To evaluate the validity, clinical utility, barriers and facilitators of the manikin-based audiometric simulator, Clinical Assistant for Research and Learning. The validity, clinical utility, barriers, facilitators and simulation accuracy were evaluated via an online questionnaire and in-person pure-tone audiometric assessments. A total of 38 participants (age range 21-63) completed the study. All participants had formal training in pure-tone audiometric assessments. Participants were audiology students, registered practicing audiologists, hearing instrument dispensers, and undergraduate students. The programmed and measured audiograms had an absolute agreement within 5 decibel hearing level. Ease of use, clarity of workflow, realism, and feasibility in clinical practice were the reported facilitators, whereas cost and availability of technical support were the identified barriers to implementation. The manikin-based simulator was shown to be an accurate and valid tool in practicing pure-tone audiometric procedures. Clinical applications and future directions were also discussed.
Craniopharyngiomas confined to the third ventricle present formidable surgical challenges owing to their deep location and proximity to critical neurovascular structures. This study evaluates the transcavernous sinus transtuber cinereum (TCSTC) approach, a technically advanced route that enables direct access to the third ventricle while preserving surrounding anatomy. Ten cadaveric heads were meticulously prepared with vascular injections, and the right side was dissected under magnification using a surgical microscope. High-resolution imaging and digital caliper measurements were used to define a safe entry zone through the tuber cinereum. The anatomic window was delineated between the mammillary bodies and pituitary stalk insertion. In the clinical setting, 5 patients with pure intraventricular craniopharyngiomas were treated using a pretemporal craniotomy combined with a partial medial transcavernous approach. The surgical outcomes and postoperative complications were reviewed. Cadaveric dissections confirmed that the TCSTC approach provides a consistent and safe anatomic corridor to the third ventricle, with a mean safe entry width of 8.2 mm (range 7.15-8.85 mm). This approach facilitates optimal visualization of the interpeduncular fossa, mammillary bodies, and basilar tip perforators. In all 5 clinical cases, gross total resection was achieved without any intraoperative complications. Postoperative outcomes included transient diabetes insipidus in 2 patients and long-term hormone replacement therapy in 3 patients. No cerebrospinal fluid leaks, infections, or recurrences were observed at the latest follow-up. The TCSTC approach is a safe and effective strategy for resection of pure intraventricular craniopharyngiomas. It offers enhanced anatomic visualization while minimizing hypothalamic and vascular injuries. With appropriate technical execution, maximal tumor removal with low morbidity is possible. Further validation using larger series and long-term follow-up is warranted.
Conventional type 1 dendritic cells (cDC1) specialize in cross-presentation and interleukin-12 production and are critical for immunity against intracellular pathogens and tumors, but remain rare in vivo , limiting mechanistic and translational studies. Existing bone marrow-derived dendritic cell (BMDC) methods do not achieve highly selective enrichment of cDC1 or scalable production at high purity. Here, we established a novel in vitro culture system for selective generation of CD103+ cDC1 from mouse bone marrow using defined media conditions together with recombinant FLT3L, GM-CSF, and Kit ligand (KitL), termed iDC1. iDC1 cultures enabled scalable generation of an estimated 1.5 x 10 9 CD103+ cDC1 at greater than 95% purity from a single mouse, representing at least a 75-fold increase relative to previous recombinant cytokine-based methods. Phenotypic and transcriptional analyses demonstrated that iDC1 closely align with the CD103+ cDC1 lineage while remaining clearly distinct from macrophage populations. Functionally, iDC1 responded robustly to innate stimulation, produced interleukin-12 and inflammatory chemokines, and efficiently cross-presented cell-associated antigen to CD8+ T cells. Mechanistically, KitL and GM-CSF regulated distinct stages of cDC1 generation, whereas proteomic, phospho-proteomic, and functional analyses demonstrated that GM-CSF suppresses apoptosis and oxidative stress while promoting cDC1 proliferation. iDC1 generation was dependent on the +32 kb Irf8 enhancer required for bona fide cDC1 development, and STAT5-and BRD4-associated regulatory programs were identified as important regulators of efficient iDC1 generation. Together, these findings establish iDC1 cultures as a scalable platform for studying cDC1 biology and developing cDC1-based immunotherapeutic strategies.
This review critically examines hybrid subcritical water extraction (SWE) systems that synergistically integrate auxiliary energy-based (ultrasound, microwave), solvent-modified (co-solvents, natural deep eutectic solvents (NADES)), and physical/biological (pulsed electric fields (PEF); enzymes) technologies to enhance the recovery of bioactive compounds. It analyzes the underlying mechanisms and comparative performance, demonstrating that these hybrid configurations significantly improve extraction kinetics, yield, and selectivity while operating at lower temperatures to preserve labile phytochemicals. For instance, ultrasound-enhanced subcritical water extraction achieved a maximum polysaccharide yield of 17.34% from Lentinus edodes, while microwave-assisted subcritical water extraction produced total phenolic yields of 211.73 mg GAE/g extract from blueberry pomace. Furthermore, ultrasound-assisted systems exhibit higher asymptotic extraction capacities (S∞) and rate constants (k) than SWE alone, indicating enhanced mass transfer efficiency. The analysis identifies key scalability challenges related to energy consumption and industrial reactor design. Notably, pilot-scale hybrid SWE systems remain scarcely documented in the literature: while Trigueros et al. successfully scaled subcritical water extraction of red algae residue from 0.5 L laboratory to 5 L pilot reactors with comparable yields (72-93% for various biopolymers), dedicated pilot-scale hybrid configurations combining SWE with ultrasound, microwave, or PEF have not yet been reported. This absence of mature, standardized hybrid SWE equipment at industrially relevant scales constitutes a major knowledge gap. Future pathways are outlined, emphasizing the need for intelligent process control, advanced kinetic modeling, and rigorous techno-economic and life-cycle assessments to validate sustainable, industrial-scale green extraction processes.
Performing direct CO2 reduction reaction (CO2RR) from flue gas streams containing low-concentrated CO2 (4-25% v/v) represents an opportunity to obtain added value products while reducing anthropogenic emissions. The heterogenization of molecular complexes offers a pathway to scale up CO2RR systems, especially under CO2 diluted conditions where the reactant is mass transport limited and the competitive hydrogen evolution reaction (HER) might be boosted. In this work, a formate-selective rhodium complex ([Rh(bpy')(Cp*)Cl]Cl, where bpy' = 4-(2-propyn-1-yloxymethyl)-4'-methyl-2,2'-bipyridine and Cp* = pentamethylcyclopentadienyl) is immobilized at high loading within tridimensional (3D) vertically aligned mesoporous silica films (VAMSF) electrochemically grown on glassy carbon electrodes. The resulting modified 3D electrodes allow direct CO2RR under both pure and diluted (10% v/v) CO2 streams, remaining selective for formate production in both organic and aqueous media and minimizing the contribution of HER from the support. In acetonitrile/1% H2O, Faradaic efficiencies (FE) for formate production of 66% in 100% CO2 and 47% in 10% CO2 were achieved, while in KHCO3 (pH= 6.8), FE of 47% and 43% were reached under pure and diluted CO2 streams, respectively. Finally, in a more acidic aqueous solution (pH= 3.8), FE of 59% was achieved under pure CO2. The electrodes work without preactivation or auxiliary overlayers and show recyclability and stability over multiple electrolysis cycles, indicating no structural degradation under operation conditions. To our knowledge, this is the first formate-selective heterogenized molecular complex tested under a diluted CO2 gas stream. These results reveal VAMSF as an attractive platform for bringing molecular CO2RR catalysis closer to realistic applications.
Fibrillated cellulose derived from forestry feedstocks represents a renewable and high-strength materials platform for circular bioeconomies. However, its practical implementation is hindered by the irreversible aggregation of nanocellulose architectures, including cellulose nanofibers (CNFs). Solvent-based dispersion offers a simple and practical route to prevent CNF aggregation. Here, we integrate classical and enhanced sampling molecular dynamics (MD) simulations with experimental suspension rheology and atomic force microscopy (AFM) to elucidate how solvent environments tune CNF-CNF interactions and dispersion stability. CNF-CNF contact free energies computed from MD simulations reveal reduced aggregation in acetone/water, γ-valerolactone (GVL)/water, and tetrahydrofuran (THF)/water and pure acetone compared with pure water, reflecting stronger CNF-solvent relative to inter-CNF interactions. Correspondingly, CNF-solvent suspensions in these solvent systems exhibit stronger inter-fibril network structures and enhanced recovery compared to water, indicating improved CNF-solvent affinity. Liquid cell AFM imaging in acetone-water mixtures and in pure acetone further confirm the presence of well-dispersed CNFs. By combining multiscale computation with targeted experiments, this study establishes a rational framework for solvent design to achieve stable nanocellulose dispersions for high-strength biobased materials and efficient bioenergy conversion.
Isolated lakes in subtropical floodplains serve as crucial biodiversity refuges within intensively managed agricultural landscapes. However, the ecological mechanisms underlying waterbird community assembly in these fragmented habitats remain poorly understood, limiting the development of effective conservation strategies. We conducted synchronous winter surveys (November 2022 - March 2024) across 18 isolated lakes in the Dongting Lake basin, China, and evaluated community-assembly patterns using a multidimensional diversity framework that integrated taxonomic, functional and phylogenetic perspectives. During the study period, we recorded 70 waterbird species. Species richness and abundance both increased significantly with lake area. Partitioning β-diversity revealed contrasting drivers. Turnover dominated the taxonomic and phylogenetic components, whereas functional β-diversity was driven mainly by nestedness, suggesting trait homogenisation among lakes. Null-model analyses showed that taxonomic, functional, and phylogenetic diversity did not differ significantly from stochastic expectations at the regional scale. At the local scale, functional richness (FRic) correlated positively with both functional and phylogenetic diversity. Both dimensions were also positively associated with standardized mean pairwise distances. Variance partitioning showed that pure spatial factors and shared environmental-spatial effects partially explained taxonomic β-diversity. Functional β-diversity was explained by pure environmental, pure spatial, and shared environmental-spatial factors. In contrast, only shared environmental-spatial factors accounted for variation in phylogenetic β-diversity. These findings highlight the importance of incorporating evolutionary and functional perspectives into biodiversity management. Overall, our study presents a multidimensional framework to guide effective conservation strategies and improve biodiversity outcomes in fragmented agricultural landscapes worldwide.
Hearing loss is linked to cognitive decline, yet its relation to specific executive functions remains unclear. This study examines associations between planning ability, pure-tone audiometry and speech-in-noise performance. Data were drawn from the Gutenberg Health Study (GHS), a large population-based cohort at the University Medical Center Mainz. Participants with complete pure-tone audiometry and planning ability data were included (N = 4,458; 2,314 males (51.9%), 2,144 (48.1%) females; mean age 58.0 ± 10.1 years, range 40-80). Audiologic testing included air- and bone-conduction pure-tone audiometry; hearing impairment was defined by WHO threshold. Speech-in-noise perception was measured using the German Matrix Test "Oldenburg Satztest". Planning ability was assessed using the Freiburg version of the Tower of London. Associations were analyzed with linear and logistic regression. Hearing loss (HL ≥ 20 dB; both ears) revealed a significant negative association with planning ability total score (β = -0.346, p < 0.01), but not significantly with clinical executive dysfunction (<16. Percentile total TOL) (OR=1.109, p = 0.43). Higher planning ability reduced the likelihood of hearing impairment (OR=0.97, p = 0.006) and was linked to better speech-in-noise perception (lower OLSA SRT, β = -0.035, p = 0.001). Hearing loss is linked to reduced planning ability, while higher planning ability decreases the likelihood of hearing impairment and increased speech perception in noise. These findings support models proposing that hearing loss imposes additional demands on working memory and attention. Longitudinal studies are needed to clarify causal directions and the potential role of interventions.
To evaluate the first audiometric outcomes of Nuance Audio hearing glasses, an over-the-counter solution integrating air conduction amplification technology into standard eyeglass frames, in individuals with mild to moderate hearing loss. Thirty-two adults (mean age 74 years) with symmetric, age-related mild to moderate sensorineural hearing loss were tested. Pure-tone and speech audiometry were performed under unaided and aided free-field conditions. Device settings were adjusted via smartphone app based on audiometric profiles and user preference. Paired t-tests assessed the differences. Nuance Audio glasses significantly improved hearing thresholds, especially at 4000-6000 Hz, with mean gains of 10-11 dB HL. Speech reception thresholds improved by 7 dB at 50% intelligibility and 6 dB at 100%. Amplification profile preferences matched audiometric slopes and no differences in benefit were found between mild and moderate hearing loss groups. Nuance Audio glasses provide clinically relevant improvements in pure-tone and speech thresholds for adults with mild to moderate presbycusis. Their discreet, open-ear design and self-fitting approach address barriers to traditional hearing aids and may support earlier adoption.
In this study, we introduce a method for deriving exact master equations from the dynamical map for finite open quantum systems coupled to (in)finite reservoirs, using the principle of minimal dissipation. The exact dynamics of the central spin model, which models a finite-bath open quantum system, is developed for two interaction types: Heisenberg and stochastic pure-dephasing interactions. The Heisenberg interaction yields a novel phase-covariant quantum channel in the strong-coupling regime, offering a new platform for studying a range of quantum information protocols. The stochastic pure-dephasing interaction provides the microscopic derivation of the paradigmatic non-Markovian random telegraph noise (RTN) channel, establishing its quantum foundation and offering insight into stochastic couplings. We derive the closed-form master equations for both models. As a demonstration, we explore the thermodynamic performance of these systems as quantum batteries. A direct relationship between quantum heat current and charging power is revealed, and RTN quantum batteries are shown to have advantages in charge storage.
This study characterized longitudinal changes in the associations between modifiable health behaviors (MHBs) and health outcomes, considering variations by menopausal status and hormone therapy (HT) use. Baseline and 3-year follow-up data from the Canadian Longitudinal Study on Aging were used. Participants were categorized into pre/perimenopausal, postmenopausal-HT-naïve, postmenopausal-current HT users, and postmenopausal-previous HT users. MHBs included diet quality (PURE diet score), total physical activity, and sleep duration; health outcomes included fat mass index (FMI), appendicular skeletal muscle index, gait speed, handgrip strength, and metabolic health z-score. Linear mixed models were used to examine the main and interaction effects of time, MHBs, and menopausal/HT group on each outcome, adjusting for age and demographic covariates. In all, 10,165 females were included (age: 61.3±9.9 y; 67.6% postmenopausal). The PURE diet score did not demonstrate time-dependent interactions with study groups. The association between physical activity and FMI was stronger over time in all postmenopausal groups (time × physical activity × group interaction: P=0.008). The associations between sleep with FMI (P<0.001) and appendicular skeletal muscle index (P=0.020) strengthened over time, but the association with gait speed (P<0.001) and handgrip strength (P<0.001) weakened. Relationships between sleep and gait speed weakened in postmenopausal-HT-naïve and postmenopausal-current HT users, while sleep-handgrip association weakened only among postmenopausal-current HT users (all P<0.005). These findings underscore the evolving influence of MHBs on key health outcomes and the importance of considering menopausal and HT status in longitudinal assessments of aging-related health.
The development of non-conjugated luminescent systems has innovated the traditional design strategy of through-bond conjugation (TBC) and inspired a deeper understanding on molecular photophysics. However, a challenge encountered by these non-conjugated structures is that the fluorescence of pure hydrocarbon systems is largely confined to the blue region (∼470 nm), raising the question of whether this is a fundamental limitation. Herein, we break this barrier by constructing a library of over 50 non-conjugated arylated alkenes via binuclear nickel-catalyzed hydroarylation of allenes. It is disclosed that synergistic multiple through-space interactions (TSIs) including molecular twisting-tuned intramolecular TSIs combined with intermolecular TSIs mediated by the double bonds of styrene units are critical for achieving the ultralong-wavelength aggregation-induced emission of these non-conjugated structures. This enables tunable light emission from blue to yellow, orange and, remarkably, even to single-compound-based warm white light. Furthermore, strategic substitution extends the fluorescence into the deep-red region, with a tail reaching 900 nm. This work demonstrates that non-conjugated pure hydrocarbons can achieve a broad spectrum of colors, fundamentally advancing the understanding of the luminescence phenomenon of non-conjugated systems and providing a novel design strategy for luminescent materials beyond the traditional TBC paradigm.
The microbial communities in activated sludge (AS) drive pollutant degradation and nutrient transformation into biomass and gaseous products, while also enabling resource recovery processes. In these systems, microorganisms grow as flocs, whose aggregation properties are essential for retaining active biomass while producing a clarified effluent. Understanding the microbial composition of AS and the functions of individual taxa is crucial for improving wastewater treatment practices and developing new treatment technologies. Although DNA-based studies have identified abundant taxa and inferred their metabolic roles, many of these organisms remain uncultured, limiting experimental validation of genome-based predictions. Here, we investigated whether antibiotics can transiently reduce community complexity and alleviate competitive exclusion during cultivation, thereby facilitating isolation of previously uncultured activated sludge bacteria. Dispersed single cells from AS were cultivated on agarose plates containing filter-sterilized AS fluid and 1 of 11 antibiotics at three concentrations. Full-length 16S rRNA gene amplicon sequencing indicated that antibiotics reduced microbial diversity and altered community composition in an antibiotic- and concentration-dependent manner. Two antibiotic conditions were selected for pure-culture isolation, resulting in 74 isolates that represented 28 different species based on genomic average nucleotide identity. These include 13 putatively novel species based on GTDB classification, and 19 species belonging to nine globally abundant AS core genera. Although several isolates belonged to genera with cultured representatives, they likely represent distinct species with potentially different ecological functions and physiological traits. These findings demonstrate that antibiotics can function as ecological selectors during cultivation and aid the targeted isolation of ecosystem-relevant activated sludge bacteria.IMPORTANCEBiological wastewater treatment relies on diverse microbial communities to degrade pollutants and drive nutrient transformations. Understanding the physiology and metabolism of these microorganisms is essential for improving the efficiency and cost-effectiveness of treatment processes. Much of our current knowledge is derived from 16S rRNA gene amplicon sequencing and metagenomic analyses. However, validating these sequencing- and genome-based insights requires bacterial species as pure cultures, and only a limited number of taxa common in wastewater treatment plants are currently available in culture. Here, we present an isolation strategy that uses antibiotics as a selective pressure to reduce microbial complexity and alleviate competitive exclusion during cultivation, while full-length 16S rRNA gene amplicon sequencing is used to monitor enrichment and guide targeted isolation, thereby facilitating the recovery of process-relevant activated sludge bacteria, including potentially uncultured taxa. These isolates can serve as model organisms for experimental validation of genome-based predictions.
CaFe-layered double hydroxides (LDHs) can effectively address the low degradation efficiency of polycyclic aromatic hydrocarbons (PAHs) in constructed wetlands (CWs). However, the lack of sustained electron donors often limits their long-term efficacy. To bridge this gap, CWs amended with pure CaFe-LDHs and CaFe-LDHs/poplar sawdust composite were established to assess their impact on benzo[a]pyrene (BaP) removal. Crucially, the poplar sawdust acted as a slow-release source of dissolved organic matter (DOM), providing sustained carbon and molecular bridges that accelerated interfacial electron transfer and strongly drove the Fe (III) and Fe (II) redox cycling of the LDHs. Driven by this synergistic mechanism, the composite substrate enhanced BaP removal efficiency by 7.3% and 16.6% compared to the pure LDHs and control groups, respectively. The continuous electron supply and DOM-mediated desorption reduced BaP retention in the solid substrate (11.5 ng/g) and facilitated plant interception, with belowground tissues (3.7 ng/g) accumulating significantly higher concentrations than aboveground parts (0.9 ng/g). Furthermore, alleviation of oxidative stress and sustained carbon supply reshaped the microbial community, evidenced by a 10.5% increase in species level and enrichment of genera associated with PAHs degradation and iron reduction (e.g., Pseudoxanthomonas, Geobacter, and Arthrobacter). Consequently, this optimized microenvironment significantly upregulated the expression of genes encoding ring-cleavage dioxygenases (catA, nahA) and stress-response enzymes (SOD). Our study elucidates the synergistic coupling of LDH-mediated iron cycling and DOM-driven metabolic processes promoted by lignin-based poplar wood within composite matrices, providing a low-cost and novel substrate-modification strategy for designing high-efficiency constructed wetlands targeting recalcitrant organic pollutants.
para-Menthane-3,8-diol (PMD) is a widely used bio-based insect repellent. However, its conventional synthesis is limited by protracted reaction times. Herein, we report an ultrasound-assisted Prins cyclization of citronellal, a monoterpenoid aldehyde, to PMD under 20 kHz irradiation. Using pure citronellal, ultrasound irradiation at 40% amplitude (∼48 µm) afforded PMD with 98% GC-FID purity within 2 h, compared with 87% PMD obtained after 10 h under conventional heating. Even at 100% amplitude (∼120 µm), the reaction proceeded within 10 min while maintaining a high PMD content of approximately 93%. For lemon eucalyptus (Eucalyptus citriodora) oil, ultrasound irradiation at 40-60% amplitude (∼48-72 µm) reduced reaction times from 15 h to 0.5-2.0 h while providing PMD contents comparable to those obtained by conventional heating. Notably, crystallization from the natural oil feedstock increased the cis-isomer content to 90%, compared with 65% obtained from pure citronellal. The observed cis stereoselectivity is proposed to arise from steric effects associated with the 3-methyl substituent of citronellal during intramolecular cyclization. Density functional theory calculations qualitatively support the proposed stereoselective mechanism. These findings provide an efficient approach for the synthesis and purification of PMD while offering mechanistic insights into stereochemical control in Prins cyclization reactions.
ZTO/PVA nanocomposite sheets were successfully fabricated using precipitation and sonochemical routes for ZnO and TiO2 nanoparticle synthesis, respectively, followed by solution casting into the PVA matrix. This process ensured uniform dispersion of ZTO nanoparticles within the polymer matrix and was completed without post-mixing thermal calcination, representing an energy-efficient and novel synthesis route. XRD analysis confirmed the incorporation of nanoparticles and revealed an anatase-to-rutile phase transformation of TiO2 after composite formation. XPS spectra confirmed the presence of Zn, O, and Ti LMM signals, indicating the presence of oxide components within the composite structure. Optical analysis showed a significant reduction in the band gap after ZTO incorporation. The indirect band gap decreased from 3.03 eV for pure PVA to 2.93, 2.72, and 2.5 eV for 2, 5, and 8 wt% ZTO/PVA, respectively, while the direct band gap decreased from 4.59 to 2.72 eV at higher filler loading. Photoluminescence results showed a slight red shift for 2 and 5 wt% ZTO/PVA due to interfacial defect states, followed by a blue shift at 8 wt% associated with near-band-edge emission and phase transformation effects. AFM analysis revealed a significant increase in surface roughness from 9.46 to 131.97 nm as ZTO content increased, indicating nanoparticle aggregation and surface heterogeneity. Thermal analysis demonstrated improved thermal stability and multi-step degradation behaviour. Dielectric measurements showed high permittivity at low frequencies due to interfacial polarisation, with non-Debye relaxation behaviour confirmed by Havriliak-Negami and Cole-Cole analysis. Magnetic measurements indicated predominantly non-magnetic behaviour with a slight enhancement after ZTO incorporation. These findings demonstrate that the addition of ZTO effectively tailors the structural, optical, thermal, dielectric, and magnetic properties of PVA nanocomposites, making them promising for multifunctional dielectric and optoelectronic applications.
The co-administration of niclosamide (NCM) with erlotinib hydrochloride (ERL) has been shown to restore ERL sensitivity in resistant non-small cell lung cancer. However, the poor physicochemical properties of both molecules necessitate a specialized delivery system for improved delivery and efficacy. Box-Behnken design was used to evaluate the key variables affecting NCM-ERL-Liposome characteristics. The design yielded a broader design space for the selected factors that can achieve superior attributes, including particle size of 93.42 ± 2.41 nm, polydispersity index of 0.356 ± 0.01, zeta potential of -9.40 ± 0.59 mV, and maximal entrapment efficiencies (NCM: 77.97 ± 2.25%; ERL: 72.75 ± 1.49%). Trehalose showed better redispersion and good physical stability, as confirmed from ATR-IR/PXRD/DSC. The formulation demonstrated sustained dual-drug release, stability for three months at 4 ± 2 °C, and hemocompatibility with minimal hemolysis. In-vitro studies showed that NCM restored ERL sensitivity, with lower IC50 values (HCC827-P: 11.27 ± 4.04 µg/mL; HCC827-ER: 7.59 ± 0.62 µg/mL) than those of pure drugs or the physical mixture. The prepared NCM-ERL-Liposomes showed enhanced internalization, triggered caspase-3/7-mediated apoptosis (1.42-fold increase), and suppressed p-EGFR/p-STAT3, indicating adequate payload protection and targeted intracellular release. These results establish a translational platform that requires PK/PD studies in resistant NSCLC models to support precision oncology therapeutics. Article highlightsThis study discusses the challenge of chemotherapeutic resistance in NSCLC and explores dual-loaded liposomal nanocarriers as a potential solution.NCM-ERL-Liposomes were developed via thin-film hydration and systematic BBD optimization.Cryoprotectant-engineered glassy matrices mitigate lyophilization stress.The HCC827-ER model mimics clinical resistance (>6-fold increase in IC50).Maximal caspase-3/7 induction reverses resistance via apoptosis.Potent p-EGFR/p-STAT3 inhibition restores erlotinib sensitivity.
Microbial arsenic (As) methylation is enhanced in flooded paddy soils, producing mainly dimethylarsenic (DMA), which can cause rice straighthead disease and large yield losses. Sulfate-reducing bacteria (SRB) have been implicated as primary As methylators, largely based on experiments employing molybdate as a selective inhibitor of SRB. However, the specificity of molybdate inhibition on SRB- and non-SRB-mediated As methylation remains inadequately evaluated. In this study, we showed that molybdate addition at 10 mmol kg-1 suppressed DMA production in flooded paddy soil by 41%, concomitant with decreased transcription of genes encoding dissimilatory sulfite reductase (by 78%) and arsenite S-adenosylmethionine methyltransferase (arsM, by 28%). Metatranscriptomic analysis showed that molybdate additions significantly suppressed the expression of 12 and 31 arsMs hosted by SRB and non-SRB, respectively. To decipher the effects of molybdate on As methylation, we performed pure culture experiments with representative SRB and non-SRB fermentative bacteria isolated from paddy soils. Molybdate specifically inhibited the growth of SRB and completely suppressed its As methylation. Molybdate also caused partial inhibition of As methylation by fermentative bacteria without affecting their growth. Integrated transcriptomic and targeted metabolomic analyses revealed that molybdate suppressed the As(III)-induced transcription of arsM and trx [encoding thioredoxin (Trx) required as a reductant for As methylation] and the biosynthesis of methyl donor S-adenosylmethionine (SAM), contributing to the partial inhibition of As methylation in non-SRB. These findings indicate that, although molybdate inhibits SRB growth specifically and the associated As methylation, it can also cause nontarget effects on As methylation mediated by fermentative bacteria, which should be taken into account when interpreting microbial contributions to As methylation in flooded paddy soils.
The extensive use of pesticides poses serious risks to the environment and human health. Developing advanced technology for pesticide degradation is a key demand in modern agriculture. In this work, we fabricated a unique Co9S8/Fe2O3 Schottky junction via in situ growth of Co9S8 onto MIL-88A(Fe) derived Fe2O3 nanotubes, and applied it for degrading a typical neonicotinoid pesticide, thiamethoxam, by photocatalytic peroxymonosulfate (PMS) activation. The established heterojunction enables rapid electron transfer from Fe2O3 to Co9S8, thereby increasing the excitation-deexcitation cycle efficiency by 20-fold and prolonging the photogenerated electron lifetime by 3-fold compared to pure Fe2O3. Remarkably, ultrafast charge transfer from Fe2O3 to Co9S8 contributes over 70% of total photogenerated charges, which significantly promotes the Co(III)/Co(II) redox cycle and enhances PMS activation for radical generation. Co9S8/Fe2O3 composites exhibit superior degradation activity in diverse natural waters and maintain stability in continuous-flow reactors. Wheat growth experiments were used to examine purification capability. The study introduces a robust, efficient photo-Fenton catalyst for removing neonicotinoid pesticides from water and reducing ecological toxicity, with impressive stability and practical application potential.
Polyvinyl alcohol (PVA) phantoms are typically isotropic and are widely used to validate ultrasound elastography techniques for soft-tissue evaluation. However, some biological soft tissues (e.g., skeletal muscle) exhibit distinct mechanical anisotropy, which necessitates the use of anisotropic PVA phantoms for the rigorous testing of elastography methods targeting these tissues. While prior studies have noted that in-house anisotropic PVA phantoms can be fabricated via stretch-integrated freeze/thaw cycles (FTCs), critical technical details (e.g., fabrication process, quality control) remain insufficiently documented. This work presents a visually detailed, reproducible protocol for fabricating anisotropic PVA phantoms, focusing on key materials, stepwise processes, and quality controls to induce stable, uniform anisotropy. Key materials include PVA as the phantom matrix, potassium sorbate as a preservative, graphite particles as acoustic scatterers, and pure water (or deionized water) as the solvent. The fabrication process comprises three core stages: 1) Preparation of a homogeneous PVA-based solution through controlled thermal conditions to ensure complete PVA dissolution; 2) Solidification via FTCs: the cooled solution is poured into 3D-printed molds, followed by stretch-free FTCs to form a preliminary structure; 3) Inducing anisotropy via stretched FTCs: additional FTCs are performed under controlled stretching to induce directional anisotropy. Quality-control measures (e.g., avoiding air bubbles during PVA dissolution) are described in detail. After fabrication, ultrasound shear wave imaging (SWI) and uniaxial tensile testing are employed to confirm the phantom's mechanical anisotropy. This paper provides a standardized approach for fabricating anisotropic tissue-mimicking phantoms to validate ultrasound elastography techniques with enhanced accuracy and consistency.