Search Results (5,152)

The past decade has witnessed an unprecedented transformation in breast cancer management, driven by parallel advances in targeted therapies, immunomodulation, drug-delivery technologies, and molecular diagnostic tools. This review summarizes the key achievements of 2015–2025, encompassing all major biological subtypes of breast cancer as well as technological innovations with substantial clinical relevance. In hormone receptor-positive (HR+)/HER2− disease, the integration of CDK4/6 inhibitors, modulators of the PI3K/AKT/mTOR pathway, oral Selective Estrogen Receptor Degraders (SERDs), and real-time monitoring of Estrogen Receptor 1 (ESR1) mutations has enabled clinicians to overcome endocrine resistance and dynamically tailor treatment based on evolving molecular alterations detected in circulating biomarkers. In HER2-positive breast cancer, treatment paradigms have been revolutionized by next-generation antibody–drug conjugates, advanced antibody formats, and technologies facilitating drug penetration across the blood–brain barrier, collectively improving systemic and central nervous system disease control. The most rapid progress has occurred in triple-negative breast cancer (TNBC), where synergistic strategies combining selective cytotoxicity via Antibody-Drug Conjugates (ADCs), DNA damage response inhibitors, immunotherapy, epigenetic modulation, and therapies targeting immunometabolic pathways have markedly expanded therapeutic opportunities for this historically challenging subtype. In parallel, photodynamic therapy has emerged as an investigational and predominantly local phototheranostic approach, incorporating nanocarriers, next-generation photosensitizers, and photoimmunotherapy capable of inducing immunogenic cell death and modulating antitumor immune responses. A defining feature of the past decade has been the surge in patent-driven innovation, encompassing multispecific antibodies, optimized ADC architectures, novel linker–payload designs, and advanced nanotechnological and photoactive delivery systems. By integrating data from clinical trials, molecular analyses, and patent landscapes, this review illustrates how multimechanistic, biomarker-guided therapies supported by advanced drug-delivery technologies are redefining contemporary precision oncology in breast cancer. The emerging therapeutic paradigm underscores the convergence of targeted therapy, immunomodulation, synthetic lethality, and localized immune-activating approaches, charting a path toward further personalization of treatment in the years ahead. Full article

To address the challenges of wear resistance for shield cutterheads and cutters in high-abrasion sandy cobble strata, this study uses the Beijing Metro Line 19 tunnel Niujie–Jinrongjie section as an engineering case study. It employs the DEM to develop a crushable sandy cobble model, evaluate the stress characteristics of fishtail cutters, rippers, and scrapers, and analyze load distribution in the cutterhead and cutters—including underlying causes. Based on simulations, the study proposes and implements targeted wear-resistant designs for field application. The results indicate that the stress variation patterns of fishtail cutters, rippers, and scrapers with respect to time and installation radius are similar. The cutterhead’s opening distribution significantly influences the intensity of normal and lateral stresses. Caused by cutting resistance, high-stress loads in cutters accumulate at the cutting edge, while those in the cutterhead localize to the soil-facing side of its spokes. Meanwhile, hindered muck flow and cutting failure of gauge cutters also cause stress concentration in the cutterhead’s transition zones and outer side of the large ring. Adopting a DEM-based method that characterizes the stress of the cutterhead and cutters to develop targeted wear-resistant designs can effectively control the wear of cutters and cutterheads in in situ engineering. The rate of abnormal cutter damage was limited to merely 5.84%, while the observed wear of the ripper cutters remained consistently below the values predicted by the IHI empirical model. This study provides a scientific basis for wear-resistant design of cutterheads in similar high-abrasion strata. Full article

Submarine power cables for offshore wind farms experience continuous cyclic loading from environmental forces and floating-platform motions, making fatigue performance a critical design factor. This study combined global and local analyses to investigate the fatigue behavior of a 66 kV dry-type submarine cable installed using a flexible pull-in installation system. A global dynamic analysis using site-specific meteorological and oceanographic data provided time-series displacement responses that were used to evaluate the fatigue damage to the metallic components of the cable. The results indicated that the minimum fatigue life of 8.71 × 10⁴ cycles occurred at the upper metallic sheath near the fixed end, with a corresponding cumulative damage of 1.147 × 10⁻⁵. Fatigue accumulation was predominantly governed by lateral (y-direction) displacement, while axial and vertical displacement components contributed minimally. Furthermore, the predicted fatigue life of the metallic sheath varied by a factor of up to 3.6 depending on the selected curve, comparing the cyclic stress amplitude and number of cycles to failure (S–N curve), highlighting the importance of accurate material fatigue data. These findings emphasize the need for careful evaluation of the environmental loading and sheath fatigue properties in flexible pull-in installation system-based submarine cable system designs. Full article

As LED devices continue to advance toward miniaturization and higher power density, heat dissipation has become a critical factor constraining their reliability and service life. Molybdenum is widely employed as a substrate material in LED devices owing to its high thermal conductivity and low coefficient of thermal expansion. However, substrate applications impose stringent requirements on surface finish, flatness, and low-damage processing. Chemical mechanical polishing (CMP) can effectively balance global and local flatness and serves as the final step in producing high-quality molybdenum substrate surfaces. To enable efficient and precise processing of molybdenum substrates, this study adopts an orthogonal experimental design for double-sided CMP to systematically investigate the effects of polishing pressure, polishing slurry pH, additives in the polishing slurry, and abrasive particle size on the material removal rate (MRR) and surface roughness (Sa). An optimal parameter combination was identified via weight-matrix optimization: a polishing pressure of 115 kPa, pH 11, H₂O₂ (0.5%) and glycine (5 mg/L) as additives, and an abrasive particle size of 0.6 μm. Under these conditions, the MRR reached 80 nm·min⁻¹ and Sa decreased to 1.1 nm, yielding a smooth, mirror-like surface. The results indicate that multi-factor synergistic optimization can substantially enhance both surface quality and processing efficiency in double-sided CMP of molybdenum substrates, providing a process basis for applications in high-power LED devices. Full article

Background/Objectives: Radiotherapy of the chest wall after mastectomy frequently leads to fibrosis, reduced tissue elasticity, erythema, pain and chronic skin-related symptoms that complicate reconstructive strategies. Autologous fat grafting has been proposed as a regenerative option for radiation induced soft tissue damage, but clinical data focused on patient-reported symptoms remain limited. The objective of this study was to describe symptomatic and clinical changes after autologous fat grafting in irradiated postmastectomy chest wall tissue. Methods: This pilot observational study included five female patients with a history of mastectomy followed by adjuvant chest wall radiotherapy. All patients underwent a single session of standard autologous fat grafting without adipose derived stem cell enrichment. Patient-reported symptoms, including pruritus, local discomfort, burning sensation and erythema, were recorded preoperatively and at six months using a standardized 0 to 5 scale. Scar pliability was assessed by two experienced physicians using the same scale. Only descriptive statistical analysis was performed. Results: All patients demonstrated lower postoperative symptom scores at six months. Mean reductions were observed for erythema (71.4 percent), burning sensation (61.1 percent) and pruritus (57.1 percent). Local discomfort decreased by 33.3 percent. Mean scar pliability scores increased from 2.2 to 3.2. No postoperative complications, such as infection, fat necrosis or oil cyst formation, were recorded. All patients completed the six month follow up. Conclusions: In this small pilot observational study, autologous fat grafting was well tolerated and associated with descriptive improvement of patient-reported symptoms and scar pliability in irradiated postmastectomy chest wall tissue. These findings suggest a potential symptomatic benefit of fat grafting, while larger studies with objective imaging and histological correlation are required to confirm efficacy and durability. Full article

Flooding is a recurrent problem in many Brazilian cities, resulting in significant losses that affect health, assets, finance, and the environment. The uncertainty regarding extreme rainfall events due to climate change makes this challenge even more severe, compounded by inadequate urban planning and the occupation of risk areas, particularly for the municipality of Catu, in the state of Bahia, which also suffers from recurrent floods. Critical hotspots include the Santa Rita neighborhood and its surroundings, the main supply center, and the city center—the municipality’s commercial hub. The focus of this research is the unprecedented quantification of the socioeconomic impact of these floods on the low-income population and the region’s informal sector (street vendors). This research focused on analyzing and modeling the destructive potential of intense rainfall in the Santa Rita region (Supply Center) of Catu, Bahia, and its effects on the local economy across different recurrence intervals. A hydrological simulation software suite based on computational and geoprocessing technologies—specifically HEC-RAS 6.4, HEC-HMS 4.11, and QGIS— 3.16 was utilized. Two-dimensional (2D) modeling was applied to assess the flood-prone areas. For the socioeconomic impact assessment, a loss procedure based on linear regression was developed, which correlated the different return periods of extreme events with the potential losses. This methodology, which utilizes validated, indirect data, establishes a replicable framework adaptable to other regions facing similar socioeconomic and drainage challenges. The results revealed that the area becomes impassable during flood events, preventing commercial activities and causing significant economic losses, particularly for local market vendors. The total financial damage for the 100-year extreme event is approximately US $30,000, with the loss model achieving an R² of 0.98. The research concludes that urgent measures are necessary to mitigate flood impacts, particularly as climate change reduces the return period of extreme events. The implementation of adequate infrastructure, informed by the presented risk modeling, and public awareness are essential for reducing vulnerability. Full article

The inner spacer module, which profoundly affects the final performance of a device, is a critical component in GAA NSFET (Gate-all-around Nanosheet Field Effect Transistor) manufacturing and necessitates systematic optimization and fundamental innovation. This work aims to develop an advanced SiGe etching process with high selectivity, uniformity and low damage to achieve an ideal inner spacer structure for logic GAA NSFETs. For three distinct dry etching technologies, ICP (Inductively Coupled Plasma Technology), RPS (Remote Plasma Source) and Gas Etching, we evaluated their potential and comparative advantages for inner spacer cavity etching under the same experimental conditions. The experimental results demonstrated that Gas Etching technology possesses the uniquely high selectivity of the SiGe sacrificial layer, making it the most suitable approach for inner spacer cavity etching to reduce Si nanosheet damage. Based on the results, in the stacked structures, the SiGe/Si selectivity ratio exhibited in Gas Etching is ~9 times higher than ICP and ~2 times higher than RPS. Through systematic optimization of pre-clean conditions, temperature and chamber pressure control, we successfully achieved a remarkable performance target of cavity etching: the average SiGe/Si etching selectivity is ~56, the inner spacer shape index is 0.92 and the local etching distance variation is only 0.65 nm across different layers. These findings provide valuable guidance for equipment selection in highly selective SiGe etching and offer critical insights into key process module development for GAA NSFETs. Full article

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality that relies on the activation of photosensitizers (PS) by specific wavelengths of light to generate reactive oxygen species (ROS), resulting in localized cytotoxicity with relative sparing of healthy tissues. Depending on the PS properties, light dose, and intrinsic cellular features, PDT can elicit multiple cell death pathways, including apoptosis, necrosis, and autophagy. Increasing evidence indicates that PDT is also a potent inducer of ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation (LPO), glutathione (GSH) depletion, and inactivation of glutathione peroxidase 4 (GPX4). PDT-derived ROS promote ferroptosis both indirectly by exhausting antioxidant defenses and directly by peroxidizing PUFAs within membrane phospholipids. At the same time, intense oxidative stress generated by PDT can activate adaptive responses such as mitophagy, a selective autophagic process that removes damaged mitochondria to limit ROS production and preserve redox homeostasis. Ferroptosis and mitophagy are therefore tightly interconnected, functioning as opposing yet complementary regulators of cell fate. PDT emerges as a key upstream modulator of the ferroptosis–mitophagy balance, as spatially and temporally confined oxidative stress can shift cellular responses from adaptive mitochondrial quality control to irreversible ferroptotic injury. Despite growing interest in both PDT and ferroptosis, their mechanistic interplay, particularly in relation to mitophagy, remains underexplored. This narrative review provides an integrated overview of current knowledge on how PDT influences ferroptosis and mitophagy, highlighting the molecular mechanisms that connect these pathways and discussing their implications for improving therapeutic efficacy and overcoming resistance. Full article

Sloshing-induced impact pressure is a key damage factor for marine liquid tanks. While research aimed at overcoming screen failure in sloshing suppression under high-frequency excitation has focused on wave height, the dataset of impact pressure remains lacking. Moreover, the pattern of pressure suppression under broadband excitation remains unclear. The primary contribution of this work is the first experimental dataset of impact pressure with vertical slat screens under broadband horizontal and vertical excitation. Second, it reveals pressure suppression patterns by screens across varying excitation frequencies and screen numbers. The results demonstrate that vertical slat screens can effectively suppress pressure. First, screen position matters more than number, proving that suppression is dominated by modal disturbance. Second, wave-height suppression does not reliably represent pressure suppression. Pressure suppression is systematically weaker. An exception occurs under vertical excitation, where pressure suppression can be stronger even when wave-height suppression fails. The results highlight the suppression mechanism dominated by modal disturbance and the instability inherent to parametric sloshing. Wave height, reflecting global potential energy, is effectively suppressed by modal disturbance. Pressure, originating from local kinetic energy, can be effectively suppressed by both modal disturbance and vortex dissipation. Full article

Glucocorticoids are widely applied intra-articularly to alleviate inflammation and pain in osteoarthritis (OA). However, repeated administration and high local concentrations can lead to crystal deposition on the cartilage surface, contributing to chondrocyte damage and extracellular matrix (ECM) degradation, potentially accelerating OA progression. Calcium-dependent mechanosensors play a critical role in mediating catabolic responses in chondrocytes, but it remains unclear whether glucocorticoids affect chondrocyte mechanosensitivity or biomechanical properties. This in vitro study examined the dose-dependent effects of triamcinolone acetonide (TA) on chondrocyte biomechanics and mechanosensitivity. Primary human chondrocytes (N = 23) were cultured for one week with TA (2 µM–2 mM) or control medium. Cytoskeletal organization was visualized by F-actin staining (N = 6), and cellular elasticity (N = 5) was quantified via atomic force microscopy (AFM). Mechanotransduction was analyzed by Ca²⁺ imaging (Fluo-4 AM) upon AFM-based indentation (500 nN). Expression of matrix-related and mechanosensitive genes (N = 9) was assessed by qPCR. TA exposure induced a concentration-dependent reorganization of the F-actin cytoskeleton, pronounced at 0.2 mM, accompanied by a significant increase in the elastic modulus (p < 0.001). TA further augmented Ca²⁺ fluorescence intensity under basal conditions and during mechanical stimulation. Blocking cationic mechanosensitive channels with GsMtx4 (N = 3) markedly reduced the TA-evoked Ca²⁺ influx (p < 0.0001). Significant reduction in MMP1 was observed on the transcriptional level (N = 9) after TA-treatment (p < 0.05). In summary, TA enhances chondrocyte stiffness through cytoskeletal condensation and amplifies Ca²⁺-dependent mechanotransduction but reduces MMP1 expression, indicating a dual biomechanical response of chondrocytes to OA under exposure of potent corticosteroid. Full article

Background/Objectives: Liver cancer is among the most frequent poor-prognosis malignancies worldwide, with currently insufficient effective treatment. The two-stage microwave hyperthermia using magnetic nanoparticles is a modern technique designed to specifically target tumor tissues and facilitate chemotherapy activation, with promising results from fundamental studies across various tumor types. The method consists of a first irradiation, performed before nano-assemblies administration. This is intended to sensitize the tumor by inducing a hyperthermic effect, leading to increasing blood supply, enhancing endothelial damage/permeation and inflammatory activation, with the final goal of improving the diffusion/retention of nano-assemblies in the tumor. Subsequently, the second microwave irradiation follows the injection in the hepatic artery and diffusion in the tumor of the activated nano-assemblies, to further determine a strong, but localized and focalized hyperthermic action. Nano-magnetic assemblies for hyperthermia accomplish the proposed chemo-thermal delivery, i.e., act per se on the tumor and also destabilize co-administered assemblies of nanoparticles loaded with chemotherapeutics, which would be consequently released locally in the most efficient way. This article aims to demonstrate the efficacy of this therapeutic approach in a rat liver model and its potential applicability in patients with liver tumors. Methods: Adult male Wistar rats were used to obtain liver samples, which were divided into three groups, each receiving a different hyperthermia protocol in terms of temperature (41–45 °C), duration, and co-administration of nanoparticles. Results: The most suitable exposure temperature for rat liver appears to be 42 °C, resulting in vacuolar degeneration lesions at the focal level. The effects of thermal conditioning do not appear to be homogeneous in the tested liver, and the controlling environment and methodology should be improved in the near future. The level of hepatic inflammation, as indicated by elevated interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels, appears negligible under the current hyperthermia protocol. Conclusions: Two-stage microwave hyperthermia using magnetic nanoparticles is a promising therapeutic modality for liver cancer, with promising results from animal studies opening the way for further research in humans. Full article

Dental caries is a major global health issue associated with biofilm formation by Streptococcus mutans (S. mutans). Conventional antimicrobials often fail to eliminate biofilms due to their structural resistance, highlighting the need for new strategies. This study investigated the antibacterial and antibiofilm effects of protamine peptides (PPs), which are cell-penetrating antimicrobial peptides derived from salmon protamine, alone and in combination with antimicrobial agents. Antimicrobial susceptibility was evaluated using alamarBlue^® and colony count assays, while biofilm formation was analyzed using crystal violet staining, confocal microscopy, and extracellular polysaccharide (EPS) quantification. PP exhibited moderate antibacterial activity but strongly suppressed EPS accumulation and biofilm development, leading to a flattened biofilm structure. Cotreatment with ε-poly-L-lysine (PL) significantly enhanced antibacterial and antibiofilm effects compared with either agent alone, whereas this effect was not observed with other cationic polymers. Fluorescence imaging revealed that PL promoted the intracellular localization of PP without increasing membrane damage, indicating a cooperative mechanism by which PL enhances membrane permeability and PP targets intracellular sites. These findings demonstrate that combining a cell-penetrating peptide with a membrane-active agent is a novel approach to overcome bacterial tolerance. The PP–PL combination effectively suppressed S. mutans growth and biofilm formation through dual action on membranes and EPS metabolism, offering a promising basis for the development of peptide-based preventive agents and biofilm-resistant dental materials. Full article

To address the limitations of traditional timber mortise-and-tenon joints, particularly their low pull-out resistance and rapid stiffness degradation under cyclic loading, this study proposes a novel integrated sleeve mortise-and-tenon steel–timber composite beam–column joint. Building upon prior experimental validation and numerical model verification, a comprehensive parametric study was conducted to systematically investigate the influence of key geometric parameters on the seismic performance of the joint. The investigated parameters included beam sleeve thickness (1–10 mm), sleeve length (150–350 mm), bolt diameter (4–16 mm), and the dimensions and thickness of stiffeners. The results indicate that a sleeve thickness of 2–3 mm yields the optimal overall performance: sleeves thinner than 2 mm are prone to yielding, while those thicker than 3 mm induce stress concentration in the timber beam. A sleeve length of approximately 250 mm provides the highest initial stiffness and a ductility coefficient exceeding 4.0, representing the best seismic behavior. Bolt diameters within the range of 8–10 mm produce full and stable hysteresis loops, effectively balancing load-carrying capacity and energy dissipation; smaller diameters lead to pinching failure, whereas larger diameters trigger premature plastic deformation in the timber. Furthermore, stiffeners with a width of 40 mm and a thickness of 2 mm effectively enhance joint stiffness, promote a uniform stress distribution, and mitigate local damage. The optimized joint configuration demonstrates excellent ductility, stable hysteretic behavior, and a high load capacity, providing a robust technical foundation for the design and practical application of advanced steel–timber composite connections. Full article

During deepwater completion and testing, the platform and riser system are subjected to long-term motions induced by ocean currents, which may cause structural damage and potential failure of the landing string. This study investigates the mechanical and fatigue performance of a subsea Christmas tree and landing string under environmental conditions of the LH11-1 Oilfield in the South China Sea. A global–local simulation framework is used to build a coupled dynamic model of the riser–landing string system and a local model for the landing string, considering load-transfer characteristics, current profiles, periodic features, and two representative environmental conditions (typhoon and non-typhoon). For seventeen typical operating scenarios, the strength of the riser–landing string system is evaluated, and wave-induced and vortex-induced fatigue analyses are performed for the key components. The stress distribution strongly depends on operating conditions, but local strength results confirm that stresses in the primary landing string components remain below allowable limits in all scenarios. Fatigue analysis indicates that the most severe wave-induced damage in the riser occurs at its bottom section, with a fatigue life of about 15.12 years, while in the landing string, it is concentrated near the lower end, with an estimated life of about 52.68 years. The maximum vortex-induced fatigue damage occurs near the riser surface region, with a corresponding fatigue life of about 18.52 years. Full article

Background: Congenital Insensitivity to Pain and Anhidrosis (CIPA) is a rare autosomal recessive disorder characterized by congenital analgesia, anhidrosis, and multisystem involvement affecting the musculoskeletal, cutaneous, oral, and para-oral structures. This case report describes the oral phenotype and multidisciplinary clinical management of a child with CIPA. Case Description: A 9-year-old boy presented with poor oral hygiene, multiple severely damaged teeth, masticatory difficulty, limited mouth opening, impaired bolus control, and para-oral traumatic injuries. Medical and orthopedic history indicated recurrent painless fractures, self-inflicted injuries, cutaneous scarring, and recurrent hyperpyrexia. Oral self-injury associated with CIPA was suspected and supported by the Nociception Assessment Test and Minor’s Iodine–Starch Test. Although the clinical findings were suggestive of CIPA, the diagnosis remained presumptive due to the absence of confirmatory molecular or histopathological testing. Management: A wearable wireless continuous temperature-monitoring device was prescribed to assist in tracking hyperpyrexia associated with CIPA (RHA-CIPA). A conservative, staged, multidisciplinary treatment was planned rather than full-mouth extraction, emphasizing prevention of dental sepsis and mitigation of future self-injury. Dental procedures were performed under local anesthesia to manage discomfort related to tactile hyperesthesia. To reduce nocturnal biting and oral trauma, a hard acrylic occlusal protector was fabricated using an intraoral scanner and a 3D-printed cast. The patient was followed for 12 months. Outcomes: At the 12-month follow-up, clinical improvement was observed, with particularly notable gains in cheek elasticity and soft tissue resilience. Conclusions: This case highlights the considerable challenges involved in the interdisciplinary management of children with CIPA, including oral self-injury prevention, limited mouth opening, and the necessity of close coordination with medical specialties. These findings are descriptive observations of a single case and do not establish efficacy or generalizability of any intervention. Full article