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16 pages, 769 KiB  
Article
[177Lu]Lu-PSMA-617 in Patients with Progressive PSMA+ mCRPC Treated With or Without Prior Taxane-Based Chemotherapy: A Phase 2, Open-Label, Single-Arm Trial in Japan
by Kouji Izumi, Ryuji Matsumoto, Yusuke Ito, Seiji Hoshi, Nobuaki Matsubara, Toshinari Yamasaki, Takashi Mizowaki, Atsushi Komaru, Satoshi Nomura, Toru Hattori, Hiroya Kambara, Shaheen Alanee, Makoto Hosono and Seigo Kinuya
Cancers 2025, 17(14), 2351; https://doi.org/10.3390/cancers17142351 - 15 Jul 2025
Viewed by 559
Abstract
Background: This Phase 2 trial evaluated the efficacy, tolerability, and safety of [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) in patients with ≥1 measurable lesion and progressive prostate-specific membrane antigen-positive (PSMA+) metastatic castration-resistant prostate cancer (mCRPC) in Japan. Methods: This study comprises four parts; [...] Read more.
Background: This Phase 2 trial evaluated the efficacy, tolerability, and safety of [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) in patients with ≥1 measurable lesion and progressive prostate-specific membrane antigen-positive (PSMA+) metastatic castration-resistant prostate cancer (mCRPC) in Japan. Methods: This study comprises four parts; data from three parts are presented here. Part 1 evaluated safety and tolerability; Parts 2 (post-taxane) and 3 (pre-taxane/taxane-naive) assessed the overall response rate (ORR; primary endpoint), overall survival (OS), radiographic progression-free survival (rPFS), disease control rate (DCR), PFS, and safety; and Part 4 is the expansion part. Patients received 7.4 GBq (±10%) 177Lu-PSMA-617 Q6W for up to six cycles. Results: Of the 35 patients who underwent a [68Ga]Ga-PSMA-11 (68Ga-PSMA-11) PET/CT scan, 30 received 177Lu-PSMA-617 (post-taxane, n = 12; pre-taxane, n = 18). No dose-limiting toxicity was noted in Part 1 (n = 3). Post- and pre-taxane patients had a median of three and five cycles, respectively. The primary endpoint, ORR, met the pre-specified threshold, with the lower limit of the 90% confidence interval (CI) above the threshold of 5% for post-taxane and 12% for pre-taxane. Post- and pre-taxane patients had an ORR of 25.0% (90% CI: 7.2–52.7) and 33.3% (90% CI: 15.6–55.4), respectively. In post- and pre-taxane patients, the DCR was 91.7% and 83.3%, the median rPFS was 3.71 and 12.25 months, and the median PFS was 3.71 and 5.59 months, respectively. The median OS was 14.42 and 12.94 months in post- and pre-taxane patients, respectively. The most common adverse events were constipation, decreased appetite, decreased platelet count, anemia, and nausea. Conclusions: The primary endpoint (ORR) was met. The safety profile of 177Lu-PSMA-617 was consistent with the VISION and PSMAfore studies, with no new safety signals in the Japanese patients with mCRPC. Full article
(This article belongs to the Section Cancer Therapy)
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14 pages, 857 KiB  
Article
Short-Term Intake of Euphorbia tirucalli Latex Modifies Kidney Function in Rats: Possible Role of Oxidative Stress and Inflammatory Response
by Edgar Hell Kampke, Maria Eduarda Souza Barroso, Leonardo da Silva Escouto, Luciana Polaco Covre, Ágata Lages Gava, Bianca Prandi Campagnaro, Ricardo Machado Kuster and Silvana Santos Meyrelles
Antioxidants 2025, 14(7), 856; https://doi.org/10.3390/antiox14070856 - 13 Jul 2025
Viewed by 407
Abstract
Medicinal plants have been traditionally used for generations, often without scientific validation. Euphorbia tirucalli (E. tirucalli), a plant native to Africa, is commonly employed in folk medicine for treating various ailments, including cancer. However, most studies involving this species are limited [...] Read more.
Medicinal plants have been traditionally used for generations, often without scientific validation. Euphorbia tirucalli (E. tirucalli), a plant native to Africa, is commonly employed in folk medicine for treating various ailments, including cancer. However, most studies involving this species are limited to in vitro models, and its systemic effects remain poorly understood. This study aimed to evaluate the impact of E. tirucalli latex on renal function in healthy Wistar rats. Animals were divided into two groups: a control group receiving water and a treated group receiving E. tirucalli latex (13.47 mg/kg) by gavage for 15 days. Renal function was assessed by measuring glomerular filtration rate (GFR), renal plasma flow (RPF), renal blood flow (RBF), renal vascular resistance (RVR), and mean arterial pressure (MAP). Additionally, oxidative stress markers, reactive oxygen/nitrogen species, and inflammatory activity were analyzed in renal tissue. E. tirucalli significantly reduced GFR, RPF, and RBF, while increasing RVR and MAP. Renal tissue exhibited elevated levels of advanced oxidation protein products, myeloperoxidase, nitric oxide, and peroxynitrite/hydroxyl radicals. These findings indicate that E. tirucalli latex adversely affects renal hemodynamics and promotes oxidative and inflammatory damage, suggesting potential nephrotoxic effects, even in healthy subjects. Full article
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19 pages, 1875 KiB  
Systematic Review
PARP Inhibitors for Metastatic CRPC: More Answers than Questions, a Systematic Review and Meta-Analysis
by Ray Manneh, Javier Molina-Cerrillo, Guillermo de Velasco, Linda Ibatá, Susan Martínez, Álvaro Ruiz-Granados and Teresa Alonso-Gordoa
Pharmaceuticals 2025, 18(7), 1015; https://doi.org/10.3390/ph18071015 - 8 Jul 2025
Viewed by 457
Abstract
PARP inhibitors (PARPi), alone or in combination with androgen receptor signaling inhibitors (ARSi), have shown clinical benefit in metastatic castration-resistant prostate cancer (mCRPC), particularly in tumors with homologous recombination repair (HRR) gene alterations. Recent data from the TALAPRO-2 trial complete the current evidence [...] Read more.
PARP inhibitors (PARPi), alone or in combination with androgen receptor signaling inhibitors (ARSi), have shown clinical benefit in metastatic castration-resistant prostate cancer (mCRPC), particularly in tumors with homologous recombination repair (HRR) gene alterations. Recent data from the TALAPRO-2 trial complete the current evidence on PARPi–ARSi combination strategies in this setting. Background/Objectives: To evaluate the efficacy and safety of PARPi-based therapies—monotherapy and combination with ARSi—in patients with mCRPC, focusing on molecular subgroups defined by DNA repair alterations. Methods: We conducted a systematic review and meta-analysis of phase III randomized controlled trials (RCTs) assessing PARPi as monotherapy or in combination with ARSi. Searches were performed in PubMed, EMBASE, the Cochrane Library, and oncology conference proceedings up to February 2025. Outcomes included radiographic progression-free survival (rPFS), overall survival (OS), second progression-free survival (PFS2), and grade ≥3 adverse events (AEs). Data were pooled using a random-effects model, with subgroup analyses by DNA repair status. Results: Five RCTs (n = 2921) were I confirmincluded: three on combination therapy (n = 2271) and two on monotherapy (n = 650). Combination therapy improved rPFS in the ITT (HR = 0.64; 95% CI: 0.56–0.74), HRRm (HR = 0.55; 95% CI: 0.44–0.68), and BRCAm (HR = 0.33; 95% CI: 0.18–0.58) subgroups. OS was also improved in the ITT (HR = 0.80; 95% CI: 0.70–0.92), HRRm (HR = 0.68; 95% CI: 0.55–0.83), and BRCAm (HR = 0.54; 95% CI: 0.34–0.85) groups. No benefit was observed in non-HRRm patients. PFS2 favored combination therapy (HR = 0.77; 95% CI: 0.64–0.91). Grade ≥3 AEs were more frequent (RR = 1.44; 95% CI: 1.20–1.73). Monotherapy improved rPFS in ITT (HR = 0.46; 95% CI: 0.20–0.81) and BRCAm (HR = 0.33; 95% CI: 0.15–0.75); OS benefit was seen only in BRCAm (HR = 0.73; 95% CI: 0.57–0.95). Conclusions: PARPi therapies improve outcomes mainly in HRR- and BRCA-mutated mCRPC. Molecular selection is key to optimizing benefit and minimizing toxicity. Further research on the activity of PARPi combinations in non-HRR mutated mCRPC is needed to better understand the underlying mechanisms of efficacy. Full article
(This article belongs to the Special Issue Advances in Prostate Cancer Therapeutics)
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16 pages, 1541 KiB  
Systematic Review
Is [177Lu]Lu-PSMA-617 Redefining Value in mCRPC Care? A Meta-Analysis of Clinical and Economic Endpoints
by Francesco Fiorica, Maria Viviana Candela, Teodoro Sava, Matteo Salgarello, Jacopo Giuliani, Singh Navdeep, Antonella Franceschetto, Daniela Grigolato, Emilia Durante, Erica Palesandro, Enrico Altiero Giusto, Consuelo Buttigliero and Marcello Tucci
Cancers 2025, 17(13), 2247; https://doi.org/10.3390/cancers17132247 - 4 Jul 2025
Viewed by 959
Abstract
Background: Radioligand therapy with [177Lu]Lu-PSMA-617 represents an emerging treatment for metastatic castration-resistant prostate cancer (mCRPC). Its clinical positioning relative to standard therapies remains under discussion. Objective: To compare overall survival (OS), radiographic progression-free survival (rPFS), PSA response, and treatment burden across [...] Read more.
Background: Radioligand therapy with [177Lu]Lu-PSMA-617 represents an emerging treatment for metastatic castration-resistant prostate cancer (mCRPC). Its clinical positioning relative to standard therapies remains under discussion. Objective: To compare overall survival (OS), radiographic progression-free survival (rPFS), PSA response, and treatment burden across randomised trials evaluating [177Lu]Lu-PSMA-617 versus androgen receptor pathway inhibitors (ARTA), Cabazitaxel, or standard of care (SOC). Evidence Acquisition: We conducted a meta-analysis of five randomised controlled trials, including 2073 patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). We assessed survival endpoints, baseline comparability, and treatment intensity. Evidence Synthesis: [177Lu]Lu-PSMA-617 significantly improved rPFS and PSA response. While modest overall, the OS benefit was more pronounced in taxane-naïve populations. Compared with Cabazitaxel, [177Lu]Lu-PSMA-617 was associated with similar or better survival despite shorter treatment duration and potentially lower cumulative toxicity and cost. Economic modelling suggests it could offer a more sustainable therapeutic option under typical willingness-to-pay thresholds. Conclusions: [177Lu]Lu-PSMA-617 shows clinical effectiveness and economic value in mCRPC, with potential advantages over Cabazitaxel and ARTA. Its use could be prioritised in early treatment lines. Patient Summary: This study suggests that PSMA-targeted radioligand therapy is at least as effective as other treatments for advanced prostate cancer, with potential benefits in terms of toxicity, duration, and overall cost. Full article
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15 pages, 1547 KiB  
Article
Screening and Validation of Reference Genes for Normalization of qRT-PCR in Rice BLB Pathogen Xanthomonas oryzae pv. oryzae Under Tetramycin Stress
by Feiyan Fang, Xinli Miao, Tong Mou, Zian Wang, Yanhe Guo, Yingfen Yang, Shunyu Gao, Zhenji Wang, Chengdong Xu and Jun Yang
Genes 2025, 16(7), 788; https://doi.org/10.3390/genes16070788 - 30 Jun 2025
Viewed by 479
Abstract
Background: Xanthomonas oryzae pv. oryzae (Xoo) causes rice leaf blight (BLB) and poses a major threat to global rice production. In rice production, tetramycin agents provide good control of rice leaf blight, while the standardization of the reference genes of Xoo [...] Read more.
Background: Xanthomonas oryzae pv. oryzae (Xoo) causes rice leaf blight (BLB) and poses a major threat to global rice production. In rice production, tetramycin agents provide good control of rice leaf blight, while the standardization of the reference genes of Xoo under tetramycin stress has not been reported. The aim of this study was to identify the most stable reference genes for quantitative PCR analysis of Xoo under tetramycin stress. Methods: Six candidate reference genes, gyrB (RNA polymerase β gene), GADPH (glyceraldehyde-3-phosphate dehydrogenase gene), recA (recombinase A gene), gyrA (citrate synthase encoding gene), dnaK (molecular chaperone protein gene), and 16S rRNA (16S ribosomal RNA gene) were selected and their expression stability was assessed under tetramycin stress conditions using real-time quantitative PCR (qRT-PCR). GeNorm, NormFinder, BestKeeper and RefFinder were used to assess the expression stability, the relative expression values of the eight genes involved QS (Quorum sensing) pathway under tetramycin stress were used to validate by the rpf (regulation of pathogenic factors) gene family. Results: 16S rRNA expression was most stable under tetracycline stress, whereas GADPH was the least. The rpf gene family showed a highly stable expression level, confirming the reliability of 16S r RNA as a reference gene in the study of Xoo under tetramycin stress. Conclusions: 16S rRNA was identified as the best reference gene for Xoo gene expression analysis under tetramycin stress. It provides a reliable support for the molecular research on the control strategy of rice BLB. Full article
(This article belongs to the Section Genes & Environments)
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12 pages, 810 KiB  
Article
Stereotactic Salvage Radiotherapy for Macroscopic Prostate Bed Recurrence After Prostatectomy: STARR (NCT05455736): An Early Analysis from the STARR Trial
by Niccolo’ Bertini, Giulio Francolini, Vanessa Di Cataldo, Pietro Garlatti, Michele Aquilano, Giulio Frosini, Olga Ruggieri, Laura Masi, Raffaela Doro, Mauro Loi, Pierluigi Bonomo, Daniela Greto, Isacco Desideri, Gabriele Simontacchi, Icro Meattini, Riccardo Campi, Lorenzo Masieri and Lorenzo Livi
Cancers 2025, 17(13), 2092; https://doi.org/10.3390/cancers17132092 - 23 Jun 2025
Viewed by 398
Abstract
Purpose/Objectives: Salvage radiotherapy (SRT) after a radical prostatectomy is a curative approach for patients with biochemical recurrence (BR). However, outcomes are often less favorable when imaging reveals macroscopic local recurrence. In such cases, dose escalation through stereotactic salvage radiotherapy (SSRT) may offer improved [...] Read more.
Purpose/Objectives: Salvage radiotherapy (SRT) after a radical prostatectomy is a curative approach for patients with biochemical recurrence (BR). However, outcomes are often less favorable when imaging reveals macroscopic local recurrence. In such cases, dose escalation through stereotactic salvage radiotherapy (SSRT) may offer improved disease control. The STARR trial (NCT05455736) is a prospective, multicenter study evaluating the efficacy and safety of SSRT in patients with macroscopic prostate bed recurrence. This interim analysis reports early findings from the initial patient cohort. Materials and Methods: Patients with BR (PSA > 0.2 ng/mL) post-prostatectomy and PET-confirmed macroscopic recurrence (PSMA or Choline PET, confirmed by MRI) were eligible. Treatment involved CyberKnife®-based SSRT delivering 35 Gy in five fractions to the visible lesion. Androgen deprivation therapy (ADT) was not permitted. Complete biochemical response (CBR) was defined as PSA < 0.2 ng/mL, and biochemical response (BR) as a ≥50% PSA reduction. Additional outcomes included biochemical, radiological, and ADT-free survival (bPFS, rPFS, aPFS). Results: As of analysis, 51 patients were enrolled, with a median follow-up of 16 months (95% CI: 16–22). CBR and BR were achieved in 45.1% and 80.4% of patients, respectively. Events affecting bPFS, rPFS, and aPFS occurred in 12, 5, and 6 patients, with median values not yet reached. Toxicity was minimal, with two cases each of acute grade 2 GI and GU events, and one late grade 2 GI event. No grade ≥ 3 toxicities were reported. Conclusion: Early data support SSRT as a safe and a promising option for macroscopic local recurrence, with encouraging response rates and minimal toxicity. Full article
(This article belongs to the Special Issue The Role of Robot‐Assisted Radical Prostatectomy in Prostate Cancer)
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14 pages, 1816 KiB  
Article
Prognostic Nutritional Index and a Blood-Based Prognostic Tool in Prostate Cancer Treated with Abiraterone, Enzalutamide or Cabazitaxel
by Hakan Taban, Mustafa Erman, Deniz Can Guven, Burak Yasin Aktas, Feride Yilmaz, Serkan Yaşar, Hasan Cagri Yildirim, Ferit Aslan and Sercan Aksoy
Medicina 2025, 61(6), 1105; https://doi.org/10.3390/medicina61061105 - 18 Jun 2025
Viewed by 492
Abstract
Background and Objectives: The prognostic nutritional index (PNI), a marker reflecting both nutritional and immune status, has been associated with prognosis in various malignancies. However, evidence in metastatic castration-resistant prostate cancer (mCRPC), particularly from non-Asian populations, remains limited. This study aimed to [...] Read more.
Background and Objectives: The prognostic nutritional index (PNI), a marker reflecting both nutritional and immune status, has been associated with prognosis in various malignancies. However, evidence in metastatic castration-resistant prostate cancer (mCRPC), particularly from non-Asian populations, remains limited. This study aimed to evaluate the prognostic value of baseline PNI and to develop a blood-based prognostic model in mCRPC patients treated with abiraterone acetate (AA), enzalutamide (ENZA), or cabazitaxel (CABA). Materials and Methods: This retrospective study included mCRPC patients treated with AA, ENZA, or CABA before or after docetaxel. PNI was calculated as: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm3). Patients were classified into low-PNI (≤40.8) and high-PNI (>40.8) groups using the median PNI value. Survival outcomes were analyzed using Kaplan–Meier and Cox regression methods. Results: A total of 299 patients were analyzed: 133 (44.5%) received AA, 106 (35.5%) ENZA, and 60 (20.0%) CABA. Patients with high PNI had significantly longer median overall survival (OS; 30.2 vs. 12.6 months, p < 0.001), radiologic progression-free survival (rPFS; 13.5 vs. 6.7 months, p < 0.001), and PSA progression-free survival (PSA-PFS; 10.2 vs. 5.1 months, p < 0.001). These associations remained significant across all treatment subgroups. In multivariate analysis, prostate surgery (HR: 0.6), high PNI (HR: 0.5), PSA response (HR: 0.5), and elevated ALP (HR: 1.6) were independent predictors of OS. A prognostic model incorporating PNI, alkaline phosphatase, and anemia stratified patients into four risk groups with distinct OS: 49.1, 30.8, 18.8, and 9.1 months, respectively. Conclusions: This is the largest study to date in a non-Asian mCRPC population showing that baseline PNI is a strong, independent prognostic factor for survival. The proposed blood-based tool may aid in clinical risk stratification, pending prospective validation. Full article
(This article belongs to the Section Oncology)
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16 pages, 3188 KiB  
Article
Sex Expression and Seed Yield Stability in Thai Hemp (Cannabis sativa L.): Seasonal Effects on Dioecious Cultivars for Optimized Seed Production
by Pheeraphan Thongplew, Jakkrapong Kangsopa, Sutheera Hermhuk, Krittiya Tongkoom, Prakash Bhuyar and Nednapa Insalud
Int. J. Plant Biol. 2025, 16(2), 67; https://doi.org/10.3390/ijpb16020067 - 13 Jun 2025
Viewed by 1003
Abstract
This study investigates the environmental regulation of sex expression and seed yield stability in four Thai dioecious hemp (Cannabis sativa L.) cultivars (RPF1, RPF2, RPF3, and RPF4) under different seasonal conditions to optimize seed production. The experiment was conducted across two planting [...] Read more.
This study investigates the environmental regulation of sex expression and seed yield stability in four Thai dioecious hemp (Cannabis sativa L.) cultivars (RPF1, RPF2, RPF3, and RPF4) under different seasonal conditions to optimize seed production. The experiment was conducted across two planting periods (in-season and off-season) to evaluate the effects of varying day lengths and temperatures on growth, reproductive development, and yield. The results showed that shorter day lengths and lower temperatures during the off-season led to an increased proportion of female plants across all cultivars, except RPF3, which exhibited a stable female-to-male ratio. RPF4 had the highest increase in female plants (16%), followed by RPF1 and RPF2 (10%). Seed yield was significantly influenced by seasonal changes, with RPF3 and RPF4 consistently outperforming the other cultivars. In the in-season, RPF3 and RPF4 produced the highest seed yields, reaching 83.4 g/plant and 81.6 g/plant, respectively. During the off-season, both cultivars experienced a decline in seed yield (by 24–26%), primarily due to a reduction in seed production in secondary inflorescences. However, RPF3 compensated for this loss with a 31% increase in seed production at main inflorescences, ensuring yield stability. RPF4 maintained its high yield potential by increasing the proportion of female plants, offsetting the decline in seed yield per plant. Additionally, cumulative growing degree days (CGDD) at harvest were comparable between seasons, with values of 2434 °Cd (in-season) and 2502 °Cd (off-season), indicating that temperature accumulation remained within an optimal range for seed maturation. The study highlights the importance of cultivar selection based on yield component stability and adaptability to seasonal variations. These findings provide valuable insights for improving hemp seed production strategies in Thailand’s diverse agro-climatic conditions. Full article
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12 pages, 251 KiB  
Article
Rumen-Protected Fat and Rumen-Protected Choline Co-Supplementation: Impacts on Performance and Meat Quality of Growing Lambs
by Haitao Liu, Fadi Li, Fei Li, Zhiyuan Ma, Tao Wang, Qinwu Li, Xinji Wang and Kaidong Li
Vet. Sci. 2025, 12(6), 525; https://doi.org/10.3390/vetsci12060525 - 28 May 2025
Viewed by 474
Abstract
This study aimed to assess the effect of co-supplementing rumen-protected fat and rumen-protected choline on growth performance, carcass traits, and meat quality in lambs. Using a randomized experimental design, 45 weaned female Tian×Hu crossbred lambs (3 months old; average body weight: 27.34 ± [...] Read more.
This study aimed to assess the effect of co-supplementing rumen-protected fat and rumen-protected choline on growth performance, carcass traits, and meat quality in lambs. Using a randomized experimental design, 45 weaned female Tian×Hu crossbred lambs (3 months old; average body weight: 27.34 ± 0.57 kg, mean ± SD) were randomly allocated to one of three dietary treatment groups. The three dietary treatments were as follows: a basal diet group (CON), a group receiving 2% rumen-protected fat in place of 2% barley (RPF), and a group supplemented with 2% rumen-protected fat and 0.4% rumen-protected choline, replacing 2% barley and 0.4% corn germ in the basal diet (RPFC). Compared to the CON group, neither the RPF nor RPFC treatments resulted in significant differences in growth performance (p > 0.05). However, the RPFC group showed a 5.3% increase in dry matter intake (DMI) compared to the RPF group (p < 0.05). Compared with the CON, the RPF treatment increased 69.23% the relative abundance of C18:2n-6t (p < 0.05), but the content of C17:0, C17:1, C18:1n-9c, and iso-C18:0 in Longissimus lumborum was decreased by 16.49%, 15.78%, 6.45% and 27.78%, respectively (p < 0.05). The RPFC treatment increased the relative abundance of C16:1 in Longissimus lumborum (p < 0.05). The RPF and RPFC treatments significantly increased serum levels of high-density lipoprotein (HDL) and total cholesterol compared to the CON group (p < 0.05). The RPF treatment raised HDL by 50.00% and total cholesterol by 38.03%, while the RPFC treatment increased HDL by 39.47% and total cholesterol by 26.03%. Furthermore, compared to the RPF group, the RPFC treatment led to a 13.47% increase in the 45 min b* color value of the Longissimus lumborum (p < 0.01) and a significant 45.45% reduction in the relative abundance of C18:2n-6t fatty acid in the same muscle (p < 0.05). In summary, rumen-protected choline reduces the negative effects of rumen-protected fat on feed intake in lambs and changes fatty acid profile in meat. Full article
15 pages, 1467 KiB  
Article
Prediction of Corroded Pipeline Failure Pressure Based on Empirical Knowledge and Machine Learning
by Hongbo Liu and Xiangzhao Meng
Appl. Sci. 2025, 15(10), 5787; https://doi.org/10.3390/app15105787 - 21 May 2025
Viewed by 444
Abstract
This paper presents a novel approach for predicting the failure pressure of corroded pipelines by integrating empirical formulas into the loss function of a neural network-based prediction model. Traditional empirical formulas, such as ASME-B31G, DNV RP-F101, and PCORRC, have been widely used for [...] Read more.
This paper presents a novel approach for predicting the failure pressure of corroded pipelines by integrating empirical formulas into the loss function of a neural network-based prediction model. Traditional empirical formulas, such as ASME-B31G, DNV RP-F101, and PCORRC, have been widely used for their simplicity but often suffer from significant prediction errors due to the complex interactions between defect parameters and material properties. In contrast, artificial neural networks (ANNs) offer more accurate predictions but require substantial training data. To address these limitations, we propose an integrated loss function that combines the strengths of empirical formulas and the powerful fitting capabilities of ANNs. The proposed loss function incorporates an additional defect factor term predicted by the neural network to compensate for errors caused by varying defect conditions, thereby enhancing the model′s adaptability and accuracy. The model is trained using a diverse dataset of 60 burst test results from various literature sources, covering a wide range of corrosion scenarios. The results demonstrate that the proposed method significantly improves prediction accuracy compared to traditional empirical formulas and ANN models trained with standard loss functions. The proposed approach achieves a mean absolute percentage error (MAPE) of 2.52%, a root mean square error (RMSE) of 0.39 MPa, and a coefficient of determination (R2) of 0.9886 on the validation set. This study highlights the effectiveness of integrating empirical knowledge with data-driven models and provides a robust and accurate solution for predicting the failure pressure of corroded pipelines, contributing to enhanced pipeline integrity assessment and safety management. Full article
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31 pages, 3425 KiB  
Article
RPF-MAD: A Robust Pre-Training–Fine-Tuning Algorithm for Meta-Adversarial Defense on the Traffic Sign Classification System of Autonomous Driving
by Xiaoxu Peng, Dong Zhou, Jianwen Zhang, Jiaqi Shi and Guanghui Sun
Electronics 2025, 14(10), 2044; https://doi.org/10.3390/electronics14102044 - 17 May 2025
Viewed by 593
Abstract
Traffic sign classification (TSC) based on deep neural networks (DNNs) plays a crucial role in the perception subsystem of autonomous driving systems (ADSs). However, studies reveal that the TSC system can make dangerous and potentially fatal errors under adversarial attacks. Existing defense strategies, [...] Read more.
Traffic sign classification (TSC) based on deep neural networks (DNNs) plays a crucial role in the perception subsystem of autonomous driving systems (ADSs). However, studies reveal that the TSC system can make dangerous and potentially fatal errors under adversarial attacks. Existing defense strategies, such as adversarial training (AT), have demonstrated effectiveness but struggle to generalize across diverse attack scenarios. Recent advancements in self-supervised learning (SSL), particularly adversarial contrastive learning (ACL) methods, have demonstrated strong potential in enhancing robustness and generalization compared to AT. However, conventional ACL methods lack mechanisms to ensure effective defense transferability across different learning stages. To address this, we propose a robust pre-training–fine-tuning algorithm for meta-adversarial defense (RPF-MAD), designed to enhance the sustainability of adversarial robustness throughout the learning pipeline. Dual-track meta-adversarial pre-training (Dual-MAP) integrates meta-learning with ACL methods, which improves the generalization ability of the upstream model to different adversarial conditions. Meanwhile, adaptive variance anchoring robust fine-tuning (AVA-RFT) utilizes adaptive prototype variance regularization to stabilize feature representations and reinforce the generalizable defense capabilities of the downstream model. Leveraging the meta-adversarial defense benchmark (MAD) dataset, RPF-MAD ensures comprehensive robustness against multiple attack types. Extensive experiments across eight ACL methods and three robust fine-tuning (RFT) techniques demonstrate that RPF-MAD significantly improves both standard accuracy (SA) by 1.53% and robust accuracy (RA) by 2.64%, effectively enhances the lifelong adversarial resilience of TSC models, achieves a 13.77% improvement in the equilibrium defense success rate (EDSR), and reduces the attack success rate (ASR) by 9.74%, outperforming state-of-the-art (SOTA) defense methods. Full article
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31 pages, 19413 KiB  
Article
Targeted Delivery Inside the Cells Directly Visualized with Förster Resonance Energy Transfer (FRET)
by Igor D. Zlotnikov, Natalya G. Belogurova and Elena V. Kudryashova
Polymers 2025, 17(6), 790; https://doi.org/10.3390/polym17060790 - 16 Mar 2025
Viewed by 727
Abstract
We established a real-time Förster resonance energy transfer (FRET) based assay to evaluate targeted drug delivery using polymeric micelles. Red fluorescent protein (RFP)-expressing E. coli cells were used as a test system to monitor the delivery of drug-fluorophore such as curcumin and umbelliferones [...] Read more.
We established a real-time Förster resonance energy transfer (FRET) based assay to evaluate targeted drug delivery using polymeric micelles. Red fluorescent protein (RFP)-expressing E. coli cells were used as a test system to monitor the delivery of drug-fluorophore such as curcumin and umbelliferones (MUmb and AMC) encapsulated in the polymeric micellar formulations. The efficiency of the drug delivery was quantified using the FRET efficiency, measured as the degree of energy transfer from the drug to the RFP. FRET efficiency directly provides the determination of the delivery efficacy, offering a versatile platform adaptable to various drugs and cell types. We used polymer micelles as a carrier for targeted delivery of fluorescent drugs to bacterial cells expressing RFP. The physicochemical characterization of the interaction between the drugs and the micelles including spectral properties, and the solubility and binding constants, were determined. We revealed a stronger affinity of MUmb for heparin-based micelles (Kd~10−5 M) compared to chitosan-based micelles (Kd~10−4 M), underscoring the influence of polymer composition on drug loading efficiency. For micelles containing MUmb, a FRET efficiency significantly exceeds (by three times) the efficiency for non-micellar MUmb, which have minimal penetration into bacterial cells. The most noticeable effect was observed with the use of the micellar curcumin providing pronounced activation of the RPF fluorescence signal, due to the interaction with curcumins (fluorophore-donor). Curcumin delivery using Chit5-OA micelle resulted in a 115% increase in RFP fluorescence intensity, and Hep-LA showed a significant seven-fold increase. These results highlight the significant effect of micellar composition on the effectiveness of drug delivery. In addition, we have developed a visual platform designed to evaluate the effectiveness of a pharmaceutical product through the visualization of the fluorescence of a bacterial culture on a Petri dish. This method allows us to quickly and accurately assess the penetration of a drug into bacteria, or those located inside other cells, such as macrophages, where the intercellular latent forms of the infection are located. Micellar formulations show enhanced antibacterial activity compared to free drugs, and formulations with Hep-OA micelles demonstrate the most significant reduction in E. coli viability. Synergistic effects were observed when combining curcumin and MUmb with moxifloxacin, resulting in a remarkable 40–50% increase in efficacy. The presented approach, based on the FRET test system with RFP expressed in the bacterial cells, establishes a powerful platform for development and optimizing targeted drug delivery systems. Full article
(This article belongs to the Special Issue Polymer Innovations in Biomedicine)
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22 pages, 3386 KiB  
Article
Evaluation of Residues of Amazonian Fruit Piquia (Caryocar villosum) as Sustainable Ingredient for Sunscreen and Cosmetic Formulations
by Izadora de Souza, Gabriella C. P. Grimmelprez, Klenicy K. L. Yamaguchi, Johannes Schleusener, Silke B. Lohan, Martina C. Meinke and Lorena R. Gaspar
Antioxidants 2025, 14(2), 122; https://doi.org/10.3390/antiox14020122 - 21 Jan 2025
Viewed by 1207
Abstract
Amazonian fruit residues like piquia shells are often discarded despite their antioxidant potential for sustainable cosmetic use. This study evaluated the photostability, phototoxicity, and photoprotection of hydroalcoholic piquia shell extract (PqSE) combined with UV filters in solutions and cosmetic formulations. PqSE formulations were [...] Read more.
Amazonian fruit residues like piquia shells are often discarded despite their antioxidant potential for sustainable cosmetic use. This study evaluated the photostability, phototoxicity, and photoprotection of hydroalcoholic piquia shell extract (PqSE) combined with UV filters in solutions and cosmetic formulations. PqSE formulations were photostable, even stabilizing photounstable UV filters. Phototoxicity tests (OECD TG 432) showed no phototoxic potential (MPE < 0.15) and reduction in the phototoxic potential of UV filters, while ocular irritation potential via HET-CAM assay indicated no irritant effects. The extract combined with UV filters enhanced protection against UVA-induced reactive oxygen species (ROS) production, achieving 60.9% effectiveness, outperforming commercial photostabilizers. Against UVB radiation, it showed cellular viability above 80%, comparable to benzophenone-3. PqSE formulations exhibited a radical protection factor (RPF) nine times higher than controls and reduced radical production by 64% after visible/near-infrared (VIS/NIR) irradiation on porcine skin, compared to 38% for controls. Confocal Raman microspectroscopy showed penetration depths below 12 µm for all time points. This study highlights the potential of reusing fruit residues like PqSE as sustainable, effective ingredients in sunscreen formulations, offering enhanced photoprotection and reduced environmental waste. Full article
(This article belongs to the Section Extraction and Industrial Applications of Antioxidants)
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21 pages, 5282 KiB  
Article
Testing Consistency: Analyzing the Reliability of Two Lower Limb Isometric Force Measurements in Strength-Trained Athletes
by Francisco Giuliano, Marcos A. Soriano, Victor Pino-Mulero and Jaime González-García
Appl. Sci. 2025, 15(1), 303; https://doi.org/10.3390/app15010303 - 31 Dec 2024
Viewed by 1399
Abstract
This study aimed to examine the intra- and inter-session reliability of kinetic variables in the isometric mid-thigh pull (IMTP) and isometric belt squat test (IBSqT) in strength-trained individuals. Fifteen men (26.9 ± 8.9 years; 1.78 ± 0.05 m; 86.9 ± 10.5 kg) and [...] Read more.
This study aimed to examine the intra- and inter-session reliability of kinetic variables in the isometric mid-thigh pull (IMTP) and isometric belt squat test (IBSqT) in strength-trained individuals. Fifteen men (26.9 ± 8.9 years; 1.78 ± 0.05 m; 86.9 ± 10.5 kg) and six women (23.8 ± 4.6 years; 1.66 ± 0.06 m; 65.8 ± 10.3 kg), experienced in strength training, completed a familiarization session followed by two experimental sessions. The peak force (PF) and relative peak force to body weight (RPF), were collected for both isometric tests. Additionally, force (F), impulse (I), and rate of force development (RFD) were analyzed across different time windows (50, 100, 150, 200, and 250 ms). The intraclass correlation coefficient (ICC), coefficient of variation (CV), standard error of measurement (SEM), smallest worthwhile change (SWC) and Bland-Altman plots were calculated and displayed. Intra-session reliability was excellent for PF and RPF (ICC ≥ 0.98, CV ≤ 10%) in both IMTP and IBSqT. However, RFD and IMP displayed higher variability (CV > 10%), with low to good reliability depending on time frames. Inter-session reliability was excellent for PF and RPF (ICC ≥ 0.96, CV ≤ 5.3%) in both tests. Force at various time points exhibited moderate to excellent reliability (ICC = 0.70–0.90). PF and RPF demonstrated the highest sensitivity to performance changes, with SWC0.2 values exceeding SEM. In contrast, RFD and impulse showed larger variabilities. These findings indicate that PF and RPF are the most reliable and sensitive metrics for monitoring performance. Coaches and practitioners can use IMTP and IBSqT to detect meaningful changes in maximal isometric force production. Full article
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12 pages, 813 KiB  
Article
Residue Analysis and Dietary Risk Assessment of 10 Neonicotinoid Insecticides in Oenanthe javanica from Hainan Province of China
by Shusheng Tang, Zikang Zeng, Rui Kang, Ying Wei, Gaohao Tan, Minni Chen, Bin Wang and Zhuhua Tang
Foods 2025, 14(1), 78; https://doi.org/10.3390/foods14010078 - 31 Dec 2024
Cited by 1 | Viewed by 851
Abstract
In this study, residues of 10 neonicotinoid insecticides were tested with 143 fresh samples of Oenanthe javanica using the QuEChERS method combined with UPLC-MS/MS. Based on the residue results, the point estimation method was used to assess dietary risks for adults and children, [...] Read more.
In this study, residues of 10 neonicotinoid insecticides were tested with 143 fresh samples of Oenanthe javanica using the QuEChERS method combined with UPLC-MS/MS. Based on the residue results, the point estimation method was used to assess dietary risks for adults and children, and the cumulative risk was assessed according to the hazard index (HI) and relative potency factor (RPF) methods. The results showed that 71 out of 143 samples of fresh Oenanthe javanica sold in Hainan tested positive for neonicotinoid insecticides, with a detection rate of 49.65%. Six neonicotinoid insecticides were detected and their detection frequencies are as follows: imidacloprid (44.76%), acetamiprid (16.08%), clothianidin (13.29%), dinotefuran (4.90%), thiamethoxam (3.50%) and flonicamid (3.50%). The most frequently co-detected combination was imidacloprid and acetamiprid, with a detection rate of 29.58%. The results of acute and chronic dietary risks showed that all the obtained values of %ADI (acceptable daily intake) and %ARfD (acute reference dose) are far below 100%, so the risks of the six detected neonicotinoid insecticides are acceptable for various population groups. Meanwhile, the results of the cumulative risk showed that all the obtained values of the hazard index and the corrected total exposure concentration are far lower than the health guidelines, indicating that the residue levels of neonicotinoid insecticides in fresh Oenanthe javanica are acceptable. However, it is notable that its acute risk is higher than its chronic risk, and the dietary risk for children is higher than adults. These findings will provide a theoretical basis and objective data for supporting the revision of MRLs for Oenanthe javanica, as well as valuable guidance for the production, consumption, regulation and standardization of Oenanthe javanica sold in Hainan. Full article
(This article belongs to the Section Food Analytical Methods)
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