Degradation or excretion of quantum dots in mouse embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>Quantum dots (QDs) have been considered as a new and efficient probe for labeling cells non-invasively in vitro and in vivo, but fairly little is known about how QDs are eliminated from cells after labeling. The purpose of this study is to investigate the metabolism of QDs in different type of cells.</p> <p>Results</p> <p>Mouse embryonic stem cells (ESCs) and mouse embryonic fibroblasts (MEFs) were labeled with QD 655. QD-labeling was monitored by fluorescence microscopy and flow cytometry for 72 hours. Both types of cells were labeled efficiently, but a quick loss of QD-labeling in ESCs was observed within 48 hours, which was not prevented by inhibiting cell proliferation. Transmission electron microscope analysis showed a dramatic decrease of QD number in vesicles of ESCs at 24 hours post-labeling, suggesting that QDs might be degraded. In addition, supernatants collected from labeled ESCs in culture were used to label cells again, indicating that some QDs were excreted from cells.</p> <p>Conclusion</p> <p>This is the first study to demonstrate that the metabolism of QDs in different type of cells is different. QDs were quickly degraded or excreted from ESCs after labeling.</p

Engineered exosomes as drug and RNA co-delivery system: new hope for enhanced therapeutics?

Chemotherapy often faces some obstacles such as low targeting effects and drug resistance, which introduce the low therapeutic efficiency and strong side effects. Recent advances in nanotechnology allows the use of novel nanosystems for targeted drug delivery, although the chemically synthesized nanomaterials always show unexpected low biocompability. The emergence of exosome research has offered a better understanding of disease treatment and created novel opportunities for developing effective drug delivery systems with high biocompability. Moreover, RNA interference has emerged as a promising strategy for disease treatments by selectively knocking down or over-expressing specific genes, which allows new possibilities to directly control cell signaling events or drug resistance. Recently, more and more interests have been paid to develop optimal delivery nanosystems with high efficiency and high biocompability for drug and functional RNA co-delivery to achieve enhanced chemotherapy. In light of the challenges for developing drug and RNA co-delivery system, exosomes have been found to show very attractive prospects. This review aims to explore current technologies and challenges in the use of exosomes as drug and RNA co-delivery system with a focus on the emerging trends and issues associated with their further applications, which may contribute to the accelerated developments of exosome-based theraputics

TOB1 modulates neutrophil phenotypes to influence gastric cancer progression and immunotherapy efficacy

IntroductionThe ErbB-2.1(TOB1) signaling transducer protein is a tumor-suppressive protein that actively suppresses the malignant phenotype of gastric cancer cells. Yet, TOB1 negatively regulates the activation and growth of different immune cells. Understanding the expression and role of TOB1 in the gastric cancer immune environment is crucial to maximize its potential in targeted immunotherapy.MethodsThis study employed multiplex immunofluorescence analysis to precisely delineate and quantify the expression of TOB1 in immune cells within gastric cancer tissue microarrays. Univariate and multivariate Cox analyses were performed to assess the influence of clinical-pathological parameters, immune cells, TOB1, and double-positive cells on the prognosis of gastric cancer patients. Subsequent experiments included co-culture assays of si-TOB1-transfected neutrophils with AGS or HGC-27 cells, along with EdU, invasion, migration assays, and bioinformatics analyses, aimed at elucidating the mechanisms through which TOB1 in neutrophils impacts the prognosis of gastric cancer patients.ResultsWe remarkably revealed that TOB1 exhibits varying expression levels in both the nucleus (nTOB1) and cytoplasm (cTOB1) of diverse immune cell populations, including CD8+ T cells, CD66b+ neutrophils, FOXP3+ Tregs, CD20+ B cells, CD4+ T cells, and CD68+ macrophages within gastric cancer and paracancerous tissues. Significantly, TOB1 was notably concentrated in CD66b+ neutrophils. Survival analysis showed that a higher density of cTOB1/nTOB1+CD66b+ neutrophils was linked to a better prognosis. Subsequent experiments revealed that, following stimulation with the supernatant of tumor tissue culture, the levels of TOB1 protein and mRNA in neutrophils decreased, accompanied by enhanced apoptosis. HL-60 cells were successfully induced to neutrophil-like cells by DMSO. Neutrophils-like cells with attenuated TOB1 gene expression by si-TOB1 demonstrated heightened apoptosis, consequently fostering a malignant phenotype in AGS and HCG-27 cells upon co-cultivation. The subsequent analysis of the datasets from TCGA and TIMER2 revealed that patients with high levels of TOB1 combined neutrophils showed better immunotherapy response.DiscussionThis study significantly advances our comprehension of TOB1’s role within the immune microenvironment of gastric cancer, offering promising therapeutic targets for immunotherapy in this context

A rheological-based printability assessment method for 3D printing Engineered Cementitious Composites considering fiber dispersion

3D concrete printing (3DCP) presents unique challenges in optimizing rheological properties of concrete mixture, while tailoring the rheology of Engineered Cementitious Composites (ECC) for 3D printing (3DP-ECC) is more intricate due to the added complexity of fiber dispersion. This study proposes an innovative printability evaluation method specifically designed for 3DP-ECC, which takes into account the impact of fiber dispersion while also emphasizing cost-effectiveness and efficiency. Additionally, the proposed method enables the calculation of the printable open time, thus adjusting the mixing time of the ECC paste. The feasibility of the proposed method was verified through actual printing test and rheological test, and experimental results showed good agreement with theoretical results. The tensile performance of 3DP-ECC was also investigated, providing further validation for the proposed methodology

Advances of Long Non-Coding RNAs as Potential Biomarkers for Tuberculosis: New Hope for Diagnosis?

Tuberculosis (TB), one of the top ten causes of death globally induced by the infection of Mycobacterium tuberculosis (Mtb), remains a grave public health issue worldwide. With almost one-third of the world’s population getting infected by Mtb, between 5% and 10% of these infected individuals are predicted to develop active TB disease, which would not only result in severe tissue damage and necrosis, but also pose serious threats to human life. However, the exact molecular mechanisms underlying the pathogenesis and immunology of TB remain unclear, which significantly restricts the effective control of TB epidemics. Despite significant advances in current detection technologies and treatments for TB, there are still no appropriate solutions that are suitable for simultaneous, early, rapid, and accurate screening of TB. Various cellular events can perturb the development and progression of TB, which are always associated with several specific molecular signaling events controlled by dysregulated gene expression patterns. Long non-coding RNAs (lncRNAs), a kind of non-coding RNA (ncRNA) with a transcript of more than 200 nucleotides in length in eukaryotic cells, have been found to regulate the expression of protein-coding genes that are involved in some critical signaling events, such as inflammatory, pathological, and immunological responses. Increasing evidence has claimed that lncRNAs might directly influence the susceptibility to TB, as well as the development and progression of TB. Therefore, lncRNAs have been widely expected to serve as promising molecular biomarkers and therapeutic targets for TB. In this review, we summarized the functions of lncRNAs and their regulatory roles in the development and progression of TB. More importantly, we widely discussed the potential of lncRNAs to act as TB biomarkers, which would offer new possibilities in novel diagnostic strategy exploration and benefit the control of the TB epidemic

Association of Maternal Dietary Patterns during Pregnancy and Offspring Weight Status across Infancy: Results from a Prospective Birth Cohort in China

Literature on maternal dietary patterns during pregnancy and offspring weight status have been largely equivocal. We aimed to investigate the association of maternal dietary patterns with infant weight status among 937 mother–infant dyads in a Chinese birth cohort. We assessed maternal diet during pregnancy using food frequency questionnaires (FFQ) and three-day food diaries (TFD) and examined infants’ body weight and length at birth, 1, 3, 6, 8 and 12 months. Maternal adherence to the “protein-rich pattern (FFQ)” was associated with lower infant body mass index z-scores (BMIZ) at birth, 3 and 6 months and lower odds of overweight and obesity (OwOb) across infancy (quartile 3 (Q3) vs. quartile 1 (Q1): odds ratio (OR): 0.50, (95% confidence interval: 0.27, 0.93)). Maternal adherence to the “vegetable–fruit–rice pattern (FFQ)” was associated with higher BMIZ at birth, 3 and 6 months and higher odds of OwOb across infancy (Q3 vs. Q1: OR: 1.79, (1.03, 3.12)). Maternal adherence to the “fried food–bean–dairy pattern (TFD)” was associated with lower BMIZ at 3, 6, 8 and 12 months and lower odds of OwOb (Q3 vs. Q1: OR: 0.54, (0.31, 0.95)). The study results may help to develop interventions and to better define target populations for childhood obesity prevention

Exploring Novel Antidepressants Targeting G Protein-Coupled Receptors and Key Membrane Receptors Based on Molecular Structures

Major Depressive Disorder (MDD) is a complex mental disorder that involves alterations in signal transmission across multiple scales and structural abnormalities. The development of effective antidepressants (ADs) has been hindered by the dominance of monoamine hypothesis, resulting in slow progress. Traditional ADs have undesirable traits like delayed onset of action, limited efficacy, and severe side effects. Recently, two categories of fast-acting antidepressant compounds have surfaced, dissociative anesthetics S-ketamine and its metabolites, as well as psychedelics such as lysergic acid diethylamide (LSD). This has led to structural research and drug development of the receptors that they target. This review provides breakthroughs and achievements in the structure of depression-related receptors and novel ADs based on these. Cryo-electron microscopy (cryo-EM) has enabled researchers to identify the structures of membrane receptors, including the N-methyl-D-aspartate receptor (NMDAR) and the 5-hydroxytryptamine 2A (5-HT2A) receptor. These high-resolution structures can be used for the development of novel ADs using virtual drug screening (VDS). Moreover, the unique antidepressant effects of 5-HT1A receptors in various brain regions, and the pivotal roles of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and tyrosine kinase receptor 2 (TrkB) in regulating synaptic plasticity, emphasize their potential as therapeutic targets. Using structural information, a series of highly selective ADs were designed based on the different role of receptors in MDD. These molecules have the favorable characteristics of rapid onset and low adverse drug reactions. This review offers researchers guidance and a methodological framework for the structure-based design of ADs

Zinc Oxide–Selenium Nanoparticles for Inhibiting the Proliferation of Porcine Reproductive and Respiratory Syndrome Virus

Porcine Reproductive and Respiratory Syndrome (PRRS) is an acute, highly contagious swine infectious disease caused by the PRRS virus (PRRSV). Due to the frequent mutation and recombination of PRRSV, the current commercial vaccines cannot provide effective protection, and there is an urgent need to develop antiviral drugs. This study aimed to prepare a kind of zinc oxide–selenium nanoparticle (ZnO–Se NPs) and investigate their inhibitory effect on PRRSV proliferation. The hybridization of ZnO and selenium resulted in the synthesis of ZnO–Se NPs, which were then examined by using dynamic laser light scattering and transmission electron microscopy for characterization. The ZnO–Se NPs showed excellent stability and dispersibility, measuring an average diameter of 90 nm. MTT assay revealed that ZnO–Se NPs had good biocompatibility and low toxicity below 2.5 μg/mL. Various experiments have shown that ZnO–Se NPs have the ability to effectively suppress the proliferation of PRRSV in a dose-dependent fashion. Moreover, this inhibition was equally effective against other subgenotypes of PRRSV and non-RNA viruses, indicating that ZnO–Se NPs had broad-spectrum antimicrobial properties. Mechanism investigations revealed that ZnO–Se NPs inhibited PRRSV primarily by targeting the replication process through upregulation of the expression of NLRX1, a protein that interacts with PRRSV Nsp9, and by inhibiting PRRSV-induced upregulation of ROS, rather than by stimulating the innate immunity. This work emphasized the antiviral impact of ZnO–Se NPs and offered compelling evidence of their potential as a promising therapy against PRRSV and other viral infections