Brassinosteroids biosynthetic gene MdBR6OX2 regulates salt stress tolerance in both apple and Arabidopsis.

Salt stress is a critical limiting factor for fruit yield and quality of apples. Brassinosteroids (BRs) play an important role in response to abiotic stresses. In the present study, application of 2,4- Epicastasterone on seedlings of Malus 'M9T337' and Malus domestica 'Gala3' alleviated the physiological effects, such as growth inhibition and leaf yellowing, induced by salt stress. Further analysis revealed that treatment with NaCl induced expression of genes involved in BR biosynthesis in 'M9T337' and 'Gala3'. Among which, the expression of BR biosynthetic gene MdBR6OX2 showed a three-fold upregulation upon salt treatment, suggesting its potential role in response to salt stress in apple. MdBR6OX2, belonging to the CYP450 family, contains a signal peptide region and a P450 domain. Expression patterns analysis showed that the expression of MdBR6OX2 can be significantly induced by different abiotic stresses. Overexpressing MdBR6OX2 enhanced the tolerance of apple callis to salt stress, and the contents of endogenous BR-related compounds, such as Typhastero (TY), Castasterone (CS) and Brassinolide (BL) were significantly increased in transgenic calli compared with that of wild-type. Extopic expression of MdBR6OX2 enhanced tolerance to salt stress in Arabidopsis. Genes associated with salt stress were significantly up-regulated, and the contents of BR-related compounds were significantly elevated under salt stress. Our data revealed that BR-biosynthetic gene MdBR6OX2 positively regulates salt stress tolerance in both apple calli and Arabidopsis.

Tumor conspicuity enhancement-based segmentation model for liver tumor segmentation and RECIST diameter measurement in non-contrast CT images.

BACKGROUND AND OBJECTIVE: Liver tumor segmentation (LiTS) accuracy on contrast-enhanced computed tomography (CECT) images is higher than that on non-contrast computed tomography (NCCT) images. However, CECT requires contrast medium and repeated scans to obtain multiphase enhanced CT images, which is time-consuming and cost-increasing. Therefore, despite the lower accuracy of LiTS on NCCT images, which still plays an irreplaceable role in some clinical settings, such as guided brachytherapy, ablation, or evaluation of patients with renal function damage. In this study, we intend to generate enhanced high-contrast pseudo-color CT (PCCT) images to improve the accuracy of LiTS and RECIST diameter measurement on NCCT images. METHODS: To generate high-contrast CT liver tumor region images, an intensity-based tumor conspicuity enhancement (ITCE) model was first developed. In the ITCE model, a pseudo color conversion function from an intensity distribution of the tumor was established, and it was applied in NCCT to generate enhanced PCCT images. Additionally, we design a tumor conspicuity enhancement-based liver tumor segmentation (TCELiTS) model, which was applied to improve the segmentation of liver tumors on NCCT images. The TCELiTS model consists of three components: an image enhancement module based on the ITCE model, a segmentation module based on a deep convolutional neural network, and an attention loss module based on restricted activation. Segmentation performance was analyzed using the Dice similarity coefficient (DSC), sensitivity, specificity, and RECIST diameter error. RESULTS: To develop the deep learning model, 100 patients with histopathologically confirmed liver tumors (hepatocellular carcinoma, 64 patients; hepatic hemangioma, 36 patients) were randomly divided into a training set (75 patients) and an independent test set (25 patients). Compared with existing tumor automatic segmentation networks trained on CECT images (U-Net, nnU-Net, DeepLab-V3, Modified U-Net), the DSCs achieved on the enhanced PCCT images are both improved compared with those on NCCT images. We observe improvements of 0.696-0.713, 0.715 to 0.776, 0.748 to 0.788, and 0.733 to 0.799 in U-Net, nnU-Net, DeepLab-V3, and Modified U-Net, respectively, in terms of DSC values. In addition, an observer study including 5 doctors was conducted to compare the segmentation performance of enhanced PCCT images with that of NCCT images and showed that enhanced PCCT images are more advantageous for doctors to segment tumor regions. The results showed an accuracy improvement of approximately 3%-6%, but the time required to segment a single CT image was reduced by approximately 50 %. CONCLUSIONS: Experimental results show that the ITCE model can generate high-contrast enhanced PCCT images, especially in liver regions, and the TCELiTS model can improve LiTS accuracy in NCCT images.

Cloning and functional identification of apple LATERAL ORGAN BOUNDARY DOMAIN 3 (LBD3) transcription factor in the regulation of drought and salt stress.

MAIN CONCLUSION: Overexpression of MdLBD3 in Arabidopsis reduced sensitivity to salt and drought stresses and was instrumental in promoting early flowering. Salt and drought stresses have serious effects on plant growth. LATERAL ORGAN BOUNDARY DOMAIN (LBD) proteins are a plant-specific transcription factors (TFs) family and play important roles in plants in resisting to abiotic stress. However, about the function of LBDs in apple and other woody plants is little known. In this study, protein sequences of the LBD family TFs in apples were identified which contained conserved LOB domains. The qRT-PCR analysis showed that the MdLBD3 gene was widely expressed in various tissues and organs. The subcellular localization assay showed that the MdLBD3 protein was localized in the nucleus. Ectopic expression of MdLBD3 in Arabidopsis positively regulated its salt and drought resistance, and promoted early flowering. Collectively, these results showed that MdLBD3 improved the abiotic stress resistance, plant growth and development. Overall, this study provided a new gene for breeding that can increase the abiotic stress tolerance in apple.

The AP2/ERF transcription factor MdDREB2A regulates nitrogen utilisation and sucrose transport under drought stress.

Drought stress is one of the main environmental factors limiting plant growth and development. Plants adapt to changing soil moisture by modifying root architecture, inducing stomatal closure, and inhibiting shoot growth. The AP2/ERF transcription factor DREB2A plays a key role in maintaining plant growth in response to drought stress, but the molecular mechanism underlying this process remains to be elucidated. Here, it was found that overexpression of MdDREB2A positively regulated nitrogen utilisation by interacting with DRE cis-elements of the MdNIR1 promoter. Meanwhile, MdDREB2A could also directly bind to the promoter of MdSWEET12, which may enhance root development and nitrogen assimilation, ultimately promoting plant growth. Overall, this regulatory mechanism provides an idea for plants in coordinating with drought tolerance and nitrogen assimilation to maintain optimal plant growth and development under drought stress.

A generic fundus image enhancement network boosted by frequency self-supervised representation learning.

Fundus photography is prone to suffer from image quality degradation that impacts clinical examination performed by ophthalmologists or intelligent systems. Though enhancement algorithms have been developed to promote fundus observation on degraded images, high data demands and limited applicability hinder their clinical deployment. To circumvent this bottleneck, a generic fundus image enhancement network (GFE-Net) is developed in this study to robustly correct unknown fundus images without supervised or extra data. Levering image frequency information, self-supervised representation learning is conducted to learn robust structure-aware representations from degraded images. Then with a seamless architecture that couples representation learning and image enhancement, GFE-Net can accurately correct fundus images and meanwhile preserve retinal structures. Comprehensive experiments are implemented to demonstrate the effectiveness and advantages of GFE-Net. Compared with state-of-the-art algorithms, GFE-Net achieves superior performance in data dependency, enhancement performance, deployment efficiency, and scale generalizability. Follow-up fundus image analysis is also facilitated by GFE-Net, whose modules are respectively verified to be effective for image enhancement.

The feasibility and safety of the brachial artery approach in the treatment of hepatic artery infusion chemotherapy: a retrospective study.

Background: Compared to hepatic artery infusion chemotherapy (HAIC) treatment through the femoral artery (TFA), the brachial artery (TBA) is more flexible and easier for patients to accept. However, the feasibility of TBA has not been studied yet. This study aims to evaluate the feasibility and safety of HAIC via the TBA. Methods: We retrospectively reviewed the medical records of 63 patients with primary liver cancer who were treated with HAIC via TBA. In this study, a total of 163 HAIC procedures were performed via the left brachial artery pathway, and each patient underwent an average of 2.59 procedures. One patient received 5 treatments, 18 patients received 4 treatments, 15 patients received 3 treatments, 12 patients received 2 treatments, and 17 patients received 1 treatment. The main evaluation indicators were the technical success rate and complication rate. Results: The main technical success rate was 99.4% (162/163). No patient required conversion to the femoral artery (TFA) access. All the complications were minor and occurred in 11 patients (6.75%). Subcutaneous ecchymosis occurred in 3 (1.84%) patients, arterial thrombosis in 2 patients (1.23%), and catheter displacement in 6 patients (3.68%). No serious complications occurred. Conclusions: TBA pathway is feasible and safe for HAIC treatment of liver cancer patients. More research is needed in the future to confirm whether TBA is superior to other pathways.

Estimation and potential ecological risk assessment of multiphase PAEs in mangrove wetlands in Dongzhai Harbor, Hainan.

With the application of plastic products, phthalates now widely occur in various environmental media. A large number of ecological risk assessment experiments have only been carried out on a single medium such as water or sediment. There are few reports of ecological risk assessments based on the phase states of phthalic acid esters (PAEs) such as the free dissolved state and the dissolved organic carbon (DOC) adsorption state. In this study, the concentrations of the free dissolved state, the DOC adsorption state, and the easily released PAEs in the sediments, as well as the dissolved organic carbon release potential and their influencing factors were calculated in the Dongzhaigang water body. The potential ecological risks posed by state-of-the-art PAEs were investigated. The average concentration of six freely dissolved PAEs in water was 0.542 (0.226-1.115) µg/L, accounting for 76.3 % of the total PAEs. The PAEs with the highest concentrations in the free dissolved state were di-n-butyl phthalate (DBP, 0.383 µg/L), followed by Di(2-ethylhexyl) phthalate (DEHP, 0.094 µg/L). The average concentration of all six PAEs (∑6PAEs) adsorbed by the DOC in the water was 0.172 µg/L, accounting for 23.74 % of all of the PAEs. The DOC-adsorbed DEHP (0.148 µg/L) accounted for about 86 % of the six adsorbed PAEs. Sediment organic carbon may affect the release potential of the DOC through changing the soluble organic carbon concentration. Most types of PAEs in water posed low risk to organisms. However, DBP posed low and medium risk to algae and crustaceans, and medium risk to fish. Medium or high risk of DEHP to algae, crustaceans and fish was observed. The high ecological risk of PAEs related to sediments were only found at S13 and S14. Generally, the potential ecological risk of PAEs in sediment was more stable than that in water bodies.

Variation in the concentration of particulate Pd in the Nandu River Estuary during spring-neap tides.

Estuaries are environmental systems with great resource potential and environmental benefits. This study investigates the role of particulate palladium (Pd) in the Nandu River Estuary in the enrichment of estuarine geochemical processes during spring-neap tides. Particulate Pd was found to show different characteristics during spring-neap tides, with the hydrodynamic condition being one of the key factors causing the difference. In addition, particulate Pd showed a decreasing trend while moving from the mouth to the upstream. The highest value of particulate Pd was 35.32 ng L-1, which occurred at the intersection of the mainstream and the branch during the neap tide, and the lowest value was 0.86 ng·L-1, which occurred in the far mouth area during the spring tide. The concentrations of particulate Pd during the neap and spring tides were 5.53 (1.01-35.32) ng·L-1 and 2.33 (0.86-5.22) ng·L-1, respectively. With the exception of stations 1, 5, 10, 11, and 15, the concentration of particulate Pd during the neap tide was greater than that during the spring tide. The variation in the particulate Pd was inconsistent between the spring tide and the neap tide, and the fluctuation in each study section during the neap tide was greater than that during the spring tide. In addition, since the emissions from catalytic converter are in the form of nanoparticles, they are difficult to be dissolve in natural water, and therefore, the concentration of particulate Pd was obviously greater in the waters near large bridges and main roads. An analysis of the physical and chemical properties of the water showed that Cl- easily combined with dissolved Pd and was one of the important factors that affected the concentration of particulate Pd. In addition, DO and Eh had little effect on the change in the particulate Pd during the tidal cycle, and pH had a significant positive correlation with particulate Pd.

Functional characterization of MdERF113 in apple.

The AP2/ERF family is an important class of transcription factors involved in plant growth and various biological processes. One of the AP2/ERF transcription factors, RAP2.6L, participates in various stresses responses. However, the function of RAP2.6L is largely unknown in apples (Malus domestica). In this study, an apple gene homologous to Arabidopsis AtRAP2.6L, MdERF113, was analyzed by bioinformatic characterization, gene expression analysis and subcellular localization assessment. MdERF113 was highly expressed in the sarcocarp and was responsive to hormonal signals and abiotic stresses. MdERF113-overexpression apple calli were less sensitive to low temperature, drought, salinity, and abscisic acid than wild-type. Subcellular localization revealed that MdERF113 was a nuclear-localized transcription factor, and yeast experiments confirmed that MdERF113 has no autonomous activation activity. Overall, this study indicated that MdERF113 plays a role in regulating plant growth under abiotic conditions.

Genome-wide analysis of the 6B-INTERACTING PROTEIN1 gene family with functional characterization of MdSIP1-2 in Malus domestica.

Trihelix transcription factors consist of five subfamilies, including GT-1, GT-2, SH4, GTγ, and SIP1, which play important roles in the responses to biotic and abiotic stresses, however, seldom is known about the role of the SIP1 genes in apples. In this study, 12 MdSIP1 genes were first identified in apples by genome-wide analysis, and contained conserved MYB/SANT-like domains. Expression patterns analyses showed that the MdSIP1 genes had different tissue expression patterns, and different transcription levels in response to abiotic stresses, indicating that MdSIP1s may play multiple roles under various abiotic stresses. Among them, the MdSIP1-2 gene was cloned and ectopic transformed into Arabidopsis, and its biology function was identified. The subcellular localization showed that MdSIP1-2 protein was specifically localized in the nucleus, and that overexpression of MdSIP1-2 promoted the development of lateral roots, increased abscisic acid (ABA) sensitivity, and improved salt and drought tolerance. These findings suggested that MdSIP1-2 plays an important role in root development, ABA synthesis, and salt and drought stress tolerance. In conclusion, these results lay a solid foundation for determining the role of MdSIP1 in the growth and development and abiotic stress tolerance of apples.

Exosomal circ_0091741 promotes gastric cancer cell autophagy and chemoresistance via the miR-330-3p/TRIM14/Dvl2/Wnt/ß-catenin axis.

The importance of cancer cell-released exosomes in the treatment of various cancers has been well-characterized. The current study aims to examine the potential biological functions of gastric cancer (GC) cell-released exosomes delivering a novel circRNA circ_0091741 in GC and the underlying molecular mechanism. Expression of circ_0091741 was examined in the GC cells, (OXA)-resistant HGC-27 (HGC-27/OXA) cells, and isolated exosomes, after which its downstream miRNA was analyzed. The role and mechanism of the circ_0091741 transmitted by GC cells-derived exosomes in GC cell autophagy and chemoresistance were assessed using various molecular biological methods. A mouse tumor xenograft model was prepared to discern the effect of circ_0091741 on tumorigenesis in vivo. GC cells and their exosomes were characterized by upregulated circ_0091741 expression. circ_0091741 transferred by GC cell-derived exosomes induced the autophagy and OXA resistance of GC cells. circ_0091741 obstructed the binding of miR-330-3p to TRIM14 and increased the expression of TRIM14. TRIM14 could cause activation of the Wnt/ß-catenin signaling pathway by stabilizing Dvl2. By this mechanism, the autophagy and OXA resistance of GC cells were augmented. In vivo assay unfolded that orthotopic implantation of exosomal circ_0091741 overexpressed GC cells into nude mice enhanced tumorigenesis. In conclusion, our study emphasized the promotive role of exosomal circ_0091741 in autophagy and chemoresistance of GC cells, thus laying the basis for the development of novel therapeutic targets for GC treatment.

LncRNA SNHG1 Facilitates Tumor Proliferation and Represses Apoptosis by Regulating PPARγ Ubiquitination in Bladder Cancer.

BACKGROUND: Long noncoding RNAs regulate various biological effects in the progression of cancers. We found that the expression of SNHG1 was significantly up-regulated in bladder cancer after analyzing data obtained from TCGA and GEO. However, the potential role of SNHG1 remains to be investigated in bladder cancer. It was validated that SNHG1 was overexpressed in bladder cancer tissues detected by qRT-PCR and FISH, which was also associated with poor clinical outcome. Additionally, SNHG1 was verified to facilitate tumor proliferation and repress apoptosis in vitro and in vivo. RESULTS: SNHG1 could act as a competitive endogenous RNA and decrease the expression of murine double minute 2 (MDM2) by sponging microRNA-9-3p. Furthermore, MDM2 induced ubiquitination and degradation of PPARγ that contributed to the development of bladder cancer. CONCLUSIONS: the study elucidated that SNHG1 played an important role in bladder cancer and provided a potential therapeutic target for bladder cancer.

MVD-Net: Semantic Segmentation of Cataract Surgery Using Multi-View Learning.

Semantic segmentation of surgery scenarios is a fundamental task for computer-aided surgery systems. Precise segmentation of surgical instruments and anatomies contributes to capturing accurate spatial information for tracking. However, uneven reflection and class imbalance lead the segmentation in cataract surgery to a challenging task. To desirably conduct segmentation, a network with multi-view decoders (MVD-Net) is proposed to present a generalizable segmentation for cataract surgery. Two discrepant decoders are implemented to achieve multi-view learning with the backbone of U-Net. The experiment is carried out on the Cataract Dataset for Image Segmentation (CaDIS). The ablation study verifies the effectiveness of the proposed modules in MVD-Net, and superior performance is provided by MVD-Net in the comparison with the state-of-the-art methods. The source code will be publicly released.

Understanding How Fundus Image Quality Degradation Affects CNN-based Diagnosis.

Quality degradation (QD) is common in the fundus images collected from the clinical environment. Although diagnosis models based on convolutional neural networks (CNN) have been extensively used to interpret retinal fundus images, their performances under QD have not been assessed. To understand the effects of QD on the performance of CNN-based diagnosis model, a systematical study is proposed in this paper. In our study, the QD of fundus images is controlled by independently or simultaneously importing quantified interferences (e.g., image blurring, retinal artifacts, and light transmission disturbance). And the effects of diabetic retinopathy (DR) grading systems are thus analyzed according to the diagnosis performances on the degraded images. With images degraded by quantified interferences, several CNN-based DR grading models (e.g., AlexNet, SqueezeNet, VGG, DenseNet, and ResNet) are evaluated. The experiments demonstrate that image blurring causes a significant decrease in performance, while the impacts from light transmission disturbance and retinal artifacts are relatively slight. Superior performances are achieved by VGG, DenseNet, and ResNet in the absence of image degradation, and their robustness is presented under the controlled degradation.

The wheat TaIQD3D-6 gene encodes a microtubule-associated protein and regulates cell morphogenesis in Arabidopsis.

A plethora of microtubule-associated proteins (MAPs) modulate the dynamics of microtubules (MTs) to ensure the proper elaboration of developmental programs in plants. Among the plant-specific MAPs are the IQ67 domain (IQD) family proteins. Despite the great progress in elucidating IQD protein functions, the majority of IQD proteins, especially IQDs in crop species, remain to be functionally explored. In this study, we identified 78 putative IQD family genes in the genome of hexaploid wheat (Triticum aestivum). Phylogenetic analysis of wheat and Arabidopsis IQDs supports the previous notion that the expansion of the IQD family coincides with plant terrestrialization. Further characterization of one TaIQD, TaIQD3D-6, revealed that TaIQD3D-6 directly binds to MTs and free tubulins in vitro and is associated with cortical MTs in interphase cells in vivo. Overexpressing TaIQD3D-6 in Arabidopsis leads to a spectrum of phenotypes that are indicative of perturbed MT homeostasis, including spiral growth, hypersensitivity to MT-destabilizing drugs, defects in cell morphogenesis, and altered organization of cMT arrays. Finally, we determined that TaIQD3D-6-GFP localizes to the expanding cell plate during cytokinesis and the overexpression of TaIQD3D-6 interferes with asymmetric cell division in the stomatal lineage in Arabidopsis. In summary, our findings establish that TaIQD3D-6 is a MAP that regulates plant cell and organ morphogenesis and provide new insights into the functions of crop IQD proteins.

ARF2-PIF5 interaction controls transcriptional reprogramming in the ABS3-mediated plant senescence pathway.

One of the hallmarks of plant senescence is the global transcriptional reprogramming coordinated by a plethora of transcription factors (TFs). However, mechanisms underlying the interactions between different TFs in modulating senescence remain obscure. Previously, we discovered that plant ABS3 subfamily MATE transporter genes regulate senescence and senescence-associated transcriptional changes. In a genetic screen for mutants suppressing the accelerated senescence phenotype of the gain-of-function mutant abs3-1D, AUXIN RESPONSE FACTOR 2 (ARF2) and PHYTOCHROME-INTERACTING FACTOR 5 (PIF5) were identified as key TFs responsible for transcriptional regulation in the ABS3-mediated senescence pathway. ARF2 and PIF5 (as well as PIF4) interact directly and function interdependently to promote senescence, and they share common target genes such as key senescence promoting genes ORESARA 1 (ORE1) and STAY-GREEN 1 (SGR1) in the ABS3-mediated senescence pathway. In addition, we discovered reciprocal regulation between ABS3-subfamily MATEs and the ARF2 and PIF5/4 TFs. Taken together, our findings reveal a regulatory paradigm in which the ARF2-PIF5/4 functional module facilitates the transcriptional reprogramming in the ABS3-mediated senescence pathway.

MOR1/MAP215 acts synergistically with katanin to control cell division and anisotropic cell elongation in Arabidopsis.

The MAP215 family of microtubule (MT) polymerase/nucleation factors and the MT severing enzyme katanin are widely conserved MT-associated proteins (MAPs) across the plant and animal kingdoms. However, how these two essential MAPs coordinate to regulate plant MT dynamics and development remains unknown. Here, we identified novel hypomorphic alleles of MICROTUBULE ORGANIZATION 1 (MOR1), encoding the Arabidopsis thaliana homolog of MAP215, in genetic screens for mutants oversensitive to the MT-destabilizing drug propyzamide. Live imaging in planta revealed that MOR1-green fluorescent protein predominantly tracks the plus-ends of cortical MTs (cMTs) in interphase cells and labels preprophase band, spindle and phragmoplast MT arrays in dividing cells. Remarkably, MOR1 and KATANIN 1 (KTN1), the p60 subunit of Arabidopsis katanin, act synergistically to control the proper formation of plant-specific MT arrays, and consequently, cell division and anisotropic cell expansion. Moreover, MOR1 physically interacts with KTN1 and promotes KTN1-mediated severing of cMTs. Our work establishes the Arabidopsis MOR1-KTN1 interaction as a central functional node dictating MT dynamics and plant growth and development.

MicroRNA-642b-3p functions as an oncomiR in gastric cancer by down-regulating the CUB and sushi multiple domains protein 1/smad axis.

Aberrant expression of microRNAs (miRNAs or miRs) has been involved in the progression of gastric cancer (GC). Our analysis of GC-related gene expression profiles identified the significantly up-regulated miR-642b-3p expression, which has been reported as a mediator in various cancers but rarely mentioned in researches on GC. Herein, this study intends to investigate the role of miR-642b-3p in GC development. Bioinformatics analysis was conducted to predict the downstream target gene of miR-642b-3p. Expression patterns of miR-642b-3p and CUB and sushi multiple domains protein 1 (CSMD1) in GC tissues and cell lines was then determined. Immunofluorescence, wound healing and Transwell invasion assays were performed to observe the malignant behaviors of GC cells with altered expression of miR-642b-3p and CSMD1. Nude mice with xenograft tumors were developed for in vivo validation. miR-642b-3p expression was increased in GC tissues and cell lines. miR-642b-3p targeted CSMD1 and reduced the expression of CSMD1, thereby inhibiting the activation of Smad signaling pathway. By this mechanism, the epithelial-mesenchymal transition (EMT), invasive and migratory potentials of GC cells were repressed. Meanwhile, in vivo data verified that miR-642b-3p enhanced the tumor growth of GC cells, which was associated with blockade of CSMD1-dependent activation of the Smad signaling pathway. Overall, miR-642b-3p acts as an oncomiR promoting tumor development in GC through suppressing CSMD1 expression and inactivating the Smad signaling pathway, which may enable the development of new therapeutic strategies for treatment of GC.