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Oxygen and nutrient deprivation are common features of solid tumors. Although abnormal alternative splicing (AS) has been found to be an important driving force in tumor pathogenesis and progression, the regulatory mechanisms of AS that underly the adaptation of cancer cells to harsh microenvironments remain unclear. Here, we found that hypoxia- and nutrient deprivation-induced asparagine endopeptidase (AEP) specifically cleaved DDX3X in a HIF1A-dependent manner. This cleavage yields truncated carboxyl-terminal DDX3X (tDDX3X-C), which translocates and aggregates in the nucleus. Unlike intact DDX3X, nuclear tDDX3X-C complexes with an array of splicing factors and induces AS events of many premRNAs; for example, enhanced exon skipping (ES) in exon 2 of the classic tumor suppressor PRDM2 leads to a frameshift mutation of PRDM2. Intriguingly, the isoform ARRB1-[DELTA]exon 13 binds to glycolytic enzymes and regulates glycolysis. By utilizing in vitro assays, glioblastoma organoids, and animal models, we revealed that AEP/tDDX3X-C promoted tumor malignancy via these isoforms. More importantly, high AEP/tDDX3X-C/ARRB1- [DELTA]exon 13 in cancerous tissues was tightly associated with poor patient prognosis. Overall, our discovery of the effect of AEP-cleaved DDX3X switching on alternative RNA splicing events identifies a mechanism in which cancer cells adapt to oxygen and nutrient shortages and provides potential diagnostic and/or therapeutic targets., Introduction In the tumor microenvironment, cells often face a certain degree of oxygen and nutrient deprivation. Cancer cells strive to survive and proliferate in this harsh environment in multiple ways, [...]

Background and Aim: The role of C6ORF120 in promoting CCL4‐induced hepatic fibrosis and its possible mechanisms were explored in C6orf120 knockout rats (C6orf120−/−) and LX‐2 cells (a type of human hepatic stellate cell line). Methods: In vivo experiments, wild‐type and C6orf120−/− rats were used to investigate the function of C6ORF120. In the in vitro experiments, C6ORF120 recombinant protein (rC6ORF120) at a concentration of 200 ng/mL was used to stimulate LX‐2 cells. Sirius Red staining, Masson staining, western blotting, polymerase chain reaction, immunohistochemistry, and immunofluorescence were used to explore fibrosis‐associated factors. Results: C6orf120−/− rats showed mild fibrosis and liver injury in the CCL4‐induced liver fibrosis model. Furthermore, RNA‐seq revealed that C6orf120−/− rats had less extracellular matrix deposition and activated stellate cells. Consistent with the in vivo, the rC6ORF120 induced LX‐2 cell activation. Moreover, mechanistic studies revealed that the p‐PI3K/PI3K, p‐Akt/Akt, and p‐mTOR/mTOR levels were significantly elevated and LY294002 (a PI3K/Akt/mTOR typical pathway inhibitor) reversed the function of C6ORF120 in activating LX‐2 cells. Conclusion: C6ORF120 could activate hepatic stellate cells and promote hepatic fibrosis via the PI3K/Akt/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Human milk is universally regarded as the gold standard to fulfill nutrition needs of infants. Lactoferrin (LF) is a major multiple bioactive glycoprotein in human milk but little is presented in infant formula. LF can resist digestion in the infant gastrointestinal tract and is absorbed into the bloodstream in an intact form to perform physiological functions. Evidence suggest that LF prevents pathogen infection, promotes immune system development, intestinal development, brain development and bone health, as well as ameliorates iron deficiency anemia. However, more clinical studies of LF need to be further elucidated to determine an appropriate dosage for application in infant formula. LF is sensitive to denaturation induced by processing of infant formula such as heat treatments and spay drying. Thus, further studies should be focus on maximizing the retention of LF activity in the infant formula process. This review summarizes the structural features of LF. Then the digestion, absorption and metabolism of LF in infants are discussed, followed by the function of LF for infants. Further, we summarize LF in infant formula and effects of processing of infant formula on bioactivities of LF, as well as future perspectives of LF research. [ABSTRACT FROM AUTHOR]

In vitro diagnosis (IVD) is pivotal in modern medicine, enabling early disease detection and treatment optimization. Omics technologies, particularly proteomics and metabolomics, offer profound insights into IVD. Despite its significance, omics analyses for IVD face challenges, including low analyte concentrations and the complexity of biological environments. In addition, the direct omics analysis by mass spectrometry (MS) is often hampered by issues like large sample volume requirements and poor ionization efficiency. Through manipulating their size, surface charge, and functionalization, as well as the nanoparticle‐fluid incubation conditions, nanomaterials have emerged as a promising solution to extract biomolecules and enhance the desorption/ionization efficiency in MS detection. This review delves into the last five years of nanomaterial applications in omics, focusing on their role in the enrichment, separation, and ionization analysis of proteins and metabolites for IVD. It aims to provide a comprehensive update on nanomaterial design and application in omics, highlighting their potential to revolutionize IVD. [ABSTRACT FROM AUTHOR]

Background: Ultrasonic for detecting and evaluating pleural effusion is an essential part of the Extended Focused Assessment with Sonography in Trauma (E‐FAST) in emergencies. Our study aimed to develop an Artificial Intelligence (AI) diagnostic model that automatically identifies and segments pleural effusion areas on ultrasonography. Methods: An Attention U‐net and a U‐net model were used to detect and segment pleural effusion on ultrasound images of 848 subjects through fully supervised learning. Sensitivity, specificity, precision, accuracy, F1 score, the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) were used to assess the model's effectiveness in classifying the data. The dice coefficient was used to evaluate the segmentation performance of the model. Results: In 10 random tests, the Attention U‐net and U‐net 's average sensitivity of 97% demonstrated that the pleural effusion was well detectable. The Attention U‐net performed better at identifying negative images than the U‐net, which had an average specificity of 91% compared to 86% for the U‐net. Additionally, the Attention U‐net was more accurate in predicting the pleural effusion region because its average dice coefficient was 0.86 as opposed to the U‐net's average dice coefficient of 0.82. Conclusions: The Attention U‐net showed excellent performance in detecting and segmenting pleural effusion on ultrasonic images, which is expected to enhance the operation and application of E‐FAST in clinical work. [ABSTRACT FROM AUTHOR]

AbstractDuring the application of Whey proteins (WPs), they often have complex interactions with saccharides (Ss), another important biopolymer in food substrate. The texture and sensory qualities of foods containing WPs and Ss are largely influenced by the interactions of WPs-Ss. Moreover, the combination of WPs and Ss is possible to produce many excellent functional properties including emulsifying properties and thermal stability. However, the interactions between WPs-Ss are complex and susceptible to some processing conditions. In addition, with different interaction ways, they can be applied in different fields. Therefore, the non-covalent interaction mechanisms between WPs-Ss are firstly summarized in detail, including electrostatic interaction, hydrogen bond, hydrophobic interaction, van der Waals force. Furthermore, the existence modes of WPs-Ss are introduced, including complex coacervates, soluble complexes, segregation, and co-solubility. The covalent interactions of WPs-Ss in food applications are often formed by Maillard reaction (dry or wet heat reaction) and occasionally through enzyme induction. Then, two common influencing factors, pH and temperature, on non-covalent/covalent bonds are introduced. Finally, the applications of WPs-Ss complexes and conjugations in improving WP stability, delivery system, and emulsification are described. This review can improve our understanding of the interactions between WPs-Ss and further promote their wider application. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) represents a severe and progressive manifestation of idiopathic interstitial pneumonia marked by an uncertain etiology along with an unfavorable prognosis. Osteoglycin (OGN), belonging to the small leucine-rich proteoglycans family, assumes pivotal functions in both tissue formation and damage response. However, the roles and potential mechanisms of OGN in the context of lung fibrosis remain unexplored., Methods: The assessment of OGN expression levels in fibrotic lungs was conducted across various experimental lung fibrosis mouse models. To elucidate the effects of OGN on the differentiation of lung myofibroblasts, both OGN knockdown and OGN overexpression were employed in vitro. The expression of integrin αv, along with its colocalization with lysosomes and latency-associated peptide (LAP), was monitored in OGN-knockdown lung myofibroblasts. Furthermore, the role of OGN in lung fibrosis was investigated through OGN knockdown utilizing adeno-related virus serotype 6 (AAV6)-mediated delivery., Results: OGN exhibited upregulation in both lungs and myofibroblasts across diverse lung fibrosis mouse models. And laboratory experiments in vitro demonstrated that OGN knockdown inhibited the TGF-β/Smad signaling pathway in lung myofibroblasts. Conversely, OGN overexpression promoted TGF-β/Smad pathway in these cells. Mechanistic insights revealed that OGN knockdown facilitated lysosome-mediated degradation of integrin αv while inhibiting its binding to latency-associated peptide (LAP). Remarkably, AAV6-targeted OGN knockdown ameliorated the extent of lung fibrosis in experimental mouse models., Conclusion: Our results indicate that inhibiting OGN signaling could serve as a promising therapeutic way for lung fibrosis., Competing Interests: Declaration of competing interest No conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, which is increasing annually. GDM can cause serious harm to both the mother and the offspring. However, the clinical indicators that predict pregnancy outcomes with GDM remain limited., Methods: This study included 3,229 pregnancies. Inflammatory markers were defective in the mother's peripheral blood. Also, the Chi-square test, logistic regression analyses and Spearman rank correlation coefficient were performed to evaluate inflammatory markers with pregnancy outcomes. The association between inflammatory markers and pregnancy outcomes was analyzed. The optimal cut-off values of inflammatory markers were calculated., Results: Finally, 3,229 women were included. 1852 (57.36%) participants suffered good pregnancy outcomes. This study revealed that the maternal age, the baseline BMI (kg/m 2 ), the times of parity, and the level of lymphocyte, SII and SIRI significantly increased in poor pregnancy outcomes groups. Additionally, inflammatory markers, such as white blood cells (WBC), neutrophils, monocytes, platelet counts, lymphocytes, systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) were related to pregnancy outcomes. Furthermore, the results revealed that the SII level had the highest odd rates (OR) [OR = 6.957; 95% CI (5.715-8.468)], followed by SIRI level [OR = 2.948; 95% CI (2.382-3.649)], the WBC counts [OR = 1.930; 95% CI (0.901-2.960)], the lymphocyte counts [OR = 1.668; 95% CI (1.412-1.970)], and baseline BMI [OR = 1.050; 95% (1.021-1.080)]., Conclusion: This study presented that the baseline SII and SIRI levels can be valuable biochemical markers to predict the pregnancy outcome with GDM with non-invasive procedures. They can help identify high-risk pregnant women with GDM early, provide a personalized intervention in time, and enhance perinatal surveillance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiu, Lin, Chen, Lin, Zu and Yan.)

Background: Current studies have demonstrated that disintegrin and metalloproteinase 17 (ADAM17) plays a critical role in the pathogenesis of sepsis. MicroRNA (miR)-145 is known to control immune responses as an anti-inflammatory modulatory molecule. However, a fundamental understanding of how miR-145 regulates ADAM17 and, more broadly, sepsis-induced inflammatory response remains unknown., Methods: We used western blotting and quantitative real-time PCR (qRT-PCR) to measure expression levels of ADAM17 and miR-145. Enzyme-linked immunosorbent assays (ELISA) were performed to measure cytokine production. To determine if ADAM17 is a target gene of miR-145, bioinformatics analyses and luciferase reporter assays were conducted. The impacts of ADAM17 and miR-145 on sepsis-induced inflammatory responses were accessed in vitro using human umbilical endothelial cells (HUVECs) treated with lipopolysaccharide (LPS). Sepsis-induced inflammatory response was measured in vivo using a polymicrobial septic mouse model induced by cecal ligation and puncture (CLP) with pre-injection of a miR-145 agomir., Results: In HUVECs treated with LPS, miR-145 expression was downregulated and miR-145 negatively regulated ADAM17 expression through direct binding to the ADAM17 transcript 3'-UTR. MiR-145 overexpression markedly reduced LPS-induced inflammatory cytokine production by targeting ADAM17 in HUVECs. In comparison to CLP-induced septic mice treated with a control agomir, treatment with a miR-145 agomir significantly reduced the expression of ADAM17, numerous downstream cytokines such as IL-6, TNF-α, IL-1β and MCP-1, and the endothelial injury factors ICAM-1, VCAM-1. The miR-145 agomir also alleviated acute lung and kidney injury and improved the survival rate of septic mice., Conclusions: This study showed that miR-145, by specifically targeting ADAM17, negatively regulates sepsis-induced inflammatory responses and vascular endothelial injury, and ultimately improved organ injury and survival during sepsis. The underlying mechanism for the regulation of ADAM17 expression by miR-145 and sepsis-induced inflammatory reactions may offer sepsis patients a novel therapeutic option., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)