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Molybdenum (Mo) is a rare and important element extensively utilised in aerospace, radar communications, optoelectronic devices, and the military. This study proposes an environmentally friendly physical method based on photon-phonon resonance absorption for the separation of Mo from sodium molybdate (Na2MoO4). We examined the vibrational spectrum of Na2MoO4 using the CASTEP code, employing first-principles density functional theory. Through dynamic process analysis, we analysed the vibrational modes and assigned peaks corresponding to experimental infrared (IR) and Raman data. We focused on the vibrational modes associated with Mo and identified that the highest-intensity IR-active peak at 858 cm-1 corresponded to Mo-O bond asymmetric stretching. Therefore, we propose the use of a high-power terahertz laser at ~25 THz to facilitate the separation of Mo from Na2MoO4. Experimental investigations are expected in the future.
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In the field of wireless strain monitoring, it is difficult for the traditional metal-made antenna sensor to conform well with steel structures and monitor large strain deformation. To solve this problem, this study proposes a flexible antenna strain sensor based on a ductile graphene film, which features a 6.7% elongation at break and flexibility due to the microscopic wrinkle structure and layered stacking structure of the graphene film. Because of the use of eccentric embedding in the feeding form, the sensor can be miniaturized and can simultaneously monitor strain in two directions. The sensing mechanism of the antenna is analyzed using a void model, and an antenna is designed based on operating frequencies of 3 GHz and 3.5 GHz. The embedding size is optimized using a Smith chart and impedance matching principle. Both the simulation and experimental results verify that the resonant frequency and strain magnitude are linearly inversely proportional. The experimental results show that the strain sensitivity is 1.752 kHz/µÎµ along the geometric length and 1.780 kHz/µÎµ along the width, with correlation coefficients of 0.99173 and 0.99295, respectively.
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Methanol is a valuable liquid C1 product in CO2 electroreduction (CO2ER); however, it is hard to achieve high selectivity and a large current density simultaneously. In this work, we construct Mn2+-doped VS2 multilayer nanowafers applied in a flow cell to yield methanol as a single liquid product to tackle this challenge. Mn doping adjusts the electronic structure of VS2 and concurrently introduces sulfur vacancies, forming a critical *COB intermediate and facilitating its sequential hydrogenation to methanol. The optimal Mn4.8%-VS2 exhibits methanol Faradic efficiencies of more than 60% over a wide potential range of -0.4 to -0.8 V in a flow cell, of which the maximal value is 72.5 ± 1.1% at -0.6 V along with a partial current density of 74.3 ± 1.1 mA cm-2. This work opens an avenue to rationally design catalysts for engineering C1 intermediates toward CO2ER to a single liquid methanol in a flow cell.
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Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The development of novel scaffolds for human monoamine oxidase B (hMAO-B) inhibitors with reversible properties represents an important strategy to improve the efficacy and safety for PD treatment. In the current work, we have devised and assessed two innovative derivative series serving as hMAO-B inhibitors. These series have utilized benzimidazole as a scaffold and strategically incorporated a primary amide group, which is recognized as a pivotal pharmacophore in subsequent activity screening and reversible mode of action. Among these compounds, 16d has emerged as the most potent hMAO-B inhibitor with an IC50 value of 67.3 nM, comparable to safinamide (IC50 = 42.6 nM) in vitro. Besides, 16d demonstrated good selectivity towards hMAO-B isoenzyme with a selectivity index over 387. Importantly, in line with the design purpose, 16d inhibited hMAO-B in a competitive and reversible manner (Ki = 82.50 nM). Moreover, 16d exhibited a good safety profile in both cellular and acute toxicity assays in mice. It also displayed ideal pharmacokinetic properties and blood-brain barrier permeability in vivo, essential prerequisites for central nervous system medicines. In the MPTP-induced PD mouse model, 16d significantly alleviated the motor impairment, especially muscle relaxation and motor coordination. Therefore, 16d, serving as a lead compound, holds instructive significance for subsequent investigations regarding its application in the treatment of PD.
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Bencimidazoles , Descubrimiento de Drogas , Inhibidores de la Monoaminooxidasa , Monoaminooxidasa , Enfermedad de Parkinson , Inhibidores de la Monoaminooxidasa/farmacología , Inhibidores de la Monoaminooxidasa/química , Inhibidores de la Monoaminooxidasa/síntesis química , Monoaminooxidasa/metabolismo , Humanos , Animales , Relación Estructura-Actividad , Ratones , Bencimidazoles/química , Bencimidazoles/farmacología , Bencimidazoles/síntesis química , Enfermedad de Parkinson/tratamiento farmacológico , Estructura Molecular , Relación Dosis-Respuesta a Droga , Masculino , Ratones Endogámicos C57BL , Antiparkinsonianos/farmacología , Antiparkinsonianos/síntesis química , Antiparkinsonianos/química , Antiparkinsonianos/uso terapéuticoRESUMEN
Diabetic cardiomyopathy is a specific type of cardiomyopathy. In DCM, glucose uptake and utilization are impaired due to insulin deficiency or resistance, and the heart relies more heavily on fatty acid oxidation for energy, resulting in myocardial lipid toxicity-related injury. MARK4 is a member of the AMPK-related kinase family, and improves ischaemic heart failure through microtubule detyrosination. However, the role of MARK4 in cardiac regulation of metabolism is unclear. In this study, after successful establishment of a diabetic cardiomyopathy model induced by streptozotocin and a high-fat diet, MARK4 expression was found to be significantly increased in STZ-induced DCM mice. After AAV9-shMARK4 was administered through the tail vein, decreased expression of MARK4 alleviated diabetic myocardial damage, reduced oxidative stress and apoptosis, and facilitated cardiomyocyte mitochondrial fusion, and promoted myocardial lipid oxidation metabolism. In addition, through the RNA-seq analysis of differentially expressed genes, we found that MARK4 deficiency promoted lipid decomposition and oxidative metabolism by downregulating the expression of ACSL4, thus reducing myocardial lipid accumulation in the STZ-induced DCM model.
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Coenzima A Ligasas , Cardiomiopatías Diabéticas , Metabolismo de los Lípidos , Miocardio , Animales , Masculino , Ratones , Apoptosis , Coenzima A Ligasas/metabolismo , Coenzima A Ligasas/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicaciones , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/patología , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/etiología , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Estrés Oxidativo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , EstreptozocinaRESUMEN
Platelet-rich fibrin, a classical autologous-derived bioactive material, consists of a fibrin scaffold and its internal loading of growth factors, platelets, and leukocytes, with the gradual degradation of the fibrin scaffold and the slow release of physiological doses of growth factors. PRF promotes vascular regeneration, promotes the proliferation and migration of osteoblast-related cells such as mesenchymal cells, osteoblasts, and osteoclasts while having certain immunomodulatory and anti-bacterial effects. PRF has excellent osteogenic potential and has been widely used in the field of bone tissue engineering and dentistry. However, there are still some limitations of PRF, and the improvement of its biological properties is one of the most important issues to be solved. Therefore, it is often combined with bone tissue engineering scaffolds to enhance its mechanical properties and delay its degradation. In this paper, we present a systematic review of the development of platelet-rich derivatives, the structure and biological properties of PRF, osteogenic mechanisms, applications, and optimization to broaden their clinical applications and provide guidance for their clinical translation.
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Electrocatalytic CO2 reduction reaction (CO2RR) to ethanol has been widely researched for potential commercial application. However, it still faces limited selectivity at a large current density. Herein, Mo4+-doped CuS nanosheet-assembled hollow spheres are constructed to address this issue. Mo4+ ion doping modifies the local electronic environments and diversifies the binding sites of CuS, which increases the coverage of linear *COL and produces bridge *COB for subsequent *COL-*COH coupling toward ethanol production. The optimal Mo9.0%-CuS can electrocatalyze CO2 to ethanol with a faradaic efficiency of 67.5% and a partial current density of 186.5 mA cm-2 at -0.6 V in a flow cell. This work clarifies that doping high valence transition metal ions into Cu-based sulfides can regulate the coverage and configuration of related intermediates for ethanol production during the CO2RR in a flow cell.
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The issue of water scarcity has drawn attention from all over the world. The coordination of the interaction between ecological and environmental development of water sources and socio-economic development is currently an essential issue that needs to be solved in order to safeguard the water resources environment for human survival. In this essay, we suggest a paradigm for assessing the sustainable exploitation of water resources. First, three ecological, economic, and social factors are investigated. Twenty essential evaluation indexes are then constructed using the Delphi approach, along with an index system for assessing the potential of water sources for sustainable development. The weights of each evaluation index were then determined using the combination assignment approach, which was then suggested. The coupled degree evaluation model of the capability for sustainable development of water sources was then developed. In order to confirm the viability and validity of the suggested model, the model was used to assess the Liwu River water source's capacity for sustainable growth in the context of the South-North Water Transfer in Shandong, China. It is believed that the aforementioned study would serve as a helpful resource when evaluating the capacity of water sources for sustainable development.
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Conservación de los Recursos Naturales , Desarrollo Sostenible , Humanos , Agua , Recursos Hídricos , China , Desarrollo Económico , CiudadesRESUMEN
Physically unclonable functions (PUFs) are crucial for enhancing cybersecurity by providing unique, intrinsic identifiers for electronic devices, thus ensuring their authenticity and preventing unauthorized cloning. The SRAM-PUF, characterized by its simple structure and ease of implementation in various scenarios, has gained widespread usage. The soft-decision Reed-Muller (RM) code, an error correction code, is commonly employed in these designs. This paper introduces the design of an RM code soft-decision attack algorithm to reveal its potential security risks. To address this problem, we propose a soft-decision SRAM-PUF structure based on the elliptic curve digital signature algorithm (ECDSA). To improve the processing speed of the proposed secure SRAM-PUF, we propose a custom ECDSA scheme. Further, we also propose a universal architecture for the critical operations in ECDSA, elliptic curve scalar multiplication (ECSM), and elliptic curve double scalar multiplication (ECDSM) based on the differential addition chain (DAC). For ECSMs, iterations can be performed directly; for ECDSMs, a two-dimensional DAC is constructed through precomputation, followed by iterations. Moreover, due to the high similarity of ECSM and ECDSM data paths, this universal architecture saves hardware resources. Our design is implemented on a field-programmable gate array (FPGA) and an application-specific integrated circuit (ASIC) using a Xilinx Virtex-7 and an TSMC 40 nm process. Compared to existing research, our design exhibits a lower bit error rate (2.7×10-10) and better area-time performance (3902 slices, 6.615 µs ECDSM latency).
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5-Aminolevulinic acid (ALA) and its derivatives, serving as the endogenous precursor of the photosensitizer (PS) protoporphyrin IX (PpIX), successfully applied in tumor imaging and photodynamic therapy (PDT). ALA and its derivatives have been used to treat actinic keratosis (AK), basal cell carcinoma (BCC), and improve the detection of superficial bladder cancer. However, the high hydrophilicity of ALA and the conversion of PpIX to heme have limited the accumulation of PpIX, hindering the efficiency and potential application of ALA-PDT. This study aims to evaluate the PDT activity of three rationally designed series of ALA-HPO prodrugs, which were based on enhancing the lipophilicity of the prodrugs and reducing the labile iron pool (LIP) through HPO iron chelators to promote PpIX accumulation. Twenty-four ALA-HPO conjugates, incorporating amide, amino acid, and ester linkages, were synthesized. Most of the conjugates, exhibited no dark-toxicity to cells, according to bioactivity evaluation. Ester conjugates 19a-g showed promoted phototoxicity when tested on tumor cell lines, and this increased phototoxicity was strongly correlated with elevated PpIX levels. Among them, conjugate 19c emerged as the most promising (HeLa, IC50 = 24.25 ± 1.43 µM; MCF-7, IC50 = 43.30 ± 1.76 µM; A375, IC50 = 28.03 ± 1.00 µM), displaying superior photodynamic anticancer activity to ALA (IC50 > 100 µM). At a concentration of 80 µM, the fluorescence intensity of PpIX induced by compound 19c in HeLa, MCF-7, and A375 cells was 18.9, 5.3, and 2.8 times higher, respectively, than that induced by ALA. In conclusion, cellular phototoxicity showed a strong correlation with intracellular PpIX fluorescence levels, indicating the potential application of ALA-HPO conjugates in ALA-PDT.
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Ácido Aminolevulínico , Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Fotoquimioterapia , Fármacos Fotosensibilizantes , Humanos , Ácido Aminolevulínico/farmacología , Ácido Aminolevulínico/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Relación Estructura-Actividad , Estructura Molecular , Piridonas/farmacología , Piridonas/química , Piridonas/síntesis química , Línea Celular Tumoral , Protoporfirinas/química , Protoporfirinas/farmacología , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Supervivencia Celular/efectos de los fármacos , Profármacos/farmacología , Profármacos/química , Profármacos/síntesis químicaRESUMEN
PtII based organometallic photosensitizers (PSs) have emerged as novel potent photodynamic inactivation (PDI) reagents through their enhanced intersystem crossing (ISC) processes. Currently, few PtII PSs have been investigated as antibacterial materials, with relatively poor performances reported and with structure-activity relationships not well described. Herein, a pair of configurational isomers are reported of Bis-BODIPY (4,4-difluoro-boradizaindacene) embedded PtII PSs. The cis-isomer (cis-BBP) displayed enhanced 1O2 generation and better bacterial membrane anchoring capability as compared to the trans-isomer (trans-BBP). The effective PDI concentrations (efficiency > 99.9%) for cis-BBP in Acinetobacter baumannii (multi-drug resistant (MDR)) and Staphylococcus aureus are 400 nM (12 J cm-2) and 100 nM (18 J cm-2), respectively; corresponding concentrations and light doses for trans-BBP in the two bacteria are 2.50 µM (30 J cm-2) and 1.50 µM (18 J cm-2), respectively. The 50% and 90% minimum inhibitory concentration (MIC50 and MIC90) ratio of trans-BBP to cis-BBP is 22.22 and 24.02 in A. baumannii (MDR); 21.29 and 22.36 in methicillin resistant S. aureus (MRSA), respectively. Furthermore, cis-BBP displays superior in vivo antibacterial performance, with acceptable dark and photoinduced cytotoxicity. These results demonstrate cis-BBP is a robust light-assisted antibacterial reagent at sub-micromolecular concentrations. More importantly, configuration of PtII PSs should be an important issue to be considered in further PDI reagents design.
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Staphylococcus aureus Resistente a Meticilina , Fármacos Fotosensibilizantes/farmacología , Relación Estructura-Actividad , Antibacterianos/farmacologíaRESUMEN
Coarse columnar grains and heterogeneously distributed phases commonly form in metallic alloys produced by three-dimensional (3D) printing and are often considered undesirable because they can impart nonuniform and inferior mechanical properties. We demonstrate a design strategy to unlock consistent and enhanced properties directly from 3D printing. Using Ti-5Al-5Mo-5V-3Cr as a model alloy, we show that adding molybdenum (Mo) nanoparticles promotes grain refinement during solidification and suppresses the formation of phase heterogeneities during solid-state thermal cycling. The microstructural change because of the bifunctional additive results in uniform mechanical properties and simultaneous enhancement of both strength and ductility. We demonstrate how this alloy can be modified by a single component to address unfavorable microstructures, providing a pathway to achieve desirable mechanical characteristics directly from 3D printing.
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This paper presents an FPGA-based lightweight and real-time infrared image processor based on a series of hardware-oriented lightweight algorithms. The two-point correction algorithm based on blackbody radiation is introduced to calibrate the non-uniformity of the sensor. With precomputed gain and offset matrices, the design can achieve real-time non-uniformity correction with a resolution of 640×480. The blind pixel detection algorithm employs the first-level approximation to simplify multiple iterative computations. The blind pixel compensation algorithm in our design is constructed on the side-window-filtering method. The results of eight convolution kernels for side windows are computed simultaneously to improve the processing speed. Due to the proposed side-window-filtering-based blind pixel compensation algorithm, blind pixels can be effectively compensated while details in the image are preserved. Before image output, we also incorporated lightweight histogram equalization to make the processed image more easily observable to the human eyes. The proposed lightweight infrared image processor is implemented on Xilinx XC7A100T-2. Our proposed lightweight infrared image processor costs 10,894 LUTs, 9367 FFs, 4 BRAMs, and 5 DSP48. Under a 50 MHz clock, the processor achieves a speed of 30 frames per second at the cost of 1800 mW. The maximum operating frequency of our proposed processor can reach 186 MHz. Compared with existing similar works, our proposed infrared image processor incurs minimal resource overhead and has lower power consumption.
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Additive manufacturing (AM), known as 3D printing, enables rapid fabrication of geometrically complex copper (Cu) components for electrical conduction and heat management applications. However, pure Cu or Cu alloys produced by 3D printing often suffer from either low strength or low conductivity at room and elevated temperatures. Here, we demonstrate a design strategy for 3D printing of high strength, high conductivity Cu by uniformly dispersing a minor portion of lanthanum hexaboride (LaB6) nanoparticles in pure Cu through laser powder bed fusion (L-PBF). We show that trace additions of LaB6 to pure Cu results in an improved L-PBF processability, an enhanced strength, an improved thermal stability, all whilst maintaining a high conductivity. The presented strategy could expand the applicability of 3D printed Cu components to more demanding conditions where high strength, high conductivity and thermal stability are required.
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Zero-valent iron (ZVI) has been extensively studied for its efficacy in removing heavy metals, nitrate, and chlorinated organic compounds from contaminated water. However, its limited effectiveness due to rapid passivation and poor selectivity is prompting for alternative solutions, such as the use of aluminium alloys. In this study, the efficacy of five distinct aluminium alloys, namely Al-Mg, Al-Fe, Al-Cu, and Al-Ni, each comprising 50 % Al by mass at a concentration of 10 g/L, was assessed using copper, nitrate and trichloromethane (TCM) as model contaminants. Results show that chemical pollutants reacted immediately with Al-Mg. On the contrary, the remaining three alloys exhibited a delay of 24 h before demonstrating significant reactivity. Remarkably, Al-Mg alloy reduced nitrate exclusively to ammonium, indicating minimal preference for nitrate reduction to N2. In contrast, the Al-Cu, Al-Ni, and Al-Fe alloys exhibited N2 selectivity of 3 %, 5 %, and 19 %, respectively. The removal efficiency of copper, nitrate and TCM reached 99 % within 24 h, 95 % within 48h and 48 % within 48h, respectively. Noteworthy findings included the correlation between Fe concentration within the Al-Fe alloy and an increased N2 selectivity from 9.3 % to 24.1 %. This resulted in an increase of Fe concentration from 10 % to 58 % albeit with a concurrent reduction in reactivity. Cu2+ removal by Al-Fe alloy occurred via direct electron transfer, while the removal of nitrate and TCM was facilitated by atomic hydrogen generated by the alloy's hydrolysis. Intriguingly, nitrate and TCM suppressed Cu2+ reduction, whereas Cu2+ improved nitrate reduction and TCM degradation. These findings demonstrate the great potential of Al-Mg and Al-Fe alloys as highly efficient agents for water remediation.
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We aimed to study the effects of different extensive confluent necrosis on complete biochemical remission, side effects of immunosuppressants, and outcomes in patients with autoimmune hepatitis (AIH). Patients with liver biopsy, receiving standard immunosuppressive therapy (IST), and regular follow-up were retrospectively recruited. Demographic and clinicopathological characteristics between Ishak confluent necrosis scores ≤4 (the non-severe AIH group) and ≥5 (the severe AIH group) were compared. The Kaplan-Meier Survival analysis, Cox regression analysis, and log-rank test were performed. Bilateral p<0.05 was considered statistical significance. One hundred and forty-two patients were enrolled, the median age was 56.0, and 83.8% were female. There were no significant differences in aminotransferases and immunological markers between the two groups. Patients in the severe AIH group had significantly worse liver synthetic function, a higher proportion of cirrhosis, and histologically a higher degree of portal inflammation, interface hepatitis, fibrosis stage, and a higher histological activity index score (all p<0.05). Patients in the severe AIH group had a lower response than the other group after four weeks (57.1% vs. 86.3%, p=0.002). However, differences in complete biochemical remission (CBR) were insignificant. Eight patients experienced end-point events. Kaplan-Meier survival analysis showed no significant difference between the two groups (p=0.343). For adverse effects of IST, patients in the severe group tended toward a higher incidence of corticosteroid adverse effects without statistical significance. Our study indicated that patients with histologically severe confluent necrosis (Ishak score≥5) had significantly worse liver synthetic function and a higher degree of liver fibrosis before IST. Compared with their counterparts, this subgroup of patients showed delayed biochemical response but eventually comparable CBRs, side effects, and long-term outcomes.
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Hepatitis Autoinmune , Inmunosupresores , Hígado , Necrosis , Humanos , Femenino , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/patología , Masculino , Persona de Mediana Edad , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Estudios Retrospectivos , Adulto , Hígado/patología , Hígado/efectos de los fármacos , Anciano , Resultado del Tratamiento , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: In order to provide accurate and reliable image guidance for augmented reality (AR) spinal surgery navigation, a spatial registration method has been proposed. METHODS: In the AR spinal surgery navigation system, grayscale-based 2D/3D registration technology has been used to register preoperative computed tomography images with intraoperative X-ray images to complete the spatial registration, and then the fusion of virtual image and real spine has been realised. RESULTS: In the image registration experiment, the success rate of spine model registration was 90%. In the spinal model verification experiment, the surface registration error of the spinal model ranged from 0.361 to 0.612 mm, and the total average surface registration error was 0.501 mm. CONCLUSION: The spatial registration method based on 2D/3D registration technology can be used in AR spinal surgery navigation systems and is highly accurate and minimally invasive.
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BACKGROUND: BRD4, belonging to the bromodomain extra-terminal (BET) protein family, plays a unique role in tumor progression. However, the potential impact of BRD4 in ameloblastoma (AM) remains largely unknown. Herein, we aimed to assess the expression and functional role of BRD4 in AM. METHODS: The expression level of BRD4 was assessed by immunohistochemistry. The proliferation, migration, invasion, and tumorigenic abilities of AM cells were assessed by a series of assays. To explore the molecular expression profile of BRD4-depleted AM cells, RNA sequencing (RNA-seq) was performed. Bioinformatic analysis was performed on AM expression matrices obtained from the Gene Expression Omnibus (GEO). The therapeutic efficacy of BET-inhibitors (BETi) was assessed with AM patient-derived organoids. RESULTS: Upregulation of BRD4 was observed in conventional AMs, recurrent AMs, and ameloblastic carcinomas. Depletion of BRD4 inhibited proliferation, invasion, migration, and tumorigenesis in AM. Administration of BETi attenuated the aggressiveness of AM and the growth of AM patient-derived organoids. Bioinformatic analysis indicated that BRD4 may promote AM progression by regulating the Wnt pathway and stemness-associated pathways. CONCLUSION: BRD4 increases the aggressiveness and promotes the recurrence of ameloblastoma by regulating the Wnt pathway and stemness-associated pathways. These findings highlight BRD4 as a promising therapeutic target in AM management.
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BACKGROUND: Studies have shown that aluminum (Al) is one of the environmental risk factors leading to Alzheimer's disease (AD), and Al exposure can cause elevated levels of BACE1mRNA, ß-secretase (BACE1), and amyloid beta (Aß) in vivo and in vitro. Previous studies by our research group have shown that this is partly caused by the negative regulation of BACE1 by miRNA29a/b1 (miR29a/b1). Despite the observed the role of nuclear factor kappa B (NF-κB) on many miRNAs, the upstream regulation of NF-κB protein on miR29 remains poorly understood. The purpose of this study was to better define the relationship between NF-κB and miR29a/b1 and the potentially relevant signaling pathways. METHODS: On the one hand, we constructed the animal model of Al exposure by the intraperitoneal injection of aluminum-maltolate (Al(mal)3) in rats. Conversely, NF- κB inhibitors were added to adrenal phaeochromocytoma (PC12) cells exposed to Al(mal)3. RESULTS: We verified that NF-κB shows an increasing trend with Al accumulation in the brain of rats, which is accompanied by a downward trend of miR29a/b1. Notably, the suppression of NF-κB significantly increased miR29a/b1 and affected the expression of BACE1mRNA and downstream proteins. CONCLUSION: Al-induced NF-κB can negatively regulate the expression of miR29a/b1, which then significantly enhances the expression of BACE1 and Aß plaques.
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Péptidos beta-Amiloides , FN-kappa B , Ratas , Animales , FN-kappa B/metabolismo , Péptidos beta-Amiloides/metabolismo , Secretasas de la Proteína Precursora del Amiloide/genética , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Aluminio/farmacología , Aluminio/metabolismo , Regulación hacia Abajo , Ácido Aspártico Endopeptidasas/genética , Ácido Aspártico Endopeptidasas/metabolismoRESUMEN
Objective. There has been a considerable amount of computer-aided diagnosis (CAD) methods highlighted in the field of ultrasonic examination (USE) of thyroid nodules. However, few researches focused on the automatic risk classification, which was the basis for determining whether fine needle aspiration (FNA) was needed. The aim of this work was to implement automatic risk level assessment of thyroid nodules.Approach. Firstly, 1862 cases of thyroid nodules with the results of USE and FNA were collected as the dataset. Then, an improved U-Net++ model was utilized for segmenting thyroid nodules in ultrasound images automatically. Finally, the segmentation result was imported into a multi-task convolutional neural network (MT-CNN), the design of which was based on the clinical guideline called KWAK TI-RADS. Apart from the category of benign and malignant, the MT-CNN also exported the classification result of four malignant features, solid component (SC), hypoechogenicity or marked hypoechogenicity (HMH), microlobulated or irregular margin (MIM), microcalcification (MC), which were used for counting the risk level in KWAK TI-RADS.Main results. The performance of the improved U-Net++ was evaluated on our test set, including 302 cases. The Dice coefficient and intersection over union reached 0.899, 0.816, respectively. The classification accuracy rates of SC, HMH, MIM, MC, were 94.5%, 92.8%, 86.1%, 88.9%, while the false positive (FP) rate was 6.0%, 5.6%, 10.6%, 12.9% respectively. As for the category of benign and malignant, the precision and recall rates were 93.7% and 94.4%.Significance. The proposed CAD method showed favourable performance in the diagnosis of thyroid nodules. Compared with other methods, it could provide reports closer to clinical practice for doctors.