REVIEW | doi:10.20944/preprints202306.2159.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: fibrosis; inflammatory; fibroblasts; extracellular matrix; therapeutic strategy
Online: 29 June 2023 (14:13:43 CEST)
Fibrosis is a prevalent and detrimental condition associated with various diseases with a high impact on global morbidity and mortality rates. Despite its diverse causes and affected organs, common underlying mechanisms drive the development and progression of the disease. These mechanisms include an exaggerated inflammatory response, excessive activation of fibroblasts, and abnormal tissue remodeling following severe or repetitive tissue injury. Although significant advancements have been achieved to enhance our understanding of fibrosis, there is still a gap between identifying potential antifibrotic targets and successfully translating them into effective clinical interventions. Novel approaches that target specific cellular and molecular processes involved in fibrosis hold promise for reducing the pathological consequences of the disease. Understanding the pathogenesis and clinical implications of fibrotic diseases is crucial for developing effective therapeutic strategies and improving patient outcomes. In this review, we introduce the concept of fibrosis, discuss the mechanisms by which it arises, and explore existing and emerging therapeutic approaches in development.
ARTICLE | doi:10.20944/preprints201801.0102.v1
Subject: Engineering, Mechanical Engineering Keywords: Planetary gear; Fault diagnosis; CEEMDAN; Permutation entropy; ANFIS
Online: 11 January 2018 (11:54:12 CET)
For planetary gear has the characteristics of small volume, light weight and large transmission ratio, it is widely used in high speed and high power mechanical system. Poor working conditions result in frequent failures of planetary gear. A method is proposed for diagnosing faults in planetary gear based on permutation entropy of Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) Adaptive Neuro-fuzzy Inference System (ANFIS) in this paper. The original signal is decomposed into 6 intrinsic mode functions (IMF) and residual components by CEEMDAN. Since the IMF contains the main characteristic information of planetary gear faults, time complexity of IMFs are reflected by permutation entropies to quantify the fault features. The permutation entropies of each IMF component are defined as the input of ANFIS, and its parameters and membership functions are adaptively adjusted according to training samples. Finally, the fuzzy inference rules are determined, and the optimal ANFIS is obtained. The overall recognition rate of the test sample used for ANFIS is 90.75%, and the recognition rate of gear with one missing tooth is relatively high. The recognition rates of different fault gears based on the method can also achieve better results. Therefore, the proposed method can be applied to planetary gear fault diagnosis effectively.
ARTICLE | doi:10.20944/preprints202309.1690.v1
Subject: Computer Science And Mathematics, Computer Vision And Graphics Keywords: Camera Calibration; Vanishing Point Detection; Transformer
Online: 26 September 2023 (02:15:36 CEST)
Previous camera self-calibration methods have exhibited certain notable shortcomings. On one hand, they either exclusively emphasized scene cues or solely focused on vehicle-related cues, resulting in a lack of adaptability to diverse scenarios and a limited number of effective features. Furthermore, these methods either solely utilized geometric features within traffic scenes or exclusively extracted semantic information, failing to comprehensively consider both aspects. This limited the comprehensive feature extraction from scenes, ultimately leading to a decrease in calibration accuracy. Additionally, conventional vanishing point-based self-calibration methods often required the design of additional edge-background models and manual parameter tuning, thereby increasing operational complexity and the potential for errors. Given these observed limitations, and in order to address these challenges, we propose an innovative roadside camera self-calibration model based on the Transformer architecture. This model possesses a unique capability to simultaneously learn scene features and vehicle features within traffic scenarios while considering both geometric and semantic information. Through this approach, our model can overcome the constraints of prior methods, enhancing calibration accuracy and robustness while reducing operational complexity and the potential for errors. Our method outperforms existing approaches on both real-world dataset scenarios and publicly available datasets, demonstrating the effectiveness of our approach.
REVIEW | doi:10.20944/preprints202002.0382.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: metastatic breast cancer; targeted therapies; fibroblast growth factors receptors drugs
Online: 26 February 2020 (01:41:54 CET)
Breast cancer (BC) is the most frequent form of malignancy and the second only to lung cancer as common cause of cancer-causing deaths in women. Notwithstanding many progresses in the field, metastatic BC has a very poor prognosis. As therapies are becoming more personalized to meet patients‘ needs, a better knowledge of the molecular biology leading to the disease unfolds the possibility to project more precise compounds or antibodies targeting definite alteration at the molecular level expressed in cancer cells of patients or as antigens on the surface of cell membranes. Fibroblast growth factor receptor (FGFR) is a druggable target -which is activated by its own ligands -namely the Fibroblast Growth Factors (FGFs). This pathway provides a vast range of interesting molecular targets pursued at different levels of clinical investigation. Herein we provide an update on the knowledge on genetic alterations of the receptors in breast cancer, their role in tumorigenesis and the most recent drugs against this particular receptor to treat the disease.
ARTICLE | doi:10.20944/preprints202304.0288.v1
Subject: Chemistry And Materials Science, Applied Chemistry Keywords: Layered double hydroxides; grease; antioxidant; oxidative induction time
Online: 13 April 2023 (03:28:21 CEST)
In this paper, MgAl Layered double hydroxides (LDH) were synthesized by co-precipitation method using a colloid mill and characterized by XRD, IR and SEM. The LDHs was repeatedly tested and compared with different bearing lifetime tester in lithium base grease, and it was found that the environmental-friendly LDHs had greater performance than the traditional antioxidant, and it was the development direction of a new generation of environmental-friendly antioxidants in the future. By adding LDHs into large electric shovel greats (GRK-A) in open-pit coal mine, it can be seen by PDSC evaluation that the service lifetime of grease is extended by 20% while the overall performance of grease is not affected. With the increase of LDHs addition, the grease sample gets the greater activation energy, the stronger thermal oxidation and decomposition resistance. Comparing the energy storage modulus and flow transition index at different temperatures, it can be seen that adding the right amount of LDHs needs close attention for the system oxidation resistance and viscoelasticity. For the electric shovel grease system, the best oxidation resistance and rheological properties can be achieved by adding 2% of LDHs. The rheological viscosity-temperature curves show that the grease samples with different ratios of solid LDHs have better low-temperature properties than the mine grease.
REVIEW | doi:10.20944/preprints202102.0150.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: CTLA-4; Treg cells: Immune checkpoint inhibitors; CD28; Antigen Presenting Cells
Online: 5 February 2021 (09:35:47 CET)
Immune checkpoint inhibitors (ICIs) have obtained durable responses in many cancers, making it possible to foresee their potential in improving the health of cancer patients. However, immunotherapies are limited at the moment to a minority of patients and there is a need for a better understanding of the basic molecular mechanisms and functions of pivotal immune regulatory molecules. Immune checkpoint cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and regulatory T (Treg) cells play pivotal roles in hindering the anticancer immunity. Treg cells suppress antigen-presenting cells (APCs) by depleting immune stimulating cytokines, producing immunosuppressive cytokines and constitutively expressing CTLA-4. CTLA-4 molecules bind with higher affinity to CD80 and CD86 than CD28 and act as competitive inhibitors of CD28 in APCs. The purpose of this review is to summarize state-of-the-art understanding of the molecular mechanisms underlining CTLA-4 immune regulation and the correlation of ICI response with CTLA-4 expression in Treg cells from preclinical and clinical studies for possibly improving CTLA-4-based immunotherapies, while highlighting the knowledge gap.
ARTICLE | doi:10.20944/preprints201912.0195.v2
Subject: Computer Science And Mathematics, Computer Science Keywords: holographic 3D display; computer generated holography; light field image rendering; pinhole array
Online: 17 January 2020 (06:46:23 CET)
A fast calculation method for the full parallax high-resolution hologram is proposed based on the elemental light field image (EI) rendering. A 3D object located near the holographic plane is firstly rendered as multiple EIs with a pinhole array. Each EI is interpolated and multiplied by a divergent sphere wave and interfered with a reference wave to form a hogel. Parallel acceleration is used to calculate the high-resolution hologram because calculation of each hogel is independent. A high-resolution hologram with the resolution of 20,0000×20,0000 pixels is calculated only within 8 minutes. Full parallax high-resolution 3D displays are realized by optical reconstructions.
Subject: Biology And Life Sciences, Food Science And Technology Keywords: Colon cancer; Plant-derived lactic acid bacteria 729; Lactobacillus plantarum; Apoptosis; Ferroptosis
Online: 16 May 2023 (10:38:21 CEST)
Colon cancer is a common malignancy of digestive tract and has high incidence and mortality worldwide. As a normal flora in the human gastrointestinal tract, lactic acid bacteria have been proved to have health benefits, such as immune-regulation, anti-infection, and anti-tumor. In the present study, the inhibitory effects of 19 heat-inactivated plant-derived lactic acid bacteria on human colon cancer cell HCT116 were investigated. The results showed that heat-inactivated plant-derived lactic acid bacteria strain 729 had the strongest inhibitory effect on HCT116 cells among all tested bacteria. Treatment with heat-inactivated bacteria strain 729 could inhibit the proliferation of HCT-116 cells in dose-dependent manner, with 54.52% inhibition at a final concentration of 1×108 CFU/mL. Moreover, the heat-inactivated bacteria strain 729 could block the cell cycle, induce apoptosis, and promote cellular ferroptosis by downregulating the expression of GPX4 and xCT at protein level. According to the 16S rDNA sequencing, the plant-derived lactic acid bacteria strain 729 was Lactobacillus plantarum. Collectively, the results indicates that lactic acid bacteria strain 729 may be developed as special ingredients targeting colon cancer, but further in vivo studies are required.
REVIEW | doi:10.20944/preprints202008.0166.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19, seroconversion, neutralizing antibody, spike protein, SARS-CoV-2, convalescent plasma, vaccine
Online: 6 August 2020 (12:16:11 CEST)
The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients’ outcome. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but also might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies, as well as preliminary clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.
REVIEW | doi:10.20944/preprints202006.0183.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; SARS-CoV-2; mortality; cytokine storm; cytokine release syndrome; chemokine; inflammation; immunopathology; IL-6; IL-1; CCL2; CCL5
Online: 14 June 2020 (15:44:38 CEST)
Coronavirus disease 2019 (COVID-19) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in tremendous morbidity and mortality worldwide. A major underlying cause of COVID-19 mortality is a hyperinflammatory cytokine storm in severe/critically ill patients. Although many clinical trials are testing the efficacy of targeting inflammatory cytokines/chemokines in COVID-19 patients, the critical inflammatory mediator initiating COVID-19 patient death is undefined. Here we suggest that the immunopathological pathway leading to COVID-19 mortality can be divided into three stages with distinct clinical features that can be used to guide therapeutic strategies. Our interpretation of the recently published clinical trials from COVID-19 patients suggests that the clinical efficacy in preventing COVID-19 mortality using IL-1 blockade is subjected to notable caveats, while that for IL-6 blockade is suboptimal. We discuss critical factors in determining appropriate inflammatory cytokine/chemokine targets, timing, and combination of treatments to prevent COVID-19 mortality.
ARTICLE | doi:10.20944/preprints202302.0002.v1
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: Extracellular calpastatin, Ca2+/ calmodulin (CaM)-dependent protein kinase kinase 2, osteocytes, osteoclasts, bone remodeling
Online: 1 February 2023 (01:11:27 CET)
Calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) regulates bone remodeling through its effects on osteoblasts and osteoclasts. However, its role in osteocytes, the most abundant bone cell type, and the master regulator of bone remodeling, remains unknown. Here we report that the conditional deletion of CaMKK2 from osteocytes using Dentine matrix protein 1 (Dmp1)-8kb-Cre mice led to enhanced bone mass only in female mice owing to a suppression of osteoclasts. Conditioned media isolated from female CaMKK2-deficient osteocytes inhibited osteoclast formation and function in in vitro assays, indicating a role for osteocyte-secreted factors. Proteomics analysis revealed significantly higher levels of extracellular calpastatin, a specific inhibitor of calcium-dependent cysteine proteases calpains, in female CaMKK2 null osteocyte conditioned media, compared to media from female control osteocytes. Further, exogenously added non-cell permeable recombinant calpastatin domain I elicited a marked, dose-dependent inhibition of female wild-type osteoclasts and depletion of calpastatin from female CaMKK2-deficient osteocyte conditioned media reversed the inhibition of matrix resorption by osteoclasts. Our findings reveal a novel role for extracellular calpastatin in regulating female osteoclast function and unravel a novel CaMKK2-mediated paracrine mechanism of osteoclast regulation by female osteocytes.