Search

[Display omitted] • Deep learning enabled predictive nucleic acid amplification tests analysis. • On-site fluorescence signal processing powered by cloud computing. • Accurate prediction can be obtained using the early 22.5% data. • Approach can be universally extended to other areas of biomedical research. Pandemics such as COVID-19 have exposed global inequalities in essential health care. Here, we proposed a novel analytics of nucleic acid amplification tests (NAATs) by combining paper microfluidics with deep learning and cloud computing. Real-time amplifications of synthesized SARS-CoV-2 RNA templates were performed in paper devices. Information pertained to on-chip reactions in time-series format were transmitted to cloud server on which deep learning (DL) models were preloaded for data analysis. DL models enable prediction of NAAT results using partly gathered real-time fluorescence data. Using information provided by the G-channel, accurate prediction can be made as early as 9 min, a 78% reduction from the conventional 40 min mark. Reaction dynamics hidden in amplification curves were effectively leveraged. Positive and negative samples can be unbiasedly and automatically distinguished. Practical utility of the approach was validated by cross-platform study using clinical datasets. Predicted clinical accuracy, sensitivity and specificity were 98.6%, 97.6% and 99.1%. Not only the approach reduced the need for the use of bulky apparatus, but also provided intelligent, distributable and robotic insights for NAAT analysis. It set a novel paradigm for analyzing NAATs, and can be combined with the most cutting-edge technologies in fields of biosensor, artificial intelligence and cloud computing to facilitate fundamental and clinical research. [ABSTRACT FROM AUTHOR]

Introduction and aim. Growth differentiation factor 11 (GDF11) is a novel member of TGF-β superfamily. Its role is confirmed in embryogenesis, rejuvenation, and aging. GDF11 is involved in inflammatory response as it inhibits the release of pro-inflammatory cytokines and NLRP3 inflammasome activation. Moreover, GDF11 has clinicopathological signifi- cance in colorectal cancer and is proposed as a possible prognostic factor. The aim of our study is to assess the activity of GDF11 during development of colitis and colorectal cancer in mice. Material and methods. Male C57BL/6 mice were used in our experiments. Colitis was induced by dextran sodium sulfate (DSS) addition into drinking water. Single injection of azoxymethane (AOM) and repeated cycles of DSS were used to induce colitis-associated colorectal cancer. At different time points mice were sacrificed. Human and mouse colorectal cancer cell lines were used in our project to verify GDF11 expression. MC-38 cells were stimulated with the cytokines for 24 hours. We isolated RNA and protein to perform real-time RT-PCR and Western Blot. Statistical analysis was performed using GraphPad Software. Results. We found that GDF11 expression at mRNA level is increased in the mouse colon during aging. GDF11 expression is elevated during the experimental colitis and during the period of recovery. GDF11 expression is changed at initial stage of colorectal cancer in mice. Its expression also differs among different human cell lines. LPS induced an increase of GDF11 expression. Conclusion. We confirmed that GDF11 is crucial at all stages of development of experimental colitis and colitis-associated colorectal cancer. [ABSTRACT FROM AUTHOR]

MicroRNAs can interfere with protein function by suppressing their messenger RNA translation or the synthesis of its related factors. The function of brain-derived neurotrophic factor (BDNF) is essential to the proper formation and function of the nervous system and is seen to be regulated by many microRNAs. However, understanding how microRNAs influence BDNF actions within cells requires a wider comprehension of their integrative regulatory mechanisms. Aim: In this literature review, we have synthesized the evidence of microRNA regulation on BDNF in cells and tissues, and provided an analytical discussion about direct and indirect mechanisms that appeared to be involved in BDNF regulation by microRNAs. Methods: Searches were conducted on PubMed.gov using the terms "BDNF" AND "MicroRNA" and "brain-derived neurotrophic factor" AND "MicroRNA", updated on 1 September 2023. Papers without open access were requested from the authors. One hundred and seventy-one papers were included for review and discussion. Results and Discussion: The local regulation of BDNF by microRNAs involves a complex interaction between a series of microRNAs with target proteins that can either inhibit or enhance BDNF expression, at the core of cell metabolism. Therefore, understanding this homeostatic balance provides resources for the future development of vector-delivery-based therapies for the neuroprotective effects of BDNF. [ABSTRACT FROM AUTHOR]

The 80+ existing autoimmune disorders (ADs) affect billions with little prevention or treatment options, except for temporary symptomatic management, leading to enormous human suffering and a monumental financial burden. The autoantibodies formed in most ADs have been identified, allowing the development of novel anti-idiotypic antibodies to mute the autoantibodies using vaccines. Nucleoside vaccines have been successfully tested as antigen-specific immunotherapies (ASI), with mRNA technology offering multi-epitope targeting to mute multiple autoantibodies. This paper proposes using mRNA technology to produce anti-idiotypic antibodies with broad effectiveness in preventing and treating them. This paper delves into the state-of-the-art mRNA design strategies used to develop novel ASIs by selecting appropriate T cell and B cell epitopes to generate anti-idiotypic antibodies. The low cost and fast development of mRNA vaccines make this technology the most affordable for the global control of ADs. [ABSTRACT FROM AUTHOR]

Oral submucous fibrosis (OSF) affecting populations is considered a public health issue in South/Southeast Asia. The purpose of this study was to analyze the scientometric characteristics and research trends of OSF. All the papers on OSF were comprehensively retrieved from the Scopus database. Regional comparison (India versus outside of India) and chronological comparison (before 2015 versus after 2015) were performed. Among all the 1357 papers on OSF, 930 (68.5%) were from India. In India, biology research on antioxidant, oxidative stress, angiogenesis, and extracellular matrix were distinctive keywords. Risk factors of smokeless tobacco and gutkha and the roles of saliva and blood sampling were also distinctive keywords in India. In outside of India, biology research on myofibroblast, alpha smooth muscle actin, microRNA, long untranslated RNA, and protein p53 were distinctive keywords. The trend of biology research on connective tissue, genotype, genetic predisposition, messenger RNA, and cytology before 2015 has changed to research on myofibroblast, biological marker, microRNA, epithelial mesenchymal transition, extracellular matrix, and oxidative stress after 2015. The trend of clinical aspects of surgery and mouth hygiene before 2015 has changed to the aspects of adverse event/effects, complication, and quality of life after 2015. This scientometric study elucidated the current scenario and research trends of OSF, and would help in improving in reciprocal collaboration and communication for this disease control in South/Southeast Asia. [ABSTRACT FROM AUTHOR]

Potatoes are developed vegetatively from tubers, and therefore potato virus transmission is always a possibility. The potato leafroll virus (PLRV) is a highly devastating virus of the genus Polerovirus and family Luteoviridae and is regarded as the second-most destructive virus after Potato virus Y. Multiple species of aphids are responsible for the persistent and non-propagating transmission of PLRV. Due to intrinsic tuber damage (net necrosis), the yield and quality are drastically diminished. PLRV is mostly found in phloem cells and in extremely low amounts. Therefore, we have attempted to detect PLRV in both potato tuber and leaves using a highly sensitive, reliable and cheap method of one-step reverse transcription-recombinase polymerase amplification (RT-RPA). In this study, an isothermal amplification and detection approach was used for efficient results. Out of the three tested primer sets, one efficiently amplified a 153-bp product based on the coat protein gene. In the present study, there was no cross-reactivity with other potato viruses and the optimal amplification reaction time was thirty minutes. The products of RT-RPA were amplified at a temperature between 38 and 42 °C using a simple heating block/water bath. The present developed protocol of one-step RT-RPA was reported to be highly sensitive for both leaves and tuber tissues equally in comparison to the conventional reverse transcription-polymerase chain reaction (RT-PCR) method. By using template RNA extracted employing a cellular disc paper-based extraction procedure, the method was not only simplified but it detected the virus as effectively as purified total RNA. The simplified one-step RT-RPA test was proven to be successful by detecting PLRV in 129 samples of various potato cultivars (each consisting of leaves and tubers). According to our knowledge, this is the first report of a one-step RT-RPA performed using simple RNA extracted from cellular disc paper that is equally sensitive and specific for detecting PLRV in potatoes. In terms of versatility, durability and the freedom of a highly purified RNA template, the one-step RT-RPA assay exceeds the RT-PCR assay, making it an effective alternative for the certification of planting materials, breeding for virus resistance and disease monitoring. [ABSTRACT FROM AUTHOR]

N4-acetylcysteine (ac4C) is a chemical modification in mRNAs that alters the structure and function of mRNA by adding an acetyl group to the N4 position of cytosine. Researchers have shown that ac4C is closely associated with the occurrence and development of various cancers. Therefore, accurate prediction of ac4C modification sites on human mRNA is crucial for revealing its role in diseases and developing new diagnostic and therapeutic strategies. However, existing deep learning models still have limitations in prediction accuracy and generalization ability, which restrict their effectiveness in handling complex biological sequence data. This paper introduces a deep learning-based model, STM-ac4C, for predicting ac4C modification sites on human mRNA. The model combines the advantages of selective kernel convolution, temporal convolutional networks, and multi-head self-attention mechanisms to effectively extract and integrate multi-level features of RNA sequences, thereby achieving high-precision prediction of ac4C sites. On the independent test dataset, STM-ac4C showed improvements of 1.81%, 3.5%, and 0.37% in accuracy, Matthews correlation coefficient, and area under the curve, respectively, compared to the existing state-of-the-art technologies. Moreover, its performance on additional balanced and imbalanced datasets also confirmed the model's robustness and generalization ability. Various experimental results indicate that STM-ac4C outperforms existing methods in predictive performance. In summary, STM-ac4C excels in predicting ac4C modification sites on human mRNA, providing a powerful new tool for a deeper understanding of the biological significance of mRNA modifications and cancer treatment. Additionally, the model reveals key sequence features that influence the prediction of ac4C sites through sequence region impact analysis, offering new perspectives for future research. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic caused much illness, many deaths, and profound disruption to society. The production of 'safe and effective' vaccines was a key public health target. Sadly, unprecedented high rates of adverse events have overshadowed the benefits. This two-part narrative review presents evidence for the widespread harms of novel product COVID-19 mRNA and adenovectorDNA vaccines and is novel in attempting to provide a thorough overview of harms arising from the new technology in vaccines that relied on human cells producing a foreign antigen that has evidence of pathogenicity. This first paper explores peer-reviewed data counter to the 'safe and effective' narrative attached to these new technologies. Spike protein pathogenicity, termed 'spikeopathy', whether from the SARS-CoV-2 virus or produced by vaccine gene codes, akin to a 'synthetic virus', is increasingly understood in terms of molecular biology and pathophysiology. Pharmacokinetic transfection through body tissues distant from the injection site by lipid-nanoparticles or viral-vector carriers means that 'spikeopathy' can affect many organs. The inflammatory properties of the nanoparticles used to ferry mRNA; N1-methylpseudouridine employed to prolong synthetic mRNA function; the widespread biodistribution of the mRNA and DNA codes and translated spike proteins, and autoimmunity via human production of foreign proteins, contribute to harmful effects. This paper reviews autoimmune, cardiovascular, neurological, potential oncological effects, and autopsy evidence for spikeopathy. With many gene-based therapeutic technologies planned, a re-evaluation is necessary and timely. [ABSTRACT FROM AUTHOR]

Abiotic stresses occur more often in combination than alone under regular field conditions limiting in more severe way crop production. Stress recognition in plants primarily occurs in the plasma membrane, modification of which is necessary to maintain homeostasis in response to it. It is known that lipid transport proteins (ns-LTPs) participate in modification of the lipidome of cell membranes. Representative of this group, ns-LTP2.8, may be involved in the reaction to abiotic stress of germinating barley plants by mediating the intracellular transport of hydrophobic particles, such as lipids, helping to maintain homeostasis. The ns-LTP2.8 protein was selected for analysis due to its ability to transport not only linear hydrophobic molecules but also compounds with a more complex spatial structure. Moreover, ns-LTP2.8 has been qualified as a member of pathogenesis-related proteins, which makes it particularly important in relation to its high allergenic potential. This paper demonstrates for the first time the influence of various abiotic stresses acting separately as well as in their combinations on the change in the ns-LTP2.8 transcript, ns-LTP2.8 protein and total soluble protein content in the embryonal axes of germinating spring barley genotypes with different ns-LTP2.8 allelic forms and stress tolerance. Tissue localization of ns-LTP2.8 transcript as well as ns-LTP2.8 protein were also examined. Although the impact of abiotic stresses on the regulation of gene transcription and translation processes remains not fully recognized, in this work we managed to demonstrate different impact on applied stresses on the fundamental cellular processes in very little studied tissue of the embryonal axis of barley. [ABSTRACT FROM AUTHOR]

Epigenetic regulation has been thoroughly investigated in recent years and has emerged as an important aspect of chronic lymphocytic leukemia (CLL) biology. Characteristic aberrant features such as methylation patterns and global DNA hypomethylation were the early findings of the research during the last decades. The investigation in this field led to the identification of a large number of genes where methylation features correlated with important clinical and laboratory parameters. Gene-specific analyses investigated methylation in the gene body enhancer regions as well as promoter regions. The findings included genes and proteins involved in key pathways that play central roles in the pathophysiology of the disease. Τhe application of these findings beyond the theoretical understanding can not only lead to the creation of prognostic and predictive models and scores but also to the design of novel therapeutic agents. The following is a review focusing on the present knowledge about single gene/gene promoter methylation or mRNA expression in CLL cases as well as records of older data that have been published in past papers. [ABSTRACT FROM AUTHOR]

Simple Summary: Cachexia and malnutrition are characteristic of oncology patients, including those with head and neck cancer (HNSCC). Fifty-six patients diagnosed with HNSCC (study group) were included in the study, and seventy patients constituted the control group. We used standardized questionnaires to assess nutritional status and cachexia. In our study, we evaluated whether ghrelin, titin, and irisin can be a useful diagnostic marker, a prognostic marker of cancer development in these patients, and whether the levels of these proteins depend on the nutritional status of the patients. We used molecular biology methods to evaluate the concentration of the selected proteins. The results indicate that the levels of ghrelin, titin, and irisin correlate well with the nutritional and cachexia status of patients with HNSCC. Until now, to our best knowledge, this is the first study assessing the changes in concentrations of these proteins in this type of cancer. The goal of this paper was the evaluation of the changes in the expression profile of irisin, ghrelin, and titin in the carcinoma tissue and in the blood of patients with head and neck squamous cell carcinoma (HNSCC), including determining the profile of their expression in relation to patient nutrition. The study included 56 patients with diagnosed squamous cell carcinoma of HNSCC in the T3 and T4 stages of the disease. Healthy control tissue specimens were collected from an area 10 mm outside the histologically negative margin. In turn, the blood and serum from the control group came from healthy volunteers treated for non-oncologic reasons (n = 70). The molecular analysis allowed us to determine the profile of irisin, ghrelin, and titin methylation, evaluate their expression on the level of mRNA (quantitative Reverse Transcription Polymerase Chain Reaction; qRT-PCR) and protein (Enzyme-Linked Immunosorbent Assay Reaction; ELISA) in the carcinoma tissue and the margin of healthy tissue, as well as in serum of patients in the study and control groups. At the start of our observations, a Body Mass Index (BMI) < 18.5 was noted in 42 of the patients, while six months after the treatment a BMI < 18.5 was noted in 29 patients. We also noted a decrease in the expression of irisin, ghrelin, and titin both on the level of mRNA and protein, as well as a potential regulation of their expression via DNA methylation. There is no convincing evidence that the proteins assayed in the present work are specific with regard to HNSSC. [ABSTRACT FROM AUTHOR]

In 2023, Katalin Karikó and Drew Weissman were awarded the Nobel Prize in Physiology or Medicine for their nucleoside base modifications research that later enabled mRNA vaccine development against COVID-19. This paper briefly reviews these achievements in the context of the development of mRNA technology and its enormous potential for medicine in the prevention of various infectious diseases and cancer treatment, including personalised therapies. It is beyond any doubt that discoveries made by Karikó and Weissman were pivotal in overcoming one of the major hurdles in the practical application of mRNA molecules, i.e., the recognition of exogenous mRNAs by endosomal Toll-like receptors and downstream innate immune response, ultimately leading to the decreased translational activity of delivered mRNA and its degradation. Although the Nobel Prize for Karikó and Weissman is fully justified, it must be stressed that mRNA technology would never unfold its potential for public health without a collective scientific effort encompassing over 40 years of research. [ABSTRACT FROM AUTHOR]

Thousands of long-distance mobile mRNAs were identified from different grafting systems, based on high-throughput sequencing technology. Moreover, the long-distance delivery of RNAs was proved to involve multiple mechanisms. Here, we analyzed the homology, motif, and tRNA-like structure (TLS) of long-distance mobile mRNAs identified by RNA-seq as well as the RNA-binding protein (RBP) in nine grafting combinations including Arabidopsis thaliana, Vitis vinifera, Cucumis sativus, Citrullus lanatus, Nicotiana benthamiana, Malus domestica, Pyrus spp., Glycine max and Phaseolus vulgaris. Although several mRNAs were found to be shared in herbaceous, woody, and related species, the vast majority of long-distance mobile mRNAs were species-specific. Four non-specific movement-related motifs were identified, while the TLS was not necessary for mRNA long distance mobility. In addition, we found that RBPs were conserved among herbaceous and woody plants as well as related species. This paper reports a further in-depth analysis of the endogenous mechanisms by which the species-specific transportable mRNAs were selected by bioinformatics, in order to provide insights for future research on long-distance mobile mRNAs. [ABSTRACT FROM AUTHOR]

Background: Since the coronavirus disease 2019 (COVID-19) has spread throughout the world, many studies on innate immunity in COVID-19 have been published, and great progress has been achieved, while bibliometric analysis on hotspots and research trends in this field remains lacking. Methods: On 17 November 2022, articles and reviews on innate immunity in COVID-19 were recruited from the Web of Science Core Collection (WoSCC) database after papers irrelevant to COVID-19 were further excluded. The number of annual publications and the average citations per paper were analyzed by Microsoft Excel. Bibliometric analysis and visualization of the most prolific contributors and hotspots in the field were performed by VOSviewer and CiteSpace software. Results: There were 1,280 publications that met the search strategy on innate immunity in COVID-19 and were published from 1 January 2020 to 31 October 2022. Nine hundred thirteen articles and reviews were included in the final analysis. The USA had the highest number of publications (Np) at 276 and number of citations without self-citations (Nc) at 7,085, as well as an H-index of 42, which contributed 30.23% of the total publications, followed by China (Np: 135, Nc: 4,798, and H-index: 23) with 14.79% contribution. Regarding Np for authors, Netea, Mihai G. (Np: 7) from the Netherlands was the most productive author, followed by Joosten, Leo A. B. (Np: 6) and Lu, Kuo-Cheng (Np: 6). The Udice French Research Universities had the most publications (Np: 31, Nc: 2,071, H-index: 13), with an average citation number (ACN) at 67. The journal Frontiers in Immunology possessed the most publications (Np: 89, Nc: 1,097, ACN: 12.52). “Evasion” (strength 1.76, 2021-2022), “neutralizing antibody” (strength 1.76, 2021-2022), “messenger RNA” (strength 1.76, 2021-2022), “mitochondrial DNA” (strength 1.51, 2021-2022), “respiratory infection” (strength 1.51, 2021-2022), and “toll-like receptors” (strength 1.51, 2021-2022) were the emerging keywords in this field. Conclusion: The study on innate immunity in COVID-19 is a hot topic. The USA was the most productive and influential country in this field, followed by China. The journal with the most publications was Frontiers in Immunology. “Messenger RNA,” “mitochondrial DNA,” and “toll-like receptors” are the current hotspots and potential targets in future research. [ABSTRACT FROM AUTHOR]

D-allulose, D-sorbose and D-tagatose are D-fructose isomers that are called rare sugars. These rare sugars have been studied intensively in terms of biological production and food application as well as physiological effects. There are limited papers with regard to the transporters mediating the intestinal absorption of these rare sugars. We examined whether these rare sugars are absorbed via sodium-dependent glucose cotransporter 1 (SGLT1) as well as via GLUT type 5 (GLUT5) using rats. High-fructose diet fed rats, which express more intestinal GLUT5, exhibited significantly higher peripheral concentrations, Cmax and AUC0–180 min when D-allulose, D-sorbose and D-tagatose were orally administrated. KGA-2727, a selective SGLT1 inhibitor, did not affect the peripheral and portal vein concentrations and pharmacokinetic parameters of these rare sugars. The results suggest that D-allulose, D-sorbose and D-tagatose are likely transported via GLUT5 but not SGLT1 in rat small intestine. [ABSTRACT FROM AUTHOR]

N4-acetylcytidine (ac4C) is a modification of cytidine at the nitrogen-4 position, playing a significant role in the translation process of mRNA. However, the precise mechanism and details of how ac4C modifies translated mRNA remain unclear. Since identifying ac4C sites using conventional experimental methods is both labor-intensive and time-consuming, there is an urgent need for a method that can promptly recognize ac4C sites. In this paper, we propose a comprehensive ensemble learning model, the Stacking-based heterogeneous integrated ac4C model, engineered explicitly to identify ac4C sites. This innovative model integrates three distinct feature extraction methodologies: Kmer, electron-ion interaction pseudo-potential values (PseEIIP), and pseudo-Ktuple nucleotide composition (PseKNC). The model also incorporates the robust Cluster Centroids algorithm to enhance its performance in dealing with imbalanced data and alleviate underfitting issues. Our independent testing experiments indicate that our proposed model improves the Mcc by 15.61% and the ROC by 5.97% compared to existing models. To test our model’s adaptability, we also utilized a balanced dataset assembled by the authors of iRNA-ac4C. Our model showed an increase in Sn of 4.1%, an increase in Acc of nearly 1%, and ROC improvement of 0.35% on this balanced dataset. The code for our model is freely accessible at https://github.com/louliliang/ST-ac4C.git, allowing users to quickly build their model without dealing with complicated mathematical equations. [ABSTRACT FROM AUTHOR]

The paper aimed to explore the mechanism by which high mobility group box-1 and nicotinamide adenine dinucleotide phosphate oxidase-derived reactive oxygen species enhance each other's influence on the amplitude of electroretinogram and the permeability of the vitreous. According to the purpose of the experiment, the experimental rats were separated into a control group, a diabetes group and a Shenling Baizhu powder group. The messenger ribonucleic acid expression of microRNA-23 and microRNA-27a in rat muscle tissue was quantitatively analyzed by real-time quantitative polymerase chain reaction. The contractility of rat soleus skeletal muscle was analyzed by electrical stimulation program. Western blot analysis of rat muscle growth protein synthesis and the expression of myostatin signaling pathway was carried out. The expression of renal fibrosis-related albumin was tested by Western blot. The messenger ribonucleic acid expression of microRNA-23, 27a in the diabetic group was lower than control group (p<0.05), and the expression in the Shenling Baizhu powder group was higher than diabetic group (p<0.05). Compared with the control group, the diabetic group had lower body weight (p<0.05), and raised blood glucose concentration and diabetes volume (p<0.05). The ratio of phosphorylated protein kinase B/protein kinase B and phospho forkhead box protein O1/forkhead box protein O1 protein expression in the Shenling Baizhu powder group was higher than diabetic group (p<0.05), while the phosphatase and tensin homolog protein expression was lower (p<0.05). The protein expression of myostatin, FBXO32 and TRIM63 in the diabetes group was higher than control group (p<0.05), and the expression in the Shenling Baizhu powder group was lower than diabetes group (p<0.05). Compared with the control group, the protein expression of transforming growth factor-beta, suppressor of mothers against decapentaplegic 2/3, alpha-smooth muscle actin, collagen-1a and fibronectin was higher in the diabetes group (p<0.05), and the expression in the Shenling Baizhu powder group was lower than diabetes group (p<0.05). Shenling Baizhu powder can improve diabetes-induced sarcopenia by up-regulating microRNA expression, activating the insulin-like growth factor 1/phosphoinositide 3-kinases/ protein kinase B signaling pathway and inhibiting the myostatin cascade. [ABSTRACT FROM AUTHOR]

Simple Summary: The growing evidence suggested that competing endogenous RNAs (ceRNAs) have significant associations with tumor occurrence and progression, yet the regulatory mechanism of them in lung adenocarcinoma remains unclear. Identification of the regulatory modules for lung adenocarcinoma is a critical and fundamental step towards understanding the regulatory mechanisms during carcinogenesis. Deep neural network (DNN) models have become a powerful tool to intelligently recognize the sophisticated relationships of ceRNAs appropriately. In this paper, multiple deep neural network models were constructed using the expression data to identify regulatory modules for lung adenocarcinoma in biological networks. Three identified regulatory modules association with lung adenocarcinoma were validated from three aspects, i.e., literature review, functional enrichment analysis, and an independent dataset. The regulatory relationships between RNAs were validated in various datasets, including CPTAC, TCGA and an expression profile from the GEO database. Our study will contribute to improving the understanding of regulatory mechanisms in the carcinogenesis of lung adenocarcinoma and provide schemes for identifying novel regulatory modules of other cancers. Lung adenocarcinoma is the most common type of primary lung cancer, but the regulatory mechanisms during carcinogenesis remain unclear. The identification of regulatory modules for lung adenocarcinoma has become one of the hotspots of bioinformatics. In this paper, multiple deep neural network (DNN) models were constructed using the expression data to identify regulatory modules for lung adenocarcinoma in biological networks. First, the mRNAs, lncRNAs and miRNAs with significant differences in the expression levels between tumor and non-tumor tissues were obtained. MRNA DNN models were established and optimized to mine candidate mRNAs that significantly contributed to the DNN models and were in the center of an interaction network. Another DNN model was then constructed and potential ceRNAs were screened out based on the contribution of each RNA to the model. Finally, three modules comprised of miRNAs and their regulated mRNAs and lncRNAs with the same regulation direction were identified as regulatory modules that regulated the initiation of lung adenocarcinoma through ceRNAs relationships. They were validated by literature and functional enrichment analysis. The effectiveness of these regulatory modules was evaluated in an independent lung adenocarcinoma dataset. Regulatory modules for lung adenocarcinoma identified in this study provided a reference for regulatory mechanisms during carcinogenesis. [ABSTRACT FROM AUTHOR]

Urotensin 2 (Uts2) is a biologically active peptide involved in the regulation of a variety of physiological and pathophysiological processes. In both the human and rat adrenal gland, the expressions of the Uts2 gene and its receptor (Uts2r) have been described. This paper focuses on the description of the hormonal control of the mRNA levels of urotensin II and its receptor in the adrenal gland of the rat, both in vitro and in vivo. The initial in vitro experiments were carried out on freshly isolated rat adrenocortical cells and their primary culture. The obtained results indicated a stimulating PKA-independent effect of ACTH on the Uts2 mRNA level in the tested cells, with no changes in the Uts2r transcript. Subsequent in vivo experiments showed that ACTH-induced adrenal growth was accompanied by an elevated level of the Uts2 mRNA, with unchanged expression of Uts2r. In the other types of in vivo gland growth studied, enucleation-induced adrenal regeneration and compensatory growth of the gland, the mRNA levels of the studied genes showed no significant differences. The only exception was hemiadrenalectomy, which led to a significant increase in Uts2 mRNA expression level 24 h after surgery. In 12-week-old rats of both sexes, gonadectomy led to a significant increase in the level of Uts2 mRNA in the adrenal gland, an effect that was prevented by sex hormones' replacement. No changes in Uts2r transcript levels were observed under these conditions. Thus, this study suggests that the regulation of Uts2 and Uts2r mRNA levels differs significantly in the rat adrenal gland. While Uts2 transcript levels appear to be mainly dependent on ACTH action, Uts2r mRNA levels are not under the control of this hormone. [ABSTRACT FROM AUTHOR]

Simple Summary: The frequency of metastatic melanoma, an extremely deadly malignancy, is rapidly increasing worldwide. Recently, messenger RNA (mRNA) injections have emerged as a promising treatment option. While mRNA therapies have demonstrated significant promise, the stability of the naked form remains a barrier, as naked mRNAs are vulnerable to common ribonucleases, and are unable to effectively penetrate plasma membranes and escape from endosomes. Thus, for this paper, we used a hyper-branched cyclodextrin-based polymer (Ppoly) as a carrier to enhance mRNA delivery for melanoma cancer. The in vitro results demonstrated that Ppoly was able to deliver the EGFP-mRNA effectively in both 2D and 3D melanoma cell lines compared to naked mRNA; in addition, Ppoly did not show any cytotoxicity. The anti-tumour effect of intratumourally injected OVA-mRNA loaded on Ppoly results showed a significant decrease in both tumour size and weight compared to other formulations by inducing an efficient adaptive immune response and OVA-specific CD8+ T cells in both spleen and tumour tissues compared to other groups. mRNA technology has demonstrated potential for use as an effective cancer immunotherapy. However, inefficient in vivo mRNA delivery and the requirements for immune co-stimulation present major hurdles to achieving anti-tumour therapeutic efficacy. Therefore, we used a cationic hyper-branched cyclodextrin-based polymer to increase mRNA delivery in both in vitro and in vivo melanoma cancer. We found that the transfection efficacy of the mRNA-EGFP-loaded Ppoly system was significantly higher than that of lipofectamine and free mRNA in both 2D and 3D melanoma cancer cells; also, this delivery system did not show cytotoxicity. In addition, the biodistribution results revealed time-dependent and significantly higher mEGFP expression in complexes with Ppoly compared to free mRNA. We then checked the anti-tumour effect of intratumourally injected free mRNA–OVA, a foreign antigen, and loaded Ppoly; the results showed a considerable decrease in both tumour size and weight in the group treated with OVA-mRNA in loaded Ppoly compared to other formulations with an efficient adaptive immune response by dramatically increasing most leukocyte subtypes and OVA-specific CD8+ T cells in both the spleen and tumour tissues. Collectively, our findings suggest that the local delivery of cationic cyclodextrin-based polymer complexes containing foreign mRNA antigens might be a good and reliable concept for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Bioluminescence imaging (BLI) is a widely used technique in preclinical scientific research, particularly in the development of mRNA-based medications and non-invasive tumor diagnostics. It has become an essential tool in current science. However, the current state of bioluminescence imaging is primarily qualitative, making it challenging to obtain quantitative measurements and to draw accurate conclusions. This fact is caused by the unique properties of optical photons and tissue interactions. In this paper, we propose an experimental setup and Geant4-simulations to gain a better understanding of the optical properties and processes involved in bioluminescence imaging. Our goal is to advance the field towards more quantitative measurements. We will discuss the details of our experimental setup, the data we collected, the outcomes of the Geant4-simulations, and additional information on the underlying physical processes. [ABSTRACT FROM AUTHOR]

Copyright of Guangdong Agricultural Sciences is the property of South China Agricultural University, Guangdong Academy of Agricultural Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The World Health Organization (WHO) set up the messenger ribonucleic acid (mRNA) technology transfer programme in June 2021 with a development hub in South Africa and 15 partner vaccine producers in middle-income countries. The goal was to support the sustainable development of and access to life-saving vaccines for people in these countries as a means to enhance epidemic preparedness and global public health. This initiative aims to build resilience and strengthen local vaccine research, and development and manufacturing capacity in different regions of the world, especially those areas that could not access coronavirus disease 2019 (COVID-19) vaccines in a timely way. This paper outlines the current global vaccine market and summarizes the findings of a case study on the mRNA technology transfer programme conducted from November 2022 to May 2023. The study was guided by the vision of the WHO Council on the Economics of Health for All to build an economy for health using its four work streams of value, finance, innovation and capacity. Based on the findings of the study, we offer a mission-oriented policy framework to support the mRNA technology transfer programme as a pilot for transformative change towards an ecosystem for health innovation for the common good. Parts of this vision have already been incorporated into the governance of the mRNA technology transfer programme, while other aspects, especially the common good approach, still need to be applied to achieve the goals of the programme. [ABSTRACT FROM AUTHOR]

INTRODUCTION Cigarette smoking is one of the most important causes of COPD and could induce the apoptosis of pulmonary microvascular endothelial cells (PMVECs). The conditional knockout of LRG1 from endothelial cells reduced emphysema in mice. However, the mechanism of the deletion of LRG1 from endothelial cells rescued by cigarette smoke (CS) induced emphysema remains unclear. This research aimed to demonstrate whether LRG1 promotes the apoptosis of PMVECs through KLK10 in COPD. METHODS Nineteen patients were divided into three groups: control non-COPD (n=7), smoker non-COPD (n=7), and COPD (n=5). The emphysema mouse model defined as the CS exposure group was induced by CS exposure plus cigarette smoke extract (CSE) intraperitoneal injection for 28 days. Primary PMVECs were isolated from the mouse by magnetic bead sorting method via CD31-Dynabeads. Apoptosis was detected by western blot and flow cytometry. RESULTS LRG1 was increased in lung tissue of COPD patients and CS exposure mice, and CSE-induced PMVECs apoptosis model. KLK10 was over-expressed in lung tissue of COPD patients and CS exposure mice, and CSE-induced PMVECs apoptosis model. LRG1 promoted apoptosis in PMVECs. LRG1 knockdown reversed CSE-induced apoptosis in PMVECs. The mRNA and protein expression of KLK10 were increased after over-expressed LRG1 in PMVECs isolated from mice. Similarly, both the mRNA and protein levels of KLK10 were decreased after LRG1 knockdown in PMVECs. The result of co-immunoprecipitation revealed a protein-protein interaction between LRG1 and KLK10 in PMVECs. KLK10 promoted apoptosis via the down-regulation of Bcl-2/Bax in PMVECs. KLK10 knockdown could reverse CSE-induced apoptosis in PMVECs. CONCLUSIONS LRG1 promotes apoptosis via up-regulation of KLK10 in PMVECs isolated from mice. KLK10 promotes apoptosis via the down-regulation of Bcl-2/Bax in PMVECs. There was a direct protein-protein interaction between LRG1 and KLK10 in PMVECs. Our novel findings provide insights into the understanding of LRG1/KLK10 function as a potential molecule in COPD. [ABSTRACT FROM AUTHOR]

Simple Summary: Alzheimer's disease (AD) is a progressive, age-related neurodegenerative disorder representing the most common cause of senile dementia and neurological dysfunction in our aging domestic population. MicroRNAs (miRNAs) are a small family of non-coding single-stranded RNAs (ssRNAs) that function in complex interactive networks to direct the post-transcriptional repression of messenger RNA (mRNA)-encoded genetic information. Current evidence suggests that these ssRNAs perform an important regulatory role in the expression of genes in the AD-affected brain and central nervous system (CNS). This review paper will focus on recent studies, developments and advancements in our appreciation and understanding of the complexity of miRNA signaling in AD-affected brain hippocampal CA1 compared to age- and gender-matched controls. AD is a complex, progressive, age-related neurodegenerative disorder representing the most common cause of senile dementia and neurological dysfunction in our elderly domestic population. The widely observed heterogeneity of AD is a reflection of the complexity of the AD process itself and the altered molecular-genetic mechanisms operating in the diseased human brain and CNS. One of the key players in this complex regulation of gene expression in human pathological neurobiology are microRNAs (miRNAs) that, through their actions, shape the transcriptome of brain cells that normally associate with very high rates of genetic activity, gene transcription and messenger RNA (mRNA) generation. The analysis of miRNA populations and the characterization of their abundance, speciation and complexity can further provide valuable clues to our molecular-genetic understanding of the AD process, especially in the sporadic forms of this common brain disorder. Current in-depth analyses of high-quality AD and age- and gender-matched control brain tissues are providing pathophysiological miRNA-based signatures of AD that can serve as a basis for expanding our mechanistic understanding of this disorder and the future design of miRNA- and related RNA-based therapeutics. This focused review will consolidate the findings from multiple laboratories as to which are the most abundant miRNA species, both free and exosome-bound in the human brain and CNS, which miRNA species appear to be the most prominently affected by the AD process and review recent developments and advancements in our understanding of the complexity of miRNA signaling in the hippocampal CA1 region of AD-affected brains. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver cancer continues to exhibit increasing incidence and mortality worldwide. Subsequently, there has been a concomitant effort to development novel therapeutics that effectively target and treat these malignancies. This paper aims to provide a thorough review of the available immunotherapy treatments that target liver cancer, with a specific focus on the role and potential therapeutic strategies available to the interventional radiologist. The underlying biochemical and molecular mechanisms underlying these diseases are discussed to highlight the specific targets for immunotherapy, the clinical efficacy and safety of available pharmaceutical treatments are analyzed, and future advancements in the field, such as combination therapies and personalized medicine, are explored as they pertain to the immunotherapy of liver cancer. Liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, is increasing in incidence and mortality across the globe. An improved understanding of the complex tumor microenvironment has opened many therapeutic doors and led to the development of novel pharmaceuticals targeting cellular signaling pathways or immune checkpoints. These interventions have significantly improved tumor control rates and patient outcomes, both in clinical trials and in real-world practice. Interventional radiologists play an important role in the multidisciplinary team given their expertise in minimally invasive locoregional therapy, as the bulk of these tumors are usually in the liver. The aim of this review is to highlight the immunological therapeutic targets for primary liver cancers, the available immune-based approaches, and the contributions that interventional radiology can provide in the care of these patients. [ABSTRACT FROM AUTHOR]