Fc Receptor-Like 1 (FCRL1), a member of the FCRL family, contains two immunoreceptor tyrosine-based activation motifs (ITAMs) in its cytoplasmic domain and plays a critical role in B-cell biology. Its expression begins in pre-B-cells, dynamically shifts during B-cell development, and contributes to the regulation of human B-cell activation. Notably, FCRL1 is overexpressed in subsets of naive and memory B-cells, as well as in malignant B-cells, including those in diffuse large B-cell lymphoma (DLBCL), an aggressive and often treatment-resistant hematological malignancy. Among FCRL family members, FCRL1 stands out as a promising immunotherapeutic target due to its selective expression in malignant B-cells and its functional role in proliferation. Given the limited efficacy of current therapies for relapsed/refractory DLBCL, targeting FCRL1 could address an unmet clinical need by offering a novel, mechanism-based approach to modulate B-cell signaling and enhance anti-tumor immunity. This mini-review highlights the therapeutic potential of FCRL1-directed strategies, supporting their further exploration in preclinical models and future clinical trials for DLBCL and other B-cell malignancies.

Stem cell fate decisions are increasingly understood through the dynamic interplay of two fundamental stress-adaptive programs: the integrated stress response (ISR) and the senescence-associated secretory phenotype (SASP). These pathways act as a Yin-Yang system, balancing beneficial and detrimental outcomes across development, tissue homeostasis, and disease. On the yin (protective) side, transient ISR activation and acute SASP signaling foster adaptation, embryonic patterning, wound healing, and regeneration. On the yang (maladaptive) side, chronic ISR signaling and unresolved SASP output drive stem cell exhaustion, fibrosis, inflammation, and tumorigenesis. This duality highlights their roles as both guardians and disruptors of stem cell integrity. Mechanistically, ISR regulates translational control via eukaryotic initiation factor 2 alpha (eIF2α) phosphorylation and activating transcription factor 4 (ATF4)-dependent transcription, while SASP reprograms the extracellular milieu through cytokines, growth factors, and proteases. Their crosstalk creates feedback loops that shape tissue niches and long-term stem cell potential. Framing ISR-SASP interactions through a Yin-Yang lens underscores the balance between resilience and decline, to offer new insights into regenerative medicine, anti-aging interventions, and cancer therapeutics.

Neutrophil extracellular traps (NET) have emerged as critical players in the pathogenesis of atherosclerosis and other cardiovascular diseases (CVD). These web-like structures, composed of DNA, histones, and granule proteins released by neutrophils, contribute significantly to both inflammation and thrombosis. This manuscript offers a comprehensive review of the recent literature on the involvement of NET in atherosclerosis, highlighting their interactions with various pathophysiological processes and their potential as biomarkers for CVD. Notably, the impact of radiation on NET formation is explored, emphasising how oxidative stress and inflammatory responses drive NET release, contributing to plaque instability. The role of histones, particularly citrullinated histones, in endothelial dysfunction and plaque progression is discussed, highlighting their significance in the pathophysiology of atherosclerosis. Furthermore, the complex relationship between lipoproteins and NET formation is examined, with a focus on how elevated low-density lipoprotein (LDL) and decreased high-density lipoprotein (HDL) levels facilitate NET release, thus promoting vascular inflammation and plaque instability. The influence of cholesterol on NET formation is also explored, underscoring its contribution to plaque development and stability. The role of Peptidylarginine deiminase 4 (PAD4) in the regulation of NETosis is reviewed, with attention given to how PAD4-driven citrullination of histones affects atherosclerosis progression. Moreover, the manuscript examines the potential of NET components-such as double-stranded DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3-as biomarkers for assessing disease severity and predicting adverse cardiovascular events, including ST-elevation myocardial infarction (STEMI) and stroke. Elevated levels of these biomarkers correlate with worse clinical outcomes, suggesting their utility in guiding therapeutic interventions. In contrast to the existing body of work, this review highlights the novelty of integrating recent findings on NET interactions with lipid metabolism, histone modifications, and PAD4 activity in the context of atherosclerosis. Overall, NET plays an integral role in the inflammatory and thrombotic processes underpinning atherosclerosis, and their components hold promise as both diagnostic markers and therapeutic targets in cardiovascular disease management.

Eosinophils are multifunctional granulocytes that contribute to the initiation and modulation of inflammation. Accumulating evidence suggests that eosinophils are adaptable leukocytes that orchestrate the resolution of inflammatory responses. The most prevalent chronic inflammatory illness, rheumatoid arthritis (RA), is typified by persistent synovitis that makes it hard for the disease to go away on its own. Interestingly, a unique subset of eosinophils known as regulatory eosinophils has been found in RA patients' synovium, especially while the disease is in remission. Pro-resolving signatures of regulatory eosinophils in the synovium are distinct from those of their lung counterparts. The most recent research on eosinophils and their function in this disease pathogenesis is compiled in this review. Based on the role of regulatory eosinophils, a new pathological model of inflammation resolution in RA is proposed, and potential therapeutic strategies aimed at enhancing the action of regulatory eosinophils in RA are proposed.

Integrins are heterodimeric transmembrane receptors that mediate bidirectional interactions between the intracellular cytoskeletal array and the extracellular matrix. These interactions are critical in tissue development and function by regulating gene expression and sustaining tissue architecture. In humans, the integrin family is composed of 18 alpha (α) and 8 beta (β) subunits, constituting 24 distinct αβ combinations. Based on their structure and ligand-binding properties, only a subset of integrins, 8 out of 24, recognizes the arginine-glycine-aspartate (RGD) tripeptide motif in the native ligand. One of the major RGD binding integrins is integrin alpha 8 beta 1 (α8β1), a central Ras homolog gene family member A (RHOA)-dependent modulator highly expressed in cells with contractile function. This review focuses on the recent advances regarding α8β1 function during organ development, with a particular interest in kidney and inner ear development. We also discuss α8β1's role in injury and disease and its importance for mesenchymal to epithelial transition during cancer development. Finally, we highlight α8β1's importance for hearing function and its future use as a potential diagnostic and therapeutic tool for disease elimination.

Osteoarthritis (OA), the most common form of joint disease, is characterized clinically by joint pain, stiffness, and deformity. OA is now considered a whole joint disease; however, the breakdown of the articular cartilage remains the major hallmark of the disease. Current treatments targeting OA symptoms have a limited impact on impeding or reversing the OA progression. Understanding the molecular and cellular mechanisms underlying OA development is a critical barrier to progress in OA therapy. Recent studies by the current authors' group and others have revealed that the nuclear factor of activated T cell 1 (NFAT1), a member of the NFAT family of transcription factors, regulates the expression of many anabolic and catabolic genes in articular chondrocytes of adult mice. Mice lacking NFAT1 exhibit normal skeletal development but display OA in both appendicular and spinal facet joints as adults. This review mainly focuses on the recent advances in the regulatory role of NFAT1 transcription factor in the activities of articular chondrocytes and its implication in the pathogenesis of OA.

Age and diabetes have long been known to induce an oxidative reaction between glucose and collagen, leading to the accumulation of advanced glycation end-products (AGEs) cross-links in collagenous tissues. More recently, AGEs content has been related to loss of bone quality, independent of bone mass, and increased fracture risk with aging and diabetes. Loss of bone quality is mostly attributed to changes in material properties, structural organization, or cellular remodeling. Though all these factors play a role in bone fragility disease, some common recurring patterns can be found between diabetic and age-related bone fragility. The main pattern we will discuss in this viewpoint is the increase of fibrillar collagen stiffness and loss of collagen-induced plasticity with AGE accumulation. This study focused on recent related experimental studies and discusses the correlation between fluorescent AGEs content at the molecular and fibrillar scales, collagen deformation mechanisms at the nanoscale, and resistance to bone fracture at the macroscale.

Protein-mediated interactions are the fundamental mechanism through which cells regulate health and disease. These interactions require physical contact between proteins and their respective targets of interest. These targets include not only other proteins but also nucleic acids and other important molecules as well. These proteins are often involved in multibody complexes that work dynamically to regulate cellular health and function. Various techniques have been adapted to study these important interactions, such as affinity-based assays, mass spectrometry, and fluorescent detection. The application of these techniques has led to a greater understanding of how protein interactions are responsible for both the instigation and resolution of acute inflammatory diseases. These pursuits aim to provide opportunities to target specific protein interactions to alleviate acute inflammation.

Since 2019, the coronavirus disease-19 (COVID-19) has been spreading rapidly worldwide, posing an unignorable threat to the global economy and human health. It is a disease caused by severe acute respiratory syndrome coronavirus 2, a single-stranded RNA virus of the genus Betacoronavirus. This virus is highly infectious and relies on its angiotensin-converting enzyme 2-receptor to enter cells. With the increase in the number of confirmed COVID-19 diagnoses, the difficulty of diagnosis due to the lack of global healthcare resources becomes increasingly apparent. Deep learning-based computer-aided diagnosis models with high generalisability can effectively alleviate this pressure. Hyperparameter tuning is essential in training such models and significantly impacts their final performance and training speed. However, traditional hyperparameter tuning methods are usually time-consuming and unstable. To solve this issue, we introduce Particle Swarm Optimisation to build a PSO-guided Self-Tuning Convolution Neural Network (PSTCNN), allowing the model to tune hyperparameters automatically. Therefore, the proposed approach can reduce human involvement. Also, the optimisation algorithm can select the combination of hyperparameters in a targeted manner, thus stably achieving a solution closer to the global optimum. Experimentally, the PSTCNN can obtain quite excellent results, with a sensitivity of 93.65%±1.86%, a specificity of 94.32%±2.07%, a precision of 94.30%±2.04%, an accuracy of 93.99%±1.78%, an F1-score of 93.97%±1.78%, Matthews Correlation Coefficient of 87.99%±3.56%, and Fowlkes-Mallows Index of 93.97%±1.78%. Our experiments demonstrate that compared to traditional methods, hyperparameter tuning of the model using an optimisation algorithm is faster and more effective.

Osteosarcoma is one of the most genomically complex cancers and as result, it has been difficult to assign genomic aberrations that contribute to disease progression and patient outcome consistently across samples. One potential source for correlating osteosarcoma and genomic biomarkers is within the non-coding regions of RNA that are differentially expressed. However, it is unsurprising that a cancer classification that is fraught with genomic instability is likely to have numerous studies correlating non-coding RNA expression and function have been published on the subject. This review undertakes the formidable task of evaluating the published literature of noncoding RNAs in osteosarcoma. This is not the first review on this topic and will certainly not be the last. The review is organized with an introduction into osteosarcoma and the epigenetic control of gene expression before reviewing the molecular function and expression of long non-coding RNAs, circular RNAs, and short non-coding RNAs such as microRNAs, piwi RNAs, and short-interfering RNAs. The review concludes with a review of the literature and how the biology of non-coding RNAs can be used therapeutically to treat cancers, especially osteosarcoma. We conclude that non-coding RNA expression and function in osteosarcoma is equally complex to understanding the expression differences and function of coding RNA and proteins; however, with the added lens of both coding and non-coding genomic sequence, researchers can begin to identify the patterns that consistently associate with aggressive osteosarcoma.

Hepatic stellate cells (HSCs) are the primary effector cells in liver fibrosis. In the normal liver, HSCs serve as the primary vitamin A storage cells in the body and retain a "quiescent" phenotype. However, after liver injury, they transdifferentiate to an "activated" myofibroblast-like phenotype, which is associated with dramatic upregulation of smooth muscle specific actin and extracellular matrix proteins. The result is a fibrotic, stiff, and dysfunctional liver. Therefore, understanding the molecular mechanisms that govern HSC function is essential for the development of anti-fibrotic medications. The actin cytoskeleton has emerged as a key component of the fibrogenic response in wound healing. Recent data indicate that the cytoskeleton receives signals from the cellular microenvironment and translates them to cellular function-in particular, increased type I collagen expression. Dynamic in nature, the actin cytoskeleton continuously polymerizes and depolymerizes in response to changes in the cellular microenvironment. In this viewpoint, we discuss the recent developments underlying cytoskeletal actin dynamics in liver fibrosis, including how the cellular microenvironment affects HSC function and the molecular mechanisms that regulate the actin-induced increase in collagen expression typical of activated HSCs.

The knowledge of interactions among functional proteins helps researchers understand disease mechanisms and design potential strategies for treatment. As a general approach, the fluorescent and affinity tags were employed for exploring this field by labeling the Protein of Interest (POI). However, the autofluorescence and weak binding strength significantly reduce the accuracy and specificity of these tags. Conversely, HaloTag, a novel self-labeling enzyme (SLE) tag, could quickly form a covalent bond with its ligand, enabling fast and specific labeling of POI. These desirable features greatly increase the accuracy and specificity, making the HaloTag a valuable system for various applications ranging from imaging to immobilization of POI. Notably, the HaloTag technique has already been successfully employed in a series of studies with excellent efficiency. In this review, we summarize the development of HaloTag and recent advanced investigations associated with HaloTag, including in vitro imaging (e.g., POI imaging, cellular condition monitoring, microorganism imaging, system development), in vivo imaging, biomolecule immobilization (e.g., POI collection, protein/nuclear acid interaction and protein structure analysis), targeted degradation (e.g., L-AdPROM), and more. We also present a systematic discussion regarding the future direction and challenges of the HaloTag technique.