Acidity-Actuated Polymer/Calcium Phosphate Hybrid Nanomotor (PCaPmotor) for Penetrating Drug Delivery and Synergistic Anticancer Immunotherapy.

Tumor acidity-driven nanomotors may offer robust propulsion for tumor-specific penetrating drug delivery. Herein, an acidity-actuated poly(amino acid) calcium phosphate (CaP) hybrid nanomotor (PCaPmotor) was designed, using a mPEG-PAsp-PPhe@THZ531 micelle (Poly@THZ) for CaP mineralization accompanied by αPD-L1 antibody encapsulation. Dissolution of the CaP layer in an acidic tumor environment gave off heat energy to propel the nanomotor to augment the cellular uptake and penetration into deeply seated cancer cells while facilitating αPD-L1 release. THZ531 delivered by the PCaPmotor inhibited CDK12 and its down-streamed phosphorylation of RNAP-II to increase the cancer immunogenicity events such as the DNA damage, cell apoptosis, immunogenic cell death, lysosomal function disturbance, and MHC-I upregulation. THZ531 and αPD-L1 cosupplied by PCaPmotor significantly increased the frequency of DCs maturation and intratumoral infiltration of CTLs, but the two free drugs did not. Consequently, the PCaP@THZ/αPD-L1 nanomotor resulted in synergistic anticancer immunotherapy in mice. This acid-actuated PCaPmotor represented a new paradigm for penetrating drug delivery.

Varying water column stability controls the denitrification process in a subtropical reservoir, Southwest China.

Reservoirs are regarded as hotspots of nitrogen transformation and potential sources of nitrous oxide (N2O). However, it remains unclear how the hydrological conditions due to dam construction control the processes of nitrogen transformation in reservoir waters. To address this issue, we examined the spatial-temporal characteristics of nitrate concentrations, δ15N-NO3-, δ18O-NO3-, δ18O-H2O, relative water column stability (RWCS), and related environmental factors in a subtropical eutrophic reservoir (Hongfeng Reservoir, HFR), Southwest China. We found that denitrification was the most important nitrogen transformation process in the HFR and that higher denitrification intensity was associated with increased RWCS in summer, which suggested hydrological control of the denitrification process. In contrast, low RWCS conditions favored the nitrification process in the HFR in winter. Additionally, dissolved oxygen (DO; p < 0.05) and nitrate concentrations (p < 0.01) had significant impacts on the denitrification rate. We also found that the spatiotemporal RWCS variations were a prerequisite for regulating DO/nitrate stratification and the coupling/decoupling of nitrification-denitrification at the local and global scales. This study would advances our knowledge of the impacts of RWCS and thermal stratification on nitrogen transformation processes in reservoirs.

Increasement of Cd adsorption capacity of rice stubble from being alive until death in a modified rice-fish system.

Soil heavy metal contamination is an increasingly urgent problem throughout the world. Phytoremediation is a cost-effective and ecologically friendly in situ method for the remediation of heavy metal contaminated soils. Rice has the potential for use in soil remediation due to its high biomass production, however, risks related to food safety and low accumulation potential exist. Therefore, in the current study, rice stubble was used as the adsorbent in a modified rice-fish system (MRFS) to assess its accumulation capacity in a model paddy field dosed with 0-40.0 mg kg-1 Cd. The weighted mean concentration (WMC) of Cd in rice stubble increased from 0.498 to 36.365 mg kg-1 to 1.038-71.180 mg kg-1 from 0 to 60 days post-harvest (dph), and the corresponding increment rate was 107.68%, 117.42%, 157.77% and 95.73%, respectively. Sixty-days post-harvest, removal rate of Cd from contaminated soils was 1.11-1.40%, which was greater than that of the Cd-hyperaccumulator Thlaspi caerulescens. The WMC of the heavy metals Cd, Zn, Pb, Cr and Cu in rice stubble increased 51.11-97.50%, and removal rate was 1.93-2.66%. Overall, rice stubble had a high capacity of heavy metal accumulation, mainly benefiting from the synthesis effects of MRFS and the changes of accumulation mechanism within the plant from being alive until death. Notably, this study also provides a new idea for in situ, herbage-based phytoremediation of heavy metal-contaminated soils.

Dynamics of sediment phosphorus affected by mobile aeration: Pilot-scale simulation study in a hypereutrophic pond.

Controlling the release of phosphorus (P) in sediments is important to prevent eutrophication and harmful algal blooms in water bodies. Here we explored the effect of mobile aerators on the control of P release from sediments in a eutrophic pond. The dissolved oxygen in the water body recovered significantly after six months of aeration, becoming 4.2-5.8 times higher than in the control. The pH and Eh values at the sediment-water interface considerably increased, while the concentration of soluble reactive phosphorus (SRP) in pore water significantly decreased, resulting in the alteration of SRP fluxes from 1.69 mg/m2 d to -53.49 mg/m2 d. Moreover, the inert P in sediments increased by 5.2% of the total P at the end of the study compared with the initial state, and the calcium-bound phosphorus (HCl-P) increased by 96.6%. However, although aeration reduced the concentration of SRP in the water column, the total P concentration was 2.45 times higher than that of the control, and the content of redox-sensitive P (BD-P) in the sediment also increased by 200%. Overall, although mobile aeration can maintain the microenvironment of the sediment interface and increase the inert P content in the sediment to reduce the P flux, it cannot reduce the risk of release of mobile P.

Computer-Aided Design and Computer-Aided Manufacturing Cutting Guides in Eminoplasty for the Treatment of Temporomandibular Joint Dislocation.

OBJECTIVE: Temporomandibular joint (TMJ) dislocation means the condyle moves out of the normal position. There are several treatments for TMJ dislocation, including conservative treatment, injection treatment, minimally invasive treatment, and open surgical treatment. In this study, we tried to review the literature related to the augmentation of the articular eminence and proposed a modified eminoplasty technique of TMJ dislocation by computer-aided design and computer-aided manufacturing (CAD/CAM) cutting guides. METHODS: The literature on eminoplasty for TMJ was reviewed with 3 charts. Besides, 2 (67 and 69 years old) patients with chronic recurrent dislocation were treated by the CAD/CAM-guided surgical technique in our study, and postoperative measures were recorded to verify the safety and effectiveness regarding this technique. RESULTS: A total of 28 studies (including 268 patients) of the augmentation of the articular eminence have been reported since 1967, including the 2 present patients. According to the analysis of the recurrence and complications in the review, we found the modified technique had an obvious advantage. The technique with cutting guides was also found having higher accuracy. CONCLUSION: The modified technique was a reliable method when treating the TMJ dislocation, and the combination of CAD/CAM cutting guides was useful for more accuracy, even reduced the operation difficulty.

Inhibition of osteogenesis surrounding the titanium implant by CGRP deficiency.

Previous studies have suggested one of the neurotransmitters, calcitonin gene-related peptide (CGRP), modulates local regulation of bone metabolism; however, the regulating signaling pathway is still being explored. The objective of this study was to determine whether CGRP deficiency affects the osteogenesis surrounding titanium implants in vivo. Titanium screws were implanted in 72 adult rats, which were divided into three groups randomly: Sham, inferior alveolar neurectomy (IAN), and IAN+CGRP. Saline solution containing CGRP (concentration: 100 nmol/L) was injected into the area surrounding the implants in the IAN+CGRP group every day post operation. According to histological observations and Micro-CT, osteogenesis surrounding the implant was suppressed in the IAN group compared to that in the Sham and IAN+CGRP groups; the highest degree of osteogenesis was observed in the Sham group. This effect was also proved via the gene expressions of osteocalcin and runt-related transcription factor 2 surrounding the implant by real-time (RT) PCR analysis. In addition, through immunofluorescence staining and RT-PCR analysis, levels of CGRP and ß-catenin were also reduced in the IAN group, while the highest expression was observed in the Sham group (p < 0.05). Our results collectively suggest that the titanium implant bone model established by IAN exhibited CGRP deficiency and reduced osteogenesis surrounding the implant. Additionally, the expression analyses suggest that the canonical Wnt signaling pathway could be involved in this process of bone metabolism in vivo.

Distribution of axial length in Chinese congenital ectopia lentis patients: a retrospective study.

BACKGROUND: Congenital ectopia lentis (CEL) usually leads to refractive error and may influence the axial length development. But few investigations have reported patient demographics and the distribution of axial length (AL) before surgery in Chinese pediatric patients with CEL. To describe the distribution of AL before surgery in CEL patients and its relationship with patients' demographics, such as age, Marfan syndrome, sex, and laterality. METHODS: This retrospective study reviewed 306 CEL patients from January 1, 2006 to December 31, 2015. One eye was randomly selected from each patient if both eyes were EL. The influences of Marfan syndrome, sex, and laterality to AL in different age subgroups were evaluated and compared. The differences of the AL between groups were assessed using the student t test or paired t-test. P-values less than 0.05 were considered statistically significant. RESULTS: Two hundred forty-seven eyes were enrolled. 58.3% of all the patients had binoculus EL, 70% of all the patients were male and 36% of all the patients were diagnosed with Marfan syndrome. The mean AL of EL patients was 25.1 ± 2.5 mm. There was no statistical difference in the AL between patients with and without Marfan syndrome, and in the AL between male and female patients. There was statistical difference in AL between the EL-affected eye and the unaffected eye in monocular EL patients younger than 12 years old. CONCLUSIONS: This study suggests that AL can be influenced by CEL, but the influence of CEL may be reduced after the age of 12 years old, which will likely provide a useful reference when considering the most appropriate time of surgery.

Upper Airway Changes After Mandibular Setback and/or Advancement Genioplasty in Obese Patients.

PURPOSE: Orthognathic surgeries, such as bilateral sagittal split ramus osteotomy (BSSO) and genioplasty, can influence the pharyngeal airway space (PAS) and this has been supported by previous studies. The purpose of this study was to assess changes of the PAS in patients with a high body mass index (BMI) likely to have narrow airways before and after setback BSSO with or without advancement genioplasty surgery by 3-dimensional computed tomography. MATERIALS AND METHODS: Thirty-five adults with a BMI of at least 24.0 kg/m2 were treated from 2010 to 2016. Samples were grouped mandibular setback (group A; n = 11), advancement genioplasty (group B; n = 12), and mandibular setback plus advancement genioplasty (group C; n = 12). Computed tomograms were obtained 1 week preoperatively (T0), 1 week postoperatively (T1), and at least 1 year postoperatively (T2). The area of the posterior nasal spine and posterior plane (PPA), the soft palate plane (SPA), the plane of the most posterior point of the tongue base (PTA), the plane of the root of the epiglottis (EA), and the volumes of the palatopharyngeal part (VP), oropharyngeal part (VO), glossopharyngeal part (VG), and laryngeal part (VL) were measured and compared within groups using analysis of variance. The P value was set at .05. RESULTS: In group A, all results showed statistically significant differences (P < .05) from T0 to T2 except for VO, VG, VL, SPA, PTA, and EA. In group B, VO, VG, VL, SPA, PTA, and EA showed statistically significant increases (P < .05) from T0 to T2. The hyoid at T2 showed significant advancement compared with T0 (P < .05). In group C, there were statistically significant decreases (P < .05) from T0 to T1 for VG, VL, PTA, and EA. CONCLUSION: In adults with a high BMI, mandibular setback BSSO could decrease the PAS, whereas advancement genioplasty could enlarge the PAS, after surgery. Therefore, undergoing advancement genioplasty concurrently with mandibular setback BSSO could help in lessening the negative effects of a PAS decrease.

TIPE2 protein prevents injury-induced restenosis in mice.

Proliferation of vascular smooth muscle cells (VSMCs) plays an important role in restenosis, a disease characterized by smooth muscle cell hyperplasia and neointimal formation. How proliferation signals are controlled to avoid restenosis is not fully understood. Here we report that TIPE2, the tumor necrosis factor (TNF) α-induced protein 8-like 2 (TNFAIP8L2), suppresses injury-induced restenosis by inhibiting VSMCs proliferation. TIPE2 was significantly upregulated in VSMCs in response to PDGF-BB stimuli and injury. Enforced TIPE2 expression significantly suppressed VSMCs proliferation and cell cycle progression, whereas TIPE2 deficiency in VSMCs promoted cell proliferation and upregulated the expression of Cyclins D1 and D3. TIPE2 likely regulated VSMC proliferation via Rac1-STAT3 and ERK1/2 signaling pathways. It blocked STAT3 activation and nuclear translocation in a Rac1-dependent manner. As a result, TIPE2-deficient VSMCs exhibited enhanced proliferation whereas TIPE2-deficient mice developed more severe restenosis in response to vascular injury. Conversely, adenovirus-mediated gene transfer of TIPE2 significantly reduced injury-induced restenosis in mice. These results indicate that TIPE2 plays a suppressive role in injury-induced restenosis and may serve as a new therapeutic target for treating the disease.

Rainfall-induced nutrient losses from manure-fertilized farmland in an alluvial plain.

Nutrient transport and loss in farmlands are affected by factors such as land cover, fertilization, soil type, rainfall, and management practices. We investigated the temporal and spatial changes in macronutrient transport and loss after fertilization and precipitation in manure-fertilized eggplant farmland in an alluvial plain. Upon adding topical fertilizer, concentrations of most nutrients in runoff and groundwater increased, and nitrogen runoff increased from 22.11 to 35.81 kg/ha, although eggplant yield did not increase correspondingly. Incorporation of fertilizer by plowing reduced nutrient losses (nitrogen runoff/fertilizer decreased from 18.40 to 12.29 %). Measurements taken along the nutrient transport route (runoff, drainage ditch, groundwater, river water, and finally rainfall) revealed that concentrations of most nutrients declined at each stage. Nutrient characteristics varied by transport, and the forms of nitrogen and phosphorus differed greatly between runoff and groundwater (nitrate/nitrogen in runoff was ~43.49 %, while in groundwater ~5.41 %). Most nutrient concentrations in runoff decreased greatly during the planting season (total nitrogen decreased from 62.25 to 4.17 mg/L), correlated positively with temperature and stage of plant growth, but little temporal change was observed in groundwater. This field investigation during one planting season exemplifies the basic principles of nutrient loss and transport from manure-fertilized farmland in an alluvial plain.

[Experimental study on anti-tumor effect of xihuang pill and its immune clearance function].

OBJECTIVE: To discuss the anti-tumor effect of Xihuang pill on tumor-bearing rats and its effect on the immune clearance function of tumor-bearing organisms. METHOD: Walker256 tumor cells were adopted to establish the tumor-bearing rat model. The rats were randomly divided into five groups: the normal control group, the model control group, the lentinan group and Xihuang pill low dose, middle dose and high dose groups, with 10 rats in each group, and continuously treated and given drugs for 14 d after modeling. Blood and tumors were collected from abdominal aorta to calculate the tumor inhibition rate. The content of CD3+, CD4+, CD8+ T cells and adhesion molecule B7-1 (CD80) in peripheral blood were detected by flow cytometry (FCM). The expressions of IL-2 and IFN-gamma in were determined by ELISA. RESULT: The tumor inhibition rate of the Xihuang pill high dose group was 33. 1 percent. Compared with the model group, the Xihuang pill large dose group showed significantly low IL-2, IFN-gamma, CD3+, CD4+, B7-1 in peripheral blood, with statistical significance in their differences (P < 0.05). CONCLUSION: Xihuang pill could show its anti-tumor effect by enhancing the immune clearance function and increasing IL-2, IFN-gamma, CD3+ T, CD4+ T, B7-1 in peripheral blood.

Explaining demographic-destination preferences for cultural ecosystem services: A set-theoretic configurational analysis.

Many fundamental studies on cultural ecosystem services (CES) and CES destination preferences still tend to focus on detecting the respective importance of destination attributes. However, this perspective needs more efforts on the fact that visitors always select a CES destination through a configurational consideration of its ecological and environmental attributes. Based on this consideration, 22 urban green spaces in Nagoya, Japan were studied, and a configurational model was developed by applying complexity theory and qualitative comparative analysis (QCA), to explain and better understand the causal patterns of CES quality and availability influencing demographic-CES destination preferences. The results showed that similar preference modes occurred between young adults and males who were very concerned about the time spent on transportation, and between older people and females who had multiple considerations regarding both CES quality and availability. Such findings on the demographic-destination preferences for CES could not only provide configurational insight into the relationships between destination attributes and travel preferences, but also help CES organizations develop multi-factor cooperative management for better CES provision.

New types of open-framework vanadium borophosphates with photocatalytic properties.

The exploration of new open-framework polyoxometalates is very significant in structural chemistry and materials science. Herein, three new organic hybrid three-dimensional vanadium borophosphates (H3O)7(H2aeae)3{[Cd(H2O)3]2[H3O⊃(V2BP2O12)6]}·15H2O (1, aeae = 2-(2-aminoethylamino)ethanol) and (H3O)5(H2aeae)3{[TM(H2O)2.5(H2aeae)0.5]2[H3O⊃ (V2BP2O12)6]}·9H2O [TM = Mn(2), Co(3)] were hydrothermally prepared and structurally characterized. The three vanadium borophosphates contain similar 12-member ring crown-shaped clusters [(V2BP2O12)6]18- based on the linkage of six [V2O8] dimers and six [BP2O10] units. The [(V2BP2O12)6]18- cluster is further bridged by the unsaturated [Cd(H2O)3]2+ or [TM(H2O)2.5(H2aeae)0.5]3+ complexes to build new types of open-framework vanadium borophosphates with pores and cavities retained by the protonated H2aeae2+, H3O+ and free H2O. Surprisingly, the monodentate H2aeae2+ ligand coordinating with a metal center was observed in 2 and 3 for the first time as the aeae molecule acted as the trichelating ligand. Their optical absorption edges were determined to be in the range of 2.61-2.68 eV using solid-state UV-vis spectroscopy. 1-3 exhibited excellent photocatalytic activity towards methylene blue (MB) degradation under visible light irradiation, which presented the first example of organic hybrid open-framework vanadium borophosphates as the photo-catalysts for MB degradation.

SMC2 knockdown inhibits malignant progression of lung adenocarcinoma by upregulating BTG2 expression.

Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer worldwide. Structural maintenance of chromosomes 2 (SMC2) serves as a predictor of poor prognosis across various cancer types. This study aims to explore the role and underlying mechanisms of SMC2 in LUAD progression. The expression of SMC2 in LUAD tissues and its correlation with prognosis were analyzed by public databases. Knockdown of SMC2 was performed to assess the proliferation, migration and invasion ability of LUAD cells. Bulk RNA sequencing analysis identified enriched cellular pathways and remarkable upregulation of BTG anti-proliferation factor 2 (BTG2) expression after SMC2 knockdown in LUAD cells. Then, BTG2 was silenced to assess the malignant behavior of LUAD cells. Subcutaneous transplantation and intracranial tumor models of LUAD cells in BALB/c nude mice were established to assess the antineoplastic effect of SMC2 knockdown in vivo. Additionally, a lung metastasis model was created to evaluate the pro-metastatic effect of SMC2. Our findings indicated that SMC2 was upregulated in LUAD tissues and cell lines, with higher expression correlating with poor prognosis. SMC2 silencing suppressed the proliferation, migration and invasion ability of LUAD cells by upregulating BTG2 expression via p53 and inactivating ERK and AKT pathways. BTG2 silencing reversed the effects of SMC2 downregulation on malignant behaviors of LUAD cells and restored the phosphorylated ERK and AKT levels. Furthermore, SMC2 knockdown effectively prevented the formation of subcutaneous, intracranial and metastatic tumor in vivo, and upregulation of BTG2 expression after SMC2 knockdown was confirmed in tumor models. This study revealed that SMC2 knockdown restrained the malignant progression of LUAD through upregulation of BTG2 expression and inactivation of ERK and AKT pathways, and SMC2 could be a potential therapeutic target for LUAD treatment.

Gut microbiome-metabolites axis: A friend or foe to colorectal cancer progression.

An expanding corpus of research robustly substantiates the complex interrelation between gut microbiota and the onset, progression, and metastasis of colorectal cancer. Investigations in both animal models and human subjects have consistently underscored the role of gut bacteria in a variety of metabolic activities, driven by dietary intake. These activities include amino acid metabolism, carbohydrate fermentation, and the generation and regulation of bile acids. These metabolic derivatives, in turn, have been identified as significant contributors to the progression of colorectal cancer. This thorough review meticulously explores the dynamic interaction between gut bacteria and metabolites derived from the breakdown of amino acids, fatty acid metabolism, and bile acid synthesis. Notably, bile acids have been recognized for their potential carcinogenic properties, which may expedite tumor development. Extensive research has revealed a reciprocal influence of gut microbiota on the intricate spectrum of colorectal cancer pathologies. Furthermore, strategies to modulate gut microbiota, such as dietary modifications or probiotic supplementation, may offer promising avenues for both the prevention and adjunctive treatment of colorectal cancer. Nevertheless, additional research is imperative to corroborate these findings and enhance our comprehension of the underlying mechanisms in colorectal cancer development.

A multicenter retrospective analysis: Factors influencing hepatic adverse events induced by immunotherapy in advanced liver cancer.

OBJECTIVES: To analyze the clinical characteristics and influencing factors of hepatotoxicity in patients with advanced hepatocellular carcinoma (HCC) treated with programmed cell death protein-1 (PD-1) inhibitors, and to provide a theoretical basis for the treatment of immune-related hepatotoxicity in patients with advanced HCC. METHODS: Retrospective analysis of clinical data of patients with advanced HCC from February 2021 to February 2023, in order to summarize and statistically analyze the influencing factors of immune-related liver adverse reactions. RESULTS: A total of 135 patients met the inclusion criteria, among whom 46 patients experienced varying degrees of immune-related liver adverse reactions, with an incidence rate of 34.1% (46/135). The time range of immune-related liver adverse reactions was 3-26 weeks, with a median time of 4 weeks. The age range of immune-related liver adverse reactions was 34-73 years, with a median age of 62 years. Statistical analysis of the influencing factors and liver adverse reactions showed that age, total bilirubin level, and Child-Pugh (C-P) grading were influencing factors for the occurrence of liver adverse reactions (p < .05), and among these three influencing factors, the proportion of males with ≥2 influencing factors was higher than that of females; liver function C-P B was an independent influencing factor for liver adverse reactions (p < .05). CONCLUSION: For male patients over 60 years old, with bilirubin levels ≥51 µmol/L and liver function C-P B, close observation of the occurrence of immune-related adverse reactions during treatment is recommended.

Differentiable Design Galleries: A Differentiable Approach to Explore the Design Space of Transfer Functions.

The transfer function is crucial for direct volume rendering (DVR) to create an informative visual representation of volumetric data. However, manually adjusting the transfer function to achieve the desired DVR result can be time-consuming and unintuitive. In this paper, we propose Differentiable Design Galleries, an image-based transfer function design approach to help users explore the design space of transfer functions by taking advantage of the recent advances in deep learning and differentiable rendering. Specifically, we leverage neural rendering to learn a latent design space, which is a continuous manifold representing various types of implicit transfer functions. We further provide a set of interactive tools to support intuitive query, navigation, and modification to obtain the target design, which is represented as a neural-rendered design exemplar. The explicit transfer function can be reconstructed from the target design with a differentiable direct volume renderer. Experimental results on real volumetric data demonstrate the effectiveness of our method.

Effect of lens surgery on health-related quality of life in preschool children with congenital ectopia lentis.

AIM: To evaluate the effect of lens surgery on health-related quality of life (HRQoL) of preschool children with congenital ectopia lentis (CEL). METHODS: A prospective self-controlled study was conducted in Zhongshan Ophthalmic Center. Children aged from 5 to 7y whom were diagnosed with CEL and underwent phacoemulsification with scleral-fixated posterior chamber intraocular lens implantation and their parents were enrolled in this study. All of them completed the child and proxy (parental) PedsQL™ 4.0 before and after the surgery. Their preoperative scores were compared to their postoperative ones. Subgroup analyses were performed based on gender and preoperative bilateral presenting visual acuity of the children. RESULTS: Thirty-two children with CEL successfully underwent surgery without any complications, among whom 8 had monocular surgery and 24 had binocular surgery. Preoperative and postoperative questionnaires were completed by 32 child-parent pairs. Surgical intervention could significantly improve the vision of affected children (P<0.001). The medians of physical, psychosocial and total health scores self-reported by the children were 68.75 (62.50, 81.25), 65.00 (60.00, 80.00) and 67.39 (60.87, 78.26) preoperatively and were 93.75 (87.50, 100.00), 90.00 (83.33, 96.67) and 89.13 (85.32, 95.65) postoperatively. The preoperative scores of the affected children were significantly lower in all scales than age-matched healthy children (P<0.001). All the postoperative scores were significantly higher than the preoperative scores in affected children and their parents (P<0.001). In the physical functioning evaluation, the preoperative score reported by parents of girls was higher than parents of boys (P=0.041), and the postoperative score of girls was higher than that of boys (P=0.036). CONCLUSION: CEL is associated with significantly worse quality of life in preschool children. Surgical intervention can significantly improve the HRQoL in affected children from both personal and family perspective.

In Situ Polymerized Self-Healing Microcapsules as Multifunctional Fillers toward Phosphate Ceramic Coatings.

The protective efficacy of chemically bonded phosphate ceramic coatings (CBPC) is notably diminished owing to the presence of micropores and inadequate self-healing capacity in prolonged corrosive environments. Consequently, it is imperative to augment the corrosion and wear resistance of phosphate ceramic coatings while imbuing them with self-healing capabilities. In this work, a novel self-healing phosphate ceramic coating (MC-PTx@CBPC, x = 0.5, 1.0, 1.5) is designed by urea-formaldehyde (UF) in situ polymerization of nanoscale microcapsules encapsulated with 1H,1H,2H,2H-perfluorodecyltriethoxysilane (PFDTES) and evaluated in detail for corrosion and wear resistance. The corrosion inhibition efficiencies of all formulated MC-PTx@CBPC (x = 0.5, 1.0, 1.5) coatings exceed 90%, with the impedance modulus at the lowest frequency (|Z|f=0.01) showing enhancements of 1-2 orders of magnitude compared to pure CBPC. Moreover, the self-healing function becomes active during prolonged immersion. This can be primarily ascribed to the formation of a unique micronanostructure facilitated by nanoscale microcapsules and micrometer-sized alumina ceramics, bonded via the AlPO4 phase. This structure enhances both the hydrophobicity and the bonding strength of the coating. Specifically, following prolonged immersion, the encapsulated PFDTES is liberated from the microcapsules, undergoing hydrolysis and subsequent polymerization upon contact with the electrolyte to form a protective thin film. This film efficiently obstructs the ingress of corrosive agents. Furthermore, the special micronanostructure enhances the hardness of the coating and the releasing PFDTES can form a lubricating film at the interface of abrasion, thus reducing the wear rate and friction coefficient of the MC-PTx@CBPC (x = 0.5, 1.0, 1.5). Therefore, MC-PTx@CBPC (x = 0.5, 1.0, 1.5) possesses excellent corrosion protection, tribological properties, and self-healing capabilities, which provide thought-provoking ideas for phosphate ceramic coatings to protect metals in harsh environments.

Trimethyl chitosan-cysteine-based nanoparticles as an effective delivery system for portulacerebroside A in the management of hepatocellular carcinoma cells in vitro and in vivo.

Portulacerebroside A (PCA), a cerebroside compound extracted from Portulaca oleracea L., has been shown to suppress hepatocellular carcinoma (HCC) cells. This study aims to investigate the effectiveness of trimethyl chitosan-cysteine (TMC-Cys) nanocarrier in delivering PCA for HCC management and to elucidate the molecular mechanisms behind PCA's function. TMC-Cys nanocarriers notably augmented PCA's function, diminishing the proliferation, migration, and invasiveness of HCC cells in vitro, reducing hepatocellular tumorigenesis in immunocompetent mice, and impeding metastasis of xenograft tumours in nude mice. Comprehensive bioinformatics analyses, incorporating Super-PRED systems alongside pathway enrichment analysis, pinpointed toll-like receptor 4 (TLR4) and epidermal growth factor receptor (EGFR) as two promising targets of PCA, enriched in immune checkpoint pathway. PCA/nanocarrier (PCA) reduced levels of TLR4 and EGFR and their downstream proteins, including programmed cell death ligand 1, thereby increasing populations and activity of T cells co-cultured with HCC cells in vitro or in primary HCC tumours in mice. However, these effects were counteracted by additional artificial activation of TLR4 and EGFR. In conclusion, this study provides novel evidence of PCA's function in immunomodulation in addition to its direct tumour suppressive effect. TMC-Cys nanocarriers significantly enhance PCA efficacy, indicating promising application as a drug delivery system.