Optimisation of Interfacial Modification by Two-Stage Microwave Irradiation.

Microwave-assisted de-emulsification is attractive in the processes of petroleum production and refining. The main advantage of microwaves is their direct influence on the surfactant layer at the oil/water interface. Previously, an effective interfacial modification was demonstrated by pulsed microwave irradiation. However, the effect of the modification diminished during the off interval of the pulse irradiation. In this study, two-stage microwave irradiation with different powers and durations was applied as a method to maintain an interfacial effect. The power of the second stage was changed to optimise the modification. Quick modification was obtained by high-power irradiation followed by low-power irradiation. It was confirmed a sustained modification was maintained by a moderate power of the second irradiation. This observation indicates a re-adsorption or re-structure process after the first irradiation is suppressed by the second irradiation. The results open new opportunities to optimise microwave operation in oil/water systems.

Ionic Distribution of an Unequal Electrolyte Near an Air/Water Surface.

The distribution of electrolytes near the air/water surface plays an essential role in many processes. While the general distribution is governed by classic Poisson-Boltzmann statistics, the analytical solution is only available for symmetric electrolytes. From the recent studies in the literature, it is evident that surface adsorption is dependent on specific ions as well as the H-bond structure at the surface. Experimental data can capture the macro properties of the surface, such as surface tension and surface potential. Yet, the underpinning mechanisms behind this experimental macro-observation remain unclear. To address the challenge, we developed a framework combining experimental studies and numerical calculations. The model was developed for electrolytes with unequal cationic and anionic charges. The asymmetric model was successfully applied to describe the surface charge of MgCl 2 aqueous solution. The results can be explained by the role of cationic size and charge on the surface layer.

Yield gap reduction of pineapple (Ananas comosus L.) by site-specific nutrient management.

Acid-sulfate soils and overuse of chemical fertilizers have been obstacles to sustainable agriculture. The variation of fertilization due to poor soil fertility has remarkably affected the yield gap and the quality of the environment, so an optimal fertilizing rate should be formulated. Therefore, this study aimed at (i) detecting obstacles in soil characteristics reducing pineapple yield between farms and (ii) assessing the effects of NPKCaMg fertilizers on soil fertility, uptakes, and pineapple yield. The on-farm experiment was carried out according to site-specific nutrient management (SSNM) arranging in acid-sulfate soil for pineapple, including (i) no fertilizers used; (ii) NPKCaMg: fully fertilizing with nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), and magnesium (Mg); (ii) PKCaMg: fertilizing without N; (iii) NKCaMg: fertilizing without P; (iv) NPCaMg: fertilizing without K; (v) NPKMg: fertilizing without Ca; (vi) NPKCa: fertilizing without Mg; and (vii) FFP: farmers' fertilizing practice. The result of the principal component analysis revealed that the soil had low availability of N, P, and K nutrients. Available P concentration was negatively correlated with concentrations of Al3+, Fe2+, and total Mn, whose correlation coefficients were -0.34 to -0.59, -0.52 to -0.74, and -0.63 to -0.70, respectively. Fertilizing NPKCaMg obtained the highest result in the uptakes of N, P, K, Ca, and Mg, which were 289.1-327.4, 25.4-29.3, 137.4-166.0, 41.9-48.9, and 39.8-43.1 kg ha-1, respectively. Fertilizing by SSNM has increased pineapple yield by 22.9 %-44.9 % compared to the FFP. This fertilizer formula should be transferred to the local farmers in order not only to enhance productivity, but also to limit the damage of chemical fertilizers on the environment. Moreover, this formula should be tested globally in other places that share similar soil characteristics.

Quantifying the Influence of Electrolytes on the Kinetics of Spontaneous Emulsification.

This study quantifies the influence of electrolytes on the kinetics of the spontaneous emulsification phenomenon (SEP) of heavy hydrocarbons in a nonionic surfactant solution. The rate of emulsifying hexadecane in Triton X-100, with the presence of sodium chloride and potassium chloride, has been measured using a technique of monitoring single oil droplet photography. The emulsion droplet size produced in the process was measured under the same conditions by using dynamic light scattering. The data obtained from the two experiments were employed to investigate the mass transfer coefficient of the surfactant molecules through the intermediate layer formed between hexadecane and the surfactant solution. It was found that the electrolytes in an aqueous solution increase the surfactant diffusion rate through the intermediate layer and reduce the emulsion droplet size. As a result, both electrolytes reduce the rate of spontaneous emulsification, with potassium chloride having a more substantial reduction. A model was developed to quantify the influence of electrolytes on the kinetics of the SEP. The data and modeling results verify the influence of ions on the kinetics of spontaneous emulsification. The results provide a significant foundation for predicting the solubilization of heavy hydrocarbons in an electrolyte solution.

Affinity of Amphiphilic Molecules to Air/Water Surface.

The affinity of amphiphiles to the water/air surface was modeled by adapting Eberhart's equation. The proposed method successfully describes surface tension for all amphiphilic structures, including alkanols, carboxylic acids, nonionic, ionic, and Gemini surfactants. The model is more effective than conventional analysis for amphiphiles with multiple ionic states. The prediction was consistently validated at different temperatures and nonaqueous solvents. The modeling results show a linear correlation between surface affinity and hydrophobicity/hydrophilicity. For alkanols, the affinity increment is 2.84 kJ/mol per CH2 group, the same as the reported hydrophobic energy from monomer to aggregate for nonionic surfactants. For carboxylic acids, the affinity increment per CH2 group is 3.18 kJ/mol, incorporating the degree of acid dissociation. The affinity-hydrophilicity correlation is approximately -0.22 kJ/mol per oxyethylene group. The affinity constant can be obtained for all classes of amphiphiles to clarify the relationship between the molecular structure and surface activity.

Synthesis of a Grease Thickener from Cashew Nut Shell Liquor.

Thickener, also known as a gelling agent, is a critical component of lubricating greases. The most critical property of thickener, temperature resistance, is determined by the molecular structure of the compounds. Currently, all high-temperature-resistant thickeners are based on 12-hydroxystearic acid, which is exclusively produced from castor oil. Since castor oil is also an important reagent for other processes, finding a sustainable alternative to 12-hydroxystearic acid has significant economic implications. This study synthesises an alternative thickener from abundant agricultural waste, cashew nut shell liquor (CNSL). The synthesis and separation procedure contains three steps: (i) forming and separating calcium anacardate by precipitation, (ii) forming and separating anacardic acid (iii) forming lithium anacardate. The obtained lithium anacardate can be used as a thickener for lubricating grease. It was found that the recovery of anacardic acid was around 80%. The optimal reaction temperature and time conditions for lithium anacardate were 100 °C and 1 h, respectively. The method provides an economical alternative to castor and other vegetable oils. The procedure presents a simple pathway to produce the precursor for the lubricating grease from agricultural waste. The first reaction step can be combined with the existing distillation of cashew nut shell processing. An effective application can promote CNSL to a sustainable feedstock for green chemistry. The process can also be combined with recycled lithium from the spent batteries to improve the sustainability of the battery industry.

Ultra High-plex Spatial Proteogenomic Investigation of Giant Cell Glioblastoma Multiforme Immune Infiltrates Reveals Distinct Protein and RNA Expression Profiles.

A deeper understanding of complex biological processes, including tumor development and immune response, requires ultra high-plex, spatial interrogation of multiple "omes". Here we present the development and implementation of a novel spatial proteogenomic (SPG) assay on the GeoMx Digital Spatial Profiler platform with next-generation sequencing readout that enables ultra high-plex digital quantitation of proteins (>100-plex) and RNA (whole transcriptome, >18,000-plex) from a single formalin-fixed paraffin-embedded (FFPE) sample. This study highlighted the high concordance, R > 0.85 and <15% change in sensitivity between the SPG assay and the single-analyte assays on various cell lines and tissues from human and mouse. Furthermore, we demonstrate that the SPG assay was reproducible across multiple users. When used in conjunction with advanced cellular neighborhood segmentation, distinct immune or tumor RNA and protein targets were spatially resolved within individual cell subpopulations in human colorectal cancer and non-small cell lung cancer. We used the SPG assay to interrogate 23 different glioblastoma multiforme (GBM) samples across four pathologies. The study revealed distinct clustering of both RNA and protein based on pathology and anatomic location. The in-depth investigation of giant cell glioblastoma multiforme (gcGBM) revealed distinct protein and RNA expression profiles compared with that of the more common GBM. More importantly, the use of spatial proteogenomics allowed simultaneous interrogation of critical protein posttranslational modifications alongside whole transcriptomic profiles within the same distinct cellular neighborhoods. Significance: We describe ultra high-plex spatial proteogenomics; profiling whole transcriptome and high-plex proteomics on a single FFPE tissue section with spatial resolution. Investigation of gcGBM versus GBM revealed distinct protein and RNA expression profiles.

Comparison between Cashew-Based and Petrochemical Hydroxyoximes: Insights from Molecular Simulations.

Solvent extraction has been ubiquitously used to recover valuable metals from wastes such as spent batteries and electrical boards. With increasing demands for energy transition, there is a critical need to improve the recycling rate of critical metals, including copper. Therefore, the sustainability of reagents is critical for the overall sustainability of the process. Yet, the recycling process relies on functional organic compounds based on the hydroxyoxime group. To date, hydroxyoxime extractants have been produced from petrol-based chemical feedstocks. Recently, natural-based cardanol has been used to produce an alternative hydroxyoxime. The natural-based oxime has been employed to recover valuable metals (Ga, Ni, Co) via a liquid/liquid extraction process. The natural compound has a distinctive structure with 15 carbons in the alkyl tail. In contrast, petrol-based hydroxyoximes have only 12 or fewer carbons. However, the molecular advantages of this natural-based compound over the current petrol-based ones remain unclear. In this study, molecular dynamics simulation was employed to investigate the effect of extractant hydrocarbon chains on the extraction of copper ions. Two hydroxyoxime extractants with 12 and 15 carbons in the alkyl chain were found to have similar interactions with Cu2+ ions. Yet, a slight molecular binding increase was observed when the carbon chain was increased. In addition, lengthening the carbon chain made the extracting stage easier and the stripping stage harder. The binding would result in a lower pH in the extraction step and a lower pH in the stripping step. The insights from this molecular study would help design the extraction circuit using natural-based hydroxyoxime extractants. A successful application of cashew-based cardanol will improve the environmental benefits of the recycling process. With cashew-producing regions in developing countries, the application also improves these regions' social and economic sustainability.

Microwaves reduce water refractive index.

Microwaves, long used as a convenient household appliance, have been increasingly used in industrial processes such as organic synthesis and oil processing. It has been proposed that microwaves can enhance these chemical processes via a non-thermal effect. Here we report the instantaneous effect of microwaves on the permittivity and phase velocity of light in water through the in-situ measurement of changes in refractive index. Microwave irradiation was found to reduce the water refractive index (RI) sharply. The reduction increased as a function of microwave power to a far greater extent than expected from the change in temperature. The phase velocity of light in water increases up to ~ 5% (RI of 1.27) during microwave irradiation. Upon stopping irradiation, the return to the equilibrium RI was delayed by up to 30 min. Our measurement shows that microwaves have a profound non-thermal and long-lasting effect on the properties of water. Further investigation is planned to verify if the observed RI reduction is restricted to the region near the surface or deep inside water bulk. The observation suggests a relationship between microwave-induced and the enhanced aqueous reactions.

Effects of Size and Surface Properties of Nanodiamonds on the Immunogenicity of Plant-Based H5 Protein of A/H5N1 Virus in Mice.

Nanodiamond (ND) has recently emerged as a potential nanomaterial for nanovaccine development. Here, a plant-based haemagglutinin protein (H5.c2) of A/H5N1 virus was conjugated with detonation NDs (DND) of 3.7 nm in diameter (ND4), and high-pressure and high-temperature (HPHT) oxidative NDs of ~40-70 nm (ND40) and ~100-250 nm (ND100) in diameter. Our results revealed that the surface charge, but not the size of NDs, is crucial to the protein conjugation, as well as the in vitro and in vivo behaviors of H5.c2:ND conjugates. Positively charged ND4 does not effectively form stable conjugates with H5.c2, and has no impact on the immunogenicity of the protein both in vitro and in vivo. In contrast, the negatively oxidized NDs (ND40 and ND100) are excellent protein antigen carriers. When compared to free H5.c2, H5.c2:ND40, and H5.c2:ND100 conjugates are highly immunogenic with hemagglutination titers that are both 16 times higher than that of the free H5.c2 protein. Notably, H5.c2:ND40 and H5.c2:ND100 conjugates induce over 3-folds stronger production of both H5.c2-specific-IgG and neutralizing antibodies against A/H5N1 than free H5.c2 in mice. These findings support the innovative strategy of using negatively oxidized ND particles as novel antigen carriers for vaccine development, while also highlighting the importance of particle characterization before use.

Impact of Crystal Habit on the Dissolution Rate and In Vivo Pharmacokinetics of Sorafenib Tosylate.

The dissolution rate is the rate-limiting step for Biopharmaceutics Classification System (BCS) class II drugs to enhance their in vivo pharmacokinetic behaviors. There are some factors affecting the dissolution rate, such as polymorphism, particle size, and crystal habit. In this study, to improve the dissolution rate and enhance the in vivo pharmacokinetics of sorafenib tosylate (Sor-Tos), a BCS class II drug, two crystal habits of Sor-Tos were prepared. A plate-shaped crystal habit (ST-A) and a needle-shaped crystal habit (ST-B) were harvested by recrystallization from acetone (ACN) and n-butanol (BuOH), respectively. The surface chemistry of the two crystal habits was determined by powder X-ray diffraction (PXRD) data, molecular modeling, and face indexation analysis, and confirmed by X-ray photoelectron spectroscopy (XPS) data. The results showed that ST-B had a larger hydrophilic surface than ST-A, and subsequently a higher dissolution rate and a substantial enhancement of the in vivo pharmacokinetic performance of ST-B.

Cyclodextrin-based host-guest complexes loaded with regorafenib for colorectal cancer treatment.

The malignancy of colorectal cancer (CRC) is connected with inflammation and tumor-associated macrophages (TAMs), but effective therapeutics for CRC are limited. To integrate therapeutic targeting with tumor microenvironment (TME) reprogramming, here we develop biocompatible, non-covalent channel-type nanoparticles (CNPs) that are fabricated through host-guest complexation and self-assemble of mannose-modified γ-cyclodextrin (M-γ-CD) with Regorafenib (RG), RG@M-γ-CD CNPs. In addition to its carrier role, M-γ-CD serves as a targeting device and participates in TME regulation. RG@M-γ-CD CNPs attenuate inflammation and inhibit TAM activation by targeting macrophages. They also improve RG's anti-tumor effect by potentiating kinase suppression. In vivo application shows that the channel-type formulation optimizes the pharmacokinetics and bio-distribution of RG. In colitis-associated cancer and CT26 mouse models, RG@M-γ-CD is proven to be a targeted, safe and effective anti-tumor nanomedicine that suppresses tumor cell proliferation, lesions neovascularization, and remodels TME. These findings indicate RG@M-γ-CD CNPs as a potential strategy for CRC treatment.

Glucocerebrosidase reduces the spread of protein aggregation in a Drosophila melanogaster model of neurodegeneration by regulating proteins trafficked by extracellular vesicles.

Abnormal protein aggregation within neurons is a key pathologic feature of Parkinson's disease (PD). The spread of brain protein aggregates is associated with clinical disease progression, but how this occurs remains unclear. Mutations in glucosidase, beta acid 1 (GBA), which encodes glucocerebrosidase (GCase), are the most penetrant common genetic risk factor for PD and dementia with Lewy bodies and associate with faster disease progression. To explore how GBA mutations influence pathogenesis, we previously created a Drosophila model of GBA deficiency (Gba1b) that manifests neurodegeneration and accelerated protein aggregation. Proteomic analysis of Gba1b mutants revealed dysregulation of proteins involved in extracellular vesicle (EV) biology, and we found altered protein composition of EVs from Gba1b mutants. Accordingly, we hypothesized that GBA may influence pathogenic protein aggregate spread via EVs. We found that accumulation of ubiquitinated proteins and Ref(2)P, Drosophila homologue of mammalian p62, were reduced in muscle and brain tissue of Gba1b flies by ectopic expression of wildtype GCase in muscle. Neuronal GCase expression also rescued protein aggregation both cell-autonomously in brain and non-cell-autonomously in muscle. Muscle-specific GBA expression reduced the elevated levels of EV-intrinsic proteins and Ref(2)P found in EVs from Gba1b flies. Perturbing EV biogenesis through neutral sphingomyelinase (nSMase), an enzyme important for EV release and ceramide metabolism, enhanced protein aggregation when knocked down in muscle, but did not modify Gba1b mutant protein aggregation when knocked down in neurons. Lipidomic analysis of nSMase knockdown on ceramide and glucosylceramide levels suggested that Gba1b mutant protein aggregation may depend on relative depletion of specific ceramide species often enriched in EVs. Finally, we identified ectopically expressed GCase within isolated EVs. Together, our findings suggest that GCase deficiency promotes accelerated protein aggregate spread between cells and tissues via dysregulated EVs, and EV-mediated trafficking of GCase may partially account for the reduction in aggregate spread.

Sociodemographic Factors Associated with Request for Labor Epidural Analgesia in a Tertiary Obstetric Hospital in Vietnam.

This study is aimed at examining the sociodemographic factors associated with the utilization of labor epidural analgesia at a large obstetric and gynecology hospital in Vietnam. This was a cross-sectional study of women who underwent vaginal delivery in September 2018 at the Hanoi Obstetrics and Gynecology Hospital. The utilization of epidural analgesia during labor was determined. Univariate and multivariate regression models were applied to evaluate the association between patient demographic and socioeconomic factors and request for labor epidural analgesia. A total of 417 women had vaginal deliveries during the study period. 207 women utilized epidural analgesia for pain relief during labor, and 210 did not. Parturients older than 35 years of age (OR 2.84, 95% CI 1.11-8.17), multiparous women (OR 2.8 95% CI 1.85-4.25), women living from an urban area, women with higher income (OR 6.47, 95% CI 2.59-19.23), and women with higher level of education were more likely to utilize labor epidurals. Factors related to a parturient request for epidural analgesia during labor at our tertiary obstetric hospital included age greater than 35 years, multiparity, and high income and education levels. Educational outreach to women about the benefits of epidural analgesia can target women who do not share these demographic characteristics.

Enhancing the Physiochemical Properties of Puerarin via L-Proline Co-Crystallization: Synthesis, Characterization, and Dissolution Studies of Two Phases of Pharmaceutical Co-Crystals.

Puerarin (PUE) is a Chinese traditional medicine known to enhance glucose uptake into the insulin cells to downregulate the blood glucose levels in the treatment of type II diabetes. Nevertheless, the bioavailability of pristine PUE is limited due to its poor solubility and low intestinal permeability. In this work, we demonstrate that the solubility of PUE can be significantly enhanced via its co-crystallization with L-Proline (PRO). Two crystalline phases, namely, the solvate-free form [PUE][PRO] (I) and the solvated form [PUE]2[PRO]∙EtOH∙(H2O)2 (II) are isolated. These two phases are characterized by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), Fourier-transformed infrared (FT-IR) spectra, nuclear magnetic resonance (NMR), and thermogravimetric analysis in association with differential scanning calorimetry (TGA-DSC). The solubility and dissolution rate of both I and II in water, gastrointestinal tract at pH 1.2, and phosphate buffer at pH 6.8 indicates a nearly doubled increase as compared to the pristine PUE. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine PUE, I and II against murine colon cancer cell lines CT-26 and human kidney cell lines HEK-293 indicated that neither compound exhibits obvious cytotoxicity after 24 h. This work showcases that the readily available and biocompatible PRO can be a promising adjuvant to enhance the physicochemical properties of PUE toward orally administered drug formulation with improved pharmacokinetics.

AIEgen-Lipid Conjugate for Rapid Labeling of Neutrophils and Monitoring of Their Behavior.

Studies on neutrophil-based nanotherapeutic engineering have shown great potentials in treating infection and inflammation disorders. Conventional neutrophil labeling methods are time-consuming and often result in undesired contamination and activation since neutrophils are terminal-differentiated cells with a half-life span of only 7 h. A simple, fast, and biocompatible strategy to construct engineered neutrophils is highly desirable but remains difficult to achieve. In this study, we present an AIEgen-lipid conjugate, which can efficiently label harvested neutrophils in 30 s with no washing step required. This fast labeling method does not affect the activation and transmigration property of neutrophils, which has been successfully used to monitor neutrophil behaviors such as the chemotaxis process and migrating function towards inflammation sites both in vitro and in vivo, offering a tantalizing prospect for neutrophil-based nanotherapeutics studies.

HClO-Activated Fluorescence and Photosensitization from an AIE Nanoprobe for Image-Guided Bacterial Ablation in Phagocytes.

Bacteria hiding in host phagocytes are difficult to kill, which can cause phagocyte disorders resulting in local and systemic tissue damage. Effective accumulation of activatable photosensitizers (PSs) in phagocytes to realize selective imaging and on-demand photodynamic ablation of bacteria is of great scientific and practical interests for precise bacteria diagnosis and treatment. Herein, HClO-activatable theranostic nanoprobes, DTF-FFP NPs, for image-guided bacterial ablation in phagocytes are introduced. DTF-FFP NPs are prepared by nanoprecipitation of an HClO-responsive near-infrared molecule FFP and an efficient PS DTF with aggregation-induced emission characteristic using an amphiphilic polymer Pluronic F127 as the encapsulation matrix. As an energy acceptor, FFP can quench both fluorescence and production of reactive oxygen species (ROS) of DTF, thus eliminating the phototoxicity of DTF-FFP NPs in normal cells and tissues. Once delivered to the infection sites, DTF-FFP NPs light up with red fluorescence and efficiently generate ROS owing to the degradation of FFP by the stimulated release of HClO in phagocytes. The selective activation of fluorescence and photosensitization is successfully confirmed by both in vitro and in vivo results, demonstrating the effectiveness and theranostic potential of DTF-FFP NPs in precise bacterial therapy.

Surface Potential of the Air/Water Interface.

The surface charge/surface potential of the air/water interface plays a key role in many natural and industrial processes. Since the first decade of the 20th century, there are many theoretical proposals to describe the surface charge in the presence of different moieties. However, a complete and consistent description of the interfacial layer remains elusive. More recently, the theoretical frameworks and experimental data get complementary support from the simulation at a molecular level. This paper reviews the recent developments from the theoretical, experimental and simulation aspects. The combined results indicated that the interaction between hydration shells of adsorbed ions and the H-bonds network of surface water plays a critical role in the ionic adsorption. The factor should be incorporated into the conventional theories to correctly predict the ion distribution near the air/water surface.

Backbone and side-chain chemical shift assignments for the ribosome-inactivating protein trichobakin (TBK).

Trichobakin (TBK) is a type-I ribosome-inactivating protein (RIP-I), acting as an extremely potent inhibitor of protein synthesis in the cell-free translation system of rabbit reticulocyte lysate (IC50: 3.5 pM). In this respect, TBK surpasses the well-studied highly homologous RIP-I trichosanthin (IC50: 20-27 pM), therefore creation of recombinant toxins based on it is of great interest. TBK needs to penetrate into cytosol through the cell membrane and specifically bind to α-sarcin/ricin loop of 28S ribosome RNA to perform the function of specific RNA depurination. At the moment, there is no detailed structural-dynamic information in solution about diverse states RIP-I can adopt at different stages on the way to protein synthesis inhibition. In this work, we report a near-complete assignment of 1H, 13C, and 15N TBK (27.3 kDa) resonances and analysis of the secondary structure based on the experimental chemical shifts data. This work will serve as a basis for further investigations of the structure, dynamics and interactions of the TBK with its molecular partners using NMR techniques.