative brain functional state into consideration. We investigated whether pre-anesthesia dynamic frontal-parietal functional connectivity was correlated with the observed interindividual differences in propofol susceptibility. Three resting-state EEG datasets were used in the study (N = 29, N = 21 and N = 20). We estimated the pre-anesthesia strength and fluctuations of frontal-parietal functional connectivity by using sliding-window analysis. Propofol served as the sole anesthetic drug, and it was administered by using a target-controlled infusion system. Individual susceptibility to propofol was assessed by the induction time, from infusion onset until a bispectral index value of 60 was reached, for subjects in dataset-1 and dataset-2, and susceptibility was assessed by behavioral data for subjects in the external dataset. We observed in the three datasets that subjects with high susceptibility to propofol had lower pre-anesthesia strength and lower fluctuation of frontal-parietal functional connectivity than the low-susceptibility group at alpha band. Moreover, the induction time was significantly correlated with the estimated pre-anesthesia frontal-parietal functional connectivity measures. We also validated the robustness of these findings by using different window lengths in sliding-window analysis. Subjects with weaker pre-anesthesia dynamic frontal-parietal communication are more likely to be anesthetized. These observations suggest that the titration procedure for propofol should consider the pre-anesthesia brain functional state. [ABSTRACT FROM AUTHOR]

• Developed an accurate prediction system for the progression of mild cognitive impairment to AD. • Used longitudinal structural MRI data without the segmentation of regions of interest. • Applied dictionary learning to exploit the nuances between mild cognitive impairment patients. Efficient prediction of the progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD) is important for the early intervention and management of AD. The aim of our study was to develop a longitudinal structural magnetic resonance imaging-based prediction system for MCI progression. A total of 164 MCI patients with longitudinal data were collected from the Alzheimer's Disease Neuroimaging Initiative (ADNI). After preprocessing, a discriminative dictionary learning framework was applied to differentiate MCI patches, avoiding the segmentation of regions of interest. Then, the proportion of patches classified as more severe atrophy patches in a patient was calculated as his or her feature to be input into a simple support vector machine. Finally, a new subject was predicted with fourfold cross-validation (CV), and the area under the receiver operating characteristic curve (AUC) was determined. The average accuracy and AUC values after fourfold CV were 0.973 and 0.984, respectively. The effects of the data from one or two time points were also investigated. The proposed prediction system achieves desirable and reliable performance in predicting progression for MCI patients. Additionally, the prediction of MCI progression with longitudinal data was more effective and accurate. The developed scheme is expected to advance the clinical research and treatment of MCI patients. [ABSTRACT FROM AUTHOR]

Background: Salt stress and bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) are key limiting factors of rice (Oryza sativa L.) yields. Members of sucrose non-fermenting 1 (SNF1)-related protein kinase 2 (SnRK2), which is a family of plant-specific Ser/Thr kinases, are important components of signaling pathways involved in plant developmental processes and responses to stresses. There are 10 members of the SnRK2 family in rice; however, their functions are poorly understood, as are the underlying molecular mechanisms. Results: In this study, we found that OsSAPK9, which belongs to the SnRK2 family, positively regulated salt-stress tolerance and strain-specific resistance to bacterial blight in rice. RNA sequencing revealed that there were 404 and 1324 genes differentially expressed in OsSAPK9-RNAi in comparison with wild-type plants under salt-stress conditions and after Xoo inoculation, respectively, which participate in basic metabolic processes. In total, 65 common differentially expressed genes involved mainly in defense responses were detected both under salt-stress conditions and after Xoo inoculation. Moreover, in vivo and in vitro experiments demonstrated that OsSAPK9 forms a protein complex with the molecular chaperones OsSGT1 and OsHsp90, and transgenic plants overexpressing OsSGT1 exhibited decreased tolerances to salt stress and significantly increased resistance levels to bacterial blight. Thus, OsSAPK9 may function as a center node regulator of salt-stress responses and disease-resistance pathways through its interaction with OsSGT1 in rice. Conclusion: This study confirms that OsSAPK9 functions as a positive regulator of salt-stress responses and disease resistance through its interaction with OsSGT1 in rice. [ABSTRACT FROM AUTHOR]

Background: High soil salinity can cause significant losses in rice productivity worldwide, mainly because salt inhibits plant growth and reduces grain yield. To cope with environmental changes, plants have evolved several adaptive mechanisms that involve the regulation of many stress-responsive genes. Results: In this study, we identified OsSTAP1, which encodes an AP2/ERF-type transcription factor, was rapidly induced by ABA, ACC, salt, cold, and PEG treatments. OsSTAP1 is localized to the nucleus and acts as a transcriptional activator in plant cells. Compared with wild type, transgenic lines overexpressing OsSTAP1 exhibited increased tolerance to salt stress with higher SOD, POD, and CAT activities, and lower Na+/K+ ratios in the shoots. In addition, many other stress-responsive genes, including other ERF- and peroxidase-encoding genes, were upregulated in the OsSTAP1-overexpression lines. Conclusion: This study suggests that OsSTAP1 functions as an AP2/ERF transcriptional activator, and plays a positive role in salt tolerance by decreasing the Na+/K+ ratio and maintaining cellular redox homeostasis. [ABSTRACT FROM AUTHOR]

Purpose: To develop and identify a MRI-based radiomics nomogram for the preoperative prediction of parametrial invasion (PMI) in patients with early-stage cervical cancer (ECC).Materials and Methods: All 137 patients with ECC (FIGO stages IB-IIA) underwent T2WI and DWI scans before radical hysterectomy surgery. The radiomics signatures were calculated with the radiomics features which were extracted from T2WI and DWI and selected by the least absolute shrinkage and selection operation regression. The support vector machine (SVM) models were built using radiomics signatures derived from T2WI and joint T2WI and DWI respectively to evaluate the performance of radiomics signatures for distinguishing patients with PMI. A radiomics nomogram was drawn based on the radiomics signatures with a better performance, patient's age, and pathological grade; its discrimination and calibration performances were estimated.Results: For T2WI and joint T2WI and DWI, the radiomics signatures yielded an AUC of 0.797 (95% CI, 0.682-0.911) vs 0.946 (95% CI, 0.899-0.994), and 0.780 (95% CI, 0.641-0.920) vs 0.921 (95% CI, 0.832-1) respectively in the primary and validation cohorts. The radiomics nomogram, integrating the radiomics signatures from joint T2WI and DWI, patient's age, and pathological grade, showed excellent discrimination, with C-index values of 0.969 (95% CI, 0.933-1) and 0.941 (95% CI, 0.868-1) in the primary and validation cohorts, respectively. The calibration curve showed a good agreement.Conclusions: The radiomics nomogram performed well for the preoperative prediction of PMI in patients with ECC and may be used as a supplementary tool to provide individualized treatment plans for patients with ECC.Key Points: • No previously reported study that has utilized radiomics nomogram to preoperatively predict PMI for patients with ECC. • Radiomics model involves radiomics features extracted from joint T2WI and DWI which characterize the heterogeneity between tumors in patients with ECC. • Radiomics nomogram can assist clinicians with individualized treatment decision-making for patients with ECC. [ABSTRACT FROM AUTHOR]

Negative symptoms in schizophrenia have been associated with functional changes in frontostriatal pathways. Dysregulation of the dopamine signal in frontostriatal pathways leads to the symptomology observed in schizophrenia. Although the catechol‐O‐methyltransferase (COMT) gene, one of the susceptibility genes for schizophrenia, has been associated with dopamine activities in prefrontal and striatal regions, it is still unclear whether the disease state and COMT val158met genotype have an interaction effect on the functional connectivity of frontostriatal pathways. In this study, we evaluated the possible interactions between COMT val158met variations and the disease state on the resting‐state functional connectivity (RSFC) of frontostriatal pathways in fifty‐one first episode schizophrenia (FES) patients (val/val: 29, met +: 22) with prominent negative symptoms and forty‐eight healthy controls (val/val: 31, met +: 17). Regions of interest were defined by the result of a meta‐analysis of frontostriatal pathways using the Neurosynth database. We found a significant genotype × disease interaction effect on the RSFC between the bilateral anterior cingulate (ACC) and right caudate, which overlapped with the main effect of the disease state. Behavioural regression analysis suggested that RSFC between the right ACC and right caudate correlated with the severity of SANS avolition–apathy scores in patients who were met carriers but not in patients who were val homozygous. Our findings suggest that the RSFC of frontostriatal pathways may differentially affected by an individual's COMT val158met genotype. [ABSTRACT FROM AUTHOR]

The recent boom of nanomaterials printing in the fields of biomedical engineering, bioanalysis and flexible electronics has greatly stimulated researchers' interest in printing technologies. However, specifically formulated nanomaterial inks have limited the types of printable nanomaterials. Here, a unique non-powered capillary force-driven stamped (CFDS) approach, combining a 3D-printed stamper with a paper substrate, is developed for directly printing patterned nanomaterials aqueous solution. The CFDS approach has two processes, including the loading process in which the capillary force of the stamper channel is stronger than gravity, and the deposition process, in which the synergistic action of the capillary force of the paper fibre tubes and gravity is approximately 20 times the capillary force of the stamper channel. Four additive-free nanomaterial aqueous solutions, including nanowires, nanosheets, nanostars and nanogels, are used to print patterns, and show slight diffusion and desired uniformity with a diffusion rate and roundness of 1.12 and 0.78, respectively, demonstrating the feasibility of this approach. Four kinds of nanogel with different fluorescence labels are simultaneously printed to challenge the approach and demonstrate its flexibility and scalability. The resolution of the approach is 0.3 mm. Without any post-processing, the stamped paper substrates directly serve as paper-based surface enhanced Raman scattering substrates with an enhancement factor of 4 × 106 and as electrodes with a resistance of 0.74 Ω, demonstrating their multi-functionality. Due to its general, flexible and scalable applicability, this simple, low-cost and non-powered approach could be widely applied to the personalized printing of nanomaterials on paper substrates. [ABSTRACT FROM AUTHOR]

The 5-hydroxytryptamine 2A receptor (5-HT2A) and dopamine D3 receptor (DRD3) have been extensively studied as promising candidate genes for schizophrenia. Magnetic resonance imaging studies have demonstrated that schizophrenia is associated with widespread structural and functional abnormalities in the brain. Serotonin and dopamine receptors play crucial roles in the development of the human cerebral cortex and brain activity. However, how the 5-HT2A and DRD3 genes impact brain structure and function in schizophrenia remains unknown. In the present study, we investigated the main effect of disease state and the interaction effect between disease state and genotype of these two genes on cortical volume, thickness, surface area and functional connectivity density (FCD) in fifty-five drug-naïve first episode schizophrenia patients and fifty-three healthy controls. We found that the differences in local FCD (lFCD) and global FCD (gFCD) between patients and healthy controls were predominantly located in brain hub regions. The significant interaction effects of disease state and 5-HT2A and DRD3 genes on brain structure and function were mainly located in the temporal cortex. Our findings may help to improve the understanding of the relationship between 5-HT2A and DRD3 genotypes and schizophrenia pathogenesis. [ABSTRACT FROM AUTHOR]

Elevated expression and genetic aberration of IRTKS, also named as BAIAP2L1, have been observed in many tumors, especially in tumor progression. however, the molecular and cellular mechanisms involved in the IRTKS-enhanced tumor progression are obscure. Here we show that higher IRTKS level specifically increases histone H3 lysine 9 trimethylation (H3K9me3) by promoting accumulation of the histone methyltransferase SETDB1. Furthermore, we reveal that IRTKS recruits the deubiquitinase OTUD4 to remove Lys48-linked polyubiquitination at K182/K1050 sites of SETDB1, thus blocking SETDB1 degradation via the ubiquitin-proteasome pathway. Interestingly, the enhanced IRTKS–OTUD4–SETDB1–H3K9me3 axis leads to a general decrease in chromatin accessibility, which inhibits transcription of CDH1 encoding E-cadherin, a key molecule essential for maintaining epithelial cell phenotype, and therefore results in epithelial-mesenchymal transition (EMT) and malignant cell metastasis. Clinically, the elevated IRTKS levels in tumor specimens correlate with SETDB1 levels, but negatively associate with survival time. Our data reveal a novel mechanism for the IRTKS-enhanced tumor progression, where IRTKS cooperates with OTUD4 to enhance SETDB1-mediated H3K9 trimethylation that promotes tumor metastasis via suppressing E-cadherin expression. This study also provides a potential approach to reduce the activity and stability of the known therapeutic target SETDB1 possibly through regulating IRTKS or deubiquitinase OTUD4. • Higher levels of IRTKS increase H3K9me3 by promoting SETDB1 accuumulation. • IRTKS recruits the deubiquitinase OTUD4 to blocking SETDB1 degradation. • The enhanced IRTKS–OTUD4–SETDB1–H3K9me3 axis decreases chromatin accessibility, and inhibits E-cadherin transcription, resulting in EMT and tumor metastasis. • Clinically, elevated IRTKS levels in tumor correlate with SETDB1 levels, and negatively associate with survival time. [ABSTRACT FROM AUTHOR]

Insulin signaling is mediated by a highly integrated network that controls glucose metabolism, protein synthesis, cell growth, and differentiation. Our previous work indicates that the insulin receptor tyrosine kinase substrate (IRTKS), also known as BAI1-associated protein 2-like 1 (BAIAP2L1), is a novel regulator of insulin network, but the mechanism has not been fully studied. In this work we reveal that IRTKS co-localizes with Src homology (SH2) containing inositol polyphosphate 5-phosphatase-2 (SHIP2), and the SH3 domain of IRTKS directly binds to SHIP2's catalytic domain INPP5c. IRTKS suppresses SHIP2 phosphatase to convert phosphatidylinositol 3,4,5-triphosphate (PI(3,4,5)P3, PIP3) to phosphatidylinositol (3,4) bisphosphate (PI(3,4)P2). IRTKS-knockout significantly increases PI(3,4)P2 level and decreases cellular PI(3,4,5)P3 content. Interestingly, the interaction between IRTKS and SHIP2 is dynamically regulated by insulin, which feeds back and affects the tyrosine phosphorylation of IRTKS. Furthermore, IRTKS overexpression elevates PIP3, activates the AKT–mTOR signaling pathway, and increases cell proliferation. Thereby, IRTKS not only associates with insulin receptors to activate PI3K but also interacts with SHIP2 to suppress its activity, leading to PIP3 accumulation and the activation of the AKT–mTOR signaling pathway to modulate cell proliferation. [ABSTRACT FROM AUTHOR]

• Feeder and local connections change in AD group. • Left putamen and precuneus had significant differences in betweenness centrality. • Three connecitons showed significant difference between AD and control groups. • Classification accuracy of current feature is superior to that of common measure. The aim of this study is to identify potential biomarkers that may distinguish people with Alzheimer's disease (AD) from cognitively intact elderly. We analyzed the features of rich-club hierarchical network between the AD and a control group by diffusion tensor imaging. We detected that the changes between the two groups were located mainly in the feeder and local connections. Then, we calculated the betweenness centrality of the rich nodes and the strength values of all feeder connections, and we chose the nodes and connections that showed the most significant differences as features. We found that 1) Feeder and local connections were changed in the AD group; 2) Rich nodes of the left putamen and precuneus had significant differences in betweenness centrality between the AD and control groups; 3) Three connections showed significant differences. The obtained features were fed into a linear discriminant analysis for classifying AD from cognitively intact elderly. The classification accuracy is superior to that of traditional biomarkers (hippocampal volume and clinical scores). Our results suggested that rich-club hierarchical network analysis is a viable tool for finding potential biomarkers. The obtained features can be applied as potential biomarkers for distinguishing AD patients from cognitively intact elderly. [ABSTRACT FROM AUTHOR]

Highlights • The RSFC of DLPFC-related pathways are increased in FES patients. • COMT val158met genotypes have significant effect on RSFC of DLPFC. • The RSFC of DLPFC have correlations with negative symptoms in FES with val/val. Abstract Catechol-O-methyltransferase (COMT) gene variants have been reported to be implicated in the pathogenesis of psychotic symptoms in schizophrenia, especially in negative symptoms. These symptoms including apathy, blunted affect, social withdrawal and motor retardation. Neuroimaging studies suggested that negative symptoms appear to be associated with impaired activities of the prefrontal cortex in particular the dorsolateral prefrontal cortex (DLPFC). Given that the COMT gene is highly expressed in the DLPFC, it is poorly understood whether the disease state and COMT val158met polymorphisms have main and interactive effect on the resting state functional connectivity (RSFC) of DLPFC-related pathways. To this end, fifty-five first episode schizophrenia (FES) and fifty-three healthy controls were genotyped using blood samples and underwent magnetic resonance imaging scanning. Seed-based voxel wise functional connectivity analysis was performed by placing bilateral pairs of seeds with DLPFC in area 46 defined by Brodmann's atlas. A two-ways ANCOVA model was performed with val158met genotypes and disease state as the between subjects factors. Significant disease × COMT interactive effect was found mainly in the left DLPFC with the left anterior cingulate cortex, right precuneus, right superior parietal gyrus, which were overlapped with disease main effect. And these RSFC had positive correlations with affective blunting scores in FES patients with val homozygotes, but not with met carriers. Our results showed that the disease and the genotypes in COMT gene have significant interactive effect on RSFC of DLPFC and provided evidence for a disease-dependent pattern of gene action. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to develop a radiomics nomogram by combining the optimized radiomics signatures extracted from 2D and/or 3D CT images and clinical predictors to assess the overall survival of patients with non-small cell lung cancer (NSCLC).Methods: One training cohort of 239 and two validation datasets of 80 and 52 NSCLC patients were enrolled in this study. Nine hundred seventy-five radiomics features were extracted from each patient's 2D and 3D CT images. Least absolute shrinkage and selection operator (LASSO) regression was used to select features and generate a radiomics signature. Cox hazard survival analysis and Kaplan-Meier were performed in both cohorts. The radiomics nomogram was developed by integrating the optimized radiomics signature and clinical predictors, its calibration and discrimination were evaluated.Results: The radiomics signatures were significantly associated with NSCLC patients' survival time. The signature derived from the combined 2D and 3D features showed a better prognostic performance than those from 2D or 3D alone. Our radiomics nomogram integrated the optimal radiomics signature with clinical predictors showed a significant improvement in the prediction of patients' survival compared with clinical predictors alone in the validation cohort. The calibration curve showed predicted survival time was very close to the actual one.Conclusions: The radiomics signature from the combined 2D and 3D features further improved the predicted accuracy of survival prognosis for the patients with NSCLC. Combination of the optimal radiomics signature and clinical predictors performed better for individualied survival prognosis estimation in patients with NSCLC. These findings might affect trearment strategies and enable a step forward for precise medicine.Key Points: • We found both 2D and 3D radiomics signature have favorable prognosis, but 3D signature had a better performance. • The radiomics signature generated from the combined 2D and 3D features had a better predictive performance than those from 2D or 3D features. • Integrating the optimal radiomics signature with clinical predictors significantly improved the predictive power in patients' survival compared with clinical TNM staging alone. [ABSTRACT FROM AUTHOR]