Cytochrome P450 SmCYP78A7a positively functions in eggplant response to salt stress via forming a positive feedback loop with SmWRKY11.

Accumulating salinity in soil critically affected growth, development, and yield in plant. However, the mechanisms of plant against salt stress largely remain unknown. Herein, we identified a gene named SmCYP78A7a, which encoded a cytochrome P450 monooxygenase and belonged to the CYP78A sub-family, and its transcript level was significantly up-regulated by salt stress and down-regulated by dehydration stress. SmCYP78A7a located in the endoplasmic reticulum. Silencing of SmCYP78A7a enhanced susceptibility of eggplant to salt stress, and significantly down-regulated the transcript levels of salt stress defense related genes SmGSTU10 and SmWRKY11 as well as increased hydrogen peroxide (H2O2) content and decreased catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) enzyme activities. In addition, SmCYP78A7a transient expression enhanced eggplant tolerance to salt stress. By chromatin immunoprecipitation PCR (ChIP-PCR), luciferase reporter assay, and electrophoretic mobility shift assay (EMSA), SmWRKY11 activated SmCYP78A7a expression by directly binding to the W-box 6-8 (W-box 6, W-box 7, and W-box 8) within SmCYP78A7a promoter to confer eggplant tolerance to salt stress. In summary, our finds reveal that SmCYP78A7a positively functions in eggplant response to salt stress via forming a positive feedback loop with SmWRKY11, and provide a new insight into regulatory mechanisms of eggplant to salt stress.

How short peptides can disassemble ultra-stable tau fibrils extracted from Alzheimer's disease brain by a strain-relief mechanism.

Reducing fibrous aggregates of protein tau is a possible strategy for halting progression of Alzheimer's dis-ease (AD). Previously we found that in vitro the D-peptide D-TLKIVWC disassembles tau fibrils from AD brains (AD-tau) into benign segments with no energy source present beyond ambient thermal agitation. This disassembly by a short peptide was unexpected, given that AD-tau is sufficiently stable to withstand disas-sembly in boiling SDS detergent. To consider D peptide-mediated disassembly as a potential therapeutic for AD, it is essential to understand the mechanism and energy source of the disassembly action. We find as-sembly of D-peptides into amyloid-like fibrils is essential for tau fibril disassembly. Cryo-EM and atomic force microscopy reveal that these D-peptide fibrils have a right-handed twist and embrace tau fibrils which have a left-handed twist. In binding to the AD-tau fibril, the oppositely twisted D-peptide fibril produces a strain, which is relieved by the disassembly of both fibrils. This strain-relief mechanism appears to operate in other examples of amyloid fibril disassembly and provides a new direction for the development of first-in-class therapeutics for amyloid diseases.

How short peptides can disassemble ultra-stable tau fibrils extracted from Alzheimer's disease brain by a strain-relief mechanism.

Reducing fibrous aggregates of protein tau is a possible strategy for halting progression of Alzheimer's disease (AD). Previously we found that in vitro the D-peptide D-TLKIVWC disassembles tau fibrils from AD brains (AD-tau) into benign segments with no energy source present beyond ambient thermal agitation. This disassembly by a short peptide was unexpected, given that AD-tau is sufficiently stable to withstand disassembly in boiling SDS detergent. To consider D peptide-mediated disassembly as a potential therapeutic for AD, it is essential to understand the mechanism and energy source of the disassembly action. We find assembly of D-peptides into amyloid-like fibrils is essential for tau fibril disassembly. Cryo-EM and atomic force microscopy reveal that these D-peptide fibrils have a right-handed twist and embrace tau fibrils which have a left-handed twist. In binding to the AD-tau fibril, the oppositely twisted D-peptide fibril produces a strain, which is relieved by disassembly of both fibrils. This strain-relief mechanism appears to operate in other examples of amyloid fibril disassembly and provides a new direction for the development of first-in-class therapeutics for amyloid diseases.

Solanum aculeatissimum and Solanum torvum chloroplast genome sequences: a comparative analysis with other Solanum chloroplast genomes.

BACKGROUND: Solanum aculeatissimum and Solanum torvum belong to the Solanum species, and they are essential plants known for their high resistance to diseases and adverse conditions. They are frequently used as rootstocks for grafting and are often crossbred with other Solanum species to leverage their resistance traits. However, the phylogenetic relationship between S. aculeatissimum and S. torvum within the Solanum genus remains unclear. Therefore, this paper aims to sequence the complete chloroplast genomes of S. aculeatissimum and S. torvum and analyze them in comparison with 29 other previously published chloroplast genomes of Solanum species. RESULTS: We observed that the chloroplast genomes of S. aculeatissimum and S. torvum possess typical tetrameric structures, consisting of one Large Single Copy (LSC) region, two reverse-symmetric Inverted Repeats (IRs), and one Small Single Copy (SSC) region. The total length of these chloroplast genomes ranged from 154,942 to 156,004 bp, with minimal variation. The highest GC content was found in the IR region, while the lowest was in the SSC region. Regarding gene content, the total number of chloroplast genes and CDS genes remained relatively consistent, ranging from 128 to 134 and 83 to 91, respectively. Nevertheless, there was notable variability in the number of tRNA genes and rRNAs. Relative synonymous codon usage (RSCU) analysis revealed that both S. aculeatissimum and S. torvum preferred codons that utilized A and U bases. Analysis of the IR boundary regions indicated that contraction and expansion primarily occurred at the junction between SSC and IR regions. Nucleotide polymorphism analysis and structural variation analysis demonstrated that chloroplast variation in Solanum species mainly occurred in the LSC and SSC regions. Repeat sequence analysis revealed that A/T was the most frequent base pair in simple repeat sequences (SSR), while Palindromic and Forward repeats were more common in long sequence repeats (LSR), with Reverse and Complement repeats being less frequent. Phylogenetic analysis indicated that S. aculeatissimum and S. torvum belonged to the same meristem and were more closely related to Cultivated Eggplant. CONCLUSION: These findings enhance our comprehension of chloroplast genomes within the Solanum genus, offering valuable insights for plant classification, evolutionary studies, and potential molecular markers for species identification.

StoMYB41 positively regulates the Solanum torvum response to Verticillium dahliae in an ABA dependent manner.

MYB transcription factor despite their solid involvement in growth are potent regulator of plant stress response. Herein, we identified a MYB gene named as StoMYB41 in a wild eggplant species Solanum torvum. The expression level of StoMYB41 was higher in root than the tissues including stem, leaf, and seed. It induced significantly by Verticillium dahliae inoculation. StoMYB41 was localized in the nucleus and exhibited transcriptional activation activity. Silencing of StoMYB41 enhanced susceptibility of Solanum torvum against Verticillium dahliae, accompanied by higher disease index. The significant down-regulation of resistance marker gene StoABR1 comparing to the control plants was recorded in the silenced plants. Moreover, transient expression of StoMYB41 could trigger intense hypersensitive reaction mimic cell death, darker DAB and trypan blue staining, higher ion leakage, and induced the expression levels of StoABR1 and NbDEF1 in the leaves of Solanum torvum and Nicotiana benthamiana. Taken together, our data indicate that StoMYB41 acts as a positive regulator in Solanum torvum against Verticillium wilt.

Genome-Wide Identification of Catalase Gene Family and the Function of SmCAT4 in Eggplant Response to Salt Stress.

Salinity is an important abiotic stress, damaging plant tissues by causing a burst of reactive oxygen species (ROS). Catalase (CAT) enzyme coded by Catalase (CAT) genes are potent in reducing harmful ROS and hydrogen peroxide (H2O2) produced. Herein, we performed bioinformatics and functional characterization of four SmCAT genes, retrieved from the eggplant genome database. Evolutionary analysis CAT genes revealed that they are divided into subgroups I and II. The RT-qPCR analysis of SmCAT displayed a differential expression pattern in response to abiotic stresses. All the CAT proteins of eggplant were localized in the peroxisome, except for SmCAT4, which localized in the cytomembrane and nucleus. Silencing of SmCAT4 compromised the tolerance of eggplant to salt stress. Suppressed expression levels of salt stress defense related genes SmTAS14 and SmDHN1, as well as increase of H2O2 content and decrease of CAT enzyme activity was observed in the SmCAT4 silenced eggplants. Our data provided insightful knowledge of CAT gene family in eggplant. Positive regulation of eggplant response to salinity by SmCAT4 provides resource for future breeding programs.

SmWRKY11 acts as a positive regulator in eggplant response to salt stress.

Salt stress is one of the most threatening abiotic stresses to plants, which can seriously affect plant growth, development, reproduction, and yield. However, the mechanisms of plant against salt stress largely remain unclear. Herein, SmWRKY11, an assumed WRKY transcription factor, was functionally characterized in eggplant against salt stress. SmWRKY11 was significantly up-regulated by salt, dehydration stress, and ABA treatment. SmWRKY11 located in the nucleus, and the Plant_zn_clust conserved domain exhibited transcriptional activation activity. Silencing of SmWRKY11 enhanced the susceptibility of eggplant to salt stress, accompanied by significantly down-regulation of transcript expression levels of salt stress defense-related genes SmNCED1, SmGSTU10, and positive regulator of salt stress response SmERF1 as well as increase of hydrogen peroxide (H2O2) content and decrease of the enzyme activities of catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX). In addition, silencing of SmERF1 also could significantly down-regulate SmWRKY11 expression in eggplant response to salt stress. By luciferase reporter assay and chromatin immunoprecipitation PCR assay, SmERF1 expression was found to be indirectly activated by SmWRKY11. These data indicate that SmWRKY11 acts as a positive regulator by forming positive feedback loop with SmERF1 via an indirect regulatory manner in eggplant response to salt stress.

Multiscale feature fusion network for 3D head MRI image registration.

BACKGROUND: Image registration technology has become an important medical image preprocessing step with the wide application of computer-aided diagnosis technology in various medical image analysis tasks. PURPOSE: We propose a multiscale feature fusion registration based on deep learning to achieve the accurate registration and fusion of head magnetic resonance imaging (MRI) and solve the problem that general registration methods cannot handle the complex spatial information and position information of head MRI. METHODS: Our proposed multiscale feature fusion registration network consists of three sequentially trained modules. The first is an affine registration module that implements affine transformation; the second is to realize non-rigid transformation, a deformable registration module composed of top-down and bottom-up feature fusion subnetworks in parallel; and the third is a deformable registration module that also realizes non-rigid transformation and is composed of two feature fusion subnetworks in series. The network decomposes the deformation field of large displacement into multiple deformation fields of small displacement by multiscale registration and registration, which reduces the difficulty of registration. Moreover, multiscale information in head MRI is learned in a targeted manner, which improves the registration accuracy, by connecting the two feature fusion subnetworks. RESULTS: We used 29 3D head MRIs for training and seven volumes for testing and calculated the values of the registration evaluation metrics for the new algorithm to register anterior and posterior lateral pterygoid muscles. The Dice similarity coefficient was 0.745 ± 0.021, the Hausdorff distance was 3.441 ± 0.935 mm, the Average surface distance was 0.738 ± 0.098 mm, and the Standard deviation of the Jacobian matrix was 0.425 ± 0.043. Our new algorithm achieved a higher registration accuracy compared with state-of-the-art registration methods. CONCLUSIONS: Our proposed multiscale feature fusion registration network can realize end-to-end deformable registration of 3D head MRI, which can effectively cope with the characteristics of large deformation displacement and the rich details of head images and provide reliable technical support for the diagnosis and analysis of head diseases.

Prognostic potential of a voxelwise invasion risk map of nasopharyngeal carcinoma based on a coordinate system of the nasopharynx.

Background: Tumor invasion risk (TIR) is an important prognostic factor in nasopharyngeal carcinoma (NPC). We propose a novel prognostic analytic method for NPC based on a voxelwise analysis of TIR in a coordinate system of the nasopharynx. Methods: A stable nasopharynx coordinate system was constructed based on anatomical landmarks to obtain an accurate TIR profile for NPC. The coordinate system was validated by image registration of the lateral pterygoid muscle (LPM). The tumors were registered to the coordinate system through shift, scale, and rotation transformations. The voxelwise TIR map for NPC was obtained by superposition of all registered and mirrored tumor regions of interest. The minimum risk (MinR) point of the tumor region was used as an independent prognostic factor for NPC. The cutoff value was calculated with density plot and validated with restricted cubic splines (RCSs), and then the patients were divided into 2 groups for overall survival (OS) analysis. Results: The first voxelwise TIR map of NPC was obtained based on 778 patients. The OS of patients with a low TIR was 76.8% and was 92.6% for patients with a high TIR [P<0.001; hazard ratio (HR) =1/0.45; 95% CI: 0.27-0.77; adjusted P=0.004]. Thus, patients with a low TIR had a poor prognosis, whereas patients with a high TIR had a good prognosis. The MinR may be better at grading the prognosis of patients compared to the American Joint Committee on Cancer (AJCC) staging or tumor/node (T/N) classification systems. Conclusions: The voxelwise TIR map provides a new method for the prognostic analysis of NPC. Potential clinical applications of voxelwise TIR mapping are clinical target volume (CTV) delineation and dose-painting for NPC.

Neurotoxicity of polystyrene nanoplastics with different particle sizes at environment-related concentrations on early zebrafish embryos.

Nanoplastics (NPs) have received global attention due to their wide application and detection in various environmental or biological media. NPs can penetrate physical barriers and accumulate in organisms after being ingested, producing a variety of toxic effects and possessing particle size-dependent effects, distinguishing them from traditional contaminants. This paper explored the neurotoxicity of polystyrene (PS)-NPs of different particle sizes on zebrafish (Danio rerio) embryos at environmental concentrations at the tissue and molecular levels using visualized transgenic zebrafish. Results showed that all particle sizes of PS-NPs produced developmental toxicity in zebrafish embryos and induced neuronal loss, axonal deletion/shortening/hybridization, and developmental and apoptotic-related genetic alterations, ultimately leading to behavioral abnormalities. PS-NPs with smaller sizes may have more severe neurotoxicity due to their entry into the embryo and brain through the chorionic pore before hatching. In addition, PS-NPs at 100 nm and 1000 nm can specifically interfere with GABAergic, cholinergic or serotonergic system and affect neuronal signaling. Our results reveal the neurotoxic risk of NPs, and smaller particle-size NPs may have a greater ecological risk. We anticipate that our study can provide a basis for exploring the toxicity mechanisms of NPs and the environmental risk assessment of NPs.

Collaborative Filtering Algorithm-Based Destination Recommendation and Marketing Model for Tourism Scenic Spots.

The information age of rapid development of tourism industry provides abundant travel information, but it also comes with the problem of information overload, which makes it difficult to meet the growing personalized needs of people. The traditional collaborative filtering recommendation algorithm (CFA) also suffers from the problem of data sparsity when the user population increases. Therefore, this study optimizes the CFA through the similarity factor and correlation factor and enhances the tourism sense of travel experience through the satisfaction balance strategy. The experimental results show that the improved CFA method has the highest average accuracy on the overall dataset and the best recommendation performance of the satisfaction balance strategy. Overall, the recommendation model in this study is useful for attraction selection of users and marketing optimization of travel companies.

Willingness to accept (WTA), willingness to pay (WTP), and the WTA/WTP disparity in Chinese social media platforms: Descriptive statistics and associations with personality and social media use.

The amount of money individuals were willing to accept (WTA) to discontinue using prominent Chinese social media platforms (WeChat/QQ), the willingness to pay (WTP) for using these platforms, as well as WTA/WTP disparities were investigated in between-groups and within-subjects design studies to examine their existence, size, and psychological correlates in the form of personality and social media use habits. Individuals were recruited at Chinese universities in three separate surveys. For between-groups investigations, four samples were investigated: WTA and WTP samples for investigations in the context of WeChat as well as WTA and WTP samples for QQ. For within-subjects investigations, individuals completed items on WTA and WTP for WeChat/QQ, the Big Five Inventory, time spent on WeChat/QQ, and the short Bergen Social Media Addiction Scale. Two samples providing data on WeChat and QQ, respectively, were investigated. Across study designs and for both WeChat and QQ we found evidence for high WTA and comparatively low WTP scores, thus, large WTA/WTP disparities. Individual differences in the disparities were negatively associated with Openness across social media platforms. The results reveal a generally low acceptance to pay for social media use, which is important against the background of discussions on monetary payment models. Moreover, a complex interplay between individual characteristics, characteristics of the service, and how and why the service is used seems to underly WTA and the WTA/WTP disparity. Finally, methodological implications of the present results for forthcoming studies assessing valuation (WTA, WTP) in the context of social media are discussed.

BSMM-Net: Multi-modal neural network based on bilateral symmetry for nasopharyngeal carcinoma segmentation.

Introduction: Automatically and accurately delineating the primary nasopharyngeal carcinoma (NPC) tumors in head magnetic resonance imaging (MRI) images is crucial for patient staging and radiotherapy. Inspired by the bilateral symmetry of head and complementary information of different modalities, a multi-modal neural network named BSMM-Net is proposed for NPC segmentation. Methods: First, a bilaterally symmetrical patch block (BSP) is used to crop the image and the bilaterally flipped image into patches. BSP can improve the precision of locating NPC lesions and is a simulation of radiologist locating the tumors with the bilateral difference of head in clinical practice. Second, modality-specific and multi-modal fusion features (MSMFFs) are extracted by the proposed MSMFF encoder to fully utilize the complementary information of T1- and T2-weighted MRI. The MSMFFs are then fed into the base decoder to aggregate representative features and precisely delineate the NPC. MSMFF is the output of MSMFF encoder blocks, which consist of six modality-specific networks and one multi-modal fusion network. Except T1 and T2, the other four modalities are generated from T1 and T2 by the BSP and DT modal generate block. Third, the MSMFF decoder with similar structure to the MSMFF encoder is deployed to supervise the encoder during training and assure the validity of the MSMFF from the encoder. Finally, experiments are conducted on the dataset of 7633 samples collected from 745 patients. Results and discussion: The global DICE, precision, recall and IoU of the testing set are 0.82, 0.82, 0.86, and 0.72, respectively. The results show that the proposed model is better than the other state-of-the-art methods for NPC segmentation. In clinical diagnosis, the BSMM-Net can give precise delineation of NPC, which can be used to schedule the radiotherapy.

The Relationship Between Social Media Digitalization and Coronavirus Disease 2019 Fear Among Service Sector Employees.

In the age of digitalization, social media has played a significant role in quickly spreading the news about current affairs. From December 2019 to now, coronavirus disease 2019 (COVID-19), with its several mutated shapes, has more transmissible potential catastrophe and has become a severe phenomenon issue worldwide. The international spread of the epidemic has created fear among people, especially employees working physically in different organizations. The present research aimed to measure the impact of social media on its users in the China. The social media users more often were influenced by shocking news instructively and destructively. The research analysis was based on service sector employees and data collected from 630 respondents via a structured questionnaire. This research was confirmed the negative impact of fear on social media on the performance of employees. This research was also confirmed the moderation impact of the COVID-19 vaccine on the relationship between social media fear and employee performance. This research recommends that the China Censor Board checked the news and its validity to reduce the fear of COVID-19 among employees. This research will become a roadmap for organizations and media controllers to understand the impact of social media during an intense situation. The telecommunication sector will reduce psychological disease and enhance the work capability of employees by controlling unnecessary and unapproved material about sensitive issues.

Investigating Links Between Fear of COVID-19, Neuroticism, Social Networks Use Disorder, and Smartphone Use Disorder Tendencies.

The present study investigates links between fear of COVID-19, the personality trait of neuroticism, social networks use disorder, and smartphone use disorder (SNUD and SmUD, respectively) tendencies. In an online survey, N = 932 participants recruited at a Chinese University (237 males and 695 females) completed self-reports on fear of COVID-19, neuroticism (and other personality traits from the Big Five Inventory-44), the Bergen Social Media Addiction Scale (assessing tendencies toward SNUD), and the Smartphone Addiction Scale short version-assessing individual differences in tendencies toward SmUD. Our findings showed that all variables of main interest were positively correlated with each other. A mediation model suggested that SNUD (in parts) mediated the association between fear of COVID-19 and SmUD. Although neuroticism was robustly correlated with all mentioned variables, no moderation effect could be observed on the investigated fear-of-COVID-19-SNUD-link. The findings of this work provide further evidence that the smartphone itself is only a device giving individuals access to software applications, which might be excessively used. Beyond that, the present data indicate neuroticism to be a risk factor with respect to fear of COVID-19, SNUD, and SmUD, although the study is limited by its cross-sectional study design.

Cryo-EM structure of the inhibited (10S) form of myosin II.

Myosin II is the motor protein that enables muscle cells to contract and nonmuscle cells to move and change shape1. The molecule has two identical heads attached to an elongated tail, and can exist in two conformations: 10S and 6S, named for their sedimentation coefficients2,3. The 6S conformation has an extended tail and assembles into polymeric filaments, which pull on actin filaments to generate force and motion. In 10S myosin, the tail is folded into three segments and the heads bend back and interact with each other and the tail3-7, creating a compact conformation in which ATPase activity, actin activation and filament assembly are all highly inhibited7,8. This switched-off structure appears to function as a key energy-conserving storage molecule in muscle and nonmuscle cells9-12, which can be activated to form functional filaments as needed13-but the mechanism of its inhibition is not understood. Here we have solved the structure of smooth muscle 10S myosin by cryo-electron microscopy with sufficient resolution to enable improved understanding of the function of the head and tail regions of the molecule and of the key intramolecular contacts that cause inhibition. Our results suggest an atomic model for the off state of myosin II, for its activation and unfolding by phosphorylation, and for understanding the clustering of disease-causing mutations near sites of intramolecular interaction.

lncRNA MT1JP Suppresses Biological Activities of Breast Cancer Cells in vitro and in vivo by Regulating the miRNA-214/RUNX3 Axis.

INTRODUCTION: The purpose of our research was to evaluate MT1JP in breast cancer. MATERIAL AND METHODS: For clinical purpose, tissues were collected, and a correlation analysis ofMT1JP and miRNA-214 gene expressions was conducted. Using an in vitro study, MDA-MB-231 and MCF-7 cell lines were used as research objects in our research. Colony, flow cytometry, TUNEL, transwell, adhesion and wound healing assay were used to discuss the biological activities of the cells. In an in vivo study, tumor weight and volume were measured, and cell apoptosis was measured by TUNEL assay. The relative mechanism's proteins were evaluated by Western blotting or immunohistochemistry assay. RESULTS: Compared with adjacent tissues, MT1JP and miRNA-214 gene expressions were significantly different (P<0.001, respectively). By in vitro and in vivo studies, the biological activities of the cells were significantly decreased in MDA-MB-231 and MCF-7 cell lines with MT1JP overexpression. The relative mechanism was correlated with miRNA-214/RUNX3 axis. CONCLUSION: The overexpression of MT1JP suppresses the biological activities of breast cancer cells by regulation miRNA-214/RUNX3 axis in vitro and vivo study.

Lattice arrangement of myosin filaments correlates with fiber type in rat skeletal muscle.

The thick (myosin-containing) filaments of vertebrate skeletal muscle are arranged in a hexagonal lattice, interleaved with an array of thin (actin-containing) filaments with which they interact to produce contraction. X-ray diffraction and EM have shown that there are two types of thick filament lattice. In the simple lattice, all filaments have the same orientation about their long axis, while in the superlattice, nearest neighbors have rotations differing by 0° or 60°. Tetrapods (amphibians, reptiles, birds, and mammals) typically have only a superlattice, while the simple lattice is confined to fish. We have performed x-ray diffraction and electron microscopy of the soleus (SOL) and extensor digitorum longus (EDL) muscles of the rat and found that while the EDL has a superlattice as expected, the SOL has a simple lattice. The EDL and SOL of the rat are unusual in being essentially pure fast and slow muscles, respectively. The mixed fiber content of most tetrapod muscles and/or lattice disorder may explain why the simple lattice has not been apparent in these vertebrates before. This is supported by only weak simple lattice diffraction in the x-ray pattern of mouse SOL, which has a greater mix of fiber types than rat SOL. We conclude that the simple lattice might be common in tetrapods. The correlation between fiber type and filament lattice arrangement suggests that the lattice arrangement may contribute to the functional properties of a muscle.

The central role of the tail in switching off 10S myosin II activity.

Myosin II is a motor protein with two heads and an extended tail that plays an essential role in cell motility. Its active form is a polymer (myosin filament) that pulls on actin to generate motion. Its inactive form is a monomer with a compact structure (10S sedimentation coefficient), in which the tail is folded and the two heads interact with each other, inhibiting activity. This conformation is thought to function in cells as an energy-conserving form of the molecule suitable for storage as well as transport to sites of filament assembly. The mechanism of inhibition of the compact molecule is not fully understood. We have performed a 3-D reconstruction of negatively stained 10S myosin from smooth muscle in the inhibited state using single-particle analysis. The reconstruction reveals multiple interactions between the tail and the two heads that appear to trap ATP hydrolysis products, block actin binding, hinder head phosphorylation, and prevent filament formation. Blocking these essential features of myosin function could explain the high degree of inhibition of the folded form of myosin thought to underlie its energy-conserving function in cells. The reconstruction also suggests a mechanism for unfolding when myosin is activated by phosphorylation.

FAT10 promotes the invasion and migration of breast cancer cell through stabilization of ZEB2.

FAT10, an ubiquitin-like protein, functions as a potential tumor promoter in several caners. However, the function and clinical significance of FAT10 in breast cancer (BC) remains unclear. Here, we found that high FAT10 expression was detected frequently in primary BC tissues, and was closely associated with malignant phenotype and shorter survival among the BC patients. Multivariate analyses also revealed that FAT10 overexpression was independent prognostic factors for poor outcome of patients with BC. Function assay demonstrated that FAT10 knockdown significantly inhibited the metastasis abilities and the epithelial-mesenchymal transition (EMT) of breast cancer cell. Further investigation revealed that FAT10 directly bound ZEB2 and decreased its ubiquitination to enhance the protein stability of ZEB2 in BC cells. Moreover, our data shown that the pro-metastasis effect of FAT10 in BC is partially dependent on ZEB2 enhancement. Collectively, our data suggest that FAT10 plays a crucial oncogenic role in BC metastasis, and we provide a novel evidence that FAT10 may be serve as a prognostic and therapeutic target for BC patients.