Unveiling the role of taurine and SLC6A6 in tumor immune evasion: Implications for gastric cancer therapy.

Metabolic changes are key drivers of tumor progression. Understanding how metabolic reprogramming promotes tumor development and identifying key metabolic activities are essential for improving tumor diagnosis and treatment. Among the numerous transporters in the body, solute carriers (SLCs) are particularly significant, often overexpressed in cancer cells to meet the tumor's demand for nutrients and energy. While the role of SLCs in nutrient absorption within the gastrointestinal tract is well-established, their specific role in gastric cancer (GC) remains unclear. Recently, Xiaodi Zhao's team investigated the critical role of taurine and its transporter, SLC6A6, in anti-tumor immunity and clinical outcomes. Notably, this research marks the first instance of taurine exhibiting a dual role. It promotes tumor growth in immunodeficient mice while inhibiting it in immunocompetent mice. The study found that taurine exerts its anti-cancer effects by modulating CD8+ T cells rather than directly inhibiting tumor cells, revealing the SP1-SLC6A6 axis as a key mechanism behind chemotherapy-induced immune evasion. Our work further explored the potential, advantages, and challenges of using taurine and SLC6A6 as biomarkers and therapeutic targets in gastric cancer. We aim to underscore their importance in both basic research and clinical applications, providing valuable insights and guidance for future investigations.

RNA splicing factor RBFOX2 is a key factor in the progression of cancer and cardiomyopathy.

BACKGROUND: Alternative splicing of pre-mRNA is a fundamental regulatory process in multicellular eukaryotes, significantly contributing to the diversification of the human proteome. RNA-binding fox-1 homologue 2 (RBFOX2), a member of the evolutionarily conserved RBFOX family, has emerged as a critical splicing regulator, playing a pivotal role in the alternative splicing of pre-mRNA. This review provides a comprehensive analysis of RBFOX2, elucidating its splicing activity through direct and indirect binding mechanisms. RBFOX2 exerts substantial influence over the alternative splicing of numerous transcripts, thereby shaping essential cellular processes such as differentiation and development. MAIN BODY OF THE ABSTRACT: Dysregulation of RBFOX2-mediated alternative splicing has been closely linked to a spectrum of cardiovascular diseases and malignant tumours, underscoring its potential as a therapeutic target. Despite significant progress, current research faces notable challenges. The complete structural characterisation of RBFOX2 remains elusive, limiting in-depth exploration beyond its RNA-recognition motif. Furthermore, the scarcity of studies focusing on RBFOX2-targeting drugs poses a hindrance to translating research findings into clinical applications. CONCLUSION: This review critically assesses the existing body of knowledge on RBFOX2, highlighting research gaps and limitations. By delineating these areas, this analysis not only serves as a foundational reference for future studies but also provides strategic insights for bridging these gaps. Addressing these challenges will be instrumental in unlocking the full therapeutic potential of RBFOX2, paving the way for innovative and effective treatments in various diseases.

MicroRNA­325: A comprehensive exploration of its multifaceted roles in cancer pathogenesis and therapeutic implications (Review).

MicroRNA (miRNA/miR) represents a category of endogenous, short-chain non-coding RNA molecules comprising ~22 nucleotides. Specifically, miR-325 is situated within the first sub-band of region 2 on the short arm of the X chromosome. Notably, aberrant expression of miR-325 has been observed across various tumor systems, spanning the nervous, endocrine, respiratory, reproductive and digestive systems. miR-325 exhibits the capacity to target a minimum of 20 protein-coding genes, thereby influencing diverse cellular processes, including cell proliferation, epithelial-mesenchymal transition, apoptosis, invasion and migration. Moreover, miR-325 serves a pivotal role in the formation of six competing endogenous RNA (ceRNA) regulatory axes, involving one circular RNA, four long non-coding RNA and one additional miRNA. By participating in various signaling pathways through gene targeting, the abnormal expression of miR-325 has been associated with clinicopathological conditions in diverse patients with cancer, significantly impacting both the clinicopathology and prognosis of affected individuals. Additionally, miR-325 has been associated with the development of resistance to oxaliplatin, cisplatin and doxorubicin in cancer cells. Its involvement in the anticancer molecular mechanisms of these agents underscores its potential significance in therapeutic contexts. However, it is noteworthy that the current study did not specifically address sex-based cell line selection. In conclusion, the present review provides a comprehensive summary of the relevant findings concerning miR-325, offering valuable insights for future research endeavors focused on determining the molecular mechanisms associated with this miRNA.

Harnessing extracellular vesicles using liquid biopsy for cancer diagnosis and monitoring: highlights from AACR Annual Meeting 2024.

Liquid biopsy, an advanced technology for analyzing body fluid samples, is gaining traction in cancer diagnostics and monitoring. Blood-based liquid biopsy, particularly focusing on cell-free DNAs (cf-DNAs), circulating tumor cells (CTCs), and extracellular vesicles (EVs), has garnered significant attention. EVs stand out for their potential in tumor diagnosis, prognosis prediction, and treatment response assessment, owing to their stable molecular cargo and clear extraction process. At the recent American Association for Cancer Research (AACR) Annual Meeting 2024, groundbreaking EVs-based liquid biopsy studies showcased promising strides in early detection and diagnosis of various cancers, including breast cancer (BC), high-grade serous ovarian cancer (HGSOC), pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), colon adenocarcinoma (COAD), head and neck cancer (HNC), neuroblastoma, and retinoblastoma (RB). Despite these advancements, challenges persist in translating EVs biomarkers into clinical practice. Overcoming these challenges promises to propel EVs-based liquid biopsy into a new era of personalized precision medicine, revolutionizing cancer detection, monitoring, and treatment.

Exploring the regulatory role of tsRNAs in the TNF signaling pathway: Implications for cancer and non-cancer diseases.

Transfer RNA-derived small RNAs (tsRNAs), a recently identified subclass of small non-coding RNAs (sncRNAs), emerge through the cleavage of mature transfer RNA (tRNA) or tRNA precursors mediated by specific enzymes. The tumor necrosis factor (TNF) protein, a signaling molecule produced by activated macrophages, plays a pivotal role in systemic inflammation. Its multifaceted functions include the capacity to eliminate or hinder tumor cells, enhance the phagocytic capabilities of neutrophils, confer resistance against infections, induce fever, and prompt the production of acute phase proteins. Notably, four TNF-related tsRNAs have been conclusively linked to distinct diseases. Examples include 5'tiRNA-Gly in skeletal muscle injury, tsRNA-21109 in systemic lupus erythematosus (SLE), tRF-Leu-AAG-001 in endometriosis (EMs), and tsRNA-04002 in intervertebral disk degeneration (IDD). These tsRNAs exhibit the ability to suppress the expression of TNF-α. Additionally, KEGG analysis has identified seven tsRNAs potentially involved in modulating the TNF pathway, exerting their influence across a spectrum of non-cancerous diseases. Noteworthy instances include aberrant tiRNA-Ser-TGA-001 and tRF-Val-AAC-034 in intrauterine growth restriction (IUGR), irregular tRF-Ala-AGC-052 and tRF-Ala-TGC-027 in obesity, and deviant tiRNA-His-GTG-001, tRF-Ser-GCT-113, and tRF-Gln-TTG-035 in irritable bowel syndrome with diarrhea (IBS-D). This comprehensive review explores the biological functions and mechanisms of tsRNAs associated with the TNF signaling pathway in both cancer and other diseases, offering novel insights for future translational medical research.

Coupled Effects of High Temperature and Steel Fiber Content on Energy Absorption Properties of Concrete.

The associated effects of temperature and steel fiber content on the energy absorption properties of concrete were examined using quasi-static uniaxial compression tests of concrete materials with varied steel fiber contents (0%, 0.5%, 1%, and 1.5%) at various temperatures (20 °C, 200 °C, 400 °C, and 520 °C). The experimental findings demonstrate that steel fibers can greatly boost concrete's ability to absorb energy and that the toughness index rises with steel fiber concentration. The energy absorption capacity of concrete under high-temperature conditions also significantly decreases as temperature rises, and the energy absorption ability of steel fiber concrete under the same temperature is superior to that of plain concrete. The coupled influence factor K of temperature-steel fiber percentage characterizing the energy-absorbing ability of concrete was determined, and the coupled influence law of temperature and steel fiber content on the energy-absorbing capacity of concrete materials was summarized and analyzed on the basis of the experimental data of high-temperature compression. Equivalent equations for steel fiber reinforcing and temperature weakening effects when they are comparable (K = 1) are developed and equivalent parameters for concrete materials are given.

Current and future perspectives on the regulation and functions of miR-545 in cancer development.

Micro ribonucleic acids (miRNAs) are a highly conserved class of single-stranded non-coding RNAs. Within the miR-545/374a cluster, miR-545 resides in the intron of the long non-coding RNA (lncRNA) FTX on Xq13.2. The precursor form, pre-miR-545, is cleaved to generate two mature miRNAs, miR-545-3p and miR-545-5p. Remarkably, these two miRNAs exhibit distinct aberrant expression patterns in different cancers; however, their expression in colorectal cancer remains controversial. Notably, miR-545-3p is affected by 15 circular RNAs (circRNAs) and 10 long non-coding RNAs (lncRNAs), and it targets 27 protein-coding genes (PCGs) that participate in the regulation of four signaling pathways. In contrast, miR-545-5p is regulated by one circRNA and five lncRNAs, it targets six PCGs and contributes to the regulation of one signaling pathway. Both miR-545-3p and miR-545-5p affect crucial cellular behaviors, including cell cycle, proliferation, apoptosis, epithelial-mesenchymal transition, invasion, and migration. Although low miR-545-3p expression is associated with poor prognosis in three cancer types, studies on miR-545-5p are yet to be reported. miR-545-3p operates within a diverse range of regulatory networks, thereby augmenting the efficacy of cancer chemotherapy, radiotherapy, and immunotherapy. Conversely, miR-545-5p enhances immunotherapy efficacy by inhibiting T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) expression. In summary, miR-545 holds immense potential as a cancer biomarker and therapeutic target. The aberrant expression and regulatory mechanisms of miR-545 in cancer warrant further investigation.

CircR-loop: a novel RNA:DNA interaction on genome instability.

CircR-loop, a recently unearthed regulatory mechanism situated at the crossroads of circular RNA and DNA interactions, constitute a subset of R-loop. This circR-loop have emerged as a crucial player in pivotal regulatory functions within both animal and plant systems. The journey into the realm of circR-loop commenced with their discovery within the human mitochondrial genome, where they serve as critical directors of mitochondrial DNA replication. In the plant kingdom, circR-loop wield influence over processes such as alternative splicing and centromere organization, impacting the intricacies of floral development and genome stability, respectively. Their significance extends to the animal domain, where circR-loop has captured attention for their roles in cancer-related phenomena, exerting control over transcription, chromatin architecture, and orchestrating responses to DNA damage. Moreover, their involvement in nuclear export anomalies further underscores their prominence in cellular regulation. This article summarizes the important regulatory mechanisms and physiological roles of circR-loop in plants and animals, and offers a comprehensive exploration of the methodologies employed for the identification, characterization, and functional analysis of circR-loop, underscoring the pressing need for innovative approaches that can effectively distinguish them from their linear RNA counterparts while elucidating their precise functions. Lastly, the article sheds light on the challenges and opportunities that lie ahead in the field of circR-loop research, emphasizing the vital importance of continued investigations to uncover their regulatory roles and potential applications in the realm of biology. In summary, circR-loop represents a captivating and novel regulatory mechanism with broad-reaching implications spanning the realms of genetics, epigenetics, and disease biology. Their exploration opens new avenues for comprehending gene regulation and holds significant promise for future therapeutic interventions.

Exploring the role of tRNA-derived small RNAs (tsRNAs) in disease: implications for HIF-1 pathway modulation.

The tRNA-derived small RNAs (tsRNAs) can be categorized into two main groups: tRNA-derived fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs). Each group possesses specific molecular sizes, nucleotide compositions, and distinct physiological functions. Notably, hypoxia-inducible factor-1 (HIF-1), a transcriptional activator dependent on oxygen, comprises one HIF-1ß subunit and one HIF-α subunit (HIF-1α/HIF-2α/HIF-3α). The activation of HIF-1 plays a crucial role in gene transcription, influencing key aspects of cancer biology such as angiogenesis, cell survival, glucose metabolism, and invasion. The involvement of HIF-1α activation has been demonstrated in numerous human diseases, particularly cancer, making HIF-1 an attractive target for potential disease treatments. Through a series of experiments, researchers have identified two tiRNAs that interact with the HIF-1 pathway, impacting disease development: 5'tiRNA-His-GTG in colorectal cancer (CRC) and tiRNA-Val in diabetic retinopathy (DR). Specifically, 5'tiRNA-His-GTG promotes CRC development by targeting LATS2, while tiRNA-Val inhibits Sirt1, leading to HIF-1α accumulation and promoting DR development. Clinical data have further indicated that certain tsRNAs' expression levels are associated with the prognosis and pathological features of CRC patients. In CRC tumor tissues, the expression level of 5'tiRNA-His-GTG is significantly higher compared to normal tissues, and it shows a positive correlation with tumor size. Additionally, KEGG analysis has revealed multiple tRFs involved in regulating the HIF-1 pathway, including tRF-Val-AAC-016 in diabetic foot ulcers (DFU) and tRF-1001 in pathological ocular angiogenesis. This comprehensive article reviews the biological functions and mechanisms of tsRNAs related to the HIF-1 pathway in diseases, providing a promising direction for subsequent translational medicine research.

RhoJ: an emerging biomarker and target in cancer research and treatment.

RhoJ is a Rho GTPase that belongs to the Cdc42 subfamily and has a molecular weight of approximately 21 kDa. It can activate the p21-activated kinase family either directly or indirectly, influencing the activity of various downstream effectors and playing a role in regulating the cytoskeleton, cell movement, and cell cycle. RhoJ's expression and activity are controlled by multiple upstream factors at different levels, including expression, subcellular localization, and activation. High RhoJ expression is generally associated with a poor prognosis for cancer patients and is mainly due to an increased number of tumor blood vessels and abnormal expression in malignant cells. RhoJ promotes tumor progression through several pathways, particularly in tumor angiogenesis and drug resistance. Clinical data also indicates that high RhoJ expression is closely linked to the pathological features of tumor malignancy. There are various cancer treatment methods that target RhoJ signaling, such as direct binding to inhibit the RhoJ effector pocket, inhibiting RhoJ expression, blocking RhoJ upstream and downstream signals, and indirectly inhibiting RhoJ's effect. RhoJ is an emerging cancer biomarker and a significant target for future cancer clinical research and drug development.

Exploring the multifaceted role of GCN1: Implications in cellular responses and disease pathogenesis.

GCN1 is a highly conserved protein present widely across eukaryotes. As an upstream activator of protein kinase GCN2, GCN1 plays a pivotal role in integrated stress responses, such as amino acid starvation and oxidative stress. Through interaction with GCN2, GCN1 facilitates the activation of GCN2, thus initiating downstream signaling cascades in response to cellular stressors. In these contexts, the activation of GCN2 necessitates the presence and action of GCN1. Notably, GCN1 also operates as a ribosome collision sensor, contributing significantly to the translation quality control pathway. These discoveries offer valuable insights into cellular responses to internal stresses, vital for maintaining cellular homeostasis. Additionally, GCN1 exhibits the ability to regulate the cell cycle and suppress inflammation, among other processes, independently of GCN2. Our review outlines the structural characteristics and biological functions of GCN1, shedding light on its significant involvement in the onset and progression of various cancer and non-cancer diseases. Our work underscores the role of GCN1 in the context of drug therapeutic effects, hinting at its potential as a promising drug target. Furthermore, our work delves deep into the functional mechanisms of GCN1, promising innovative avenues for the diagnosis and treatment of diseases in the future. The exploration of GCN1's multifaceted roles not only enhances our understanding of its mechanisms but also paves the way for novel therapeutic interventions. The ongoing quest to unveil additional functions of GCN1 holds the promise of further enriching our comprehension of its mode of action.

Unveiling a novel fusion gene enhances CAR T cell therapy for solid tumors.

The efficacy of Adoptive Cell Transfer Therapy (ACT) in combating hematological tumors has been well-documented, yet its application to solid tumors faces formidable hurdles, chief among them being the suboptimal therapeutic response and the immunosuppressive milieu within the tumor microenvironment (TME). Recently, Garcia, J. et al. present compelling findings shedding light on potential breakthroughs in this domain. Their investigation reveals the pronounced augmentation of anti-tumor activity in CAR T cells through the introduction of a T cell neoplasm fusion gene, CARD11-PIK3R3. The incorporation of this gene into engineered T cell therapy holds promise as a formidable tool in the arsenal of cancer immunotherapy. The innovative strategy outlined not only mitigates the requirement for high doses of CAR T cells but also enhances tumor control while exhibiting encouraging safety profiles. The exploration of the CARD11-PIK3R3 fusion gene represents an advancement in our approach to bolstering the anti-tumor efficacy of immunotherapeutic interventions. Nonetheless, the imperative for further inquiry to ascertain its transfection efficiency and long-term safety cannot be overstated. Nevertheless, this seminal investigation offers a beacon of hope in surmounting the formidable treatment impediments posed by solid tumors, paving the way for a transformative era in cancer therapeutics.

Unveiling the role of tRNA-derived small RNAs in MAPK signaling pathway: implications for cancer and beyond.

tRNA-derived small RNAs (tsRNAs) are novel small non-coding RNAs originating from mature or precursor tRNAs (pre-tRNA), typically spanning 14 to 30 nt. The Mitogen-activated protein kinases (MAPK) pathway orchestrates cellular responses, influencing proliferation, differentiation, apoptosis, and transformation. tsRNAs influence the expression of the MAPK signaling pathway by targeting specific proteins within the pathway. Presently, four MAPK-linked tsRNAs have implications in gastric cancer (GC) and high-grade serous ovarian cancer (HGSOC). Notably, tRF-Glu-TTC-027 and tRF-Val-CAC-016 modulate MAPK-related protein expression, encompassing p38, Myc, ERK, CyclinD1, CyclinB, and c-Myc, hindering GC progression via MAPK pathway inhibition. Moreover, tRF-24-V29K9UV3IU and tRF-03357 remain unexplored in specific mechanisms. KEGG analysis posits varied tsRNAs in MAPK pathway modulation for diverse non-cancer maladies. Notably, high tRF-36-F900BY4D84KRIME and tRF-23-87R8WP9IY expression relates to varicose vein (VV) risk. Elevated tiRNA-Gly-GCC-001, tRF-Gly-GCC-012, tRF-Gly-GCC-013, and tRF-Gly-GCC-016 target spinal cord injury (SCI)-related brain-derived neurotrophic factor (BDNF), influencing MAPK expression. tRF-Gly-CCC-039 associates with diabetes foot sustained healing, while tRF-5014a inhibits autophagy-linked ATG5 in diabetic cardiomyopathy (DCM). Additionally, tsRNA-14783 influences keloid formation by regulating M2 macrophage polarization. Upregulation of tRF-Arg-ACG-007 and downregulation of tRF-Ser-GCT-008 are associated with diabetes. tsRNA-04002 alleviates Intervertebral disk degeneration (IDD) by targeting PRKCA. tsRNA-21109 alleviates Systemic lupus erythematosus (SLE) by inhibiting macrophage M1 polarization. The upregulated tiNA-Gly-GCC-002 and the downregulated tRF-Ala-AGC-010, tRF-Gln-CTG-005 and tRF-Leu-AAG-001 may be involved in the pathogenesis of Lupus nephritis (LN) by affecting the expression of MAPK pathway. Downregulation of tsRNA-1018, tsRNA-3045b, tsRNA-5021a and tsRNA-1020 affected the expression of MAPK pathway, thereby improving Acute lung injury (ALI). This review comprehensively dissects tsRNA roles in MAPK signaling across cancers and other diseases, illuminating a novel avenue for translational medical exploration.

Dynamic constitutive identification of concrete based on improved dung beetle algorithm to optimize long short-term memory model.

In order to improve the accuracy of concrete dynamic principal identification, a concrete dynamic principal identification model based on Improved Dung Beetle Algorithm (IDBO) optimized Long Short-Term Memory (LSTM) network is proposed. Firstly, the apparent stress-strain curves of concrete containing damage evolution were measured by Split Hopkinson Pressure Bar (SHPB) test to decouple and separate the damage and rheology, and this system was modeled by using LSTM network. Secondly, for the problem of low convergence accuracy and easy to fall into local optimum of Dung Beetle Algorithm (DBO), the greedy lens imaging reverse learning initialization population strategy, the embedded curve adaptive weighting factor and the PID control optimal solution perturbation strategy are introduced, and the superiority of IDBO algorithm is proved through the comparison of optimization test with DBO, Harris Hawk Optimization Algorithm, Gray Wolf Algorithm, and Fruit Fly Algorithm and the combination of LSTM is built to construct the IDBO-LSTM dynamic homeostasis identification model. The final results show that the IDBO-LSTM model can recognize the concrete material damage without considering the damage; in the case of considering the damage, the IDBO-LSTM prediction curves basically match the SHPB test curves, which proves the feasibility and excellence of the proposed method.

CLLU1 as an emerging biomarker in chronic lymphoid leukemia.

CLLU1, a disease-specific gene associated with chronic lymphoid leukemia (CLL), is located on chromosome 12q22. Previous studies considered CLLU1 to be a non-coding RNA; however, recent research has discovered that its coding sequence region possesses the potential to encode a short peptide similar to interleukin-4. Remarkably, abnormally elevated expression of CLLU1 has only been detected in chronic lymphoid leukemia among all hematological cancers. High CLLU1 expression often indicates more malignant pathological features and an unfavorable prognosis for patients. Importantly, the expression level of CLLU1 remains unaffected by the passage of time or therapeutic interventions, thus rendering it a novel prognostic marker. This article provides a comprehensive summary of relevant research findings on CLLU1 in the context of CLL prognosis and clinical applications, aiming to guide subsequent theoretical and clinical investigations in this field.

Prediction of compressive strength of concrete based on improved artificial bee colony-multilayer perceptron algorithm.

There are many factors that affect the compressive strength of concrete. The relationship between compressive strength and these factors is a complex nonlinear problem. Empirical formulas commonly used to predict the compressive strength of concrete are based on summarizing experimental data of several different mix proportions and curing periods, and their generality is poor. This article proposes an improved artificial bee colony algorithm (IABC) and a multilayer perceptron (MLP) coupled model for predicting the compressive strength of concrete. To address the shortcomings of the basic artificial bee colony algorithm, such as easily falling into local optima and slow convergence speed, this article introduces a Gaussian mutation operator into the basic artificial bee colony algorithm to optimize the initial honey source position and designs an MLP neural network model based on the improved artificial bee colony algorithm (IABC-MLP). Compared with traditional strength prediction models, the ABC-MLP model can better capture the nonlinear relationship of the compressive strength of concrete and achieve higher prediction accuracy when considering the compound effect of multiple factors. The IABC-MLP model built in this study is compared with the ABC-MLP and particle swarm optimization (PSO) coupling algorithms. The research shows that IABC can significantly improve the training and prediction accuracy of MLP. Compared with the ABC-MLP and PSO-MLP coupling models, the training accuracy of the IABC-MLP model is increased by 1.6% and 4.5%, respectively. This model is also compared with common individual learning algorithms such as MLP, decision tree (DT), support vector machine regression (SVR), and random forest algorithms (RF). Based on the comparison of prediction results, the proposed method shows excellent performance in all indicators and demonstrates the superiority of heuristic algorithms in predicting the compressive strength of concrete.

Cuproptosis-associated ncRNAs predict breast cancer subtypes.

BACKGROUND: Cuproptosis is a novel copper-dependent mode of cell death that has recently been discovered. The relationship between Cuproptosis-related ncRNAs and breast cancer subtypes, however, remains to be studied. METHODS: The aim of this study was to construct a breast cancer subtype prediction model associated with Cuproptosis. This model could be used to determine the subtype of breast cancer patients. To achieve this aim, 21 Cuproptosis-related genes were obtained from published articles and correlation analysis was performed with ncRNAs differentially expressed in breast cancer. Random forest algorithms were subsequently utilized to select important ncRNAs and build breast cancer subtype prediction models. RESULTS: A total of 94 ncRNAs significantly associated with Cuproptosis were obtained and the top five essential features were chosen to build a predictive model. These five biomarkers were differentially expressed in the five breast cancer subtypes and were closely associated with immune infiltration, RNA modification, and angiogenesis. CONCLUSION: The random forest model constructed based on Cuproptosis-related ncRNAs was able to accurately predict breast cancer subtypes, providing a new direction for the study of clinical therapeutic targets.