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38 pages, 471 KiB  
Review
Sleep Disorders and Stroke: Pathophysiological Links, Clinical Implications, and Management Strategies
by Jamir Pitton Rissardo, Ibrahim Khalil, Mohamad Taha, Justin Chen, Reem Sayad and Ana Letícia Fornari Caprara
Med. Sci. 2025, 13(3), 113; https://doi.org/10.3390/medsci13030113 - 5 Aug 2025
Abstract
Sleep disorders and stroke are intricately linked through a complex, bidirectional relationship. Sleep disturbances such as obstructive sleep apnea (OSA), insomnia, and restless legs syndrome (RLS) not only increase the risk of stroke but also frequently emerge as consequences of cerebrovascular events. OSA, [...] Read more.
Sleep disorders and stroke are intricately linked through a complex, bidirectional relationship. Sleep disturbances such as obstructive sleep apnea (OSA), insomnia, and restless legs syndrome (RLS) not only increase the risk of stroke but also frequently emerge as consequences of cerebrovascular events. OSA, in particular, is associated with a two- to three-fold increased risk of incident stroke, primarily through mechanisms involving intermittent hypoxia, systemic inflammation, endothelial dysfunction, and autonomic dysregulation. Conversely, stroke can disrupt sleep architecture and trigger or exacerbate sleep disorders, including insomnia, hypersomnia, circadian rhythm disturbances, and breathing-related sleep disorders. These post-stroke sleep disturbances are common and significantly impair rehabilitation, cognitive recovery, and quality of life, yet they remain underdiagnosed and undertreated. Early identification and management of sleep disorders in stroke patients are essential to optimize recovery and reduce the risk of recurrence. Therapeutic strategies include lifestyle modifications, pharmacological treatments, medical devices such as continuous positive airway pressure (CPAP), and emerging alternatives for CPAP-intolerant individuals. Despite growing awareness, significant knowledge gaps persist, particularly regarding non-OSA sleep disorders and their impact on stroke outcomes. Improved diagnostic tools, broader screening protocols, and greater integration of sleep assessments into stroke care are urgently needed. This narrative review synthesizes current evidence on the interplay between sleep and stroke, emphasizing the importance of personalized, multidisciplinary approaches to diagnosis and treatment. Advancing research in this field holds promise for reducing the global burden of stroke and improving long-term outcomes through targeted sleep interventions. Full article
24 pages, 3788 KiB  
Review
Advances in Photoacoustic Imaging of Breast Cancer
by Yang Wu, Keer Huang, Guoxiong Chen and Li Lin
Sensors 2025, 25(15), 4812; https://doi.org/10.3390/s25154812 - 5 Aug 2025
Abstract
Breast cancer is the leading cause of cancer-related mortality among women world-wide, and early screening is critical for improving patient survival. Medical imaging plays a central role in breast cancer screening, diagnosis, and treatment monitoring. However, conventional imaging modalities—including mammography, ultrasound, and magnetic [...] Read more.
Breast cancer is the leading cause of cancer-related mortality among women world-wide, and early screening is critical for improving patient survival. Medical imaging plays a central role in breast cancer screening, diagnosis, and treatment monitoring. However, conventional imaging modalities—including mammography, ultrasound, and magnetic resonance imaging—face limitations such as low diagnostic specificity, relatively slow imaging speed, ionizing radiation exposure, and dependence on exogenous contrast agents. Photoacoustic imaging (PAI), a novel hybrid imaging technique that combines optical contrast with ultrasonic spatial resolution, has shown great promise in addressing these challenges. By revealing anatomical, functional, and molecular features of the breast tumor microenvironment, PAI offers high spatial resolution, rapid imaging, and minimal operator dependence. This review outlines the fundamental principles of PAI and systematically examines recent advances in its application to breast cancer screening, diagnosis, and therapeutic evaluation. Furthermore, we discuss the translational potential of PAI as an emerging breast imaging modality, complementing existing clinical techniques. Full article
(This article belongs to the Special Issue Optical Imaging for Medical Applications)
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13 pages, 7209 KiB  
Article
Evolutionary Analysis of the Land Plant-Specific TCP Interactor Containing EAR Motif Protein (TIE) Family of Transcriptional Corepressors
by Agustín Arce, Camila Schild, Delfina Maslein and Leandro Lucero
Plants 2025, 14(15), 2423; https://doi.org/10.3390/plants14152423 - 5 Aug 2025
Abstract
The plant-specific TCP transcription factor family originated before the emergence of land plants. However, the timing of the appearance of their specific transcriptional repressor family, the TCP Interactor containing EAR motif protein (TIE), remains unknown. Here, through phylogenetic analyses, we traced the origin [...] Read more.
The plant-specific TCP transcription factor family originated before the emergence of land plants. However, the timing of the appearance of their specific transcriptional repressor family, the TCP Interactor containing EAR motif protein (TIE), remains unknown. Here, through phylogenetic analyses, we traced the origin of the TIE family to the early evolution of the embryophyte, while an earlier diversification in algae cannot be ruled out. Strikingly, we found that the number of TIE members is highly constrained compared to the expansion of TCPs in angiosperms. We used co-expression data to identify potential TIE-TCP regulatory targets across Arabidopsis thaliana and rice. Notably, the expression pattern between these species is remarkably similar. TCP Class I and Class II genes formed two distinct clusters, and TIE genes cluster within the TCP Class I group. This study provides a comprehensive evolutionary analysis of the TIE family, shedding light on its conserved role in the regulation of gene transcription in flowering plant development. Full article
(This article belongs to the Special Issue Plant Molecular Phylogenetics and Evolutionary Genomics III)
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28 pages, 5831 KiB  
Article
An Italian Single-Center Genomic Surveillance Study: Two-Year Analysis of SARS-CoV-2 Spike Protein Mutations
by Riccardo Cecchetto, Emil Tonon, Asia Palmisano, Anna Lagni, Erica Diani, Virginia Lotti, Marco Mantoan, Livio Montesarchio, Francesca Palladini, Giona Turri and Davide Gibellini
Int. J. Mol. Sci. 2025, 26(15), 7558; https://doi.org/10.3390/ijms26157558 (registering DOI) - 5 Aug 2025
Abstract
The repeated occurrence of SARS-CoV-2 variants, largely driven by virus–host interactions, was and will remain a public health concern. Spike protein mutations shaped viral infectivity, transmissibility, and immune escape. From February 2022 to April 2024, a local genomic surveillance program in Verona, Italy, [...] Read more.
The repeated occurrence of SARS-CoV-2 variants, largely driven by virus–host interactions, was and will remain a public health concern. Spike protein mutations shaped viral infectivity, transmissibility, and immune escape. From February 2022 to April 2024, a local genomic surveillance program in Verona, Italy, was conducted on 1333 SARS-CoV-2-positive nasopharyngeal swabs via next generation full-length genome sequencing. Spike protein mutations were classified based on their prevalence over time. Mutations were grouped into five categories: fixed, emerging, fading, transient, and divergent. Notably, some divergent mutations displayed a “Lazarus effect,” disappearing and later reappearing in new lineages, indicating potential adaptive advantages in specific genomic contexts. This two-year surveillance study highlights the dynamic nature of spike protein mutations and their role in SARS-CoV-2 evolution. The findings underscore the need for ongoing mutation-focused genomic monitoring to detect early signals of variant emergence, especially among mutations previously considered disadvantageous. Such efforts are critical for driving public health responses and guiding future vaccine and therapeutic strategies. Full article
(This article belongs to the Special Issue The Interaction Between Cell and Virus, 3rd Edition)
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11 pages, 1311 KiB  
Case Report
Multisystemic Tuberculosis Masquerading as Aggressive Cardiac Tumor Causing Budd–Chiari Syndrome Disseminated to the Brain Resulting in Death of a Six-Year-Old Boy
by Eman S. Al-Akhali, Sultan Abdulwadoud Alshoabi, Halah Fuad Muslem, Fahad H. Alhazmi, Amirah F. Alsaedi, Kamal D. Alsultan, Amel F. Alzain, Awatif M. Omer, Maisa Elzaki and Abdullgabbar M. Hamid
Pathogens 2025, 14(8), 772; https://doi.org/10.3390/pathogens14080772 (registering DOI) - 5 Aug 2025
Abstract
Tuberculosis (TB) is an ancient and re-emerging granulomatous infectious disease that continues to challenge public health. Early diagnosis and prompt effective treatment are crucial for preventing disease progression and reducing both morbidity and mortality. These steps play a vital role in infection control [...] Read more.
Tuberculosis (TB) is an ancient and re-emerging granulomatous infectious disease that continues to challenge public health. Early diagnosis and prompt effective treatment are crucial for preventing disease progression and reducing both morbidity and mortality. These steps play a vital role in infection control and in lowering death rates at both individual and population levels. Although diagnostic methods have improved sufficiently in recent decades, TB can still present with ambiguous laboratory and imaging features. This ambiguity can lead to diagnostic pitfalls and potentially disastrous outcomes due to delayed diagnosis. In this article, we present a case of TB that was difficult to diagnose. The disease had invaded the mediastinum, right atrium, right coronary artery, and inferior vena cava (IVC), resulting in Budd–Chiari syndrome. This rare presentation created clinical, laboratory, and radiological confusion, resulting in a diagnostic dilemma that ultimately led to open cardiac surgery. The patient initially presented with progressive shortness of breath on exertion and fatigue, which suggested possible heart disease. This suspicion was reinforced by computed tomography (CT) imaging, which showed infiltrative mass lesions predominantly in the right side of the heart, invading the right coronary artery and IVC, with imaging features mimicking angiosarcoma. Although laboratory findings revealed an exudative effusion with lymphocyte predominance and elevated adenosine deaminase (ADA), the Gram stain was negative for bacteria, and an acid-fast bacilli (AFB) smear was also negative. These findings contributed to diagnostic uncertainty and delayed the confirmation of TB. Open surgery with excisional biopsy and histopathological analysis ultimately confirmed TB. We conclude that TB should not be ruled out solely based on negative Mycobacterium bacteria in pericardial effusion or AFB smear. TB can mimic aggressive tumors such as angiosarcoma or lymphoma with invasion of the surrounding tissues and blood vessels. Awareness of the clinical presentation, imaging findings, and potential diagnostic pitfalls of TB is essential, especially in endemic regions. Full article
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14 pages, 221 KiB  
Review
Metabolic Dysfunction-Associated Steatotic Liver Disease in People with Type 1 Diabetes
by Brynlee Vermillion and Yuanjie Mao
J. Clin. Med. 2025, 14(15), 5502; https://doi.org/10.3390/jcm14155502 - 5 Aug 2025
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a significant comorbidity in individuals with type 1 diabetes (T1D), despite its historical association with type 2 diabetes. This review focuses on summarizing current findings regarding the role of insulin resistance in the [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a significant comorbidity in individuals with type 1 diabetes (T1D), despite its historical association with type 2 diabetes. This review focuses on summarizing current findings regarding the role of insulin resistance in the development of MASLD in T1D, as well as examining the relationship between MASLD and diabetes-related complications. We will also briefly discuss the prevalence, diagnostic challenges, associated complications, and potential mechanisms underlying MASLD in T1D. Although insulin resistance is well established in MASLD among those with type 2 diabetes, its role in T1D requires further clarification. Emerging markers, such as the estimated glucose disposal rate, offer early insight into this relationship. MASLD in T1D is linked to both microvascular and macrovascular complications, including nephropathy, retinopathy, neuropathy, and cardiovascular disease. Variability in prevalence estimates reflects inconsistencies among imaging modalities, emphasizing the need for standardized, non-invasive diagnostic approaches. Recognizing and addressing MASLD and its links to insulin resistance and diabetes complications in T1D is vital for mitigating long-term complications and enhancing clinical outcomes. Full article
(This article belongs to the Section Endocrinology & Metabolism)
21 pages, 1359 KiB  
Article
Diagnostic Accuracy of Radiological Bone Age Methods for Assessing Skeletal Maturity in Central Precocious Puberty Girls from the Canary Islands
by Sebastián Eustaquio Martín Pérez, Isidro Miguel Martín Pérez, Ruth Molina Suárez, Jesús María Vega González and Alfonso Miguel García Hernández
Endocrines 2025, 6(3), 39; https://doi.org/10.3390/endocrines6030039 (registering DOI) - 5 Aug 2025
Abstract
Background: Central precocious puberty (CPP), defined as the onset of secondary sexual characteristics before age 8 in girls, is increasingly prevalent worldwide. CPP is often caused by early activation of the HPG axis, leading to accelerated growth and bone maturation. However, the diagnostic [...] Read more.
Background: Central precocious puberty (CPP), defined as the onset of secondary sexual characteristics before age 8 in girls, is increasingly prevalent worldwide. CPP is often caused by early activation of the HPG axis, leading to accelerated growth and bone maturation. However, the diagnostic accuracy of standard bone age (BA) methods remains uncertain in this context. Objective: To compare the diagnostic accuracy of the Greulich–Pyle atlas (GPA) and Tanner–Whitehouse 3 (TW3) methods in estimating skeletal age in girls with CPP and to assess the predictive value of serum hormone levels for estimating chronological age (CA). Methods: An observational, cross-sectional diagnostic study was conducted, involving n = 109 girls aged 6–12 years with confirmed CPP (Ethics Committee approval: CHUC_2023_86; 13 July 2023). Left posteroanterior hand–wrist (PA–HW) radiographs were assessed using the GPA and TW3 methods. Anthropometric measurements were recorded, and serum concentrations of estradiol, LH, FSH, DHEA-S, cortisol, TSH, and free T4 were obtained. Comparisons between CA and BA estimates were conducted using repeated-measures ANOVA, and ANCOVA was applied to examine the hormonal predictors of CA. Results: Both GPA and TW3 overestimated CA between 7 and 12 years, with the GPA showing larger deviations (up to 4.8 months). The TW3 method provided more accurate estimations, particularly at advanced pubertal stages. Estradiol (η2p = 0.188–0.197), LH (η2p = 0.061–0.068), and FSH (η2p = 0.008–0.023) emerged as the strongest endocrine predictors of CA, significantly enhancing the explanatory power of both radiological methods. Conclusions: The TW3 method demonstrated superior diagnostic accuracy over GPA in girls with CPP, especially between 7 and 12 years. Integrating estradiol, LH, and FSH into BA assessment significantly improved the accuracy, supporting a more individualized and physiologically grounded diagnostic approach. Full article
(This article belongs to the Section Pediatric Endocrinology and Growth Disorders)
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12 pages, 569 KiB  
Systematic Review
Intravascular Lithotripsy in the Aorta and Iliac Vessels: A Literature Review of the Past Decade
by Nicola Troisi, Giulia Bertagna, Sofia Pierozzi, Valerio Artini and Raffaella Berchiolli
J. Clin. Med. 2025, 14(15), 5493; https://doi.org/10.3390/jcm14155493 - 4 Aug 2025
Abstract
Background/Objectives: Nowadays, intravascular lithotripsy (IVL) has emerged as a novel technique for treatment of vascular calcifications, first in coronary and then in peripheral arteries. In the current literature there is little evidence that describes IVL as an effective and safe solution in [...] Read more.
Background/Objectives: Nowadays, intravascular lithotripsy (IVL) has emerged as a novel technique for treatment of vascular calcifications, first in coronary and then in peripheral arteries. In the current literature there is little evidence that describes IVL as an effective and safe solution in treating severe aortic and aorto-iliac calcifications. The aim of this study is to report current available data about the use of IVL in treating aortic and aorto-iliac calcified lesions and its application in facilitating other endovascular procedures. Methods: the present review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) Guidelines. Preliminary searches were conducted on MEDLINE and Pubmed from January 2015 to February 2025. Studies were divided into 3 main categories depending on the location of calcifications and the type of treatment: IVL in visceral and infrarenal obstructive disease (group 1), IVL in aorto-iliac obstructive disease (group 2), IVL used to facilitate other endovascular procedures. Main primary outcomes in the perioperative period were technical and clinical successes and perioperative complications. Primary outcomes at 30 days and mid-term (2 years) were overall survival, limb salvage rate, primary patency, primary assisted patency, secondary patency, and residual stenosis. Results: Sixteen studies were identified for a total of 1674 patients. Technical and clinical successes were 100%, with low rates of perioperative complications. Dissection rate reaches up to 16.1% in some studies, without any differences compared to plain old balloon angioplasty (POBA) alone (22.8%; p = 0.47). At 30 days, limb salvage and survival rates were 100%. At 2 years, primary patency, assisted primary patency, and secondary patency were 95%, 98%, and 100%, respectively, with no difference compared to IVL + stenting. Conclusions: IVL has emerged as a novel approach to treat severe calcified lesions in visceral and aorto-iliac atherosclerotic disease and to facilitate other endovascular procedures. This technique seems to offer satisfactory early and mid-term outcomes in terms of primary, primary assisted patency, and secondary patency with low complication rates. Full article
(This article belongs to the Special Issue Endovascular Surgery: State of the Art and Clinical Perspectives)
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34 pages, 1543 KiB  
Review
Treatment Strategies for Cutaneous and Oral Mucosal Side Effects of Oncological Treatment in Breast Cancer: A Comprehensive Review
by Sanja Brnić, Bruno Špiljak, Lucija Zanze, Ema Barac, Robert Likić and Liborija Lugović-Mihić
Biomedicines 2025, 13(8), 1901; https://doi.org/10.3390/biomedicines13081901 - 4 Aug 2025
Abstract
Cutaneous and oral mucosal adverse events (AEs) are among the most common non-hematologic toxicities observed during breast cancer treatment. These complications arise across various therapeutic modalities including chemotherapy, targeted therapy, hormonal therapy, radiotherapy, and immunotherapy. Although often underrecognized compared with systemic side effects, [...] Read more.
Cutaneous and oral mucosal adverse events (AEs) are among the most common non-hematologic toxicities observed during breast cancer treatment. These complications arise across various therapeutic modalities including chemotherapy, targeted therapy, hormonal therapy, radiotherapy, and immunotherapy. Although often underrecognized compared with systemic side effects, dermatologic and mucosal toxicities can severely impact the patients’ quality of life, leading to psychosocial distress, pain, and reduced treatment adherence. In severe cases, these toxicities may necessitate dose reductions, treatment delays, or discontinuation, thereby compromising oncologic outcomes. The growing use of precision medicine and novel targeted agents has broadened the spectrum of AEs, with some therapies linked to distinct dermatologic syndromes and mucosal complications such as mucositis, xerostomia, and lichenoid reactions. Early detection, accurate classification, and timely multidisciplinary management are essential for mitigating these effects. This review provides a comprehensive synthesis of current knowledge on cutaneous and oral mucosal toxicities associated with modern breast cancer therapies. Particular attention is given to clinical presentation, underlying pathophysiology, incidence, and evidence-based prevention and management strategies. We also explore emerging approaches, including nanoparticle-based delivery systems and personalized interventions, which may reduce toxicity without compromising therapeutic efficacy. By emphasizing the integration of dermatologic and mucosal care, this review aims to support clinicians in preserving treatment adherence and enhancing the overall therapeutic experience in breast cancer patients. The novelty of this review lies in its dual focus on cutaneous and oral complications across all major therapeutic classes, including recent biologic and immunotherapeutic agents, and its emphasis on multidisciplinary, patient-centered strategies. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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14 pages, 278 KiB  
Review
Novel Biomarkers for Rejection in Kidney Transplantation: A Comprehensive Review
by Michael Strader and Sam Kant
J. Clin. Med. 2025, 14(15), 5489; https://doi.org/10.3390/jcm14155489 - 4 Aug 2025
Abstract
Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. Despite significant advances in graft survival, rejection continues to pose a major clinical challenge. Conventional monitoring tools, such as serum creatinine, donor-specific antibodies, and proteinuria, lack sensitivity and specificity for [...] Read more.
Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. Despite significant advances in graft survival, rejection continues to pose a major clinical challenge. Conventional monitoring tools, such as serum creatinine, donor-specific antibodies, and proteinuria, lack sensitivity and specificity for early detection of graft injury. Moreover, while biopsy remains the current gold standard for diagnosing rejection, it is prone to confounders, invasive, and associated with procedural risks. However, non-invasive novel biomarkers have emerged as promising alternatives for earlier rejection detection and improved immunosuppression management. This review focuses on the leading candidate biomarkers currently under clinical investigation, with an emphasis on their diagnostic performance, prognostic value, and potential to support personalised immunosuppressive strategies in kidney transplantation. Full article
(This article belongs to the Special Issue Clinical Advancements in Kidney Transplantation)
17 pages, 3138 KiB  
Article
Seasonal and Interannual Variations (2019–2023) in the Zooplankton Community and Its Size Composition in Funka Bay, Southwestern Hokkaido
by Haochen Zhang, Atsushi Ooki, Tetsuya Takatsu and Atsushi Yamaguchi
Oceans 2025, 6(3), 49; https://doi.org/10.3390/oceans6030049 - 4 Aug 2025
Abstract
Funka Bay, located in southwest Hokkaido, is a vital fishing area with a shallow depth of less than 100 m. Seasonal flows of the Oyashio and Tsugaru Warm Current affect the marine environment, leading to significant changes in zooplankton communities, yet limited information [...] Read more.
Funka Bay, located in southwest Hokkaido, is a vital fishing area with a shallow depth of less than 100 m. Seasonal flows of the Oyashio and Tsugaru Warm Current affect the marine environment, leading to significant changes in zooplankton communities, yet limited information is available on these variations. This study used ZooScan imaging to analyze seasonal and interannual changes in zooplankton abundance, biovolume, community structure, and size composition from 2019 to 2023. Water temperature was low in March–April and high in September–November, with chlorophyll a peaks occurring from February to April. Notable taxa such as Thaliacea, Noctiluca, and cladocerans were more common in the latter half of the year. Interannual variations included a decline in large cold-water copepods, Eucalanus bungii and Neocalanus spp., which were abundant in 2019 but decreased by 2023. Zooplankton abundance and biovolume showed synchronized seasonal changes, correlating with shifts in the Normalized Biovolume Size Spectra (NBSS) index, which measures size composition. Cluster analysis identified eight zooplankton communities, with Community A dominant from July to December across all years, while Community D was prevalent in early 2019 but was replaced in subsequent years. Community E emerged from March to April in 2021–2023. In 2019, large cold-water copepods were dominant, but from 2020 to 2023, appendicularians became the dominant group during the March–April period. The decline in large copepods is likely linked to marine heat waves, influencing yearly zooplankton community changes. Full article
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20 pages, 4055 KiB  
Article
Biphasic Salt Effects on Lycium ruthenicum Germination and Growth Linked to Carbon Fixation and Photosynthesis Gene Expression
by Xinmeng Qiao, Ruyuan Wang, Lanying Liu, Boya Cui, Xinrui Zhao, Min Yin, Pirui Li, Xu Feng and Yu Shan
Int. J. Mol. Sci. 2025, 26(15), 7537; https://doi.org/10.3390/ijms26157537 (registering DOI) - 4 Aug 2025
Abstract
Since the onset of industrialization, the safety of arable land has become a pressing global concern, with soil salinization emerging as a critical threat to agricultural productivity and food security. To address this challenge, the cultivation of economically valuable salt-tolerant plants has been [...] Read more.
Since the onset of industrialization, the safety of arable land has become a pressing global concern, with soil salinization emerging as a critical threat to agricultural productivity and food security. To address this challenge, the cultivation of economically valuable salt-tolerant plants has been proposed as a viable strategy. In the study, we investigated the physiological and molecular responses of Lycium ruthenicum Murr. to varying NaCl concentrations. Results revealed a concentration-dependent dual effect: low NaCl levels significantly promoted seed germination, while high concentrations exerted strong inhibitory effects. To elucidate the mechanisms underlying these divergent responses, a combined analysis of metabolomics and transcriptomics was applied to identify key metabolic pathways and genes. Notably, salt stress enhanced photosynthetic efficiency through coordinated modulation of ribulose 5-phosphate and erythrose-4-phosphate levels, coupled with the upregulation of critical genes encoding RPIA (Ribose 5-phosphate isomerase A) and RuBisCO (Ribulose-1,5-bisphosphate carboxylase/oxygenase). Under low salt stress, L. ruthenicum maintained intact cellular membrane structures and minimized oxidative damage, thereby supporting germination and early growth. In contrast, high salinity severely disrupted PS I (Photosynthesis system I) functionality, blocking energy flow into this pathway while simultaneously inducing membrane lipid peroxidation and triggering pronounced cellular degradation. This ultimately suppressed seed germination rates and impaired root elongation. These findings suggested a mechanistic framework for understanding L. ruthenicum adaptation under salt stress and pointed out a new way for breeding salt-tolerant crops and understanding the mechanism. Full article
(This article belongs to the Section Molecular Biology)
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41 pages, 1115 KiB  
Review
Resveratrol as a Novel Therapeutic Approach for Diabetic Retinopathy: Molecular Mechanisms, Clinical Potential, and Future Challenges
by Snježana Kaštelan, Suzana Konjevoda, Ana Sarić, Iris Urlić, Ivana Lovrić, Samir Čanović, Tomislav Matejić and Ana Šešelja Perišin
Molecules 2025, 30(15), 3262; https://doi.org/10.3390/molecules30153262 - 4 Aug 2025
Abstract
Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut [...] Read more.
Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut microbiota dysregulation. While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities. Resveratrol (RSV), a naturally occurring polyphenol, has emerged as a promising candidate due to its potent antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties. This review provides a comprehensive analysis of the molecular mechanisms by which RSV exerts protective effects in DR, including modulation of oxidative stress pathways, suppression of inflammatory cytokines, enhancement of mitochondrial function, promotion of autophagy, and inhibition of pathological neovascularisation. Despite its promising pharmacological profile, the clinical application of RSV is limited by poor aqueous solubility, rapid systemic metabolism, and low ocular bioavailability. Various routes of administration, including intravitreal injection, topical instillation, and oral and sublingual delivery, have been investigated to enhance its therapeutic potential. Recent advances in drug delivery systems, including nanoformulations, liposomal carriers, and sustained-release intravitreal implants, offer potential strategies to address these challenges. This review also explores RSV’s role in combination therapies, its potential as a disease-modifying agent in early-stage DR, and the relevance of personalised medicine approaches guided by metabolic and genetic factors. Overall, the review highlights the therapeutic potential and the key translational challenges in positioning RSV as a multi-targeted treatment strategy for DR. Full article
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25 pages, 2418 KiB  
Review
Contactless Vital Sign Monitoring: A Review Towards Multi-Modal Multi-Task Approaches
by Ahmad Hassanpour and Bian Yang
Sensors 2025, 25(15), 4792; https://doi.org/10.3390/s25154792 - 4 Aug 2025
Abstract
Contactless vital sign monitoring has emerged as a transformative healthcare technology, enabling the assessment of vital signs without physical contact with the human body. This review comprehensively reviews the rapidly evolving landscape of this field, with particular emphasis on multi-modal sensing approaches and [...] Read more.
Contactless vital sign monitoring has emerged as a transformative healthcare technology, enabling the assessment of vital signs without physical contact with the human body. This review comprehensively reviews the rapidly evolving landscape of this field, with particular emphasis on multi-modal sensing approaches and multi-task learning paradigms. We systematically categorize and analyze existing technologies based on sensing modalities (vision-based, radar-based, thermal imaging, and ambient sensing), integration strategies, and application domains. The paper examines how artificial intelligence has revolutionized this domain, transitioning from early single-modality, single-parameter approaches to sophisticated systems that combine complementary sensing technologies and simultaneously extract multiple vital sign parameters. We discuss the theoretical foundations and practical implementations of multi-modal fusion, analyzing signal-level, feature-level, decision-level, and deep learning approaches to sensor integration. Similarly, we explore multi-task learning frameworks that leverage the inherent relationships between vital sign parameters to enhance measurement accuracy and efficiency. The review also critically addresses persisting technical challenges, clinical limitations, and ethical considerations, including environmental robustness, cross-subject variability, sensor fusion complexities, and privacy concerns. Finally, we outline promising future directions, from emerging sensing technologies and advanced fusion architectures to novel application domains and privacy-preserving methodologies. This review provides a holistic perspective on contactless vital sign monitoring, serving as a reference for researchers and practitioners in this rapidly advancing field. Full article
(This article belongs to the Section Biomedical Sensors)
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17 pages, 1812 KiB  
Article
Systemic Metabolic Alterations Induced by Etodolac in Healthy Individuals
by Rajaa Sebaa, Reem H. AlMalki, Hatouf Sukkarieh, Lina A. Dahabiyeh, Maha Al Mogren, Tawfiq Arafat, Ahmed H. Mujamammi, Essa M. Sabi and Anas M. Abdel Rahman
Pharmaceuticals 2025, 18(8), 1155; https://doi.org/10.3390/ph18081155 - 4 Aug 2025
Abstract
Background/Objective: Pharmacological interventions often exert systemic effects beyond their primary targets, underscoring the need for a comprehensive evaluation of their metabolic impact. Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) that alleviates pain, fever, and inflammation by inhibiting cyclooxygenase-2 (COX-2), thereby reducing prostaglandin synthesis. [...] Read more.
Background/Objective: Pharmacological interventions often exert systemic effects beyond their primary targets, underscoring the need for a comprehensive evaluation of their metabolic impact. Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) that alleviates pain, fever, and inflammation by inhibiting cyclooxygenase-2 (COX-2), thereby reducing prostaglandin synthesis. While its pharmacological effects are well known, the broader metabolic impact and potential mechanisms underlying improved clinical outcomes remain underexplored. Untargeted metabolomics, which profiles the metabolome without prior selection, is an emerging tool in clinical pharmacology for elucidating drug-induced metabolic changes. In this study, untargeted metabolomics was applied to investigate metabolic changes following a single oral dose of etodolac in healthy male volunteers. By analyzing serial blood samples over time, we identified endogenous metabolites whose concentrations were positively or inversely associated with the drug’s plasma levels. This approach provides a window into both therapeutic pathways and potential off-target effects, offering a promising strategy for early-stage drug evaluation and multi-target discovery using minimal human exposure. Methods: Thirty healthy participants received a 400 mg dose of Etodolac. Plasma samples were collected at five time points: pre-dose, before Cmax, at Cmax, after Cmax, and 36 h post-dose (n = 150). Samples underwent LC/MS-based untargeted metabolomics profiling and pharmacokinetic analysis. A total of 997 metabolites were significantly dysregulated between the pre-dose and Cmax time points, with 875 upregulated and 122 downregulated. Among these, 80 human endogenous metabolites were identified as being influenced by Etodolac. Results: A total of 17 metabolites exhibited time-dependent changes closely aligned with Etodolac’s pharmacokinetic profile, while 27 displayed inverse trends. Conclusions: Etodolac influences various metabolic pathways, including arachidonic acid metabolism, sphingolipid metabolism, and the biosynthesis of unsaturated fatty acids. These selective metabolic alterations complement its COX-2 inhibition and may contribute to its anti-inflammatory effects. This study provides new insights into Etodolac’s metabolic impact under healthy conditions and may inform future therapeutic strategies targeting inflammation. Full article
(This article belongs to the Special Issue Advances in Drug Analysis and Drug Development, 2nd Edition)
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