RESUMEN

Electrocatalytic reduction of nitrate to ammonia has been considered a promising and sustainable pathway for pollutant treatment and ammonia has significant potential as a clean energy. Therefore, the method has received much attention. In this work, Cu/Fe 2D bimetallic metal-organic frameworks were synthesized by a facile method applied as cathode materials without high-temperature carbonization. Bimetallic centers (Cu, Fe) with enhanced intrinsic activity demonstrated higher removal efficiency. Meanwhile, the 2D nanosheet reduced the mass transfer barrier between the catalyst and nitrate and increased the reaction kinetics. Therefore, the catalysts with a 2D structure showed much better removal efficiency than other structures (3D MOFs and Bulk MOFs). Under optimal conditions, Cu/Fe-2D MOF exhibited high nitrate removal efficiency (87.8%) and ammonium selectivity (89.3%) simultaneously. The ammonium yielded up to significantly 907.2 µg/(hr·mgcat) (7793.8 µg/(hr·mgmetal)) with Faradaic efficiency of 62.8% at an initial 100 mg N/L. The catalyst was proved to have good stability and was recycled 15 times with excellent effect. DFT simulations confirm the reduced Gibbs free energy of Cu/Fe-2D MOF. This study demonstrates the promising application of Cu/Fe-2D MOF in nitrate reduction to ammonia and provides new insights for the design of efficient electrode materials.

Asunto(s)

Amoníaco , Cobre , Hierro , Estructuras Metalorgánicas , Nitratos , Contaminantes Químicos del Agua , Amoníaco/química , Cobre/química , Nitratos/química , Estructuras Metalorgánicas/química , Hierro/química , Contaminantes Químicos del Agua/química , Catálisis , Modelos Químicos , Oxidación-Reducción , Cinética

RESUMEN

Endoscopic ultrasound (EUS)-guided pancreatic duct drainage includes two procedures: EUS-guided drainage/anastomosis (EUS-D/A) and trans-papillary drainage with EUS-assisted pancreatic rendezvous. EUS-guided pancreatogastrostomy is the most common EUS-D/A procedure and is recommended as a salvage procedure in cases in which endoscopic retrograde cholangiopancreatography fails or is difficult. However, initial EUS-D/A is performed in patients with surgically altered anatomy at our institution. It is one of the most difficult interventional EUS procedures and has a high incidence of adverse events. The technical difficulties differ according to etiology, and the incidence of adverse events varies between initial EUS-D/A and subsequent trans-endosonographically/EUS-guided created route procedures. Hence, it is important to meticulously prepare a procedure based on the patient's condition and the available devices. The technical difficulties in EUS-D/A include: (1) determination of the puncture point, (2) selection of a puncture needle and guidewire, (3) guidewire manipulation, and (4) dilation of the puncture route and stenting. Proper technical procedures are important to increase the success rate and reduce the incidence and severity of adverse events. The complexity of EUS-D/A is also contingent on the severity of pancreatic fibrosis and stricture. In post-pancreatectomy cases, determination of the puncture site is important for success because of the remnant pancreas. Trans-endosonographically/EUS-guided created route procedures following initial EUS-D/A are also important for achieving the treatment goal. This article focuses on effective strategies for initial EUS-D/A, based on the etiology and condition of the pancreas. We mainly discuss EUS-D/A, including its indications, techniques, and success-enhancing strategies.

RESUMEN

Tissue on a chip or organ-on-chip (OOC) is a technology that's dignified to form a transformation in drug discovery through the use of advanced platforms. These are 3D in-vitro cell culture models that mimic micro-environment of human organs or tissues on artificial microstructures built on a portable microfluidic chip without involving sacrificial humans or animals. This review article aims to offer readers a thorough and insightful understanding of technology. It begins with an in-depth understanding of chip design and instrumentation, underlining its pivotal role and the imperative need for its development in the modern scientific landscape. The review article explores into the myriad applications of OOC technology, showcasing its transformative impact on fields such as radiobiology, drug discovery and screening, and its pioneering use in space research. In addition to highlighting these diverse applications, the article provides a critical analysis of the current challenges that OOC technology faces. It examines both the biological and technical limitations that hinder its progress and efficacy and discusses the potential advancements and innovations that could drive the OOC technology forward. Through this comprehensive review, readers will gain a deep appreciation of the significance, capabilities, and evolving landscape of OOC technology.

RESUMEN

Three-dimensional (3D) chromosome structures are closely related to various chromosomal functions, and deep analysis of the structures is crucial for the elucidation of the functions. In recent years, chromosome conformation capture (3C) techniques combined with next-generation sequencing analysis have been developed to comprehensively reveal 3D chromosome structures. Micro-C is one such method that can detect the structures at nucleosome resolution. In this chapter, I provide a basic method for Micro-C analysis. I present and discuss a series of data analyses ranging from mapping to basic downstream analyses, including loop detection.

Asunto(s)

Secuenciación de Nucleótidos de Alto Rendimiento , Programas Informáticos , Flujo de Trabajo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Cromosomas/genética , Biología Computacional/métodos , Mapeo Cromosómico/métodos , Nucleosomas/química , Nucleosomas/genética , Nucleosomas/metabolismo

RESUMEN

Hi-C and Micro-C are the three-dimensional (3D) genome assays that use high-throughput sequencing. In the analysis, the sequenced paired-end reads are mapped to a reference genome to generate a two-dimensional contact matrix for identifying topologically associating domains (TADs), chromatin loops, and chromosomal compartments. On the other hand, the distance distribution of the paired-end mapped reads also provides insight into the 3D genome structure by highlighting global contact frequency patterns at distances indicative of loops, TADs, and compartments. This chapter presents a basic workflow for visualizing and analyzing contact distance distributions from Hi-C data. The workflow can be run on Google Colaboratory, which provides a ready-to-use Python environment accessible through a web browser. The notebook that demonstrates the workflow is available in the GitHub repository at https://github.com/rnakato/Springer_contact_distance_plot.

Asunto(s)

Secuenciación de Nucleótidos de Alto Rendimiento , Programas Informáticos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Biología Computacional/métodos , Navegador Web , Flujo de Trabajo , Humanos , Cromatina/genética , Genómica/métodos

RESUMEN

Over a decade has passed since the development of the Hi-C method for genome-wide analysis of 3D genome organization. Hi-C utilizes next-generation sequencing (NGS) technology to generate large-scale chromatin interaction data, which has accumulated across a diverse range of species and cell types, particularly in eukaryotes. There is thus a growing need to streamline the process of Hi-C data analysis to utilize these data sets effectively. Hi-C generates data that are much larger compared to other NGS techniques such as chromatin immunoprecipitation sequencing (ChIP-seq) or RNA-seq, making the data reanalysis process computationally expensive. In an effort to bridge this resource gap, the 4D Nucleome (4DN) Data Portal has reanalyzed approximately 600 Hi-C data sets, allowing users to access and utilize the analyzed data. In this chapter, we provide detailed instructions for the implementation of the common workflow language (CWL)-based Hi-C analysis pipeline adopted by the 4DN Data Portal ecosystem. This reproducible and portable pipeline generates standard Hi-C contact matrices in formats such as .hic or .mcool from FASTQ files. It enables users to output their own Hi-C data in the same format as those registered in the 4DN Data portal, facilitating comparative analysis using data registered in the portal. Our custom-made scripts are available on GitHub at https://github.com/kuzobuta/4dn_cwl_pipeline .

Asunto(s)

Cromatina , Secuenciación de Nucleótidos de Alto Rendimiento , Programas Informáticos , Flujo de Trabajo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Cromatina/genética , Cromatina/metabolismo , Humanos , Genómica/métodos , Biología Computacional/métodos , Secuenciación de Inmunoprecipitación de Cromatina/métodos

RESUMEN

The Hi-C method has emerged as an indispensable tool for analyzing the 3D organization of the genome, becoming increasingly accessible and frequently utilized in chromatin research. To effectively leverage 3D genomics data obtained through advanced technologies, it is crucial to understand what processes are undertaken and what aspects require special attention within the bioinformatics pipeline. This protocol aims to demystify the Hi-C data analysis process for field newcomers. In a step-by-step manner, we describe how to process Hi-C data, from the initial sequencing of the Hi-C library to the final visualization of Hi-C contact data as heatmaps. Each step of the analysis is clearly explained to ensure an understanding of the procedures and their objectives. By the end of this chapter, readers will be equipped with the knowledge to transform raw Hi-C reads into informative visual representations, facilitating a deeper comprehension of the spatial genomic structures critical to cellular functions.

Asunto(s)

Cromatina , Biología Computacional , Genómica , Programas Informáticos , Cromatina/genética , Biología Computacional/métodos , Genómica/métodos , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos

RESUMEN

Three-dimensional (3D) genome structure plays crucial roles in biological processes and disease pathogenesis. Hi-C and Micro-C, well-established methods for 3D genome analysis, can identify a variety of 3D genome structures. However, selecting appropriate pipelines and tools for the analysis and setting up the required computing environment can sometimes pose challenges. To address this, we have introduced CustardPy, a Docker-based pipeline specifically designed for 3D genome analysis. CustardPy is designed to compare and evaluate multiple samples and wraps several existing tools to cover the entire workflow from FASTQ mapping to visualization. In this chapter, we demonstrate how to analyze and visualize Hi-C data using CustardPy and introduce several 3D genome features observed in Hi-C data.

Asunto(s)

Programas Informáticos , Biología Computacional/métodos , Genómica/métodos , Humanos , Genoma

RESUMEN

Hi-C methods reveal 3D genome features but lack correspondence to dynamic chromatin behavior. PHi-C2, Python software, addresses this gap by transforming Hi-C data into polymer models. After the optimization algorithm, it enables us to calculate 3D conformations and conduct dynamic simulations, providing insights into chromatin dynamics, including the mean-squared displacement and rheological properties. This chapter introduces PHi-C2 usage, offering a tutorial for comprehensive 4D genome analysis.

Asunto(s)

Algoritmos , Cromatina , Programas Informáticos , Cromatina/genética , Cromatina/química , Cromatina/metabolismo , Humanos , Genómica/métodos , Genoma , Biología Computacional/métodos

RESUMEN

This chapter describes the computational pipeline for the processing and visualization of Protec-Seq data, a method for purification and genome-wide mapping of double-stranded DNA protected by a specific protein at both ends. In the published case, the protein of choice was Saccharomyces cerevisiae Spo11, a conserved topoisomerase-like enzyme that makes meiotic double-strand breaks (DSBs) to initiate homologous recombination, ensuring proper segregation of homologous chromosomes and fertility. The isolated DNA molecules were thus termed double DSB (dDSB) fragments and were found to represent 34 to several hundred base-pair long segments that are generated by Spo11 and are enriched at DSB hotspots, which are sites of topological stress. In order to allow quantitative comparisons between dDSB profiles across experiments, we implemented calibrated chromatin immunoprecipitation sequencing (ChIP-Seq) using the meiosis-competent yeast species Saccharomyces kudriavzevii as calibration strain. Here, we provide a detailed description of the computational methods for processing, analyzing, and visualizing Protec-Seq data, comprising the download of the raw data, the calibrated genome-wide alignments, and the scripted creation of either arc plots or Hi-C-style heatmaps for the illustration of chromosomal regions of interest. The workflow is based on Linux shell scripts (including wrappers for publicly available, open-source software) as well as R scripts and is highly customizable through its modular structure.

Asunto(s)

Roturas del ADN de Doble Cadena , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Secuenciación de Inmunoprecipitación de Cromatina/métodos , Programas Informáticos , Meiosis/genética , Genoma Fúngico , Mapeo Cromosómico/métodos , Endodesoxirribonucleasas/metabolismo , Endodesoxirribonucleasas/genética , Biología Computacional/métodos , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , ADN de Hongos/genética , ADN de Hongos/metabolismo

RESUMEN

Biofilm-associated infections (BAIs) continue to pose a major challenge in the medical field. Nanomedicine, in particular, promises significant advances in combating BAIs through the introduction of a variety of nanomaterials and nano-antimicrobial strategies. However, studies to date have primarily focused on the removal of the bacterial biofilm and neglect the subsequent post-biofilm therapeutic measures for BAIs, rendering pure anti-biofilm strategies insufficient for the holistic recovery of affected patients. Herein, we construct an emerging dual-functional composite nanosheet (SiHx@Ga) that responds to pHs fluctuation in the biofilm microenvironment to enable a sequential therapy of BAIs. In the acidic environment of biofilm, SiHx@Ga employs the self-sensitized photothermal Trojan horse strategy to effectively impair the reactive oxygen species (ROS) defense system while triggering oxidative stress and lipid peroxidation of bacteria, engendering potent antibacterial and anti-biofilm effects. Surprisingly, in the post-treatment phase, SiHx@Ga adsorbs free pathogenic nucleic acids released after biofilm destruction, generates hydrogen with ROS-scavenging and promotes macrophage polarization to the M2 type, effectively mitigating damaging inflammatory burst and promoting tissue healing. This well-orchestrated strategy provides a sequential therapy of BAIs by utilizing microenvironmental variations, offering a conceptual paradigm shift in the field of nanomedicine anti-infectives.

Asunto(s)

Antibacterianos , Biopelículas , Galio , Especies Reactivas de Oxígeno , Biopelículas/efectos de los fármacos , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Galio/química , Galio/farmacología , Ratones , Portadores de Fármacos/química , Células RAW 264.7 , Humanos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología

RESUMEN

Objectives: A relationship between endoscopic submucosal dissection (ESD) and deep vein thrombosis has been recognized. We previously reported that a high corrected midazolam dose (total midazolam dose/initial dose of midazolam used to induce sedation) is related to elevated D-dimer levels after ESD. In this study, the effect of compression stockings (CSs) in preventing thrombosis following ESD under sedation was evaluated by measuring D-dimer levels before and after ESD. Methods: The participants were patients who underwent ESD for upper gastrointestinal tumors during the period between April 2018 and October 2022. Patients with pre-ESD D-dimer levels ≥1.6 µg/m and patients with corrected midazolam doses ≤3.0 were excluded. A retrospective investigation of the relationship between CS use and high post-ESD D-dimer levels (difference in D-dimer levels ≥1.0 µg/mL between before and after ESD) was conducted. Results: There were 27 patients in the non-CS group (NCS) and 33 patients in the CS group. The number of patients with high post-ESD D-dimer levels was 13 (48.2%) in the non-CS group and six (18.2%) in the CS group; the number in the CS group was significantly lower (p = 0.024). On logistic regression analysis, a relationship was seen between the wearing of CSs and a lower number of patients with high post-ESD D-dimer levels (odds ratio 0.24, 95% confidence interval 0.08-0.79, p = 0.019). Conclusion: Wearing CSs was related to a lower risk of high post-ESD D-dimer levels. This result suggests that thrombus formation is a cause of elevated D-dimer levels after ESD.

RESUMEN

Microplastics (MPs) are ubiquitous in the environment, continuously undergo aging processes and release toxic chemical substances. Understanding the environmental behaviors of MPs is critical to accurately evaluate their long-term ecological risk. Generalized two-dimensional correlation spectroscopy (2D-COS) is a powerful tool for MPs studies, which can dig more comprehensive information hiding in the conventional one-dimensional spectra, such as infrared (IR) and Raman spectra. The recent applications of 2D-COS in analyzing the behaviors and fates of MPs in the environment, including their aging processes, and interactions with natural organic matter (NOM) or other chemical substances, were summarized systematically. The main requirements and limitations of current approaches for exploring these processes are discussed, and the corresponding strategies to address these limitations and drawbacks are proposed as well. Finally, new trends of 2D-COS are prospected for analyzing the properties and behaviors of MPs in both natural and artificial environmental processes.

Asunto(s)

Monitoreo del Ambiente , Microplásticos , Microplásticos/análisis , Monitoreo del Ambiente/métodos , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Contaminantes Químicos del Agua/análisis

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Viral pneumonia is the leading cause of death after SARS-CoV-2 infection. Despite effective at early stage, long-term treatment with glucocorticoids can lead to a variety of adverse effects and limited benefits. The Chinese traditional herb Pogostemonis Herba is the aerial part of Pogostemon Cablin (Blanco) Benth., which has potent antiviral, antibacterial, anti-inflammatory, and anticancer effects. It was used widely for treating various throat and respiratory diseases, including COVID-19, viral infection, cough, allergic asthma, acute lung injury and lung cancer. AIM OF THE STUDY: To investigate the antiviral and anti-inflammatory effects of chemical compounds from Pogostemonis Herba in SARS-CoV-2-infected hACE2-overexpressing mouse macrophage RAW264.7 cells and hACE2 transgenic mice. MATERIALS AND METHODS: The hACE2-overexpressing RAW264.7 cells were exposed with SARS-CoV-2. The cell viability was detected by CCK8 assay and cell apoptotic rate was by flow cytometric assay. The expressions of macrophage M1 phenotype markers (TNF-α and IL-6) and M2 markers (IL-10 and Arg-1) as well as the viral loads were detected by qPCR. The mice were inoculated intranasally with SARS-CoV-2 omicron variant to induce viral pneumonia. The levels of macrophages, neutrophils, and T cells in the lung tissues of infected mice were analyzed by full spectrum flow cytometry. The expressions of key proteins were detected by Western blot assay. RESULTS: Diosmetin-7-O-ß-D-glucopyranoside (DG) presented the strongest anti-SARS-CoV-2 activity. Intervention with DG at the concentrations of 0.625-2.5 µM not only reduced the viral replication, cell apoptosis, and the productions of inflammatory cytokines (IL-6 and TNF-α) in SARS-CoV-2-infected RAW264.7 cells, but also reversed macrophage polarity from M1 to M2 phenotype. Furthermore, treatment with DG (25-100 mg/kg) alleviated acute lung injury, and reduced macrophage infiltration in SARS-COV-2-infected mice. Mechanistically, DG inhibited SARS-COV-2 gene expression and HK3 translation via targeting YTHDF1, resulting in the inactivation of glycolysis-mediated NF-κB pathway. CONCLUSIONS: DG exerted the potent antiviral and anti-inflammatory activities. It reduced pneumonia in SARS-COV-2-infected mice via inhibiting the viral replication and accelerating M2 macrophage polarization via targeting YTHDF1, indicating its potential for COVID-19 treatment.

Asunto(s)

Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Macrófagos , SARS-CoV-2 , Replicación Viral , Animales , Ratones , Células RAW 264.7 , Replicación Viral/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/virología , SARS-CoV-2/efectos de los fármacos , Antivirales/farmacología , Ratones Transgénicos , Pogostemon/química , Citocinas/metabolismo , Apoptosis/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/virología , Pulmón/patología , Glucósidos/farmacología , Glucósidos/aislamiento & purificación , Flavonoides/farmacología , Flavonoides/aislamiento & purificación , Flavonoides/uso terapéutico , Enzima Convertidora de Angiotensina 2/metabolismo , Antiinflamatorios/farmacología , Masculino , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , Humanos

RESUMEN

Rapid screening for foodborne pathogens is crucial for food safety. A rapid and one-step electrochemical sensor has been developed for the detection of Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Salmonella typhimurium (S. typhimurium). Through the construction of aptamer/two-dimensional carboxylated Ti3C2Tx (2D C-Ti3C2Tx)/two-dimensional Zn-MOF (2D Zn-MOF) composites, the recognition elements, signal tags, and signal amplifiers are integrated on the electrode surface. Pathogens are selectively captured using the aptamer, which increases the impedance of the electrode surface，leads to a decrease in the 2D Zn-MOF current. Bacteria can be rapidly quantified using a one-step detection method and the replacement of aptamers. The detection limits for E. coli, S. aureus, and S. typhimurium are 6, 5, and 5 CFU·mL-1, respectively. The sensor demonstrated reliable detection capabilities in real-sample testing. Therefore, the one-step sensor based on the 2D Zn-MOF and 2D C-Ti3C2Tx has significant application value in the detection of foodborne pathogens.

Asunto(s)

Técnicas Electroquímicas , Escherichia coli , Salmonella typhimurium , Staphylococcus aureus , Zinc , Staphylococcus aureus/aislamiento & purificación , Salmonella typhimurium/aislamiento & purificación , Zinc/análisis , Escherichia coli/aislamiento & purificación , Técnicas Electroquímicas/instrumentación , Técnicas Biosensibles/instrumentación , Estructuras Metalorgánicas/química , Microbiología de Alimentos , Titanio/química , Límite de Detección , Electrodos , Contaminación de Alimentos/análisis

RESUMEN

Making health-enhancing tea from Forsythia suspensa leaves has been a tradition of Chinese folk culture for centuries. However, these leaves were not officially recognized as a new food source until 2017 by the Chinese government. In this study, ethyl acetate fractions from Forsythia suspensa fruit and leaves exhibited excellent antioxidant activity in vitro antioxidant assays and in vivo D-galactose-induced aging mice model. The antioxidant activity of the leaves was higher than that of fruit both in vitro and in vivo. The chemical constituents present in these ethyl acetate fractions were comprehensively analyzed using UHPLC-Q-Exactive-Orbitrap/MS. A total of 20 compounds were identified, among which forsythoside E, (+)-epipinoresinol, dihydromyricetin, chlorogenic acid, and ursolic acid were exclusively detected in the ethyl acetate fraction of Forsythia suspensa leaves, but absent in the ethyl acetate fraction derived from its fruit. This study provides theoretical support for the utilization of Forsythia suspensa fruit and leaves.

Asunto(s)

Envejecimiento , Antioxidantes , Forsythia , Frutas , Galactosa , Extractos Vegetales , Hojas de la Planta , Animales , Forsythia/química , Hojas de la Planta/química , Ratones , Frutas/química , Extractos Vegetales/química , Cromatografía Líquida de Alta Presión , Antioxidantes/química , Antioxidantes/farmacología , Envejecimiento/efectos de los fármacos , Masculino , Humanos , Espectrometría de Masas

RESUMEN

Acute myeloid leukemia (AML) is a deadly form of leukemia with ineffective traditional treatment and frequent chemoresistance-associated relapse. Personalized drug screening holds promise in identifying optimal regimen, nevertheless, primary AML cells undergo spontaneous apoptosis during cultures, invalidating the drug screening results. Here, we reconstitute a 3D osteogenic niche (3DON) mimicking that in bone marrow to support primary AML cell survival and phenotype maintenance in cultures. Specifically, 3DON derived from osteogenically differentiated mesenchymal stem cells (MSC) from healthy and AML donors are co-cultured with primary AML cells. The AML cells under the AML_3DON niche showed enhanced viability, reduced apoptosis and maintained CD33+ CD34-phenotype, associating with elevated secretion of anti-apoptotic cytokines in the AML_3DON niche. Moreover, AML cells under the AML_3DON niche exhibited low sensitivity to two FDA-approved chemotherapeutic drugs, further suggesting the physiological resemblance of the AML_3DON niche. Most interestingly, AML cells co-cultured with the healthy_3DON niche are highly sensitive to the same sample drugs. This study demonstrates the differential responses of AML cells towards leukemic and healthy bone marrow niches, suggesting the impact of native cancer cell niche in drug screening, and the potential of re-engineering healthy bone marrow niche in AML patients as chemotherapeutic adjuvants overcoming chemoresistance, respectively.

Asunto(s)

Supervivencia Celular , Leucemia Mieloide Aguda , Células Madre Mesenquimatosas , Fenotipo , Microambiente Tumoral , Humanos , Leucemia Mieloide Aguda/patología , Microambiente Tumoral/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Supervivencia Celular/efectos de los fármacos , Técnicas de Cocultivo/métodos , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Médula Ósea/patología , Médula Ósea/efectos de los fármacos , Nicho de Células Madre/efectos de los fármacos , Células de la Médula Ósea/citología , Masculino , Diferenciación Celular/efectos de los fármacos , Femenino

RESUMEN

Extracellular matrix (ECM) stiffness is a major driver of stem cell fate. However, the involvement of the three-dimensional (3D) genomic reorganization in response to ECM stiffness remains unclear. Here, we generated comprehensive 3D chromatin landscapes of mesenchymal stem cells (MSCs) exposed to various ECM stiffness. We found that there were more long-range chromatin interactions, but less compartment A in MSCs cultured on stiff ECM than those cultured on soft ECM. However, the switch from compartment B in MSCs cultured on soft ECM to compartment A in MSCs cultured on stiff ECM included genes encoding proteins primarily enriched in cytoskeleton organization. At the topologically associating domains (TADs) level, stiff ECM tends to have merged TADs on soft ECM. These merged TADs on stiff ECM include upregulated genes encoding proteins enriched in osteogenesis, such as SP1, ETS1, and DCHS1, which were validated by quantitative real-time polymerase chain reaction and found to be consistent with the increase of alkaline phosphatase staining. Knockdown of SP1 or ETS1 led to the downregulation of osteogenic marker genes, including COL1A1, RUNX2, ALP, and OCN in MSCs cultured on stiff ECM. Our study provides an important insight into the stiff ECM-mediated promotion of MSC differentiation towards osteogenesis, emphasizing the influence of mechanical cues on the reorganization of 3D genome architecture and stem cell fate.

Asunto(s)

Diferenciación Celular , Matriz Extracelular , Células Madre Mesenquimatosas , Osteogénesis , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/genética , Matriz Extracelular/metabolismo , Diferenciación Celular/genética , Humanos , Células Cultivadas , Animales

RESUMEN

According to the United Nations, around 53 million metric tons of electronic waste is produced every year, worldwide, the big majority of which goes unprocessed. With the rapid advances in AI technologies and adoption of smart gadgets, the demand for powerful logic and memory chips is expected to boom. Therefore, the development of green electronics is crucial to minimizing the impact of the alarmingly increasing e-waste. Here, it is shown the application of a green synthesized, chemically stable, carbonyl-decorated 2D organic, and biocompatible polymer as an active layer in a memristor device, sandwiched between potentially fully recyclable electrodes. The 2D polymer's ultramicro channels, decorated with C═O and O─H groups, efficiently promote the formation of copper nanofilaments. As a result, the device shows excellent bipolar resistive switching behavior with the potential to mimic synaptic plasticity. A large resistive switching window (103), low SET/RESET voltage of ≈0.5/-1.5 V), excellent device-to-device stability and synaptic features are demonstrated. Leveraging the device's synaptic characteristics, its applications in image denoising and edge detection is examined. The results show a reduction in power consumption by a factor of 103 compared to a traditional Tesla P40 graphics processing unit, indicating great promise for future sustainable AI-based applications.

RESUMEN

BACKGROUND AND OBJECTIVES: Observational studies suggest a link between D3 lymphadenectomy and improved disease-free survival in some colon cancer patients. However, high-quality randomized controlled trials are needed to confirm its advantage over D2 lymphadenectomy. Concerns about potential complications with D3 have limited its use outside of Japan. This study examines short-term outcomes following D3 lymphadenectomy for right-sided colon cancer compared to the established D2 procedure. Materials and Methods: This retrospective cohort single center study analyzed data on patients with right-sided colon cancer who underwent curative surgery within our healthcare trust between January 2019 and November 2022. Only patients treated by surgeons who routinely perform D3 lymphadenectomy were included for a homogenous study population. The decision to perform D3 was at the discretion of the operating surgeon. Data were collected from both paper charts and electronic medical records. Non-parametric statistical tests were used for data analysis. Results: A total of 214 patients met the criteria, with 170 undergoing D2 lymphadenectomy and 44 undergoing D3 lymphadenectomy. There were no significant differences between the groups in terms of surgery duration, blood loss, postoperative hemoglobin levels, or transfusion needs. Interestingly, the D3 group had a lower complication rate (25%) compared to the D2 group (41.2%). However, the D3 group also had a higher rate of lymph node spread (45.5% vs. 30.6% for D2) and more lymph nodes removed (19 [16, 25] vs. 23 [18, 28]). Importantly, both groups achieved similar complete tumour removal rates. Conclusions: This study suggests D3 lymphadenectomy for right-sided colon cancer might be safe with potential benefits, especially for younger patients with suspected lymph node involvement. However, the limited sample size necessitates larger, randomized trials to confirm these findings and potentially establish D3 lymphadenectomy as standard care.

Asunto(s)

Neoplasias del Colon , Estudios de Factibilidad , Escisión del Ganglio Linfático , Humanos , Escisión del Ganglio Linfático/métodos , Neoplasias del Colon/cirugía , Neoplasias del Colon/patología , Masculino , Femenino , Estudios Retrospectivos , Anciano , Londres , Persona de Mediana Edad , Resultado del Tratamiento , Hospitales Generales , Hospitales de Distrito , Supervivencia sin Enfermedad , Estadificación de Neoplasias , Anciano de 80 o más Años