Characterization of Transthyretin Mutation G47V Associated with Hereditary Cardiac Amyloidosis.

INTRODUCTION: Amyloidosis caused by TTR mutations (ATTRv) is a rare inherited and autosomal dominant disease. More than 150 mutants of TTR have been reported, whereas some of them remain to be investigated. METHODS: A 52-year-old male presented with heart failure and clinically diagnosed ATTR cardiac amyloidosis (ATTR-CA) was recruited. Whole exome sequencing (WES) was performed. Biochemical and biophysical experiments characterized protein stability using urea-mediated tryptophan fluorescence. Drug response was analyzed by fibril formation assay. Finally, tetramer TTR concentration in patient' serum sample was measured by ultra-performance liquid chromatography (UPLC). RESULTS: For the proband, whole exome sequencing revealed a mutation (c.200G>T; p.Gly67Val and referred to as G47V) in TTR gene. Biochemical and biophysical kinetics study showed that the thermodynamic stability of G47V-TTR (Cm = 2.4 M) was significantly lower than that of WT-TTR (Cm = 3.4 M) and comparable to that of L55P-TTR (Cm = 2.3 M), an early age-of-onset mutation. G47V:WT-TTR heterozygous tetramers kinetic stability (t1/2 = 1.4 h) was further compromised compared to that of the homozygous G47V-TTR (t1/2 = 3.1 h). Among three small molecule stabilizers, AG10 exhibited the best inhibition of the fibrillation of G47V-TTR homozygous protein. Using a UPLC assay, nearly 40% of TTR in this patient was calculated to be non-tetrameric. CONCLUSION: In this work, we reported a patient presented early onset of clinically typical ATTR-CM due to G47V-TTR mutation. Our work not only for the first time characterized the biochemical properties of G47V-TTR mutation, but also provided hints for the pathogenicity of this mutation.

DNA Methylation-Regulated HOXC8's Role in HER2-Positive Breast Cancer Function and its Contribution to Herceptin Resistance.

BACKGROUND: The epidermal growth factor receptor 2 (HER2) is overexpressed in 30% of breast cancers, and this overexpression is strongly correlated with a poor prognosis. Herceptin is a common treatment for HER2-positive breast cancer; however, cancer cells tend to adapt gradually to the drug, rendering it ineffective. The study revealed an association between the methylation status of the Homeobox C8 (HOXC8) gene and tumor development. Therefore, it is of paramount importance to delve into the interaction between HOXC8 and HER2-positive breast cancer, along with its molecular mechanisms. This exploration holds significant implications for a deeper understanding of the pathophysiological processes underlying HER2-positive breast cancer. METHOD: Tumor tissue and pathological data from patients with HER2-positive breast cancer were systematically collected. Additionally, the human HER2-positive breast cancer cell line, SKBR3, was cultured in vitro to assess both the expression level of HOXC8 and the degree of DNA methylation. The study aimed to explore the relationship between the relative expression of HOXC8 and the clinical characteristics of breast cancer patients. The expression level of HOXC8 and the promoter methylation of HOXC8 were verified by methylation treatment of SKBR3 breast cancer cells. The regulation of HOXC8 was meticulously carried out, leading to the division of the cells into distinct groups. The study further analyzed the expression levels and biological capabilities within each group. Finally, the in vitro and in vivo sensitivity of the cells to Herceptin, a common treatment for HER2-positive breast cancer, was measured to assess the efficacy of the drug. RESULT: In HER2-positive breast cancer cases characterized by poor methylation, there was an up-regulation of HOXC8. Its expression was found to be correlated with key clinical factors such as tumor size, lymph node status, clinical tumor, node, metastasis (cTNM) staging, and Herceptin resistance (p < 0.05). Upon methylation of breast cancer cells, there was a significant decrease in HOXC8 expression (p < 0.05). The study revealed that overexpression of HOXC8 resulted in increased proliferation, cloning, and metastasis of HER2-positive breast cancer cells, along with a reduced apoptosis rate (p < 0.05). Conversely, interference with HOXC8 expression reversed this scenario (p < 0.05). A Herceptin-resistant substrain, POOL2, was established using SKBR3 cells. Animal studies demonstrated that overexpressing HOXC8 accelerated tumor development and enhanced POOL2 cells' resistance to Herceptin (p < 0.05). However, following interference with HOXC8, POOL2 cells exhibited increased responsiveness to Herceptin, leading to a gradual reduction in tumor size (p < 0.05). CONCLUSIONS: In HER2-positive breast cancer, the expression of HOXC8 is elevated in a manner dependent on DNA methylation, and this elevated expression is closely linked to the pathology of the patient. Interfering with HOXC8 expression demonstrates the potential to partially inhibit the development and spread of breast cancer, as well as to alleviate resistance to Herceptin.

Effect of hornification on the isolation of anionic cellulose nanofibrils from Kraft pulp via maleic anhydride esterification.

Cellulose nanofibrils (CNF) isolation based on a catalyst-free maleic anhydride esterification has proven to be effective, however, the effects of pulp hornification on CNF isolation by this strategy have yet to be explored, which could present significant impacts for CNF isolation. Herein, dried northern bleached softwood Kraft pulp (D-NBSK) and never-dried northern bleached softwood Kraft pulp (ND-NBSK) were selected as the substrates. After esterification with maleic anhydride (MA), the esterified ND-NBSK pulp (E-ND) shows a significantly smaller size and more fragmented structure than the esterified D-NBSK pulp (E-D). Meanwhile, higher degree of esterification can be realized for the never dried pulp as compared to the dried pulp, which is corroborated by the significantly stronger characteristic peaks of CO (1720 cm-1) and -COO- (1575 cm-1) from the FTIR spectra and the higher surface charge content (0.86 ± 0.04 mmol/g vs. 0.55 ± 0.05 mmol/g). A comparison of the characteristics of the resulting CNF similarly demonstrated the negative impact of hornification. Overall, this work indicates that hornification tends to reduce the accessibility of chemical reagents to the pulp, leading to insufficient deconstruction. Such negative impact of hornification should be considered when performing nanocellulose isolation, especially when using pulp as feedstock.

A Biomimetic "Salting Out-Alignment-Locking" Tactic to Design Strong and Tough Hydrogel.

Recently, hydrogel-based soft materials have demonstrated huge potential in soft robotics, flexible electronics as well as artificial skins. Although various methods are developed to prepare tough and strong hydrogels, it is still challenging to simultaneously enhance the strength and toughness of hydrogels, especially for protein-based hydrogels. Herein, a biomimetic "salting out-alignment-locking" tactic (SALT) is introduced for enhancing mechanical properties through the synergy of alignment and the salting out effect. As a typical example, tensile strength and modulus of initially brittle gelatin hydrogels increase 940 folds to 10.12 ± 0.50 MPa and 2830 folds to 34.26 ± 3.94 MPa, respectively, and the toughness increases up to 1785 folds to 14.28 ± 3.13 MJ m-3. The obtained strength and toughness hold records for the previously reported gelatin-based hydrogel and are close to the tendons. It is further elucidated that the salting out effect engenders hydrophobic domains, while prestretching facilitates chain alignment, both synergistically contributing to the outstanding mechanical properties. It is noteworthy that the SALT demonstrates remarkable versatility across different salt types and polymer systems, thus opening up new avenues for engineering strong, tough, and stiff hydrogels.

Molecular mechanism of NAD+ and NMN binding to the Nudix homology domains of DBC1.

Deleted in breast cancer 1 (DBC1) is a human nuclear protein that modulates the activities of various proteins involved in cell survival and cancer progression. Oxidized form of nicotinamide adenine dinucleotide (NAD+) is suggested to bind to the Nudix homology domains (NHDs) of DBC1, thereby regulating DBC1-Poly (ADP-ribose) polymerase 1 (PARP1) interactions, resulting in the restoration of DNA repair. Using Nuclear Magnetic Resonance (NMR) and Isothermal Titration Calorimetry (ITC), we confirmed NAD+ and its precursor nicotinamide mononucleotide (NMN) both bind the NHD domain of DBC1 (DBC1354-396). NAD+ likely interacts with DBC1354-396 through hydrogen bonding, with a binding affinity (8.99 µM) nearly twice that of NMN (17.0 µM), and the key binding sites are primarily residues E363 and D372, in the agreement with Molecular Docking experiments. Molecular Dynamics (MD) simulation further demonstrated E363 and D372's anchoring role in the binding process. Additional mutagenesis experiments of E363 and D372 confirmed their critical involvement of ligand-protein interactions. These findings lead to a better understanding of how NAD+ and NMN regulate DBC1, thereby offering insights for the development of targeted therapies and drug research focused on DBC1-associated tumors.

3D Printed Cellulose Nanofiber Aerogel Scaffold with Hierarchical Porous Structures for Fast Solar-Driven Atmospheric Water Harvesting.

Hygroscopic salt-based composite sorbents are considered ideal candidates for solar-driven atmospheric water harvesting. The primary challenge for the sorbents lies in exposing more hygroscopically active sites to the surrounding air while preventing salt leakage. Herein, a hierarchically structured scaffold is constructed by integrating cellulose nanofiber and lithium chloride (LiCl) as building blocks through 3D printing combined with freeze-drying. The milli/micrometer multiscale pores can effectively confine LiCl and simultaneously provide a more exposed active area for water sorption and release, accelerating both water sorption and evaporation kinetics of the 3D printed structure. Compared to a conventional freeze-dried aerogel, the 3D printed scaffold exhibits a water sorption rate that is increased 1.6-fold, along with a more than 2.4-fold greater water release rate. An array of bilayer scaffolds is demonstrated, which can produce 0.63 g g-1 day-1 of water outdoors under natural sunlight. This article provides a sustainable strategy for collecting freshwater from the atmosphere.

Extracellular Matrix Disorganization Caused by ADAMTS16 Deficiency Leads to Bicuspid Aortic Valve With Raphe Formation.

BACKGROUND: A better understanding of the molecular mechanism of aortic valve development and bicuspid aortic valve (BAV) formation would significantly improve and optimize the therapeutic strategy for BAV treatment. Over the past decade, the genes involved in aortic valve development and BAV formation have been increasingly recognized. On the other hand, ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene family members have been reported to be able to modulate cardiovascular development and diseases. The present study aimed to further investigate the roles of ADAMTS family members in aortic valve development and BAV formation. METHODS: Morpholino-based ADAMTS family gene-targeted screening for zebrafish heart outflow tract phenotypes combined with DNA sequencing in a 304 cohort BAV patient registry study was initially carried out to identify potentially related genes. Both ADAMTS gene-specific fluorescence in situ hybridization assay and genetic tracing experiments were performed to evaluate the expression pattern in the aortic valve. Accordingly, related genetic mouse models (both knockout and knockin) were generated using the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) method to further study the roles of ADAMTS family genes. The lineage-tracing technique was used again to evaluate how the cellular activity of specific progenitor cells was regulated by ADAMTS genes. Bulk RNA sequencing was used to investigate the signaling pathways involved. Inducible pluripotent stem cells derived from both BAV patients and genetic mouse tissue were used to study the molecular mechanism of ADAMTS. Immunohistochemistry was performed to examine the phenotype of cardiac valve anomalies, especially in the extracellular matrix components. RESULTS: ADAMTS genes targeting and phenotype screening in zebrafish and targeted DNA sequencing on a cohort of patients with BAV identified ADAMTS16 (a disintegrin and metalloproteinase with thrombospondin motifs 16) as a BAV-causing gene and found the ADAMTS16 p. H357Q variant in an inherited BAV family. Both in situ hybridization and genetic tracing studies described a unique spatiotemporal pattern of ADAMTS16 expression during aortic valve development. Adamts16+/- and Adamts16+/H355Q mouse models both exhibited a right coronary cusp-noncoronary cusp fusion-type BAV phenotype, with progressive aortic valve thickening associated with raphe formation (fusion of the commissure). Further, ADAMTS16 deficiency in Tie2 lineage cells recapitulated the BAV phenotype. This was confirmed in lineage-tracing mouse models in which Adamts16 deficiency affected endothelial and second heart field cells, not the neural crest cells. Accordingly, the changes were mainly detected in the noncoronary and right coronary leaflets. Bulk RNA sequencing using inducible pluripotent stem cells-derived endothelial cells and genetic mouse embryonic heart tissue unveiled enhanced FAK (focal adhesion kinase) signaling, which was accompanied by elevated fibronectin levels. Both in vitro inducible pluripotent stem cells-derived endothelial cells culture and ex vivo embryonic outflow tract explant studies validated the altered FAK signaling. CONCLUSIONS: Our present study identified a novel BAV-causing ADAMTS16 p. H357Q variant. ADAMTS16 deficiency led to BAV formation.

Multiscale Design for Robust, Thermal Insulating, and Flame Self-Extinguishing Cellulose Foam.

Cellulose foams are in high demand in an era of prioritizing environmental consciousness. Yet, transferring the exceptional mechanical properties of cellulose fibers into a cellulose network remains a significant challenge. To address this challenge, an innovative multiscale design is developed for producing cellulose foam with exceptional network integrity. Specifically, this design relies on a combination of physical cross-linking of the microfibrillated cellulose (MFC) networks by cellulose nanofibril (CNF) and aluminum ion (Al3+), as well as self-densification of the cellulose induced by ice-crystal templating, physical cross-linking, solvent exchange, and evaporation. The resultant cellulose foam demonstrates a low density of 40.7 mg cm-3, a high porosity of 97.3%, and a robust network with high compressive modulus of 1211.5 ± 60.6 kPa and energy absorption of 77.8 ± 1.9 kJ m-3. The introduction of CNF network and Al3+ cross-linking into foam also confers excellent wet stability and flame self-extinguish ability. Furthermore, the foam can be easily biodegraded in natural environments , re-entering the ecosystem's carbon cycle. This strategy yields a cellulose foam with a robust network and outstanding environmental durability, opening new possibilities for the advancement of high-performance foam materials.

Novel combinations of variations in KCNQ1 were associated with patients with long QT syndrome or Jervell and Lange-Nielsen syndrome.

OBJECTIVES: Long QT syndrome (LQTS) is one of the primary causes of sudden cardiac death (SCD) in youth. Studies have identified mutations in ion channel genes as key players in the pathogenesis of LQTS. However, the specific etiology in individual families remains unknown. METHODS: Three unrelated Chinese pedigrees diagnosed with LQTS or Jervell and Lange-Nielsen syndrome (JLNS) were recruited clinically. Whole exome sequencing (WES) was performed and further validated by multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. RESULTS: All of the probands in our study experienced syncope episodes and featured typically prolonged QTc-intervals. Two probands also presented with congenital hearing loss and iron-deficiency anemia and thus were diagnosed with JLNS. A total of five different variants in KCNQ1, encoding a subunit of the voltage-gated potassium channel, were identified in 3 probands. The heterozygous variants, KCNQ1 c.749T > C was responsible for LQTS in Case 1, transmitting in an autosomal dominant pattern. Two patterns of compound heterozygous variants were responsible for JLNS, including a large deletion causing loss of the exon 16 and missense variant c.1663 C > T in Case 2, and splicing variant c.605-2 A > G and frame-shift variant c.1265del in Case 3. To our knowledge, the compound heterozygous mutations containing a large deletion and missense variant were first reported in patients with JLNS. CONCLUSION: Our study expanded the LQTS genetic spectrum, thus favoring disease screening and diagnosis, personalized treatment, and genetic consultation.

An information encrypted heterogeneous hydrogel with programmable mechanical properties enabled by 3D patterning.

Heterogeneous architectures with defined patterns found in nature have stimulated the burgeoning development of biomimetic materials. However, the construction of soft matter like hydrogels that mimic biological materials with a combination of strong mechanical performance and unique functionality remains difficult. In this work, we developed a simple and adaptable strategy of a 3D printing complex structure within hydrogels utilising all-cellulosic materials (hydroxypropyl cellulose/cellulose nanofibril, HPC/CNF) as ink. The structural integrity of the patterned hydrogel hybrid is ascertained by the interfacial interaction between cellulosic ink and the surrounding hydrogels. Through designing the geometry of the 3D printed pattern, programmable mechanical properties of hydrogels are achieved. In addition, the thermally induced phase separation properties of HPC confer thermally responsive behaviour on patterned hydrogels, providing them potential to be assembled into double information encryption devices and shape-morphing materials. We anticipate that this all-cellulose ink-enabled 3D patterning technique within hydrogels can serve as a promising and sustainable alternative for designing biomimetic hydrogels with desired mechanical properties and functions for a variety of applications.

Characterization of wheat Wrab18 gene promoter and expression analysis under abiotic stress.

BACKGROUND: Promoters play key roles in plant gene expression in complex and varied natural environments. The type and amount of cis-acting elements in the promoter sequence tend to indicate the response of genes to induction factors. WRAB18 is a group III member of the late embryogenesis abundant (LEA) protein family that performs multiple functions in plant stress physiology. To elucidate the particularly biological effects of WRAB18 on stress, exploration of its promoter sequence is necessary. METHODS AND RESULTS: In this study, the full-length and promoter sequences of Wrab18 were isolated from the Zhengyin 1 cultivar of Triticum aestivum. The gene sequences and cis-acting elements in the promoter were analyzed using the Plant Promoter Database and bioinformatics methods. The results showed that Wrab18 possessed one intron with 100 bp, the promoter sequence contained various stress-related cis-acting elements, and the functionality of the promoter was checked using green fluorescent protein (GFP) marker protein expression by transient assay in Nicotiana benthamiana. Furthermore, based on promoter prediction analysis, quantitative real-time fluorescent PCR results confirmed the response of gene expression levels to stress factors. CONCLUSIONS: In summary, the promoter sequence of Wrab18 plays a role in plant stress responses, contains multiple cis-acting elements, and provides insights into the role of WRAB18 in plant resilience to stress. This study has guiding significance for further studies of gene function and mechanism of action, and lays a theoretical foundation for improving wheat quality.

Minimally invasive bioprinting for in situ liver regeneration.

In situ bioprinting is promising for developing scaffolds directly on defect models in operating rooms, which provides a new strategy for in situ tissue regeneration. However, due to the limitation of existing in situ biofabrication technologies including printing depth and suitable bioinks, bioprinting scaffolds in deep dermal or extremity injuries remains a grand challenge. Here, we present an in vivo scaffold fabrication approach by minimally invasive bioprinting electroactive hydrogel scaffolds to promote in situ tissue regeneration. The minimally invasive bioprinting system consists of a ferromagnetic soft catheter robot for extrusion, a digital laparoscope for in situ monitoring, and a Veress needle for establishing a pneumoperitoneum. After 3D reconstruction of the defects with computed tomography, electroactive hydrogel scaffolds are printed within partial liver resection of live rats, and in situ tissue regeneration is achieved by promoting the proliferation, migration, and differentiation of cells and maintaining liver function in vivo.

Automatic registration of urban high-resolution remote sensing images based on characteristic spatial objects.

Automatic registration of high-resolution remote sensing images (HRRSIs) has always been a severe challenge due to the local deformation caused by different shooting angles and illumination conditions. A new method of characteristic spatial objects (CSOs) extraction and matching is proposed to deal with this difficulty. Firstly, the Mask R-CNN model is utilized to extract the CSOs and their positioning points on the images automatically. Then, an encoding method is provided to encode each object with its nearest adjacent 28 objects according to the object category, relative distance, and relative direction. Furthermore, a code matching algorithm is applied to search the most similar object pairs. Finally, the object pairs need to be filtered by position matching to construct the final control points for automatic image registration. The experimental results demonstrate that the registration success rate of the proposed method reaches 88.6% within a maximum average error of 15 pixels, which is 28.6% higher than that of conventional optimization method based on local feature points. It is reasonable to believe that it has made a beneficial contribution to the automatic registration of HRRSIs more accurately and efficiently.

Research on Preparation and Properties of Carbon Fiber Reinforced Zinc-Based Aluminum Rich Alloy Composite.

Aiming at the problems of poor bonding between the carbon fiber and the metal matrix and the friction and wear performance of the composite material during the preparation of carbon fiber reinforced zinc-based aluminum rich alloy composites, the carbon fiber surface metallization process was studied. Taking ZA27 as the research object, a new type of zinc-based aluminum rich alloy composite material was prepared by using surface metallized chopped carbon fibers with different contents as reinforcement materials. The microscopic morphology, element distribution and phase composition of the surface metallized carbon fiber and composite materials were characterized, and the hardness and friction and wear properties of the composite materials were tested. The results show that: the surface metallization of carbon fiber effectively reduces the diffusion of carbon elements into the matrix material during the sintering process, and improves the interface bonding between the carbon fiber and the matrix material; Compared with ZA27 alloy, the hardness of 6vt% carbon fiber is increased by 29.6%, and the average friction coefficient and wear rate are reduced by about 18.4% and 96%, respectively, indicating that the carbon fiber reinforced zinc-based aluminum rich alloy composite material optimizes the friction and wear performance of traditional materials.

Lightweight, strong, and form-stable cellulose nanofibrils phase change aerogel with high latent heat.

Phase change material (PCM) is promising for energy storage and release. However, the deformation and leaking during phase change generally limit its application. Herein, a lightweight, strong, and form-stable PCM aerogel was fabricated using Pickering emulsion templating technique. Cellulose nanofibrils (CNFs) were used to stabilize PCM into Pickering emulsion, which was further integrated into a 3D interconnected CNF network forming CNF/PCM composite aerogel. The composite aerogel is strong that can support over 5000 times of its own weight, and demonstrates exceptional form stability at 80 °C, showing no leakage after 20 heating/cooling cycles. The latent heat of CNF/PCM composite aerogel could reach 173.59 J·g-1, approximately 84.4% of the paraffin. The CNF/PCM composite aerogel showed relatively low thermal conductivity of 32.0-37.7 mW·m-1·K-1. The sustainability and impressive thermal regulating properties of the CNF/PCM composite aerogel make it an ideal candidate for applications in smart textile, smart building, batteries, and electronic devices.

Induced phase separation of mutant NF2 imprisons the cGAS-STING machinery to abrogate antitumor immunity.

Missense mutations of the tumor suppressor Neurofibromin 2 (NF2/Merlin/schwannomin) result in sporadic to frequent occurrences of tumorigenesis in multiple organs. However, the underlying pathogenicity of NF2-related tumorigenesis remains mostly unknown. Here we found that NF2 facilitated innate immunity by regulating YAP/TAZ-mediated TBK1 inhibition. Unexpectedly, patient-derived individual mutations in the FERM domain of NF2 (NF2m) converted NF2 into a potent suppressor of cGAS-STING signaling. Mechanistically, NF2m gained extreme associations with IRF3 and TBK1 and, upon innate nucleic acid sensing, was directly induced by the activated IRF3 to form cellular condensates, which contained the PP2A complex, to eliminate TBK1 activation. Accordingly, NF2m robustly suppressed STING-initiated antitumor immunity in cancer cell-autonomous and -nonautonomous murine models, and NF2m-IRF3 condensates were evident in human vestibular schwannomas. Our study reports phase separation-mediated quiescence of cGAS-STING signaling by a mutant tumor suppressor and reveals gain-of-function pathogenesis for NF2-related tumors by regulating antitumor immunity.

Superelastic, Hygroscopic, and Ionic Conducting Cellulose Nanofibril Monoliths by 3D Printing.

Compressible and superelastic 3D printed monoliths have shown great promise in various applications including energy storage, soft electronics, and sensors. Although such elastic monoliths have been constructed using some limited materials, most notably graphene, it has not yet been achieved in nature's most abundant material, cellulose, partly due to the strong hydrogen-bonding network within cellulose. Here, we report a 3D-printed cellulose nanofibril monolith that demonstrates superb elasticity (over 91% strain recovery after 500 cycles of compressive test), compressibility (up to 90% compressive strain), and pressure sensitivity (0.337 kPa-1) at 43% relative humidity. Such a high-performance CNF monolith is achieved through both hierarchical architecture design by 3D printing and freeze-drying and incorporation of hygroscopic salt for water absorption. The facile and efficient design strategy for a highly flexible CNF monolith is expected to expand to materials beyond cellulose and can realize much broader applications in flexible sensors, thermal insulation, and many other fields.

Effect of K-/S- segments on subcellular localization and dimerization of wheat dehydrin WZY1-2.

Dehydrins (DHNs) belong to group Ⅱ late embryogenesis abundant (LEA) proteins which perform multiple functions in plants during stress conditions. Both K- and S-segments are conserved domains in the dehydrin protein family; however, there are only a few in vivo functional studies for these two conserved segments. In this study, the DHN gene wzy1-2 was isolated from Triticum aestivum and its K-/S-segment-truncated derivatives were generated. In order to explore the biological function of these two conserved fragments, subcellular localization and dimerization detection assays were performed for the K-/S-segment-truncated derivatives. Results of GFP fusion and bimolecular fluorescence complementation (BiFC) assays indicated that WZY1-2 localized to nucleus as a homologous dimer. The S-segment partially regulated the nuclear localization of WZY1-2 but did not affect its dimerization, while the K-segment influenced neither the dimer formation nor the subcellular localization.

MiR-483 Targeted SOX3 to Suppress Glioma Cell Migration, Invasion and Promote Cell Apoptosis.

OBJECTIVE: Glioma is the most common malignant brain tumor that has high aggressiveness. The aim of this study was to investigate the potential therapeutic targets for gliomas. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to calculate the expression of miRNA and genes. The connection between the expression of miR-483 and patients' overall survival rate was evaluated using Kaplan-Meier analysis. In addition, the underlying mechanism was detected using luciferase assay. RESULTS: The expression level of miR-483 was significantly decreased in glioma tissue samples and cell lines, compared to the adjacent tissues and normal cell lines. Downregulation of miR-483 or upregulation of SOX3 was associated with overall survival of glioma patients. Additionally, overexpression of miR-483 promotes cell invasion and migration and inhibits apoptosis. In addition, miR-483 directly targeted to SOX3, and the expression of miR-483 has a negative correlation with SOX3 in glioma tissues. SOX3 reversed partial functions of miR-483 on cell migration, invasion, and promoted cell apoptosis in glioma. CONCLUSION: MiR-483 inhibited glioma cell migration, invasion, and promoted glioma cell apoptosis by targeting SOX3. MiR-483 maybe acted as a potential target for the treatment of glioma.