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22 pages, 4238 KB  
Article
Tailored Annealing for Interfacial Design and Mechanical Optimization of Cu18150/Al1060/Cu18150 Trilayer Composites
by Yuchao Zhao, Mahmoud Ebrahimi, Linfeng Wu, Shokouh Attarilar and Qudong Wang
Metals 2026, 16(2), 176; https://doi.org/10.3390/met16020176 (registering DOI) - 1 Feb 2026
Abstract
Copper–aluminum layered composites offer a promising combination of high conductivity, light weight, and cost-effectiveness, making them attractive for applications in electric vehicles, electronics, and power transmission. However, achieving reliable interfacial bonding while avoiding excessive work hardening and brittle intermetallic formation remains a significant [...] Read more.
Copper–aluminum layered composites offer a promising combination of high conductivity, light weight, and cost-effectiveness, making them attractive for applications in electric vehicles, electronics, and power transmission. However, achieving reliable interfacial bonding while avoiding excessive work hardening and brittle intermetallic formation remains a significant challenge. In this study, a Cu18150/Al1060/Cu18150 trilayer composite was fabricated through a three-stage high-temperature oxygen-free rolling process. Subsequently, the produced composite was subjected to annealing treatments to systematically investigate the effects of rolling passes, annealing temperature/time on interfacial evolution and mechanical behavior. Results indicate that rolling passes primarily influence interfacial topography and defect distribution. Fewer passes lead to wavy, mechanically bonded interfaces, while more passes improve flatness but reduce intermetallic continuity. Annealing temperature critically governs diffusion kinetics; temperatures up to 400 °C promote the formation of a uniform Al2Cu layer, whereas 450 °C accelerates the growth of brittle Al4Cu9, thickening the intermetallic layer to 18 μm and compromising toughness. Annealing duration further modulates diffusion mechanisms, with short-term (0.5 h) treatments favoring defect-assisted diffusion, resulting in a porous, rapidly thickened layer. In contrast, longer annealing (≥1 h) shifts toward lattice diffusion, which densifies the interface but risks excessive brittle phase formation if prolonged. Mechanical performance evolves accordingly; as-rolled strength increases with the number of rolling passes, but at the expense of ductility. Annealing transforms bonding from a mechanical to a metallurgical condition, shifting fracture from delamination to collaborative failure. The identified optimal process, single-pass rolling followed by annealing at 420 °C for 1 h, yields a balanced interfacial structure of Al2Cu, AlCu, and Al4Cu9 phases, achieving a tensile strength of 258.9 MPa and an elongation of 28.2%, thereby satisfying the target performance criteria (≥220 MPa and ≥20%). Full article
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15 pages, 853 KB  
Article
Prospective Bi-Centric Real-World Outcomes of Upadacitinib in Biologic-Experienced Patients with Crohn’s Disease
by Janina Lüke, Clara Zippel, Phil-Robin Tepasse, Frank Lenze, Markus Strauss, Arne Bokemeyer, Joost Buskermolen, Tina Schomacher, Julia Fischer, Jonel Trebicka and Richard Vollenberg
Diseases 2026, 14(2), 54; https://doi.org/10.3390/diseases14020054 (registering DOI) - 1 Feb 2026
Abstract
Background: The efficacy of upadacitinib in patients with Crohn’s disease (CD) has been shown in pivotal randomized controlled trials. However, real-world data is needed to assess its effectiveness and safety in routine clinical care with biologic-experienced patients. This study aimed to evaluate the [...] Read more.
Background: The efficacy of upadacitinib in patients with Crohn’s disease (CD) has been shown in pivotal randomized controlled trials. However, real-world data is needed to assess its effectiveness and safety in routine clinical care with biologic-experienced patients. This study aimed to evaluate the clinical and endoscopic efficacy, patient-reported outcomes (PROs), and safety of upadacitinib in biologic-experienced patients with CD in a real-world setting. Methods: This prospective bi-centric real-world study enrolled 28 anti-TNF-experienced patients with CD receiving upadacitinib 45 mg daily for 12 weeks (induction), followed by 30 mg daily maintenance through week 52. Primary endpoints included endoscopic response (≥50% SES-CD reduction or ≥2-point decrease from baseline for baseline SES-CD ≤ 4) and clinical remission (Harvey–Bradshaw Index [HBI] ≤ 4). Secondary endpoints included endoscopic remission, clinical response (HBI decrease ≥ 3 points), and quality of life (IBD-Disk). Statistical analysis used the Wilcoxon signed-rank test with 95% confidence intervals (CIs). Results: Median patient age was 37 years; 75% had ≥3 prior biologic failures. Clinical remission rates (HBI) were 59% (95% CI: 41–75%) at week 12, 44% (95% CI: 27–63%) at week 26, and 53% (95% CI: 29–76%) at week 52. Endoscopic response rates were 48% (95% CI: 44–52%) at week 26 and 46% (95% CI: 21–72%) at week 52. Endoscopic remission was achieved in 43% (95% CI: 40–48%) at week 26 and 27% (95% CI: 10–57%) at week 52. Clinical response (HBI) improved progressively from 65% at week 2 to 71% at week 52. Quality of life, as assessed by the IBD-Disk, showed significant improvement: Reduced Disease Burden (defined as a decrease of 70% or a CED-Disk Score of ≤15) was observed in 33% of patients at week 12 and 35% at week 52. Median SES-CD decreased from 9 points (IQR: 6–17) at baseline to 5 points (IQR: 1–12, p = 0.005) at week 52. Adverse events occurred in 11% of patients (4% lymphopenia, 7% skin disease), with no serious adverse events or deaths. Conclusions: Upadacitinib demonstrates significant clinical and endoscopic efficacy in biologic-experienced, anti-TNF-pretreated patients with CD, achieving remission rates comparable to or exceeding those of the pivotal trials despite a highly refractory population (75% with ≥3 prior biologic failures). The favorable safety profile supports upadacitinib as an important therapeutic option in sequential treatment of refractory CD. Full article
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32 pages, 2622 KB  
Review
Recent Advances in Nanoparticle-Based Drug Delivery Strategies to Cross the Blood–Brain Barrier in Targeted Treatment of Alzheimer’s Disease
by Hoa Le, Giang T. T. Vu, Amos Abioye and Adeboye Adejare
Pharmaceutics 2026, 18(2), 192; https://doi.org/10.3390/pharmaceutics18020192 (registering DOI) - 1 Feb 2026
Abstract
The blood–brain barrier (BBB) is a major obstacle to the development of brain-targeted drug delivery systems, restricting greater than 98% of small molecules (<500 Da) and virtually all large-molecule drugs from entering the brain tissues from the bloodstream, resulting in suboptimal drug doses [...] Read more.
The blood–brain barrier (BBB) is a major obstacle to the development of brain-targeted drug delivery systems, restricting greater than 98% of small molecules (<500 Da) and virtually all large-molecule drugs from entering the brain tissues from the bloodstream, resulting in suboptimal drug doses and therapeutic failure in the treatment of Alzheimer’s disease (AD). However, the advent of nanotechnology has provided significant solutions to the BBB challenges, enabling particle size reduction, enhanced drug solubility, reduced premature drug degradation, extended and sustained drug release, enhanced drug transport across the BBB, increased drug target specificity and enhanced therapeutic efficacy. In corollary, a library of brain-targeted surface-functionalized nanotherapeutics has been widely reported in the current literature. These promising in vitro, in vivo and pre-clinical results from the existing literature provide quantitative evidence for the relative clinical utility of each of the techniques, indicating remarkable capacity for brain-targeted carrier systems; many of them are still being tested in human clinical trials. However, despite the recorded research successes in drug transport across the BBB, there are currently no clinically proven medications that can slow or reverse the progression of AD because most of the novel therapeutics have not been successful during the clinical trials. Therefore, the main option for the treatment of AD is symptomatic treatment using cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. Although these therapies help to alleviate symptoms of AD and improve patients’ quality of life, they neither slow the progression of disease nor cure it. Thus, an effective disease-modifying therapy for the treatment of AD is an unmet clinical need. It is apparent that a deeper understanding of the structural complexity and controlling dynamic functions of the BBB in tandem with a comprehensive elucidation of AD pathogenesis are crucial to the development of novel nanocarriers for the effective treatment of AD. Therefore, this narrative review describes the contextual analysis of several promising strategies that enhance brain-targeted drug delivery across the BBB in AD treatment and recent research efforts on two major AD biomarkers that have revolutionized AD diagnosis, amyloid-beta plaques and phosphorylated tau protein tangle, as potential targets in AD drug development. This has led to the Food and Drug Administration (FDA)’s approval of two intravenous (IV) anti-amyloid monoclonal antibodies, Lecanemab (Leqembi®) and Donanemab (Kisunla®), which were developed based on the Aβ cascade hypothesis for the treatment of early AD. This review also discusses the recent shift in the Aβ cascade hypothesis to Aβ oligomer (conformer), a soluble intermediate of Aβ, which is the most toxic mediator of AD and could be the most potent drug target in the future for a more accurate and effective drug development model for the treatment of AD. Furthermore, various promising nanoparticle-based drug carriers (therapeutic nanoparticles) that were developed from intensive research are discussed, including their clinical utility, challenges and prospects in the treatment of AD. Overall, it suffices to state that the advent of nanotechnology provided several innovative techniques for overcoming the BBB and improving drug delivery to the brain; however, their long-term biosafety is a relevant concern. Full article
(This article belongs to the Special Issue Smart Polymeric Nanoparticle-Based Drug Delivery Systems)
38 pages, 2562 KB  
Review
Advances in Solid Lubricating Layers for Gears: A Review
by Hongyang Zhang, Shuchong Wu, Jinghua Li and Yang Li
Lubricants 2026, 14(2), 66; https://doi.org/10.3390/lubricants14020066 (registering DOI) - 31 Jan 2026
Abstract
As a core component of industrial power transmission and motion control, the surface quality and dynamic performance of gears are pivotal to the transmission efficiency, durability, and reliability of mechanical equipment. Driven by extreme service conditions and the demands of high-precision applications, surface [...] Read more.
As a core component of industrial power transmission and motion control, the surface quality and dynamic performance of gears are pivotal to the transmission efficiency, durability, and reliability of mechanical equipment. Driven by extreme service conditions and the demands of high-precision applications, surface lubrication failures (such as contact fatigue and scuffing) have become a critical bottleneck limiting gear performance, making the development of advanced surface-strengthening technologies a vital direction for industrial innovation. This paper provides a systematic review of research progress in gear-related surface-strengthening technologies, with a particular focus on techniques for preparing solid lubricant layers. It elaborates on the microstructures, lubrication mechanisms, and application performance of typical solid lubricant layers (e.g., iron sulfides, nitrides, molybdenum disulfide (MoS2), diamond-like carbon (DLC) films, and graphite-like carbon (GLC) films) in gear systems. Furthermore, it offers an in-depth analysis of the synergistic mechanisms between single-surface treatments and composite-strengthening processes. Additionally, it outlines innovative applications of additive manufacturing (AM) in gear manufacturing. Full article
14 pages, 1193 KB  
Article
Effect of Short-Term and Long-Term Non-Physiological T3 Concentrations on Cardiac Stromal Cells: From Cellular Response to In Vivo Adaptation
by Ahmad Alhamid, Yoshishige Urata, Kodai Nishi, Hiroshi Kurazumi, Ryo Suzuki, Koji Ueno, Akihito Mikamo, Kimikazu Hamano and Tao-Sheng Li
Med. Sci. 2026, 14(1), 66; https://doi.org/10.3390/medsci14010066 (registering DOI) - 31 Jan 2026
Abstract
Background/Objectives: Epidemiological and clinical studies have linked both hypothyroidism and hyperthyroidism to adverse cardiac outcomes, including heart failure and myocardial fibrosis. Triiodothyronine (T3), a biologically active thyroid hormone, is important for cardiovascular homeostasis. While the effects of physiological and non-physiological T3 levels on [...] Read more.
Background/Objectives: Epidemiological and clinical studies have linked both hypothyroidism and hyperthyroidism to adverse cardiac outcomes, including heart failure and myocardial fibrosis. Triiodothyronine (T3), a biologically active thyroid hormone, is important for cardiovascular homeostasis. While the effects of physiological and non-physiological T3 levels on cardiomyocytes have been extensively investigated, the impact of hypothyroidism and hyperthyroidism on cardiac stromal cells (CSCs), which constitute the majority of the cells in the heart, remains understudied. Given CSCs’ essential role in extracellular matrix (ECM) remodeling and paracrine signaling, understanding their response to altered T3 states is necessary to fully elucidate the thyroid hormone-induced cardiac responses. Methods: Cardiac stromal cells were isolated from human atrial appendages and cultured under hypothyroid (0 nM T3), euthyroid (2.5 nM T3), and hyperthyroid (25 nM T3) conditions for 24 (short term) and 120 h (long term). The cells were harvested after 24 h of treatment using trypsin and automatically counted, and their ECM-related gene and growth factor expression levels were assessed using quantitative RT-PCR. Cardiac glucose uptake in hypothyroid, euthyroid, and hyperthyroid mice was monitored using [18F]-FDG PET/CT at acute (7 days) and chronic (42 days) time points. Results: Both hypo- and hyperthyroidism significantly increased the number of CSCs harvested after 24 h. There were acute alterations in the expression of the ECM-related genes COL1A1, COL3A1, TIMP3 (p < 0.05), and TIMP1 (p < 0.01). Similarly, growth factors such as PDGF-A (p < 0.001), TGF-b, and IGF1 (p < 0.05) were transiently upregulated under non-physiological T3 conditions, especially hypothyroidism. Most of these alterations were attenuated or reversed at the 120 h time point. In vivo PET imaging revealed significant increases in cardiac glucose uptake under acute hypothyroidism (p < 0.05) and decreases under acute hyperthyroidism (p < 0.05). However, these metabolic shifts normalized with chronic exposure, paralleling the transient nature of the gene expression changes observed in vitro. Conclusions: Non-physiological T3 concentrations induce proliferation and changes in ECM-related and growth factor gene expression in CSCs. Most of these changes are acute and return to normal levels after chronic exposure. These transient cellular responses correlate closely with the cardiac metabolic response patterns to acute and chronic hypothyroidism and hyperthyroidism. Full article
13 pages, 399 KB  
Article
Pharmacovigilance-Based Safety Profile of Bortezomib: A Disproportionality Analysis Using FAERS Data
by Matthew Nho, Ayushi Mittal, Ahmed Abdel-Latif and Anand Prakash Singh
Cardiovasc. Med. 2026, 29(1), 4; https://doi.org/10.3390/cardiovascmed29010004 (registering DOI) - 31 Jan 2026
Abstract
Bortezomib is a 26S proteasome inhibitor used to treat multiple myeloma and systemic amyloidosis. While effective in prolonging survival, bortezomib has been increasingly associated with cardiovascular adverse events (CVAEs), including cardiac failure and arrhythmias, yet a comprehensive post-marketing cardiac safety profile remains incompletely [...] Read more.
Bortezomib is a 26S proteasome inhibitor used to treat multiple myeloma and systemic amyloidosis. While effective in prolonging survival, bortezomib has been increasingly associated with cardiovascular adverse events (CVAEs), including cardiac failure and arrhythmias, yet a comprehensive post-marketing cardiac safety profile remains incompletely defined. We analyzed cardiovascular adverse events reported between May 2003 and May 2025 using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) via the OpenVigil 2.1 platform. Disproportionality analysis was performed using reporting odds ratios (RORs) with 95% confidence intervals (CIs). Among over 9 million drug-related adverse events in FAERS, 552 cardiac events were linked to bortezomib. Several cardiac outcomes, including atrial flutter, left ventricular dysfunction, cardiac failure, cardiomyopathy, atrial fibrillation, right ventricular failure, myocarditis, and supraventricular tachycardia, demonstrated elevated disproportionality signals. Separately, cardiac amyloidosis exhibited the highest disproportionality signal (ROR: 35.58; 95% CI: 28.16–44.95), a finding that reflects underlying disease severity rather than treatment-emergent cardiotoxicity. Cardiac failure accounted for the greatest number of hospitalizations (301) and deaths (208), followed by atrial fibrillation and cardiac amyloidosis. Older adults (≥65 years) and patients with amyloidosis or multiple myeloma were the most vulnerable populations. Overall, bortezomib was associated with serious cardiac adverse events, particularly cardiac failure and atrial arrhythmias, underscoring the need for routine cardiovascular risk assessment and proactive monitoring in high-risk patients. Full article
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28 pages, 1932 KB  
Review
Drug-Coated Balloons in Coronary Bifurcation Disease: A State-of-the-Art Review
by Saad M. Ezad, Natasha Khullar, Peter O’Kane and Jonathan Hinton
J. Pers. Med. 2026, 16(2), 75; https://doi.org/10.3390/jpm16020075 (registering DOI) - 31 Jan 2026
Abstract
Coronary bifurcation disease remains one of the more challenging lesion subsets to treat with percutaneous coronary intervention due to bifurcation geometry and increased risk of target lesion failure. Whilst a provisional approach is preferred in most bifurcations, two-stent techniques may be required where [...] Read more.
Coronary bifurcation disease remains one of the more challenging lesion subsets to treat with percutaneous coronary intervention due to bifurcation geometry and increased risk of target lesion failure. Whilst a provisional approach is preferred in most bifurcations, two-stent techniques may be required where there is a high risk of side branch compromise or a bailout; however, this further increases procedure complexity. Drug-coated balloons (DCBs) are emerging as a promising alternative that allow vessel healing without leaving behind a permanent metallic implant by delivering antiproliferative medication directly to the vessel wall and simplifying procedures. This state-of-the-art review summarises the current evidence and the evolving role of DCBs in the management of coronary bifurcation lesions with a focus on patient- and lesion-specific factors that might influence the treatment strategy choice. Full article
(This article belongs to the Special Issue Complex and High-Risk Coronary Interventional Procedures)
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22 pages, 1173 KB  
Review
Current Treatment Standards for Metastatic Uveal Melanoma
by Paweł Rogala, Anna M. Czarnecka, Monika Dudzisz-Śledź, Anna Dawidowska, Kacper J. Piwowarek and Piotr Rutkowski
Cancers 2026, 18(3), 475; https://doi.org/10.3390/cancers18030475 (registering DOI) - 31 Jan 2026
Abstract
Background/Objectives: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, most commonly arising in the choroid. Its development is associated with phenotypic characteristics, ultraviolet radiation, and germline or somatic genetic alterations. Despite progress in diagnostics and local therapies, UM remains [...] Read more.
Background/Objectives: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, most commonly arising in the choroid. Its development is associated with phenotypic characteristics, ultraviolet radiation, and germline or somatic genetic alterations. Despite progress in diagnostics and local therapies, UM remains characterized by high metastatic risk and poor overall prognosis. This review aimed to summarize current knowledge on epidemiology, clinical features, genetic background, prognostic factors, and therapeutic approaches in metastatic UM. Methods: A structured literature review was conducted to evaluate epidemiological trends, genetic alterations, prognostic markers, clinical presentation, and therapeutic strategies. The results of different systemic treatments were analyzed, with special attention to liver-directed interventions and emerging systemic therapies. Results: The incidence of UM in Europe increases with latitude, ranging from two per million in the southern regions to more than eight per million in the North. The median age at diagnosis is 62 years, and most cases are detected incidentally during ophthalmological examinations due to nonspecific symptoms. Some genetic alterations serve as important prognostic indicators. Local treatment consists of globe-preserving procedures, including radiation therapy, surgery, laser therapy, or enucleation, with failure rates between 6.15% and 20.8%. Up to 70% of patients develop distant metastases, predominantly in the liver. Metastatic UM (mUM) carries a poor prognosis, with overall survival ranging from 3 to 30 months. Liver-directed therapies, particularly surgical resection, provide the most favorable outcomes. Systemic therapies demonstrate limited efficacy; however, tebentafusp has shown an overall survival benefit in HLA-A*02:01 (human leukocyte antigen A*02:01)-positive patients. Conclusions: UM is a rare but aggressive malignancy with limited treatment options once metastatic. Liver-directed strategies remain the mainstay of management, while novel systemic approaches, including tebentafusp, represent promising advances. Further research is required to improve survival and expand therapeutic opportunities. Full article
(This article belongs to the Special Issue Advances in Treatment of Uveal Melanoma)
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13 pages, 571 KB  
Article
High-Risk Prostate Cancer Treated with Radiation Therapy: Favorable Outcomes in Men with PSA > 20 as the Sole High-Risk Factor
by Aoi Shimomura, Abed R. Kawakibi, Muzamil Arshad and Stanley L. Liauw
J. Clin. Med. 2026, 15(3), 1119; https://doi.org/10.3390/jcm15031119 - 30 Jan 2026
Abstract
Background/Objectives: The National Comprehensive Cancer Network (NCCN) classifies prostate cancer with PSA > 20 ng/mL as high risk; however, outcomes within this group are heterogeneous. Emerging data suggest that men with PSA > 20 ng/mL as the sole high-risk feature may have more [...] Read more.
Background/Objectives: The National Comprehensive Cancer Network (NCCN) classifies prostate cancer with PSA > 20 ng/mL as high risk; however, outcomes within this group are heterogeneous. Emerging data suggest that men with PSA > 20 ng/mL as the sole high-risk feature may have more favorable disease biology. We evaluated outcomes of men with prostate cancer treated with definitive radiation therapy (RT), focusing on the prognostic significance of individual high-risk factors. Methods: We analyzed 742 men with prostatic adenocarcinoma treated with curative-intent RT between 2005 and 2021, including 282 meeting traditional NCCN high-risk criteria. Treatment consisted of dose-escalated RT (median 78 Gy), with androgen deprivation therapy (ADT) administered to 94% (median duration 28 months). Primary endpoints were freedom from biochemical failure (FFBF) and distant metastasis (FFDM). Outcomes were assessed using Kaplan–Meier methods and Cox proportional hazards modeling. Results: At 5 years, high-risk patients demonstrated FFBF of 83% and FFDM of 89%, with significantly worse outcomes among very high-risk subgroups. Men with PSA > 20 ng/mL as their only high-risk feature (n = 49) achieved superior outcomes compared with other high-risk patients (5-year FFBF 94% vs. 74%; FFDM 97% vs. 82%; both p = 0.05), comparable to intermediate-risk disease. On multivariable analysis, Gleason score and clinical T-stage independently predicted poorer outcomes, whereas PSA >20 alone did not. Conclusions: PSA > 20 ng/mL as an isolated high-risk feature is associated with favorable outcomes following definitive RT and appears to be the weakest NCCN high-risk criterion. These findings support refined risk stratification and raise the possibility of treatment de-escalation in select patients. Full article
17 pages, 5014 KB  
Article
Mechanical Properties of Granite Residual Soil Reinforced by Permeable Water-Reactive Polyurethane
by Shuzhong Tan, Jinyong Li, Dingfeng Cao, Tao Xiao and Jiajia Zheng
Polymers 2026, 18(3), 381; https://doi.org/10.3390/polym18030381 - 30 Jan 2026
Abstract
Granite residual soil (GRS) is highly susceptible to water-induced softening, posing significant risks of slope instability and collapse. Conventional impermeable grouting often exacerbates these hazards by blocking groundwater drainage. This study investigates the efficacy of a permeable water-reactive polyurethane (PWPU) in stabilizing GRS, [...] Read more.
Granite residual soil (GRS) is highly susceptible to water-induced softening, posing significant risks of slope instability and collapse. Conventional impermeable grouting often exacerbates these hazards by blocking groundwater drainage. This study investigates the efficacy of a permeable water-reactive polyurethane (PWPU) in stabilizing GRS, aiming to resolve the conflict between mechanical reinforcement and hydraulic conductivity. Uniaxial compression tests were conducted on specimens with varying initial water contents (5%, 10%, and 15%) and PWPU contents (5%, 10%, and 15%). To reveal the multi-scale failure mechanism, synchronous acoustic emission (AE) monitoring and digital image correlation (DIC) were employed, complemented by scanning electron microscopy (SEM) for microstructural characterization. Results indicate that PWPU treatment significantly enhances soil ductility, shifting the failure mode from brittle fracturing to strain-hardening, particularly at higher moisture levels where failure strains exceeded 30%. This enhancement is attributed to the formation of a flexible polymer network that acts as a micro-reinforcement system to restrict particle sliding and dissipate strain energy. An optimal PWPU content of 10% yielded a maximum compressive strength of 4.5 MPa, while failure strain increased linearly with polymer dosage. SEM analysis confirmed the formation of a porous, reticulated polymer network that effectively bonds soil particles while preserving permeability. The synchronous monitoring quantitatively bridged the gap between internal micro-crack evolution and macroscopic strain localization, with AE analysis revealing that tensile cracking accounted for 79.17% to 96.35% of the total failure events. Full article
(This article belongs to the Section Polymer Processing and Engineering)
17 pages, 608 KB  
Article
Comparison Between Alpelisib Plus Endocrine Therapy and Everolimus Plus Endocrine Therapy After CDK4/6 Inhibitors Progression in Patients with PIK3CA-Mutant Metastatic Breast Cancer: A Single-Center Retrospective Study
by Sotiris Loizidis, Damianos Michaelides, Yiola Marcou, Eleni Kakouri, Ifigenia Konstantinou, Anastasia Constantinidou, Stavroula Theophanous-Kitiri, Elisavet Papageorgiou, Kyriaki Michailidou and Myria Galazi
Cancers 2026, 18(3), 468; https://doi.org/10.3390/cancers18030468 - 30 Jan 2026
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Abstract
Background: Evidence on the efficacy of alpelisib in combination with fulvestrant after progression on CKD4/6 inhibitors (CDK4/6i) is derived from a single non-comparative prospective study. Conversely, the effectiveness of everolimus plus exemestane on PIK3CA-mutant metastatic breast cancer (BC) after CDK4/6i failure has [...] Read more.
Background: Evidence on the efficacy of alpelisib in combination with fulvestrant after progression on CKD4/6 inhibitors (CDK4/6i) is derived from a single non-comparative prospective study. Conversely, the effectiveness of everolimus plus exemestane on PIK3CA-mutant metastatic breast cancer (BC) after CDK4/6i failure has never been investigated in a prospective study. In this retrospective study, we compared alpelisib plus endocrine therapy (ET) with everolimus plus exemestane in patients with PIK3CA-mutant metastatic BC post-CDK4/6i progression. Methods: We tracked 40 patients treated with alpelisib plus ET and 22 treated with everolimus plus exemestane. We further identified 42 patients who did not harbor PIK3CA mutations (PIK3CA-wild-type group) and received everolimus as a subsequent treatment after progression on CDK4/6i. The timeframe spanned from 1st March 2020 to 30th November 2024. Results: The median progression-free survival (PFS) for the alpelisib group was 4.9 months compared to 4.5 months for the everolimus group [Hazard ratio (HR), 1.22; 95% CI, 0.65–2.28; p-value = 0.53]. The median overall survival (OS) was 9.6 months and 18.3 months for alpelisib and everolimus, respectively (HR, 0.67; 95% CI, 0.25–1.76; p-value = 0.47). Median PFS in the PIK3CA-mutant everolimus plus ET group was 4.5 months (95% CI, 2.8–6.7) compared to 5 months (95% CI, 3.5–6.9) for the PIK3CA-wild-type everolimus plus ET group (HR, 0.77; 95% CI, 0.46–1.29; p-value = 0.32). The most common side effects in the alpelisib group were hyperglycemia (57.5%), rash (27.5%), and anorexia (22.5%), while the most common side effects in the everolimus group were fatigue (40.9%) and stomatitis (27.3%). Conclusion: Our results regarding the efficacy of alpelisib plus ET were inferior to those reported in the current literature. Conversely, outcomes of everolimus plus exemestane were consistent with the current literature, denoting that the combination is an acceptable treatment option for patients with PIK3CA-mutant metastatic BC. Full article
(This article belongs to the Section Cancer Drug Development)
25 pages, 9313 KB  
Article
Effect of Salt Frost Cycles on the Normal Bond Behavior of the CFRP–Concrete Interface
by Hao Cheng, Yushi Yin, Tian Su and Dongjun Chen
Buildings 2026, 16(3), 586; https://doi.org/10.3390/buildings16030586 - 30 Jan 2026
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Abstract
The durability of the carbon fiber-reinforced polymer (CFRP)–concrete interface is a critical indicator for assessing the service life of composite structures in cold regions. This study systematically investigates the normal bond behavior under coupled deicing salt and freeze–thaw cycles through single-sided salt-frost tests [...] Read more.
The durability of the carbon fiber-reinforced polymer (CFRP)–concrete interface is a critical indicator for assessing the service life of composite structures in cold regions. This study systematically investigates the normal bond behavior under coupled deicing salt and freeze–thaw cycles through single-sided salt-frost tests on 126 specimens. The influence of surface roughness, number of freeze–thaw cycles, concrete strength grade, and CFRP material type was systematically evaluated. The results demonstrate that bond behavior is positively correlated with surface roughness, with the f2 interface exhibiting optimal performance and increasing the ultimate capacity by up to 76.61% compared to the smooth interface. CFRP cloth showed superior bond retention compared to CFRP plates, which experienced a bond strength loss rate up to 26.90% higher than cloth specimens after six cycles. A critical performance threshold was identified between six and eight cycles, where the failure mode transitioned from cohesive adhesive failure to brittle interfacial debonding. Concrete matrix strength had a negligible effect compared to the dominant environmental damage. A two-parameter prediction model based on cycle count and roughness was established with high accuracy. SEM analysis confirmed that epoxy resin cracking, fiber–matrix debonding, and microcrack propagation in the concrete surface layer were the fundamental causes of macroscopic mechanical degradation. These findings provide a theoretical foundation for optimizing interface treatment and predicting the structural integrity of CFRP-strengthened systems in salt-frost regions. Full article
(This article belongs to the Special Issue Advanced Studies in Structure Materials—2nd Edition)
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17 pages, 3381 KB  
Article
Trace Element Supplementation Enables Sustainable High-Straw Dry Anaerobic Digestion by Suppressing Acidification and Boosting Biogas via Microbial Network Rewiring
by Wenguang Liang, Gang Li, Yigao Dai, Hanbao Zhou, Yeyu Wang, Yingcai Han, Yiheng Qi, Dongmei Wang, Keyang Jiang and Qiuheng Zhu
Sustainability 2026, 18(3), 1395; https://doi.org/10.3390/su18031395 - 30 Jan 2026
Viewed by 49
Abstract
The global output of organic solid residues (e.g., crop straw) is substantial, creating an urgent sustainability need for low-impact pathways that avoid open burning or disposal while recovering renewable energy. Dry anaerobic digestion (AD) offers a water-saving, high-solids valorization route for straw-rich substrates, [...] Read more.
The global output of organic solid residues (e.g., crop straw) is substantial, creating an urgent sustainability need for low-impact pathways that avoid open burning or disposal while recovering renewable energy. Dry anaerobic digestion (AD) offers a water-saving, high-solids valorization route for straw-rich substrates, but its deployment is often constrained by acidification that suppresses methanogenesis, reducing reliability and limiting practical adoption. Here, at laboratory scale, we formulated a co-digestion substrate dominated by wheat straw (50%) with swine manure and household organic waste, and evaluated whether co-supplementation of trace metals (Fe, Ni, Co) can enhance process stability and energy recovery, thereby strengthening the sustainability of high-solids straw treatment. System performance was assessed by pH, biogas production, volatile fatty acids (VFAs), functional genes, and microbial community profiles to elucidate micronutrient effects and microbial responses. Micronutrient addition stabilized pH (minimum 6.5) and enhanced biogas output. Specific yields in the supplemented digester were 260.64 ± 11.83 mL g−1 TS and 319.89 ± 14.27 mL g−1 VS, compared with 220.31 ± 9.45 mL g−1 TS and 270.33 ± 11.72 mL g−1 VS in the control; cumulative gas production was higher by 18.33%. Community analyses showed marked enrichment of Methanosarcina, increasing from 7.28% on day 10 to 44.00% on day 30. Molecular ecological network analysis indicated a transition from a sparse, fragmented configuration to a highly connected, centralized one: the number of nodes decreased from 74 to 70; the number of edges increased from 46 to 223 (a 4.85-fold rise); network density increased from 0.0170 to 0.0923; mean degree increased from 1.24 to 6.37; the number of modules declined from 39 to 5; and the proportion of positive versus negative links shifted from 85%/15% to 70%/30%, evidencing stronger interspecies coupling and functional robustness. Consistently, methyl-coenzyme reductase subunit A gene copy numbers were about 1.60-fold higher on day 30 and about 1.51-fold higher on day 50 than in the control. Overall, Fe-Ni-Co co-supplementation enhances methane potential and suppresses acidification in straw-rich dry anaerobic digestion, providing a low-input and practical strategy to stabilize high-solids systems. By improving microbial robustness, this approach enables efficient renewable energy recovery with reduced water demand and lower risk of process failure, thereby supporting scalable straw valorization and advancing circular bioeconomy pathways for agricultural and organic solid residues. Full article
(This article belongs to the Special Issue Solid Waste Management and Sustainable Environmental Remediation)
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9 pages, 379 KB  
Review
Cardiac Rehabilitation After Left Ventricular Assist Device Implantation: A Narrative Review
by Rita Gravino, Luigi Falco, Dario Catapano, Cristiano Amarelli, Fabio Valente, Marina Verrengia, Claudio Marra, Emilio Di Lorenzo, Pierino Di Silverio, Michelle Kittleson and Daniele Masarone
J. Clin. Med. 2026, 15(3), 1089; https://doi.org/10.3390/jcm15031089 - 30 Jan 2026
Viewed by 46
Abstract
Over the past decade, given safety, reduced heart failure-related hospitalizations, and, above all, 5-year mortality rates nearly identical to those of heart transplants, left ventricular assist devices (LVADs) have increasingly become a treatment option for patients with advanced heart failure. However, improvements in [...] Read more.
Over the past decade, given safety, reduced heart failure-related hospitalizations, and, above all, 5-year mortality rates nearly identical to those of heart transplants, left ventricular assist devices (LVADs) have increasingly become a treatment option for patients with advanced heart failure. However, improvements in functional capacity after LVAD implantation are minimal or modest, depending on pre-implantation right ventricular function, the patient’s hemodynamic status, the optimization of guideline-directed medical therapy, and noncardiac factors (physical deconditioning, skeletal muscle alterations, anemia, and alterations in alveolar gas exchange). Therefore, cardiac rehabilitation (CR) is a fundamental element from the early stages after LVAD implantation, as it is not only safe but also highly effective, leading to improved functional capacity and fewer episodes of worsening heart failure, and may be associated with reduced mortality. To perform safe and effective CR in patients with LVADs, it is crucial to account for the unique issues in this group. This includes the difficulty of detecting an arterial pulse with standard tools during CPR and the importance of closely monitoring the transmission line and LVAD controller to prevent unintended damage. Overall, the clinical trial indicates that exercise-based CR has the potential to improve functional capacity. Furthermore, some data suggest that CR is associated with fewer HF-related hospitalizations and may be linked to lower mortality; however, there is no consensus on this matter, partly because most studies supporting this assertion are observational. Full article
(This article belongs to the Special Issue New Clinical Perception of Cardiac Rehabilitation)
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17 pages, 886 KB  
Systematic Review
Systematic Review of the Application of Pulmonary Hypertension Treatments in Ventricular Septal Defect, Pulmonary Atresia, and Major Aortopulmonary Collateral Arteries
by Keiichi Hirono, Keiko Uchida, Taku Ishii, Hidekazu Ishida, Shinichi Takatsuki, Hiroyuki Fukushima, Kei Inai, Susumu Hosokawa, Reina Ishizaki, Hirofumi Sawada, Naofumi F. Sumitomo, Ayako Chida-Nagai, Yuichi Ishikawa, Hirohiko Motoki, Atsushi Yao, Shigetoyo Kogaki, Hiroyuki Yamagishi and Shozaburo Doi
J. Clin. Med. 2026, 15(3), 1087; https://doi.org/10.3390/jcm15031087 - 30 Jan 2026
Viewed by 50
Abstract
Background: Pulmonary atresia (PA) with ventricular septal defect (VSD) and major aortopulmonary collateral arteries (MAPCAs), a life-threatening congenital heart defect (CHD), is frequently associated with abnormal pulmonary blood flow and vascular remodeling, causing hypoxia and heart failure. Segmental pulmonary hypertension (PH), a distinct [...] Read more.
Background: Pulmonary atresia (PA) with ventricular septal defect (VSD) and major aortopulmonary collateral arteries (MAPCAs), a life-threatening congenital heart defect (CHD), is frequently associated with abnormal pulmonary blood flow and vascular remodeling, causing hypoxia and heart failure. Segmental pulmonary hypertension (PH), a distinct PH type, may exist in some patients. Pulmonary vasodilators have been considered for treatment; however, evidence of their efficacy and safety remains lacking. Methods: A systematic review was conducted using PubMed, MEDLINE, The Cochrane Library, and Ichushi Web, encompassing studies from inception to May 2023. Inclusion criteria focused on patients with PA/VSD/MAPCAs treated with PH medications. Results: Of 86 studies screened, 6 met the inclusion criteria, including 1 cohort study and 5 case reports, comprising 22 patients. The most frequently administered medications were sildenafil (14 cases) and bosentan (12 cases), with 16 patients receiving monotherapy. Clinical improvements were observed in pulmonary vascular resistance (8/8 patients), oxygen saturation (8/19 patients), and symptoms (19/21 patients). Adverse effects were noted in five patients, including treatment discontinuation in two. Conclusions: PH medications may benefit some patients with PA/VSD/MAPCAs; however, the extremely limited sample size (n = 22) and substantial heterogeneity in anatomy, age, surgical status, and treatment regimens severely limit interpretability and clinical applicability. Considering the potential benefits and risks associated with these medications, their use should be considered cautiously and restricted to specialized centers with expertise in CHD and PH management. Full article
(This article belongs to the Section Cardiology)
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