Cang-ai volatile oil alleviates nasal inflammation via Th1/Th2 cell imbalance regulation in a rat model of ovalbumin-induced allergic rhinitis.

We previously revealed that Cang-ai volatile oil (CAVO) regulates T-cell activity, enhancing the immune response in people with chronic respiratory diseases. However, the effects of CAVO on allergic rhinitis (AR) have not been investigated. Herein, we established an ovalbumin (OVA)-induced AR rat model to determine these effects. Sprague-Dawley (SD) rats were exposed to OVA for 3 weeks. CAVO or loratadine (positive control) was given orally once daily for 2 weeks to OVA-exposed rats. Behavior modeling nasal allergies was observed. Nasal mucosa, serum, and spleen samples of AR rats were analyzed. CAVO treatment significantly reduced the number of nose rubs and sneezes, and ameliorated several hallmarks of nasal mucosa tissue remodeling: inflammation, eosinophilic infiltration, goblet cell metaplasia, and mast cell hyperplasia. CAVO administration markedly upregulated expressions of interferon-γ, interleukin (IL)-2, and IL-12, and downregulated expressions of serum tumor necrosis factor-α, IL-4, IL-5, IL-6, IL-13, immunoglobulin-E, and histamine. CAVO therapy also increased production of IFN-γ and T-helper type 1 (Th1)-specific T-box transcription factor (T-bet) of the cluster of differentiation-4+ T-cells in splenic lymphocytes, and protein and mRNA expressions of T-bet in nasal mucosa. In contrast, levels of the Th2 cytokine IL-4 and Th2-specific transcription factor GATA binding protein-3 were suppressed by CAVO. These cumulative findings demonstrate that CAVO therapy can alleviate AR by regulating the balance between Th1 and Th2 cells.

Brain-Derived Neurotrophic Factor-Loaded Low-Temperature-Sensitive liposomes as a drug delivery system for repairing podocyte damage.

Podocytes, cells of the glomerular filtration barrier, play a crucial role in kidney diseases and are gaining attention as potential targets for new therapies. Brain-Derived Neurotrophic Factor (BDNF) has shown promising results in repairing podocyte damage, but its efficacy via parenteral administration is limited by a short half-life. Low temperature sensitive liposomes (LTSL) are a promising tool for targeted BDNF delivery, preserving its activity after encapsulation. This study aimed to improve LTSL design for efficient BDNF encapsulation and targeted release to podocytes, while maintaining stability and biological activity, and exploiting the conjugation of targeting peptides. While cyclic RGD (cRGD) was used for targeting endothelial cells in vitro, a homing peptide (HITSLLS) was conjugated for more specific uptake by glomerular endothelial cells in vivo. BDNF-loaded LTSL successfully repaired cytoskeleton damage in podocytes and reduced albumin permeability in a glomerular co-culture model. cRGD conjugation enhanced endothelial cell targeting and uptake, highlighting an improved therapeutic effect when BDNF release was induced by thermoresponsive liposomal degradation. In vivo, targeted LTSL showed evidence of accumulation in the kidneys, and their BDNF delivery decreased proteinuria and ameliorated kidney histology. These findings highlight the potential of BDNF-LTSL formulations in restoring podocyte function and treating glomerular diseases.

l-Carnosine loaded on carboxymethyl cellulose hydrogels for promoting wound healing.

Wound management remains a challenge in clinical practice. Nowadays, patients have an increasing demand for wound repair with enhanced speed and quality; therefore, there is a great need to seek therapeutic strategies that can promote rapid and effective wound healing. In this study, we developed a carboxymethyl cellulose hydrogel loaded with l-carnosine (CRN@hydrogel) for potential application as a wound dressing. In vitro experiments confirmed that CRN@hydrogel can release over 80% of the drug within 48 h and demonstrated its favorable cytocompatibility and blood compatibility, thus establishing its applicability for safe utilization in clinical practice. Using a rat model, we found that this hydrogel could promote and accelerate wound healing more effectively. These results indicate that the novel hydrogel can serve as an efficient therapeutic strategy for wound treatment.

Improvement of thermostability by increasing rigidity in the finger regions and flexibility in the catalytic pocket area of Pseudoalteromonas porphyrae κ-carrageenase.

Poor thermostability reduces the industrial application value of κ-carrageenase. In this study, the PoPMuSiC algorithm combined with site-directed mutagenesis was applied to improve the thermostability of the alkaline κ-carrageenase from Pseudoalteromonas porphyrae. The mutant E154A with improved thermal stability was successfully obtained using this strategy after screening seven rationally designed mutants. Compared with the wild-type κ-carrageenase (WT), E154A improved the activity by 29.4% and the residual activity by 51.6% after treatment at 50 °C for 30 min. The melting temperature (Tm) values determined by circular dichroism were 66.4 °C and 64.6 °C for E154A and WT, respectively. Molecular dynamics simulation analysis of κ-carrageenase showed that the flexibility decreased within the finger regions (including F1, F2, F3, F5 and F6) and the flexibility improved in the catalytic pocket area of the mutant E154A. The catalytic tunnel dynamic simulation analysis revealed that E154A led to enlarged catalytic tunnel volume and increased rigidity of the enzyme-substrate complex. The increasing rigidity within the finger regions and more flexible catalytic pocket of P. porphyrae κ-carrageenase might be a significant factor for improvement of the thermostability of the mutant κ-carrageenase E154A. The proposed rational design strategy could be applied to improve the enzyme kinetic stability of other industrial enzymes. Moreover, the hydrolysates of κ-carrageenan digested by the mutant E154A demonstrated increased scavenging activities against hydroxyl (OH) radicals and 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) radicals compared with the undigested κ-carrageenan.

Music therapy for cognitive deficits of neuropsychiatric disorders.

Music therapy has evolved as a supplementary treatment for a diverse range of mental and physical conditions. In recent years, the application of music therapy in addressing cognitive deficits has garnered growing interest. It has demonstrated the capacity to enhance memory, focus, and emotional expression in individuals. Furthermore, it contributes to positive outcomes in social interaction, psychological and physical well-being, and overall quality of life for patients. As a result, there is a compelling rationale for further exploration and investigation into the effectiveness of this therapeutic approach.

The role of mitochondrial damage-associated molecular patterns in acute pancreatitis.

Acute pancreatitis (AP) is one of the most common gastrointestinal tract diseases with significant morbidity and mortality. Current treatments remain unspecific and supportive due to the severity and clinical course of AP, which can fluctuate rapidly and unpredictably. Mitochondria, cellular power plant to produce energy, are involved in a variety of physiological or pathological activities in human body. There is a growing evidence indicating that mitochondria damage-associated molecular patterns (mtDAMPs) play an important role in pathogenesis and progression of AP. With the pro-inflammatory properties, released mtDAMPs may damage pancreatic cells by binding with receptors, activating downstream molecules and releasing inflammatory factors. This review focuses on the possible interaction between AP and mtDAMPs, which include cytochrome c (Cyt c), mitochondrial transcription factor A (TFAM), mitochondrial DNA (mtDNA), cardiolipin (CL), adenosine triphosphate (ATP) and succinate, with focus on experimental research and potential therapeutic targets in clinical practice. Preventing or diminishing the release of mtDAMPs or targeting the mtDAMPs receptors might have a role in AP progression.

Recent developments in synthesis of attapulgite composite materials for refractory organic wastewater treatment: a review.

Attapulgite clay, due to its unique crystalline hydrated magnesium-aluminium silicate composition and layer-chain structure, possesses exceptional adsorption and catalytic properties, which enable it or its composites to be utilized as adsorbents and catalysts for wastewater treatment. But the drawbacks of attapulgite are also very obvious, such as relatively low specific surface area (compared to traditional adsorbents such as activated carbon and activated alumina), easy aggregation, and difficulty in dispersion. In order to fully utilize and improve the performance of attapulgite, researchers have conducted extensive research on its modification, but few specialized works have comprehensively evaluated the synthesis, applications and challenges for attapulgite-based composite materials in refractory organic wastewater treatments. This paper provides a comprehensive review of controllable preparation strategies, characterization methods and mechanisms of attapulgite-based composite materials, as well as the research progress of these materials in refractory organic wastewater treatment. Based on this review, constructive recommendations, such as deep mechanism analysis from molecular level multi-functional attapulgite-based material developments, and using biodegradable materials in attapulgite-based composites, were proposed.

Polycomb proteins RING1A/B promote H2A monoubiquitination to regulate female gametophyte development in Arabidopsis.

A functional female gametophyte is the basis of successful sexual reproduction in flowering plants. During female gametophyte development, the megaspore mother cell (MMC), differentiated from a single subepidermal somatic cell in the nucellus, undergoes meiosis to produce four megaspores; only the one at the chalazal end, referred to as functional megaspore (FM), undergoes three rounds of mitosis and develops into a mature embryo sac. Here, we reported that RING1A and RING1B (RING1A/B), two functionally redundant Polycomb proteins in Arabidopsis, are critical for female gametophyte development. The mutations of RING1A/B resulted in defects in MMC and FM's specification and subsequent mitosis of FM, thereby leading to aborted ovules. Gene expression analysis revealed several genes essential for female gametophyte development, including Argonaute (AGO) family genes and critical transcription factors, were ectopically expressed in ring1a ring1b. Furthermore, RING1A/B bound some of these genes to promote H2A monoubiquitination (H2Aub) deposition. Together, RING1A/B promote H2Aub modification at genes essential for female gametophyte development, suppressing their expression to ensure the progression of female gametophyte development.

PPIP5K2 Facilitates Proliferation and Metastasis of Non-Small Lung Cancer (NSCLC) through AKT Signaling Pathway.

Through facilitating DNA homologous recombination repair, PPIP5K2 has been proven to be essential for improving colorectal cancer survival in our previous research. However, its function in the tumorigenesis of NSCLC, the most common cancer and the primary cause of cancer-related death globally, is still unknown. Here, we initially discovered that PPIP5K2 had significant effects on proliferation of NSCLC cells through loss- and gain-of-function assays in vitro and in vivo. Moreover, PPIP5K2 is capable of regulating NSCLC cells metastasis in an EMT-dependent manner. In terms of mechanism exploration, we found that PPIP5K2 knockdown can significantly inhibit the phosphorylation of AKT/mTOR signaling pathway, whereas the overexpression of PPIP5K2 resulted in converse effects. By employing AKT signaling related agonists or antagonists, we further demonstrated that PPIP5K2 regulates NSCLC tumorigenesis partly via the AKT/mTOR pathway. In conclusion, PPIP5K2 plays a key oncogenic role in NSCLC by the activation of the AKT/mTOR signaling axis. It is anticipated that targeting PPIP5K2 might emerge as a viable therapeutic approach for NSCLC patients.

Improving the thermostability of Pseudoalteromonas Porphyrae κ-carrageenase by rational design and MD simulation.

The industrial applications of the κ-carrageenases have been restricted by their poor thermostability. In this study, based on the folding free energy change (ΔΔG) and the flexibility analysis using molecular dynamics (MD) simulation for the alkaline κ-carrageenase KCgCD from Pseudoalteromonas porphyrae (WT), the mutant S190R was identified with improved thermostability. After incubation at 50 °C for 30 min, the residual activity of S190R was 63.7%, 25.7% higher than that of WT. The Tm values determined by differential scanning calorimetry were 66.2 °C and 64.4 °C for S190R and WT, respectively. The optimal temperature of S190R was 10 °C higher than that of WT. The κ-carrageenan hydrolysates produced by S190R showed higher xanthine oxidase inhibitory activity compared with the untreated κ-carrageenan. MD simulation analysis of S190R showed that the residues (V186-M194 and P196-G197) in F5 and the key residue R150 in F3 displayed the decreased flexibility, and residues of T169-N173 near the catalytic center displayed the increased flexibility. These changed flexibilities might be the reasons for the improved thermostability of mutant S190R. This study provides a useful rational design strategy of combination of ΔΔG calculation and MD simulation to improve the κ-carrageenase's thermostability for its better industrial applications.

Novel anionic surfactant-modified chlorhexidine and its potent antimicrobial properties.

Chlorhexidine dodecyl sulfate (CHX-DS) was synthesized and characterized via single-crystal X-ray diffraction (SC-XRD), 1H nuclear magnetic resonance (NMR) spectroscopy, 1H nuclear Overhauser effect spectroscopy (NOESY), and attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR). The solid-state structure, comprising a 1 : 2 stoichiometric ratio of chlorhexidine cations [C22H30Cl2N10]2+ to dodecyl sulfate anions [C12H25SO4]-, is the first report of chlorhexidine isolated with a surfactant. CHX-DS exhibits broad-spectrum antibacterial activity and demonstrates superior efficacy for reducing bacteria-generated volatile sulfur compounds (VSCs) as compared to chlorhexidine gluconate (CHG). The minimum inhibitory concentrations (MICs) of CHX-DS were 7.5, 2.5, 2.5, and 10 µM for S. enterica, E. coli, S. aureus, and S. mutans, respectively. Furthermore, MIC assays for E. coli and S. mutans demonstrate that CHX-DS and CHX exhibit a statistically significant efficacy enhancement in 2.5 µM treatment as compared to CHG. CHX-DS was incorporated into SBA-15, a mesoporous silica nanoparticle (MSN) framework, and its release was qualitatively measured via UV-vis in aqueous media, which suggests its potential as an advanced functional material for drug delivery applications.

Evaluation of three-dimensional reconstructed palatal morphology in skeletal class III subjects with different vertical patterns using cone beam computed tomography.

BACKGROUND: This study aims to evaluate the difference of three-dimensional (3D) reconstructed palatal morphology between subjects with skeletal Class III and skeletal Class I in different vertical patterns using cone beam computed tomography (CBCT). METHODS: In this study, 89 subjects with skeletal Class III (49 females, 40 males; 25.45 ± 3.81 years) and 85 subjects with skeletal Class I (45 females, 40 males; 23.95 ± 4.45 years) were collected retrospectively and divided into hyperdivergent, normodivergent and hypodivergent groups. Dolphin software was used to reorient the CBCT images of these subjects. After segmenting 3D object of maxilla from the 3D skull by ProPlan software, Geomagic Studio was used to reconstruct 3D palatal morphology and establish an average 3D palatal morphology for each group. The differences of 3D palatal morphology between different groups were compared by deviation patterns on 3D colored map analysis. RESULTS: 3D colored map analysis showed the posterior part of male's palate was higher and wider than that of female's palate in skeletal Class III subjects. In skeletal Class III subjects, males with hyperdivergent pattern had a higher and narrower palate compared with hypodivergent subjects, while females with hyperdivergent had a higher but not obviously narrower palate compared with hypodivergent subjects. In the similar vertical patterns, skeletal Class III subjects had a flatter but not narrower palate compared with skeletal Class I subjects, along with a smaller palate volume. CONCLUSIONS: This method allows more intuitive between-group comparisons of the differences of 3D palatal morphology. In skeletal Class III subjects, as the vertical dimension increased, the palate tends to be higher and narrower. Therefore, the influence of vertical patterns on the palatal morphology should be fully considered in the orthodontic and orthognathic treatment of skeletal Class III subjects.

Anticancer effect of hUC-MSC-derived exosome-mediated delivery of PMO-miR-146b-5p in colorectal cancer.

Antisense oligonucleotide (ASO) is a novel therapeutic platform for targeted cancer therapy. Previously, we have demonstrated that miR-146b-5p plays an important role in colorectal cancer progression. However, a safe and effective strategy for delivery of an ASO to its targeted RNA remains as a major hurdle in translational advances. Human umbilical cord mesenchymal cell (hUC-MSC)-derived exosomes were used as vehicles to deliver an anti-miR-146b-5p ASO (PMO-146b). PMO-146b was assembled onto the surface of exosomes (e) through covalent conjugation to an anchor peptide CP05 (P) that recognized an exosomal surface marker, CD63, forming a complex named ePPMO-146b. After ePPMO-146b treatment, cell proliferation, uptake ability, and migration assays were performed, and epithelial-mesenchymal transition progression was evaluated in vitro. A mouse xenograft model was used to determine the antitumor effect and distribution of ePPMO-146b in vivo. ePPMO-146b was taken up by SW620 cells and effectively inhibited cell proliferation and migration. The conjugate also exerted antitumor efficacy in a xenograft mouse model of colon cancer by systematic administration, where PPMO-146b was enriched in tumor tissue. Our study highlights the potential of hUC-MSC-derived exosomes anchored with PPMO-146b as a novel safe and effective approach for PMO backboned ASO delivery.

Pomegranate juice-containing serum inhibits migration of hepatocellular carcinoma cells and promotes apoptosis by induction of mitochondrial dysfunction.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, with an insidious onset and poor prognosis. Pomegranate is a fruit rich in many natural products with anti-cancer potential; however, its direct biological effects are difficult to evaluate in vitro because of changes in its active components after absorption and metabolism. This study was conducted to prepare pomegranate juice-containing serum (PJ serum) by gavage of pomegranate juice (PJ) in rats and to collect serum. The aim was to investigate the components and the effects of PJ serum on HCC cells by serum pharmacology. 56 compounds were identified in the PJ serum, including 6 prototype components. PJ serum selectively inhibited HCC cells proliferation and migration, and it promoted apoptosis of HCC cells without affecting LO2 cells activity. Furthermore, PJ serum reduced the mitochondrial membrane potential and increased the calcium ion concentration in HCC cells. Mechanistically, PJ serum up-regulated the expression of the Bax family, Caspases and TIMP2/MMP2, and down-regulated the expression of MMP9. This study revealed that PJ serum inhibited HCC cell migration by regulating the TIMP2/MMP2 balance and MMP9 expression and promoted HCC cell apoptosis by inducing mitochondrial dysfunction and causing a Caspase cascade. The polyphenols and flavonoids in PJ may be important components responsible for its anti-HCC activity after metabolism.

The association of maternal serum uric acid with the risk of small for gestational age newborn: a retrospective cohort study.

PROBLEM: Prior results on the association between serum uric acid (UA) levels in the early trimester and the risk of small for gestational age (SGA) remain unclear. This study evaluated the association of maternal first-, second-, and third-trimester UA levels with the risk of SGA infants. METHOD OF STUDY: A total of 23, 194 singleton mothers from the International Peace Maternity and Child Health Hospital between January 2014 and January 2017 were included. Maternal UA levels were measured at 12.1 ± 1.08th (UA1) and 32.2 ± 1.03th (UA2) gestational weeks. △UA was calculated as the difference between UA2 and UA1. Logistic regression and restricted cubic spline (RCS) were performed to evaluate the association between maternal UA and △UA during pregnancy and SGA. Receiver operating characteristic (ROC) analysis was employed to assess the serum uric acid prediction value. RESULTS: Women in the higher quartiles of UA1 had a significantly higher risk of SGA. A clear increased risk for SGA was observed with higher quartiles for UA2 (p for trend <0.05). An approximately "J-shaped" relationship was observed between UA2 and △UA, and the risk of SGA was observed. When compared with those with a lower level of UA in the first trimester, those with a higher level of UA1, the more increase in the later UA levels were associated with a higher risk of SGA [adjusted odds ratio (aOR) = 1.67, 95% CI:1.37-2.05]. The ROC curve areas were 0.525 for UA1, 0.582 for UA2 and 0.576 for △UA. CONCLUSIONS: The findings suggested that non-preeclamptic and non-hypertensive women who experienced early pregnancy with high UA levels had an elevated risk of SGA. Moreover, a high maternal UA level in the earlier trimester may be an early predictor of SGA.

A Phase-Field Study of Spinodal Decomposition Impeded by Irradiation in U-Mo and U-Mo-Zr Alloys.

The phase-field method, coupled with the micro-elastic model and irradiation-induced cascade mixing model, has been employed to investigate the spinodal decomposition in U-Mo and U-Mo-Zr alloys. The microstructure evolution of U-Mo or U-Mo-Zr alloys under different initial conditions, such as the alloy composition, aging temperature and irradiation intensity, were simulated to study the effect of cascade mixing on the miscibility gap, morphology and volume fraction of the decomposed phases. The simulation results demonstrate that irradiation-induced cascade mixing impedes the process of spinodal decomposition, and that irradiation shrinks the composition range of the miscibility gap in the alloys. Irradiation-induced cascade mixing slows down the anisotropic growth rate of the spinodal decomposition, yet this phenomenon can be weakened with increasing aging temperature. Adding an appropriate amount of Zr to a U-Mo alloy can effectively prevent the contraction of the miscibility gap caused by irradiation.

Rosa Roxburghii Tratt Fruit Extract Prevents Dss-Induced Ulcerative Colitis in Mice by Modulating the Gut Microbiota and the IL-17 Signaling Pathway.

Ulcerative colitis (UC) is a non-specific inflammatory bowel illness characterized by intestinal mucosal barrier degradation, inflammation, oxidative damage, and gut microbiota imbalances. Rosa roxburghii Tratt Fruit extract (RRTE) was extracted from Rosa roxburghii Tratt fruit, exhibiting an excellent prevention effect against UC; RRTE could prevent the damage of DSS-induced human normal colonic epithelial (NCM 460) cells, especially in cell viability and morphology, and oxidative damage. Additionally, in UC mice, RRTE could limit the intestinal mucosal barrier by increasing the expression of intestinal tight junction proteins and mucin, reducing inflammation and oxidative damage in colon tissue. More importantly, RRTE can increase the abundance of beneficial bacteria to regulate gut microbiota such as Ruminococcus, Turicibacter, and Parabacteroides, and reduce the abundance of harmful bacteria such as Staphylococcus and Shigella. Furthermore, transcriptomics of colonic mucosal findings point out that the beneficial effect of RRTE on UC could be attributed to the modulation of inflammatory responses such as the IL-17 and TNF signaling pathways. The qPCR results confirm that RRTE did involve the regulation of several genes in the IL-17 signaling pathway. In conclusion, RRTE could prevent DSS-induced damage both in vitro and in vivo.

Chemopreventive Effects of Polysaccharides and Flavonoids from Okra Flowers in Azomethane/Dextran Sulfate Sodium-Induced Murine Colitis-Associated Cancer.

Okra flowers are a good source of polysaccharides and flavonoids, with biological activities of anti-inflammatory action and modulation of the gut microbiota. Previously, we reported that flavonoid-rich extracts from okra flowers (AFE) presented effective anti-colorectal cancer (CRC) activity in CRC cells as well as xenograft models, but their role in colitis-associated cancer (CAC) is unidentified. In this study, we aimed to evaluate the effects of AFE and APE (polysaccharides extracted from okra flowers) on the CAC symptoms of azoxymethane (AOM)/dextran sodium sulfate (DSS)-intervened mice. The results showed that APE and AFE exert potent efficacy in inhibiting colitis and colorectal tumorigenesis stimulated by AOM/DSS, characterized by decreased colonic shortening, DAI score, and tumor numbers. Compared with the control group, APE/AFE alleviated the microbiota dysbiosis driven by AOM/DSS. In addition, AFE elicited its anticancer activity through regulation of NFκB/IL-6/Stat3, JAK2/Stat3, MAPKs, PI3K/AKT, and Wnt/ß-catenin signal transductions in AOM/DSS mice, which was consistent with a vitro model of CT26 cells, while APE treatment exhibited anticancer activity through regulation of Nrf2/IL-6, MAPKs, PI3K/AKT, and Wnt/ß-catenin signal transductions in the AOM/DSS mouse model. Collectively, our studies revealed, for the first time, that flavonoids and polysaccharides from okra flowers possess the ability to attenuate colitis and colorectal tumorigenesis, with them having great potential to become promising candidates against CRC.

Preparation of barium sulfate chelating agent DTPA-5Na and molecular dynamics simulation of chelating mechanism.

Barium sulfate (BaSO4) scale is dense and hard, making it difficult to remove using conventional acid and alkali treatments. Diethylenetriaminepentaacetic acid (DTPA) and its complexes have been identified as important chelating agents for the removal of BaSO4 scale. However, DTPA has good solubility only under strong alkali conditions, which in turn exacerbate scaling. To improve the solubility and chelation effectiveness of DTPA, penta sodium diethylenetriamine-pentaacetate (DTPA-5Na) was synthesized using chloroacetic acid, diethylenetriamine, sodium carbonate, and sodium hydroxide as raw materials. The structure of DTPA-5Na was characterized by infrared spectroscopy and 1H-NMR, and its chelation effectiveness was evaluated. Experimentation demonstrated that under conditions of 50 °C and with a molar ratio of chloroacetic acid (ClCH2COOH), sodium carbonate (Na2CO3), sodium hydroxide (NaOH), and diethylenetriamine (DETA) of 5.00 : 2.50 : 5.25 : 1.00, the reaction for 6 hours resulted in the optimal chelation value of DTPA-5Na at 76.8 mg CaCO3·per g. Analysis of the chelation and dissolution of BaSO4 scale using DTPA-5Na and microstructural scanning electron microscopy of the BaSO4 crystal indicate that DTPA-5Na functions through solubilization, lattice distortion, and flaking dispersion to remove BaSO4. Molecular dynamics simulation software was used to simulate the chelation mechanism of DTPA-5Na, where the results indicated strong adsorption of DTPA-5Na to the surface of BaSO4. The adsorption energy follows the order of (120) surface > (001) surface > (100) surface > (210) surface. The adsorption is mainly a result of the interaction between the carboxylic "O" atom in DTPA-5Na and the (001), (100), and (120) surfaces of BaSO4 scale, while N atoms in DTPA-5Na structure primarily interact with the (210) surface. The adsorption of "O" atoms is stronger than that of "N" atoms in the DTPA-5Na structure.

Lipid-assisted PEG-b-PLA nanoparticles with ultrahigh SN38 loading capability for efficient cancer therapy.

The topoisomerase I inhibitor, 7-ethyl-10-hydroxycamptothecin (SN38), has demonstrated potent anticancer activity. However, its clinical application is hindered by its low solubility and high crystallization propensity, which further complicates its encapsulation into nanoparticles for systemic delivery. Herein, we explore the utilization of lipid-assisted poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-b-PLA) nanoparticles to achieve ultrahigh loading capability for SN38. Through the introduction of cationic, anionic, or neutral lipids, the SN38 loading efficiency and loading capacity is elevated to >90% and >10% respectively. These lipids efficiently attenuate the intermolecular π-π stacking of SN38, thereby disrupting its crystalline structure. Moreover, we assess the therapeutic activity of SN38-loaded formulations in various tumor models and identify an anionic lipid 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) sodium salt (DOPG)-assisted formulation that exhibits the highest anticancer activity and has favorable biosafety. Overall, our findings present a simple and robust strategy to achieve ultrahigh loading efficiency of SN38 using commonly employed PEG-b-PLA nanoparticles, opening up a new avenue for the systemic delivery of SN38.