Diverse Types Research Articles

Inhibition of GPR68 induces ferroptosis and radiosensitivity in diverse cancer cell types

Radioresistance is thought to be a major consequence of tumor milieu acidification resulting from the Warburg effect. Previously, using ogremorphin (OGM), a small molecule inhibitor of GPR68, an extracellular proton sensing receptor, we demonstrated that GPR68 is a key pro-survival pathway in glioblastoma cells. Here, we demonstrate that GPR68 inhibition also induces ferroptosis in lung cell carcinoma (A549) and pancreatic ductal adenocarcinoma (Panc02) cells. Moreover, OGM synergized with ionizing radiation to induce lipid peroxidation, a hallmark of ferroptosis, as well as reduce colony size in 2D and 3D cell culture. GPR68 inhibition is not acutely detrimental but increases intracellular free ferrous iron, which is known to trigger reactive oxygen species (ROS) generation. In summary, GPR68 inhibition induces lipid peroxidation in cancer cells and sensitizes them to ionizing radiation in part through the mobilization of intracellular free ferrous iron. Our results suggest that GPR68 is a key mediator of cancer cell radioresistance activated by acidic tumor microenvironment.

Broad-spectrum tolerance to disinfectant-mediated bacterial killing due to mutation of the PheS aminoacyl tRNA synthetase.

Disinfectants are essential tools for controlling infectious diseases and maintaining sterile conditions in many medical and food-industry settings. Recent work revealed that a deficiency in the carbohydrate phosphotransferase system (PTS) confers pan-tolerance to killing by diverse disinfectant types through its interaction with the cAMP-CRP regulatory network. The present work characterized a pan-tolerance mutant obtained by enrichment using phenol as a lethal probe and an Escherichia coli PTS null mutant as a parental strain. The resulting super-pan-tolerant mutant, which harbored an F158C substitution in PheS, inhibited bacterial killing by multiple disinfectant classes with surprisingly little effect on antimicrobial lethality. The PheS substitution, which was expected to lower substrate recognition efficiency and result in deacylated tRNAphe occupying the ribosomal A site, activated relA expression and synthesis of ppGpp, even in the absence of disinfectant exposure. ppGpp, along with DksA, increased RpoS function by activating promoters of dsrA and iraP, two genes whose products increase the expression and stability of RpoS. Subsequently, RpoS upregulated the expression of genes encoding a universal stress protein (UspB) and an oxidative stress peroxidase (KatE), which preconditioned bacteria to better survive a variety of disinfectants. Disinfectant-mediated accumulation of reactive oxygen species (ROS) and bacterial killing were abolished/reduced by exogenous dimethyl sulfoxide and by a PheS F158C substitution up-regulating genes encoding ROS-detoxifying enzymes (katE, sodA, oxyR, ahpC). These data identify a pheS mutation-triggered, ppGpp-stimulated transcriptional regulatory cascade that negates biocide-mediated lethality, thereby tying the stringent response to protection from ROS-mediated biocide lethality.

One-step Centimeter-Scale Growth of Sub-100-nm Perovskite Single-Crystal Arrays in Ambient Air for Color Painting.

Halide perovskite single crystals have demonstrated enormous potential for next-generation integrated optoelectronic devices. However, there is a lack of a facile method to realize the controllable growth of large-scale, high-quality, and high-resolution perovskite single crystal arrays on diverse types of substrates, which hinders their application in practical scenarios. Here, a one-step wettability-guided blade coating approach is reported for the rapid in situ crystallization of large-scale, multicolor, and sub-100 nm perovskite single-crystal arrays in the ambient environment. By this strategy, the physical dimensions of perovskite single crystals can be precisely regulated from 90 to 260 nm, with a size variation coefficient < 10% and an area of over 900 mm2. All three typicalhalogen perovskites for multi-color luminescence, CsPbX3 (X = Cl, Br, I) and their mixtures (Cl/Br or Br/I systems), are appliable to this fabrication process through the demonstration of complex RGB patterns with remarkable photoluminescence properties. Moreover, various rigid substrates such as silicon oxide (SiO2), silicon (Si), and glass can also be used to construct the wettability-constrast templates where perovskite crystal nucleate and grow. After that, the perovskite single-crystal arrays or complex patterns can be transferred onto flexible substrates, for instance, COC. This method combines convenient solution processing with conventional photolithography to prepare the high-resolution, large-area, and superior-quality perovskite single crystal arrays in a high-throughput manner, showing great potential in the integration of perovskite nano-optoelectronic devices and chips.

Impact of mechanotransduction on gene expression changes in periodontal ligament during orthodontic tooth movement.

The periodontal ligament (PDL) is a structure between the alveolar bone and cementum, essential for tooth stability and composed of diverse cell types. Mohawk homeobox (Mkx) is a master transcription factor that regulates tendon and ligament homeostasis. However, the specific cell populations expressing Mkx and its role in mechanotransduction during orthodontic tooth movement (OTM) remain unclear. We conducted single-cell RNA sequencing on wild-type rat PDL at 0day, 1week, and 2weeks of post-OTM using coil springs to elucidate Mkx's function and the changes in cell populations under continuous mechanical stimulation. In addition, RT-qPCR was performed to assess the relationship between tenogenic gene expression and Mkx expression in human PDL cells. The rat PDL was identified to consist of 14 clusters, with Mkx and Scleraxis (Scx) expressed in distinct cell populations. Collagen and ECM production increased throughout the OTM period, while the sterile inflammatory response was initially heightened and later diminished, indicating that bone remodeling occurs later in the inflammatory response. Overexpression of MKX in human PDL cells enhanced COL1A1 and DECORIN expression. Mechanical stimulation of the PDL appears to trigger an aseptic inflammatory response that disrupts PDL homeostasis and promotes bone remodeling. Mkx may exert a protective effect on the PDL during mechanical stimulation.

Hydronephrosis and survival in cervical cancer patients: The role of urinary diversion.

We aimed to assess the impact of urinary diversion on survival in patients with advanced cervical cancer (CC) and hydronephrosis. Additionally, we examined the influence of other patient factors and urinary diversion type on survival. A retrospective study analyzed survival in cervical cancer (CC) patients with hydronephrosis treated at two Mexican hospitals from 2011 to 2023. Patient data, including demographics, clinical, and pathological characteristics, were collected. Urinary diversion details and complications were recorded. Survival analysis was performed using Kaplan-Meier method and Cox regression model to identify predictors of survival. A total of 228 cervical cancer patients presenting with hydronephrosis were analyzed. Median follow-up was 9months. The majority of patients were in stage IVA (44.3%), with 66.7% exhibiting bilateral renal involvement. Urinary diversion was performed in 192 patients (84.2%). Median overall survival (OS) was 15.5months. Multivariate analysis identified stage, disease course, oncologic treatment, laterality, performance status, and urinary diversion as independent prognostic factors for survival. In patients undergoing urinary diversion, bilateral renal involvement (HR 2.0) and deteriorated performance status (HR 3.6) were risk factors for mortality. Neither the laterality (unilateral or bilateral) nor the type of diversion significantly affected overall survival. Survival in CC patients with hydronephrosis is influenced by factors such as: bilateral involvement, performance status, clinical stage, course and treatment of the underlying malignancy and urinary diversion. Urinary diversion improves survival, regardless of the specific diversion type or whether the diversion is unilateral or bilateral.

Modulating the blood-brain barrier in CNS disorders: A review of the therapeutic implications of secreted protein acidic and rich in cysteine (SPARC).

Secreted protein acidic and rich in cysteine (SPARC), an essential stromal cell protein, plays a crucial role in angiogenesis and maintaining endothelial barrier function. This protein is expressed by diverse cell types, including endothelial cells, fibroblasts, and macrophages, with increased expression found in regions of tissues undergoing active remodeling, repair, and proliferation. The role of SPARC in non-neural tissues is of significant interest. In the central nervous system (CNS), SPARC is highly expressed in blood vessels during early development. It becomes down-regulated as the brain matures, a pattern consistent with its role in angiogenesis and blood-brain barrier (BBB) establishment. In this review, we explore the multifaceted roles of SPARC in regulating CNS disorders, particularly its action in angiogenesis, inflammatory responses, neural system development and repair, barrier establishment, maintenance of BBB function, and the pathogenesis of CNS disorders triggered by BBB dysfunction.

Innovations in Quantitative Rapid Testing: Early Prediction of Health Risks.

As health monitoring becomes increasingly intricate, the demand for innovative solutions to predict and assess health status is more pressing than ever. This review focuses on the transformative potential of multi-sensor technologies in health monitoring, emphasizing their role in early health status prediction. By integrating diverse sensor types ranging from wearable fitness trackers to implantable devices and environmental monitors healthcare professionals can gain a richer, more nuanced understanding of an individual's physiological state. We analyze various configurations of multi-sensor networks and their efficacy in identifying early indicators of health issues, such as cardiovascular diseases, diabetes, and respiratory ailments. For example, the combination of biometric sensors that track vital signs with environmental data on pollutants can yield invaluable insights into a patient's overall health. This integrated approach not only improves the accuracy of health assessments but also facilitates timely interventions. Furthermore, we address the challenges inherent in multi-sensor systems, including data integration, device interoperability, and the need for advanced algorithms capable of processing complex datasets. Recent advancements in machine learning and artificial intelligence are underscored as pivotal in enhancing the capabilities of these technologies for predictive health analytics. Ultimately, this review highlights how multi-sensor systems can redefine early health status prediction, paving the way for proactive healthcare strategies that significantly improve patient outcomes and optimize healthcare delivery.

Cancer-associated fibroblast-derived exosomes in cancer progression: a focus on hepatocellular carcinoma.

The tumor microenvironment (TME) has drawn much interest recently in the search for innovative cancer therapeutics, especially in light of the growing body of evidence supporting the efficacy of immune checkpoint inhibitors (ICIs). The TME comprises various cell types within the extracellular matrix (ECM), such as immune cells, endothelial cells, and cancer-associated fibroblasts (CAFs). Throughout the malignancy, these cells interact with cancerous cells and with one another. Inside the TME, CAFs are predominant and diverse cell types essential in regulating immune escape, angiogenesis, chemotherapeutic resistance, and cancer cells to invade and metastasize. Extracellular vesicles (EVs) and soluble substances are secreted by CAFs, which also remodel the extracellular matrix to partially coordinate their actions. A subclass of EVs called exosomes comprises proteins, lipids, and nucleic acids. Exosomes contain macromolecules that can transfer from one cell to another, changing the recipient cell's activity. Since exosomes are also circulating, it is possible to investigate their composition as potential biomarkers for cancer patient's diagnosis and prognosis. In this review, we focus on the function of exosomes derived from CAFs in the communications between CAFs and other TME cells and cancerous cells. Initially, we explain the various roles of CAFs in carcinogenesis. Subsequently, we address the processes by which CAFs interact with hepatocellular carcinoma (HCC) cells and other cells within the TME, with a special focus on the function of exosomes. We then go into greater detail regarding the processes by which exosomes derived from CAFs aid in the development of HCC, in addition to the clinical implications of exosomes. Finally, we address facets of exosomes that warrant additional research, such as novel discoveries regarding the enhancement of immune checkpoint inhibitor blockade therapy.

Advanced computational models for accurate fracture toughness prediction in diverse concrete types: Insights from a robust laboratory database

Advanced computational models for accurate fracture toughness prediction in diverse concrete types: Insights from a robust laboratory database

The Gastric Cancer Registry: A multi-omic cellular and molecular resource for cancer biomarker and therapeutic discovery.

491 Background: The Gastric Cancer Registry (GCR) is a comprehensive clinical and genomic data resource focused on gastric cancer (GC) patients and individuals with a family history of GC or a germline CDH1 mutation. As part of the GCR’s ongoing enrollment, patients contribute cancer history information, archival tumor samples and other biospecimens. The cancer samples undergo extensive molecular and cellular analysis that includes genomic sequencing and spatial analysis. We have generated a robust dataset, publicly accessible online through the GCR Genome Explorer (GCR-GE). This genomic, molecular and cellular resource provides a rich data set that accelerates multidisciplinary research aimed at improving detection and treatment strategies for GC. GC disproportionately affects Latin American populations - we have included new cohorts from Latin America. The GCR enables researchers, clinicians and patients to address specific questions about the molecular and cellular basis of GC. Methods: GC samples underwent whole genome, whole exome, and bulk RNA sequencing were conducted. The genomic features identified include copy number variation, gene mutations, gene expression, microbiome composition, estimation of tumor-infiltrating immune cells, tumor neoantigens, MSI/MSS status, and HLA subtypes. In addition to genomic data, clinical data was compiled from survey responses and pathology reports and integrated into the GCR-GE. We have incorporated single cell and spatial analysis that includes diverse cell types, single cell gene expression and cellular architecture in native tumor tissues. This data was released to the GCR Genome Explorer website. Results: A total of 817 subjects have enrolled in the GCR including 598 diagnosed with GC and 219 at high-risk for GC through family history of GC and/or a CDH1 mutation. Of the 598 with GC, some met multiple criteria including at least 40 with a family history of GC, 10 with a CDH1 mutation, and 18 with both a family history of GC and a CDH1 mutation. The GCR-GE includes data from 257 gastric tumors in addition to external datasets from TCGA. In the latest data release, clinical and genomic data from 78 gastric tumors from patients in Latin America were integrated into the GCR-GE. Conclusions: The GCR is a comprehensive database of crucial clinical and genomic data necessary for driving forward GC research. Through global expansion, the GCR has generated a more representative dataset by increasing racial diversity and including underrepresented populations that are at higher risk for GC.

Leveraging Hypernetworks and Learnable Kernels for Consumer Energy Forecasting Across Diverse Consumer Types

Leveraging Hypernetworks and Learnable Kernels for Consumer Energy Forecasting Across Diverse Consumer Types

Recent advances in TGF-β signaling pathway in COVID-19 pathogenesis: A review.

The coronavirus disease 2019 (COVID-19) has resulted in approximately 7.0 million fatalities between 2019 and 2022, underscoring a pressing need for comprehensive research into its underlying mechanisms and therapeutic avenues. A distinctive feature of severe COVID-19 is the dysregulated immune response characterized by excessive activation of immune cells and the consequent cytokine storms. Recent advancements in our understanding of cellular signaling pathways have illuminated the role of Transforming Growth Factor Beta (TGF-β) as a pivotal signaling molecule with significant implications for the pathogenesis of infectious diseases, including COVID-19. Emerging evidence reveals that TGF-β signaling, when activated by viral components or secondary pathways, adversely affects diverse cell types, particularly immune cells, and lung tissue, leading to complications such as pulmonary fibrosis. In our review article, we critically evaluate recent literature on the involvement of TGF-β signaling in the progression of COVID-19. We discuss a range of pharmacological interventions, including nintedanib, pirfenidone, corticosteroids, proton pump inhibitors, and histone deacetylase inhibitors, and their potential to modulate the TGF-β pathway in the context of COVID-19 treatment. Additionally, we explore ongoing clinical trials involving mesenchymal stem cells, low-dose radiation therapy, and artemisinin derivatives to assess their impact on TGF-β levels and subsequent clinical outcomes in COVID-19 patients. This review is particularly relevant at this juncture as the global health community continues to grapple with the ramifications of the COVID-19 pandemic, highlighting the urgent need for targeted therapeutic strategies aimed at TGF-β modulation to mitigate disease severity and improve patient outcomes.

MFAP5 Strengthened the Stem Cell Features of Non-small Cell Lung Cancer Cells by Regulating the FBW/Sox9 Axis.

Non-small cell lung cancer (NSCLC) is a type of malignant tumor with high morbidity as well as mortality. The process of lung cancer may be driven by cancer stem cells. It was known that MFAP5 enhanced the occurrence of diverse types of cancer. Also, MFAP5 has the potential to induce the degradation of FBW7 which is a tumor suppressor. Lower levels of FBW7 enhance the stability of Sox9, which is the cancer stem cell-related protein. However, whether the MFAP5 can modulate the stem cell features of NSCLC cells by modulating the FBW7/Sox9 axis is unclear. Therefore, this study aimed to explore the role of MFAP5/FBW7/Sox9 axis on the stem cell features of NSCLC cells and develop a new treatment of this carcinoma. In this study, we explored the effects of MFAP5 on the stem cell features of NSCLC cells for the first time. We established MFAP5 overexpression and knockdown NSCLC cells. Clone formation assays and cell sphere culture assays were conducted for the exploration of the growth and stem cell features of these cells. Western blotting was applied for the detection of Sox9 and FBW7 expression in these cells. CHX was applied for the treatment of these cells for the detection of degradation of Sox9. Finally, we overexpressed the Sox9 in MFAP5 knockdown NSCLC cells. MFAP5 promoted the growth and stem cell features of these cells. Knockdown of MFAP5 induced higher levels of FBW7 while restricting the expression of Sox9. Knockdown of MFAP5 aggravated the degradation of Sox9. Overexpression of Sox9 abrogated the efficacy of MFAP5 inhibition on the growth as well as stem cell features of these cells. The results of this study clarified the role of MFAP5/FBW7/Sox9 axis on the development of non-small cell lung cancer cells, providing the potential therapeutic target for the clinical treatment of NSCLC. MFAP5 maintained the stem cell features of non-small cell lung cancer cells by modulating FBW7/Sox9 axis.

DigiSort: Smart Asset Organization

Abstract: The exponential growth of digital files in recent years has posed significant challenges in managing, organizing, and retrieving data efficiently. This paper introduces the Digital Asset Organizer (DAO), a robust solution designed to address these challenges by leveraging advanced categorization techniques. DAO intelligently classifies files into "Basic" and "Advanced" categories through multi-criteria evaluation, including file content analysis, size thresholds, and file extensions. By integrating a seamless web interface, users can upload files, specify organizational filters, and download categorized assets in compressed ZIP formats, enhancing portability and storage management. DAO's classification system incorporates keyword detection and metadata analysis, ensuring accuracy and adaptability across diverse file types. Its responsive design further allows users to access and organize assets from any device, streamlining workflows and reducing digital clutter. This innovative research represents a significant step toward simplifying digital asset management and lays a foundation for scalable and intelligent file handling systems

Tumor microenvironment regulation by reactive oxygen species-mediated inflammasome activation.

Tumor microenvironment (TME) is composed of diverse cell types whose interactions, both direct and indirect, significantly influence tumorigenesis and therapeutic outcomes. Within TME, reactive oxygen species (ROS) are produced by various cells and exhibit a dual role: moderate ROS levels promote tumor initiation and progression, whereas excessive levels induce cancer cell death, influencing the efficacy of anticancer therapies. Inflammasomes, cytosolic multiprotein complexes, are pivotal in multiple stages of tumorigenesis and play a crucial role in establishing the inflammatory TME. By releasing cytokines such as IL-1β and IL-18, inflammasomes contribute to immune cell recruitment and sustain a chronic inflammatory state that supports tumor growth. ROS are critical regulators of inflammasome activation, with the impact of ROS-mediated activation differing across cell types, leading to distinct influences on tumor progression and therapeutic responses. This review explores how ROS drive inflammasome activation in various TME-associated cells and the reciprocal ROS generation induced by inflammasomes, examining their multifaceted impact on tumorigenesis and therapeutic efficacy. By elucidating the complex interplay between ROS and inflammasomes in TME, we provide insights into potential therapeutic approaches that could modulate cancer progression and enhance treatment outcomes.

The zinc-finger transcription factor Blimp1/Prdm1 is required for uterine remodelling and repair in the mouse.

The zinc finger transcription factor Blimp1/PRDM1 regulates gene expression in diverse cell types. Its activity controls the maternal decidual response at early post-implantation stages of development. The present experiments demonstrate surprisingly that Blimp1 activity in the uterus is required for tissue remodelling at sites of embryonic failure. Moreover Blimp1 mutant females are refractory to RU486 induced decidual shedding. RNA-seq together with immunostaining experiments strongly suggest that the failure to up-regulate expression of the matrix metalloprotease Mmp10 in combination with insufficient suppression of BMP signalling, likely explain Blimp1-dependent phenotypic changes. In the post-partum uterus Blimp1 together with Mmp10 are highly upregulated at sites of tissue repair following placental detachment. Conditional Blimp1 removal significantly impairs the re-epithelization process and severely impacts involution of the endometrium and luminal epithelium. Overall these results identify Blimp1 as a master regulator of uterine tissue remodelling and repair.

Common cutaneous manifestations in hematological malignancies

Hematologic malignancies (HMs) are among the most prevalent and diverse types of cancer. Patients with HMs may experience a wide range of skin-related issues. These dermatological manifestations can be grouped into three main categories: Direct skin infiltration by malignant cells or their byproducts, cutaneous effects indirectly linked to the malignancy, and skin changes resulting from treatment. Such dermatological issues can significantly impact a patient’s quality of life. Managing these complex conditions requires a collaborative, multidisciplinary approach. Close coordination between dermatologists and hematologists is crucial for accurate diagnosis, personalized treatment planning, and ongoing monitoring.

Improved lung nodule segmentation with a squeeze excitation dilated attention based residual UNet.

The diverse types and sizes, proximity to non-nodule structures, identical shape characteristics, and varying sizes of nodules make them challenging for segmentation methods. Although many efforts have been made in automatic lung nodule segmentation, most of them have not sufficiently addressed the challenges related to the type and size of nodules, such as juxta-pleural and juxta-vascular nodules. The current research introduces a Squeeze-Excitation Dilated Attention-based Residual U-Net (SEDARU-Net) with a robust intensity normalization technique to address the challenges related to different types and sizes of lung nodules and to achieve an improved lung nodule segmentation. After preprocessing the images with the intensity normalization method and extracting the Regions of Interest by YOLOv3, they are fed into the SEDARU-Net with dilated convolutions in the encoder part. Then, the extracted features are given to the decoder part, which involves transposed convolutions, Squeeze-Excitation Dilated Residual blocks, and skip connections equipped with an Attention Gate, to decode the feature maps and construct the segmentation mask. The proposed model was evaluated using the publicly available Lung Nodule Analysis 2016 (LUNA16) dataset, achieving a Dice Similarity Coefficient of 97.86%, IoU of 96.40%, sensitivity of 96.54%, and precision of 98.84%. Finally, it was shown that each added component to the U-Net's structure and the intensity normalization technique increased the Dice Similarity Coefficient by more than 2%. The proposed method suggests a potential clinical tool to address challenges related to the segmentation of lung nodules with different types located in the proximity of non-nodule structures.

Innovation in services business through diversification of service types to increase customer satisfaction at markas grafis business

Innovation in services business through diversification of service types to increase customer satisfaction at markas grafis business

Effects of Chemical Pretreatments of Wood Cellulose Nanofibrils on Protein Adsorption and Biological Outcomes.

Wood-based nanocellulose is emerging as a promising nanomaterial in the field of tissue engineering due to its unique properties and versatile applications. Previously, we used TEMPO-mediated oxidation (TO) and carboxymethylation (CM) as chemical pretreatments prior to mechanical fibrillation of wood-based cellulose nanofibrils (CNFs) to produce scaffolds with different surface chemistries. The aim of the current study was to evaluate the effects of these chemical pretreatments on serum protein adsorption on 2D and 3D configurations of TO-CNF and CM-CNF and then to investigate their effects on cell adhesion, spreading, inflammatory mediator production in vitro, and the development of foreign body reaction (FBR) in vivo. Mass spectrometry analysis revealed that the surface chemistry played a key role in determining the proteomic profile and significantly influenced the behavior of periodontal ligament fibroblasts and osteoblast-like cells (Saos-2). The surface of TO-CNF 2D samples showed the highest protein adsorption followed by TO-CNF 3D samples. CM-CNF 2D samples adsorbed a higher number of proteins than their 3D counterparts. None of the CNF scaffolds showed toxicity in vitro or in vivo. However, carboxymethylation pretreatment negatively affected the adhesion, morphology, and spreading of both cell types. Although the CNF materials displayed clear differences in surface chemistry and proteomic profiles, both triggered the same foreign body response after being subcutaneously implanted in rats for 90 days. This observation highlights that the degradation rate of CNF scaffolds plays a central role in maintaining the foreign body response in vivo. It is imperative to comprehend the impact of chemical pretreatments of CNFs on protein adsorption and their interaction with diverse host cell types prior to the investigation of potential modifications. This knowledge is indispensable for the advancement of CNFs in regenerative applications within tissue engineering.