Search Results (53,644)

Background/Objectives: Recent advancements in immunotherapy have significantly reduced recurrence rates and improved distant outcomes of patients with non-small cell lung cancer. This review synthesizes literature from 2020 to 2025, concentrating on preoperative immunotherapy outcomes. Methods: We analyzed treatment regimens, focusing on primary endpoints, the percentage of patients who underwent initial surgery, type of surgery, R0 rate, immune-related adverse events and chemotherapy-related toxicities as well as the rate of surgery delays and cancelations. Results: Our findings emphasize the importance of optimizing patient selection, effectively managing adverse events, and implementing strategies to minimize surgical delays and cancelations. Conclusions: We defined areas for improvement, such as increasing the implementation of minimally invasive surgeries and avoiding pneumonectomies. These priorities are essential for increasing the efficacy of immunotherapy in surgical settings for NSCLC, and improving patient outcomes. Full article

Lead (Pb) is a persistent and highly toxic heavy metal that poses significant ecological and human health risks due to its high bioaccumulation potential. In this study, nitrogen-doped biochar (NBC) was synthesized from straw-derived biochar via ball-milling and ammonium nitrate modification to remediate Pb-contaminated soil. Batch adsorption experiments demonstrated that the adsorption process was best described by the Langmuir isotherm model, indicating monolayer adsorption. X-ray photoelectron spectroscopy (XPS) revealed that Pb(II) immobilization by NBC occurred through multiple mechanisms, primarily precipitation and complexation with hydroxyl and pyrrolic-N functional groups. Subsequent pot experiments confirmed that NBC outperformed pristine biochar (BC) in reducing Pb bioavailability. This superior performance was attributed to the ability of NBC to increase soil pore water pH and significantly decrease soil redox potential (Eh). Moreover, compared to the control, a 5% NBC treatment (NBC2) significantly increased soil organic matter (SOM) by 136.24% while concurrently increasing soil available nitrogen (SAN), phosphorus (SAP), and potassium (SAK) by 46.91%, 75.72%, and 42.79%, respectively. Microbiological analyses indicated that NBC application enhanced soil alpha diversity (Chao1, ACE, and Shannon indices) and enriched beneficial bacterial phyla, such as Proteobacteria and Firmicutes. Random forest analysis identified the acid-soluble Pb fraction and SOM as the main drivers of bacterial operational taxonomic unit (OTU) composition. Specifically, NBC increased the relative abundance of the family Hungateiclostridiaceae, which may promote soil sulfide production and facilitate the precipitation of Pb into highly insoluble forms, further reducing its mobility and toxicity. Collectively, these findings demonstrate that NBC is a promising soil amendment that leverages both physicochemical and microbial pathways to immobilize Pb, mitigate environmental toxicity, and restore soil ecological health. Full article

Rosmarinic acid (RA), a naturally occurring polyphenolic compound, has demonstrated promising anticancer activity; however, its combinatorial potential with conventional chemotherapeutic agents remains incompletely characterized. This study investigated the cytotoxic, pro-apoptotic, oxidative stress-associated, and cytokine-associated effects of RA alone and in combination with doxorubicin (DOX) in 4T1 murine breast cancer cells and HaCaT human keratinocyte cells as a non-cancerous control model. Cellular viability, apoptosis, cell cycle progression, oxidative stress, mitochondrial function, cytokine responses, and apoptosis-associated molecular alterations were evaluated using complementary cellular and molecular approaches. In addition, three-dimensional (3D) tumor spheroid experiments were performed to assess treatment responses under physiologically relevant tumor-like conditions. Results demonstrated that RA synergistically enhanced DOX-induced cytotoxicity in 4T1 cells while exhibiting comparatively lower toxicity toward HaCaT cells. Combination treatment significantly increased apoptotic cell death, mitochondrial depolarization, intracellular reactive oxygen species (ROS) accumulation, apoptotic DNA fragmentation, and G₂/M-phase accumulation. N-acetylcysteine (NAC)-mediated rescue experiments partially reversed ROS elevation and treatment-associated cytotoxicity in both monolayer and 3D spheroid models. Furthermore, the RA+DOX combination markedly disrupted spheroid integrity and reduced spheroid viability compared with monotherapies. Collectively, these findings indicate that RA enhances the anticancer activity of DOX and support further investigation of this combination strategy in breast cancer models. Full article

Cadmium (Cd) pollution adversely affects crop productivity and grain quality. Durum wheat (Triticum turgidum L. subsp. durum (Desf.) Husn.), a widely consumed cereal crop, can accumulate substantial levels of Cd in edible tissues, threatening human health. Therefore, advances in understanding Cd toxicity in plants and the molecular mechanisms underlying Cd accumulation and detoxification are needed to develop resistant cultivars and ensure safe food production. Although Cd homeostasis has been previously studied in bread wheat, its accumulation varies among species and cultivars owing to differences in their physiological and genetic makeup. However, the molecular mechanisms underlying Cd homeostasis in durum wheat have not been comprehensively reviewed. Here, we synthesize current knowledge on the molecular basis of Cd uptake, transport, and detoxification in durum wheat. Specialized transporter families, including MRPs/ABCCs, HMAs, and members of the YSL, ZIFL, and IREG families, play critical roles in mediating Cd compartmentalization and limiting its cytosolic toxicity. Genes such as HMT1, TdHMA3-B1a, and members of the NAS gene family significantly reduced Cd accumulation in grains. Future studies should focus on the integration of physiological, molecular genetics, and multi-omics approaches to uncover the regulatory networks controlling Cd homeostasis in durum wheat. Full article

Triptolide (TP) is an effective anti-inflammatory and immunosuppressive agent, yet its clinical application is constrained by significant male reproductive toxicity. Curcumin, a natural antioxidant, exhibits protective effects; however, whether it protects against TP-induced damage during mouse spermatogenesis and the underlying mechanisms remain incompletely understood. Methods: Proteomic analysis was performed to investigate the protective mechanism of curcumin in mouse GC-1 cells, followed by multiple validation assays including CCK-8 assay, apoptosis detection, measurement of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and Fe²⁺ levels, quantitative polymerase chain reaction (qPCR), Western blotting (WB), hematoxylin-eosin (HE) staining, and immunofluorescence. Results: Proteomic analysis revealed that curcumin primarily ameliorated TP-induced damage in mouse spermatogonia by modulating ferroptosis-related pathways. Curcumin elevated GSH levels; reduced MDA, ROS, and Fe²⁺ levels; alleviated lipid peroxidation; and regulated ferroptosis-related pathways in both TP-induced GC-1 cells and testicular tissue. These effects were associated with upregulation of the mRNA and protein expression of Nrf2, Gclc, and Map1lc3a and downregulation of Tfrc and Dmt1. Collectively, these findings demonstrate the protective effect of curcumin against TP-induced spermatogonial damage. Conclusions: Curcumin regulated ferroptosis-related pathways by modulating the expression of Nrf2, Gclc, Map1lc3a, Tfrc, and Dmt1, thereby significantly ameliorating TP-induced damage in mouse spermatogonia. Full article

Daunomycin (daunorubicin) is one of the most clinically significant anthracyclines used in chemotherapy, and its efficient production remains a major objective for biotechnological researchers. Industrial manufacturing relies on the fermentation of Streptomyces peucetius and Streptomyces coeruleorubidus, which produce daunomycin as a secondary metabolite under controlled conditions. This review will focus on the methods to enhance the total efficiency of biotechnological production, from upstream biosynthesis to downstream processing. Given the complexity of the daunomycin biosynthetic pathway in Streptomyces spp., substantial progress has been made in strain improvement to increase yield, metabolic robustness, and process stability. Advances in classical mutagenesis, pathway engineering, regulatory network modulation, and precursor supply optimization, along with rational medium design and advanced process control, have led to substantial increases in product titers and productivity. At the same time, innovations in downstream processes, such as extraction, purification and process integration, have increased recovery efficiency, product quality, and economic feasibility. With improvements in the production process, novel drug delivery modalities have been developed (e.g., drug carriers based on erythrocytes, drug nanocarriers based on hyaluronic acid) with increased efficiency and lower systemic toxicity. These developments indicate an evolution from pathway-level engineering to industrial-scale manufacturing and clinical application, underlining the evolution of daunomycin research and biotechnological production. Full article

The development of eco-friendly magnesium (Mg)-based materials that possess acceptable mechanical properties, good biodegradability, and non-toxicity in biomedical applications has become more attractive in recent years, particularly for engineering and biomedical applications. This work investigates the effects of nano-ZnO (2 wt.%) reinforcement and cryogenic treatment (CT) on the microstructural, mechanical, thermal, and corrosion behavior of a non-toxic Mg-1Zn-1Ca alloy. Disintegrated melt deposition (DMD) was the synthesis starting point, while refrigeration at −20 °C (RF20) and liquid-nitrogen exposure at −196 °C (LN) were employed as the CT methods. CT significantly refined the grain size of the alloy and composite materials by more than 31.3%, down to 4.4–4.5 μm in diameter, leading to enhanced mechanical performance through grain boundary strengthening. RF20-treated Mg-1Zn-1Ca alloy exhibited the best damping properties (attenuation coefficient and damping capacity improved by 52.1% and 48.7%, respectively). Compressive response was also improved due to the combined effect of refined grains and reinforcement, with LN-treated Mg-1Zn-1Ca-2ZnO exhibiting the best combination of compression properties, i.e., YS—165 MPa, UCS—634 MPa, ε—43.6%, and W_f—175 MJ/m³. Ignition resistance was also improved with the addition of ZnO reinforcement (3.8% increase in ignition temperature). A significant reduction in corrosion rate was achieved with RF20 treatment, leading to corrosion rate reductions of 62% and 40% in PBS (simulated human body fluid) and salt solution, respectively, primarily due to equiaxed grains and stable microstructure. These results demonstrate the efficacy of ZnO reinforcement and CT conducted at different temperatures in selectively enhancing and tailoring the properties of eco-friendly, biocompatible Mg-alloys and composites for biomedical and strength-based applications. Full article

Polystyrene nanoplastic (PS-NP) contamination poses an emerging threat to aquaculture species, yet time-resolved assessments integrating host physiology, gut microbial ecology, and tissue bioaccumulation remain limited. Here, we evaluated the temporal effects of 100 mg/L PS-NPs (100 nm) on Cherax quadricarinatus (Von Martens, 1868) over a 3-week exposure period. Crayfish were assigned to a control group (Group A) and three treatment groups exposed for 1 (Group B), 2 (Group C), or 3 (Group D) weeks. No mortality occurred. Hepatopancreatic antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) displayed a hormetic response (upregulation at weeks 1–2 followed by depletion at week 3), indicating oxidative stress overload. Alkaline phosphatase activity declined progressively, reflecting cumulative immunosuppression. Histological examination revealed time-dependent structural damage in the hepatopancreas: hepatic tubule enlargement, increased vacuolation, B cell hypertrophy, and cellular disorganization/lysis after three weeks. 16S rRNA sequencing revealed that PS-NPs induced time-dependent gut dysbiosis, characterized by depletion of beneficial taxa and enrichment of opportunistic pathogens. Alpha-diversity metrics (ACE, Chao1, Shannon) were significantly reduced in Group D compared to controls, confirming loss of microbial evenness and richness. Pyrolysis gas chromatography–mass spectrometry quantification demonstrated marked PS-NP bioaccumulation in the hepatopancreas, with concentrations rising from 6.94 μg/g in controls to 65.38 μg/g in Group D, a 9.4-fold increase. Collectively, prolonged PS-NP exposure is associated with oxidative stress, immune dysfunction, progressive gut dysbiosis, and substantial hepatopancreatic nanoplastic burden in C. quadricarinatus. These findings carry implications for ecological risk assessment and highlight the need for further investigation into food safety risks associated with human consumption of crayfish from PS-NP-contaminated environments. Full article

Callosobruchus maculatus (Fabricius, 1775) is a major postharvest pest of stored legumes, causing significant quantitative and qualitative losses. This study evaluated host preference, biochemical determinants of susceptibility, and the insecticidal efficacy of plant powders and aqueous and ethanolic extracts against C. maculatus among selected pulse species. In free-choice assays, oviposition preference did not correspond with developmental success, as Phaseolus vulgaris Linnaeus, 1753, received the highest number of eggs but supported minimal adult emergence, whereas Vigna radiata (Linnaeus) A. Jussieu, 1954, exhibited the highest level of infestation and seed damage. Biochemical analysis revealed correlational patterns: higher carbohydrate and lipid contents were positively associated with infestation and seed weight loss, whereas fiber content showed a negative association with pest performance. Protein content was correlated with oviposition, while moisture and fiber were associated with reduced developmental success. Plant-derived treatments significantly affected all biological parameters of C. maculatus in a concentration- and time-dependent manner, with the exception of sex ratio. Among the tested botanicals, Azadirachta indica A. Jussieu (1830) consistently showed the highest toxicity, with the lowest LC₅₀ values across exposure periods. Ethanolic extracts showed greater insecticidal activity than aqueous extracts, indicating solvent-dependent extraction of bioactive compounds. Mortality increased progressively with exposure duration, accompanied by decreasing LC₅₀ values, suggesting cumulative toxic and developmental effects. Overall, the results demonstrate that host suitability is governed by the interaction between nutritional composition and structural seed traits, while botanical extracts, particularly those from A. indica, offer effective, eco-friendly alternatives for managing C. maculatus in stored legumes. Full article

Conventional photothermal therapy often relies on high-intensity laser excitation due to the limited photothermal conversion efficiency (PCE) of existing photothermal agents (PTAs), which compromises treatment safety and restricts clinical translation. To address this limitation, we designed and synthesized a series of boron-dipyrromethene (BODIPY)-based derivatives (BDP 1–4) featuring gradient-enhanced donor–acceptor (D-A) push–pull electronic effects for efficient photothermal antitumor therapy. The structure–activity relationships were systematically elucidated through photophysical characterization and in vitro/in vivo photobiological evaluation. From BDP 1 to BDP 4, the progressively strengthened push–pull effect leads to enhanced intramolecular charge transfer (ICT), which, in turn, results in a narrowed HOMO-LUMO gap, redshifted absorption into the near-infrared (NIR) region (up to 843 nm), markedly attenuated fluorescence emission, and a remarkable increase in PCE up to 88.3%. To improve water dispersibility and tumor targeting, these molecules were further encapsulated into nanoparticles using DSPE-PEG₂₀₀₀, and the nanoformulations retained high PCE. Both in vitro and in vivo studies demonstrated that under low-power laser irradiation (0.5 W·cm⁻², 808 nm), the nanoformulation of BDP 4, which exhibited the highest PCE among the series, achieved pronounced photothermal tumor ablation without inducing systemic toxicity. Overall, this study proposes a molecular design strategy that synergistically modulates NIR absorption and photothermal conversion by enhancing the D-A push–pull effect. This strategy provides a design rationale for developing efficient, low-toxicity organic PTAs, and demonstrates potential applicability in low-power PTT modalities. Full article

Carbon dots (CDs) have been widely employed in diverse fields by virtue of their excellent water solubility, low toxicity, high fluorescence stability, and favorable biocompatibility. Nevertheless, traditional preparation methods for CDs generally suffer from drawbacks that run counter to the concept of green chemistry. This review comprehensively summarizes the green synthesis technologies, machine learning (ML)-assisted synthesis strategies, and diversified application fields of fluorescent CDs. Specifically, it discusses the characteristics of synthetic organic molecular/polymeric materials and natural sources (e.g., plants and fruit peels, etc.) and elaborates on the top-down and bottom-up green synthesis methods, analyzing their advantages. It also focuses on ML’s core role in precisely regulating CD emission wavelengths, enhancing and predicting fluorescence quantum yields to optimize synthesis processes. Additionally, this review highlights the representative biological applications of CDs, including biosensing and biomedicine (e.g., bioimaging, drug delivery, and photodynamic therapy), while briefly covering their applications in other fields. Finally, the review points out current challenges in green synthesis, ML-assisted applications and industrial translation, and puts forward future research directions, aiming to promote the greenization, intellectualization and large-scale development of CDs. Full article

Background: β-haemoglobinopathies, including sickle cell disease and transfusion-dependent β-thalassaemia, are among the most common monogenic disorders worldwide and represent a major global health burden. Conventional treatments, such as blood transfusions, iron chelation, fetal haemoglobin induction, and allogeneic haematopoietic stem cell transplantation, have improved outcomes but remain limited by treatment-related toxicity, donor availability, and incomplete curative potential. Methods: A narrative literature review was conducted using PubMed up to 2025. Search terms included “sickle cell disease,” “sickle cell anemia,” “β-thalassemia,” “transfusion-dependent beta-thalassemia,” “gene therapy,” “gene addition,” “gene editing,” “CRISPR-Cas9,” “lentiviral vector,” “children,” “paediatric,” and “pediatric.” Relevant clinical trials, reviews, consensus statements, and guidelines were selected and qualitatively analysed. Results: Gene therapy for β-haemoglobinopathies is based mainly on two strategies: gene addition and gene editing. Gene addition uses lentiviral vectors to introduce functional or modified β-globin genes into autologous haematopoietic stem cells, whereas gene editing targets regulatory pathways, particularly BCL11A, to reactivate fetal haemoglobin synthesis or correct disease-causing mutations. Clinical studies have shown encouraging outcomes, including transfusion independence in many patients with β-thalassaemia and marked reduction or elimination of vaso-occlusive crises in sickle cell disease. Paediatric and adolescent data are increasingly promising, although still limited. Conclusions: Gene therapy is reshaping the treatment landscape of β-haemoglobinopathies by offering a personalised and potentially curative approach. However, long-term safety, conditioning toxicity, fertility preservation, accessibility, costs, and implementation in high-prevalence regions remain critical challenges. Further studies are needed to optimise patient selection and expand equitable access. Full article

The use of copper complexes as pharmacotherapy represents an emerging strategy with multiple therapeutic advantages, including their enhanced bioavailability, antimicrobial activity, and ability to participate in diverse cellular processes. These molecules, combined with micro- and nanosystems, offer an advanced approach to the sustained delivery of copper, optimizing its absorption while potentially reducing adverse effects. In this review, we highlight the application of copper complexes reported in recent studies for dermatological diseases and infection management. Furthermore, evidence indicates that copper promotes cell regeneration in wounds and burns, accelerating wound healing. However, their clinical translation requires careful consideration of copper homeostasis, as dysregulation may lead to oxidative stress and toxicity. In perspective, the combination of micro- and nanoformulations with specific copper complexes offers new opportunities for tailored therapies, as well as for the optimization of pharmacokinetics, positioning copper as a multifunctional therapeutic agent in regenerative and supplementation medicine. However, further investigation is required to establish safety, optimal dosing, and long-term effects. Full article

Heavy metal ion pollution has emerged as a global issue. These contaminants are not only present in water sources but are also commonly detected in air, soil, food, and consumer products, posing serious risks to ecosystems and human health. Even at very low concentrations, heavy metal ions can exhibit substantial toxicity. Traditional methods for the detection of heavy metal ions typically require complex laboratory equipment and specialized technicians, making them inadequate for rapid on-site monitoring. Microfluidic technology, as an innovative platform capable of precisely controlling and manipulating minute volumes of fluid, has demonstrated enormous potential in analytical chemistry, biomedicine, and environmental monitoring. In the rapidly developing field of microfluidics, paper-based microfluidic platforms have become prominent due to their low cost, straightforward fabrication, and eco-friendly nature, offering powerful tools for the detection of heavy metal ions in diverse samples. This survey consolidates the major advances reported from 2015 to 2025 in utilizing paper-based microfluidic systems for identifying heavy metal ion pollutants in diverse sample types, including air, explosive residues, water sources, herbal supplements, skin-whitening cosmetics, environmental aerosols, urine, soil, gunshot residues, cucumber plants, and food. The review analyzes in detail the principles and applications of detection strategies based on colorimetric methods, fluorescent methods, electrochemical methods, dual-detection systems, and other methods, as well as the role of nanomaterials and selective recognition elements in improving detection sensitivity and specificity. These portable, low-cost, and easy-to-operate detection systems provide viable solutions for environmental and public health monitoring, particularly suitable for resource-limited regions and scenarios requiring rapid detection. Full article

This manuscript will present an advancement of transformative research that has been conducted at Oak Ridge National Laboratory (ORNL) over a 25-year period (2000–2025) on a variety of environmental and biological matrices. These investigations derived a fundamental understanding of how elemental detection and analysis of these matrices led to the knowledge and discovery of natural processes in plants and the environment. Each project led to the initiation of a new research area which unearthed awesome and novel breakthroughs. Highlights are listed below: 1. The preliminary research at ORNL centered on the detection of aerosols utilizing Laser-induced Breakdown Spectroscopy (LIBS) technology. The Clean Air Act Amendment (CAAA) of 1990 highlighted the importance of identifying hazardous air pollutants (HAPs) due to their impact on environmental and human health, thereby underscoring the need to detect various toxic elements. Research in aerosol chemistry aimed to identify these harmful elements released by factories during periods of increased emissions in their manufacturing processes. LIBS emerged as the most effective method for real-time, in situ measurements of metal species in both gaseous and aerosol phases. 2. An understanding of the presence of total carbon in soils gives perspective on how to develop carbon sequestration strategies. The recognition that carbon sinks can evolve back to carbon sources to emit back to the atmosphere was an important consideration. Also, the concentration of carbon in soil indicates the health of land areas for growing crops successfully. 3. The direct detection of most of the elements in a wood sample in a single emission spectrum, without sample preparation, encouraged the research to use the LIBS technique for preservative treated wood coupled with use of multivariate statistical methodology. Additionally, it encouraged the researchers to try to differentiate natural woods from different parts of the country, and it was successfully demonstrated that LIBS coupled with MVA analysis could differentiate wood of different species from each other and of similar species grown in different environments based on their elemental spectra. This was a breakthrough since it revealed a systematic approach to connect elemental scarcity and abundance to either drought or typical rainfall conditions for the hardwood trees grown in specific areas. 4. Furthermore, the research progressed to reveal physiological and developmental processes contributing to biomass production such that the variation in leaf elemental composition increases our understanding of terrestrial nutrient cycles, as well as tracking the transfer of toxic elements from soils to living organisms. 5. Recently another breakthrough viz., ionomics initiated the correlation of elements to specific genes, uncovering the function that the element performed in the plant. More recently, this has been extended from plants to fungi as well as fungi growing in symbiotic relations with plants. Full article