Demethylase FTO inhibits the occurrence and development of triple-negative breast cancer by blocking m 6A-dependent miR-17-5p maturation-induced ZBTB4 depletion.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer, and its mechanisms of occurrence and development remain unclear. In this study, we aim to investigate the role and molecular mechanisms of the demethylase FTO (fat mass and obesity-associated protein) in TNBC. Through analysis of public databases, we identify that FTO may regulate the maturation of miR-17-5p and subsequently influence the expression of zinc finger and BTB domain-containing protein 4 (ZBTB4), thereby affecting the occurrence and progression of TNBC. We screen for relevant miRNAs and mRNAs from the GEO and TCGA databases and find that the FTO gene may play a crucial role in TNBC. In vitro cell experiments demonstrate that overexpression of FTO can suppress the proliferation, migration, and invasion ability of TNBC cells and can regulate the maturation of miR-17-5p through an m 6A-dependent mechanism. Furthermore, we establish a xenograft nude mouse model and collect clinical samples to further confirm the role and impact of the FTO/miR-17-5p/ZBTB4 regulatory axis in TNBC. Our findings unveil the potential role of FTO and its underlying molecular mechanisms in TNBC, providing new perspectives and strategies for the research and treatment of TNBC.

Mechanistic Insights into Synaptic Plasticity Behaviors of Electrolyte-Gated Flexible Transistor Devices.

Biological synaptic function simulation using flexible electronic devices based on low-dimensional semiconductor materials is an emerging and rapidly evolving research field with promising applications in brain-like computers and artificial intelligence systems. In this work, we present the fabrication of solution compatible MoS2 thin-film transistors on the ultrathin polymethyl methacrylate substrates via layer-by-layer assembly followed by a one-step transfer printing method. The MoS2 transport channel is controlled by ionic liquid gating with 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, resulting in excellent synaptic performances for emulating memory and perception synapse functions. To investigate the synaptic behaviors, we conduct a series of synaptic spike-dependent experiments and propose an advanced model that delineates the long-term plasticity and short-term plasticity with separate characteristic factors. These findings provide insights into the fundamental mechanisms of synaptic plasticity in electric double-layer devices and contribute to a better understanding of their synaptic performances. In addition, we examine the effects of bending conditions on synaptic plasticity and synaptic weights, unveiling the synergistic interplay between mechanical deformation and synaptic behaviors. Our experimental results, combined with the developed model, are in good agreement and shed light on the influence of mechanical flexibility on the synaptic properties of the devices. In summary, this study establishes a solid foundation for further development of flexible synaptic devices from both practical and theoretical perspectives.

TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium-induced inflammatory bowel disease through activation of the TLR4/NF-κBs pathway.

INTRODUCTION: Inflammatory bowel disease (IBD), which mainly leads to diarrhea, fatigue, stool blood, abdominal pain, and cramping, is threatening public health. Tripartite motif-containing 52 (TRIM52) has been reported to play an important role in inflammatory responses via activating the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. However, the causes of IBD need to be elucidated, and the function of TRIM52 in IBD remains unclear. Here, we demonstrated that TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium (DSS)-induced IBD by activating TLR4/NF-κBs pathway. METHODS: The colitis model was established on mice through DSS induction. For the TRIM52 knockdown, the mice were infected with a recombinant adenoviral vector expressing sgRNAs targeting TRIM52. RT-qPCR, western blot, and immunohistochemistry were performed to verify TRIM52 expression in DSS-induced IBD. The body weight, disease activity index, colon length, and H&E staining were used to assess the IBD symptoms in mice with TRIM52 knockdown. The inflammatory responses were examined by RT-qPCR and ELISA measuring tumor necrosis factor-α (TNF-α), inter-leukin 6 (IL-6), and interleukin 1ß (IL-1ß). Furthermore, the pyroptosis in colon tissue was detected by western blot. Finally, the TLR4/NF-κBs pathway activity was also examined by western blot. RESULTS: TRIM52 expression was up-regulated in DSS-induced IBD, and knockdown of TRIM52 could alleviate the symptoms of IBD. TRIM52 knockdown retarded DSS-induced inflammatory response and inhibited DSS-induced pyroptosis in colon tissue. In addition, TRIM52 played a role in activating TLR4/NF-κBs pathway. CONCLUSION: Knockdown of TRIM52 alleviated inflammation and pyroptosis in IBD by regulating TLR4/NF-κBs pathway. TRIM52 is expected to be a novel diagnostic indicator for IBD and a target of therapeutic treatment.

TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium-induced inflammatory bowel disease through activation of the TLR4/NF-kBs pathway

Introduction: Inflammatory bowel disease (IBD), which mainly leads to diarrhea, fatigue, stool blood, abdominal pain, and cramping, is threatening public health. Tripartite motif-containing 52 (TRIM52) has been reported to play an important role in inflammatory responses via activating the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. However, the causes of IBD need to be elucidated, and the function of TRIM52 in IBD remains unclear. Here, we demonstrated that TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium (DSS)-induced IBD by activating TLR4/NF-κBs pathway. Methods: The colitis model was established on mice through DSS induction. For the TRIM52 knockdown, the mice were infected with a recombinant adenoviral vector expressing sgRNAs targeting TRIM52. RT-qPCR, western blot, and immunohistochemistry were performed to verify TRIM52 expression in DSS-induced IBD. The body weight, disease activity index, colon length, and H&E staining were used to assess the IBD symptoms in mice with TRIM52 knockdown. The inflammatory responses were examined by RT-qPCR and ELISA measuring tumor necrosis factor-α (TNF-α), inter-leukin 6 (IL-6), and interleukin 1β (IL-1β). Furthermore, the pyroptosis in colon tissue was detected by western blot. Finally, the TLR4/NF-κBs pathway activity was also examined by western blot. Results: TRIM52 expression was up-regulated in DSS-induced IBD, and knockdown of TRIM52 could alleviate the symptoms of IBD. TRIM52 knockdown retarded DSS-induced inflammatory response and inhibited DSS-induced pyroptosis in colon tissue. In addition, TRIM52 played a role in activating TLR4/NF-κBs pathway. Conclusion: Knockdown of TRIM52 alleviated inflammation and pyroptosis in IBD by regulating TLR4/NF-κBs pathway. TRIM52 is expected to be a novel diagnostic indicator for IBD and a target of therapeutic treatment (AU)

Thin-Film Transistors from Electrochemically Exfoliated In2Se3 Nanosheets.

The wafer-scale fabrication of two-dimensional (2D) semiconductor thin films is the key to the preparation of large-area electronic devices. Although chemical vapor deposition (CVD) solves this problem to a certain extent, complex processes are required to realize the transfer of thin films from the growth substrate to the device substrate, not to mention its harsh reaction conditions. The solution-based synthesis and assembly of 2D semiconductors could realize the large-scale preparation of 2D semiconductor thin films economically. In this work, indium selenide (In2Se3) nanosheets with uniform sizes and thicknesses were prepared by the electrochemical intercalation of quaternary ammonium ions into bulk crystals. Layer-by-layer (LbL) assembly was used to fabricate scalable and uniform In2Se3 thin films by coordinating In2Se3 with poly(diallyldimethylammonium chloride) (PDDA). Field-effect transistors (FETs) made from a single In2Se3 flake and In2Se3 thin films showed mobilities of 12.8 cm2·V−1·s−1 and 0.4 cm2·V−1·s−1, respectively, and on/off ratios of >103. The solution self-assembled In2Se3 thin films enriches the research on wafer-scale 2D semiconductor thin films for electronics and optoelectronics and has broad prospects in high-performance and large-area flexible electronics.

Fabrication, characterization and photoelectrochemical properties of CdS/CdSe nanofilm co-sensitized ZnO nanorod arrays on Zn foil substrate.

The photoelectrochemical (PEC) performance of ZnO is restricted by its low light absorption ability and high recombination rate of photogenerated carriers. In order to overcome these drawbacks, ZnO/CdS/CdSe heterostructures are prepared on Zn foil substrate using facile three-step methods containing hydrothermal growth, successive ionic layer adsorption reaction (SILAR) and modified chemical bath deposition (CBD). The effects of process parameters containing the number of SILAR cycles of CdS, sensitization sequence of CdS and CdSe, and precursors of CdSe on PEC performance of ZnO/CdS/CdSe heterostructures, and ZnO NRAs on PEC performance of CdS/CdSe co-sensitizer have been scrutinized. Through CdS and CdSe co-sensitization, a layer of CdS/CdSe nanofilm is conformally deposited on ZnO nanorod arrays (NRAs) observed by transmission electron microscopy (TEM). Both the visible-light absorption ability and separation efficiency of photogenerated carriers of ZnO NRAs are significantly enhanced evidenced by UV-vis diffuse reflectance absorption spectra, photoluminescence (PL) spectra and electrochemical impedance spectra. Due to the synergistic effect of ZnO NRAs and CdS/CdSe co-sensitizer, the ZnO/CdS/CdSe heterostructures with five SILAR cycles and one modified CBD cycle (ZnO-CdS5-CdSe) show efficient PEC properties with photocurrent density of 6.244 mA/cm2 at -0.2 V vs Ag/AgCl under light illumination of 100 mW/cm2, which are 57.28 and 4.73 times higher than those of pristine ZnO NRAs and CdS/CdSe clusters, respectively. Moreover, the photoconversion efficiency and incident photon to current conversion efficiency (IPCE) of the ZnO-CdS5-CdSe photoanode reach 4.381% and 80.92%, respectively. The heterostructures based on Zn foil substrate in this study can be a promising candidate for practical PEC application and other applications such as photocatalytic degradation and solar cell due to its low manufacturing cost, large-scale production and efficient PEC ability.

Polymer Knot in Solution near the θ Point.

We study knot effects on polymer dynamics in aqueous solution by dissipative particle dynamics. A methodology to identify the θ point is developed by combining simulation data and analytical methods. Polymer internal motions are investigated systematically by gradually changing solvent quality from a good to poor case. In a good solvent, the knot length grows with fluctuations (breathing stage) and then moves to chain ends (moving stage) to release. Nearby the θ point from the good solvent side, the breathing effect becomes stronger with a weak moving effect. As a result, it is easy for the knot to release because of strong fluctuations in chain conformation. In a poor solvent, both breathing and moving effects are weak. A knot is confined in the chain and suppresses polymer condensation because of the excluded volume effect. Our results are useful for the interpretation of relevant experiments and industrial applications of polymer knots.

Metal-Layer Assisted Growth of Ultralong Quasi-2D MOF Nanoarrays on Arbitrary Substrates for Accelerated Oxygen Evolution.

Controlled growth of metal-organic frameworks (MOFs) nanocrystals on requisite surfaces is highly desired for myriad applications related to catalysis, energy, and electronics. Here, this challenge is addressed by overlaying arbitrary surfaces with a thermally evaporated metal layer to enable the well-aligned growth of ultralong quasi-2D MOF nanoarrays comprising cobalt ions and thiophenedicarboxylate acids. This interfacial engineering approach allows preferred chelation of carboxyl groups in the ligands with the metal interlayers, thereby making possible the fabrication and patterning of MOF nanoarrays on substrates of any materials or morphologies. The MOF nanoarrays grown on porous metal scaffolds demonstrate high electrocatalytic capability for water oxidation, exhibiting a small overpotential of 270 mV at 10 mA cm-2 , or 317 mV at 50 mA cm-2 as well as negligible decay of performance within 30 h. The enhanced performance stems from the improved electron and ion transport in the hierarchical porous nanoarrays consisting of in situ formed oxyhydroxide nanosheets in the electrochemical processes. This approach for mediating the growth of MOF nanoarrays can serve as a promising platform for diverse applications.

PRSS3 is a prognostic marker in invasive ductal carcinoma of the breast.

OBJECTIVE: Serine protease 3 (PRSS3) is an isoform of trypsinogen, and plays an important role in the development of many malignancies. The objective of this study was to determine PRSS3 mRNA and protein expression levels in invasive ductal carcinoma of the breast and normal surrounding tissue samples. RESULTS: Both PRSS3 mRNA and protein levels were significantly higher in invasive ductal carcinoma of the breast tissues than in normal or benign tissues (all P < 0.05). High PRSS3 protein levels were associated with patients' age, histological grade, Her-2 expression level, ki-67 expression, and the 5.0-year survival rate. These high protein levels are independent prognostic markers in invasive ductal carcinoma of the breast. MATERIALS AND METHODS: We used real-time quantitative polymerase chain reactions (N = 40) and tissue microarray immunohistochemistry analysis (N = 286) to determine PRSS3 mRNA and protein expression, respectively. PRSS3 protein levels in invasive ductal carcinoma of the breast tissues were correlated with the clinical characteristics of patients with invasive ductal carcinoma of the breast and their 5.0-year survival rate. CONCLUSIONS: PRSS3 acts as an oncogene in invasive ductal carcinoma of the breast development and progression. This finding implies that detection of PRSS3 expression can be a useful prognosis marker and the targeting of PRSS3 can potentially represent a new strategy for invasive ductal carcinoma of the breast treatment.

The C-terminal amyloidogenic peptide contributes to self-assembly of Avibirnavirus viral protease.

Unlike other viral protease, Avibirnavirus infectious bursal disease virus (IBDV)-encoded viral protease VP4 forms unusual intracellular tubule-like structures during viral infection. However, the formation mechanism and potential biological functions of intracellular VP4 tubules remain largely elusive. Here, we show that VP4 can assemble into tubules in diverse IBDV-infected cells. Dynamic analysis show that VP4 initiates the assembly at early stage of IBDV infection, and gradually assembles into larger size of fibrils within the cytoplasm and nucleus. Intracellular assembly of VP4 doesn't involve the host cytoskeleton, other IBDV-encoded viral proteins or vital subcellular organelles. Interestingly, the last C-terminal hydrophobic and amyloidogenic stretch (238)YHLAMA(243) with two "aggregation-prone" alanine residues was found to be essential for its intracellular self-assembly. The assembled VP4 fibrils show significantly low solubility, subsequently, the deposition of highly assembled VP4 structures ultimately deformed the host cytoskeleton and nucleus, which was potentially associated with IBDV lytic infection. Importantly, the assembly of VP4 significantly reduced the cytotoxicity of protease activity in host cells which potentially prevent the premature cell death and facilitate viral replication. This study provides novel insights into the formation mechanism and biological functions of the Avibirnavirus protease-related fibrils.

Expression and prognostic implications of FOXO3a and Ki67 in lung adenocarcinomas.

To investigate the significance of FOXO3a and Ki67 in human lung adenocarcinomas. Envision immunohistochemical staining and Western blotting were used to examine the protein expression of FOXO3a in 127 cases of human lung adenocarcinoma specimens. The positive rate in lung adenocarcinoma (55.9%) was lower than that in normal tissues (80%). We found that the expression of FOXO3a was closely related with the degree of differentiation, TNM staging, lymph node metastasis and survival. In addition, significant differences in the different pathological types of lung adenocarcinoma cases (P<0.01). The FOXO3a positive rate of the acini as the main type (APA) (86.7%) and the lepidic as the main type (LPA) (82.4%) was higher than the solid as the main type (SPA) (50.0%), the papilla as the main type (PPA) (42.9%) and the micropapilla as the main type (MPA) (9.4%). Moreover, the expression of FOXO3a was negatively related with Ki67 expression. Our results suggested that the expression of FOXO3a is closely correlated with the aggressiveness of lung adenocarcinoma. It was indicated that disregulation of FOXO3a might play key roles in the occurrence and development of lung adenocarcinoma and joint detection of the two markers might play an important role in diagnosing tumors.