Search Results (128)

Drug resistance remains a critical barrier to effective treatment in several cancers, particularly triple-negative breast cancer (TNBC). Estrogen receptor α36 (ERα36), a variant of the estrogen receptor in ER-negative breast cancer cells, plays important roles in cancer cell proliferation. We investigated the role of ERα36 in regulating multidrug resistance protein 1 (MDR1) in MDA-MB-231 human breast cancer cells. The activation of ERα36 by BSA-conjugated estradiol (BSA-E2) increased cell viability under Adriamycin exposure, suggesting its involvement in promoting drug resistance. BSA-E2 treatment significantly reduced the intracellular rhodamine-123 levels by activating the MDR1 efflux function, which was linked to increased MDR1 transcription and protein expression. The mechanical ERα36-mediated BSA-E2-induced activation of EGFR and downstream signaling via c-Src led to an activation of the Akt/ERK pathways and transcription factors, NF-κB and CREB. Additionally, ERα36 is involved in activating Wnt/β-catenin pathways to induce MDR1 expression. The silencing of ERα36 inhibited the BSA-E2-induced phosphorylation of Akt and ERK, thereby reducing MDR1 expression via downregulation of NF-κB and CREB as well as Wnt/β-catenin signaling. These findings demonstrated that ERα36 promotes MDR1 expression through multiple non-genomic signaling cascades, including Akt/ERK-NF-κB/CREB and Wnt/β-catenin pathways, and highlight the role of ERα36 as a promising target to enhance chemotherapeutic efficacy in TNBC. Full article

Planar heaters are designed to deliver uniform heat across broad surfaces and serve as critical components in applications requiring energy efficiency, safety, and mechanical flexibility, such as wearable electronics and smart textiles. However, conventional metal-based heaters are limited by poor adaptability to curved or complex surfaces, low mechanical compliance, and susceptibility to oxidation-induced degradation. To overcome these challenges, we applied a protein-assisted electroless copper (Cu) plating strategy to electrospun poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) nanofiber substrates to fabricate flexible, conductive planar heating membranes. For interfacial functionalization, a protein-based engineering approach using bovine serum albumin (BSA) was employed to facilitate palladium ion coordination and seed formation. The resulting membrane exhibited a dense, continuous Cu coating, low sheet resistance, excellent durability under mechanical deformation, and stable heating performance at low voltages. These results demonstrate that the BSA-assisted strategy can be effectively extended to complex three-dimensional fibrous membranes, supporting its scalability and practical potential for next-generation conformal and wearable planar heaters. Full article

B₄C is beneficial for forming a glassy film that is effective at impeding oxygen diffusion and improving the oxidation resistance of coatings at high temperature. The effect of B₄C content on the oxidation resistance of a B₄C-SiO₂–Albite/Al₂O₃ (BSA/AO) double-layer coating by the slurry brushing method at 900 °C was investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM) with energy-dispersive spectroscopy (EDS), and differential scanning calorimetry (DSC) with thermogravimetric analysis (TGA) in this work. It is indicated that the composite coating with 20 wt% B₄C exhibits excellent oxidation resistance at high temperature, which shows a mass loss of only 0.11% for the coated carbon block after being exposed to 900 °C for 196 h. This is attributed to the in situ formation of a thin, dense glass layer with good self-healing ability at the interface of the B₄C-SiO₂–Albite/Al₂O₃ composite coating within 1 h and the persistence and stability of the dense glass layer during exposure. The mechanism is discussed in detail. Full article

Precise separation and antifouling capabilities are critical for the application of membrane separation technology. In this work, we developed a multiplayer layer-by-layer assembly strategy to sequentially deposit tannic acid (TA) and lysozyme (Lys) onto polyethersulfone/iron (PES/Fe) ultrafiltration membrane substrates, enabling the simple and efficient fabrication of a biofouling-resistant loose nanofiltration (LNF) membrane with superior dye/salt separation performance. This approach fully leverages the multifunctionality of TA by exploiting its coordination with Fe³⁺ and non-covalent interactions with Lys. The obtained PES/Fe-TA-Lys LNF membrane exhibits a pure water flux of 57.5 L·m⁻²·h⁻¹, along with exceptional dye rejection rates (98.3% for Congo Red (CR), 99.2% for Methyl Blue (MB), 98.4% for Eriochrome Black T (EBT), and 67.6% for Acid Orange 74 (AO74)) while maintaining minimal salt retention (8.2% for Na₂SO₄, 4.3% for MgSO₄, 3.5% for NaCl, and 2.4% for MgCl₂). The PES/Fe-TA-Lys LNF membrane also displays outstanding antifouling performance against bovine serum albumin (BSA), humic acid (HA), and CR, along with strong biofouling resistance against Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) via synergistic anti-adhesion and biofilm inhibiting effects. This work presents a novel and scalable approach to fabricating biofouling-resistant LNF membranes, offering great potential for dye/salt separation in textile wastewater treatment. Full article

Irbesartan (IRB) is a commonly used BCS Class II antihypertensive drug requiring dissolving capacity enhancement to address oral bioavailability limitations. In this work, seven new IRB salts were successfully synthesized, including one carboxylate (IRB-MAL) and six sulfonate salts (IRB-TOSA, IRB-BSA, IRB-4-CBSA, IRB-2, 5-CBSA, IRB-MSA, and IRB-CPSA). Their vitro dissolution, intrinsic dissolution rates (IDRs), thermal/hygroscopic stability (via thermal analysis, dynamic vapor sorption, and accelerated stability tests), and phase transition process (monitored by in situ Raman spectroscopy) were evaluated. The results revealed that IRB-TOSA, IRB-MAL, IRB-BSA, IRB-4-CBSA, and IRB-MSA salts exhibited IDRs of 0.3194–0.7383 mg/(cm²·min), all significantly higher than IRB, with dissolution concentrations increased by 14.9–113.6%. IRB-TOSA and IRB-4-CBSA salts demonstrated excellent hydrothermal stability. Single crystal structure analysis confirmed proton transfer from coformers’ sulfonic/carboxylic acids (deprotonation site, H-out) to IRB’s diazaheterocycles (protonation site, H-in) in IRB salts. Six sulfonate salts exhibited N_H-in–H···O_H-out and N_non-H-in–H···O_H-out hydrogen bonds, with the former absent in IRB-MAL. Furthermore, supramolecular synthon studies revealed distinct hydrogen-bonding patterns (e.g., bifurcated bonds in 2,5-CBSA and CPSA salts) that correlate with moisture resistance. Quantitative analysis of IRB salts suggested hydrogen bond strengths may influence their melting points (decomposition temperatures). This study demonstrates that IRB salts hold promise for advanced pharmaceutical applications. Full article

Glycation is a process in which reducing sugars bind to proteins, resulting in the formation of advanced glycation end products (AGEs). These AGEs accumulate in the skin, promote excessive collagen crosslinking, and disrupt the extracellular matrix (ECM), impairing normal cellular functions and contributing to skin aging. To evaluate the anti-glycation efficacy of lotus stamen extract (LSE), we employed the BSA–fructose system and a high glucose (HG)-induced fibroblast glycation model. The results demonstrated that LSE effectively inhibited cellular glycation and also exhibited anti-inflammatory, antioxidative, and anti-senescent effects in HG-induced human skin fibroblasts (HSF). Further investigation into the anti-glycation mechanism and component analysis of the lotus stamen ethyl acetate extract (LSEE) led to the identification of 15 flavonoids. The anti-glycation results indicated that these flavonoids are likely the primary active constituents in LSE. Mechanistic studies revealed that GLO1 plays a crucial role in cellular resistance to glycation, and LSEE enhanced GLO1 expression through the Nrf2/Keap1 pro-survival pathway, thereby mitigating intracellular AGE production. In summary, LSEE and its multiple flavonoid components exhibit potent intracellular anti-glycation activity and present significant potential to be developed as a natural and organic product for cosmetic and healthcare applications. Full article

Control of natural organic matter (NOM) reversible and irreversible fouling with ceramic membranes for drinking water applications with chemically enhanced backwash (CEB) protocols is limited. This research examines the efficiency of various chemical combinations with non-ionic surfactants to control the NOM fouling caused by humic acid (HA) and protein foulants. Two commercially available non-ionic surfactants, Tween 80 and Triton X100, combined with conventional cleaning solutions, were analyzed with respect to membrane fouling and cleaning using the resistance in series (RIS) model, membrane permeability, carbon mass balance, and contact angle measurements. The results demonstrated that in all cases, CEB outperformed hydraulic backwashing; in addition, the inclusion of surfactants demonstrated enhanced the fouling control with protein foulants more than humic acid. The transmembrane pressure (TMP) with surfactant CEB was controlled to within a range of 83–105 kPa compared to hydraulic backwash at approx. 128 kPa for HA and BSA. The carbon mass balance analysis indicates that Tween 80 surfactant-based CEB demonstrated effective fouling control, leaving only 20% irreversible fouling with HA and 30% with BSA while the hydraulic backwash resulted in 57% irreversible fouling of carbon on the membrane for HA and BSA. Full article

Sulfonylureas (SUs)—a class of drugs primarily used to treat type 2 diabetes—have recently attracted interest for their potential anticancer properties. While some studies have explored the chemical modification or design of new SU derivatives, our work instead centers on biological evaluations of all commercially available SUs in combination with doxorubicin (DOXO). These antidiabetic agents act by stimulating insulin secretion via K_ATP channel inhibition, and because K_ATP channels share structural features with ATP-binding cassette (ABC) transporters involved in multidrug resistance (e.g., P-glycoprotein, MRP1, and MRP2), SUs may also reduce cancer cell drug efflux. In this study, we systematically examined each commercially available SU for potential synergy with DOXO in a panel of human cancer cell lines. Notably, combining DOXO with glimepiride (GLIM), the newest SU, results in a 4.4-fold increase in cytotoxicity against MCF-7 breast cancer cells relative to DOXO alone. Mechanistic studies suggest that the observed synergy may arise from increased intracellular accumulation of DOXO. Preliminary in vivo experiments support these findings, showing that DOXO (5 mg/kg, i.v.) plus GLIM (4 mg/kg, i.p.) is more effective at inhibiting 4T1 tumor growth in mice than DOXO alone. Additionally, we show that adding a small amount of the surfactant Tween-80 to culture media affects SU binding to bovine serum albumin (BSA), potentially unmasking anticancer effects of SUs that strongly bind to proteins. Overall, these results underscore the potential of repurposing existing SUs to enhance standard chemotherapy regimens. Full article

Cold tolerance in rapeseed is closely related to its growth, yield, and geographical distribution. However, the mechanisms underlying cold resistance in rapeseed remain unclear. This study aimed to explore cold resistance genes and provide new insights into the molecular mechanisms of cold resistance in rapeseed. Rapeseed M98 (cold-sensitive line) and D1 (cold-tolerant line) were used as parental lines. In their F₂ population, 30 seedlings with the lowest cold damage levels and 30 with the highest cold damage levels were selected to construct cold-tolerant and cold-sensitive pools, respectively. The two pools and parental lines were analyzed using bulk segregant sequencing (BSA-seq). The G’-value analysis indicated a single peak on Chromosome C09 as the candidate interval, which had a 2.59 Mb segment with 69 candidate genes. Combined time-course and weighted gene co-expression network analyses were performed at seven time points to reveal the genetic basis of the two-parent response to low temperatures. Twelve differentially expressed genes primarily involved in plant cold resistance were identified. Combined BSA-seq and transcriptome analysis revealed BnaC09G0354200ZS, BnaC09G0353200ZS, and BnaC09G0356600ZS as the candidate genes. Quantitative real-time PCR validation of the candidate genes was consistent with RNA-seq. This study facilitates the exploration of cold tolerance mechanisms in rapeseed. Full article

Leaf stripe disease, caused by Pyrenophora graminea, is a seed-borne fungal disease that significantly impacts hulless barley (Hordeum vulgare var. nudum) production on the Qinghai-Tibet Plateau. This study aimed to identify genetic factors conferring resistance to the leaf stripe by analyzing an F₃ population derived from a cross between the resistant landrace Teliteqingke and the susceptible landrace Dulihuang. Genetic analysis revealed that resistance in Teliteqingke was governed by two dominant genes. Using bulked segregant analysis combined with an SNP array (BSA-SNP) and RNA-seq, we identified two candidate regions on chromosomes 3H and 7H. Further analysis focused on chromosome 3H, which revealed a candidate genomic region containing seven potential disease-resistance genes. Among these, RT-qPCR experiments demonstrated significant expression induction of HORVU.MOREX.r3.3HG0232110.1 (encoding a RING/U-box superfamily protein) and HORVU.MOREX.r3.3HG0232410.1 (encoding a bZIP transcription factor) showed significant expression induction following inoculation with P. graminea. These genes are strong candidates for the resistance mechanism against leaf stripes in Teliteqingke. These results provide a foundation for functional validation of these genes and offer valuable insights for breeding disease-resistant hulless barley. Full article

T-cell redirecting therapies, which include chimeric antigen receptor T-cells (CAR-Ts) and bispecific antibodies (BSAs), have revolutionized the treatment of relapsed\refractory large B-cell lymphoma (LBCL). Expanding clinical experience with these advanced therapies shows the potential for the optimization of their use with combination or consolidation strategies, which necessitates the prognostic stratification of patients. While traditional clinical prognostic factors identified in the era of chemotherapy are characterized by limited value, the tumor microenvironment (TME) is becoming a new prognostic cluster. We examine how the heterogeneity of LBCL, characterized by variations in tumor parameters and differences in TME immune cell composition, immune checkpoint expression, and cytokine milieu, correlates with both positive responses and resistance to treatment. While classical parameters such as histological subtype, cell of origin, and target antigen expression lack proven prognostic value for T-cell redirecting therapies, the density and functional state of tumor-infiltrating lymphocytes, tumor-associated macrophages, and immune checkpoint molecules are shown to be critical determinants of therapeutic success, particularly in CAR-T therapy. We identify several gaps in the current knowledge and suggest that the insights gained from CAR-T experience could be instrumental in refining BSA applications. This report also highlights limitations in the current knowledge, as TME data derive from a limited number of registrational trials with varying methodologies, complicating cross-study comparisons and often focusing on immediate response metrics rather than long-term outcomes. By dissecting the complex interactions within the TME, this review aims to identify new prognostic factors and targets, ultimately fostering more effective and tailored treatment strategies for LBCL patients. Full article

The development of ultrafiltration (UF) polymeric membranes with high flux and enhanced antifouling properties bridges a critical gap in the polymeric membrane fabrication research field. In the present work, the preparation of novel PES membranes incorporated with carrageenan (CAR), which is a natural polymer derived from edible red seaweed, is reported for the first time. The PES/CAR membranes were prepared by using the nonsolvent-induced phase separation (NIPS) method at 0.1–4.0 wt.% CAR loadings in the casting solutions. The use of dimethylsulfoxide (DMSO), which is a bio-based and low-toxic solvent, is reported. Scanning electron microscopy, atomic force microscopy, water contact angle, porosity, and zeta potential measurements were used to evaluate the surface morphology, structure, pore size, hydrophilicity, and surface charge of the prepared membranes. The filtration performance of PES/CAR membranes was tested with bovine serum albumin (BSA) solutions. It was shown that CAR incorporation in the casting solutions notably increased hydrophilicity, porosity, pore size, surface charge, and fouling resistance of the prepared membranes compared with plain PES membranes due to the hydrophilic nature and pore-forming properties of CAR. The PES/CAR membranes showed a significant reduction in irreversible and total fouling during filtration of BSA solutions by 38% and 32%, respectively, an enhancement in the flux recovery ratio by 20–40%, and an improvement in mechanical properties by 1.5-fold when compared with plain PES membranes. The findings of the present study indicate that CAR can be used as a promising additive for the development of PES UF membranes with enhanced properties and performance for water treatment applications. Full article

Electro-conductive membranes coupled with a low-voltage electric field can enhance pollutant removal and mitigate membrane fouling, demonstrating significant potential for electrified wastewater treatment. However, efficient fabrication of conductive membranes poses challenges. An in situ oxidative polymerization approach was applied to prepare PVDF-based conductive membranes (PVDF-CMs) and response surface methodology (RSM) was adopted to optimize modification conditions enhancing membrane performance. The anti-fouling property of the conductive membranes was analyzed using model pollutants. The results indicate that when the concentrations of the pyrrole, BVIMBF₄, and FeCl₃·6H₂O are 0.9 mol/L, 4.8 mmol, and 0.8 mol/L, respectively, the electrical resistance of the PVDF-CM is 93 Ω/sq with the water contact angle of 31°, demonstrating good conductivity and hydrophilicity. Batch membrane filtration experiments coupled with negative voltage indicated that when an external voltage of 2.0 V is applied, membrane fouling rates for the conductive membrane filtering BSA and SA solutions are reduced by 17.7% and 17.2%, respectively, compared to the control (0 V). When an external voltage of 0.5 V is applied, the membrane fouling rate for the conductive membrane filtering HA solution is reduced by 72.6%. This study provides a valuable reference for the efficient preparation of conductive membranes for cost-effective wastewater treatment. Full article

Nanoparticles are known to have a high specific surface area, which accounts for an increased probability of their interaction with bacterial cells. Therefore, the application of silver(I) nanoparticles (AgNPs) and their nanocomposites as antimicrobial agents against drug-resistant bacterial strains appears to be prospective. A critical point for the advancement of AgNPs into clinical practice is a fundamental understanding of their behavior in biological systems, including protein binding and interaction with blood components, which reflects their toxicity. The latter is primarily determined by the physicochemical properties of AgNPs, namely their size, shape, surface chemistry, etc. Therefore, nanotoxicity may be substantially reduced through the manipulation of certain physicochemical characteristics of AgNPs, increasing their biocompatibility and hence paving the way for possible biomedical applications. In this study we have focused on estimating the binding affinity of the synthesized Ag(I) complexes of 2-(4,6-di-tert-butyl-2,3-dihydroxyphenylsulfanyl)-acetic acid and 4,6-di-tert-butyl-2,3-dihydroxybenzaldehyde isonicotinoyl hydrazone, as well as AgNPs derived thereof to bovine serum albumin (BSA) and hemoglobin by the fluorimetric method. Furthermore, cellular toxicity of the AgNPs towards human erythrocytes was measured in a hemolysis assay. Organosols formed by the Ag(I) complexes upon their reduction to AgNPs in acetonitrile and DMSO were characterized by the transmission electron microscopy (TEM) method and atomic force microscopy (AFM). Full article

The fouling of protein on the surface of reverse osmosis (RO) membranes is a surface phenomenon strongly dependent on the physical and chemical characteristics of both the membrane surface and the foulant molecule. Much of the focus on fouling mitigation is on the synthesis of more hydrophilic membrane materials. However, hydrophilicity is only one of several factors affecting foulant attachment. A more systematic and rationalized methodology is needed to screen the membrane materials for the synthesis of fouling-resistant materials, which will ensure the prevention of the accumulation of foulants on the membrane surfaces, avoiding the trial and error methodology used in most membrane synthesis in the literature. If a clear correlation is found between various membrane surface properties, in combination or singly, and the amount of fouling, this will facilitate the establishment of a systematic strategy of screening materials and enhance the selection of membrane materials and therefore will reflect on the efficiency of the membrane process. In this work, eight commercial reverse osmosis membranes were tested for bovine serum albumin (BSA) protein fouling. The work here focused on three surface membrane properties: the surface roughness, the water contact angle (hydrophilicity), and finally the Hansen solubility parameter (HSP) distance between the foulant understudy (BSA protein) and the membrane surface. The HSP distance was investigated as it represented the affinities of materials to each other, and therefore, it was believed to have an important contribution to the tendency of foulant to stick to the surface of the membrane. The results showed that the surface roughness and the HSP distance contributed to membrane fouling more than the hydrophilicity. We recommend taking into account the HSP distance between the membrane material and foulants when selecting membrane materials. Full article