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Full-length transcription in the majority of human genes depends on U1 snRNP (U1) to co-transcriptionally suppress transcription-terminating premature 3' end cleavage and polyadenylation (PCPA) from cryptic polyadenylation signals (PASs) in introns. However, the mechanism of this U1 activity, termed telescripting, is unknown. Here, we captured a complex, comprising U1 and CPA factors (U1-CPAFs), that binds intronic PASs and suppresses PCPA. U1-CPAFs are distinct from U1-spliceosomal complexes; they include CPA's three main subunits, CFIm, CPSF, and CstF; lack essential splicing factors; and associate with transcription elongation and mRNA export complexes. Telescripting requires U1:pre-mRNA base-pairing, which can be disrupted by U1 antisense oligonucleotide (U1 AMO), triggering PCPA. U1 AMO remodels U1-CPAFs, revealing changes, including recruitment of CPA-stimulating factors, that explain U1-CPAFs' switch from repressive to activated states. Our findings outline this U1 telescripting mechanism and demonstrate U1's unique role as central regulator of pre-mRNA processing and transcription.
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Núcleo Celular/metabolismo , Fator de Especificidade de Clivagem e Poliadenilação/metabolismo , Clivagem do RNA , Precursores de RNA/biossíntese , RNA Mensageiro/biossíntese , Ribonucleoproteína Nuclear Pequena U1/metabolismo , Transcrição Gênica , Regiões 3' não Traduzidas , Transporte Ativo do Núcleo Celular , Sítios de Ligação , Núcleo Celular/genética , Fator de Especificidade de Clivagem e Poliadenilação/genética , Fator Estimulador de Clivagem/genética , Fator Estimulador de Clivagem/metabolismo , Células HeLa , Humanos , Complexos Multiproteicos , Poli A/metabolismo , Ligação Proteica , Precursores de RNA/genética , RNA Mensageiro/genética , Ribonucleoproteína Nuclear Pequena U1/genéticaRESUMO
DNA double-strand break (DSB) repair via homologous recombination is initiated by end resection. The extent of DNA end resection determines the choice of the DSB repair pathway. Nucleases for end resection have been extensively studied. However, it is still unclear how the potential DNA structures generated by the initial short resection by MRE11-RAD50-NBS1 are recognized and recruit proteins, such as EXO1, to DSB sites to facilitate long-range resection. We found that the MSH2-MSH3 mismatch repair complex is recruited to DSB sites through interaction with the chromatin remodeling protein SMARCAD1. MSH2-MSH3 facilitates the recruitment of EXO1 for long-range resection and enhances its enzymatic activity. MSH2-MSH3 also inhibits access of POLθ, which promotes polymerase theta-mediated end-joining (TMEJ). Collectively, we present a direct role of MSH2-MSH3 in the initial stages of DSB repair by promoting end resection and influencing the DSB repair pathway by favoring homologous recombination over TMEJ.
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Reparo do DNA , Exodesoxirribonucleases , Proteína 2 Homóloga a MutS , Proteína 3 Homóloga a MutS , DNA/metabolismo , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , Exodesoxirribonucleases/metabolismo , Recombinação Homóloga , Proteína 2 Homóloga a MutS/metabolismo , Humanos , Linhagem Celular , DNA Helicases/metabolismo , Proteína 3 Homóloga a MutS/metabolismoRESUMO
Modern semiconductor fabrication is challenged by difficulties in overcoming physical and chemical constraints. A major challenge is the wet etching of dummy gate silicon, which involves the removal of materials inside confined spaces of a few nanometers. These chemical processes are significantly different in the nanoscale and bulk. Previously, electrical double-layer formation, bubble entrapment, poor wettability, and insoluble intermediate precipitation have been proposed. However, the exact suppression mechanisms remain unclear due to the lack of direct observation methods. Herein, we investigate limiting factors for the etching kinetics of silicon with tetramethylammonium hydroxide at the nanoscale by using liquid-phase transmission electron microscopy, three-dimensional electron tomography, and first-principles calculations. We reveal suppressed chemical reactions, unstripping phenomena, and stochastic etching behaviors that have never been observed on a macroscopic scale. We expect that solutions can be suggested from this comprehensive insight into the scale-dependent limiting factors of fabrication.
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The prevalence of head and neck squamous cell carcinoma (HNSCC) has continued to rise for decades. However, drug resistance to chemotherapeutics and relapse, mediated by cancer stem cells (CSCs), remains a significant impediment in clinical oncology to achieve successful treatment. Therefore, we focused on analyzing CSCs in HNSCC and demonstrated the effect of melatonin (Mel) and verteporfin (VP) on SCC-25 cells. HNSCC CSCs were enriched in the reactive oxygen species-low state and in sphere-forming cultures. Combination treatment with Mel and VP decreased HNSCC viability and increased apoptosis without causing significant damage to normal cells. Sphere-forming ability and stem cell population were reduced by co-treatment with Mel and VP, while mitochondrial ROS level was increased by the treatment. Furthermore, the expression of mitophagy markers, parkin and PINK1, was significantly decreased in the co-treated cells. Mel and VP induced mitochondrial depolarization and inhibited mitochondrial function. Parkin/TOM20 was localized near the nucleus and formed clusters of mitochondria in the cells after treatment. Moreover, Mel and VP downregulated the expression of markers involved in epithelial-mesenchymal transition and metastasis. The migration capacity of cells was significantly decreased by co-treatment with Mel and VP, accompanied by the down-regulation of MMP-2 and MMP-9 expression. Taken together, these results indicate that co-treatment with Mel and VP induces mitochondrial dysfunction, resulting in the apoptosis of CSCs. Mel and VP could thus be further investigated as potential therapies for HNSCC through their action on CSCs.
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Neoplasias de Cabeça e Pescoço , Melatonina , Linhagem Celular Tumoral , Humanos , Melatonina/farmacologia , Dinâmica Mitocondrial , Células-Tronco Neoplásicas , Carcinoma de Células Escamosas de Cabeça e Pescoço , VerteporfinaRESUMO
Ubiquitination and deubiquitination of signaling molecules are critical regulatory mechanisms in various biological contexts such as inflammatory signaling and the DNA damage response. Thus, finely tuned regulation of protein ubiquitination is essential for maintaining cellular homeostasis. Here, we showed that the RING finger protein RNF126 interacts with TRAF3 and promotes its K63-linked polyubiquitination, which is a crucial step in the TRAF3-dependent antiviral response. We found that RNF126 also interacts with OTUB1, a deubiquitinating enzyme that negatively regulates K63-linked ubiquitination of TRAF3. RNF126 promotes ubiquitination of OTUB1, leading to reduced deubiquitinating activity toward TRAF3. Moreover, RNF126 promotes ubiquitination of OTUB1 on cysteine 91, which is reportedly required for its catalytic activity. Taken together, our results suggest that RNF126 positively regulates the antiviral response by directly promoting K63-linked polyubiquitination of TRAF3 and by reducing OTUB1 activity.
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Fator 3 Associado a Receptor de TNFRESUMO
Near-field electrospinning (NFES) was developed to overcome the intrinsic instability of traditional electrospinning processes and to facilitate the controllable deposition of nanofibers under a reduced electric field. This technique offers a straightforward and versatile method for the precision patterning of two-dimensional (2D) nanofibers. However, three-dimensional (3D) stacked structures built by NFES have been limited to either micron-scale sizes or special shapes. Herein, we report on a direct-write 3D NFES technique to construct self-aligned, template-free, 3D stacked nanoarchitectures by simply adding salt to the polymer solution. Numerical simulations suggested that the electric field could be tuned to achieve self-aligned nanofibers by adjusting the conductivity of the polymer solution. This was confirmed experimentally by using poly(ethylene oxide) (PEO) solutions containing 0.1-1.0 wt% NaCl. Using 0.1 wt% NaCl, nanowalls with a maximum of 80 layers could be built with a width of 92 ± 3 nm, height of 6.6 ± 0.1 µm, and aspect ratio (height/width) of 72. We demonstrate the 3D printing of nanoskyscrapers with various designs, such as curved "nanowall arrays", nano "jungle gyms," and "nanobridges". Further, we present an application of the 3D stacked nanofiber arrays by preparing transparent and flexible polydimethylsiloxane films embedded with Ag-sputtered nanowalls as 3D nanoelectrodes. The conductivity of the nanoelectrodes can be precisely tuned by adjusting the number of 3D printed layers, without sacrificing transmittance (98.5%). The current NFES approach provides a simple, reliable route to build 3D stacked nanoarchitectures with high-aspect ratios for potential application in smart materials, energy devices, and biomedical applications.
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This article describes an electrochemical method to remove bacterial biofilm from a stainless steel (SS) surface using a potential pulse/reverse pulse technique. This technique employs a periodic waveform that consists of anodic and cathodic pulses. The pulses can effectively strip a thin layer of metal off the SS surface, along with the adherent biofilm, in a saline solution. Not only can the pulses effectively remove biofilm from the SS surface, but they also regenerate the original mirror-like shiny surface. The importance of this electrochemical biofilm removal method is its wide applicability for any types of biofilms. That is, instead of directly removing the biofilm, it removes a very thin layer of the metal under the biofilm. Thus, the removal process is independent to the nature of the biofilms. Furthermore, this electrochemical biofilm removal method is rapid (less than 30 s of potential pulse time) and does not require hazardous chemicals.
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Biofilmes , Técnicas Eletroquímicas/métodos , Eletrodos , Aço Inoxidável , Staphylococcus epidermidisRESUMO
Circulating tumor cells (CTCs) have great potential to provide minimally invasive ways for the early detection of cancer metastasis and for the response monitoring of various cancer treatments. Despite the clinical importance and progress of CTC-based cancer diagnostics, most of the current methods of enriching CTCs are difficult to implement in general hospital settings due to complex and time-consuming protocols. Among existing technologies, size-based isolation methods provide antibody-independent, relatively simple, and high throughput protocols. However, the clogging issues and lower than desired recovery rates and purity are the key challenges. In this work, inspired by antifouling membranes with liquid-filled pores in nature, clog-free, highly sensitive (95.9 ± 3.1% recovery rate), selective (>2.5 log depletion of white blood cells), rapid (>3 mL/min), and label-free isolation of viable CTCs from whole blood without prior sample treatment is achieved using a stand-alone lab-on-a-disc system equipped with fluid-assisted separation technology (FAST). Numerical simulation and experiments show that this method provides uniform, clog-free, ultrafast cell enrichment with pressure drops much less than in conventional size-based filtration, at 1 kPa. We demonstrate the clinical utility of the point-of-care detection of CTCs with samples taken from 142 patients suffering from breast, stomach, or lung cancer.
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Separação Celular/instrumentação , Técnicas Analíticas Microfluídicas/instrumentação , Neoplasias/patologia , Células Neoplásicas Circulantes/patologia , Linhagem Celular Tumoral , Separação Celular/economia , Separação Celular/métodos , Tamanho Celular , Desenho de Equipamento , Humanos , Extração Líquido-Líquido/economia , Extração Líquido-Líquido/instrumentação , Extração Líquido-Líquido/métodos , Técnicas Analíticas Microfluídicas/economia , Técnicas Analíticas Microfluídicas/métodos , Neoplasias/sangue , Fatores de TempoRESUMO
In this Article, we report a coulometric sensing platform that is capable of sensing analytes on a working electrode and providing a visual readout of the analyte concentration on a silver (Ag) band counter electrode in a microchannel. The display mechanism relies on the electro-oxidation of metallic Ag as a complementary reaction to the sensing reduction reaction. The Ag band counter electrode is arranged longitudinally in a microchannel while the frontal tip of the band electrode directly faces a gold (Au) working electrode, which lies across the microchannel. The Ag oxidation always occurs at the band electrode's tip region that faces the working electrode due to the Ohmic potential drop across the solution in the microchannel. The decrement of the Ag electrode, which is clearly measurable with the naked eye, correlates linearly with an analyte concentration (e.g., 0.1-2.5 mM p-benzoquinone) and with an analyte feeding rate (i.e., a sample solution flow rate of 1.0-75.0 µL min(-1)). The platform design is also effective for a model analyte of horseradish peroxidase (HRP)-avidin in the dynamic range of 0.1-3.0 µg mL(-1).
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BACKGROUND: Keloids and hypertrophic scars result from abnormal collagen accumulation and the inhibition of its degradation. Although the pathogenesis remains unclear, excessive accumulation of the extracellular matrix (ECM) is believed to be associated with the TGF-ß/SMAD pathway. Zinc-alpha-2-glycoprotein (ZAG) inhibits TGF-ß-mediated epithelial-to-mesenchymal transdifferentiation and impacts skin barrier functions. In this study, we investigated the potential of a small ZAG-derived peptide against hypertrophic scars and keloids. METHODS: The study examined cell proliferation and mRNA expression of collagen types I and III in human dermal fibroblast (HDF) cell lines and keloid-derived fibroblasts (KF) following ZAG peptide treatment. A rat incisional wound model was used to evaluate the effect of ZAG peptide in scar tissue. RESULTS: Significantly lower mRNA levels of collagen types I and III were observed in ZAG-treated fibroblasts, whereas matrix metalloproteinase (MMP)-1 and MMP-3 mRNA levels were significantly increased in HDFs and KFs. Furthermore, ZAG peptide significantly reduced protein expression of collagen type I and III, TGF-ß1, and p-Smad2/3 complex in KFs. Rat incisional scar models treated with ZAG peptide presented narrower scar areas and reduced immature collagen deposition, along with decreased expression of collagen type I, α-SMA, and p-Smad2/3. CONCLUSION: ZAG peptide effectively suppresses the TGF-ß and p-Smad2/3 pathway and inhibits excessive cell proliferation during scar formation, suggesting its potential therapeutic implications against keloids and hypertrophic scars.
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BACKGROUND/OBJECTIVES: Chronic alcohol consumption causes oxidative stress in the body, which may accumulate excessively and cause a decline in memory; problem-solving, learning, and exercise abilities; and permanent damage to brain structure and function. Consequently, chronic alcohol consumption can cause alcohol-related diseases. MATERIALS/METHODS: In this study, the protective effects of Phyllostachys edulis (Carrière) J. Houz (PE) against alcohol-induced neuroinflammation and cognitive impairment were evaluated using a mouse model. Alcohol (16%, 5 g/kg/day for 6 weeks) and PE (100, 250, and 500 mg/kg/day for 21 days) were administered intragastrically to mice. RESULTS: PE showed a protective effect against memory deficits and cognitive dysfunction caused by alcohol consumption, confirmed through behavioral tests such as the T-maze, object recognition, and Morris water maze tests. Additionally, PE attenuated oxidative stress by reducing lipid oxidation, nitric oxide, and reactive oxygen species levels in the mice's brains, livers, and kidneys. Improvement of neurotrophic factors and downregulation of apoptosis-related proteins were confirmed in the brains of mice fed low and medium concentrations of PE. Additionally, expression of antioxidant enzyme-related proteins GPx-1 and SOD-1 was enhanced in the liver of PE-treated mice, related to their inhibitory effect on oxidative stress. CONCLUSION: This suggests that PE has both neuroregenerative and antioxidant effects. Collectively, these behavioral and histological results confirmed that PE could improve alcohol-induced cognitive deficits through brain neurotrophic and apoptosis protection and modulation of oxidative stress.
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Multifunctional, flexible, and robust thin films capable of operating in demanding harsh temperature environments are crucial for various cutting-edge applications. This study presents a multifunctional Janus film integrating highly-crystalline Ti3C2Tx MXene and mechanically-robust carbon nanotube (CNT) film through strong hydrogen bonding. The hybrid film not only exhibits high electrical conductivity (4250 S cm-1), but also demonstrates robust mechanical strength and durability in both extremely low and high temperature environments, showing exceptional resistance to thermal shock. This hybrid Janus film of 15 µm thickness reveals remarkable multifunctionality, including efficient electromagnetic shielding effectiveness of 72 dB in X band frequency range, excellent infrared (IR) shielding capability with an average emissivity of 0.09 (a minimal value of 0.02), superior thermal camouflage performance over a wide temperature range (- 1 to 300 °C) achieving a notable reduction in the radiated temperature by 243 °C against a background temperature of 300 °C, and outstanding IR detection capability characterized by a 44% increase in resistance when exposed to 250 W IR radiation. This multifunctional MXene/CNT Janus film offers a feasible solution for electromagnetic shielding and IR shielding/detection under challenging conditions.
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This study investigates the effects of drop size and viscosity on spreading dynamics, including response time, maximum velocity, and spreading pattern transition, in response to various DC voltages, based on both experiment and theoretical modeling. It is experimentally found that both switching time (i.e., time to reach maximum wetted radius) and settling time (i.e., time to reach equilibrium radius) are proportional to 1.5th power of the effective base radius. It is also found that the maximum velocity is slightly dependent on drop size but linearly proportional to the electrowetting number. The viscosity effect on drop spreading is investigated by observing spreading patterns with respect to applied voltages, and the critical viscosity at which a spreading pattern changes from under- to overdamped response is obtained. Theoretical models with contact angle hysteresis predict the spreading dynamics of drops with low and high viscosities fairly well. By fitting the theoretical models to experimental results, we obtain the friction coefficient, which is nearly proportional to 0.6th power of viscosity and is rarely influenced by applied voltage and drop size. Finally, we find that drop viscosity has a weak effect on maximum velocity but not a clear one on contact line friction.
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PURPOSE: Obesity, a feature of metabolic syndrome, is a risk factor for cardiovascular disease, and elevated plasma homocysteine is associated with increased cardiovascular risk. However, little published information is available concerning the effect of obesity on homocysteine metabolism. METHODS: Hepatic homocysteine metabolism was determined in male C57BL/6 mice fed a high-fat diet for 12 weeks. RESULTS: High-fat diet increased plasma homocysteine but decreased hepatic homocysteine levels. Hepatic S-adenosylhomocysteine hydrolase levels were down-regulated in the obese mice, which was in part responsible for the decrease in hepatic S-adenosylmethionine/S-adenosylhomocysteine, which served as an index of transmethylation potential. Despite the decrease in hepatic cysteine, hepatic taurine synthesis was activated via up-regulation of cysteine dioxygenase. Hepatic levels of methionine adenosyltransferase I/III, methionine synthase, methylene tetrahydrofolate reductase, and gamma-glutamylcysteine ligase catalytic subunit were unchanged. Obese mice showed elevated betaine-homocysteine methyltransferase and decreased cystathionine beta-synthase activities, although the quantities of these enzymes were unchanged. CONCLUSION: This study suggests that plasma homocysteine level is increased in obesity-associated hepatic steatosis, possibly as a result of increased hepatic homocysteine efflux along with an altered sulfur amino acid metabolism.
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Aminoácidos Sulfúricos/metabolismo , Dieta Hiperlipídica , Homocisteína/sangue , Fígado/efeitos dos fármacos , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/metabolismo , Adenosil-Homocisteinase/genética , Adenosil-Homocisteinase/metabolismo , Animais , Doenças Cardiovasculares/complicações , Cistationina beta-Sintase/genética , Cistationina beta-Sintase/metabolismo , Cisteína Dioxigenase/genética , Cisteína Dioxigenase/metabolismo , Dipeptídeos/genética , Dipeptídeos/metabolismo , Regulação para Baixo , Peroxidação de Lipídeos , Fígado/metabolismo , Masculino , Metionina Adenosiltransferase/genética , Metionina Adenosiltransferase/metabolismo , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Risco , S-Adenosil-Homocisteína/metabolismo , S-Adenosilmetionina/genética , S-Adenosilmetionina/metabolismo , Triglicerídeos/sangue , Regulação para CimaRESUMO
Maintaining and transferring intact genomes from one generation to another plays a pivotal role in all living organisms. DNA damage caused by numerous endogenous and exogenous factors must be adequately repaired, as unrepaired and accumulated DNA mutations can cause severe deleterious effects, such as cell death and cancer. To prevent adverse consequences, cells have established DNA damage response mechanisms that address different forms of DNA damage, including DNA double-strand breaks, mismatches, nucleotide excision, and base excision. Among several sources of exogenous DNA damage, bacterial infections cause inflammation in the host, generating reactive oxygen species (ROS) and causing oxidative DNA damage. Recent studies have revealed the importance of the oral microbiome in inflammation and several systemic host diseases. Dysbiosis of oral bacteria can induce chronic inflammation, which enhances ROS-induced DNA damage, and improperly repaired damage can lead to carcinogenesis. This review describes the various DNA repair pathways that are affected by chronic inflammation and the discovery of the DNA damage response induced by oral bacteria such as Porphyromonas gingivalis and Fusobacterium nucleatum.
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BACKGROUND: Peri-implantitis is similar to periodontitis, but there are some differences. For the effective control of peri-implantitis, it is necessary to clarify its similarities and differences with periodontitis in terms of gene expression. METHODS: This cross-sectional study included 20 participants (10 healthy subjects and 10 patients with periodontitis and peri-implantitis). Gingival tissue samples (10 healthy, 10 periodontitis, and 10 peri-implantitis tissues) were collected, RNAs were extracted, and RNA sequencing and analysis were performed. RESULTS: Differentially expressed gene (DEG) analysis identified 757 upregulated and 159 downregulated genes common between periodontitis and peri-implantitis. Periodontitis tissues uniquely showed 186 overexpressed and 22 suppressed genes compared with peri-implantitis and healthy tissues, while peri-implantitis had 1974 and 642, respectively. Each common and unique differential gene set showed distinct enriched biological features between periodontitis and peri-implantitis after the pathway enrichment analysis. The expression pattern of selected DEGs focused on the representability of the disease was validated by RT-qPCR. CONCLUSIONS: Although periodontitis and peri-implantitis showed common gene expression that was clearly differentiated from healthy conditions, there were also unique gene patterns that were differentially expressed only in peri-implantitis. These findings will help elucidate the mechanisms involved in the progression of peri-implantitis.
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Ti3C2Tx MXene, a two-dimensional transition metal carbide, has attracted substantial interest due to its unique physical properties and a wide range of potential applications. Although the properties of devices using MXene have been substantially enhanced in recent years, it is not fully understood how the oxygen concentration in Ti3AlC2 MAX affects oxide formation in Ti3C2-based MXene nanosheets and their fundamental properties. To this end, we compared two types of MAX phases: MAX with low oxygen content (LO-MAX) and MAX synthesized by a conventional process. Since the conventional MAX synthesis employs metal (Ti) as a primary material, it is referred to as metal-based MAX (MB-MAX) from here. The oxygen content of the LO-MAX was only 0.56 wt %, which was about 20% compared to that of MAX synthesized using conventional methods. We compared the properties of MXene nanosheets prepared from the LO-MAX with MXene nanosheets obtained from the MB-MAX. Microscopic and chemical analyses revealed smooth and wrinkle-free morphology and small amounts of oxygen in MXene nanosheets prepared from LO-MAX (LO-MXene). The LO-MXene nanosheet film exhibited an exceptionally high conductivity of 10,540 S/cm and an ultralow surface roughness of 1.7 nm, which originated from inhibited surface oxide formation. Moreover, the inhibition of oxide formation strengthened the function of -O or -OH groups on the surface of MXene, thereby facilitating strong hydrogen bonding to the polymer with hydroxyl groups. To clearly reveal these properties, we prepared a pressure sensor by coating these MXene nanosheets on nylon/polyester fibers. The fabricated sensor exhibited a high sensitivity of up to 85.6/kPa and excellent stretch stability and reliability. These results clearly revealed that lowering the oxygen content in MAX can make a decisive contribution to improving the fundamental properties of MXene nanosheets prepared therefrom.
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Since the first description of the keystone perforator island flap (KPIF) in 2003, several modifications have been suggested to enhance its coverage ability. However, locoregional flaps have limited its use in chronic wounds due to decreased elasticity around the defect. We investigated the use of a bipedicled KPIF (bKPIF), which covers a defect while completely elevating the median part of the flap from the fascia. A retrospective chart review of 20 consecutive patients who underwent classical type I KPIF (n = 10) or bKPIF (n = 10) reconstruction from June 2020 to December 2022 was performed. Baseline characteristics, indications, operative details, healing time, and complications were analyzed and compared between the two groups. The average defect size was 30 cm2 in type I KPIF and 36.6 cm2 in bKPIF, and an average flap size of 86.5 cm2 was covered in type I KPIF, larger than bKPIF at 73.8 cm2. The flap/defect ratio was significantly lower in the bKPIF group (p < 0.02), with an average of only 55% pedicular area. The average advancement distance in the bKPIF group was 1.85 cm (standard deviation 0.78) greater than that in the type 1 KPIF group. There was no significant difference between the groups in terms of operation time, complete healing time, and complications. All ten bKPIFs were successful without any flap necrosis. Even though the mean pedicular area in the bKPIF group was nearly half compared with that in the type I KPIF group, it was sufficient to perfuse the entire flap without any major complications. This novel technique using bKPIF has potential clinical relevance, as evidenced by the enhanced ability to cover chronic defects with severe scarring. Lateralizing the hotspots to the bilateral corners of the flap is the mechanism that facilitates this potential.
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Retalho Perfurante , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Humanos , Estudos Retrospectivos , Cicatrização , Retalho Perfurante/cirurgia , Lesões dos Tecidos Moles/cirurgia , Resultado do TratamentoRESUMO
MXenes are an emerging class of 2D materials with unique properties including metallic conductivity, mechanical flexibility, and surface tunability, which ensure their utility for diverse applications. However, the synthesis of MXenes with high crystallinity and atomic stoichiometry in a low-cost process is still challenging because of the difficulty in controlling the oxygen substitute in the precursors and final products of MXenes, which limits their academic understanding and practical applications. Here, a novel cost-effective method is reported to synthesize a highly crystalline and stoichiometric Ti3 C2 Tx MXene with minimum substitutional oxygen impurities by controlling the amount of excess carbon and time of high-energy milling in carbothermal reduction of recycled TiO2 source. The highest used content (2 wt%) of excess-carbon yields TiC with the highest carbon content and minimal oxygen substitutes, which leads to the Ti3 AlC2 MAX phase with improved crystallinity and atomic stoichiometry, and finally Ti3 C2 Tx MXene with the highest electrical conductivity (11738 S cm-1 ) and superior electromagnetic shielding effectiveness. Additionally, the effects of carbon content and substitutional oxygen on the physical properties of TiC and Ti3 AlC2 are elucidated by density-functional-theory calculations. This inexpensive TiO2 -based method of synthesizing high-quality Ti3 C2 Tx MXene can facilitate large-scale production and thus accelerate global research on MXenes.
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N6-methyladenosine (m6A) modification in RNA affects various aspects of RNA metabolism and regulates gene expression. This modification is modulated by many regulatory proteins, such as m6A methyltransferases (writers), m6A demethylases (erasers), and m6A-binding proteins (readers). Previous studies have suggested that alterations in m6A regulatory proteins induce genome-wide alternative splicing in many cancer cells. However, the functional effects and molecular mechanisms of m6A-mediated alternative splicing have not been fully elucidated. To understand the consequences of this modification on RNA splicing in cancer cells, we performed RNA sequencing and analyzed alternative splicing patterns in METTL3-knockdown osteosarcoma U2OS cells. We detected 1,803 alternatively spliced genes in METTL3-knockdown cells compared to the controls and found that cell cycle-related genes were enriched in differentially spliced genes. A comparison of the published MeRIP-seq data for METTL14 with our RNA sequencing data revealed that 70-87% of alternatively spliced genes had an m6A peak near 1 kb of alternative splicing sites. Among the 19 RNA-binding proteins enriched in alternative splicing sites, as revealed by motif analysis, expression of SFPQ highly correlated with METTL3 expression in 12,839 TCGA pan-cancer patients. We also found that cell cycle-related genes were enriched in alternatively spliced genes of other cell lines with METTL3 knockdown. Taken together, we suggest that METTL3 regulates m6A-dependent alternative splicing, especially in cell cycle-related genes, by regulating the functions of splicing factors such as SFPQ.