Removal of particulate matter and dissolved organic matter from sedimentation sludge water during pre-sedimentation process: Performances and mechanisms.

Sedimentation sludge water (SSW), a prominent constituent of wastewater from drinking water treatment plants, has received limited attention in terms of its treatment and utilization likely due to the perceived difficulties associated with managing SSW sludge. This study comprehensively evaluated the water quality of SSW by comparing it to a well-documented wastewater (filter backwash water (FBW)). Furthermore, it investigated the pollutant variations in the SSW during pre-sedimentation process, probed the underlying reaction mechanism, and explored the feasibility of employing a pilot-scale coagulation-sedimentation process for SSW treatment. The levels of most water quality parameters were generally comparable between SSW and FBW. During the pre-sedimentation of SSW, significant removal of turbidity, bacterial counts, and dissolved organic matter (DOM) was observed. The characterization of DOM components, molecular weight distributions, and optical properties revealed that the macromolecular proteinaceous biopolymers and humic acids were preferentially removed. The characterization of particulates indicated that high surface energy, zeta potential, and bridging/adsorption/sedimentation/coagulation capacities in aluminum residuals of SSW, underscoring its potential as a coagulant and promoting the generation and sedimentation of inorganic-organic complexes. The coagulation-sedimentation process could effectively remove pollutants from low-turbidity SSW ([turbidity]0 < 15 NTU). These findings provide valuable insights into the water quality dynamics of SSW during the pre-sedimentation process, facilitating the development of SSW quality management and enhancing its reuse rate.

Enzymatic bioremediation of polycyclic aromatic hydrocarbons (PAHs) in contaminated soil: a study on the recombinant laccase TVL.

Polycyclic aromatic hydrocarbons (PAHs) are pervasive and persistent pollutants in contaminated soil, posing a severe health and environmental threat. Enzymatic bioremediation presents a viable solution for the remediation of PAH-contaminated soil. In this study, a recombinant laccase with the encoding gene originating from Trametes villosa and recombinantly expressed in Aspergillus oryzae, designated as TVL, was discovered to possess strong PAH reduction capabilities. The specific enzyme activity of TVL was 73485 and 5102 LAMU/g enzyme protein at pH 5.0/7.0 and 37°C. Furthermore, it exhibited significant benzo[a]pyrene degradation, with 100% and 90.48% degradation at pH 5.0/7.0 after 24 h in the liquid phase. The degradation process of benzo[a]pyrene in soil was thoroughly investigated. Optimal conditions were identified as 15 mg/g NK-BSoil-3 and 1.35 mg/g HBT, resulting in a removal rate of 37.54% within 7 days when 0.01 U/g of TVL was applied. The potential mechanisms were investigated using molecular docking simulation. The binding energy between benzo[a]pyrene and TVL protein is notably robust, suggesting a higher propensity for enzyme binding. The TVL protein pocket contains nine amino acids that can interact most strongly with benzo[a]pyrene. Consequently, the recombinant laccase TVL holds considerable practical significance in bioremediation.

Reversible chemoresistance of pancreatic cancer grown as spheroids.

Better in vitro models are needed to identify active drugs to treat pancreatic adenocarcinoma (PAC) patients. We used 3D hanging drop cultures to produce spheroids from five PAC cell lines and tested nine FDA-approved drugs in clinical use. All PAC cell lines in 2D culture were sensitive to three drugs (gemcitabine, docetaxel and nab-paclitaxel), however most PAC (4/5) 3D spheroids acquired profound chemoresistance even at 10 µM. In contrast, spheroids retained sensitivity to the investigational drug triptolide, which induced apoptosis. The acquired chemoresistance was also transiently retained when cells were placed back into 2D culture and six genes potentially associated with chemoresistance were identified by microarray and confirmed using quantitative RT-PCR. We demonstrate the additive effect of gemcitabine and erlotinib, from the 12 different combinations of nine drugs tested. This comprehensive study shows spheroids as a useful multicellular model of PAC for drug screening and elucidating the mechanism of chemoresistance.

Developing a Palladium(II) Agent to Overcome Multidrug Resistance and Metastasis of Liver Tumor by Targeted Multiacting on Tumor Cell, Inactivating Cancer-Associated Fibroblast and Activating Immune Response.

To targeted overcome the multidrug resistance (MDR) and metastasis of liver tumors, we proposed to develop a palladium (Pd) agent based on a specific residue of human serum albumin (HSA) for multiacting on tumor cell and other components in the tumor microenvironment. To this end, a series of Pd(II) 2-acetylpyridine thiosemicarbazone compounds were optimized to obtain a Pd(II) compound (5b) with significant cytotoxicity against HepG2/ADM cells. Subsequently, we constructed a HSA-5b complex delivery system and revealed the structural mechanism of HSA delivering 5b. Importantly, 5b/HSA-5b effectively inhibited the growth and metastasis of multidrug resistant liver tumors, and HSA enhanced the targeting ability of 5b and reduced its side effects in vivo. Furthermore, we confirmed the mechanisms of 5b/HSA-5b integrating to overcome MDR and metastasis of liver tumors: multiacting on cancer cell, activating immune response, and inactivating cancer-associated fibroblasts.

Antifungal Activity of Phloroglucinol Derivatives against Botrytis cinerea and Monilinia fructicola.

Naturally derived compounds show promise as treatments for microbial infections. Polyphenols, abundantly found in various plants, fruits, and vegetables, are noted for their physiological benefits including antimicrobial effects. This study introduced a new set of acylated phloroglucinol derivatives, synthesized and tested for their antifungal activity in vitro against seven different pathogenic fungi. The standout compound, 3-methyl-1-(2,4,6-trihydroxyphenyl) butan-1-one (2b), exhibited remarkable fungicidal strength, with EC50 values of 1.39 µg/mL against Botrytis cinerea and 1.18 µg/mL against Monilinia fructicola, outperforming previously screened phenolic compounds. When tested in vivo, 2b demonstrated effective antifungal properties, with cure rates of 76.26% for brown rot and 83.35% for gray mold at a concentration of 200 µg/mL, rivaling the commercial fungicide Pyrimethanil in its efficacy against B. cinerea. Preliminary research suggests that 2b's antifungal mechanism may involve the disruption of spore germination, damage to the fungal cell membrane, and leakage of cellular contents. These results indicate that compound 2b has excellent fungicidal properties against B. cinerea and holds potential as a treatment for gray mold.

A tartaric acid (TA)-coated iron-based biochar as heterogeneous Fenton catalyst for enhanced degradation of dibutyl phthalate.

Iron-biochar composite is a promising catalyst in Fenton-like system for removal of organic pollutants. Nevertheless, low cycling rate of Fe(III) / Fe(II), high iron leaching and low H2O2 utilization efficiency impedes its application. Herein, a iron-based biochar (C-Fe) coated with tartaric acid (TA) was synthesized. The specific structure of inherent graphitized carbon and TA coating improved the removal efficiency of dibutyl phthalate (DBP) to 93%, promoted 2-fold increase in HO• production in H2O2 activation, improved the cycling rate of Fe(III) / Fe(II), and mitigated Fe leaching significantly. The developed HO• and 1O2 dominated Fenton-like system had an excellent pH universality and anti-interference to inorganic ions and real water matrixes. Moreover, C-Fe-TA has been shown to efficiently degrade DBP by using the dissolved oxygen in water to generate HO•. This work provided a novel insight for sustainable and efficient HO• and 1O2 generation, which motivated the development of new water treatment technology based on efficient iron-biochar catalyst.

Anticancer Tetranuclear Cu(I) Complex Catalyzes a Click Reaction to Synthesize a Chemotherapeutic Agent in situ to Achieve Targeted Dual-Agent Combination Therapy for Cancer.

To develop next-generation metal-based drugs and dual-drug combination therapy for cancer, we proposed to develop a copper (Cu) complex that exerts anticancer function by integrating chemotherapy, immunotherapy and catalyzes a click reaction for the in situ synthesis of a chemotherapeutic agent, thereby achieving targeted dual-agent combination therapy. We designed and synthesized a tetranuclear Cu(I) complex (Cu4) with remarkable cytotoxicity and notable catalytic ability for the in situ synthesis of a chemotherapeutic agent via Cu(I)-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC). We also constructed an apoferritin (AFt)-Cu4 nanoparticles (NPs) delivery system. AFt-Cu4 NPs not only showed an enhanced performance of tumor growth inhibition, but also improved the targeting ability and reduced the systemic toxicity of Cu4 in vivo. Importantly, the anticancer effect was enhanced by combining the AFt-Cu4 NPs with the resveratrol analogue obtained from the CuAAC reaction in situ. Finally, we revealed the anticancer mechanism of the Cu4/AFt-Cu4 NPs, which involves both cuproptosis and cuproptosis-induced systemic immune response.

Aggregated health risk assessment of perfluoroalkyl acids migrated from convenience food contact materials.

Ingestion of perfluoroalkyl acids (PFAAs) via contaminated food contact materials (FCMs) is an important human exposure source. This study adopts a toxicity equivalent approach to evaluate the collective health risk of multiple PFAAs in FCMs. A comprehensive extraction and analysis of 21 PFAAs in FCMs was performed. Among the analyzed substances, 15 PFAAs were detected. Migration experiment using three food simulants revealed the migration range of seven PFAAs from FCMs into the simulant to be 0.47-46.7 ng/cm2. The hazard quotient results suggest minimal health risk, except for 9% of packaged samples where perfluorooctanoic acid (PFOA) poses a higher risk. Utilizing PFOA toxic equivalent concentrations, comprehensive risk calculations showed ∼77% of samples potentially posing elevated health risks due to PFAA exposure. This emphasizes the substantial contribution of PFAAs beyond PFOA and underscores the importance of considering them in related assessments. The aggregated risk assessment reflects actual exposure circumstances more accurately.

Organophosphorus flame retardants in the Qiantang River of China: occurrence, source and ecological risk assessment.

In recent years, the prevalence and danger of organophosphorus flame retardants (OPFRs) have drawn attention from all around the world. This study examined twenty-five OPFRs observed in water and sediment samples from the Qiantang River in eastern China, as well as their occurrence, spatial distribution, possible origins, and ecological hazards. All the 25 OPFRs were detected in water and sediment samples. The levels of Σ25OPFRs in water and sediment were 35.5-192 ng/L and 8.84-48.5 ng/g dw, respectively. Chlorinated OPFRs were the main contributions in water, whereas alkyl-OPFRs were the most common congeners found in sediment. Spatial analysis revealed that sample locations in neighboring cities had somewhat higher water concentrations of OPFRs. Slowing down the river current and making the reservoir the main sink of OPFRs, the dam can prevent OPFRs from moving via the Qiantang River. Positive matrix factorization indicated that plasticizer in polyvinyl chloride, polyester resins, and polyurethane foam made the greatest contributions in water, whereas polyurethane foam and textile were the predominant source in sediment. Analysis of sediment-water exchange of OPFRs showed that twelve OPFRs in sediments can re-enter into the water body. The risk quotients showed the ecological risk was low to medium, but trixylyl phosphate exposures posed high ecological risk to aquatic organisms.

A quantitative theory and atomistic simulation study on the soft-sphere crystal-melt interfacial properties. I. Kinetic coefficients.

By employing non-equilibrium molecular dynamics (NEMD) simulations and time-dependent Ginzburg-Landau (TDGL) theory for solidification kinetics [Cryst. Growth Des. 20, 7862 (2020)], we predict the kinetic coefficients of FCC(100) crystal-melt interface (CMI) of soft-spheres modeled with an inverse-sixth-power repulsive potential. The collective dynamics of the local interfacial liquid phase at the equilibrium FCC(100) CMIs are calculated based on a recently proposed algorithm [J. Chem. Phys. 157, 084 709 (2022)] and are employed as the resulting parameter that eliminates the discrepancy between the predictions of the kinetic coefficient using the NEMD simulations and the TDGL solidification theory. A speedup of the two modes of the interfacial liquid collective dynamics (at wavenumbers equal to the principal and the secondary reciprocal lattice vector of the grown crystal) is observed. With the insights provided by the quantitative predictive theory, the variation of the solidification kinetic coefficient along the crystal-melt coexistence boundary is discussed. The combined methodology (simulation and theory) presented in this study could be further applied to investigate the role of the inter-atomic potential (e.g., softness parameter s = 1/n of the inverse-power repulsive potential) in the kinetic coefficient.

Multimodal Approach in Dry Eye Disease Combining In Vivo Confocal Microscopy and HLA-DR Expression.

Purpose: The purpose of this study was to determine the association between corneal images provided by in vivo confocal microscopy (IVCM) with clinical parameters and conjunctival expression of HLA-DR antigen in patients with dry eye disease (DED). Methods: Two hundred fourteen eyes of 214 patients with DED were analyzed, consisting of 2 groups of patients - 63 with autoimmune dry eye disease (AIDED) and 151 with non-autoimmune dry eye disease (NAIDED). Patients underwent a full clinical examination, including symptom screening, using the Ocular Surface Disease Index (OSDI) questionnaire, and objective analysis of DED signs by Schirmer's testing, tear break-up time (TBUT), Oxford's test, and IVCM corneal imaging. The IVCM scoring criteria were based on corneal sub-basal nerve density (ND), nerve morphology (NM), and inflammatory cell (IC) density. Quantification of conjunctival HLA-DR antigen was performed by flow cytometry. Results: The total IVCM score (T-IVCM) as well as the IVCM-IC subscore (sc) were positively correlated with HLA-DR levels with r = 0.3, P < 0.001 and r = 0.3, P < 0.01, respectively in the total population of patients with DED. The IVCM-NDsc was negatively correlated with TBUT in patients with AIDED (r = -0.2, P < 0.05) and with the Schirmer's test in patients with NAIDED (r = -0.24, P < 0.05). However, the IVCM-NMsc was positively correlated with the Oxford score only in patients with AIDED (r = 0.3, P < 0.05). Conclusions: The proposed IVCM scoring system showed significant correlations with clinical parameters along with conjunctival HLA-DR quantification in patients with DED. Translational Relevance: The IVCM grading score represents an interesting point of commonality among clinical parameters, imaging, and molecular investigation of the ocular surface.

Tailoring Polyamide Nanofiltration Membranes by Switching Charge of Nanocellulose Interlayers.

The interlayer strategy has emerged as an effective approach for modulating the interfacial polymerization process and improving the permeability and selectivity of polyamide membranes. However, the underlying mechanisms by which charged interlayers influence the interfacial polymerization process remain inadequately understood. In this study, we utilized two distinct charged cellulose nanofibers, namely, carboxylated cellulose (⊖-CNF) and quaternized cellulose ([Formula: see text]-CNF), as interlayers to regulate the interfacial polymerization process. Through simulation results, isothermal titration calorimetry (ITC) and UV tests, we demonstrated that the [Formula: see text]-CNF interlayer, which possesses stronger hydration capability and better piperazine affinity, enhanced the diffusion of piperazine across the reaction interface compared with the ⊖-CNF interlayer. This led to an acceleration of the interfacial polymerization process and the formation of a denser membrane structure. Further investigation revealed that the charged interlayers significantly influenced the surface charging properties of the resulting nanofiltration membranes within a 30 nm range of electrostatic effects. Specifically, the ⊖-CNF interlayer conferred a higher negative charge to the membrane surface, while the [Formula: see text]-CNF interlayer endowed the membranes with a lower surface negative charge. Leveraging these differences, the ⊖-i-TFC membranes exhibited exceptional separation performance for divalent anions, achieving a SO42-/Cl- selectivity of 136. Conversely, the [Formula: see text]-i-TFC membrane demonstrated an enhanced separation of divalent cations, displaying a Mg2+/Na+ selectivity of 3.5. This study lays the groundwork for regulating the surface charging properties of polyamide membranes, offering potential advancements in nanofiltration applications.

Rhodium(III) Complex Noncanonically Potentiates Antitumor Immune Responses by Inhibiting Wnt/ß-Catenin Signaling.

Metal-based chemoimmunotherapy has recently garnered significant attention for its capacity to stimulate tumor-specific immunity beyond direct cytotoxic effects. Such effects are usually caused by ICD via the activation of DAMP signals. However, metal complexes that can elicit antitumor immune responses other than ICD have not yet been described. Herein, we report that a rhodium complex (Rh-1) triggers potent antitumor immune responses by downregulating Wnt/ß-catenin signaling with subsequent activation of T lymphocyte infiltration to the tumor site. The results of mechanistic experiments suggest that ROS accumulation following Rh-1 treatment is a critical trigger of a decrease in ß-catenin and enhanced secretion of CCL4, a key mediator of T cell infiltration. Through these properties, Rh-1 exerts a synergistic effect in combination with PD-1 inhibitors against tumor growth in vivo. Taken together, our work describes a promising metal-based antitumor agent with a noncanonical mode of action to sensitize tumor tissues to ICB therapy.

Prenylated Flavonoids Isolated from the Root of Sophora flavescens as Potent Antifungal Agents against Botrytis cinerea.

Sophora flavescens, a traditional Chinese herb, produces a wide range of secondary metabolites with a broad spectrum of biological activities. In this study, we isolated six isopentenyl flavonoids (1-6) from the roots of S. flavescens and evaluated their activities against phytopathogenic fungi. In vitro activities showed that kurarinone and sophoraflavanone G displayed broad spectrum and superior activities, among which sophoraflavanone G displayed excellent activity against tested fungi, with EC50 values ranging from 4.76 to 13.94 µg/mL. Notably, kurarinone was easily purified and showed potential activity against Rhizoctonia solani, Botrytis cinerea, and Fusarium graminearum with EC50 values of 16.12, 16.55, and 16.99 µg/mL, respectively. Consequently, we initially investigated the mechanism of kurarinone against B. cinerea. It was found that kurarinone disrupted cell wall components, impaired cell membrane integrity, increased cell membrane permeability, and affected cellular energy metabolism, thereby exerting its effect against B. cinerea. Therefore, kurarinone is expected to be a potential candidate for the development of plant fungicides.

Removal of benzo[a]pyrene from the soil by adsorption coupled with degradation on saponin-modified bentonite immobilized crude enzymes.

Bentonite is a non-metallic mineral with montmorillonite as the main component. It is an environmentally friendly mineral material with large reserves, wide distribution, and low price. Bentonite can be easily modified organically using the surfactant saponin to obtain saponin-modified bentonite (Sap-BT). This study investigates the immobilization of crude enzymes obtained from Trametes versicolor by physical adsorption with Sap-BT. Thus, saponin-modified bentonite immobilized crude enzymes (CE-Sap-BT) were developed to remove benzo[a]pyrene. Immobilization improves the stability of free enzymes. CE-Sap-BT can maintain more than 80% of activity at 45 °C and after storage for 15 d. Additionally, CE-Sap-BT exhibited a high removal rate of benzo[a]pyrene in soil, with 65.69% after 7 d in highly contaminated allotment soil and 52.90% after 6 d in actual soil contaminated with a low concentration of benzo[a]pyrene at a very low laccase dosage (0.1 U/3 g soil). The high catalytic and removal performance of CE-Sap-BT in contaminated sites showed more excellent practical application value.

Rational Design of a Hetero-multinuclear Gadolinium(III)-Copper(II) Complex: Integrating Magnetic Resonance Imaging, Photoacoustic Imaging, Mild Photothermal Therapy, Chemotherapy and Immunotherapy of Cancer.

For more accurate diagnosis and effective treatment of cancer, we proposed to develop a hetero-multinuclear metal complex based on the property of apoferritin (AFt) for targeting tumor theranostics by integrating dual-modality imaging diagnosis and multimodality therapy. To this end, we rational designed and synthesized a trinuclear Gd(III)-Cu(II) thiosemicarbazone complex (Gd-2Cu) and then constructed a Gd-2Cu@AFt nanoparticle (NP) delivery system. Gd-2Cu/Gd-2Cu@AFt NPs not only had significant T1-weighted magnetic resonance imaging and photoacoustic imaging of the tumor but also effectively inhibited tumor growth through a combination of mild photothermal therapy, chemotherapy, and immunotherapy. Gd-2Cu@AFt NPs optimized the behavior of imaging diagnosis and therapy of Gd-2Cu, improved its targeting ability, and reduced the side effects in vivo. Besides, we revealed and clarified the anticancer mechanism of Gd-2Cu: interrupting energy metabolism of the tumor cell, inducing apoptosis of the tumor cell, and activating a systemic immune response by inducing immunogenic cell death of cancer cells.

GREMI: an Explainable Multi-omics Integration Framework for Enhanced Disease Prediction and Module Identification.

Multi-omics integration has demonstrated promising performance in complex disease prediction. However, existing research typically focuses on maximizing prediction accuracy, while often neglecting the essential task of discovering meaningful biomarkers. This issue is particularly important in biomedicine, as molecules often interact rather than function individually to influence disease outcomes. To this end, we propose a two-phase framework named GREMI to assist multi-omics classification and explanation. In the prediction phase, we propose to improve prediction performance by employing a graph attention architecture on sample-wise co-functional networks to incorporate biomolecular interaction information for enhanced feature representation, followed by the integration of a joint-late mixed strategy and the true-class-probability block to adaptively evaluate classification confidence at both feature and omics levels. In the interpretation phase, we propose a multi-view approach to explain disease outcomes from the interaction module perspective, providing a more intuitive understanding and biomedical rationale. We incorporate Monte Carlo tree search (MCTS) to explore local-view subgraphs and pinpoint modules that highly contribute to disease characterization from the global-view. Extensive experiments demonstrate that the proposed framework outperforms state-of-the-art methods in seven different classification tasks, and our model effectively addresses data mutual interference when the number of omics types increases. We further illustrate the functional- and disease-relevance of the identified modules, as well as validate the classification performance of discovered modules using an independent cohort. Code and data are available at https://github.com/Yaolab-fantastic/GREMI.

Insights into virtual reality-based training for unexplained disease outbreaks: A qualitative exploration of Chinese standardized training nurses' experiences.

BACKGROUND: An unexplained disease outbreak refers to a scenario wherein a group of individuals encounters similar health issues within a short timeframe, yet healthcare professionals find it challenging to promptly identify the specific cause or pathogenic factors triggering the outbreak. Emerging as a vital force in China, standardized training nurses can significantly mitigate the impact of unforeseen events. OBJECTIVE: This study aims to illuminate the experiences of Chinese standardized training nurses engaged in training for unexplained disease outbreaks utilizing virtual reality (VR) technology. DESIGN: A qualitative descriptive research design was employed. PARTICIPANTS: Thirty Chinese standardized training nurses participated in semi-structured interviews. METHODS: Data were collected through semi-structured interviews conducted from April 2023 to June 2023. Braun and Clark's thematic analysis method was applied for data analysis. RESULTS: The study revealed five prominent themes: Surpassing Expectations, Enjoyable Learning, Self-challenge, Reflective Learning, and Promotion-Worthy. In essence, Chinese standardized training nurses perceived VR training as effective, meaningful, and conducive to reflective opportunities. Nevertheless, they expressed challenges in composing epidemiological reports, particularly when lacking expertise in epidemiology and having limited exposure to simulated training. CONCLUSION: Virtual Reality (VR) technology plays a crucial role in continuing education after graduation (standardized training for nurses) in China, contributing to the enhancement of clinical practice standards and the promotion of teamwork collaboration. Its broader application is considered worthy of promotion.

Bioremediation of PAHs-contaminated site in a full-scale biopiling system with immobilized enzymes: Removal efficiency and microbial communities.

Bioremediation of PAHs-contaminated soil by immobilized enzymes is a promising technology. Nevertheless, the practical implementation of highly efficient enzymatic remediation remains confined to laboratory settings, with limited experience in full-scale applications. In this study, the extracellular enzymes from white rot fungi are fully applied to treat sites contaminated with PAHs by combining a new hydrogel microenvironment and a biopiling system. The full-scale project was conducted on silty loam soil contaminated with PAHs. In line with China's guidelines for construction land, 7 out of the 12 PAHs identified are considered to be a threat to the soil quality of construction sites, with benzo[a]pyrene levels reaching 1.50 mg kg-1, surpassing the acceptable limit of 0.55 mg kg-1 for the first type of land. After 7 days of remediation, the benzo[a]pyrene level decreased from 1.50 mg kg-1 to 0.51 mg kg-1, reaching the remediation standard of Class I screening values, with a removal rate of 66%. Microbiomes were utilized to assess the microbial biodiversity and structure analyses for PAHs biodegradation. The remediation enhanced the abundance of dominant bacterium (Marinobacter, Pseudomonas, and Truepera) and fugin (Thielavia, Neocosmospora, and Scedosporium). The research offers further insights into the exploration of soil remediation on the full-scale of the immobilized enzyme and biopiling technology.