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The fibroblast growth factor (FGF) 15/19-FGF receptor (FGFR) 4 signaling pathway is a crucial endocrine regulatory pathway within the FGF family. The FGF15/19-FGFR4 signaling pathway plays multiple key roles in the liver, involving core physiological processes such as metabolic regulation, bile acid homeostasis maintenance, and hepatocyte proliferation and repair, and is also closely related to the pathogenesis of various liver diseases. At present, targeted therapeutic strategies for the FGF19-FGFR4 signaling axis have shown significant therapeutic potential. Agonists that simulate the physiological functions of FGF19 have been proven to effectively regulate bile acid and lipid metabolism in metabolic diseases and improve liver steatosis and fibrosis. Meanwhile, drugs that selectively inhibit FGFR4 have also demonstrated positive anti-tumor activity in specific tumor types driven by FGF19 overexpression. Given the crucial role of FGF19-FGFR4, clarifying the key mechanisms of this pathway in both physiology and pathology, as well as summarizing targeted therapy, is of vital importance. This review highlights the key role of FGF15/19-FGFR4 signaling in regulating liver physiological functions and reveals how its abnormal expression contributes to the occurrence of benign and malignant liver diseases. In addition, this review points out the potential of FGF15/19-FGFR4 signaling as a biomarker in different liver diseases and briefly discusses the existing treatment strategies for this signaling pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic respiratory disease with an unknown origin and complex pathogenic mechanisms. A deeper understanding of these mechanisms is essential for effective treatment. Pulmonary fibrosis is associated with the senescence of alveolar type II epithelial (ATⅡ) cells. Additionally, ATⅡ senescence can lead to a senescence-associated secretory phenotype, which affects cellular communication and disrupts lung tissue repair, contributing to the development of IPF. The role of mitochondrial dysfunction in senescence-related diseases is increasingly recognized. It can induce ATⅡ senescence through apoptosis, impaired autophagy, and disrupted energy metabolism, potentially playing a key role in IPF progression. This article explores the therapeutic potential of targeting cellular senescence and mitochondrial dysfunction, emphasizing their significant roles in IPF pathogenesis.

As the U.S. Navy further develops the concept of distributed maritime operations (DMOs), where individual components of the naval force will be more geographically dispersed, smaller vessels may be operating at a significant time and distance from more advanced medical capabilities. Therefore, Role 1 maritime caregivers will need to manage injured and disease non-battle injury patients for prolonged periods during current and future contested DMOs. We developed a hypothetical burn injury patient scenario to present an innovative approach to teaching complex operational medicine concepts including austere burn resuscitation, wound care, and Prolonged Casualty Care (PCC) to austere Role 1 maritime caregivers using the Joint Trauma System PCC and Tactical Combat Casualty Care clinical practice guidelines (CPGs) and other standard references. The format includes basic epidemiology of burn injury in the operational maritime environment. The scenario includes a stem clinical vignette, followed by expected clinical changes for the affected patient at specific time points (e.g., time 0, 1 hour, 2 hours, and 48 hours) with expected interventions based on the PCC CPG, appropriate guidelines, and available standard shipboard equipment. Through this process, opportunities to improve both training, clinical skills sustainment, and standard shipboard medical supplies are identified.

Survivin (BIRC5) plays a key role in inhibiting apoptosis and is highly expressed in many cancers, including gliomas and breast cancer, where it contributes to tumor progression, therapeutic resistance and poor patient outcomes. With a dual function in promoting cell proliferation and survival, coupled with its potential immunogenicity, survivin is a compelling therapeutic target for cancer; yet, it has no FDA-approved agents to date. Here, we review key findings from preclinical models that emphasize how survivin contributes to chemoresistance and radioresistance; summarize the clinical landscape of survivin-targeted strategies, highlighting both the successes and limitations of these approaches; and outline next steps to optimize survivin-targeted therapies, including the need to integrate biomarker-focused patient selection and the potential for combination therapies. These insights establish survivin as a key driver of cancer progression and a promising target for future therapeutic development.

Phytophthora is a long-established, well-known, and globally important genus of plant pathogens. Phylogenetic evidence has shown that the biologically distinct, obligate biotrophic downy mildews evolved from Phytophthora at least twice. Because, cladistically, this renders Phytophthora "paraphyletic," it has been proposed that Phytophthora evolutionary clades be split into multiple genera (Crous et al. 2021; Runge et al. 2011; Thines 2023, 2024). In this letter, we review arguments for the retention of the generic name Phytophthora with a broad circumscription made by Brasier et al. (2022) and by many delegates at an open workshop organized by The American Phytopathological Society. We present our well-considered responses to the genus splitting proposals, both in general terms and in terms of the specific proposals for new genera, alongside new information regarding the biological properties and mode of origin of the Phytophthora clades. We consider that the proposals are mostly non-rigorous and not supported by the scientific evidence. Further, given (i) the apparent lack of any distinguishing biological characteristics (synapomorphies) between the Phytophthora clades; (ii) the fundamental monophyly of Phytophthora in the original Haeckelian sense (Haeckel 1877); (iii) the fact that paraphyly is not a justification for taxonomic splitting; and (iv) the considerable likely damage to effective scientific communication and disease management from an unnecessary breakup of the genus, we report that workshop delegates voted unanimously in favor of preserving the current generic concept and for seeking endorsement of this view by a working group of the International Commission on the Taxonomy of Fungi. [Formula: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

This study explores how customer value is destroyed in Lean-managed public healthcare by applying the concepts of value destruction and value co-destruction. The study draws on a qualitative analysis of customer feedback (n = 507) collected in 2024 from general practitioner and nurse consultations and oral healthcare services, including telephone interactions related to these services, within a Finnish wellbeing services county operating under Lean management principles. The dataset was limited to responses with a Net Promoter Score of 0, accompanied by open-ended comments detailing reasons for perceived value loss. An abductive content analysis was conducted, guided by existing theories of value destruction and co-destruction. Customer value was destroyed or co-destroyed due to restricted access to care, dysfunctional service processes and inadequate service encounters. Some mechanisms reflected systemic failures that excluded customers from interaction altogether, while others emerged during deteriorated service encounters. These issues resulted in confusion, compromised self-care, emotional harm and a breakdown of trust. This study contributes to service research by operationalising the concepts of value destruction and value co-destruction using empirical data from a Lean-managed public healthcare organisation. It challenges the assumptions of public service logic, which positions value co-creation as a normative ideal, by demonstrating that co-creation may become structurally impossible when essential conditions such as service accessibility, continuity of care and professional communication are absent.

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Meldonium is a substance with known anti-anginal effects demonstrated by numerous studies and human clinical trials; however, it does not possess marketing authorization within the European Union, only in ex-Soviet republics. Since 2016, meldonium has been included by the World Anti-doping Agency (WADA) on the S4 list of metabolic modulators. In performance athletes, meldonium is now considered a doping agent due to its capacity to decrease lactate production during and after exercise, its capability to enhance the storage and utilization of glycogen, and its protective action against oxidative stress. Together, these attributes can significantly improve aerobic endurance, cardiac function, and capacity as well as shorten recovery times (allowing higher intensity training), thereby enhancing performance. The purpose of this review is to highlight the most important mechanisms underlying the protective effect of meldonium against mitochondrial dysfunction (MD), which is responsible for oxidative stress, inflammation, and the cardiac changes known as "athletic heart syndrome." Meldonium acts as an inhibitor of γ-butyrobetaine hydroxylase (BBOX), preventing the de novo synthesis of carnitine and its absorption at the intestinal level via the organic cation/carnitine transporter 2 (OCTN2) and directing the oxidation of fatty acids to the peroxisomes. The decrease in mitochondrial β-oxidation of fatty acids leads to a reduction in lipid peroxidation products that cause oxidative stress and prevent the formation of acyl/acetyl-carnitines involved in numerous pathological disorders. Given the recent findings of the potentially detrimental effects of prolonged high-intensity exercise on cardiovascular health and coronary atherosclerosis, there may be legitimate arguments for the justification of the use of substances like meldonium as protective supplements for athletes.

During distributed maritime operations, individual components of the naval force are more geographically dispersed. As the U.S. Navy further develops this concept, smaller vessels may be operating at a significant time and distance away from more advanced medical capabilities. Therefore, during both current and future contested Distributed Maritime Operations, Role 1 maritime caregivers such as Independent Duty Corpsman will have to manage patients for prolonged periods of time. This manuscript presents an innovative approach to teaching complex operational medicine concepts (including Prolonged Casualty Care [PCC]) to austere Role 1 maritime caregivers using a hypothetical scenario involving a patient with sepsis and septic shock. The scenario incorporates the Joint Trauma System PCC Clinical Practice Guidelines (CPG) and other standard references. The scenario includes a stem clinical vignette, expected clinical changes for the affected patient at specific time points (e.g., time 0, 1, 2, and 48h), and expected interventions based on the PCC CPG and available shipboard equipment. Epidemiology of sepsis in the deployed environment is also reviewed. This process also identifies opportunities to improve training, clinical skills sustainment, and standard shipboard medical supplies.

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The long-term effects of low-dose radiation exposure are a topic that has been lightly touched on in medical literature. We present a case of a 66-year-old male, who grew up near uranium mines, with several pathologies that are believed to be well explained by his chronic exposure to low-dose radiation. We postulate that screening for etiologies with known associations with radiation may help avoid long-term complications in at-risk populations.

In recent years, immunotherapy has made remarkable progress in treating certain tumors and hematological malignancies. However, the efficacy of natural killer (NK) cells, which are an important subset of innate lymphocytes used in anticancer immunotherapy, remains limited. Hypoxia, a critical characteristic of the tumor microenvironment (TME), is involved in tumor development and resistance to radiotherapy, chemotherapy, and immunotherapy. Moreover, hypoxia contributes to the impairment of NK cell function and may be a significant factor that limits their therapeutic effects. Targeted hypoxia therapy has emerged as a promising research area for enhancing the efficacy of NK cell therapy. Therefore, understanding how the hypoxic TME influences NK cell function is crucial for improving antitumor treatment outcomes.

An ideal photosensitizer for photodynamic therapy should not only possess high reactive oxygen species (ROS) generation efficiency but also maximize utilization of the in situ produced ROS species, where the latter is closely related to its intracellular location. However, rational design of such photosensitizer without tedious conjugation procedures remains a grand challenge. Here, we report the one-pot preparation of carbon dots (CDs)-based photosensitizer from levofloxacin and neutral red featuring both high 1O2 quantum yield (φΔ = 38.85%) and superior RNA selectivity. Moreover, the φΔ value shows a further 40% improvement and reaches 54.33% in response to RNA binding. Owing to these combined attributes, the CDs could exert great damage to the cellular RNA system (termed the RNA-destroyer) under extremely low dosage of light irradiation (15 mW cm-2, 1 min). It induces pyroptotic cell death and causes rapid release of different cytokines that served as molecular markers in photodynamic immunotherapy. This work represents the meticulously designed CDs with high ROS generation and utilization efficiency via good organization of the photosensitive and targeting modularity. Moreover, it is the first CDs-based pyroptosis inducer to the best of our knowledge.