Development of FK506-loaded maleimide-functionalized cationic niosomes for prolonged retention and therapeutic efficacy in dry eye disease.

Tacrolimus (FK506) is widely used in ocular diseases such as corneal transplantation-host disease, uveitis, conjunctivitis, and dry eye disease (DED). However, its low aqueous solubility and poor ocular retention pose challenges for its application in the eye diseases. This study developed a novel FK506-loaded maleimide-functionalized cationic niosomes (FK506 M-CNS), aiming to prolong the retention time of FK506 in the eye and enhance its therapeutic efficacy. FK506 M-CNS had a particle size of 87.69 ± 1.05 nm and zeta potential of 22.06 ± 1.01 mV. Results of histological evaluation through H&E staining and in vitro cytotoxicity of human corneal epithelial cells consistently revealed the excellent biocompatibility of FK506 M-CNS. FK506 M-CNS exhibited superior ocular retention compared to the market product Talymus®. FK506 M-CNS significantly alleviated the symptoms of DED and promoted the recovery of corneal epithelia. FK506 M-CNS group had the lowest expression levels of inflammatory factors associated with DED. These superiorities might be due to the electrostatic interaction between cationic niosomes and negatively charged mucin in the eye, and the covalent binding of maleimide with the thiol group in the mucin. The maleimide group improved the ocular retention and efficacy of FK506, but did not increase the toxicity. Results indicated that FK506 M-CNS had great potential as a nanopharmaceutical in the treatment of ocular diseases, and M-CNS could be a promising drug carrier for ophthalmic drug delivery systems.

Promoting effects of ferric ions on Microcystis aeruginosa growth and arsenate accumulation and reduction at different phosphorus environments.

The effects of different dissolved organic phosphorus (DOP) associated with distinct iron conditions (iron deficient (dFe), ferric ions (Fe3+), and colloidal iron (CFe)) on algal growth and arsenate (As(V)) metabolism were systematically evaluated and compared in Microcystis aeruginosa. Two chemical forms of DOP (D-glucose-6-phosphate (GP) and phytic acid (PA)), as well as dissolved inorganic phosphorus (DIP), were employed as distinct phosphorus environments. The results revealed that As(V) metabolism of M. aeruginosa was more influenced by different phosphorus forms than by different iron conditions. Conversely, the release of microcystins in the media was found to be significantly more affected by the different phosphorus forms than by the iron conditions. Moreover, DOP was observed to promote arsenic (As) biotransformation, particularly the efflux of methylated As from a single algal cell, whereas DIP was found to primarily facilitate As(V) accumulation in algae. The total As metabolism amount per algal cell under PA was observed to be five times that observed under DIP and GP. The influence of iron conditions on the synthesis of algal metabolites was notable, as evidenced by the metabolites identified in algae of aliphatic (δ 1.28-1.68), humic acid-like and aromatic protein-like substances through 1H-NMR spectra and three-dimensional excitation-emission matrix fluorescence spectroscopy analysis. This impact was particularly notable at Fe3+ conditions, due to the role of Fe3+ as a micronutrient with highly bioavailable forms, which enhanced the synthesis of organic compounds in algae and promoted algal growth. Consequently, Fe3+ could inhibit As accumulation under DIP but promote it under DOP. The obtained results facilitate a more comprehensive understanding of the combined role of different phosphorus forms and iron conditions in algal bloom outbreaks and As(V) metabolism.

Self-delivery nanodrug to manipulate tumor microenvironment for boosting photodynamic cancer immunotherapy.

Immunotherapy has captured attention for its high clinical efficacy. However, its efficacy is limited by inadequate immune activation. Therefore, a platform to activate the immune system and amplify the host's immune response against tumors is urgently needed. Herein, a self-delivery photodynamic nanodrug (VAC@HSA) is reported as inducing immunogenic cell death (ICD), promoting the recruitment of dendritic cells (DCs), and normalizing tumor blood vessels. Firstly, verteporfin with laser assistance releases tumor-associated antigen to induce ICD, while celecoxib downregulates prostaglandin E2 and releases CCL5 to activate DC recruitment. Moreover, vasculature is normalized through axitinib, which contributes to reducing tumor hypoxia and reversing the immunosuppressive effects of vascular endothelial growth factor. This joint action promotes the infiltration of immune effector cells into the tumor. Therefore, the amplified photodynamic nanodrug with excellent biocompatibility effectively inhibits tumor growth and lung metastasis and produces a cascade of immune responses. Our study demonstrates a practically innovative strategy for activating cancer immunotherapy, which can alter the "cold" properties of tumors.

The molecular binding sequence transformation of soil organic matter and biochar dissolved black carbon antagonizes the transport of 2,4,6-trichlorophenol.

Dissolved organic matter (DOM) and dissolved black carbon (DBC) are significant environmental factors that influence the transport of organic pollutants. However, the mechanisms by which their molecular diversity affects pollutant transport remain unclear. This study elucidates the molecular binding sequence and adsorption sites through which DOM/DBC compounds antagonize the transport of 2,4,6-trichlorophenol (TCP) using column experiments and modelling. DBC exhibits a high TCP adsorption rate (kn = 5.32 × 10-22 mol1-n∙Ln-1∙min-1) and conditional stability constant (logK = 5.19-5.74), indicating a strong binding affinity and antagonistic effect on TCP. This is attributed to the high relative content of lipid/protein compounds in DBC (25.65 % and 30.28 %, respectively). Moreover, the small molecule lipid compounds showed stronger TCP adsorption energy (Ead = -0.0071 eV/-0.0093 eV) in DOM/DBC, combined with two-dimensional correlation spectroscopy model found that DOM/DBC antagonized TCP transport in the environment through binding sequences that transformed from lipid/protein small molecule compounds to lignin/tannin compounds. This study used a multifaceted approach to comprehensively assess the impact of DOM/DBC on TCP transport. It reveals that the molecular diversity of DOM/DBC is a critical factor affecting pollutant transport, providing important insights into the environmental trend and ecological effects of pollutants.

Insights into the Roles of Natural Killer Cells in Osteoarthritis.

Osteoarthritis (OA) is now widely acknowledged as a low-grade inflammatory condition, in which the intrinsic immune system plays a significant role in its pathogenesis. While the involvement of macrophages and T cells in the development of OA has been extensively reviewed, recent research has provided mounting evidence supporting the crucial contribution of NK cells in both the initiation and advancement of OA. Accumulated evidence has emerged in recent years indicating that NK cells play a critical role in OA development and progression. This review will outline the ongoing understanding of the utility of NK cells in the etiology of OA, focusing on how NK cells interact with chondrocytes, synoviocytes, osteoclasts, and other immune cells to influence the course of OA disease.

Co-delivery of Paclitaxel/Atovaquone/Quercetin to regulate energy metabolism to reverse multidrug resistance in ovarian cancer by PLGA-PEG nanoparticles.

Ovarian cancer is a malignant tumor that seriously endangers the lives of women, with chemotherapy being the primary clinical treatment. However, chemotherapy encounters the problem of generating multidrug resistance (MDR), mainly due to drug efflux induced by P-glycoprotein (P-gp), which decreases intracellular accumulation of chemotherapeutic drugs. The drugs efflux mediated by P-gp requires adenosine triphosphate (ATP) hydrolysis to provide energy. Therefore, modulating energy metabolism pathways and inhibiting ATP production may be a potential strategy to reverse MDR. Herein, we developed a PTX-ATO-QUE nanoparticle (PAQNPs) based on a PLGA-PEG nanoplatform capable of loading the mitochondrial oxidative phosphorylation (OXPHOS) inhibitor atovaquone (ATO), the glycolysis inhibitor quercetin (QUE), and the chemotherapeutic drug paclitaxel (PTX) to reverse MDR by inhibiting energy metabolism through multiple pathways. Mechanistically, PAQNPs could effectively inhibit the OXPHOS and glycolytic pathways of A2780/Taxol cells by suppressing the activities of mitochondrial complex III and hexokinase II (HK II), respectively, ultimately decreasing intracellular ATP levels in tumor cells. Energy depletion can effectively inhibit cell proliferation and reduce P-gp activity, increasing the chemotherapeutic drug PTX accumulation in the cells. Moreover, intracellular reactive oxygen species (ROS) is increased with PTX accumulation and leads to chemotherapy-resistant cell apoptosis. Furthermore, PAQNPs significantly inhibited tumor growth in the A2780/Taxol tumor-bearing NCG mice model. Immunohistochemical (IHC) analysis of tumor tissues revealed that P-gp expression was suppressed, demonstrating that PAQNPs are effective in reversing MDR in tumors by inducing energy depletion. In addition, the safety study results, including blood biochemical indices, major organ weights, and H&E staining images, showed that PAQNPs have a favorable in vivo safety profile. In summary, the results suggest that the combined inhibition of the two energy pathways, OXPHOS and glycolysis, can enhance chemotherapy efficacy and reverse MDR in ovarian cancer.

A comparative study on the preparation and evaluation of solubilizing systems for silymarin.

Silymarin (SM) exhibits clinical efficacy in treating liver injuries, cirrhosis, and chronic hepatitis. However, its limited water solubility and low bioavailability hinder its therapeutic potential. The primary objective of this study was to compare the in vitro and in vivo characteristics of the four distinct SM solubilization systems, namely SM solid dispersion (SM-SD), SM phospholipid complex (SM-PC), SM sulfobutyl ether-ß-cyclodextrin inclusion complex (SM-SBE-ß-CDIC) and SM self-microemulsifying drug delivery system (SM-SMEDDS) to provide further insights into their potential for enhancing the solubility and bioavailability of SM. The formation of SM-SD, SM-PC, and SM-SBE-ß-CDIC was thoroughly characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and powder X-ray diffractometry (PXRD) techniques to analyze the changes in their microscopic structure, molecular structure, and crystalline state. The particle size and polydispersity index (PDI) of SM-SMEDDS were 71.6 ± 1.57 nm, and 0.13 ± 0.03, respectively. The self-emulsifying time of SM-SMEDDS was 3.0 ± 0.3 min. SM-SMEDDS exhibited an improved in vitro dissolution rate and demonstrated the highest relative bioavailability compared to pure SM, SM-SD, SM-PC, SM-SBE-ß-CDIC, and Legalon®. Consequently, SMEDDS shows promise as a drug delivery system for orally administered SM, offering enhanced solubility and bioavailability.

Effectively synthesized functional Si-doped carbon dots with the applications in tyrosinase detection and lysosomal imaging.

There has been significant interest in the preparation and versatile applications of carbon dots (CDs) due to their immense potential value in sensors and imaging. In this work, silicon-doped green carbon dots (Si-CDs) with high quantum yield and rich epoxypropyl were effectively synthesized. Given the clinical diagnostic importance of abnormal levels of tyrosinase (TYR), sensitive detection of TYR is significant for clinical research. A fluorescence signal-off strategy with Si-CDs as probe was constructed to determine TYR based on the oxidation of dopamine by TYR. The detection ranges of this method were 0.01-1.5 and 10-30 U/mL with the detection limit of 0.0046 U/mL, the lower limit of quantification (LLOQ) was 0.01 U/mL, and TYR was successfully and accurately monitored in human serum. Additionally, due to the role of lysosomes in cellular regulatory processes, including TYR levels and fluorescence stability characteristics of Si-CDs in acidic conditions, it was envisaged to use Si-CDs as probe to establish real-time monitoring of lysosomes. According to fluorescence colocation analysis, Si-CDs had intrinsic lysosomal targeting ability to HepG2 and L-02 (with Pearson correlation coefficients were 0.90 and 0.91, respectively). The targeting of Si-CDs to lysosomes was due to the acidophilic effect of the epoxypropyl on its surface.

Tough, recyclable and biocompatible carrageenan-modified polyvinyl alcohol ionic hydrogel with physical cross-linked for multimodal sensing.

Biocompatibility hydrogel conductors are considered as sustainable bio-electronic materials for the application of wearable sensors and implantable devices. However, they mostly face the limitations of mismatched mechanical properties with skin tissue and the difficulty of recycling. In this regard, here, a biocompatible, tough, reusable sensor based on physical crosslinked polyvinyl alcohol (PVA) ionic hydrogel modified with ι-carrageenan (ι-CG) helical network was reported. Through simulating the ion transport and network structure of biological systems, the ionic hydrogels with skin-like mechanical features exhibit large tensile strain of 640 %, robust fracture strength of 800 kPa, soft modulus and high fatigue resistance. Meanwhile, the ionic hydrogel-based sensors possess a high response to strain/pressure over a wide range and could be utilized for multimodal sensing of human activity signals. Benefit from biosafety and temperature reversibility of ι-CG and PVA endow hydrogels with not only biocompatibility, but also meaningfully recyclability. The as-prepared hydrogels could be freely reconstructed into new flexible electronics and safely integrated with the human skin. It could be anticipated that the physically cross-linked ionic hydrogel conductor could expand the options for next-generation bio-based sensors.

Review on typical organophosphate diesters (di-OPEs) requiring priority attention: Formation, occurrence, toxicological, and epidemiological studies.

The impact of primary metabolites of organophosphate triesters (tri-OPEs), namely, organophosphate diesters (di-OPEs), on the ecology, environment, and humans cannot be ignored. While extensive studies have been conducted on tri-OPEs, research on the environmental occurrence, toxicity, and health risks of di-OPEs is still in the preliminary stage. Understanding the current research status of di-OPEs is crucial for directing future investigations on the production, distribution, and risks associated with environmental organophosphate esters (OPEs). This paper specifically reviews the metabolization process from tri-OPEs to di-OPEs and the occurrence of di-OPEs in environmental media and organisms, proposes typical di-OPEs in different media, and classifies their toxicological and epidemiological findings. Through a comprehensive analysis, six di-OPEs were identified as typical di-OPEs that require prioritized research. These include di-n-butyl phosphate (DNBP), bis(2-butoxyethyl) phosphate (BBOEP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis(2-chloroethyl) phosphate (BCEP), bis(1-chloro-2-propyl) phosphate (BCIPP), and diphenyl phosphate (DPHP). This review provides new insights for subsequent toxicological studies on these typical di-OPEs, aiming to improve our understanding of their current status and provide guidance and ideas for research on the toxicity and health risks of di-OPEs. Ultimately, this review aims to enhance the risk warning system of environmental OPEs.

Cubosomes-assisted transdermal delivery of doxorubicin and indocyanine green for chemo-photothermal combination therapy of melanoma.

Melanoma is a highly aggressive form of skin cancer with limited therapeutic options. Chemo-photothermal combination therapy has demonstrated potential for effectively treating melanoma, and transdermal administration is considered the optimal route for treating skin diseases due to its ability to bypass first-pass metabolism and enhance drug concentration. However, the stratum corneum presents a formidable challenge as a significant barrier to drug penetration in transdermal drug delivery. Lipid-nanocarriers, particularly cubosomes, have been demonstrated to possess significant potential in augmenting drug permeation across the stratum corneum. Herein, cubosomes co-loaded with doxorubicin (DOX, a chemotherapeutic drug) and indocyanine green (ICG, a photothermal agent) (DOX-ICG-cubo) transdermal drug delivery system was developed to enhance the therapeutic efficiency of melanoma by improving drug permeation. The DOX-ICG-cubo showed high encapsulation efficiency of both DOX and ICG, and exhibited good stability under physiological conditions. In addition, the unique cubic structure of the DOX-ICG-cubo was confirmed through transmission electron microscopy (TEM) images, polarizing microscopy, and small angle X-ray scattering (SAXS). The DOX-ICG-cubo presented high photothermal conversion efficiency, as well as pH and thermo-responsive DOX release. Notably, the DOX-ICG-cubo exhibited enhanced drug permeation efficiency, good biocompatibility, and improved in vivo anti-melanoma efficacy through the synergistic effects of chemo-photothermal therapy. In conclusion, DOX-ICG-cubo presented a promising strategy for melanoma treatment.

Stretchable Organohydrogel with Adhesion, Self-Healing, and Environment-Tolerance for Wearable Strain Sensors.

Stretchable hydrogels as landmark soft materials have been efficiently utilized in the field of wearable sensing devices. However, these soft hydrogels mostly cannot integrate transparency, stretchability, adhesiveness, self-healing, and environmental adaptability into one system. Herein, a fully physically cross-linked poly(hydroxyethyl acrylamide)-gelatin dual-network organohydrogel is prepared in a phytic acid-glycerol binary solvent via a rapid ultraviolet light initiation. The introduction of gelatin as the second network endows the organohydrogel with desirable mechanical performance (high stretchability up to 1240%). The presence of phytic acid not only synergizes with glycerol to impart environment-tolerance to the organohydrogel (from -20 to 60 °C) but also increases the conductivity. Moreover, the organohydrogel demonstrates a durable adhesive performance toward diverse substrates, a high self-healing efficiency through heat treatment, and favorable optical transparency (transmittance of 90%). Furthermore, the organohydrogel achieves high sensitivity (gauge factor of 2.18 at 100% strain) and rapid response time (80 ms) and could detect both tiny (a low detection limit of 0.25% strain) and large deformations. Therefore, the assembled organohydrogel-based wearable sensors are capable of monitoring human joint motions, facial expression, and voice signals. This work proposes a facile route for multifunctional organohydrogel transducers and promises the practical application of flexible wearable electronics in complex scenarios.

Different oil-modified cross-linked starches: In vitro digestibility and its relationship with their structural and rheological characteristics.

This study investigated the structure, rheological behaviors and in vitro digestibility of oil-modified cross-linked starches (Oil-CTS). Gelatinized Oil-CTS were hard to be digested due to its intact granule shapes and the presence of surface-oil, which acted as physical barriers that inhibited the diffusion and penetration of enzymes to starch. Besides, the less amylose content in Oil-CTS (23.19-26.96%) than other starches (26.84-29.20%) contributed to its low digestibility because amylose with less α-1,6 linkages was more easily attacked by amyloglucosidase than amylopectin. Moreover, heat treatment during oil could shorten the amylopectin chain length and destroy the ordered structures, thus increasing enzymatic hydrolysis on starch. Pearson correlation analysis indicated rheological parameters were not significantly correlated with digestion parameters (p > 0.05). Overall, despite the damage caused by heat to molecular structures, physical barrier effect caused by surface-oil layers and integrity of swollen granules was the most critical contributor to the low digestibility of Oil-CTS.

Drug Self-Delivery Nanocubes Enhance O2 -Economized Photodynamic-Immunotherapy of Triple-Negative Breast Cancer by Downregulating Wnt/ß-catenin Signaling.

Although the combination of chemotherapy and immune checkpoint inhibitors (ICIs) can treat triple-negative breast cancer (TNBC), the severe effects of chemotherapy on immune cells significantly reduce the efficacy of the ICIs. Photodynamic therapy (PDT) with high selectivity is an alternative to chemotherapy that can also effectively treat hypoxic TNBC. However, high levels of immunosuppressive cells, and low infiltration of cytotoxic T lymphocytes (CTLs) limit the efficacy of PDT combined with ICIs. This study aims to evaluate the role of drug self-delivery nanocubes (ATO/PpIX-SMN) combined with anti-PD-L1 in TNBC treatment. Anti-malarial atovaquone (ATO) enhances protoporphyrin IX (PpIX)-mediated PDT-induced immunogenic cell death and downregulates tumor Wnt/ß-catenin signaling. Furthermore, the nanocubes combined with anti-PD-L1, which synergistically induce maturation of dendritic cells, promote infiltration of CTLs, reduce regulatory T cells, and significantly activate the host immune system, thus treating primary and distal tumors. This work demonstrates that ATO/PpIX-SMN can enhance the response rate of anti-PD-L1 in TNBC treatment via O2 -economized photodynamic-downregulating Wnt/ß-catenin signaling.

Integrating Fly Ash-Controlled Surface Morphology and Candle Grease Coating: Access to Highly Hydrophobic Poly (L-lactic Acid) Composite for Anti-Icing Application.

New ways of recycling fly ash are of great significance for reducing the environmental pollution. In this work, biodegradable hydrophobic poly (L-lactic acid)/fly ash composites for anti-icing application were successfully fabricated via a facile solvent-volatilization-induced phase separation approach. A silane coupling agent of 3-(Trimethoxysilyl) propyl methacrylate was used to decorate a fly ash surface (FA@KH570) for strengthening the interface bonding between fly ash and poly (L-lactic acid). Moreover, FA@KH570 could obviously enhance the crystallinity of poly (L-lactic acid) (PLLA)/FA@KH570 composites, which accelerated the conversion from the liquid-liquid to the liquid-solid phase separation principle. Correspondingly, the controllable surface morphology from smooth to petal-like microspheres was attained simply by adjusting the FA@KH570 content. After coating nontoxic candle grease, the apparent contact angle of 5 wt% PLLA/FA@KH570 composite was significantly increased to an astonishing 151.2°, which endowed the composite with excellent anti-icing property. This strategy paves the way for recycling waste fly ash and manufacturing hydrophobic poly (L-lactic acid) composite for potential application as an anti-icing material for refrigerator interior walls.

Hypoxia-ameliorated photothermal manganese dioxide nanoplatform for reversing doxorubicin resistance.

Drug resistance is a huge hurdle in tumor therapy. Tumor hypoxia contributes to chemotherapy resistance by inducing the hypoxia-inducible factor-1α (HIF-1α) pathway. To reduce tumor hypoxia, novel approaches have been devised, providing significant importance to reverse therapeutic resistance and improve the effectiveness of antitumor therapies. Herein, the nanosystem of bovine serum albumin (BSA)-templated manganese dioxide (MnO2) nanoparticles (BSA/MnO2 NPs) loaded with doxorubicin (DOX) (DOX-BSA/MnO2 NPs) developed in our previous report was further explored for their physicochemical properties and capacity to reverse DOX resistance because of their excellent photothermal and tumor microenvironment (TME) response effects. The DOX-BSA/MnO2 NPs showed good biocompatibility and hemocompatibility. Meanwhile, DOX-BSA/MnO2 NPs could greatly affect DOX pharmacokinetic properties, with prolonged circulation time and reduced cardiotoxicity, besides enhancing accumulation at tumor sites. DOX-BSA/MnO2 NPs can interact with H2O2 and H+ in TME to form oxygen and exhibit excellent photothermal effect to further alleviate hypoxia due to MnO2, reversing DOX resistance by down-regulating HIF-1α expression and significantly improving the antitumor efficiency in DOX-resistant human breast carcinoma cell line (MCF-7/ADR) tumor model. The hypoxia-ameliorated photothermal MnO2 platform is a promising strategy for revering DOX resistance.

The generation of environmentally persistent free radicals on photoaged microbeads from cosmetics enhances the toxicity via oxidative stress.

Microbeads used in personal care products have been one of the important sources of microplastics (MPs), and little has been reported on their environmental behaviors and health risks. The characteristics of environmentally persistent free radicals (EPFRs) and the toxicity assessment of MPs (environmentally relevant concentrations) from cosmetics during photoaging remains largely unknown. In this study, the formation of EPFRs on polyethylene (PE) microbeads from facial scrubs under light irradiation and their toxicity were investigated using C. elegans as a model organism. The results suggested that light irradiation induced the generation of EPFRs, which accelerates the aging process and alters the physicochemical properties of PE microbeads. Acute exposure to PE (1 mg/L) at photoaged times of 45-60 d significantly decreased the physiological indicators (e.g., head thrashes, body bends, and brood size). The oxidative stress response and stress-related gene expression were also enhanced in nematodes. The addition of N-acetyl-l-cysteine induced significant inhibition of toxicity and oxidative stress in nematodes exposed to 45-60 d of photoaged PE. The Pearson correlation results showed that the concentration of EPFRs was significantly correlated with physiological indicators, oxidative stress, and related-genes expression in nematodes. The data confirmed that the generation of EPFRs combined with heavy metals and organics contributed to toxicity induced by photoaged PE, and oxidative stress might be involved in regulating adverse effects in C. elegans. The study provides new insight into the potential risks of microbeads released into the environment during photoaging. The findings also highlight the necessity for considering the role of EPFRs formation in evaluating the impacts of microbeads.

Effect of oil-modified crosslinked starch as a new fat replacer on gel properties, water distribution, and microstructures of pork meat batter.

This work investigated the effects of oil-modified crosslinked starch (Oil-CTS) as a fat replacer on the gel properties, water distribution, microstructures, and fatty acid composition of pork meat batter. Results showed that the replacement of pork back fat by Oil-CTS could improve the gel performance in terms of rheological property, texture, and water-holding capacity (WHC), and reduce the water mobility of pork meat gels, which caused by the formation of a more ordered and denser protein network structure. Additionally, when the fat was replaced by Oil-CTS partially or totally (25-100 %), the total fat content in pork meat gels decreased by 16.5-82 % and the saturated fatty acids (SFAs) content decreased from 5.87 g/100 g in untreated sample to 1.17-4.88 g/100 g in starch-replacing-fat samples, indicating Oil-CTS could be used as a fat replacer to prepare the low-fat meat products.

Remote Loading of Hydrophilic Drug into Cubosomes by Transmembrane pH-Gradient and Characterization of Drug-Loaded Cubosomes Prepared by Different Method.

The encapsulation efficiency (EE) of hydrophobic drug into cubosomes was high by conventional methods, while poor for the hydrophilic drug. In this study, a remote loading method based on transmembrane pH-gradient was applied to prepare hydrophilic drug loaded cubosomes. Several hydrophilic drugs were selected and studied. Results showed just part of the investigated drugs were successfully loaded into cubosomes by the remote loading method, whereas all the drugs failed to be encapsulated by the high-pressure homogenization method. The EE based on remote loading method was affected by the solubility, LogP, number of rings, and polarizability of the drug independent of the number of hydrogen acceptor and hydrogen donor. And the drugs that had high EE by remote loading method were BCS class 1 or 2. In addition, the EE base on remote loading method was significantly affected by the external water pH of cubosomes and drug concentration. The size of drug-loaded cubosomes by remote loading method mainly depended on the pre-formed blank cubosomes, which was bigger than that by high-pressure homogenization method. The preparation method affected the liquid crystalline structure of acidic drug loaded cubosomes, while showed no obvious effect on that of basic drug loaded cubosomes. The release of drug was susceptible to the pH of release medium independent of the preparation method. The drug-loaded cubosomes prepared by different method all showed favorable stability during storage. The remote loading method was a promising approach for the efficient encapsulation of hydrophilic drug into cubosomes. This study laid a foundation for the application of remote loading method on the preparation of hydrophilic drug loaded cubosomes.

Triphenyl phosphate induced reproductive toxicity through the JNK signaling pathway in Caenorhabditis elegans.

Triphenyl phosphate (TPHP) is a widely used aryl organophosphate flame retardant (OPFR) that has attracted attention due to its frequent detection in the environment and living organisms. To date, the reproductive toxicity of TPHP has been investigated in organisms, but its molecular mechanisms are not fully understood. Caenorhabditis elegans (C. elegans) is the ideal animal for the study of reproductive toxicity following environmental pollutants, with short generation times, intact reproductive structures, and hermaphroditic fertilization. This study aimed to explore the reproductive dysfunction and molecular mechanisms induced by TPHP exposure in C. elegans. Specifically, exposure to TPHP resulted in a reduction in the number of eggs laid and developing embryos in utero, an increase in the number of apoptotic gonadal cells, and germ cell cycle arrest. The JNK signaling pathway is a potential pathway inducing reproductive toxicity following TPHP exposure based on transcriptome sequencing (RNA-seq). Moreover, TPHP exposure induced down-regulation of vhp-1 and kgb-2 gene transcription levels, and the knockout of vhp-1 and kgb-2 in the mutant strains exhibited more severe toxicity in apoptotic gonad cells, embryos, and eggs developing in utero, suggesting that vhp-1 and kgb-2 genes play a crucial role in TPHP-induced reproductive toxicity. Our data provide convergent evidence showing that TPHP exposure results in reproductive dysfunction through the JNK signaling pathway and improve our understanding of the ecotoxicity and toxicological mechanisms of aryl-OPFRs.