Visual object detection is an essential task for the intelligent navigation of an Unmanned Surface Vehicle (USV), which can sense the obstacles while navigating. However, the harsh illumination ...conditions and large scale variation of the objects significantly harm the performance of object detection methods. To address the above problems, we propose a robust water surface object detection method named multi-scale feature fusion network with intrinsic decomposition generative adversarial network data augmentation (MFFDet-IDGAN). We introduce intrinsic decomposition as data augmentation for the object detection to achieve illumination adapting. And an intrinsic decomposition generative adversarial network (IDGAN) is proposed to achieve unsupervised intrinsic decomposition. Moreover, the multi-scale feature fusion network (MFFDet) adopts an improved bidirectional feature pyramid network (BiFPN) and spatial pyramid pooling (SPP) blocks to fuse features of different resolution for better multi-scale detection. And an improved weighted stochastic weight averaging (SWA) is proposed and applied in the training process to improve the generalization performance. We conduct extensive experiments on the Water Surface Object Detection Dataset (WSODD), and the results show that the proposed method can achieve 44% improvement over the baseline. And we further test our method on a real USV in the sailing process, the results show that our method can exceeding the baseline by 4.5%.
Lung cancer is the most lethal malignancy, with non-small cell lung cancer (NSCLC) being the most common type (~ 85%). Abnormal activation of epidermal growth factor receptor (EGFR) promotes the ...development of NSCLC. Chemoresistance to tyrosine kinase inhibitors, which is elicited by EGFR mutations, is a key challenge for NSCLC treatment. Therefore, more thorough understanding of EGFR expression and dynamics are needed.
Human non-small cell lung cancer cells and HEK293FT cells were used to investigate the molecular mechanism of gasdermin E (GSDME) regulating EGFR stability by Western blot analysis, immunoprecipitation and immunofluorescence. GSDME and EGFR siRNAs or overexpression plasmids were used to characterize the functional role of GSDME and EGFR in vitro. EdU incorporation, CCK-8 and colony formation assays were used to determine the proliferation ability of non-small cell lung cancer cells.
GSDME depletion reduced the proliferation of non-small cell lung cancer cells in vitro. Importantly, both GSDME-full length (GSDME-FL) and GSDME-N fragment physically interacted with EGFR. GSDME interacted with cytoplasmic fragment of EGFR. GSDME knockdown inhibited EGFR dimerization and phosphorylation at tyrosine 1173 (EGFR
), which activated ERK1/2. GSDME knockdown also promoted phosphorylation of EGFR at tyrosine 1045 (EGFR
) and its degradation.
These results indicate that GSDME-FL increases the stability of EGFR, while the GSDME N-terminal fragment induces EGFR degradation. The GSDME-EGFR interaction plays an important role in non-small cell lung cancer development, reveal a previously unrecognized link between GSDME and EGFR stability and offer new insight into cancer pathogenesis. Video abstract.
Extracellular vesicles (EVs) are increasingly used for disease diagnosis and treatment. Among them, red blood cell-derived EVs (RBC-EVs) have attracted great attention due to their abundant sources ...and low risks of gene transfer (RBC-EVs lack nuclear and mitochondrial DNA). Here, we first revealed the high expression level of membrane protein solute carrier family 4 member 1 (SLC4A1) in RBC-EVs through proteomic analysis. We then identified several binding peptides with high affinity for the SLC4A1 extracellular domain (SLC4A1-EC) from phage display library screening. A high affinity of SLC4A1-EC and the three peptides (XRB2, XRE4, and XRH7) were assessed in vitro using surface plasmon resonance analysis and SDS–polyacrylamide gel electrophoresis (SDS–PAGE). The binding sites of SLC4A1-EC and polypeptides were further predicted by LigPlot + analysis, and the results showed that these three polypeptides could bind to part of the hydrophobic residues of SLC4A1-EC. The binding efficiency of the anchor peptides to the RBC-EVs was further verified by flow cytometry and fluorescence imaging. In conclusion, we successfully screened three specific RBC-EV-targeting peptides which could potentially be utilized for isolating RBC-derived EVs from serum samples. More importantly, this peptide could be coupled with targeting peptides to modify RBC-EVs for drug delivery. Our work will provide a viable method for optimizing the function of RBC-EVs.
Liposome-based drug delivery systems have been widely used in drug and gene delivery. However, issues such as instability, immune clearance, and poor targeting have significantly limited their ...clinical utility. Consequently, there is an urgent need for innovative strategies to improve liposome performance. In this study, we explore the interaction mechanisms of hyaluronic acid (HA), a linear anionic polysaccharide composed of repeating disaccharide units of d-glucuronic acid and N-acetyl-d-glucosamine connected by alternating β-1,3 and β-1,4 glycosidic linkages, and its octanoylated derivates (OHA) with liposomes using extensive coarse-grained molecular dynamics simulations. The octyl moieties of OHA spontaneously inserted into the phospholipid bilayer of liposomes, leading to their effective coating onto the surface of liposome and enhancing their structural stability. Furthermore, encapsulating liposome with OHA neutralized their surface potential, interfering with the formation of a protein corona known to contribute to liposomal immune clearance. Importantly, the encapsulated OHA maintained its selectivity and therefore targeting ability for CD44, which is often overexpressed in tumor cells. These molecular-scale findings shed light on the interaction mechanisms between HA and liposomes and will be useful for the development of next-generation liposome-based drug delivery systems.
Interfacial water is closely related to many core scientific and technological issues, covering a broad range of fields, such as material science, geochemistry, electrochemistry and biology. The ...understanding of the structure and dynamics of interfacial water is the basis of dealing with a series of issues in science and technology. In recent years, atomic force microscopy (AFM) with ultrahigh resolution has become a very powerful option for the understanding of the complex structural and dynamic properties of interfacial water on solid surfaces. In this perspective, we provide an overview of the application of AFM in the study of two dimensional (2D) or three dimensional (3D) interfacial water, and present the prospect and challenges of the AFM-related techniques in experiments and simulations, in order to gain a better understanding of the physicochemical properties of interfacial water.
Ovarian cancer is the most lethal gynecological malignancy. Abnormal homologous recombination repair, high level of reactive oxygen species (ROS) and upregulation of antioxidant genes are ...characteristic features of ovarian cancer. However, the molecular mechanisms governing the redox homeostasis in ovarian cancer cells remain to be fully elucidated. We here demonstrated a critical role of RAD51, a protein essential for homologous recombination, in the maintenance of redox homeostasis. We found that RAD51 is overexpressed in high grade serous ovarian cancer and is associated with poor prognosis. Depletion or inhibition of RAD51 results in G2/M arrest, increased production of reactive oxygen species and accumulation of oxidative DNA damage. Importantly, antioxidant N-acetylcysteine (NAC) significantly attenuated the induction of DNA damage and the perturbation of proliferation caused by RAD51 depletion. We further demonstrated that RAD51 inhibition or depletion led to elevated production of mitochondrial superoxide and increased accumulation of mitochondria. Moreover, CHK1 activation is required for the G2/M arrest and the generation of mitochondrial stress in response to RAD51 depletion. Together, our results indicate that nuclear DNA damage caused by RAD51 depletion may trigger mitochondria-originated redox dysregulation. Our findings suggest that a vicious cycle of nuclear DNA damage, mitochondrial accumulation and oxidative stress may contribute to the tumor-suppressive effects of RAD51 depletion or inhibition.
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•RAD51 is overexpressed in ovarian cancer and is associated with poor prognosis.•Depletion of RAD51 leads to increased mitochondrial superoxide production and oxidative DNA damage.•Increased production of mitochondrial ROS requires CHK1-mediated G2/M arrest.•mROS increase is independent of mtDNA.
Abstract
SPOP, an E3 ubiquitin ligase, acts as a prostate-specific tumor suppressor with several key substrates mediating oncogenic function. However, the mechanisms underlying SPOP regulation are ...largely unknown. Here, we have identified G3BP1 as an interactor of SPOP and functions as a competitive inhibitor of Cul3
SPOP
, suggesting a distinctive mode of Cul3
SPOP
inactivation in prostate cancer (PCa). Transcriptomic analysis and functional studies reveal a G3BP1-SPOP ubiquitin signaling axis that promotes PCa progression through activating AR signaling. Moreover, AR directly upregulates G3BP1 transcription to further amplify G3BP1-SPOP signaling in a feed-forward manner. Our study supports a fundamental role of G3BP1 in disabling the tumor suppressive Cul3
SPOP
, thus defining a PCa cohort independent of SPOP mutation. Therefore, there are significantly more PCa that are defective for SPOP ubiquitin ligase than previously appreciated, and these G3BP1
high
PCa are more susceptible to AR-targeted therapy.
Abstract
Introduction
De novo balanced reciprocal translocations mosaicism in fetus conceived using preimplantation genetic testing from a different balanced translocation carrier parent has been ...rarely reported.
Methods
Chromosomal microarray analysis, karyotype analysis and fluorescent in situ hybridization were performed to verify the type and heredity of the rearrangement. STR analysis was conducted to identify potential contamination and verify kinship. In addition, a local BLAST engine was performed to locate potentially homologous segments which might contribute to the translocation in breakpoints of chromosome.
Results
A rare de novo balanced reciprocal translocations mosaicism mos 46,XY,t(1;3)(q42;q25)40/46,XY39 was diagnosed in a fetus conceived using preimplantation genetic testing due to a 46,XY,t(12;14)(q22;q13) balanced translocation carrier father through multiplatform genetic techniques. Two of the largest continuous high homology segments were identified in chromosomal band 1q42.12 and 3q25.2. At the 21-months follow up, infant has achieved all psychomotor development milestones as well as growth within the normal reference range.
Conclusion
We present a prenatal diagnosis of a rare de novo balanced reciprocal translocations mosaicism in a fetus who conceived by preimplantation genetic testing. The most reasonable driving mechanism was that a de novo mitotic error caused by nonallelic homologous recombination between 1q42.12 and 3q25.2 in a zygote within the first or early cell divisions, which results in a mosaic embryo with the variant present in a half proportion of cells.
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