MRI analysis of hydrogel-loaded apatinib for local therapy of hepatocellular carcinoma model in nude mice.

AIM: To investigate the effect of local treatment of gadolinium-polyethylene glycol (Gd-PEG) hydrogel containing apatinib injected into hepatocellular carcinoma model of HepG2 in nude mice, and to evaluate the MRI findings in vivo. METHODS: HepG2 cells were treated in vitro and OD 450 value were measured. The four groups (n = 6) were Apatinib-Gd-PEG hydrogel, Gd-PEG hydrogel, Apatinib, and Saline. T1WI and DWI scans were performed before and 1d, 3d, and 14d postoperatively. The samples were examined by histomorphology and immunohistochemistry for CD34 and VEGFR2. Microvessel density (MVD) was evaluated and the average optical density (AOD) of VEGFR2 was obtained by IPP6.0 image software. RESULTS: The OD450-time curves of Gd-PEG hydrogel and phosphate buffer saline (PBS) were similar and that of apatinib at all concentrations are located below; the higher the concentration, the lower the curve. On T1WI and DWI, the newly injected Gd-PEG hydrogel showed significant high signal and was immobilized in the tumor. Subsequently, the size and signal of Gd-PEG hydrogel gradually decreased with time. In Apatinib-Gd-PEG hydrogel group, compared with other three groups, MRI and histomorphology showed that the necrotic area of hepatocellular carcinoma model was larger, immunohistochemistry displayed minimal expression of CD34 and VEGFR2, the AOD of VEGFR2 and MVD differed markedly. CONCLUSION: Gd-PEG hydrogel can significantly enhance and prolong the inhibitory effect of apatinib. It can be visualized by MRI, which can be used to evaluate the local therapeutic effect.

Piezocatalytic Schottky Junction Treats Atherosclerosis by a Biomimetic Trojan Horse Strategy.

The atherosclerotic vulnerable plaque is characterized by the foamy macrophage burden, involving impaired cholesterol efflux and deficient efferocytosis. Correspondingly, piezocatalytic therapy is an emerging solution for eliminating the foamy macrophage burden with satisfactory spatiotemporal controllability and deep penetration depth. Herein, a biomimetic Trojan horse (Au-ZnO@MM) is engineered by coating the macrophage membrane (MM) onto the surface of a rod-like Au-ZnO Schottky Junction to effectively relieve the atherosclerotic progression. These Trojan horses with the coating of MM are actively transported into subsistent foamy macrophages and generate abundant reactive oxygen species (ROS) via ultrasound-activated piezocatalysis. ROS-initiated autophagy and mitochondrial dysfunction induce substantial cell apoptosis, alleviating the burden of subsistent foamy macrophages. The resulting apoptotic fragments further significantly facilitate cholesterol excretion and trigger efferocytosis of intraplaque fresh macrophages. Ultimately, the biomimetic Au-ZnO@MM piezocatalyst not only inhibits the foaming capacity of macrophages, but also improves the function of removing cell debris, which can stabilize atherosclerotic vulnerable plaque. Meanwhile, the plasmon resonance effect of integrated gold nanoparticles enables favorable photoacoustic molecular imaging for real-time image-guided atherosclerotic therapy. This proposed biomimetic Trojan horse strategy provides the paradigm of employing ultrasound-activated piezocatalytic methodology for enhanced atherosclerotic theranostics.

Niobium carbide MXenzyme-Driven comprehensive cholesterol regulation for photoacoustic image-guided and anti-inflammatory photothermal ablation in atherosclerosis.

Foam cells play a pivotal role in the progression of atherosclerosis progression by triggering inflammation within arterial walls. They release inflammatory molecules that attract additional immune cells, leading to further macrophage recruitment and plaque development. In this study, we develop an osteopontin (OPN) antibody-conjugated niobium carbide (Nb2C-aOPN) MXenzyme designed to selectively target and mildly ablate foam cells while reducing inflammation in the plaque microenvironment. This approach utilizes photonic hyperthermia to decrease plaque size by enhancing cholesterol regulation through both passive cholesterol outflow and positive cholesterol efflux. Nb2C-aOPN MXenzyme exhibits multiple enzyme-mimicking properties, including catalase, superoxide dismutase, peroxidase and glutathione peroxidase, and acts as a scavenger for reactive oxygen and nitrogen species. The inhibition of reactive oxygen and nitrogen species synergizes with photothermal ablation to promote positive cholesterol efflux, leading to reduced macrophage recruitment and a shift in macrophage phenotype from M1 to M2. This integrative strategy on cholesterol regulation and anti-inflammation highlights the potential of multifunctional 2D MXenzyme-based nanomedicine in advancing atherosclerotic regression.

Combinational Intercalation-Conversion-Intercalation reaction of CuInS2@PPy anode for Sodium-Ion batteries.

Polypyrrole-coated CuInS2 (CuInS2@PPy) composite was prepared through the chemical vapor transport method and subsequent in situ polymerized coating strategy. In this unique nanoarchitecture, the PPy coating layer plays a crucial role in improving the conductivity of the composite, suppressing the volume change of CuInS2, and maintaining the structural integrity of electrode material upon cycling. In addition, the electrochemical reaction mechanism and kinetics of CuInS2@PPy were investigated in-depth. Benefitting from the synergism of its combinational intercalation-conversion-intercalation reaction mechanism and the high conductivity of the PPy coating layer, CuInS2@PPy electrode exhibits superior rate capability and cycling stability for sodium-ion batteries, with a capacity of 404.8 mA h g-1 at 4 A g-1 over 2500 cycles.

Real-world evidence of combined treatment of biologics and exclusive enteral nutrition in patients with ileum-dominant Crohn's disease: A multicenter study.

BACKGROUND & AIMS: Although biologics were prescribed to achieve and maintain clinical remission of active Crohn's disease (CD), almost half of patients experienced a loss of response or intolerance. Here, we investigated the efficacy of combined treatment of biologics and 16-weeks exclusive enteral nutrition (EEN) in moderate-to-severe CD patients with small intestine lesions. METHODS: This was a real-world, multicenter retrospective study, from October 2016 to March 2023, medical records of patients registered at three IBD centers were reviewed for patients with ileal or ileocolonic CD in moderate-to-severe activity. All patients received treatment of biologics with concomitant 16-week EEN (BioEEN) or biologics alone (Bio). The clinical outcomes and endoscopic outcomes were assessed at week 16 and 52. RESULTS: There was no statistically significant difference between Bio (97 patients) and BioEEN group (100 patients) at baseline for demographic and clinical characteristics. Compared to treatment with biologics alone, patients with BioEEN treatment achieved higher rates of clinical response (95.0% vs. 66.0%), clinical remission (87.0% vs. 52.6%), endoscopic response (91.4% vs. 47.4%) including mucosal healing (85.7% vs. 23.7%) at week 16. The superiority of BioEEN sustained in maintenance, with 84.7% (vs. 49.1%) clinical response, 77.8% (vs. 38.6%) clinical remission, 69.2% (vs. 32.6%) endoscopic response and 51.9% (vs. 18.6%) mucosal healing at week 52. CONCLUSIONS: Combined treatment of biologics and 16-week EEN was an efficient therapeutic strategy with affirmative effectiveness for small intestine diseases of active CD.

Nanomedicine for Diagnosis and Treatment of Atherosclerosis.

With the changing disease spectrum, atherosclerosis has become increasingly prevalent worldwide and the associated diseases have emerged as the leading cause of death. Due to their fascinating physical, chemical, and biological characteristics, nanomaterials are regarded as a promising tool to tackle enormous challenges in medicine. The emerging discipline of nanomedicine has filled a huge application gap in the atherosclerotic field, ushering a new generation of diagnosis and treatment strategies. Herein, based on the essential pathogenic contributors of atherogenesis, as well as the distinct composition/structural characteristics, synthesis strategies, and surface design of nanoplatforms, the three major application branches (nanodiagnosis, nanotherapy, and nanotheranostic) of nanomedicine in atherosclerosis are elaborated. Then, state-of-art studies containing a sequence of representative and significant achievements are summarized in detail with an emphasis on the intrinsic interaction/relationship between nanomedicines and atherosclerosis. Particularly, attention is paid to the biosafety of nanomedicines, which aims to pave the way for future clinical translation of this burgeoning field. Finally, this comprehensive review is concluded by proposing unresolved key scientific issues and sharing the vision and expectation for the future, fully elucidating the closed loop from atherogenesis to the application paradigm of nanomedicines for advancing the early achievement of clinical applications.

CEO successor origins, top management team faultline, and strategic change-empirical evidence from China.

Building on the upper echelons theory and demographic faultline theory, this paper investigates the role of the top management team (TMT) faultline as a mediator and explores the moderating effect of CEO power as an important contextual factor. We utilize a sample of A-share listed companies on the Shanghai and Shenzhen Stock Exchanges from 2009 to 2020. Our findings show that outside CEO successors are significantly and positively related to corporate strategic change. TMT faultline mediates the effect of CEO successor origins on corporate strategic change, while CEO power reinforces the relationship between the two. Heterogeneity tests reveal that the effect of outside CEO successors on strategic change is insignificant in state-owned enterprises (SOEs) but has a significant impact on firms at their growth and maturity stages. Furthermore, our findings suggest that outside CEO successors inhibit the positive role of strategic change in promoting firm value.

Renal cell carcinoma: preoperative evaluate the grade of histological malignancy using volumetric histogram analysis derived from magnetic resonance diffusion kurtosis imaging.

BACKGROUND: To investigate the value of histogram analysis of magnetic resonance (MR) diffusion kurtosis imaging (DKI) in the assessment of renal cell carcinoma (RCC) grading before surgery. METHODS: A total of 73 RCC patients who had undergone preoperative MR imaging and DKI were classified into either a low- grade group or a high-grade group. Parametric DKI maps of each tumor were obtained using in-house software, and histogram metrics between the two groups were analyzed. Receiver operating characteristic (ROC) curve analysis was used for obtaining the optimum diagnostic thresholds, the area under the ROC curve (AUC), sensitivity, specificity and accuracy of the parameters. RESULTS: Significant differences were observed in 3 metrics of ADC histogram parameters and 8 metrics of DKI histogram parameters (P<0.05). ROC curve analyses showed that Kapp mean had the highest diagnostic efficacy in differentiating RCC grades. The AUC, sensitivity, and specificity of the Kapp mean were 0.889, 87.9% and 80%, respectively. CONCLUSIONS: DKI histogram parameters can effectively distinguish high- and low- grade RCC. Kapp mean is the best parameter to distinguish RCC grades.

Evaluating the inflammatory activity in Crohn's disease using magnetic resonance diffusion kurtosis imaging.

OBJECTIVES: To explore the feasibility of diffusion kurtosis imaging (DKI) for evaluating inflammatory activity in Crohn's disease (CD). MATERIALS AND METHODS: In all, 51 CD patients were included, who were performed with consecutive enteroscopy, MR and DKI (b values = 0-2000 mm2/s). The lesions of bowel segments were graded as inactive (0-2), mild (3-6), and moderate-severe group (> 6) based on simplified endoscopic activity score for Crohn's disease (SES-CD), The abilities of the parameters of DKI and DWI in grading different activity lesions were compared. RESULTS: One hundred and twenty-seven bowel segments including inactive (15), mild (45) and moderate-severe (67) were analyzed. ADC (r = - 0.627, p < 0.001), Dapp (r = - 0.381, p < 0.001) and Kapp (r = 0.641, p < 0.001) were correlated with SES-CD. These parameters were significantly different among the three groups (all p < 0.001). ROC analysis found ADC had the highest accuracy (AUC = 0.884, p < 0.001) to differentiate inactive from active group with the threshold at 0.865 × 10-3 mm2/s, which was slightly higher than Kapp (AUC = 0.867, p < 0.001) with the threshold at 0.645, and was obviously higher than Dapp (AUC = 0.726, p = 0.005). Similarly, ADC also had the highest accuracy (AUC = 0.846, p < 0.001) to differentiate inactive-mild from moderate-severe group with the threshold at 0.825 × 10-3 mm2/s, and minimally higher than Kapp (AUC = 0.843, p < 0.001) with the threshold at 0.695, and obviously higher than Dapp (AUC = 0.690, p < 0.001). CONCLUSION: DKI is feasible and comparable to conventional DWI for the evaluation of inflammatory activity in CD.

Corrigendum to "Computed Tomography Enterography: Quantitative Evaluation on Crohn's Disease Activity".

[This corrects the article DOI: 10.1155/2018/7351936.].

Computed Tomography Enterography: Quantitative Evaluation on Crohn's Disease Activity.

OBJECTIVE: To explore the feasibility of computed tomography enterography (CTE) in the quantitative evaluation of the activity of Crohn's disease (CD). METHODS: There were 49 CD patients with whole clinical, enteroscopy, and CTE data to be analyzed retrospectively. The patients were graded as inactive (0-2), mild (3-6), and moderate-severe group (>6) based on simplified endoscopic activity score for Crohn's disease (SES-CD). The differences in bowel wall thickening, mural hyperenhancement in the portal vein period, and the ΔCT values were analyzed among groups using ANOVA (analysis of variance) and q test. Then, the parameters were correlated with SES-CD, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). RESULTS: In the 49 patients, 13 ones were inactive, 19 ones were mild, and 17 ones were moderate-severe; the thickness of bowel wall, mural hyperenhancement in the portal vein period, and ΔCT value among groups were all significantly different (P < 0.001 in all). Correlative analysis showed that compared with the SES-CD, the bowel wall thickening (r = 0.564, P < 0.001), mural hyperenhancement in the portal vein period (r = 0.585, P < 0.001), and ΔCT value (r = 0.533, P < 0.001) were moderately correlated. CONCLUSION: The mural hyperenhancement in the portal vein period, bowel wall thickening, and ΔCT value can accurately and quantitatively assess the activity of CD lesions and are potential visual biomarkers of CD lesions.

A facile approach to preparation of silica double-shell hollow particles, and their application in gel composite electrolytes.

Double-shell hollow particles (DSHPs) have attracted significant attention due to their diverse potential applications. DSHPs are usually obtained by multi-step sacrificial template method which is tedious and inefficient. In this work, a facile synthesis of silica DSHPs has been developed via a novel one-step template method, which is using single-hole hollow particles (SHHPs) as the templates. The shapes and internal structures of the DSHPs were determined by SEM and TEM, and the average diameters of inner and outer shells were about 0.6 and 1.6 µm, respectively. According to FTIR analyses, the compositions of silica DSHPs were identified as well. Furthermore, the silica DSHPs was applied to Li-ion batteries as a modifier of gel polymer electrolyte (GPEs), and the results showed that the gel composite electrolytes (GCEs) could display higher capability, higher ionic conductivity and better rate performance at high current density for GCEs-cell. Properties of the silica DSHPs such as larger specific surface area, more porous structures and Lewis acid-base effect were important for high-performance Li-ion batteries.