Search Results (51)

The article presents an energy, economic and environmental (3-E) analysis of a reference wastewater treatment plant (WWTP) with a capacity of 200,000 population equivalent (PE). The analysis includes sewage sludge treatment, anaerobic digestion (AD), combined heat and power (CHP), and mono-incineration of solar-dried sludge. The specific investment cost for the reference WWTP is 435 €/PE. Annual costs for operation and maintenance are estimated at 26 €/(PE·y) and the energy costs are 5 €/(PE·y). The annual energy demands are 32 kWh_el/(PE·y) of electricity and 14 kWh_th/(PE·y) of thermal energy for digesters’ heating. For a specific sludge quantity of 20 kg_DS/(PE·year), the biogas production is 245 Nm³/t_DS or 5 m³/(PE·y). Biogas-driven CHP supplies 10.3 kWh/(PE·year) of electricity and 14.7 kWh/(PE·year) of thermal energy, which meets 30% of the electrical demand and 100% of the thermal energy demand. Total (capital and operation) costs of sludge mono-incineration are evaluated at 300 €/t_DM or 6 €/PE. The heating value of digested and solar-dried sludge is 2 kWh/kg_WM. The total cost of the solar drying system is 30 €/PE while the sludge solar drying rate is 370 kg_DM/(m²·y). The environmental analysis showed that the on-site carbon footprint of the reference WWTP is 50 kg_CO2eq/(PE·y), with the largest contributions arising from N₂O emissions during wastewater treatment, CO₂ from sludge mono-incineration, and CO₂ from biogas combustion in the CHP unit. Full article

Background: Triple-negative breast cancer (TNBC), devoid of actionable targets for endocrine or HER2-directed therapy, is highly aggressive with elevated risks of recurrence and metastasis; surgical resection remains the mainstay of treatment, and postoperative chemotherapy serves as a key adjuvant modality for controlling residual disease. Doxorubicin (DOX), although widely used, shows limited tumor selectivity, considerable systemic toxicity, and poor control over drug release at the tumor site. To address these issues, we developed near-infrared (NIR)-responsive gold-decorated phase-change nanodroplets (AuNPs-DOX-NDs) that combine photothermal conversion, liquid-to-gas phase transition, and controlled DOX release in a single platform. Methods: The nanodroplets consisted of a perfluorohexane (PFH) core, a DOX-loaded lipid shell, and polyethyleneimine-modified gold nanoparticles (PEI-AuNPs) conjugated to the surface as the NIR photothermal component. Physicochemical characterization was performed to evaluate morphology, colloidal dispersity, and storage stability. Under 808 nm laser irradiation, the photothermal behavior, PFH vaporization, and DOX release properties of AuNPs-DOX-NDs were investigated. In vitro studies using 4T1 TNBC cells were conducted to assess intracellular DOX accumulation, cell proliferation, migration, and apoptosis. Results: Physicochemical characterization showed that the nanodroplets had a uniform nanoscale morphology, good colloidal dispersity, and acceptable storage stability. Under 808 nm laser irradiation, AuNPs-DOX-NDs exhibited concentration-dependent photothermal heating, which induced PFH vaporization and accelerated DOX release, indicating a clear stimulus-responsive release behavior. In vitro studies using 4T1 TNBC cells showed enhanced intracellular DOX accumulation after treatment with AuNPs-DOX-NDs. Upon laser irradiation, the nanodroplets further inhibited cell proliferation and migration and promoted apoptosis, suggesting an enhanced combined photothermal–chemotherapeutic effect in 4T1 TNBC cells. Conclusions: These results indicate that AuNPs-DOX-NDs may serve as a useful NIR-responsive platform for externally controlled drug release and enhanced combined photothermal-chemotherapy, and deserve further evaluation in vivo. Full article

Pancreatic ductal adenocarcinoma is highly malignant with poor prognosis. Its dense tumor microenvironment severely limits the efficacy of conventional chemotherapy and causes severe side-effects. Herein, we adopt the established Schiff-base crosslinked thermoresponsive injectable self-healing poly(2-(2-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol) methyl ether methacrylate-co-aldehyde 2-hydroxyethyl methacrylate)/carboxymethyl chitosan (APMOH/CMCS) hydrogel as the delivery scaffold. By regulating monomer composition, the volume phase transition temperature (T_VPT) of the hydrogel was tuned to around 43 °C to match the therapeutic temperature requirement. Subsequently, copper–metal organic framework (Cu-MOF) nanoparticles co-loaded with 2,2′-azobis(2-methylimidazoline) dihydrochloride (AIPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) cationic radicals (ABTS·⁺) (denoted as AB@Cu-MOF) were uniformly incorporated into the hydrogel network. Under near-infrared (NIR) irradiation, ABTS·⁺ acts as a photothermal agent to generate hyperthermia for tumor ablation; the elevated temperature further activates AIPH to produce alkyl radicals, which can oxidize inactivated ABTS back to ABTS·⁺ and construct a sustainable photothermal therapy–thermodynamic therapy (PTT-TDT) circulation. Meanwhile, Cu-MOF can consume intracellular glutathione (GSH) to protect active components from deactivation and initiate chemodynamic therapy (CDT) via Fenton-like reactions to produce toxic reactive oxygen species. Benefiting from the thermoresponsive characteristic, the hydrogel undergoes volume shrinkage upon heating, achieving NIR-triggered on-demand drug release with a cumulative release rate of 81.1%. In vitro and in vivo experiments verified that this integrated platform realizes remarkable triple synergistic efficacy of PTT, TDT, and CDT. The tumor volume of the treatment group was merely 13.3% of the control group, and the system also exhibited excellent biocompatibility. Collectively, it offers a feasible and promising intelligent platform for precise local treatment of pancreatic cancer. Full article

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited targeted therapeutic options, underscoring the urgent need for novel treatment strategies. Feilike (FLK), a Traditional Chinese Medicine formula with heat-clearing and detoxifying properties, aligns with key pathological features implicated in breast cancer progression. In addition, several of its components have demonstrated anti-tumor activity, positioning FLK as a potential therapeutic candidate for TNBC. In this study, we employed an integrated approach combining network pharmacology, transcriptomic analysis, and experimental validation to investigate the anti-TNBC effects of FLK. Our results demonstrate that FLK significantly inhibits the proliferation of TNBC cell lines and patient-derived organoids and induces typical pyroptotic features, including cell swelling and increased lactate dehydrogenase (LDH) release. Mechanistically, FLK triggers a mutant p53 signaling cascade involving calcium dysregulation, endoplasmic reticulum stress (ERS) activation, mitochondrial dysfunction, and reactive oxygen species (ROS) accumulation, which collectively activate the P38/JNK–Caspase-3/GSDME pathway to induce pyroptosis. In vivo, FLK markedly suppresses tumor growth in a 4T1 orthotopic mouse model and enhances the anti-tumor efficacy of Cyclophosphamide. Furthermore, Licochalcone B (LCB) is identified as a key bioactive constituent that recapitulates the pyroptosis-inducing effects of FLK. Collectively, our findings uncover a previously unrecognized mutant p53–ERS–ROS–MAPK signaling axis underlying FLK-induced pyroptosis and provide mechanistic insight and experimental evidence supporting the repurposing of FLK as a potential therapeutic strategy for TNBC. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Our previous study demonstrated that combination therapy with local hyperthermia (HT) and anti-CTLA-4 antibody (C4), an immune checkpoint inhibitor, induced regression of both local and distant tumors. However, tumor microenvironment (TME) changes in local and distant tumors following local HT and C4 remain unclear. Here, we aimed to evaluate TME changes in local and distant tumors induced by local HT + C4 therapy. Methods: Murine TNBC cells were inoculated in both legs of male BALB/cAJcl mice, and only one leg was treated with HT (42.5 °C for 20 min). C4 was administered intraperitoneally every 3 days for a total of 3 doses. For CD4⁺ T cell depletion experiments, anti-CD4 antibody (αCD4) was administered intraperitoneally every 3 days for a total of 12 doses. Tumor-infiltrating immune cells in locally heated tumors and unheated distant tumors were analyzed 9 days after the initial treatment. Furthermore, tumor growth in heated tumors and unheated distant tumors under αCD4 administration was evaluated. Results: HT + C4 therapy increased the proportion of helper T cells and elevated the ratio of cytotoxic T cells plus helper T cells to myeloid-derived suppressor cells in both heated tumors and unheated distant tumors. The HT + C4 + αCD4 group exhibited significantly larger tumor growth, compared with the HT + C4 group in both heated (p < 0.01) and unheated distant tumors (p < 0.01). Conclusions: These results suggest that combination therapy of HT and C4 favorably modulates the TME. CD4⁺ T cell infiltration may contribute to both local and distant antitumor effects. Full article

Aflatoxin B1 (AFB1) poses a serious threat to global food and feed safety. Laccase-based enzymatic degradation represents a promising green strategy for AFB1 removal; however, its industrial application is severely limited by the rapid thermal inactivation of wild-type enzymes under high-temperature processing conditions (>70 °C). Here, we engineered the thermal stability of a laccase from Bacillus amyloliquefaciens B10 through an integrated strategy combining computational structural biology with semi-rational design. By coupling molecular dynamics (MD) simulations with folding free-energy (ΔΔG) calculations, we identified key flexible regions associated with thermal instability and subsequently implemented iterative saturation mutagenesis. The best single mutant, R196C, retained more than 96% relative activity after heat treatment at 80 °C for 10 min. Further iterative mutational stacking progressively enhanced thermostability: the R90E/R196C double mutant showed 1.25-fold higher activity at 80 °C than R196C, and the R90E/R196C/H54F triple mutant showed a further 1.16-fold increase over the double mutant. The final quadruple mutant, R90E/R196C/H54F/R253I, achieved 86.9% AFB1 degradation at 80 °C after 24 h. High-temperature MD simulations (100 ns at 353.15 K) indicated that the enhanced thermostability was associated with reduced conformational flexibility, lower radius of gyration (Rg) and solvent-accessible surface area (SASA), and a coil-to-β-sheet transition that contributed to stabilization of the protein core. In addition, efficient secretory expression of the engineered enzyme was achieved in Pichia pastoris, reaching 3.0 U/mL, while the crude enzyme maintained more than 70% activity at 80 °C. Collectively, these results provide a practical basis for the rational engineering and scalable production of thermostable biocatalysts for AFB1 detoxification-related applications of AFB1 control, and offer broader insights into the targeted enhancement of thermal stability in industrial enzymes. Full article

The present study focuses on redesigning the composition of the conventional M50 steel grade, which is widely used for high-temperature bearings. Through thermodynamic calculations, a new steel variant was developed in the laboratory with the aim of refining carbides and improving hardness. After undergoing quenching at 1070 °C and triple tempering at 540 °C, the hardness reached 66 HRC, which is 7.57% higher than that of M50 steel (61 HRC). Meanwhile, the hardness at 400 °C reached 60 HRC. In addition to the typical M₂C and M₆C carbides found in M50 steel, the presence of Fe and Cr-rich M₂₃C₆ carbides was detected in the redesigned steel after triple tempering. These carbides play a significant role in enhancing hardness. Furthermore, the heat treatment process effectively eliminated the uneven and coarse carbides. The average size of primary carbides is 4.6 ± 0.6 μm, which represents a 27.0% reduction compared to M50 steel (6.3 ± 0.1 μm). The detrimental V-rich MC carbides commonly found in M50 were eliminated. Full article

Metallothioneins (MTs) and heat shock protein 70 (HSP70) are key regulators of cellular stress response and metal homeostasis and play important roles in tumor biology. The aim of this study was to examine their expression patterns and potential prognostic significance in different molecular subtypes of breast cancer (BC), with special emphasis on triple-negative breast cancer (TNBC) and the Luminal A subtype, compared with benign breast lesions (fibroadenomas). A total of 90 tissue samples were included, and the expression of MTs in the cytoplasm and nucleus and HSP70 in the nucleus of tumor cells was analyzed immunohistochemically and correlated with clinicopathological features and treatment outcomes. Distinct expression patterns of HSP70 and MTs were observed between malignant and benign samples, as well as among the analyzed molecular subtypes of BC, suggesting their involvement in cellular adaptive mechanisms associated with malignant transformation. TNBC was characterized by less favorable clinicopathological features compared to the Luminal A subtype, including higher histological grade, increased proliferative activity, and a higher incidence of recurrence and metastatic disease. Survival analyses confirmed a worse outcome for patients with TNBC, while HSP70 and MTs expression did not show independent prognostic value in multivariate models. In conclusion, although HSP70 and MTs play important biological roles in the cellular response to stress and tumor adaptation, their expression in this study does not represent an independent prognostic indicator of clinical outcome. Nevertheless, the observed expression patterns provide insight into the complex mechanisms of tumor adaptation and emphasize the need for integrative approaches in BC biomarker research. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) exhibits pronounced biological heterogeneity, aggressive behavior, and a high risk of recurrence and metastasis. The conventional treatments for TNBC have notable limitations: surgical resection may leave residual tumor cells; chemotherapy (CT) frequently induces systemic toxicity and drug resistance; and radiotherapy damages surrounding organs and compromises the patients’ immune function. Methods: Herein, we designed a carrier-free nanodrug delivery system composed of self-assembled Curcumin nanoparticles (NPs) coated with a tannic acid (TA)/Fe(III) network (denoted as CUR@TA-Fe(III) NPs). We systematically evaluated the in vitro cytotoxicity and photothermal–ferroptosis synergistic therapeutic efficacy of CUR@TA-Fe(III) NPs in 4T1 breast cancer cells, as well as the in vivo antitumor activity using 4T1 tumor-bearing mouse models. Results: CUR@TA-Fe(III) NPs had high drug loading efficiency (LE) of 27.99%, good dispersion stability, and photothermal properties. Curcumin could inhibit the growth of 4T1 cancer cells, while TA-Fe(III) efficiently converted light energy into heat upon exposure to near-infrared (NIR) light, leading to direct thermal ablation of 4T1 cells. Additionally, TA-Fe(III) could supply Fe(II) via TA, increase intracellular Fe(II) content, and generate reactive oxygen species (ROS) through the Fenton reaction, in turn inducing lipid peroxidation (LPO), a decrease in mitochondrial membrane potential (MMP), and glutathione depletion, eventually triggering ferroptosis. Conclusions: This treatment strategy, which integrates CT, PTT, and ferroptosis, is expected to overcome the limitations of traditional single-treatment methods and provide a more effective method for the treatment of TNBC. Full article

Mechanistic relationships between heat shock protein 90 (HSP90) and human epidermal growth factor receptor 2 (HER2) are complex and clinical correlations in breast cancer remain inconsistent. We investigated the role of HSP90 expression in the response of breast cancer cells to HER2-targeted treatments, by measuring cell viability/proliferation and protein expression after genetic and pharmacologic HER2/HSP90 modulation. HSP90 expression was also assessed by immunohistochemistry in a series of 72 metastatic, HER2+ breast cancer patients. In HER2+ breast cancer models (AU565, BT474, MCF7-HER2), HER2 downregulation induced HSP90 upregulation and growth inhibitory synergism between trastuzumab and docetaxel. HSP90 downregulation blunted the response to trastuzumab and docetaxel and their synergistic interactions. The addition of pertuzumab caused little additional growth inhibition, but HSP90 silencing unmasked a synergistic growth inhibitory effect with the triple combination. Conversely, HSP90 downregulation blunted the therapeutic response to trastuzumab/pertuzumab/tamoxifen or trastuzumab–emtansine. In HER2+ breast cancer patients, high HSP90 expression was associated with significant progression-free survival benefit with the triple combination, as compared with trastuzumab and chemotherapy, although the interaction test was not statistically significant. Overall, our results highlight a mechanistic role for HSP90 in determining the response of breast cancer cells to HER2-targeted agents and suggest that trastuzumab/pertuzumab combinations may be particularly advantageous in HSP90-high, HER2+ breast cancer. Full article

Controlling multiple phases by adjusting elemental ratios and applying heat treatments effectively balances the strength and ductility of refractory high-entropy alloys. In this study, five types of V-Ti-Cr-Nb-Mo alloys were designed by varying the contents of V, Ti, and Nb, followed by annealing at 1200 °C for 8 h. The alloys’ crystal structures, microstructure evolution, and mechanical properties were systematically investigated. The V-Ti-Cr-Nb-Mo alloys exhibited a typical dendritic structure with a dual-phase (BCC + HCP) matrix. When the Nb content was maintained at 35 at.% with increasing V content, the volume fraction of the HCP phase increased, and the C14 Laves phase emerged. The as-cast alloy V₁₅Ti₃₀Cr₅Nb₃₅Mo₁₅, with a triple-phase (BCC + HCP + Laves) structure, exhibited excellent mechanical properties, including a compressive strength of 1775 MPa and a ductility of 18.2%. After annealing, the HCP phase coarsened and partially dissolved, the Laves phase precipitation reduced, and while the hardness and strength decreased, the ductility improved significantly. The annealed alloy V₅Ti₃₅Cr₅Nb₄₀Mo₁₅, with a dual-phase (BCC + HCP) structure, achieved a ductility of 26.9% under a compressive strength of 1530 MPa. This work demonstrates that multi-phase refractory high-entropy alloys can significantly enhance the strength–ductility synergy, providing an experimental foundation for the compositional design and performance optimization of refractory high-entropy alloys. Full article

Neuropilin-1 is henceforth a relevant target in cancer treatment; however, its way of action remains partly elusive, and the development of small inhibitory molecules is therefore required for its study. Here, we report that two small-sized neuropilin antagonists (NRPa-47 and NRPa-48), VEGF-A₁₆₅/NRP-1 binding inhibitors, are able to decrease VEGF-Rs phosphorylation and to modulate their downstream cascades in the triple-negative breast cancer cell line (MDA-MB-231). Nevertheless, NRPas exert a divergent pathway regulation of MAPK phosphorylation, such as JNK-1/-2/-3, ERK-1/-2, and p38β/γ/δ-kinases, as well as their respective downstream targets. However, NRPa-47 and NRPa-48 apply a common down-regulation of the p38α-kinase phosphorylation and their downstream targets, emphasising its central regulating role. More importantly, none of the 40 selected kinases, including SAPK2a/p38α, are affected in vitro by NRPas, strengthening their specificity. Taken together, NRPas induced cell death by the down-modulation of pro-apoptotic and anti-apoptotic proteins, cell death receptors and adaptors, heat shock proteins (HSP-27/-60/-70), cell cycle proteins (p21, p27, phospho-RAD17), and transcription factors (p53, HIF-1α). In conclusion, we showed for the first time how NRPas may alter tumour cell signalling and contribute to the down-modulation of the cancer therapeutic key factor p38α-kinase phosphorylation. Thus, the efficient association of NRPas and p38α-kinase inhibitor strengthened this hypothesis. Full article

Edible oils are essential dietary components that provide crucial micronutrients. However, their quality can deteriorate during frying—a common cooking method—and with prolonged light exposure due to chemical reactions such as hydrolysis, oxidation, and polymerization. These processes lead to the formation of harmful compounds, particularly aldehydes. This study investigates how thermal and light exposure impact the chemical composition of five widely used edible oils: olive, rapeseed, sunflower, sesame, and peanut oils. For the thermal treatment, the oils were heated to 190 ± 5 °C in a commercial fryer, with samples taken at the start and after 10 min and 60 min of heating, while intermittently frying chicken nuggets to simulate typical frying conditions. For the light exposure treatment, the oil samples were exposed to direct sunlight for 3 and 8 h, with control samples being collected beforehand. The oil composition was analyzed using an advanced 800 MHz nuclear magnetic resonance (NMR) instrument with a triple-resonance inverse cryoprobe, providing high sensitivity and resolution. The results revealed a significant increase in various aldehyde compounds in all oils under both thermal and light exposure conditions. Notably, this study identified the generation of genotoxic and cytotoxic α,β-unsaturated aldehydes, including 4-hydroperoxy-(E)-2-alkenals, 4-hydroxy-(E)-2-alkenals, and 4,5-epoxy-(E)-2-alkenals. Given the established association of aldehydes with health risks, including cancer, Alzheimer’s, and Parkinson’s diseases, these findings highlight the importance of monitoring oil degradation during cooking and the appropriate storage of oils to minimize light exposure to reduce potential health risks. Full article

With rapid urbanization and industrialization, Vietnam is facing many challenges in solid waste management and increasing energy demand. In this context, the development of renewable energy from solid waste not only solves the problem of environmental pollution but also makes an important contribution to energy security and sustainable economic development. Solid waste to energy is a system of solid waste reatment by thermal methods, in which the heat generated from this treatment process is recovered and utilized to produce energy. Site selection is one of the biggest challenges for renewable energy projects. In addition to technical factors, this decision must also consider environmental impacts, including protecting ecosystems, minimizing noise, and limiting impacts on public health. To solve this problem, multi-criteria decision making (MCDM) methods combined with fuzzy numbers are often used. These methods allow planners to evaluate and balance competing factors, thereby determining the most optimal location for the project. In this study, the authors proposed a Spherical Fuzzy Multi-Criteria Decision-making Model (SFMCDM) for site selection in solid waste-to-energy projects. In the first stage, all criteria affecting the decision-making process are defined based on literature review, experts and triple bottom line model (social, environmental, and economic), and analytic hierarchy process (AHP), and fuzzy theory is applied for calculating the weights in the second stage. The weighted aggregated sum product assessment (WASPAS) method is utilized for ranking four potential locations in the final stage. The contribution of the proposed process is its structured, systematic, and innovative approach to solving the location selection problem for renewable energy projects. Choosing the right location not only ensures the success of the project but also contributes to the sustainable development of renewable energy. Full article

This study discusses the tribological characteristics of Polyvinylidene Fluoride (PVDF)/nanoclay composites, focusing on the effects of nanoclay content (0, 1, 2 and 3 wt.%), load, sliding speed, and sliding distance on the wear rate, friction coefficient, specific wear rate, and temperature. A Taguchi Design of Experiments technique was applied to optimize and assess these aspects. The results demonstrated that nanoclay addition considerably improved the wear resistance and frictional stability of the PVDF composites. Specifically, a nanoclay concentration of 3 wt.% gave the lowest wear rate (0.05 mg/m) with a 10 N load and 100 m sliding distance, lowering wear by roughly 23% compared to unreinforced PVDF. The friction coefficient was similarly lowered by 12% with 3 wt.% nanoclay, reaching a value of 0.38 at the highest load of 40 N. Interaction effects demonstrate that load and sliding distance are key elements impacting wear performance, with large loads and long distances virtually tripling the wear rate. ANOVA results quantify nanoclay’s contribution to a wear rate reduction of 51.29%, whereas load and sliding distance contributed 22.47% and 16.98%, respectively. Temperature increases due to frictional heating reached 10 °C under rigorous test conditions, although nanoclay treatment decreased this increase by an average of 15%. Characterization by XRD and FTIR verified the nanoclay dispersion inside the PVDF matrix, whereas the SEM images demonstrated smoother surfaces and fewer wear tracks in the nanoclay-reinforced samples. These findings illustrate the efficiency of nanoclay in increasing the wear resistance of PVDF, making these composites appropriate for high-performance applications. This research provides useful insights into enhancing PVDF/nanoclay composites, with possible uses in situations that demand endurance and thermal stability. Full article