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30 pages, 5976 KiB  
Review
Electrochemical Sensors for Chloramphenicol: Advances in Food Safety and Environmental Monitoring
by Matiar M. R. Howlader, Wei-Ting Ting and Md Younus Ali
Pharmaceuticals 2025, 18(9), 1257; https://doi.org/10.3390/ph18091257 (registering DOI) - 24 Aug 2025
Abstract
Excessive use of antibiotics can lead to antibiotic resistance, posing a significant threat to human health and the environment. Chloramphenicol (CAP), once widely used, has been banned in many regions for over 20 years due to its toxicity. Detecting CAP residues in food [...] Read more.
Excessive use of antibiotics can lead to antibiotic resistance, posing a significant threat to human health and the environment. Chloramphenicol (CAP), once widely used, has been banned in many regions for over 20 years due to its toxicity. Detecting CAP residues in food products is crucial for regulating safe use and preventing unnecessary antibiotic exposure. Electrochemical sensors are low-cost, sensitive, and easily detect CAP. This paper reviews recent research on electrochemical sensors for CAP detection, with a focus on the materials and fabrication techniques employed. The sensors are evaluated based on key performance parameters, including limit of detection, sensitivity, linear range, selectivity, and the ability to perform simultaneous detection. Specifically, we highlight the use of metal and carbon-based electrode modifications, including gold nanoparticles (AuNPs), nickel–cobalt (Ni-Co) hollow nano boxes, platinum–palladium (Pt-Pd), graphene (Gr), and covalent organic frameworks (COFs), as well as molecularly imprinted polymers (MIPs) such as polyaniline (PANI) and poly(o-phenylenediamine) (P(o-PD)). The mechanisms by which these modifications enhance CAP detection are discussed, including improved conductivity, increased surface-to-volume ratio, and enhanced binding site availability. The reviewed sensors demonstrated promising results, with some exhibiting high selectivity and sensitivity, and the effective detection of CAP in complex sample matrices. This review aims to support the development of next-generation sensors for antibiotic monitoring and contribute to global efforts to combat antibiotic resistance. Full article
(This article belongs to the Special Issue Application of Biosensors in Pharmaceutical Research)
27 pages, 2880 KiB  
Article
The Role of miRNAs in the Differential Diagnosis of Alzheimer’s Disease and Major Depression: A Bioinformatics-Based Approach
by Gözde Öztan, Halim İşsever and Tuğçe İşsever
Int. J. Mol. Sci. 2025, 26(17), 8218; https://doi.org/10.3390/ijms26178218 (registering DOI) - 24 Aug 2025
Abstract
Alzheimer’s disease (AD) and major depressive disorder (MDD) are prevalent central nervous system (CNS) disorders that share overlapping symptoms but differ in underlying molecular mechanisms. Distinguishing these mechanisms is essential for developing targeted diagnostic and therapeutic strategies. In this study, we integrated multi-tissue [...] Read more.
Alzheimer’s disease (AD) and major depressive disorder (MDD) are prevalent central nervous system (CNS) disorders that share overlapping symptoms but differ in underlying molecular mechanisms. Distinguishing these mechanisms is essential for developing targeted diagnostic and therapeutic strategies. In this study, we integrated multi-tissue transcriptomic datasets from brain and peripheral samples to identify differentially expressed microRNAs (miRNAs) in AD and MDD. Functional enrichment analyses (KEGG, GO) revealed that dysregulated miRNAs in AD were associated with MAPK, PI3K–Akt, Ras, and PD-1/PD-L1 signaling, pathways linked to synaptic plasticity, neuroinflammation, and immune regulation. In contrast, MDD-associated miRNAs showed enrichment in Hippo signaling and ubiquitin-mediated proteolysis, implicating altered neurogenesis and protein homeostasis. Network analysis highlighted key disease- and tissue-specific miRNAs, notably hsa-miR-1202 and hsa-miR-24-3p, with potential roles in neuronal survival and molecular network regulation. These findings suggest that miRNAs may serve as non-invasive biomarkers for diagnosis, prognosis, and treatment monitoring in both disorders. While therapeutic targeting of miRNAs offers promise, challenges such as blood–brain barrier penetration and tissue-specific delivery remain. This integrative approach provides a translational framework for advancing miRNA-based strategies in CNS disease research. Full article
(This article belongs to the Special Issue Molecular Insights in Neurodegeneration)
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21 pages, 6545 KiB  
Article
Profiling of Breast Cancer Stem Cell Types/States Shows the Role of CD44hi/CD24lo-ALDH1hi as an Independent Prognostic Factor After Neoadjuvant Chemotherapy
by Hazem Ghebeh, Jumanah Y. Mirza, Taher Al-Tweigeri, Monther Al-Alwan and Asma Tulbah
Int. J. Mol. Sci. 2025, 26(17), 8219; https://doi.org/10.3390/ijms26178219 (registering DOI) - 24 Aug 2025
Abstract
Multiple markers exist for breast cancer stem cells (CSCs), which are believed to represent the phenotypes of various CSC types and/or states. The relationship between each CSC subpopulation/state and the primary hallmarks of cancer has not been sufficiently clarified. In this study, six [...] Read more.
Multiple markers exist for breast cancer stem cells (CSCs), which are believed to represent the phenotypes of various CSC types and/or states. The relationship between each CSC subpopulation/state and the primary hallmarks of cancer has not been sufficiently clarified. In this study, six CSC markers (CD44hi/CD24lo, CD24, Ep-CAM, ALDH1, CD10, and BMI1) were assessed in a surgical cohort of 73 breast cancer patients. The expression of a single or multiple CSC markers was correlated with clinicopathological parameters, including markers of immune evasion, proliferation, epithelial–mesenchymal transition (EMT), and survival. All CSC phenotypes, except for CD10, correlated with markers indicative of higher proliferation. The CD44hi/CD24lo phenotype correlated with markers of EMT and PD-L1 expression, unlike ALDH1hi. Both Ep-CAMhi and CD24hi breast cancer were associated with indicators of immune evasion, including PD-L1 expression, and the infiltration of FOXP3+ and PD-1+ tumor-infiltrating lymphocytes (TIL). While the CD44hi/CD24lo, Ep-CAMhi, and ALDH1hi phenotypes correlated with shorter overall survival (OS), CD24hi correlated with reduced disease-free survival (DFS). Interestingly, among all tested CSC markers, the CD44hi/CD24lo-ALDH1hi combination phenotype correlated with the worst DFS (HR 2.8, p = 0.014 in univariate/multivariate analysis) and OS (p < 0.001, HR 6.4 in univariate and 5.4 in multivariate analysis). A side-by-side comparison of multiple CSC markers demonstrated the differential linkage of CSC phenotype/state with distinct features of breast cancer. This comparison demonstrates the advantage of the CD44hi/CD24lo-ALDH1hi combination marker for prognostication, especially after neoadjuvant chemotherapy. In the future, distinct markers of CSCs can hopefully be leveraged to trace/monitor different disease characteristics or treatment outcomes. Full article
(This article belongs to the Section Molecular Oncology)
21 pages, 2464 KiB  
Article
Neuroprotective Effects of Calpain Inhibition in Parkinson’s Disease: Insights from Cellular and Murine Models
by Vandana Zaman, Amy Gathings, Kelsey P. Drasites, Donald C. Shields, Narendra L. Banik and Azizul Haque
Cells 2025, 14(17), 1310; https://doi.org/10.3390/cells14171310 (registering DOI) - 24 Aug 2025
Abstract
Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, and key pathways such as neuroinflammation, oxidative stress, and autophagy are believed to significantly contribute to the mechanisms of neurodegeneration. Calpain activation plays a critical role in [...] Read more.
Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, and key pathways such as neuroinflammation, oxidative stress, and autophagy are believed to significantly contribute to the mechanisms of neurodegeneration. Calpain activation plays a critical role in neuroinflammation and neurodegeneration, as demonstrated by its impact on microglial activation, reactive oxygen species (ROS) production, and neuronal survival. In this study, we investigated the effects of calpain inhibition using calpeptin (CP) and calpain-2-specific inhibitors in cellular and murine models of neuroinflammation and PD. In BV2 microglial cells, LPS-induced production of pro-inflammatory cytokines (TNF-α, IL-6) and chemokines (MCP-1, IP-10) were significantly reduced by CP treatment with a concomitant decrease in ROS generation. Similarly, in VSC-4.1 motoneuron cells, calpain inhibition attenuated IFN-γ-induced ROS production and improved cell viability, demonstrating its neuroprotective effects. Moreover, in a murine MPTP model of PD, calpain inhibition reduced astrogliosis, ROCK2 expression, and levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-7, and IL12p70) and chemokines (MCP-1 and IP-10) in the dorsal striatum and plasma. The specific role of calpain-2 in immune modulation was further highlighted in human microglia, SV-40 cells. With respect to immune modulation in these cells, siRNA-mediated knockdown of calpain-2, but not calpain-1, significantly reduced antigen presentation to CD4+ T cells. Thus, calpain-2 is likely involved in regulating antigen presentation and activation of inflammatory CD4+ T cells. These findings underscore the therapeutic potential of calpain-2 inhibition in mitigating neuroinflammation and neurodegeneration, particularly in PD, by targeting microglial activation, ROS production, and neuronal survival pathways. Full article
(This article belongs to the Special Issue Role of Calpains in Health and Diseases)
10 pages, 222 KiB  
Article
Acute Peritoneal Dialysis in Critical Preterm Infants: A Case Series and Review of the Literature
by Francesca Riitano, Serena Ferretti, Simonetta Costa, Eloisa Tiberi, Antonio Gatto and Giovanni Vento
Children 2025, 12(9), 1113; https://doi.org/10.3390/children12091113 (registering DOI) - 24 Aug 2025
Abstract
Background: Acute kidney injury (AKI) in critically ill neonates is usually of pre-renal origin and, often, pharmacological treatment is not sufficient for resolution, requiring kidney replacement therapy (KRT). Due to the small body size and the unavailability of adequate devices for these [...] Read more.
Background: Acute kidney injury (AKI) in critically ill neonates is usually of pre-renal origin and, often, pharmacological treatment is not sufficient for resolution, requiring kidney replacement therapy (KRT). Due to the small body size and the unavailability of adequate devices for these patients, peritoneal dialysis (PD) appears to be the most easily achievable procedure. However, guidelines for PD management are lacking in this population. Objective: We aimed to report a single-center experience with preterm infants who underwent PD, describing the technical issues and the outcomes, and to review the existing literature. Methods: This retrospective study included preterm infants undergoing PD because of AKI unresponsive to pharmacological treatment. Data were compared to those available in the current literature. Results: Neonatal outcomes of twelve preterm infants were reported. PD was started before the onset of anuria in two oliguric patients, while it was started within 60 h of anuria in four patients, and between 72 and 144 h of anuria in the remaining six patients. One oliguric patient and one who started PD after 60 h of anuria had a complete recovery of kidney function with normalization of diuresis and renal function parameters. The other infants did not achieve complete resolution of AKI. The mortality rate was 91.7%, and even one of the two infants who had recovered kidney function later died due to an infectious complication. Conclusions: Our experience with a limited sample size did not allow us to obtain definitive conclusions. Our data and the current literature suggested that the prognosis is still negative, with a high mortality rate. Further research is needed to develop guidelines to optimize the management of preterm infants with AKI. Full article
(This article belongs to the Special Issue Providing Care for Preterm Infants)
20 pages, 5563 KiB  
Article
Differential Absorbance and PPG-Based Non-Invasive Blood Glucose Measurement Using Spatiotemporal Multimodal Fused LSTM Model
by Jinxiu Cheng, Pengfei Xie, Huimeng Zhao and Zhong Ji
Sensors 2025, 25(17), 5260; https://doi.org/10.3390/s25175260 (registering DOI) - 24 Aug 2025
Abstract
Blood glucose monitoring is crucial for the daily management of diabetic patients. In this study, we developed a differential absorbance and photoplethysmography (PPG)-based non-invasive blood glucose measurement system (NIBGMS) using visible–near-infrared (Vis-NIR) light. Three light-emitting diodes (LEDs) (625 nm, 850 nm, and 940 [...] Read more.
Blood glucose monitoring is crucial for the daily management of diabetic patients. In this study, we developed a differential absorbance and photoplethysmography (PPG)-based non-invasive blood glucose measurement system (NIBGMS) using visible–near-infrared (Vis-NIR) light. Three light-emitting diodes (LEDs) (625 nm, 850 nm, and 940 nm) and three photodetectors (PDs) with different source–detector separation distances were used to detect the differential absorbance of tissues at different depths and PPG signals of the index finger. A spatiotemporal multimodal fused long short-term memory (STMF-LSTM) model was developed to improve the prediction accuracy of blood glucose levels by multimodal fusion of optical spatial information (differential absorbance and PPG signals) and glucose temporal information. The validity of the NIBGMS was preliminarily verified using multilayer perceptron (MLP), support vector regression (SVR), random forest regression (RFR), and extreme gradient boosting (XG Boost) models on datasets collected from 15 non-diabetic subjects and 3 type-2 diabetic subjects, with a total of 805 samples. Additionally, a continuous dataset consisting 272 samples from four non-diabetic subjects was used to validate the developed STMF-LSTM model. The results demonstrate that the STMF-LSTM model indicated improved prediction performance with a root mean square error (RMSE) of 0.811 mmol/L and a percentage of 100% for Parkes error grid analysis (EGA) Zone A and B in 8-fold cross validation. Therefore, the developed NIBGMS and STMF-LSTM model show potential in practical non-invasive blood glucose monitoring. Full article
(This article belongs to the Section Biomedical Sensors)
15 pages, 7210 KiB  
Article
Diagnosis-Related Outcome Following Palliative Spatially Fractionated Radiation Therapy (Lattice) of Large Tumors
by Gabriela Studer, Tino Streller, David Jeller, Dirk Huebner, Bruno Fuchs and Christoph Glanzmann
Cancers 2025, 17(17), 2752; https://doi.org/10.3390/cancers17172752 (registering DOI) - 23 Aug 2025
Abstract
Background: Lattice Radiotherapy (LRT), a spatially fractionated stereotactic radiotherapy (SBRT) technique, has shown promising results in the palliative treatment of large tumors. The focus of our first analysis of 56 lesions >/=7cm was on the extent of shrinkage following palliative LRT (mean 50%) [...] Read more.
Background: Lattice Radiotherapy (LRT), a spatially fractionated stereotactic radiotherapy (SBRT) technique, has shown promising results in the palliative treatment of large tumors. The focus of our first analysis of 56 lesions >/=7cm was on the extent of shrinkage following palliative LRT (mean 50%) and assessment of its effect duration (: mean 6 months). Herewith we present an updated analysis of our single-center LRT cohort, with a focus on LRT outcome across diagnoses and applied LRT regimens. Methods: We assessed the clinical outcome following LRT in 66 patients treated for 81 lesions between 01.2022 and 05.2025. LRT protocols included simultaneous integrated boost (sib-) LRT in 49 lesions (5 × 4–5 Gy to the entire mass with sib of 9–13 Gy to lattice vertices). Alternatively mainly in pre-irradiated and/or very large lesions—a single-fraction stereotactic LRT (SBRT-LRT) of 1 × 20 Gy to vertices only was delivered to 26 lesions. In six cases with modest response to single fraction SBRT-LRT, the sib-LRT schedule was added 4–8 weeks later. Results: The median age was 68 years (18–93). Main tumor locations were abdomino-pelvic (n = 34) and thoracic (n = 17). Histopathological diagnoses included carcinoma (n = 34), sarcoma (n = 31), and melanoma (n = 16). 31% of all lesions have been previously irradiated. 73% of cases underwent concurrent or peri-LRT systemic therapy. The mean/median overall survival (OS) time of the cohort was 7.6/4.6 months (0.4–40.2), 11.9/5.8 months in 16/66 alive, and 6.4/4.3 months in deceased patients, respectively. 82% of symptomatic patients reported immediate subjective improvement (PROM), with a lifelong response duration in most cases. Progressive disease (PD: >10% increase in initial volume) was found in 9%, stable disease (SD +/−10% of initial volume) in 19% of scanned lesions, and shrinkage (>10% reduction in initial volume) in 75%, with a mean/median tumor volume reduction of 51/60%. The extent of shrinkage was found to be 11–30%/31–60%/61–100% in 38/24/38% of lesions. Response rates (PD, SD, shrinkage) following the two applied LRT regimens, as well as those related to sarcoma and carcinoma diagnoses, were found to be comparable. Treatment tolerance was excellent (G0-1). Conclusions: Palliative LRT provides rapid subjective relief in ~80% of symptomatic patients. Radiologic shrinkage was stated in 75% of FU-scanned lesions, with a lifelong effect duration in most patients. LRT was found effective across histologies, with a similar extent of shrinkage in carcinoma and sarcoma following 1F SBRT- and 5F sib-LRT regimens, respectively. Full article
(This article belongs to the Special Issue Palliative Radiotherapy for Cancer)
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14 pages, 877 KiB  
Systematic Review
Pleurectomy/Decortication Versus Extrapleural Pneumonectomy in Pleural Mesothelioma: A Systematic Review and Meta-Analysis of Survival, Mortality, and Surgical Trends
by Margherita Brivio, Matteo Chiari, Claudia Bardoni, Antonio Mazzella, Monica Casiraghi, Lorenzo Spaggiari and Luca Bertolaccini
J. Clin. Med. 2025, 14(17), 5964; https://doi.org/10.3390/jcm14175964 (registering DOI) - 23 Aug 2025
Abstract
Background: The optimal surgical approach for malignant pleural mesothelioma (PM) remains a topic of debate. While extrapleural pneumonectomy (EPP) offers radical resection, it is associated with significant morbidity. Pleurectomy/decortication (P/D) is less extensive but may offer comparable oncologic outcomes with reduced perioperative risk. [...] Read more.
Background: The optimal surgical approach for malignant pleural mesothelioma (PM) remains a topic of debate. While extrapleural pneumonectomy (EPP) offers radical resection, it is associated with significant morbidity. Pleurectomy/decortication (P/D) is less extensive but may offer comparable oncologic outcomes with reduced perioperative risk. This study aimed to conduct a comprehensive systematic review and meta-analysis to systematically evaluate and quantitatively compare survival outcomes, 30-day postoperative mortality, and baseline characteristics between patients undergoing P/D and EPP for PM. Methods: A systematic review was conducted in accordance with the PRISMA guidelines. MEDLINE, Embase, and Scopus were searched up to May 2025. Studies comparing EPP and P/D in PM that reported on survival, mortality, or baseline demographics were included. Data from 24 retrospective studies were extracted. Pooled estimates were calculated using random-effects models. Meta-regression and subgroup analyses were performed by geographic region and publication year. Results: P/D was associated with a significantly improved overall survival compared to EPP in the primary analysis (mean difference = 7.01 months; 95% CI: 1.15–12.86; p = 0.018), with substantial heterogeneity (I2 = 98.5%). In a sensitivity analysis excluding one statistical outlier, the survival benefit remained significant (mean difference = 4.31 months; 95% CI: 1.69–6.93), and heterogeneity was markedly reduced. The 30-day mortality rate was also significantly lower for P/D (odds ratio = 0.34; 95% CI: 0.13–0.88; p = 0.027). Patients undergoing P/D were, on average, 3.78 years older than those undergoing EPP (p < 0.001), whereas no significant difference was observed in the sex distribution between groups. Subgroup analyses by region and publication year confirmed the robustness of the findings. Meta-regression did not reveal substantial modifiers of survival. Conclusions: P/D demonstrates superior overall survival and reduced perioperative mortality compared to EPP, without evidence of baseline demographic confounding. These findings, derived from retrospective comparative studies, support the preferential use of P/D in eligible patients, particularly in high-volume centers, given its favorable safety profile and superior median survival. However, the absence of randomized trials directly comparing P/D and EPP and the potential influence of patient selection warrant cautious interpretation, and surgical decisions should be tailored to individual patient factors within a multidisciplinary setting. Full article
(This article belongs to the Section Respiratory Medicine)
22 pages, 1593 KiB  
Article
In Silico Analysis of Possible microRNAs Involved in the Pathogenesis of White-Nose Syndrome in Myotis lucifugus
by Anouska Agarwal, Craig K. R. Willis and Anuraag Shrivastav
Int. J. Mol. Sci. 2025, 26(17), 8200; https://doi.org/10.3390/ijms26178200 (registering DOI) - 23 Aug 2025
Abstract
Since 2007, white-nose syndrome (WNS), caused by the fungus Pseudogymnoascus destructans, has killed millions of bats across North America by disrupting hibernation cycles, causing premature fat depletion and starvation. Little brown bats (Myotis lucifugus) from some populations persisting after WNS [...] Read more.
Since 2007, white-nose syndrome (WNS), caused by the fungus Pseudogymnoascus destructans, has killed millions of bats across North America by disrupting hibernation cycles, causing premature fat depletion and starvation. Little brown bats (Myotis lucifugus) from some populations persisting after WNS store larger pre-hibernation fat reserves than bats did before WNS, which may help bats survive winter starvation and mount an immune response to Pd in spring. MicroRNAs (miRNAs) are highly conserved, small, non-coding RNA molecules that regulate gene expression post-transcriptionally. Aberrant miRNA expression can affect metabolic pathways in mammals and has been linked to various diseases. If fat reserves and immune mechanisms influence survival from WNS, then miRNAs regulating metabolic and immune-related genes might affect WNS pathogenesis and bat survival. A previous study identified 43 miRNAs differentially expressed in bats with WNS. We analyzed these miRNAs for their roles in metabolism and immune-related pathways, using DIANA Tools and KEGG analysis, to determine a subset that could serve as biomarkers of pathophysiology or survival in WNS-affected bats. We identified miR-543, miR-27a, miR-92b, and miR-328 as particularly important because they regulate multiple pathways likely important for WNS (i.e., immune response, lipogenesis, insulin signaling, and FOXO signaling). As proof-of-concept, we used reverse transcription quantitative real-time PCR (RT-qPCR) to quantify the prevalence of these miRNAs in plasma samples of bats (n = 11) collected from a post-WNS population during fall fattening. All the selected miRNAs were detectable in at least some bats during fall fattening although prevalence varied among miRNAs. Future in vivo validation studies would help confirm functional roles and biomarker utility of these miRNAs for WNS-affected bats. Full article
(This article belongs to the Special Issue Regulation by Non-Coding RNAs 2025)
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10 pages, 307 KiB  
Brief Report
Association Between Optical Coherence Tomography Angiography (OCTA)-Based Retinal Vascular Densities and Empathy in Young Adults
by Bess Yin-Hung Lam, Carole Leung, Ka-Shun Lei, Kaiyip Choi and Henry H. L. Chan
Bioengineering 2025, 12(9), 902; https://doi.org/10.3390/bioengineering12090902 - 22 Aug 2025
Abstract
With the use of Optical Coherence Tomography Angiography (OCTA), the present study is the first study to examine if retinal vascular densities (vessel densities and perfusion densities) could be associated with empathetic levels in young and non-clinical adults. Methods: Fifty-one university students aged [...] Read more.
With the use of Optical Coherence Tomography Angiography (OCTA), the present study is the first study to examine if retinal vascular densities (vessel densities and perfusion densities) could be associated with empathetic levels in young and non-clinical adults. Methods: Fifty-one university students aged from 18 to 25 years (26 males and 24 females) were recruited from a university in Hong Kong. OCTA was conducted to assess their retinal vessel density (VD) and perfusion density (PD) in different scan patterns over the macula (1 mm center subfield, 3 × 3 mm scan, 6 × 6 mm scan). Empathy (cognitive, affective, and somatic) was measured by using the Cognitive, Affective, and Somatic Empathy Scales (CASES). Results: After controlling for age, the multiple linear regression results showed that both the VD and PD in the 1 mm center subfield were significantly and negatively associated with the empathy total score, the affective empathy subscore, and the somatic empathy subscore, respectively (ps < 0.05). Conclusion: The present findings indicate that a lower level of empathy is associated with increased retinal vascular densities in the 1 mm center subfield, specifically involving variations in vascular density (VD) and perfusion density (PD). This suggests the dilation of retinal venules might lead to lower empathy. These results establish a foundation for future studies investigating the underlying mechanism of retinal imaging and empathy in healthy individuals. Full article
(This article belongs to the Special Issue Retinal Circuit Engineering)
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12 pages, 1108 KiB  
Article
Aqueous Singlet Oxygen Sensitization of Porphyrin-Embedded Silica Particles with Long-Term Stability
by Pengcheng Zhu, Zilong Guo, Yulin Sha, Yonghang Li, Xiaoyu Zhang, Yandong Han, Wensheng Yang and Xiaonan Ma
Inorganics 2025, 13(9), 279; https://doi.org/10.3390/inorganics13090279 - 22 Aug 2025
Abstract
Aqueous singlet oxygen (1O2) sensitization is of high interest due to its wide application in bio-imaging and photodynamic therapy. For organic photosensitizers like porphyrin derivatives, surfactant-assisted micelles have been intensively explored for dispersing hydrophobic sensitizers in aqueous phase; however, [...] Read more.
Aqueous singlet oxygen (1O2) sensitization is of high interest due to its wide application in bio-imaging and photodynamic therapy. For organic photosensitizers like porphyrin derivatives, surfactant-assisted micelles have been intensively explored for dispersing hydrophobic sensitizers in aqueous phase; however, they can suffer from poor long-term stability. In this work, palladium octaethylporphyrin (PdOEP)-embedded silica particles were prepared with assistance from Tween micelles, and their corresponding application in aqueous 1O2 sensitization was explored. With assistance from Tween 80 at a >3 mg/mL concentration, superior (>95%) solubilization of PdOEP was observed in aqueous solution, leading to a high 1O2 quantum yield (ΦΔ ≈ 93%). By optimizing the synthesis conditions, >95% of micellar PdOEP was embedded into silica particles, exhibiting comparable ΦΔ (up to 70%) to micellar systems by effectively suppressing PdOEP aggregation in particles. The PdOEP-embedded silica particles exhibited dramatically enhanced long-term stability (more than one year) compared to corresponding micelles with a half-life of ~38 days. In addition, aqueous 1O2 sensitization by PdOEP-embedded silica particles was demonstrated upon two-photon excitation in a near-infrared regime (λex = 1030 nm), highlighting the great potential of this method for future biological applications. Full article
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23 pages, 1624 KiB  
Article
SARS-CoV-2 Infection in Children: Revisiting Host–Virus Interactions Through Post-Infection Immune Profiling
by Catarina Gregório Martins, Miguel Ângelo-Dias, Maria de Jesus Chasqueira, Maria João Brito, Tiago Milheiro Silva, Maria Vitória Matos, Maria Teresa Lopes, Hélio Crespo, Mariana Mata, Luís Miguel Borrego and Paulo Paixão
Pathogens 2025, 14(9), 838; https://doi.org/10.3390/pathogens14090838 - 22 Aug 2025
Abstract
Children with COVID-19 typically experience milder symptoms and lower hospitalization rates, though severe cases do occur. Understanding age-related immune responses is crucial for future preparedness. We characterized immune response dynamics to SARS-CoV-2 in 145 samples from 119 pediatric patients (<18 years) with confirmed [...] Read more.
Children with COVID-19 typically experience milder symptoms and lower hospitalization rates, though severe cases do occur. Understanding age-related immune responses is crucial for future preparedness. We characterized immune response dynamics to SARS-CoV-2 in 145 samples from 119 pediatric patients (<18 years) with confirmed infection, assessed at four distinct time points: <14 days, 14 days–3 months, 3–6 months, and 6–12 months post-infection. At infection, patients presented increased activated T-cells, higher levels of exhaustion (i.e., PD-1+), lower numbers of unswitched memory B-cells, and increased antibody-secreting cells (ASCs). Both humoral and cellular anti-SARS-CoV-2 responses increased over time (all patients showed measurable responses in the last assessment). Asymptomatic/mildly symptomatic patients (58.6%) showed increased specific cellular responses from infection onwards, along with enriched memory B-cell subsets (but not ASCs), and distinct T-cell activation profiles. Children with severe disease were younger, predominantly boys, displayed altered T/B-cell ratios, and reduced PHA responses when infected. Compared to adolescents, younger children showed lower antibody titers and weaker cellular responses to SARS-CoV-2, possibly underlining the higher prevalence of severe manifestations in younger children. Our study illustrates important age-, gender-, and disease severity-dependent variations in immune responses to SARS-CoV-2, which can be helpful in improving patient management and immunization strategies adjusted to age groups. Full article
(This article belongs to the Special Issue Emerging Viral Infections in the Respiratory Tract)
10 pages, 1075 KiB  
Article
UK Real-World Evidence of Using Durvalumab Plus Cisplatin and Gemcitabine in Advanced Biliary Tract Cancer via an Early Access Scheme
by Harry Daniels, Mona Hassan, Omer Babiker, William Rowley, Aitzaz Qaisar, Emma Phillips, Ellana Griffin, Catherine Bell, Bahaaeldin Baraka, Shyamika Acharige, Maia Aquino, Rachel Plant, Justin Mencel, Samuel Chan, Dominique Parslow, Arvind Arora, Martin Scott-Brown, Shelize Khakoo, Chiara Braconi, Daniel Palmer, Yuk Ting Ma and Shivan Sivakumaradd Show full author list remove Hide full author list
Cancers 2025, 17(17), 2732; https://doi.org/10.3390/cancers17172732 - 22 Aug 2025
Abstract
Background: Durvalumab (anti-PD-L1) in combination with gemcitabine and cisplatin has become the first-line treatment for patients with locally advanced, surgically unresectable, or metastatic biliary tract cancer, following the survival benefit demonstrated in the TOPAZ-1 phase III trial. This study presents real-world data from [...] Read more.
Background: Durvalumab (anti-PD-L1) in combination with gemcitabine and cisplatin has become the first-line treatment for patients with locally advanced, surgically unresectable, or metastatic biliary tract cancer, following the survival benefit demonstrated in the TOPAZ-1 phase III trial. This study presents real-world data from UK centres in patients who received early access to the regimen via AstraZeneca’s scheme. The aim was to assess the safety and efficacy of this treatment approach in routine clinical practice and compare it to outcomes reported in the TOPAZ-1 trial. Method: This retrospective study included patients with locally advanced, surgically unresectable, or metastatic biliary tract adenocarcinoma who received durvalumab in combination with gemcitabine and cisplatin. Data were collected across ten UK centres. The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS), overall response rate (ORR), and safety outcomes, encompassing both chemotherapy and immunotherapy-related adverse events (AEs). Results: A total of 134 patients treated between April 2022 and December 2023 were included. The median follow-up was 12.8 months (95% CI: 11–16.8). The median PFS was 8.83 months (95% CI: 5.73–11.7), closely aligning with the 7.2 months reported in TOPAZ-1 (95% CI: 6.7–7.4). The median OS was 12 months (95% CI: 10.7–13.9), slightly below the 12.8 months observed in TOPAZ-1 (95% CI: 11.1–14.0). The ORR was 29.1% (TOPAZ-1: 26.7%), and the disease control rate was 61.2%. In terms of safety, 64 patients (52.3%) experienced any-grade AEs, and 9 patients (6.8%) had grade 3–4 AEs, representing a lower toxicity profile than TOPAZ-1. Immunotherapy-related AEs occurred in 25 patients (18.7%), with grade 3–4 events in 3%. Conclusions: These real-world findings from UK cancer centres support the outcomes of the TOPAZ-1 trial, demonstrating comparable efficacy and a favourable safety profile for durvalumab combined with gemcitabine-cisplatin as first-line treatment for advanced biliary tract cancer. Full article
(This article belongs to the Section Cancer Drug Development)
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29 pages, 4800 KiB  
Article
Claudin-1 Contributes to Gastrointestinal Stromal Tumors (GIST) Resistance to Imatinib Mesylate (IM) via Regulation of FGFR-Signaling
by Sergei Boichuk, Firyuza Bikinieva, Pavel Dunaev, Aigul Galembikova, Ekaterina Mikheeva, Elena Valeeva, Shinjit Mani, Natalia Khromova, Pavel Kopnin, Leyla Shigapova, Ruslan Deviatiarov, Elena Shagimardanova, Sergey Ryzhkin and Alexey Sabirov
Int. J. Mol. Sci. 2025, 26(17), 8138; https://doi.org/10.3390/ijms26178138 - 22 Aug 2025
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Abstract
We previously demonstrated that the activation of FGFR signaling in GIST may be a mechanism of GIST resistance to imatinib mesylate (IM). We show here that IM-resistant GIST cells lacking secondary KIT mutations overexpress claudin-1 on both transcriptional and translational levels. In contrast, [...] Read more.
We previously demonstrated that the activation of FGFR signaling in GIST may be a mechanism of GIST resistance to imatinib mesylate (IM). We show here that IM-resistant GIST cells lacking secondary KIT mutations overexpress claudin-1 on both transcriptional and translational levels. In contrast, a knockdown of CLDN1 or inhibition of its activity by PDS-0330 effectively restored GIST’s sensitivity to IM both in vitro and in vivo. This was evidenced by the increased expression of apoptotic markers (e.g., cleaved PARP and caspase-3) and the decreased proliferation rate of IM-resistant GIST T-1R cells treated with a combination of IM and PDS-0330 (or siRNA CLDN1). In concordance with these findings, a significant synergy was observed between IM and PDS-0330 in GIST T-1R cells. Importantly, decreased tumor size and weight were observed in IM-resistant GIST xenografts treated with a combination of IM and PDS-0330. Furthermore, the combined treatment of IM-resistant tumors induced an increase in intratumoral apoptosis and other changes, as defined by the histopathologic response rate. Based on the co-immunoprecipitation and immunofluorescence microscopy data, we also demonstrated the strong interaction pattern between CLDN1 and FGFR2. Of note, the inhibition or knockdown of CLDN1 effectively decreased the phosphorylation of FGFR2 and FRS-2, a well-known FGFR adaptor protein, thereby illustrating CLDN1’s ability to regulate FGFR-signaling and thereby promote FGFR-mediated survival in KIT-inhibited GIST. Consequently, CLDN1 inhibition in GIST effectively disrupted the FGFR-mediated pathway and re-sensitized tumor cells to IM. In concordance with these data, molecular profiling of CLDN1-inhibited GIST T-1R cells illustrated a significant decrease in the majority of FGFR transcripts, including FGFR2, 3, and 4. Additionally, several FGFR ligands (e.g., FGF14, -19, and -23) were also down-regulated in PDS-0330-treated GIST. Notably, exogenous FGF-2 increased CLDN1 expression in a time-dependent manner. In contrast, pan-FGFR inhibitors effectively reduced CLDN1 levels in IM-resistant GIST T-1R cells, thereby illustrating a cross-talk between CLDN1- and FGFR-mediated pathways in IM-resistant GIST. Based on subcellular fractionation and immunofluorescence microscopy data, we also observed partial relocalization of CLDN1 into the cytoplasm in IM-resistant GIST. Notably, PDS-0330 effectively abrogated this relocalization, suggesting that changes in CLDN1 subcellular distribution might also impact GIST resistance to IM. Lastly, based on our small cohort clinical study (n = 24), we observed the increased expression of CLDN1 in most “high-risk” primary GIST known to be associated with poor prognosis and aggressive behavior, thereby illustrating the prognostic value of increased CLDN1 expression in GIST and providing a further rationale to evaluate the effectiveness of CLDN1 inhibition for GIST therapy. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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18 pages, 1083 KiB  
Article
Optimizing Gait Outcomes in Parkinson’s Disease: The Effects of Musical Groove and Familiarity
by Emily A. Ready, Jeffrey D. Holmes, Eryn P. Lonnee and Jessica A. Grahn
Brain Sci. 2025, 15(9), 901; https://doi.org/10.3390/brainsci15090901 - 22 Aug 2025
Viewed by 29
Abstract
Background. Parkinson’s Disease (PD) is a neurological condition that can severely impair gait, often through changes to gait parameters including stride length, velocity, and variability. Therapeutic interventions such as Rhythmic Auditory Stimulation (RAS®) target gait dysfunction in PD by using the [...] Read more.
Background. Parkinson’s Disease (PD) is a neurological condition that can severely impair gait, often through changes to gait parameters including stride length, velocity, and variability. Therapeutic interventions such as Rhythmic Auditory Stimulation (RAS®) target gait dysfunction in PD by using the regular beat of music or metronome clips to cue normalized walking patterns. Previous research has suggested that auditory cue properties (e.g., familiarity and groove) and individual factors (e.g., beat perception ability and susceptibility to dual-task interference) influence auditory cueing treatment efficacy in healthy young and older adults; however, optimization of rhythmic cueing across individuals with PD remains understudied. Methods. To address this, we explored the effects of familiarity, groove, beat perception ability, and synchronization instructions on gait in patients with PD during accelerated auditory cues. Individuals with idiopathic PD were randomized to walk freely or synchronized to music and metronome cues played 10% faster than their baseline walking cadence. Musical stimuli varied in self-reported familiarity and perceived groove and beat perception ability was assessed to classify participants as good or poor beat perceivers. Results. Overall, high-groove music and synchronized walking elicited faster gait patterns compared to low-groove music and free walking, respectively, as demonstrated by increased gait velocity and cadence. Familiarity and beat perception ability did not significantly affect gait in individuals with PD. Discussion. Altogether, our results indicate that high-groove music and synchronized walking lead to the greatest gait improvements during cueing, regardless of beat perception ability. Conclusion. Future studies and clinical interventions should consider stimulus type and synchronization instructions when implementing cueing therapies for gait dysfunction in PD in order to optimize treatment responses. Full article
(This article belongs to the Special Issue Focusing on the Rhythmic Interventions in Movement Disorders)
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