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1.
Bioorg Med Chem Lett ; 112: 129915, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39127242

RESUMO

Many reports have shown that stabilization of secondary structure by stapling functional peptides enhances the intracellular bioactivity. However, no report has discussed the correlation between stabilization and biological activity based on the configuration of amino acid residues used as anchors for stapling. To clarify this, we investigated the helix content and apoptotic efficiency of an apoptosis-inducing peptide, Bim, and four stapled Bim peptides containing stapling-related Cys residues introduced with different configurations within the sequence. The results demonstrated that the configuration of Cys residues in stapled Bim peptides affected the secondary structure and intracellular activity of the peptides, and furthermore, there was a correlation between these latter two variables.

2.
Heliyon ; 10(15): e35308, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39170363

RESUMO

Infrastructure operation and maintenance is essential for societal safety, particularly in Japan where the aging of infrastructures built during the period of high economic growth is advancing. However, there are issues such as a shortage of engineers and inefficiencies in work, requiring improvements in efficiency and automation for their resolution. Nevertheless, there are still many inefficiencies in the current procedures for bridge inspections. Usually, inspection engineers check for damage on bridges through close visual inspections at the site, then photograph the damaged parts, measure the size by touch, and create a report. A three-dimensional representation, considering the front and back of the structural elements, is needed for identifying damage, necessitating the creation of multi-directional three-dimensional drawings. However, this process is labor-intensive and prone to errors. Furthermore, due to the lack of uniformity in records, it is challenging to refer to past inspection histories. Especially for long bridges, without resolving such issues, the required labor and the number of mistakes could exceed acceptable limits, making proper management difficult. Therefore, in this study, we developed a method for automatically measuring the position and area of corroded parts by capturing images of the lower surface of the stiffening girder using a bridge inspection vehicle and utilizing image diagnosis technology. By integrating these results into a 3D model called BIM (Building Information Modeling), it becomes possible to manage the bridge more efficiently. We verified this method on actual long bridges and confirmed its effectiveness.

3.
J Cancer Res Clin Oncol ; 150(8): 380, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39095579

RESUMO

PURPOSE: This study aims to determine whether Pokemon regulates Bim activity in colorectal carcinoma (CRC) carcinogenesis. METHODS: Clinical tissue samples were analyzed to detect the expression and clinicopathological significance of Pokemon and Bim in CRC. Proliferation, apoptosis, and invasion assays were conducted to identify the regulatory effect of Pokemon on Bim. The combined treatment effects of Pokemon knockdown and diamminedichloroplatinum (DDP) were also examined. RESULTS: Immunohistochemical analysis of 80 samples of colorectal epithelia (CRE), 80 cases of colorectal adenoma (CRA), and 160 of CRC samples revealed protein expression rates of 23.8%, 38.8%, and 70.6% for Pokemon, and 88.8%, 73.8%, and 31.9% for Bim, respectively. A significant negative correlation was observed between Pokemon and Bim expression across the CRE, CRA, and CRC lesion stages. In CRC, higher Pokemon and lower Bim expression correlated with higher histological grades, advanced Dukes stages, and increased cancer invasion. In both LoVo and HCT116 cells, overexpression of Pokemon significantly reduced Bim expression, leading to increased proliferation, resistance to anoikis, and cell invasion. Additionally, Pokemon overexpression significantly decreased DDP-induced Bim expression, reduction of anti-apoptosis and invasion, whereas Pokemon knockdown resulted in the opposite effects. CONCLUSION: These findings suggest that Pokemon inhibits Bim transcription, thereby promoting CRC proliferation, resistance to apoptosis, invasion, and advancing histological grade and Dukes staging. Pokemon knockdown enhances the therapeutic efficacy of DDP in the treatment of CRC.


Assuntos
Proteína 11 Semelhante a Bcl-2 , Proliferação de Células , Neoplasias Colorretais , Invasividade Neoplásica , Fatores de Transcrição , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Proteína 11 Semelhante a Bcl-2/genética , Proteína 11 Semelhante a Bcl-2/metabolismo , Feminino , Masculino , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Pessoa de Meia-Idade , Anoikis/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Estadiamento de Neoplasias , Idoso , Gradação de Tumores , Regulação Neoplásica da Expressão Gênica , Transcrição Gênica , Apoptose , Linhagem Celular Tumoral
4.
Heliyon ; 10(12): e32852, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975124

RESUMO

Nowadays with the increase of high-rise buildings, emergency evacuation is an indispensable part of urban environment management. Due to various disaster incidents occurred in indoor environments, research has concentrated on ways to deal with the different difficulties of indoor emergency evacuation. Although global navigation satellite systems (GNSSs) such as global positioning system (GPS) come in handy in outdoor spaces, they are not of much use in enclosed places, where satellite signals cannot penetrate easily. Therefore, other approaches must be considered for pedestrian navigation to cope with the indoor positioning problem. Another problem in such environments is the information of the building indoor space. The majority of the studies has used prepared maps of the building, which limits their methodology to that specific study area. However, in this study we have proposed an end-to-end method that takes advantage of BIM model of the building, thereby applicable to every structure that has an equivalent building information model (BIM). Moreover, we have used a mixture of Wi-Fi fingerprinting and pedestrian dead reckoning (PDR) method with relatively higher accuracy compared to other similar methods for navigating the user to the exit point. For implementing PDR, we used the sensors in smartphones to calculate user steps and direction. In addition, the navigational information was superimposed on the smartphone screen using augmented reality (AR) technology, thus communicating the direction information in a user-friendly manner. Finally, the AR mobile emergency evacuation application developed was assessed with a sample audience. After an experience with the app, they filled out a questionnaire which was designed in the system usability scale test (SUS) format. The evaluation results showed that the app achieved an acceptable suitability for usage.

5.
Sensors (Basel) ; 24(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39000929

RESUMO

Defect inspection of existing buildings is receiving increasing attention for digitalization transfer in the construction industry. The development of drone technology and artificial intelligence has provided powerful tools for defect inspection of buildings. However, integrating defect inspection information detected from UAV images into semantically rich building information modeling (BIM) is still challenging work due to the low defect detection accuracy and the coordinate difference between UAV images and BIM models. In this paper, a deep learning-based method coupled with transfer learning is used to detect defects accurately; and a texture mapping-based defect parameter extraction method is proposed to achieve the mapping from the image U-V coordinate system to the BIM project coordinate system. The defects are projected onto the surface of the BIM model to enrich a surface defect-extended BIM (SDE-BIM). The proposed method was validated in a defect information modeling experiment involving the No. 36 teaching building of Nantong University. The results demonstrate that the methods are widely applicable to various building inspection tasks.

6.
Heliyon ; 10(12): e33026, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39005904

RESUMO

The integration of BIM with other digital advancements has demonstrably led to an increase of performance in the Architecture, Engineering, Construction and Operation (AECO) industry. This integration not only is showing promising results in boosting the industry's performance, but also the productivity and promotes data-driven decision-making. Despite these benefits, there are limited studies that address the integration of BIM and digital data for managing built-assets in general and in developing countries in particular. To fill this gap, a closer assessment of current built-asset information management practice is necessary. The assessment of the practice examines how digital processes and/or technology can be seamlessly integrated into existing practices. In this regard, this study aims to provide valuable insights into increasing the maturity of built-asset information management by integrating digital data with BIM. The study uses a case-based research design using built-assets (universities in Addis Ababa) as public building representative to capture the prevailing information management practices in Ethiopian public buildings. The findings reveal that traditional paper-based practices still dominate the management of built-assets. This leads to difficulties in terms of data loss, unavailability, inaccuracy, and unreliability, all of which are detrimental to the overall performance. Based on these findings, a conceptual framework is designed to improve the performance of built-assets and help owners, end-users, and managers in defining data and information requirements for BIM-enabled asset information management. The framework delineates processes for structured information requirements definition and validation of various asset data from varying sources. The framework utilizes a BIM-enabled platform as a single source of truth and offers a comprehensive solution to the identified challenges. The findings of this study holds significant promise for improving the existing practice of built-asset information management within the study context.

7.
Sci Rep ; 14(1): 15298, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961179

RESUMO

Within the global architecture, engineering, and construction industry, the use of Building Information Modeling (BIM) technology has significantly expanded. However, given the unique characteristics of road infrastructure, the application of BIM technology is still being explored. This article focuses on the Yuanchen Expressway, exploring innovative applications of BIM technology in comprehensive construction management. The project employs advanced technologies, including BIM, Geographic Information Systems (GIS), and the Internet of Things (IoT), to precisely identify critical nodes and breakthroughs. Supported by a detailed BIM model and a multi-level, diversified digital management platform, the project effectively addresses construction challenges in multiple tunnels, bridges, and complex interchanges, achieving intelligent construction innovation throughout the Yuanchen Expressway with BIM technology. By guiding construction through BIM models, utilizing a BIM+GIS-based management cloud platform system, and employing VR safety briefings, the project effectively reduces the difficulty of communication and coordination in project management, shortens the project measurement cycle, improves on-site work efficiency, and ensures comprehensive control and safety management. This article provides an exemplary case for the application of full-line construction management using BIM technology in the highway sector both in China and globally, offering new perspectives and strategies for highway construction management.

8.
Int J Nanomedicine ; 19: 4779-4801, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828196

RESUMO

Background: Messenger RNA (mRNA)-based immunogene therapy holds significant promise as an emerging tumor therapy approach. However, the delivery efficiency of existing mRNA methods and their effectiveness in stimulating anti-tumor immune responses require further enhancement. Tumor cell lysates containing tumor-specific antigens and biomarkers can trigger a stronger immune response to tumors. In addition, strategies involving multiple gene therapies offer potential optimization paths for tumor gene treatments. Methods: Based on the previously developed ideal mRNA delivery system called DOTAP-mPEG-PCL (DMP), which was formed through the self-assembly of 1.2-dioleoyl-3-trimethylammonium-propane (DOTAP) and methoxypoly (ethylene glycol)-b-poly (ε-caprolactone) (mPEG-PCL), we introduced a fused cell-penetrating peptide (fCPP) into the framework and encapsulated tumor cell lysates to form a novel nanovector, termed CLSV system (CLS: CT26 tumor cell lysate, V: nanovector). This system served a dual purpose of facilitating the delivery of two mRNAs and enhancing tumor immunogene therapy through tumor cell lysates. Results: The synthesized CLSV system had an average size of 241.17 nm and a potential of 39.53 mV. The CLSV system could not only encapsulate tumor cell lysates, but also deliver two mRNAs to tumor cells simultaneously, with a transfection efficiency of up to 60%. The CLSV system effectively activated the immune system such as dendritic cells to mature and activate, leading to an anti-tumor immune response. By loading Bim-encoded mRNA and IL-23A-encoded mRNA, CLSV/Bim and CLSV/IL-23A complexes were formed, respectively, to further induce apoptosis and anti-tumor immunity. The prepared CLSV/dual-mRNA complex showed significant anti-cancer effects in multiple CT26 mouse models. Conclusion: Our results suggest that the prepared CLSV system is an ideal delivery system for dual-mRNA immunogene therapy.


Assuntos
Neoplasias do Colo , Terapia Genética , Imunoterapia , Nanopartículas , RNA Mensageiro , Animais , RNA Mensageiro/genética , RNA Mensageiro/administração & dosagem , Linhagem Celular Tumoral , Neoplasias do Colo/terapia , Neoplasias do Colo/genética , Terapia Genética/métodos , Imunoterapia/métodos , Nanopartículas/química , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos Penetradores de Células/química , Polietilenoglicóis/química , Humanos , Poliésteres/química , Feminino , Compostos de Amônio Quaternário , Ácidos Graxos Monoinsaturados
9.
Heliyon ; 10(11): e31886, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38841493

RESUMO

The construction industry wields significant influence in the economies of various countries. However, compared to sectors like manufacturing and aeronautics, it has lagged in terms of digitalization of processes and project management advancement. This study aims to explore how the integration of Lean principles, Building Information Modeling (BIM), and Project Lifecycle Management methodologies within an information system can enhance decision-making in construction project management as a complex environment. A comprehensive literature review was conducted to establish a conceptual framework and gather necessary information for designing an information system. The design was based on the viable systems model and the soft systems methodology, from a systemic perspective that encourages the synergistic interaction of these methodologies. The resulting abstract model would facilitate a comprehensive understanding of the interconnectedness of these methodologies, emphasizing collaborative work environments for efficient information management. This approach aims to replace the current isolated application of each of those methodologies and promises improved project management performance.

10.
Sci Rep ; 14(1): 13536, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866821

RESUMO

Reduced Reinforced Concrete Material Waste (RRCMW) in building projects is regarded as a critical issue that must be managed. The main purpose of the research is to illustrate the importance of BIM in construction. Also, it is found that the main objectives of this paper are to study the improvement of practicing BIM in Egypt and, practicing of BIM in construction industry in Egypt is also measured. Two questionnaires survey are conducted. The first questionnaire is to measure the improvement of using BIM during the last 7 years and it is discovered that there is a massive improvement in using BIM in this period. The second questionnaire is to determine the adopting value of BIM in Egyptian projects in order to meet the study objective. So, based on the questionnaire analysis, it is discovered that about 94% of consultants actually practicing BIM in 3D while about 72% of contractors agree with practicing BIM in 3D. Also it is found that about 86% and 78% of consultants actually practicing BIM in 4D and 5D while only about 43% and 40% of contractors agree with practicing BIM 4D and 5D model respectively. Only about 61% and 58% considered that BIM is important in 6D and 7D respectively because it isn't widely used in Egypt and engineers use BIM up to 5D. As a result, the findings reveal that the number of consultant's site engineer's respondents are more than contractors because the usage of BIM is effective in the field of design and consultancy more than using in site and while BIM isn't extensively utilized in Egypt, engineers should be familiar with it because it will be a useful tool in the future. So, the main purpose of this study is to illustrate practicing of BIM in the Egyptian construction projects and study the improvement of using BIM during the last 7 years in Egypt because BIM is considered as an important technology used to reduce waste in construction projects from design stage to construction and operation stage but still not used in Egypt in a wide range till now, so it is very crucial to study this issue. Also, another main objective of this study is to compare the development done in using BIM during the last 8 years to make sure that using BIM in Egypt is going on and developed.

11.
Sensors (Basel) ; 24(12)2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38931546

RESUMO

The growing interest in building data management, especially the building information model (BIM), has significantly influenced urban management, materials supply chain analysis, documentation, and storage. However, the integration of BIM into 3D GIS tools is becoming more common, showing progress beyond the traditional problem. To address this, this study proposes data transformation methods involving mapping between three domains: industry foundation classes (IFC), city geometry markup language (CityGML), and web ontology framework (OWL)/resource description framework (RDF). Initially, IFC data are converted to CityGML format using the feature manipulation engine (FME) at CityGML standard's levels of detail 4 (LOD4) to enhance BIM data interoperability. Subsequently, CityGML is converted to the OWL/RDF diagram format to validate the proposed BIM conversion process. To ensure integration between BIM and GIS, geometric data and information are visualized through Cesium Ion web services and Unreal Engine. Additionally, an RDF graph is applied to analyze the association between the semantic mapping of the CityGML standard, with Neo4j (a graph database management system) utilized for visualization. The study's results demonstrate that the proposed data transformation methods significantly improve the interoperability and visualization of 3D city models, facilitating better urban management and planning.

12.
BMC Cancer ; 24(1): 619, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773471

RESUMO

BACKGROUND: Breast cancer is one of the common malignancies in women. Evidence has demonstrated that FBXO45 plays a pivotal role in oncogenesis and progression. However, the role of FBXO45 in breast tumorigenesis remains elusive. Exploration of the regulatory mechanisms of FBXO45 in breast cancer development is pivotal for potential therapeutic interventions in patients with breast cancer. METHODS: Hence, we used numerous approaches to explore the functions of FBXO45 and its underlaying mechanisms in breast cancer pathogenesis, including CCK-8 assay, EdU assay, colony formation analysis, apoptosis assay, RT-PCR, Western blotting, immunoprecipitation, ubiquitination assay, and cycloheximide chase assay. RESULTS: We found that downregulation of FBXO45 inhibited cell proliferation, while upregulation of FBXO45 elevated cell proliferation in breast cancer. Silencing of FBXO45 induced cell apoptosis, whereas overexpression of FBXO45 inhibited cell apoptosis in breast cancer. Moreover, FBXO45 interacted with BIM and regulated its ubiquitination and degradation. Furthermore, knockdown of FBXO45 inhibited cell proliferation via regulation of BIM pathway. Notably, overexpression of FBXO45 facilitated tumor growth in mice. Strikingly, FBXO45 expression was associated with poor survival of breast cancer patients. CONCLUSION: Our study could provide the rational for targeting FBXO45 to obtain benefit for breast cancer patients. Altogether, modulating FBXO45/Bim axis could be a promising strategy for breast cancer therapy.


Assuntos
Apoptose , Proteína 11 Semelhante a Bcl-2 , Neoplasias da Mama , Proliferação de Células , Progressão da Doença , Proteínas F-Box , Ubiquitinação , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Feminino , Animais , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Camundongos , Proteína 11 Semelhante a Bcl-2/metabolismo , Proteína 11 Semelhante a Bcl-2/genética , Linhagem Celular Tumoral , Proteólise , Regulação Neoplásica da Expressão Gênica , Camundongos Nus
13.
Heliyon ; 10(9): e30650, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38756612

RESUMO

The European Union supports the use of technology to improve public procurement, acknowledging Building Information Modeling (BIM) as a catalyst for cost-effective public works and innovation. The purpose of this paper is to evaluate BIM implementation practices in Spanish public procurement. The methodology used in this study is a mixed research method involving a questionnaire survey and semi-structured expert interviews. The findings reveal market maturity as a barrier to BIM adoption in Spanish public procurement throughout the asset lifecycle. Selecting the right instrument for implementation proves challenging for public organizations. This study has contributed to the development of more practical and effective strategies to ensure full adoption of BIM within the public procurement sector of Spain. It proposes a framework approach for the pre-contractual phase, helping contracting authorities to make the optimal instrument selection. Two criteria are considered: the maturity of the public client and sector, and the economic value classification of tenders.

14.
Cell Mol Immunol ; 21(7): 752-769, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38822080

RESUMO

The development of distinct dendritic cell (DC) subsets, namely, plasmacytoid DCs (pDCs) and conventional DC subsets (cDC1s and cDC2s), is controlled by specific transcription factors. IRF8 is essential for the fate specification of cDC1s. However, how the expression of Irf8 is regulated is not fully understood. In this study, we identified TRIM33 as a critical regulator of DC differentiation and maintenance. TRIM33 deletion in Trim33fl/fl Cre-ERT2 mice significantly impaired DC differentiation from hematopoietic progenitors at different developmental stages. TRIM33 deficiency downregulated the expression of multiple genes associated with DC differentiation in these progenitors. TRIM33 promoted the transcription of Irf8 to facilitate the differentiation of cDC1s by maintaining adequate CDK9 and Ser2 phosphorylated RNA polymerase II (S2 Pol II) levels at Irf8 gene sites. Moreover, TRIM33 prevented the apoptosis of DCs and progenitors by directly suppressing the PU.1-mediated transcription of Bcl2l11, thereby maintaining DC homeostasis. Taken together, our findings identified TRIM33 as a novel and crucial regulator of DC differentiation and maintenance through the modulation of Irf8 and Bcl2l11 expression. The finding that TRIM33 functions as a critical regulator of both DC differentiation and survival provides potential benefits for devising DC-based immune interventions and therapies.


Assuntos
Proteína 11 Semelhante a Bcl-2 , Diferenciação Celular , Células Dendríticas , Homeostase , Fatores Reguladores de Interferon , Camundongos Endogâmicos C57BL , Fatores de Transcrição , Animais , Fatores Reguladores de Interferon/metabolismo , Fatores Reguladores de Interferon/genética , Células Dendríticas/metabolismo , Células Dendríticas/citologia , Camundongos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteína 11 Semelhante a Bcl-2/metabolismo , Proteína 11 Semelhante a Bcl-2/genética , Transcrição Gênica , Apoptose , RNA Polimerase II/metabolismo , Quinase 9 Dependente de Ciclina/metabolismo , Transativadores/metabolismo , Transativadores/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Camundongos Knockout , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia
15.
Sci Prog ; 107(2): 368504241228130, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38689543

RESUMO

Smart building equipment monitoring is a well-established field focused on enhancing contemporary building comfort. The proliferation of Internet connectivity, facilitated by the internet of things (IoT), has transformed buildings from static structures into interactive environments. IoT has witnessed substantial growth across various aspects of daily life, from monitoring environmental conditions to managing building systems and storing data in the cloud. One critical application is the intelligent monitoring and control of building equipment, such as air conditioners, to optimize energy efficiency-a matter of increasing concern for building owners, design experts, and system integrators. Achieving comprehensive energy savings demands a meticulous approach to energy-efficient design and control. This paper's primary objective is to explore and analyze IoT-based energy-saving optimization techniques for intelligent building equipment, integrating building information modeling (BIM) technology. It particularly delves into the energy conservation control algorithm for air-conditioning systems. The research presents a challenge rooted in energy-saving optimization, established upon specific objective functions, followed by a detailed explanation of the energy-saving control algorithm. To validate their approach, the paper outlines a comprehensive experimental design. Over three sessions in August, they conducted control experiments in two distinct areas. Area 1 implemented the energy-saving control methodology discussed in the paper, utilizing virtual parameter enhancement mechanisms, while Area 2 adhered to conventional control methods. The results were enlightening. Area 1 demonstrated superior energy efficiency, consuming 735 kWh compared to Area 2's 819 kWh, signifying an impressive 11.43% reduction in energy consumption thanks to the optimized control strategy. This research underscores the practicality and significance of implementing IoT-based energy-saving strategies, with a focus on smart thermostats, HVAC controllers, and daylight sensors, in intelligent building equipment management to achieve substantial energy conservation gains.

16.
Biochem Pharmacol ; 223: 116198, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38588830

RESUMO

Agents that inhibit bromodomain and extra-terminal domain (BET) proteins have been actively tested in the clinic as potential anticancer drugs. NEDD8-activating enzyme (NAE) inhibitors, represented by MLN4924, target the only activation enzyme in the neddylation pathway that has been identified as an attractive target for cancer therapy. In this study, we focus on the combination of BET inhibitors (BETis) and NAE inhibitors (NAEis) as a cancer therapeutic strategy and investigate its underlying mechanisms to explore and expand the application scope of both types of drugs. The results showed that this combination synergistically inhibited the proliferative activity of tumor cells from different tissues. Compared to a single drug, combination therapy had a weak effect on cycle arrest but significantly enhanced cell apoptosis. Furthermore, the growth of NCI-H1975 xenografts in nude mice was significantly inhibited by the combination without obvious body weight loss. Research on the synergistic mechanism demonstrated that combination therapy significantly increased the mRNA and protein levels of the proapoptotic gene BIM. The inhibition and knockout of BIM significantly attenuated the apoptosis induced by the combination, whereas the re-expression of BIM restored the synergistic effects, indicating that BIM induction plays a critical role in mediating the enhanced apoptosis induced by the co-inhibition of BET and NAE. Together, the enhanced transcription mediated by miR-17-92 cluster inhibition and reduced degradation promoted the increase in BIM levels, resulting in a synergistic effect. Collectively, these findings highlight the need for further clinical investigation into the combination of BETi and NAEi as a promising strategy for cancer therapy.


Assuntos
Antineoplásicos , Neoplasias , Animais , Humanos , Camundongos , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Ciclopentanos/farmacologia , Camundongos Nus , Proteína 11 Semelhante a Bcl-2/metabolismo
17.
Sensors (Basel) ; 24(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38610327

RESUMO

Structural health monitoring (SHM) is critical for ensuring the safety of infrastructure such as bridges. This article presents a digital twin solution for the SHM of railway bridges using low-cost wireless accelerometers and machine learning (ML). The system architecture combines on-premises edge computing and cloud analytics to enable efficient real-time monitoring and complete storage of relevant time-history datasets. After train crossings, the accelerometers stream raw vibration data, which are processed in the frequency domain and analyzed using machine learning to detect anomalies that indicate potential structural issues. The digital twin approach is demonstrated on an in-service railway bridge for which vibration data were collected over two years under normal operating conditions. By learning allowable ranges for vibration patterns, the digital twin model identifies abnormal spectral peaks that indicate potential changes in structural integrity. The long-term pilot proves that this affordable SHM system can provide automated and real-time warnings of bridge damage and also supports the use of in-house-designed sensors with lower cost and edge computing capabilities such as those used in the demonstration. The successful on-premises-cloud hybrid implementation provides a cost effective and scalable model for expanding monitoring to thousands of railway bridges, democratizing SHM to improve safety by avoiding catastrophic failures.

18.
MethodsX ; 12: 102685, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38577408

RESUMO

Building Information Modelling (BIM), a new concept and methodology, has received much attention lately. Various Structural Engineering Firms (SEFs) have observed substantial competitive benefits after its deployment. BIM offers a wide range of advantages, but its capacity has not even been completely exploited. The challenges of firm implementation, a procedure that necessitates significant alterations in firm business structure, are a major factor in this. However, there hasn't been much in-depth research on the assessment and integration of the research around the application of BIM in firms. To address the planning phase's complexity, which makes implementing BIM in these workplaces challenging, this article provides a framework for BIM deployment in the SEF. Additionally, a brand-new hybrid African Buffalo and African Vulture Optimization (AB-AVO) has been created to assess the state of technology. The technique suggested for BIM execution within SEF obviously and effectively recognises the firm's expectations and resources, sets out the needs required to create the BIM technique, and offers technical and clinical suggestions for monitoring and planning the execution. It is categorised by resource utilization, versatility, and adaptability.•This paper introduces a new concept and methodology of using BIM•The technique suggested for BIM execution within SEF obviously and effectively recognises the firm's expectations and resources•The method establishes guidelines for structural firm to adopt BIM in their monitoring, and planning the execution.

19.
Heliyon ; 10(8): e28585, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38644840

RESUMO

In smart buildings, digital construction technologies can support more efficient management of data and information related to building components. This paper aims to draw a robust linking mechanism between digital construction technologies that support smart buildings and smart city development to satisfy building users' expectations. Data was attained using a qualitative approach via secondary data from literature and primary data in the context of case study with building users. The study suggests the importance of recognising single/multi-purposed data to support better synergy between digital construction technologies and in smart buildings and smart city development to satisfy building users' expectations.

20.
Carbohydr Polym ; 334: 122066, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38553206

RESUMO

Most current flexible electronic devices are based on petroleum materials that are difficult to degrade. The exploration of sustainable and eco-friendly materials has become a major focus in both the scientific and industrial communities. In this study, BC-Zn-BIM (bacterial cellulose-Zn-benzimidazole), a novel composite electrode material based on biodegradable BC was developed. Here, BC acted as a conductive medium involved in the conductive behavior of the composite material. We've explored the charge transport mechanisms of BC-Zn-BIM by density functional theory (DFT) calculations, and applied it in the electrochemical detection of Bisphenol A (BPA). The results indicated that the oxygen-containing groups in BC and the nitrogen-containing heterocycles in BIM have a tendency to lose electrons, whereas zinc ions actively acquire electrons from these groups. This process promoted charge transfer within BC-Zn-BIM and endowed it with semiconductor-like properties, enhancing the electrocatalytic reaction of BPA. The detection limit of the electrochemical biosensor was 12 nM, and the sample recovery was 95.1%105.6%. This study clarified the mechanism of the higher electrical properties achieved in Zn-BIM complex grown in-situ on dielectric BC. This will further promote the development of low-cost, environmentally friendly flexible electronic devices.


Assuntos
Celulose , Zinco , Celulose/química , Bactérias
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