Search Results (240,733)

Immune dysregulation presents a significant clinical challenge due to its rapid progression and complex interplay between hyperinflammatory and immunosuppressive responses. Different responses from the innate and adaptive immune systems can result in diseases such as immunoparalysis, cytokine storms, and secondary infections. Current diagnostic methods remain non-specific and time-consuming, delaying targeted interventions. A compartmentalized approach to immune monitoring, distinguishing innate and acquired immune response functional differentiation, is essential for distinguishing between hyperactivation and suppression. Key biomarkers, including cytokines, Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), and CD4/CD8 counts, as well as Programmed Death Ligand-1 (PDL-1) and V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) regulators, can guide personalized treatment strategies. Although they need more clinical validation, novel therapeutic methods such as cytokine inhibitors, immunological stimulants, and immunomodulators have demonstrated promise. Early diagnosis and precision medicine developments could lead to better patient outcomes. Advances in non-coding RNAs have led to specific diagnostic panels based on microRNA (MiRNA) levels. A deeper understanding of immune imbalance in sepsis is critical for optimizing treatment and reducing mortality rates. This review highlights emerging diagnostic and therapeutic strategies to address the multifaceted nature of sepsis-related immune dysregulation. Full article

We evaluated the potential of Fourier-transform infrared (FTIR) microspectroscopy for non-invasive biochemical profiling of rhesus macaque embryonic stem cells (rhESCs) cultured in either conventional FGF2/KOSR medium or a novel formulation, ALGöX. Cells from both conditions were analyzed by immunocytochemistry, RNA sequencing, and high-resolution FTIR profiling. Molecular marker expression patterns and transcriptional profiles revealed that rhESCs maintained in FGF2/KOSR were in the primed pluripotent state, whereas those cultured in ALGöX adopted a naïve-like state. FTIR spectra showed consistent differences in protein, lipid, and nucleic acid signatures, with ALGöX-cultured cells displaying higher amide I/II and nucleic acid absorbance and FGF2/KOSR-cultured cells exhibiting stronger lipid-associated bands. Principal component analysis (PCA) separated the two groups along PC−1 (64% variance), and partial least squares discriminant analysis (PLS-DA) classified samples with 100% specificity and 100% sensitivity. These findings demonstrate that FTIR microspectroscopy can reliably discriminate pluripotent state–specific biochemical features in non-human primate PSCs, providing a rapid and label-free approach for monitoring stem cell identity and quality. Full article

A new species, Fragilaria longwania sp. nov. from Sihailongwan Maar Lake in northeastern China is described on the basis of observations made using light microscopy (LM) and scanning electron microscopy (SEM) that reveal the distinctive features that separate this new taxon from the other species currently placed in the genus Fragilaria. Fragilaria longwania sp. nov. has relatively short valve length, high stria density, spindle-shaped valves with a swollen, and sometimes deformed central area and capitate valve apices, short spines and weakly developed apical pore fields. This combination of character was found to be unique when the new species was compared with morphologically similar taxa. This species was found in various samples collected from Sihailongwan Maar Lake between 2003 and 2017. The analysis of the diatom assemblages collected in the sediment trap samples allowed an assessment of the cell size variation, seasonal occurrences and ecological requirements of this species. Fragilaria longwania appears to be a planktonic diatom most often associated with the spring season. Full article

Soft tissue sarcomas (STSs) are a rare and highly heterogeneous group of tumours originating from mesenchymal cells, characterized by significant clinical and biological diversity. Due to this complexity, STSs present considerable challenges in both diagnosis and treatment, requiring an expert, multidisciplinary, and coordinated approach. To address these challenges, a multidisciplinary team of experts from the Spanish Group for Research in Sarcomas (GEIS) has developed a comprehensive, evidence-based consensus guideline that incorporates the latest advancements in biology, imaging techniques, and treatment options. The primary objective of this guideline is to provide clear and practical, up-to-date recommendations addressing the key questions that arise in the management of STSs. This approach aims to support therapeutic decision-making, enhance overall patient management, and ultimately improve clinical outcomes for patients affected by STSs. Key recommendations include the use of MRI as the preferred imaging modality prior to biopsy and ensuring that all patients are referred to specialised sarcoma centres with a multidisciplinary team for diagnosis and treatment. Full article

Primary podocytopathies, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), are caused by a circulating factor or factors injurious to the podocyte. An immunologic origin seems likely based on responsiveness to corticosteroids or other immunosuppressive agents, including calcineurin inhibitors targeting T-cells and rituximab targeting B-cells. Potential non-antibody-mediated circulating factors have been identified, including cardiotrophin-like cytokine 1, soluble urokinase plasminogen activator receptor, and angiopoietin-like 4, among others. More recent research supports a primary antibody pathogenesis, with anti-nephrin antibodies found in a significant percentage of cases. Such antibodies also predict recurrence after transplantation. Other potential antigenic targets besides nephrin include annexin, the proteosome, podocin, and CD40. Additionally, high-resolution confocal microscopy has identified punctate immunoglobulin deposits along the slit diaphragm and podocyte cell body that may or may not colocalize with abnormal punctate nephrin staining and may correlate with detectable circulating antibodies. The success of rituximab in observational studies in both native kidneys and transplants supports a primary role for autoantibodies. We discuss in detail the data supporting putative non-antibody circulating factors, as well as the recent data supporting antibody pathogenesis, which may provide some clues on treating the individual patient. Full article

This paper introduces a power-driven systems engineering methodology for the early-phase design of highly miniaturized satellites: PlanarSats. We derive an analytical framework linking power requirements, contingency policies, solar-cell performance, and subsystem integration to determine the absolute minimum satellite size. Through idealized and detailed case studies, we explore the trade-offs inherent in subsystem selection and integration constraints. Sensitivity analysis identifies critical factors affecting minimum area and operational envelopes. Our framework provides a clear tool for balancing functionality, reliability, and physical limits in next-generation ultra-small satellite missions. Full article

This study introduces an efficient, all-aqueous emulsion-templating strategy for fabricating highly tunable yeast immobilization carriers with superior biocatalytic performance. Utilizing cellulose nanocrystals (CNCs) to stabilize dextran/polyethylene glycol (Dex/PEG) water-in-water emulsions, an architecture-controlled void is obtained by crosslinking the PEG-rich phase with variable concentrations of polyethylene glycol diacrylate (PEGDA) (10–25 wt%). This approach successfully yielded macroporous networks, enabling precise tuning of void diameters from 10.4 to 6.6 μm and interconnected pores from 2.2 to 1.4 μm. The optimally designed carrier, synthesized with 15 wt% PEGDA, featured 9.6 μm voids and robust mechanical strength (0.82 MPa), and facilitated highly efficient yeast encapsulation (~100%). The immobilized yeast demonstrated exceptional fermentation activity, remarkable storage stability (maintaining > 95% productivity after 4 weeks), and high reusability (85% activity retention after seven cycles). These enhancements are attributed to the material’s excellent water retention capacity and the provision of a stable microenvironment. This green and straightforward method represents a significant advance in industrial cell immobilization, offering unparalleled operational stability, protection, and design flexibility. Full article

Plant growth regulators Gibberellin A3 (GA₃) and N-(2-chloro-4-pyridyl)-N′-phenylurea (CPPU) are widely used in ‘Shine Muscat’ cultivation to regulate berry shape and size. However, the molecular mechanisms underlying their regulation of berry shape remain poorly understood. This study was designed to elucidate the cytological processes and molecular basis through which GA₃ and CPPU modulate berry morphology in ‘Shine Muscat’. The results showed that spraying GA₃ or CPPU alone increases the hormone levels of endogenous auxin (IAA) and GA₃ and reduces the levels of endogenous 6-benzyladenine (6-BA). GA₃ treatment resulted in the number of cells per unit area being significantly reduced and the cell transverse and longitudinal diameters being significantly increased. CPPU treatment increases the number of cells per unit area, cell transverse and longitudinal diameters. In the results of CKvsG2 and CKvsC2 transcriptome sequencing, 2793 and 1082 differentially expressed genes (DEGs) were identified, respectively. These DEGs are significantly enriched in Gene Ontology (GO) terms related to plant hormones; the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the zeatin biosynthesis pathway (ko03030) is significantly enriched. The Arabidopsis response regulator (ARR) is down-regulated in response to GA₃ application and up-regulated in response to CPPU application. Transient overexpression of VvARR (OE-VvARR) in ‘Shine Muscat’ berry increased the number of berry cells and cell transverse and longitudinal diameters. Furthermore, virus-induced gene silencing of VvARR (VIGS-VvARR) reduced the number of berry cells but increased cell transverse and longitudinal diameters. The OE-VvARR grape hormone levels of endogenous GA₃, 6-BA, and IAA were significantly increased. In VIGS-VvARR grape, the levels of endogenous IAA and 6-BA are significantly increased, but there is no significant difference in endogenous GA₃. These findings offer novel insights into the molecular mechanisms by which GA₃ and CPPU govern berry development, corroborating the hypothesis that VvARR acts as a pivotal regulator mediating the effects of these plant growth regulators on berry cell morphology and, consequently, berry shape. Full article

Dipeptidyl-peptidase IV (DPP4) inhibitors have shown potential anti-tumor properties. This study investigates the therapeutic potential of evogliptin, a DPP4 inhibitor, both as a single agent and in combination with temozolomide (TMZ), in glioma models. In vitro studies were performed using U87 and U373 glioma cell lines exposed to different concentrations of TMZ (250, 500 μM) and evogliptin (250, 500 ng/mL), either alone or together, for 24, 48, and 72 h. Cell viability was determined with the MTT assay. In vivo effectiveness was tested in a xenograft mouse model treated with intraperitoneal injections of evogliptin (60 mg/k g/day), TMZ (15 mg/kg/day), or their combination over 3 weeks. The combination of TMZ and evogliptin markedly reduced cell viability compared to single-agent treatments. DPP4 mRNA levels decreased more substantially with combination therapy. miRNA expression profiling with Affymetrix arrays indicated that certain miRNAs, such as miR-4440 and miR-6780b-5p, were upregulated after treatment with evogliptin or the combination regimen, whereas others were downregulated. These miRNAs could play a role in limiting glioma growth through DPP4 regulation. In the animal model, evogliptin alone did not provide a survival advantage. Analysis of TCGA data showed that glioma patients with decreased DPP4 expression had improved survival rates. The co-administration of evogliptin and temozolomide resulted in distinct miRNA profile changes. Nevertheless, both in vitro and in vivo, the added cytotoxicity from the combination was minimal. Full article

Glaucoma is a chronic, progressive optic neuropathy characterized by the degeneration of retinal ganglion cells. It is one of the leading causes of blindness worldwide, with elevated intraocular pressure (IOP) being the most significant modifiable risk factor. The objective of this paper is to assess the effectiveness of Direct Selective Laser Trabeculoplasty (DSLT) in the management of glaucoma and OHT based on analysis of available literature. Topical hypotensive medications are the preferred first-line therapy for both newly diagnosed open angle glaucoma (OAG) and ocular hypertension (OHT) over other treatment modalities for most patients. Medical glaucoma management, despite proven efficacy, is limited by issues of patient adherence, quality-of-life decrease, side effects, and ocular surface disease (OSD). Selective Laser Trabeculoplasty (SLT) has emerged as a safe, effective, and repeatable alternative to medical therapy for patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). Direct Selective Laser Trabeculoplasty (DSLT) is a novel, non-contact laser treatment that delivers energy transsclerally to the trabecular meshwork (TM) without the use of a gonioscope. In recent studies, DSLT has demonstrated comparable efficacy to conventional SLT, including the multicenter randomized GLAUrious trial. It reduces IOP by 18–27%, often enabling reduction in or discontinuation of hypotensive topical medications. The non-contact, automated nature of DSLT simplifies the procedure, enhances patient comfort, and may expand access to laser therapy across diverse clinical settings. In conclusion, DSLT represents an innovative advancement in laser therapy for glaucoma, combining the clinical benefits of SLT with enhanced procedural efficiency and safety. Further long-term studies are needed to validate its durability, but existing evidence supports its use as a first-line or adjunctive treatment for OAG and OHT. Full article

Background/Objectives: The high prevalence of oral squamous cell carcinoma (OSCC) has driven the development of surgical and oncologic techniques to improve survival. Despite advancements in surgical technique and chemoradiation protocols, survival rates for locally advanced OSCC remain low due to high recurrence and metastasis. This has driven the exploration of neoadjuvant treatment protocols as a potential pathway towards improving organ-preserving resection, de-escalating adjuvant treatment, and improving overall and recurrence-free survival. Methods: This is a narrative review summarizing the current literature and ongoing trials on neoadjuvant treatment for OSCC. PubMed was searched using a snowballing technique to capture all relevant clinical trials. Results: 21 clinical trials were identified. Although neoadjuvant chemotherapy was associated with favorable pathologic outcomes, clinical trials demonstrated variable survival outcomes. In contrast, neoadjuvant immunotherapy for OSCC demonstrated improved pathologic responses and survival outcomes, with a low incidence of grade 3–4 adverse events. Conclusions: Neoadjuvant therapy in OSCC shows promise but does not yet constitute standard of care. Neoadjuvant immunotherapy has encouraging response rates and lower treatment-related toxicities in comparison to neoadjuvant chemotherapy. Although recent clinical trials have presented strong evidence to support the use of neoadjuvant immunotherapy in the treatment of locally advanced OSCC, further randomized trials are required to establish standardized neoadjuvant protocols and biomarkers to assess treatment response. Full article

Therapy resistance is a major obstacle to cancer treatment, and transforming growth factor-beta (TGF-β) signaling has emerged as a major instigator across many cancer types and therapeutic regimens. Solid tumors overexpress TGF-β ligands, and canonical and non-canonical TGF-β signaling pathways drive molecular changes in most cell types within the tumor to hijack therapeutic responses. Cancer therapies further stimulate TGF-β release to potentiate this problem. Molecular mechanisms of TGF-β action supporting resistance include upregulation of drug efflux pumps, enhanced DNA Damage Repair, elaboration of stiffened extracellular matrix, and decreased neoantigen presentation. TGF-β also activates pro-survival pathways, such as epidermal growth factor receptor, B-cell lymphoma-2 expression, and AKT-mTOR signaling. TGF-β-induced epithelial-to-mesenchymal transformation leads to tumor heterogeneity and acquisition of stem-like states. In the tumor microenvironment, TGF-β induces extracellular matrix production, contractility, and secretion of immunosuppressive cytokines by cancer-associated fibroblasts that contribute to drug resistance. TGF-β also blunts cytotoxic T and NK cell activities and stimulates recruitment and differentiation of immunosuppressive cells, including T-regulatory cells, M2 macrophages, and myeloid-derived suppressor cells. The importance of TGF-β signaling in development of drug resistance cannot be understated and should be further explored mechanistically to identify novel molecular approaches and combinatorial drug dosing strategies to prevent drug-resistance. Full article

Lactate is a key metabolite with applications ranging from monitoring training efficiency to early sepsis detection and monitoring the metabolic state of cell cultures. In this study, a paper-based lactate sensor utilizing a fluorescent readout was developed. Unlike common lactate dehydrogenase (LDH)-based methods, these sensors use a green fluorescent protein (GFP) or mApple-coupled lactate binding domain, which provides a fluorescent readout upon lactate binding. We demonstrate that immobilizing these proteins on paper does not affect their ability to bind lactate and produce a fluorescent readout, by monitoring lactate levels in the cell culture supernatant applying different cell culture conditions. Full article

Mesenchymal stem cells (MSCs) are characterized by their unique therapeutic properties, which include the ability to differentiate, secrete paracrine factors, and migrate toward sites of tissue injury. Although classical molecular markers facilitate phenotypic characterization, they do not always reflect the true functional capacity of MSCs. This article introduces deformability, i.e., the capacity of cells to deform under mechanical forces, as a novel, integrative marker of MSC biological quality. It examines the relationship between cellular mechanical deformability and key therapeutic attributes, such as stemness, homing ability, and differentiation status. It overviews current measurement techniques, categorized by resolution, throughput, and clinical applicability. The potential applications of deformability in quality control and cell sorting for therapeutic purposes are also discussed. The article proposes that, in addition to molecular features, deformability may serve as a functional biomarker, potentially enhancing the effectiveness of MSC-based therapies. Full article

Lymphomas remain a significant cause of morbidity and mortality among patients living with HIV. Although the introduction of antiretroviral therapy has led to a reduction in the incidence of AIDS-related lymphomas (ARL) and an overall improvement in prognosis, these malignancies continue to pose a considerable clinical challenge. Beyond the inherent complexity of lymphoma treatment itself, the management of comorbidities, particularly infections, represents a therapeutic obstacle. Here, we review the published evidence on ARL complicated by COVID-19. Despite the fact that nearly 800 million confirmed cases of SARS-CoV-2 infection have been reported so far, only five cases of ARL and COVID-19 have been published, among whom most patients experienced a mild course of SARS-CoV-2 infection, with only one case progressing to severe COVID-19 that required oxygen therapy and prolonged hospitalization. Additionally, we present another case of a 49-year-old male patient with newly diagnosed ARL, Epstein–Barr virus (EBV)-positive, diffuse large B-cell lymphoma, not otherwise specified, complicated by prolonged SARS-CoV-2 infection. Although initially asymptomatic, the patient subsequently experienced transient respiratory failure. Despite administration of molnupiravir, both SARS-CoV-2 antigen and RT-qPCR tests remained positive for a minimum of 113 days. The prolonged SARS-CoV-2 infection, in conjunction with other opportunistic infections, impeded the delivery of adequate chemotherapy dose intensity and contributed to disease progression and ultimately the patient’s death. This case and review of the literature underscores the diversity of the clinical course of SARS-CoV-2 infection in patients with ARL and highlights the associated challenges in delivering optimal anti-lymphoma therapy in those patients. Full article