Search Results (227)

Background: Second-generation androgen receptor signaling inhibitors are one of the main treatment options in metastatic castration-resistant prostate cancer (mCRPC). Nonetheless, a considerable proportion show limited response to treatment, which indicates the need for convenient, easily accessible predictor biomarkers, a role suited for liquid biopsy. Methods: We conducted a PRISMA-compliant systematic review of four databases (Embase, Medline, Scopus, Web of Science) to identify all studies (observational studies and clinical trials) investigating cell-free DNA, circulating tumor cells, exosomes, and circulating RNAs as prognostic markers in metastatic castration-resistant patients starting androgen receptor signaling inhibitors. We excluded studies that evaluated combination therapies, rare histological subtypes or included nonmetastatic or castrate-sensitive disease. We also evaluated whether published papers followed reporting guidelines (REMARK, STROBE, or CONSORT for abstracts). Results: We identified a total of 123 reports, from which we identified only a few well-studied and consistent biomarkers: androgen receptor overexpression/copy number gain and splice variant 7, as well as disease burden markers (circulating tumor DNA fraction and circulating tumor cell concentration). Alterations or copy number loss in tumor suppressors PTEN, RB1, and TP53 were second in terms of quantity and consistency of evidence. However, a large majority of identified biomarkers were relatively understudied or inconsistent. We identified two potential vulnerabilities: inconsistent adherence to reporting guidelines and the under-inclusion of patients of non-Western European ancestry. Conclusions: A large number of biomarkers were linked to worse outcomes in prostate cancer; nonetheless, in most cases, the evidence is limited or inconsistent, or even contradictory. The main exceptions pertain to androgen receptor signaling and disease burden, and, to a smaller extent, to certain tumor suppressor genes. Further studies are needed to confirm their clinical utility, using clear and consistent methodologies and including patients from currently understudied populations. Full article

Worldwide, lung cancer is one of the most common cancers, with non-small cell lung cancer (NSCLC) including up to 80–85% of all lung cancer diagnoses. The landscape of NSCLC is characterized by a heterogeneous spectrum of gene alterations, with tyrosine kinase inhibitors (TKIs) and targeted treatments that significantly improve survival outcomes for patients with oncogene-addicted NSCLC, offering superior efficacy, and often favorable safety and tolerability profiles compared to chemotherapy-based treatments. However, the complexity of NSCLC extends to co-occurring genomic alterations or amplifications in tumor suppressors and other oncogenes, such as TP53, STK11, KEAP1, PIK3CA, RB1, and others, that significantly influence disease progression, therapeutic resistance, and clinical outcomes. These co-mutations often contribute to the development of primary and acquired resistance to targeted therapies, complicating decision-making strategies. This review provides a timely and comprehensive synthesis of current insights into co-mutations in NSCLC, with a particular focus on their clinical implications, and offers a novel perspective by integrating recent molecular insights with therapeutic challenges, addressing existing knowledge gaps through a more integrative and clinically oriented analysis of co-mutations. Advances in next-generation sequencing (NGS) and molecular profiling have enabled the identification of these co-alterations, paving the way for more personalized therapeutic approaches. However, challenges remain in interpreting the functional interplay of co-mutations and translating these insights into effective clinical interventions. This review also highlights the significance of co-mutations in shaping NSCLC biology, and discusses their impact on current therapeutic paradigms, emphasizing the need for integrative biomarker-driven approaches to improve outcomes in NSCLC. Full article

Reduced Beam Sections (RBS) are used in steel design to promote ductile behavior by shifting inelastic deformation away from critical joints, enhancing seismic performance through controlled energy dissipation. While current design guidelines assist in detailing RBS connections, moment–rotation curves—essential for understanding energy dissipation—require extensive testing and/or modeling. Machine learning (ML) offers a promising alternative for predicting these curves, yet few studies have explored ML-based approaches, and none, to the best of the authors’ knowledge, have applied Explainable Artificial Intelligence (XAI) to interpret model predictions. This study presents an ML framework using Artificial Neural Networks (ANN), Random Forest (RF), Support Vector Machines (SVM), Gradient Boosting (GB), and Ridge Regression (RR) trained on 500 numerical models to predict the moment–rotation backbone curve of RBS connections under cyclic loading. Among all the models applied, the ANN obtained the highest R² value of 99.964%, resulting in superior accuracy. Additionally, Shapley values from XAI are employed to evaluate the influence of input parameters on model predictions. The average SHAP values provide important insights into the performance of RBS connections, revealing that cross-sectional characteristics significantly influence moment capacity. In particular, flange thickness (t_f), flange width (b_f), and the parameter “c” are critical factors, as the flanges contribute the most substantially to resisting bending moments. Full article

Photodegradation is a sustainable green technology that has been studied worldwide, especially for wastewater treatment. The calcination temperature has an important impact on the physicochemical properties of the prepared photocatalysts. In this study, a ternary photocatalyst of Cu₂O/WO₃/TiO₂ (CWT) was successfully synthesized using an ultrasonic-assisted hydrothermal technique, and the calcination temperature was varied from 500 to 800 °C. The characterization outcomes proved that the anatase phase titanium dioxide (TiO₂) in the CWT composite transformed to rutile phase TiO₂ when the calcination temperature reached 700 °C and 800 °C. The surface area of the CWT composite decreased from 35.77 to 8.09 m².g⁻¹ and the particle size of the CWT composite increased from 39.11 to 180.25 nm with an increasing calcination temperature from 500 to 800 °C. Photoelectrochemical (PEC) studies showed the charge-transfer resistance of 208.10 Ω, electron lifetime of 32.48 ms, current density of 1.40 mA.cm⁻², transient photovoltage of 0.53 V, and p-n heterojunction properties for CWT-500. Reactive Black 5 (RB5) was used as the model pollutant to examine the photodegradation performance. The photodegradation rate of CWT-500 was the highest (0.70 × 10⁻² min⁻¹) due to its large surface area, effective separation of photoexcited electron-hole pairs, and low photoexcited charge carrier recombination rate. Full article

Background: The genus Enterococcus includes a diverse group of bacteria that are commonly found in the gastrointestinal tracts of humans and animals, as well as in various environmental habitats. Methods: In this study, Enterococcus lactis RB10, isolated from goat feces, was subjected to comprehensive genomic and functional analysis to assess its safety and potential as a probiotic strain. Results: The genome of E. lactis RB10, with a size of 2,713,772 bp and a GC content of 38.3%, was assembled using Oxford Nanopore Technologies (ONT). Genome annotation revealed 3375 coding sequences (CDSs) and highlighted key metabolic pathways involved in carbohydrate, protein, and amino acid metabolism. The strain was susceptible to important antibiotics, including ampicillin, chloramphenicol, tetracycline, and vancomycin, but exhibited resistance to aminoglycosides, a common trait in Enterococcus species with non-hemolytic activity. Genomic analysis further identified two intrinsic antimicrobial resistance genes (ARGs). The strain also demonstrated antimicrobial activity against Bacillus cereus DMST 11098 and Salmonella Typhi DMST 22842, indicating pathogen-specific effects. Key genes for adhesion, biofilm formation, and stress tolerance were also identified, suggesting that RB10 could potentially colonize the gut and compete with pathogens. Moreover, the presence of bacteriocin and secondary metabolite biosynthetic gene clusters suggests its potential for further evaluation as a biocontrol agent and gut health promoter. Conclusions: However, it is important to note that E. lactis RB10 was isolated from goat feces, a source that may harbor both commensal and opportunistic bacteria, and therefore additional safety assessments are necessary. While further validation is needed, E. lactis RB10 exhibits promising probiotic properties with low pathogenic risk, supporting its potential use in food and health applications. Full article

The short-term performance of ground heat exchangers (GHEs) is crucial for the optimal design of ground-source heat pumps (GSHPs), enhancing their contribution to sustainable energy solutions. Local short-time thermal response functions, or short-time g-functions (STGFs) derived from thermal response tests (TRTs), are of great interest for predicting the heat exchange due to their fast and simple applicability. The aim of this work is to perform a sensitivity analysis to assess the impact of thermal parameter variability and TRT operating conditions on the accuracy of the average fluid temperature (T_f) predictions obtained through a local STGF. First, the uncertainties associated with the borehole thermal resistance (R_b), transmitted from the soil volumetric heat capacity (C_S) or some models dependent on GHE characteristics, such as the Zeng model, were found to have a low impact in T_f resulting in long-term deviations of ±0.2 K. Second, several TRTs were carried out on the same borehole, changing input parameters such as the volumetric flow rate and heat injection rate, in order to obtain their corresponding STGF. Validation results showed that each T_f profile consistently aligned well with experimental data when applying intermittent heat rate pulses (being the most unfavorable scenario), implying deviations of ±0.2 K, despite the variabilities in soil conductivity (λ_S), soil volumetric heat capacity (C_S), and borehole thermal resistance (R_b). Full article

The effects of wound healing on crop stand and productivity were examined on the potato (Solanum tuberosum L.) cultivars Alturas (Alt), Russet Burbank (RB), and Clearwater Russet (CW). Tuber yields increased linearly with an advancing wound healing period irrespective of the cultivar (R² = 0.91). In contrast to unhealed controls, RB and CW wound-healed for 8 days produced a 6% and 8% greater yield, respectively, while a shorter wound healing period of 2 days increased Alt yield by 7%. Increases in tuber yield, a consequence of enhanced specific tuber weight across wound healing periods, contributed towards increased relative crop value in Alt (13%), RB (22%), and CW (19%). In further lab evaluations, Alt exhibited increased desiccation resistance and was associated with an earlier induction (24 h post-wounding) of feruloyl transferase (FHT) compared to CW and RB. Since FHT facilitates suberin and wax development, delayed FHT induction likely promoted fresh-weight loss in CW and RB compared to Alt. Enzymatic evaluations to assess the production of reactive oxygen species to protect fresh-cut seed found that RB had the highest activities of superoxide dismutase and peroxidase. This study demonstrates the broad benefits of planting wound-healed seed while highlighting opportunities to improve best practices and genetic improvement for wound healing response. Full article

Targeting the cell cycle has become a focus of cancer research bearing impressive results with the introduction of CDK4/6 inhibitors in the treatment of ER-positive/HER2-negative breast cancers. However, no definitive benefit in other cancers has been observed. In gastrointestinal cancers, despite preclinical studies pinpointing positive effects on cancer inhibition in pre-clinical models, no positive clinical trials have been published with CDK4/6 inhibitors. Several biomarkers have been proposed in breast cancers, where the field is more advanced, and include up-regulations of the inhibited kinases CDK4 and CDK6 and their partner cyclin D as well as the main target of phosphorylation, RB. Up-regulation of Cyclin E, an E2F1/RB regulated gene, also arises as a marker of CDK4/6 inhibition resistance. Signaling from receptor tyrosine kinase pathways through KRAS/BRAF/MEK and PI3K/AKT/mTOR are also implicated in feedback CDK4/6 activation and inhibitors resistance. In gastrointestinal cancers, some of these biomarkers have also proven valuable in predicting sensitivity to CDK4/6 inhibitors and would lead markers to guide clinical development. Modulation of the tumor microenvironment, where immune cells are prominent components, arises as a feature of CDK4/6 inhibition and could be harnessed in therapeutic combinations. Full article

Due to rising antibiotic resistance, it is necessary to develop alternative ways to combat pathogenic bacteria. One alternative is photodynamic antibacterial chemotherapy (PACT). This work presents the conjugation of the photosensitizer Rose Bengal (RB) to lectins to improve its efficacy against Gram-positive and Gram-negative bacteria. Two lectins, concanavalin A (ConA) and wheat germ agglutinin (WGA), were covalently linked to RB. Spectroscopic and chromatographic data confirmed successful conjugation. Microscopic examination demonstrated that both lectins agglutinate cells of Gram-positive S. aureus, including clinical multidrug-resistant MRSA strains, and Gram-negative E. coli, P. aeruginosa, and S. paratyphi B, although ConA showed a more pronounced reaction. Photodynamic assays showed that ConA-RB achieved complete eradication of S. aureus at significantly lower concentrations and light doses than free RB or WGA-RB. ConA-RB also exhibited higher efficacy against Gram-negative bacteria compared to free RB at lower concentrations and shorter illumination periods. WGA-RB was less effective, showing preferential activity against S. aureus. Our findings suggest that lectin–RB conjugates offer a promising approach for selective antibacterial treatment under illumination. Full article

Candida albicans is a significant pathogen in various fungal infections, including oral candidiasis and denture stomatitis. As antifungal resistance rises globally, there is an urgent need for alternative treatment strategies. Antimicrobial photodynamic therapy (aPDT), utilizing a photosensitizer and light to produce reactive oxygen species (ROS), has emerged as a promising approach. Rose Bengal (RB), a xanthene dye, exhibits a high singlet oxygen quantum yield, making it a candidate for aPDT. However, its efficacy in C. albicans treatment has been inconsistent, particularly against biofilm-associated infections, which are more resistant to conventional therapies. This systematic review evaluates the efficacy of Rose Bengal-mediated aPDT in combating C. albicans infections by synthesizing data from studies conducted over the past decade. We focus on the effectiveness of RB across different experimental conditions, including planktonic and biofilm forms of C. albicans. The review also explores the synergy between RB and other agents, such as potassium iodide, and compares the outcomes of RB-mediated aPDT to other photosensitizers and conventional antifungal treatments. Despite its potential, RB-aPDT shows variable effectiveness due to differences in experimental protocols, such as the photosensitizer concentration, incubation times, and light parameters. The review identifies the key limitations, such as RB’s poor biofilm penetration and high dark toxicity at elevated concentrations, which hinder its clinical applicability. The combination of RB with potassium iodide enhances its antifungal efficacy, suggesting that further optimization could improve its clinical potential. Overall, while Rose Bengal-mediated aPDT holds promise as a novel antifungal treatment, further research is needed to standardize protocols, enhance delivery systems, and validate its efficacy in vivo and clinical settings. Full article

Objectives: Trauma to maxillary incisors is frequent, and requires timely, conservative management for optimal prognosis. This in vitro study evaluated the fracture resistance (FR) and orthodontic bracket bond strength (BS) of incisors following incisal fragment reattachment using various restorative techniques. Materials and Methods: Two independent tests—FR testing (Newtons) and BS testing (megapascals)—were conducted. Eighty intact human maxillary central incisors (n = 40/test), standardized in size and shape using a digital caliper (Mitutoyo, ±0.01 mm), were embedded in acrylic resin and numbered. An uncomplicated crown fracture was induced in 64 teeth (n = 32/test), and the teeth were randomly assigned (simple randomization using Excel’s RAND function) to five groups (n = 8/group/test): (1) intact teeth (negative control, NC); (2) nanohybrid composite buildup using Filtek Z250 and Single Bond 2 (positive control, CB); (3) fragment reattachment using flowable composite (Filtek Supreme, FL); (4) reattachment with a palatal veneer using a nanohybrid composite (PV); and (5) reattachment reinforced with a polyethylene fiber band (Ribbond Inc., RB). In BS testing groups, stainless steel orthodontic brackets (PINNACLE) were bonded using Transbond XT, centered over the fracture line. Light curing was performed using an LED unit (Mini LED Standard, Acteon, 1250 mW/cm², 20 s/bond, 40 s/composite, 2 mm curing tip distance). Specimens were stored in distilled water at room temperature for 24 h before reattachment. FR and BS were evaluated using a universal testing machine (Instron) until failure. Failure modes were analyzed, and data were statistically evaluated using one-way ANOVA, Tukey’s post hoc test, and Pearson’s correlation analysis. Results: Significant differences were observed among groups for both FR and BS (p < 0.05). The NC group exhibited the highest FR (514.4 N) and BS (17.6 MPa). The RB group recorded the second-highest FR (324.6), followed by the PV (234.6), CB (224.9), and FL (203.7) groups. The CB group demonstrated the second-best BS (16.6), followed by the RB (15.2), FL (13.4), and PV (6.5) groups. FR and BS were negatively correlated. Mixed failures predominated in the reattachment groups, except for the PV group, which showed mainly adhesive failures. In BS testing, mixed failures dominated in the NC and CB groups, while adhesive failures predominated in the PV and FL groups. Conclusions: Ribbond reinforcement improves the mechanical performance of reattached incisal fragments, and composite buildup may provide more reliable bracket bonding than fragment reattachment. Clinical Relevance: In cases where biomimetic, minimally invasive reattachment is indicated, Ribbond fiber reinforcement appears to offer a reliable restorative solution. Full article

With the development of Artificial Intelligence (AI) technology, more and more AI chatbots (e.g., ChatGPT and DeepSeek) are beginning to affect work and lifestyles. Although AI chatbots have brought many opportunities to education and teacher trainees, they have also caused many problems and resistance among some teacher trainees. However, previous studies have focused more on the influence of positive acceptance factors induced by AI chatbots and less on the negative barrier model induced by AI chatbots. Therefore, this study starts from the negative barrier factors induced by AI chatbots and builds an influencing barrier model of AI chatbot resistance guided by Innovation Resistance Theory (IRT) and appropriately draws on Cultural Dimension Theory (CDT), Unified Theory of Acceptance and Use of Technology (UTAUT), and practical characteristics. The questionnaires mainly adopt convenience sampling and snowball sampling methods, and the data are empirically analyzed. The results show that Uncertainty Avoidance, the Social Influence Barrier, and Technology Anxiety have a significant and direct influence on teacher trainees’ resistance to AI chatbots. Meanwhile, Uncertainty Avoidance, the Social Influence Barrier, and Technology Anxiety play significant mediating roles in the impact of the Usage Barrier (UB), Image Barrier (IB), Value Barrier (VB), Risk Barrier (RB), and Tradition Barrier (TB) on resistance behaviors, revealing the complex path through which cognition-emotion-society factors jointly shape technology resistance behaviors. Therefore, this study not only contributes to enriching the theoretical results of combining Innovation Resistance Theory with AI chatbots and adding new research paths (e.g., the mediating role of Uncertainty Avoidance) but also provides a practical guide for the dissemination of AI chatbots among teacher trainees and future technological talents in a sustainable future. Full article

Stable and efficient inorganic lead-free double perovskites are crucial for high-reliability optoelectronic devices. However, dual-doped perovskite phosphors often suffer from poor color stability due to differences in thermal activation energies and electron–phonon interactions between the doped ions. To address this, single-doped Sb³⁺-incorporated Rb₂HfCl₆ perovskite crystals were synthesized via a co-precipitation method. Under UV excitation, Rb₂HfCl₆:Sb exhibits broad dual emission bands, attributed to singlet and triplet self-trapped exciton radiative transitions induced by Jahn–Teller distortion in [SbCl₆]³⁻ octahedra. This dual emission endows the material with high sensitivity to excitation wavelengths, enabling tunable luminescence from cyan to orange-red across 400–800 nm. Utilizing this dual emission, a white LED was fabricated, showcasing a high color rendering index and excellent long-term stability. Remarkably, the material exhibits breakthrough thermal stability, maintaining more than 90% of its emission intensity at 100 °C, while also exhibiting remarkable resistance to humidity and oxygen exposure. Compared to co-doped phosphors, Rb₂HfCl₆:Sb offers advantages such as environmental friendliness, simple fabrication, and stable performance, making it an ideal candidate for WLEDs. This study demonstrates notable progress in developing thermally stable and reliable optoelectronic devices. Full article

Melanoma is an aggressive cancer with rising incidence, particularly among older individuals. Despite advancements in targeted therapies for BRAF and MEK proteins and immunotherapies, many patients either fail to respond or develop resistance. For those progressing on immunotherapy, limited treatment options remain. The Cyclin D–CDK4/6–RB pathway is commonly dysregulated in melanoma, with up to 90% of cases showing alterations that activate it. Although targeting Cyclin–CDK complexes has shown promise in preclinical models, clinical responses have been suboptimal. This review explores the molecular mechanisms behind Cyclin–CDK dysregulation in melanoma and the challenges of targeting this pathway. It also discusses strategies to improve the efficacy of CDK4/6 inhibitors, including combination therapies to overcome resistance and enhance patient outcomes. Understanding these mechanisms can guide the development of more effective treatments for melanoma. Full article

Among medicinal plants, the Panax genus (family: Araliaceae) includes plant species widely recognized for their multi-faceted pharmacological attributes. The triterpenoids, designated as ginsenosides, are increasingly recognized as drug-like molecules in cancer therapies due to their therapeutic role in restricting tumor invasion, proliferation, metastasis, apoptosis, and drug resistance reversal in tumor cells. In the nanobiotechnological era, nano-delivery systems provide feasible solutions to address bottlenecks associated with traditional drug delivery methods (low bioavailability, instability in the gastrointestinal tract, high dosage requirements, side effects, poor absorption, and incomplete drug utilization in the body). The dedicated efforts for precise and effective treatment have directed the development of ginsenoside-based nano-delivery systems to achieve potent anticancer efficacies and address the limitations in ginseng pharmacokinetics, facilitating drug development trials. Studies into ginseng pharmacokinetics showed a remarkable prolonged clearance and free drug levels of ~15% (ginsenoside RB1 nanoparticles) in mice (compared to only ~5% for ginsenosides) and better antitumor efficacies, demonstrating key success in ginseng biotechnology for drug development. Delving into the nanobiotechnological interventions in ginseng-derived therapeutics, this study summarizes current advances and achievements, particularly in cancer treatment, tackles existing gaps, focuses on feasible solutions, and examines prospects of translational success. Full article